The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart.

Systemic hypertension increases cardiac workload and subsequently induces signaling networks in heart that underlie myocyte growth (hypertrophic response) through expansion of sarcomeres with the aim to increase contractility. However, conditions of increased workload can induce both adaptive and maladaptive growth of heart muscle. Previous studies implicate two members of the AP-1 transcription factor family, junD and fra-1, in regulation of heart growth during hypertrophic response. In this study, we investigate the function of the AP-1 transcription factors, c-jun and c-fos, in heart growth. Using pressure overload-induced cardiac hypertrophy in mice and targeted deletion of Jun or Fos in cardiomyocytes, we show that c-jun is required for adaptive cardiac hypertrophy, while c-fos is dispensable in this context. c-jun promotes expression of sarcomere proteins and suppresses expression of extracellular matrix proteins. Capacity of cardiac muscle to contract depends on organization of principal thick and thin filaments, myosin and actin, within the sarcomere. In line with decreased expression of sarcomere-associated proteins, Jun-deficient cardiomyocytes present disarrangement of filaments in sarcomeres and actin cytoskeleton disorganization. Moreover, Jun-deficient hearts subjected to pressure overload display pronounced fibrosis and increased myocyte apoptosis finally resulting in dilated cardiomyopathy. In conclusion, c-jun but not c-fos is required to induce a transcriptional program aimed at adapting heart growth upon increased workload.

The London School of Hygiene and Tropical Medicine: a new century of malaria research

The global malaria situation has scarcely improved in the last 100 years, despite major advances in our knowledge of the basic biology, epidemiology and clinical basis of the disease. Effective malaria control, leading to a significant decrease in the morbidity and mortality attributable to malaria, will require a multidisciplinary approach. New tools - drugs, vaccine and insecticides - are needed but there is also much to be gained by better use of existing tools: using drugs in combination in order to slow the development of drug resistance; targeting resources to areas of greatest need; using geographic information systems to map the populations at risk and more sophisticated marketing techniques to distribute bed nets and insecticides. Sustainable malaria control may require the deployment of a highly effective vaccine, but there is much that can be done in the meantime to reduce the burden of disease.

Pork Value Chains: A Comparison of Catalonia, Spain and Manitoba, Canada

The purpose of this paper is to provide a comparative analysis of pork value chains in Catalonia, Spain and Manitoba, Canada. Intensive hog production models were implemented in Catalonia in the 1960s as a result of agriculture crises and fostered by feedstuffs factories. The expansion of the hog sector in Manitoba is more recent (in the 1990s) and brought about in large part by the opening of the Maple Leaf Meats processing plant in Brandon, Manitoba. This plant is capable of processing 90,000 hogs per week. Both hog production models ‐ the ‘older’ one in Catalonia (Spain) and the ‘newer’ in Manitoba‐ have been, until recently, examples of success. Inventories and production have been increasing substantially and both regions have proven to have great export potential. Recently, however, tensions have been developing with the hog production models of both regions, particularly as they relate to environmental concerns. The purpose of the paper is to compare the value chains with respect to their origins (e.g. supply a growing demand for pork, ensure farm profitability) and present states (e.g. environmental concerns, profitability). Keywords: pork value chain, hog farms, agri‐food studies. JEL: Q10, Q13, O57

The molluscicidal activity of the latex of Euphorbia splendens var. hislopii on Melanoides tuberculata (Thiaridae), a snail associated with habitats of Biomphalaria glabrata (Planorbidae)

The use of the latex of Euphorbia splendens var. hislopii was considered as an effective control method for Biomphalaria glabrata in Sumidouro, Rio de Janeiro. However, the appearance and expansion of the snail Melanoides tuberculata since August 1997, with the concomitant reduction of the population of B. glabrata suggest that competitive exclusion might be taking place. Depending on the susceptibility of the thiarid to the E. splendens toxin, the natural control that is occurring could be interrupted by the employment of the latex if the planorbid were less susceptible to the toxin. The aim of this study is to investigate the molluscicidal activity of the latex on M. tuberculata. We used 420 M. tuberculata, from Sumidouro. Fourteen different latex concentrations were tested using World Health Organization general methodology. Probit analysis was used for LD90 and LD50 determination. The LD50 was 3.57 mg/l and LD90 was 6.22 mg/l. At the highest concentration (10 mg/l) there was no survival. No significant differences among replicas (chi2 = 8.31; gl = 13; p > 0.05) were found. The LD90 dose for M. tuberculata was 13.8 times greater than that for B. glabrata, so that the molluscicide in the presence of the thiarid may have a synergic effect on reduction of Biomphalaria populations.

Heterogeneity of human monocytes: an optimized four-color flow cytometry protocol for analysis of monocyte subsets.

Monocytes are central mediators in the development of atherosclerotic plaques. They circulate in blood and eventually migrate into tissue including the vessel wall where they give rise to macrophages and dendritic cells. The existence of monocyte subsets with distinct roles in homeostasis and inflammation suggests specialization of function. These subsets are identified based on expression of the CD14 and CD16 markers. Routinely applicable protocols remain elusive, however. Here, we present an optimized four-color flow cytometry protocol for analysis of human blood monocyte subsets using a specific PE-Cy5-conjugated monoclonal antibody (mAb) to HLA-DR, a PE-Cy7-conjugated mAb to CD14, a FITC-conjugated mAb to CD16, and PE-conjugated mAbs to additional markers relevant to monocyte function. Classical CD14(+)CD16(-) monocytes (here termed "Mo1" subset) expressed high CCR2, CD36, CD64, and CD62L, but low CX(3)CR1, whereas "nonclassical" CD14(lo)CD16(+) monocytes (Mo3) essentially showed the inverse expression pattern. CD14(+)CD16(+) monocytes (Mo2) expressed high HLA-DR, CD36, and CD64. In patients with stable coronary artery disease (n = 13), classical monocytes were decreased, whereas "nonclassical" monocytes were increased 90% compared with healthy subjects with angiographically normal coronary arteries (n = 14). Classical monocytes from CAD patients expressed higher CX(3)CR1 and CCR2 than controls. Thus, stable CAD is associated with expansion of the nonclassical monocyte subset and increased expression of inflammatory markers on monocytes. Flow cytometric analysis of monocyte subsets and marker expression may provide valuable information on vascular inflammation. This may translate into the identification of monocyte subsets as selective therapeutic targets, thus avoiding adverse events associated with indiscriminate monocyte inhibition.

Ex vivo detectable activation of Melan-A-specific T cells correlating with inflammatory skin reactions in melanoma patients vaccinated with peptides in IFA.

The purpose of this study was to test melanoma vaccines consisting of peptides and immunological adjuvants for optimal immunogenicity and to evaluate laboratory immune monitoring for in vivo relevance. Forty-nine HLA-A2 positive patients with Melan-A positive melanoma were repeatedly vaccinated with Melan-A peptide, with or without immune adjuvant AS02B (QS21 and MPL) or IFA. Peptide-specific CD8 T cells in PBLs were analyzed ex vivo using fluorescent HLA-A2/Melan-A multimers and IFN-gamma ELISPOT assays. The vaccines were well tolerated. In vivo expansion of Melan-A-specific CD8 T cells was observed in 13 patients (1/12 after vaccination with peptide in AS02B and 12/17 after vaccination with peptide in IFA). The T cells produced IFN-gamma and downregulated CD45RA and CD28. T-cell responses correlated with inflammatory skin reactions at vaccine injection sites (P < 0.001) and with DTH reaction to Melan-A peptide (P < 0.01). Twenty-six of 32 evaluable patients showed progressive disease, whereas 4 patients had stable disease. The two patients with the strongest Melan-A-specific T-cell responses experienced regression of metastases in skin, lymph nodes, and lung. We conclude that repeated vaccination with Melan-A peptide in IFA frequently leads to sustained responses of specific CD8 T cells that are detectable ex vivo and correlate with inflammatory skin reactions.

Prevalence of thinness in children and adolescents in the Seychelles: comparison of two international growth references.

BACKGROUND: : Thinness in children and adolescents is largely under studied, a contrast with abundant literature on under-nutrition in infants and on overweight in children and adolescents. The aim of this study is to compare the prevalence of thinness using two recently developed growth references, among children and adolescents living in the Seychelles, an economically rapidly developing country in the African region. METHOD: S: Weight and height were measured every year in all children of 4 grades (age range: 5 to 16 years) of all schools in the Seychelles as part of a routine school-based surveillance program. In this study we used data collected in 16,672 boys and 16,668 girls examined from 1998 to 2004. Thinness was estimated according to two growth references: i) an international survey (IS), defining three grades of thinness corresponding to a BMI of 18.5, 17.0 and 16.0 kg/m2 at age 18 and ii) the WHO reference, defined here as three categories of thinness (-1, -2 and -3 SD of BMI for age) with the second and third named "thinness" and "severe thinness", respectively. RESULTS: : The prevalence of thinness was 21.4%, 6.4% and 2.0% based on the three IS cut-offs and 27.7%, 6.7% and 1.2% based on the WHO cut-offs. The prevalence of thinness categories tended to decrease according to age for both sexes for the IS reference and among girls for the WHO reference. CONCLUSION: The prevalence of the first category of thinness was larger with the WHO cut-offs than with the IS cut-offs while the prevalence of thinness of "grade 2" and thinness of "grade 3" (IS cut-offs) was similar to the prevalence of "thinness" and "severe thinness" (WHO cut-offs), respectively.

Nurses' and Midwives' - Understanding and Experiences of Empowerment in Ireland

Nurses’ and Midwives’ Understanding and Experiences of Empowerment in Ireland With the recently launched national health strategy (Department of Health and Children, 2001) and a tightening fiscal policy there is a requirement for a more innovative use of existing resources dedicated to healthcare in Ireland. Nurses and midwives, one of the largest professional groups within the health service, will play a critical role in developing this â?onewâ?Âù health service. Click here to download PDF 745kb

Selective absence of CD8+ TCRalpha beta+ intestinal epithelial cells in transgenic mice expressing beta2-microglobulin-associated ligands exclusively on thymic cortical epithelium.

Whereas interactions between the TCRalpha beta and self MHC:peptide complexes are clearly required for positive selection of mature CD4(+) and CD8(+) T cells during intrathymic development, the role of self or foreign ligands in maintaining the peripheral T cell repertoire is still controversial. In this report we have utilized keratin 14-beta2-microglobulin (K14-beta2m)-transgenic mice expressing beta2m-associated ligands exclusively on thymic cortical epithelial cells to address the possible influence of TCR:ligand interactions in peripheral CD8(+) T cell homeostasis. Our data indicate that CD8(+) T cells in peripheral lymphoid tissues are present in normal numbers in the absence of self MHC class I:peptide ligands. Surprisingly, however, steady state homeostasis of CD8(+) T cells in the intestinal epithelium is severely affected by the absence of beta2m-associated ligands. Indeed TCRalpha beta(+) IEL subsets expressing CD8alpha beta or CD8alpha alpha are both dramatically reduced in K14-beta2m mice, suggesting that the development, survival or expansion of CD8(+) IEL depends upon interaction of the TCR with MHC class I:peptide or other beta2m-associated ligands elsewhere than on thymic cortical epithelium. Collectively, our data reveal an unexpected difference in the regulation of CD8(+) T cell homeostasis by beta2m-associated ligands in the intestine as compared to peripheral lymphoid organs.

Instruction of haematopoietic lineage choices, evolution of transcriptional landscapes and cancer stem cell hierarchies derived from an AML1-ETO mouse model.

The t(8;21) chromosomal translocation activates aberrant expression of the AML1-ETO (AE) fusion protein and is commonly associated with core binding factor acute myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely resembles the slow evolution and the mosaic AE expression pattern of human t(8;21) CBF AML with global transcriptome sequencing, we find that disease progression was characterized by two principal pathogenic mechanisms. Initially, AE expression modified the lineage potential of haematopoietic stem cells (HSCs), resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was followed by a second substantial rewiring of transcriptional networks occurring in the trajectory to manifest leukaemia. We also find that both HSC and lineage-restricted granulocyte macrophage progenitors (GMPs) acquired leukaemic stem cell (LSC) potential being capable of initiating and maintaining the disease. Finally, our data demonstrate that long-term expression of AE induces an indolent myeloproliferative disease (MPD)-like myeloid leukaemia phenotype with complete penetrance and that acute inactivation of AE function is a potential novel therapeutic option.

Report of the National Taskforce on Obesity: Obesity - the policy challenges: Executive Summary

The prevalence of overweight and obesity has increased with alarming speed over the past twenty years. It has recently been described by the World Health Organisation as a ‘global epidemic’. In the year 2000 more than 300 million people worldwide were obese and it is now projected that by 2025 up to half the population of the United States will be obese if current trends are maintained. The disease is now a major public health problem throughout Europe. In Ireland at the present time 39% of adults are overweight and 18% are obese. Of these, slightly more men than women are obese and there is a higher incidence of the disease in lower socio-economic groups. Most worrying of all is the fact that childhood obesity has reached epidemic proportions in Europe, with body weight now the most prevalent childhood disease. While currently there are no agreed criteria or standards for assessing Irish children for obesity some studies are indicating that the numbers of children who are significantly overweight have trebled over the past decade. Extrapolation from authoritative UK data suggests that these numbers could now amount to more than 300,000 overweight and obese children on the island of Ireland and they are probably rising at a rate of over 10,000 per year. A balance of food intake and physical activity is necessary for a healthy weight. The foods we individually consume and our participation in physical activity are the result of a complex supply and production system. The growing research evidence that energy dense foods promote obesity is impressive and convincing. These are the foods that are high in fat, sugar and starch. Of these potentially the most significant promoter of weight gain is fat and foods from the top shelf of the food pyramid including spreads (butter and margarine), cakes and biscuits, and confectionery, when combined are the greatest contributors to fat intake in the Irish diet. In company with their adult counterparts Irish children are also consuming large amounts of energy dense foods outside the home. A recent survey revealed that slightly over half of these children ate sweets at least once a day and roughly a third of them had fizzy drinks and crisps with the same regularity. Sugar sweetened carbonated drinks are thought to contribute to obesity and for this reason the World Health Organisation has expressed serious concerns at the high and increasing consumption of these drinks by children. Physical activity is an important determinant of body weight. Over recent decades there has been a marked decline in demanding physical work and this has been accompanied by more sedentary lifestyles generally and reduced leisure-time activity. These observable changes, which are supported by data from most European countries and the United States, suggest that physical inactivity has made a significant impact on the increase in overweight and obesity being seen today. It is now widely accepted that adults shoud be involved in 45-60 minutes, and children should be involved in at least 60 minutes per day of moderate physical activity in order to prevent excess weight gain. Being overweight today not only signals increased risk of medical problems but also exposes people to serious psychosocial problems due mainly to widespread prejudice against fat people. Prejudice against obese people seems to border on the socially acceptable in Ireland. It crops up consistently in surveys covering groups such as employers, teachers, medical and healthcare personnel, and the media. It occurs among adolescents and children, even very young children. Because obesity is associated with premature death, excessive morbidity and serious psychosocial problems the damage it causes to the welfare of citizens is extremely serious and for this reason government intervention is necessary and warranted. In economic terms, a figure of approximately â,¬30million has been estimated for in-patient costs alone in 2003 for a number of Irish hospitals. This year about 2,000 premature deaths in Ireland will be attributed to obesity and the numbers are growing relentlessly. Diseases which proportionally more obese people suffer from than the general population include hypertension, type 2 diabetes, angina, heart attack and osteoarthritis. There are indirect costs also such as days lost to the workplace due to illness arising from obesity and output foregone as a result of premature death. Using the accepted EU environmental cost benefit method, these deaths alone may be costing the state as much as â,¬4bn per year. The social determinants of physical activity include factors such as socio-economic status, education level, gender, family and peer group influences as well as individual perceptions of the benefits of physical activity. The environmental determinants include geographic location, time of year, and proximity of facilities such as open spaces, parks and safe recreational areas generally. The environmental factors have not yet been as well studied as the social ones and this research gap needs to be addressed. Clearly there is a public health imperative to ensure that relevant environmental policies maximise opportunities for active transport, recreational physical activity and total physical activity. It is clear that concerted policy initiatives must be put in place if the predominantly negative findings of research regarding the determinants of food consumption and physical activity are to be accepted, and they must surely be accepted by government if the rapid increase in the incidence of obesity with all its negative consequences for citizens is to be reversed. So far actions surrounding nutrition policies have concentrated mostly on actions that are within the remit of the Department of Health and Children such as implementing the dietary guidelines. These are important but government must now look at the totality of policies that influence the type and supply of food that its citizens eat and the range and quality of opportunities that are available to citizens to engage in physical activity. This implies a fundamental examination of existing agricultural, industrial, economic and other policies and a determination to change them if they do not enable people to eat healthily and partake in physical activity. The current crisis in obesity prevalence requires a population health approach for adults and children in addition to effective weight-reduction management for individuals who are severely overweight. This entails addressing the obesogenic environment where people live, creating conditions over time which lead to healthier eating and more active living, and protecting people from the widespread availability of unhealthy food and beverage options in addition to sedentary activities that take up all of their leisure time. People of course have a fundamental right to choose to eat what they want and to be as active as they wish. That is not the issue. What the National Taskforce on Obesity has had to take account of is that many forces are actively impeding change for those well aware of the potential health and well-being consequences to themselves of overweight and obesity. The Taskforce’s social change strategy is to give people meaningful choice. Choice, or the capacity to change (because the strategy is all about change), is facilitated through the development of personal skills and preferences, through supportive and participative environments at work, at school and in the local community, and through a dedicated and clearly communicated public health strategy. High-level cabinet support will be necessary to implement the Taskforce’s recommendations. The approach to implementation must be characterised by joined-up thinking, real practical engagement by the public and private sectors, the avoidance of duplication of effort or crosspurpose approaches, and the harnessing of existing strategies and agencies. The range of government departments with roles to play is considerable. The Taskforce outlines the different contributions that each relevant department can make in driving its strategy forward. It also emphasises its requirement that all phases of the national strategy for healthy eating and physical activity are closely monitored, analysed and evaluated. The vision of the Taskforce is expressed as: An Irish society that enables people through health promotion, prevention and care to achieve and maintain healthy eating and active living throughout their lifespan. Its high-level goals are expressed as follows: Its recommendations, over eighty in all, relate to actions across six broad sectors: high-level government; education; social and community; health; food, commodities, production and supply; and the physical environment. In developing its recommendations the Taskforce has taken account of the complex, multisectoral and multi-faceted determinants of diet and physical activity. This strategy poses challenges for government, within individual departments, inter-departmentally and in developing partnerships with the commercial sector. Equally it challenges the commercial sector to work in partnership with government. The framework required for such initiative has at its core the rights and benefits of the individual. Health promotion is fundamentally about empowerment, whether at the individual, the community or the policy level.

Obesity - the policy challenges: The report of the National Taskforce on Obesity

Click here to download PDF The prevalence of overweight and obesity has increased with alarming speed over the past twenty years. It has recently been described by the World Health Organisation as a ‘global epidemic’. In the year 2000 more than 300 million people worldwide were obese and it is now projected that by 2025 up to half the population of the United States will be obese if current trends are maintained. The disease is now a major public health problem throughout Europe. In Ireland at the present time 39% of adults are overweight and 18% are obese. Of these, slightly more men than women are obese and there is a higher incidence of the disease in lower socio-economic groups. Most worrying of all is the fact that childhood obesity has reached epidemic proportions in Europe, with body weight now the most prevalent childhood disease. While currently there are no agreed criteria or standards for assessing Irish children for obesity some studies are indicating that the numbers of children who are significantly overweight have trebled over the past decade. Extrapolation from authoritative UK data suggests that these numbers could now amount to more than 300,000 overweight and obese children on the island of Ireland and they are probably rising at a rate of over 10,000 per year. A balance of food intake and physical activity is necessary for a healthy weight. The foods we individually consume and our participation in physical activity are the result of a complex supply and production system. The growing research evidence that energy dense foods promote obesity is impressive and convincing. These are the foods that are high in fat, sugar and starch. Of these potentially the most significant promoter of weight gain is fat and foods from the top shelf of the food pyramid including spreads (butter and margarine), cakes and biscuits, and confectionery, when combined are the greatest contributors to fat intake in the Irish diet. In company with their adult counterparts Irish children are also consuming large amounts of energy dense foods outside the home. A recent survey revealed that slightly over half of these children ate sweets at least once a day and roughly a third of them had fizzy drinks and crisps with the same regularity. Sugar sweetened carbonated drinks are thought to contribute to obesity and for this reason the World Health Organisation has expressed serious concerns at the high and increasing consumption of these drinks by children. Physical activity is an important determinant of body weight. Over recent decades there has been a marked decline in demanding physical work and this has been accompanied by more sedentary lifestyles generally and reduced leisure-time activity. These observable changes, which are supported by data from most European countries and the United States, suggest that physical inactivity has made a significant impact on the increase in overweight and obesity being seen today. It is now widely accepted that adults shoud be involved in 45-60 minutes, and children should be involved in at least 60 minutes per day of moderate physical activity in order to prevent excess weight gain. Being overweight today not only signals increased risk of medical problems but also exposes people to serious psychosocial problems due mainly to widespread prejudice against fat people. Prejudice against obese people seems to border on the socially acceptable in Ireland. It crops up consistently in surveys covering groups such as employers, teachers, medical and healthcare personnel, and the media. It occurs among adolescents and children, even very young children. Because obesity is associated with premature death, excessive morbidity and serious psychosocial problems the damage it causes to the welfare of citizens is extremely serious and for this reason government intervention is necessary and warranted. In economic terms, a figure of approximately â,¬30million has been estimated for in-patient costs alone in 2003 for a number of Irish hospitals. This year about 2,000 premature deaths in Ireland will be attributed to obesity and the numbers are growing relentlessly. Diseases which proportionally more obese people suffer from than the general population include hypertension, type 2 diabetes, angina, heart attack and osteoarthritis. There are indirect costs also such as days lost to the workplace due to illness arising from obesity and output foregone as a result of premature death. Using the accepted EU environmental cost benefit method, these deaths alone may be costing the state as much as â,¬4bn per year. The social determinants of physical activity include factors such as socio-economic status, education level, gender, family and peer group influences as well as individual perceptions of the benefits of physical activity. The environmental determinants include geographic location, time of year, and proximity of facilities such as open spaces, parks and safe recreational areas generally. The environmental factors have not yet been as well studied as the social ones and this research gap needs to be addressed. Clearly there is a public health imperative to ensure that relevant environmental policies maximise opportunities for active transport, recreational physical activity and total physical activity. It is clear that concerted policy initiatives must be put in place if the predominantly negative findings of research regarding the determinants of food consumption and physical activity are to be accepted, and they must surely be accepted by government if the rapid increase in the incidence of obesity with all its negative consequences for citizens is to be reversed. So far actions surrounding nutrition policies have concentrated mostly on actions that are within the remit of the Department of Health and Children such as implementing the dietary guidelines. These are important but government must now look at the totality of policies that influence the type and supply of food that its citizens eat and the range and quality of opportunities that are available to citizens to engage in physical activity. This implies a fundamental examination of existing agricultural, industrial, economic and other policies and a determination to change them if they do not enable people to eat healthily and partake in physical activity. The current crisis in obesity prevalence requires a population health approach for adults and children in addition to effective weight-reduction management for individuals who are severely overweight. This entails addressing the obesogenic environment where people live, creating conditions over time which lead to healthier eating and more active living, and protecting people from the widespread availability of unhealthy food and beverage options in addition to sedentary activities that take up all of their leisure time. People of course have a fundamental right to choose to eat what they want and to be as active as they wish. That is not the issue. What the National Taskforce on Obesity has had to take account of is that many forces are actively impeding change for those well aware of the potential health and well-being consequences to themselves of overweight and obesity. The Taskforce’s social change strategy is to give people meaningful choice. Choice, or the capacity to change (because the strategy is all about change), is facilitated through the development of personal skills and preferences, through supportive and participative environments at work, at school and in the local community, and through a dedicated and clearly communicated public health strategy. High-level cabinet support will be necessary to implement the Taskforce’s recommendations. The approach to implementation must be characterised by joined-up thinking, real practical engagement by the public and private sectors, the avoidance of duplication of effort or crosspurpose approaches, and the harnessing of existing strategies and agencies. The range of government departments with roles to play is considerable. The Taskforce outlines the different contributions that each relevant department can make in driving its strategy forward. It also emphasises its requirement that all phases of the national strategy for healthy eating and physical activity are closely monitored, analysed and evaluated. The vision of the Taskforce is expressed as: An Irish society that enables people through health promotion, prevention and care to achieve and maintain healthy eating and active living throughout their lifespan. Its high-level goals are expressed as follows: Its recommendations, over eighty in all, relate to actions across six broad sectors: high-level government; education; social and community; health; food, commodities, production and supply; and the physical environment. In developing its recommendations the Taskforce has taken account of the complex, multisectoral and multi-faceted determinants of diet and physical activity. This strategy poses challenges for government, within individual departments, inter-departmentally and in developing partnerships with the commercial sector. Equally it challenges the commercial sector to work in partnership with government. The framework required for such initiative has at its core the rights and benefits of the individual. Health promotion is fundamentally about empowerment, whether at the individual, the community or the policy level.

Differential requirement for CD4 help in the development of an antigen-specific CD8+ T cell response depending on the route of immunization.

Previous studies in our laboratory have shown that DBA/2 mice injected i.p. with syngeneic P815 tumor cells transfected with the HLA-CW3 gene (P815-CW3) showed a dramatic expansion of activated CD8+CD62L- T cells expressing exclusively the Vbeta10 segment. We have used this model to study the regulatory mechanisms involved in the development of the CW3-specific CD8+ response, with respect to different routes of immunization. Whereas both intradermal (i.d.) and i.p. immunization of DBA/2 mice with P815-CW3 cells led to a strong expansion of CD8+CD62L-Vbeta10+ cells, only the i.d. route allowed this expansion after immunization with P815 cells transfected with a minigene coding for the antigenic epitope CW3 170-179 (P815 miniCW3). Furthermore, depletion of CD4+ T cells in vivo completely abolished the specific response of CD8+CD62L-Vbeta10+ cells and prevented the rejection of P815-CW3 tumor cells injected i.p., whereas it did not affect CD8S+CD62L-Vbeta10+ cell expansion after i.d. immunization with either P815-CW3 or P815 miniCW3. Finally, the CW3-specific CD8+ memory response was identical whether or not CD4+ T cells were depleted during the primary response. Collectively, these results suggest that the CD8+ T cell response to P815-CW3 tumor cells injected i.p. is strictly dependent upon recognition of a helper epitope by CD4+ T cells, whereas no such requirement is observed for i.d. injection.

Effects of immunosuppressive drugs on T helper cells subsets and potential to promote tolerance in a stringent experimental transplantation model.

To achieve the goal of sustained donor-specifi c transplantation (Tx) tolerance, research efforts are now focusing on therapies based on specifi c cell subsets with regulatory properties. We and others have previously highlighted the therapeutic potential of naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTreg) in promoting long-term graft acceptance. Using more stringent experimental Tx models, we were however confronted to limitations. Indeed, while the transfer of antigenspecifi c nTreg promoted long-term MHC-mismatched skin allograft acceptance in lymphopenic mice in the absence of any immunosuppressive drug, allograft survival was only slightly prolonged when nTreg were transferred alone into non-lymphopenic mice. This suggested that in more stringent conditions, adjuvant therapies may be needed to effectively control alloreactive T cells (Teff). Whether and how the expansion of the Treg pool could be best combined with current immunosuppressive regimens in clinical settings remains to be defi ned. In this study, we have used in vitro assays and an in vivo skin Tx model to investigate the effects of various immunosuppressive drugs on the survival, proliferation and effector function of Teff and nTreg in response to alloantigens. Teff proliferation was inhibited in a dose-dependent manner by rapamycin and cyclosporine A, while anti-CD154 mAb only marginally affected Teff survival, proliferation and effector fucntion in vitro. Rapamycin promoted apoptosis of Teff as compared to nTreg that were more resistant in the presence of IL-2. In vivo, the transfer and/or expansion of Treg could be advantageously combined with rapamycin and anti-CD154 mAb treatment to signifi cantly prolong MHC-mismatched skin allografts survival in non-lymphopenic recipients. Taken together our data indicate that immunosuppressive drugs differentially target T-cell subsets and that some regimens could promote Treg expansion while controlling the Teff pool in response to alloantigens.

The development of professional guidelines for the eye examination of people with dementia

Recently published guidelines��in the UK��relating to sight tests among people with dementia go some of the way to addressing the specific needs of this group. However, there is still a long way to go in terms of improving the provision of eye care services and optimising the visual health of this group.A��study, published by the Thomas Pocklington Trust,��which examines this subject - The development of professional guidelines for the eye examination of people with dementia - was presented at the first ever national “Dementia and Sight Loss conference” in London (1st December) - a forum where 100 dementia and sight loss professionals met to discuss ways to tackle the challenge of concurrent dementia and sight loss. The study, by researchers at the University of Bradford Schools of Optometry and Health Studies, reviewed procedures for sight tests and eye examinations among those with dementia. It found that policy and practice were hampered by a serious lack of basic research into concurrent dementia and sight loss and prompted recommendations which could lead to improved procedures, tools and techniques.Recommendations prompted by the study outline seven steps towards improving policy and practice:Conduct a systematic study of the availability and uptake of sight tests among people with dementia. Set up a website for people with dementia and their carers with information on how dementia affects eye health, and the importance of eye examinations. Develop education and training for optometrists and care home staff. Compile a list of optometrists experienced in providing eye care for people with dementia. Develop a template for recording the results of eye examinations in people with dementia – something which can be endorsed by professional bodies and made available to care homes. Measure the effectiveness of eye care, such as sight tests and cataract removals, on the quality of life of people with dementia. Research clinical testing methods so that guidelines can be strengthened. Measuring contrast sensitivity, for example, in someone with dementia could be vital as an inability to judge contrasts can make daily tasks impossible.To access the discussion paper please follow this link: The development of professional guidelines for the eye examination of people with dementia ��