TNFR1 is essential for CD40, but not for lipopolysaccharide-induced sickness behavior and clock gene dysregulation

Autoimmune and infectious diseases are associated with behavioral changes referred to as sickness behavior syndrome (SBS). In autoimmunity, the generation of anti-self T lymphocytes and autoantibodies critically involves binding of CD40 ligand on T-cells to its receptor CD40 on B-cells, dendritic cells and macrophages. Activation of CD40 leads to production of proinflammatory cytokines and, as shown here, induces SBS. Here we report that these behavioral changes depend on the expression of tumor necrosis factor alpha receptor 1 (TNFR1), but not on interleukin-1 receptor 1 or interleukin-6. Moreover, the intensity of SBS correlates with suppression of E-box controlled clock genes, including Dbp, and upregulation of Bmal1. However, the absence of TNFR1 does not interfere with the development of SBS and dysregulation of clock genes in mice treated with lipopolysaccharide. Thus, our results suggest that TNFR1 mediates SBS and dysregulation of clock genes in autoimmune diseases.

Reproducibility of acute mountain sickness in children and adults: a prospective study

Although a history of previous acute mountain sickness (AMS) is commonly used for providing advice and recommending its prophylaxis during subsequent exposure, the intraindividual reproducibility of AMS during repeated high-altitude exposure has never been examined in a prospective controlled study.

Systemic vascular dysfunction in patients with chronic mountain sickness

Chronic mountain sickness (CMS) is a major public health problem characterized by exaggerated hypoxemia and erythrocytosis. In more advanced stages, patients with CMS often present with functional and structural changes of the pulmonary circulation, but there is little information on the systemic circulation. In patients with diseases associated with chronic hypoxemia at low altitude, systemic vascular function is altered. We hypothesized that patients with CMS have systemic vascular dysfunction that may predispose them to increased systemic cardiovascular morbidity.

Predictors of sickness absence in patients with a new episode of low back pain in primary care

This study examines predictors of sickness absence in patients presenting to a health practitioner with acute/ subacute low back pain (LBP). Aims of this study were to identify baseline-variables that detect patients with a new LBP episode at risk of sickness absence and to identify prognostic models for sickness absence at different time points after initial presentation. Prospective cohort study investigating 310 patients presenting to a health practitioner with a new episode of LBP at baseline, three-, six-, twelve-week and six-month follow-up, addressing work-related, psychological and biomedical factors. Multivariate logistic regression analysis was performed to identify baseline-predictors of sickness absence at different time points. Prognostic models comprised 'job control', 'depression' and 'functional limitation' as predictive baseline-factors of sickness absence at three and six-week follow-up with 'job control' being the best single predictor (OR 0.47; 95%CI 0.26-0.87). The six-week model explained 47% of variance of sickness absence at six-week follow-up (p<0.001). The prediction of sickness absence beyond six-weeks is limited, and health practitioners should re-assess patients at six weeks, especially if they have previously been identified as at risk of sickness absence. This would allow timely intervention with measures designed to reduce the likelihood of prolonged sickness absence.

Exercise induces rapid interstitial lung water accumulation in patients with chronic mountain sickness

Chronic mountain sickness (CMS) is a major public health problem in mountainous regions of the world. In its more advanced stages, exercise intolerance is often found, but the underlying mechanism is not known. Recent evidence indicates that exercise-induced pulmonary hypertension is markedly exaggerated in CMS. We speculated that this problem may cause pulmonary fluid accumulation and aggravate hypoxemia during exercise.

[How can the mentally ill achieve sustained employment? Supported employment versus pre-vocational training]

People with severe mental disorders are often without work, although work may have a positive effect on their health. The paper presents some results in this field from the German S3 guidelines on psychosocial therapies. In terms of evidence-based medicine supported employment (SE - first place then train) has proven to be most effective. Nevertheless, SE is still rare in Germany. Pre-vocational training, however, follows the concept first train then place and is offered in rehabilitation of the mentally ill (RPK) centres in Germany. There is some evidence that the programs are beneficial for users. The UN Convention for the Rights of Persons with Disabilities outlines an obligation for work on an equal basis with others and for vocational training. So far, the German mental health system only partly meets these requirements.

A randomised controlled trial of the efficacy of supported employment

Although numerous randomised controlled trials indicated the superiority of supported employment (SE), we still have too little evidence that SE is more effective than traditional vocational rehabilitation programmes (TVR) in Western European countries with highly developed social security and welfare systems, sophisticated rehabilitation programmes and high thresholds to the open labour market. The aim of this study is to prove the efficacy of SE in Switzerland.

Social Policy Facing the Problems of Youth Employment

Rumiana Stoilova (Bulgaria). Social Policy Facing the Problems of Youth Employment. Ms. Stoilova is a researcher in the Institute of Sociology in Sofia and worked on this project from October 1996 to September 1998. This project involved collecting both statistical and empirical data on the state of youth employment in Bulgaria, which was then compared with similar data from other European countries. One significant aspect was the parallel investigation of employment and unemployment, which took as a premise the continuity of professional experience where unemployment is just a temporary condition caused by external and internal factors. These need to be studied and changed on a systematic basis so as to create a more favourable market situation and to improve individuals' resources for improving their market opportunities. A second important aspect of the project was an analysis of the various entities active on the labour market, including government and private institutions, associations of unemployed persons, of employers or of trade unions, all with their specific legal powers and interests, and of the problems in communication between these. The major trends in youth unemployment during the period studied include a high proportion of the registered unemployed who are not eligible for social assistance, a lengthening of the average period of unemployment, an increase in the percentage of people who are unemployed for the first time and an increasing percentage of these who are not eligible for assistance, particularly among newly registered young people. At the same time the percentage of those for who work has been found is rising and during the last three years an increasing number of the unemployed have started some independent economic activity. Regional differences are also considerable and in the case of the Haskovo region represent a danger of losing the youngest generation, with resulting negative demographic effects. One major weakness of the existing institutional structure is the large scale of the black labour market, with clear negative implications for the young people drawn into it. The role of non-governmental organisations in providing support and information for the unemployed is growing and the government has recently introduced special preferences for organisations offering jobs to unemployed persons. Social policy in the labour market has however been largely restricted to passive measures, mostly because of the risk that poverty poses to people continuously excluded from the labour market. Among the active measures taken, well over half are concerned with providing jobs for the unemployed and there are very limited programmes for providing or improving qualifications. The nature of youth employment in Bulgaria can be seen in the influence of sustained structures (generation) and institutions (family and school). Ms. Stoilova studied the situation of the modern generation through a series of profiles, mostly those of continuously unemployed and self-employed persons, but also distinguishing between students and the unemployed, and between high school and university students. The different categories of young people were studied in separate mini-studies and the survey was carried out in five town in order to gather objective and subjective information on the state of the labour market in the different regions. She conducted interviews with several hundred young people covering questions of family background, career plans, attitudes to the labour situation and government measures to deal with it, and such questions as independence, mobility, attitude to work, etc. The interviews with young people unemployed for a long period of time show the risk involved in starting work and its link with dynamics of economic development. Their approval of structural reforms, of the financial restrictions connected with the introduction of a currency board and the inevitability of unemployment was largely declarative. The findings indicate that the continuously unemployed need practical knowledge and skills to "translate" the macroeconomic realities in concrete alternatives of individual work and initiative. The unemployed experience their exclusion from the labour market not only as a professional problem but also as an existential threat, of poverty, forced mobility and dependence on their parents' generation. The exclusion from the market of goods and services means more than just exercising restraint in their consumption, as it places restrictions on their personal development. Ms. Stoilova suggests that more efficient ways of providing financial aid and mobilisation are needed to counteract the social disintegration and marginalisation of the continuously unemployed. In measuring the speed of reform, university students took both employment opportunities and the implementation of the meritocratic principle in employment into account. When offered a hypothetical choice between a well-paid job and work in one's own profession, 62% would prefer opt for the well-paid job and for working for a company that offered career opportunities rather than employment in a family or own company. While most see the information gained during their studies as useful and interesting, relatively few see their education as competitive on a wider level and many were pessimistic about employment opportunities based on their qualifications. Very similar attitudes were found among high school students, with differences being due rather to family and personal situations. The unemployed, on the other hand, placed greater emphasis on possibilities of gaining or improving qualifications on a job and for the opportunities it would offer for personal contacts. High school students tend to attribute more significance to opportunities for personal accomplishment. A significant difference that five times fewer high school students were willing to work for state-owned companies, and many fewer expected to find permanent employment or to find a job in the area where they lived, Within the family situation, actual support for children seems to be higher than the feelings of confidence expressed in interviews. The attitudes of the families towards past experience seems to be linked with their ability to cope with the difficulties of the present, with those families which show an optimistic and active attitude towards the future having a greater respect for parents experience and tolerance in communication between parents and children.