Parkinson’s disease is a brain disease caused by toxic protein accumulations inducing damage to brain cells. Research suggests Parkinson’s disease may start outside of the brain because intestinal symptoms often appear decades before diagnosis. It is now thought that the toxic protein accumulates migrate from the gut to the brain through the vagus nerve, a nerve bundle that connects both organs while coinciding with inflammation. This project uses advanced lab models, like organ-on-chip technology, to study how Parkinson’s disease precisely spreads and induces inflammation in the brain, aiming to uncover new insights and potential treatment.

In the core of a brain infarct, energy supply is insufficient to remain ion gradients across the neuronal plasma membrane: loss of neuronal function is followed by neuronal death within minutes. Surrounding the infarct core there is an area with higher remaining perfusion levels. In this so-called penumbra, neurons are silent, but structurally intact. These may eventually recover, or proceed to cell death, but the mechanisms behind these diverging scenarios are not clearly understood. Therapies to prevent collateral damage of penumbral brain tissue have a large potential to improve neurological outcome of stroke patients, but are lacking. Synaptic failure due to impeded Synapsin-I phosphorylation is responsible for the initial, potentially reversible dysfunction. A pilot study in cultured cortical networks confirmed synaptic failure, and showed largely reduced activity levels, while individual neuronal functioning remained intact. We will investigate the reversibility of the initial synaptic failure, and two putative mechanisms leading to irreversible damage in the absence of primary cell death. First, we hypothesize that, depending on hypoxic depth and duration, apart from energy depletion, synaptic dysfunction may directly lead to secondary neuronal cell death. Here, secondary damage is related to insufficient activation, and we will investigate whether mild activation may delay or reduce cell death. Second, experimental data show that low neuronal activity levels trigger homeostatic processes that up-regulate excitatory connectivity, which may indirectly lead to secondary damage. Namely, the consequent energy demand from homeostatic processes further reduces the amount of ATP available for Synapsin-I phosphorylation and neurotransmitter release, thus creating a vicious circle. Mild activation should also avoid low activity induced homeostatic processes. Additionally, targeted pharmacological treatment will be validated to avoid activity dependent cell death as well as homeostatic interference.

Prognosis of outcome of patients in coma after cardiac arrest is crucial for decision making on (continuation of) treatment. Recent research has shown that visual classification of continuous EEG enables ultra-early, high quality prognosis of poor outcome within 24 hours. This technological innovation, in particular when translated in a quantitative index, may deepen existing controversies with regard to expected quality of life of surviving patients. It may also aggravate tensions between personal values (life of relatives) and societal concerns (cost reduction). Finally, introduction of EEG-based technology enabling ultra-early prognostication may create new controversies regarding timing of the prognosis and subsequent decision making. This project aims to develop the EEG-based prognostic technology in such a way that it contributes to good prognostic practice for comatose patients after cardiac arrest, and thus can be considered a responsible innovation. It explores how EEG-enabled prognosis might affect values in care for comatose patients, comparing the Netherlands, the USA and Germany. A mixture of qualitative (ethical ethnography, interviews) and quantitative methods (stated preference survey) is used. Subsequently, the project investigates by way of stakeholder workshops and normative analysis which conditions need to be satisfied to ensure that introducing EEG-monitoring is ethically and socially desirable. The ultimate aim is to embed these conditions in the material (hard- and software) and the social components (clinical practice, regulation) of prognostic practice, using methods derived from value sensitive design. Finally, the usefulness of the insights gained for innovation of coma prognostics and responsible innovation more generally will be explored.

Virtual Reality (VR) is increasingly applied in higher education. VR immerses users in virtual environments to present realistic learning experiences. However, the application and effectiveness of VR on learning remain unclear. In this project, we explore how the feeling of really being (presence) in the simulation contributes to learning; We also investigate to what extent it matters if VR applications do not perfectly match real working environments (surface and structure (dis)similarity); Finally, we examine how repeated use of VR contributes to learning. This research provides directions concerning how we learn how, and why VR can improve learning outcomes.

In The Netherlands applicants outnumber the medical school admission slots 3:1 (8400:2800). Since 2000 the weighted lottery method to select medical students has been gradually replaced by selection processes, specific to every medical school, involving testing and interviewing of the applicants. This happened because the lottery process was perceived as unfair by the applicants. Selection processes are expensive, and time and effort intensive. Moreover, contrary to expectations, scientific evaluation of the selection processes has revealed that the performance of the selected students is not consistently superior to students chosen by lottery. Highly disturbing is the observation that potentially successful applicants from parents with lower income or educational levels, and ethnic minority backgrounds shy away from selection processes and medical school. Even if they do dare to apply, they face barriers in getting selected. As a result the cohorts trained to become doctors are not representative of the population they serve. Underrepresentation of doctors with non-standard backgrounds poses a severe threat to the quality of health care as diversity is an essential component for promoting excellence in health education and care. This proposal involves one pharmacy and four (technical) medical schools. Student representatives from the VUmc "Diversity, Openness, Culture, Students" committee and Erasmus MC will also participate in this research team. The broad research question is, “How to select health professions education students so that they represent the demographic distribution in the Dutch population?”. This research aims to generate recommendations for selection processes for all applied science and healthcare education programmes.