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Apeldoorn, Netherlands

Galjart N.,Erasmus MC
Current Biology | Year: 2010

Microtubules are cytoskeletal elements that are essential for a large number of intracellular processes, including mitosis, cell differentiation and migration, and vesicle transport. In many cells, the microtubule network is organized in a radial manner, with one end of a microtubule (the minus end) embedded near the nucleus and the other end (the plus end) exploring cytoplasmic space, switching between episodes of growth and shrinkage. Mammalian plus-end-tracking proteins (+TIPs) localize to the ends of growing microtubules and regulate both the dynamic behavior of microtubules as well as the interactions of microtubules with other cellular components. Because of these crucial roles, +TIPs and the mechanisms underlying their association with microtubule ends have been intensively investigated. Results indicate that +TIPs reach microtubule ends by motor-mediated transport or diffusion. Individual +TIP molecules exchange rapidly on microtubule end-binding sites that are formed during microtubule polymerization and that have a slower turnover. Most +TIPs associate with the end-binding (EB) proteins, and appear to require these 'core' +TIPs for localization at microtubule ends. Accumulation of +TIPs may also involve structural features of the microtubule end and interactions with other +TIPs. This complexity makes it difficult to assign discrete roles to specific +TIPs. Given that +TIPs concentrate at microtubule ends and that each +TIP binds in a conformationally distinct manner, I propose that the ends of growing microtubules are 'nano-platforms' for productive interactions between selected proteins and that these interactions might persist and be functional elsewhere in the cytoplasm than at the microtubule end at which they originated. © 2010 Elsevier Ltd. All rights reserved. Source

Dohle G.R.,Erasmus MC
International Journal of Urology | Year: 2010

The number of men surviving cancer at a young age has increased dramatically in the past 20 years as a result of early detection and improved cancer treatment protocols; more than 75% of young cancer patients nowadays are long-term survivors. Quality of life has become an important issue in childhood and adult cancer patients. The commonest cancers in patients of reproductive age are leukaemia, Hodgkin's lymphomas and testicular germ cell tumors. Fertility is often impaired after chemotherapy and radiation therapy. Cryopreservation of semen before cancer treatment starts is currently the only method to preserve future male fertility. In some malignancies, especially in germ cell tumors, sperm quality is already abnormal at the time of diagnosis. In approximately 12% of men, no viable spermatozoa are present for cryopreservation before the start of chemotherapy. Cytotoxic therapy influences spermatogenesis at least temporarily and in some cases permanently. The amount of damage inflicted by chemotherapy on spermatogenesis depends on the combination of drugs used and on the cumulative dose given for cancer treatment. Alkylating agents, such as cyclophosphamide and procarbazine, are most detrimental to germ cells. Radiation therapy, especially whole-body irradiation, is also associated with the risk of permanent sterility. Besides the cancer treatment, tumor type and pretreatment fertility are of prognostic value for future fertility in male cancer survivors. After cancer treatment, many men need artificial reproductive techniques to achieve fatherhood; usually in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is indicated for successful treatment. About 15% of men will use their cryopreserved semen because of persistent azoospermia after cancer treatment. Treatment results with cryopreserved semen are generally good and comparable to general IVF and ICSI results. So far, no studies have reported an increased rate of congenital abnormalities or malignancies in children born from fathers who had cancer treatment is the past, but close follow up is warranted, especially in children born after IVF/ICSI. © 2010 The Japanese Urological Association. Source

Variations in 'culture' are often invoked to explain cross-national variations in health, but formal analyses of this relation are scarce. We studied the relation between three sets of cultural values and a wide range of health behaviours and health outcomes in Europe. Cultural values were measured according to Inglehart's two, Hofstede's six, and Schwartz's seven dimensions. Data on individual and collective health behaviours (30 indicators of fertility-related behaviours, adult lifestyles, use of preventive services, prevention policies, health care policies, and environmental policies) and health outcomes (35 indicators of general health and of specific health problems relating to fertility, adult lifestyles, prevention, health care, and violence) in 42 European countries around the year 2010 were extracted from harmonized international data sources. Multivariate regression analysis was used to relate health behaviours to value orientations, controlling for socioeconomic confounders. In univariate analyses, all scales are related to health behaviours and most scales are related to health outcomes, but in multivariate analyses Inglehart[U+05F3]s 'self-expression' (versus 'survival') scale has by far the largest number of statistically significant associations. Countries with higher scores on 'self-expression' have better outcomes on 16 out of 30 health behaviours and on 19 out of 35 health indicators, and variations on this scale explain up to 26% of the variance in these outcomes in Europe. In mediation analyses the associations between cultural values and health outcomes are partly explained by differences in health behaviours. Variations in cultural values also appear to account for some of the striking variations in health behaviours between neighbouring countries in Europe (Sweden and Denmark, the Netherlands and Belgium, the Czech Republic and Slovakia, and Estonia and Latvia).This study is the first to provide systematic and coherent empirical evidence that differences between European countries in health behaviours and health outcomes may partly be determined by variations in culture. Paradoxically, a shift away from traditional 'survival' values seems to promote behaviours that increase longevity in high income countries. © 2014 Elsevier Ltd. Source

Mackenbach J.P.,Erasmus MC
Journal of Epidemiology and Community Health | Year: 2011

England was the first European country to pursue a systematic policy to reduce socio-economic inequalities in health. This paper assesses whether this strategy has worked, and what lessons can be learnt. A review of documents was conducted, as well as an analysis of entry-points chosen, specific policies chosen, implementation of these policies, changes in intermediate outcomes, and changes in final health outcomes. Despite some partial successes, the strategy failed to reach its own targets, that is, a 10% reduction in inequalities in life expectancy and infant mortality. This is due to the fact that it did not address the most relevant entry-points, did not use effective policies and was not delivered at a large enough scale for achieving populationwide impacts. Health inequalities can only be reduced substantially if governments have a democratic mandate to make the necessary policy changes, if demonstrably effective policies can be developed, and if these policies are implemented on the scale needed to reach the overall targets. Source

MacKenbach J.P.,Erasmus MC
European Journal of Epidemiology | Year: 2013

It has been noted that national life expectancies have diverged in Europe in recent decades, but it is unknown how these recent trends compare to longer term developments. Data on life expectancy, cause-specific mortality and determinants of mortality were extracted from harmonized international data-bases. Variation was quantified with the inter-quartile range, and the contribution of changing economic conditions was analyzed by comparing observed life expectancy variations with those expected on the basis of changes in levels of national income and/or changes in the relation between national income and life expectancy. During the first decades of the 20th century, variation in life expectancy in Europe increased to reach peak values around 1920, then decreased to reach its lowest values in 1960 (among men) and 1970 (among women), and finally increased strongly again. The first widening was due to less rapid decline in mortality in Southern and Central and Eastern Europe, particularly from infectious diseases, and coincided with an increasing strength of the national income - life expectancy relation. The second widening was due to stagnating or increasing mortality in Central and Eastern Europe, particularly from cardiovascular diseases, and coincided with a very strong rise of between-country differences in national income. Despite some similarities, differences between both episodes of widening differences in life expectancy cast doubt on the idea that the current episode of widening represents a simple delay of epidemiological transitions. Instead, it is an alarming phenomenon that should be a main focus of European policy making. © 2012 Springer Science+Business Media Dordrecht. Source

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