Suboptimal diet is a major modifiable risk factor in cardiovascular disease. Governments, individuals, educational institutes, healthcare facilities and the industry all share the responsibility to... Show moreSuboptimal diet is a major modifiable risk factor in cardiovascular disease. Governments, individuals, educational institutes, healthcare facilities and the industry all share the responsibility to improve dietary habits. Healthcare facilities in particular present a unique opportunity to convey the importance of healthy nutrition to patients, visitors and staff. Guidelines on cardiovascular disease do include policy suggestions for population-based approaches to diet in a broad list of settings. Regrettably, healthcare facilities are not explicitly included in this list. The authors propose to explicitly include healthcare facilities as a setting for policy suggestions in the current and future ESC Guidelines for cardiovascular disease prevention in clinical practice. (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
The primary aim of this thesis was to investigate the complex relationship between pain, neuropsychiatric symptoms, and ADL functioning in persons with dementia. Furthermore, we studied the... Show moreThe primary aim of this thesis was to investigate the complex relationship between pain, neuropsychiatric symptoms, and ADL functioning in persons with dementia. Furthermore, we studied the psychometric properties of a new and universal observational pain assessment instrument Pain Assessment In Impaired Cognition: PAIC.The results of this thesis show that pain in nursing home residents with dementia is related to a decline in ADL functions, independent of dementia severity. Specifically, a decline in the ADL activities transferring and bathing.Additionally, the psychometric evaluation of the PAIC presented in this thesis not only results in a promising measurement instrument, but also provides useful information for the development and improvement of educational programmes that contribute to the utilization of the PAIC15. Show less
Ding, J.L.; Chen, X.Z.; Silva, M.S. da; Lingeman, J.; Han, F.; Meijer, O.C. 2020
The Single Prolonged Stress protocol is considered a model for PTSD, as it induces long lasting changes in rat behaviour and endocrine regulation. Previous work demonstrated that some of these... Show moreThe Single Prolonged Stress protocol is considered a model for PTSD, as it induces long lasting changes in rat behaviour and endocrine regulation. Previous work demonstrated that some of these changes can be prevented by treatment with the glucocorticoid receptor antagonist RU486, administered a week after the stressor. The current study evaluated the effects of an earlier intervention with RU486, as evaluated 1 week after SPS-exposure. Most RU486 effects occurred independent of prior stress, except for the reversal of a stress-induced increase in locomotor behaviour. The accompanying changes in gene expression depended on gene, brain region, and time. DNA methylation of the robustly down-regulated Fkbp5 gene was dissociated of changes in mRNA expression. The findings reinforce the long term effects of GR antagonist treatment, but also emphasize the need to evaluate changes over time to allow the identification of robust correlates between gene expression and behavioural/endocrine outcome of stressful experiences. Show less
Warreman, E.B.; Lambregts, M.M.C.; Wouters, R.H.P.; Visser, L.G.; Staats, H.; Dijk, E. van; Boer, M.G.J. de 2019
The suprachiasmatic nucleus (SCN) functions as a circadian clock that drives 24-hour rhythms in physiology and behavior. The SCN neurons function as cell-autonomous oscillators, and the... Show more The suprachiasmatic nucleus (SCN) functions as a circadian clock that drives 24-hour rhythms in physiology and behavior. The SCN neurons function as cell-autonomous oscillators, and the production of a coherent SCN rhythm is dependent upon synchronization among single cells. We investigated how changes in phase-synchronization between individual cells effect the ability of the SCN to phase-shift its rhythm. Empirical and modelling studies revealed larger phase-shifts in synchronized SCN than in desynchronized SCN. The major external stimulus affecting the SCN is light. We explored the ability of melanopsin and rod- and cone photoreceptors to mediate the effects of light on SCN discharge, and found that melanopsin and cones are able to mediate light responses of the SCN. Studies performed in nocturnal species have indicated that the SCN’s rhythmicity is also influenced by the animal’s own behavioral activity. We assessed the effect behavioral activity on the amplitude of the circadian rhythm in SCN electrical discharge rate in the day-active Arvicanthis ansorgei. The results showed acute enhancements of SCN discharge during episodes of behavioral activity. The studies described in this thesis indicate that the SCN is part of a brain network that includes the retina and areas involved in behavioral activity and sleep. Show less
Winter, C.F. de; Baas, M.; Bijlsma, E.K.; Heukelingen, J. van; Routledge, S.; Hennekam, R.C.M. 2016
Previous regulatory models for the online environment have been designed with a foundation and premise that users are fictional Homo Economicus – beings capable of optimizing all available... Show morePrevious regulatory models for the online environment have been designed with a foundation and premise that users are fictional Homo Economicus – beings capable of optimizing all available information into order to make sound decisions. Sometime these decisions will be rational and predictable. However, on other occasions users will make irrational, yet predictable mistakes; other times those errors will be unpredictably irrational. To overcome these shortcomings in rational economist models, behavioural economists like Daniel Kahneman, Amos Tversky and Richard Thaler and lawyers like Cass Sunstein have advocated using lessons from psychology to help people make better decisions. By deploying 'choice’ architecture to overcome less than rational decisions, Homo Sapiens can be 'nudged' to making better choices. Building from this foundation, our paper inquires what role big data may play in developing better regulation. For example, can insights from big data help to overcome erroneous assumptions that regulators may make about the way users rationally behave in online environments? What potential is there for harnessing ‘big data’ to provide insights into user behaviour? Can big data be used as an additional tool by lawmakers to improve regulatory settlements? Show less
The results in this thesis showed for the first time doublecortin-like (DCL)-specific expression in the adult mouse brain. Besides the expected regions with the capacity to generate new neurons ... Show moreThe results in this thesis showed for the first time doublecortin-like (DCL)-specific expression in the adult mouse brain. Besides the expected regions with the capacity to generate new neurons (hippocampus and olfactory forebrain), DCL expression was found in three novel brain areas namely hypothalamic tanycytes, suprachiasmatic nucleus and Islands of Calleja. A state of the art conditional shRNA expressing mouse model was used to target DCL mRNA. The analysis of these DCL knockdown animals using qPCR and Western blot revealed strong reduction of DCL protein expression. Subsequent stereological analysis using BrdU and several stem cell and neuronal markers revealed increased progenitor proliferation, but impaired neurogenesis in the hippocampus. This impaired neurogenesis was associated, however, with an apparent normal spatial and contextual fear memory formation in circular hole board and in a contextual fear conditioning paradigm. Therefore, DCL-regulated adult neurogenesis seems not crucial for hippocampus-dependent learning. However, more subtle functions like pattern separation and context distinction might be regulated by DCL. DCL knockdown also increased D2 activity within the hypothalamus. Altogether, the DCL-KD mouse seems a good working model to study adult neurogenesis and the role of DCL in this process. Show less
Synthetic glucocorticoids such as dexamethasone are frequently used to enhance pulmonary development in preterm ventilator-dependent infants. In contrast to the short-term benefit on survival and... Show moreSynthetic glucocorticoids such as dexamethasone are frequently used to enhance pulmonary development in preterm ventilator-dependent infants. In contrast to the short-term benefit on survival and lung maturation, early glucocorticoid exposure has been shown to adversely affect neurodevelopmental processes. Both human and animal studies have reported acute and long-lasting impairments, including shortening of the lifespan in rodents. Therefore, the objective of the studies described in this thesis was to investigate, using an animal model: 1) the short- and long-term consequences of neonatal dexamethasone treatment and 2) the possibility to prevent these effects using pharmacological and behavioural intervention strategies. We reported that systemic dexamethasone treatment acutely affects brain development by suppressing cell proliferation and glial activity. These acute effects on the brain can be partially prevented by central glucocorticoid receptor antagonist pre-treatment, which might serve as a protective strategy against the adverse effects of dexamethasone treatment on the developing brain. Although neonatal dexamethasone exposure clearly affects the developmental trajectory, we did not observe the frequently described detrimental long-lasting consequences of this treatment. We showed that daily handling of the neonate, which was an inevitable component of our experimental design and leads to enhanced levels of maternal care towards the offspring, may compensate for some of the adverse effects of dexamethasone treatment. We conclude that the impact of neonatal glucocorticoid exposure highly depends on interactions with other components of the early environment and is therefore susceptible to pharmacological and behavioural intervention strategies. Show less
Stress and oxidative stress (OS) might act synergistically to exacerbate the neuronal decay associated with aging. Recent evidence has shown a redox regulation of the function of the glucocorticoid... Show moreStress and oxidative stress (OS) might act synergistically to exacerbate the neuronal decay associated with aging. Recent evidence has shown a redox regulation of the function of the glucocorticoid receptors as nuclear transcription factors. The lack of the p66Shc gene reduces OS and increases lifespan in mice. Main aim of the study was to elucidate whether the interactions linking OS and the neuroendocrine system represent a crucial determinant of aging in p66Shc-/- mice. Thus, the contribution of p66Shc to behaviour and neuroendocrine regulations was assessed from early post-natal life to senescence. Mutant old mice were characterized by a slow-down in physical and emotional aging; adult subjects showed increased behavioural plasticity and lower emotionality associated to increased central levels of Brain-derived neurotrophic factor, reduced oxidative stress markers and greater resilience to stress-induced changes in the internal milieu. A role has been recently described for p66Shc in regulating energetic metabolism. Intriguingly, we found metabolic and emotional aspects to be strictly related and possibly mediated by maternal behaviour in these mutants. Our results shed light on the role played by OS and metabolism in longevity and emotionality/mood disorders and point to p66Shc as a candidate gene in the trade-off between fertility and lifespan. Show less
Humankind has resulted to the wild for food and medication since prehistory. Kenya for instance has been named the Cradle of Humankind due to the many findings by the Leakey family, where it has... Show moreHumankind has resulted to the wild for food and medication since prehistory. Kenya for instance has been named the Cradle of Humankind due to the many findings by the Leakey family, where it has been confirmed that most of our early ancestors were gatherers. While this could be seen as a phenomenon of the past, current studies reveal that many communities in Kenya today, have depended on wild plants for centuries. The Meru, a community living on the Eastern slopes of Mt. Kenya, bears witness to this where plants have been used in many ways as in medicine, food, material, social, fuel, environmental, non-vertebrate poisons and as bee plants. A model adopted accordingly by the Leiden Ethnosystems and Developments Program (LEAD) of Leiden University has helped to look into the visible and invisible factors that influence this community in its daily use of wild plants. The result reveals several factors that reveal significant strengths and bonds that powerfully influence human behaviour towards their knowledge and use of their wild plants. This has culminated into the construction of a working model for this region, and further paved way to understanding implications that result from wild plants use behaviour in Meru. Show less
This thesis describes the Leiden Artificial Reproductive Techniques Follow-up Project. In this project, the potential long-term effects of intracytoplasmic sperm injection (ICSI) were assessed in 5... Show moreThis thesis describes the Leiden Artificial Reproductive Techniques Follow-up Project. In this project, the potential long-term effects of intracytoplasmic sperm injection (ICSI) were assessed in 5 __ 8-year-old singleton children. ICSI is the method of artificial reproduction in which a sperm cel is injected into an oocyte using a microinjection pipette. The technique is mainly successful in overcoming male factor infertility. Concerns about the development and health of ICSI-children have existed since the introduction of the technique in 1992, because ICSI is more invasive than the more widespread technique of in vitro fertilisation (IVF). In this project, 87 ICSI-children born as a singleton were compared with 87 singletons born after IVF and 85 singletons born after natural conception at 5-8 years of age, on various parameters: neuromotor development, cognitive development, pregnancy, perinatal outcome, congenital malformations, general health, growth, medical care utilisation, behaviour, parenting stress, and child quality of life. Although the results remain inconclusive on some outcomes, the majority of concerns regarding development and health of ICSI-children can be dispelled up to 8 years of age, in particular when ICSI is compared to IVF. Show less
