The primary headaches: genetics, epigenetics and a behavioural genetic model

The primary headaches, migraine with (MA) and without aura (MO) and cluster headache, all carry a substantial genetic liability. Familial hemiplegic migraine (FHM), an autosomal dominant mendelian disorder classified as a subtype of MA, is due to mutations in genes encoding neural channel subunits. MA/MO are considered multifactorial genetic disorders, and FHM has been proposed as a model for migraine aetiology. However, a review of the genetic studies suggests that the FHM genes are not involved in the typical migraines and that FHM should be considered as a syndromic migraine rather than a subtype of MA. Adopting the concept of syndromic migraine could be useful in understanding migraine pathogenesis. We hypothesise that epigenetic mechanisms play an important role in headache pathogenesis. A behavioural model is proposed, whereby the primary headaches are construed as behaviours, not symptoms, evolutionarily conserved for their adaptive value and engendered out of a genetic repertoire by a network of pattern generators present in the brain and signalling homeostatic imbalance. This behavioural model could be incorporated into migraine genetic research

The Rotterdam Study: 2012 objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods

IgE binds asymmetrically to its B cell receptor CD23.

The antibody IgE plays a central role in allergic disease mechanisms. Its effector functions are controlled through interactions between the Fc region and two principal cell surface receptors FcεRI and CD23. The interaction with FcεRI is primarily responsible for allergic sensitization and the inflammatory response, while IgE binding to CD23 is involved in the regulation of IgE synthesis and allergen transcytosis. Here we present the crystal structure of a CD23/IgE-Fc complex and conduct isothermal titration calorimetric binding studies. Two lectin-like "head" domains of CD23 bind to IgE-Fc with affinities that differ by more than an order of magnitude, but the crystal structure reveals only one head bound to one of the two identical heavy-chains in the asymmetrically bent IgE-Fc. These results highlight the subtle interplay between receptor binding sites in IgE-Fc and their affinities, the understanding of which may be exploited for therapeutic intervention in allergic disease

PLEE Methodology and Experiences at the University of Twente

For some years engineering has been in trouble. Fewer students have applied in general and the consequences have been merging and closing down of universities and departments. However, an initiative known as EPS (European Project Semester) was started in 1995 by this author. Students come together to work on multidisciplinary projects in international teams. This has shown to be an effective way to attract students and to give them international experience and develop their enhanced technical skills. Students of both gender from engineering, business and technology feel attracted to participate in this international semester. Many engineering schools have been inspired to provide the same set-up at their own institution. Several universities in Europe i.e. in Denmark, the Netherlands, Norway, Poland, Germany, France, Finland, Belgium, Portugal and two universities in Spain are now offering this international semester course at their universities. Future competition will be fierce and we need engineers in our companies. Industry must find or invent responsible ways to increase production without environmental consequences. This ought to inspire our students to consider a career in engineering. Obviously, the present engineering education needs some adjustment in order to satisfy industry´s requirements and the wishes of future students. The required skills base has changed. A continuous intake of engineering students is needed in our societies to create new developments and to have somebody to take over where others finish. We must persuade people to choose engineering. In that regard a big credit should be given to The Smallpeice Trust, Warwickshire, England. The Trust has for years done a tremendous work trying to attract young people into engineering

Comparing psychological adjustment across cleft and other craniofacial conditions: Implications for outcome measurement and intervention

© 2018, American Cleft Palate-Craniofacial Association. Although cleft lip and/or palate (CL/P) has been a focus of psychological research for a number of years, investigation of adjustment to other, rarer craniofacial anomalies (CFAs) has been scarce. Yet, many features of the journey experienced by patients with CL/P could also have relevance for those affected by other CFAs and vice versa. This brief article summarizes the literature pertaining to psychological adjustment across both craniofacial groups, as represented by several prominent review articles. Similarities across the 2 patient groups in relation to key domains of psychological adjustment and corresponding factors are identified. Consequently, a standardized approach to measurement across all congenital craniofacial conditions is proposed, alongside suggestions for the potential application of similar intervention frameworks and clinical approaches