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The Y402H variant confers a 2-fold higher risk of late-AMD per copy in individuals of European descent. This was stable to stratification by study design and AMD classification and not modified by smoking. The lack of association in non-Europeans requires further verification. These findings are of direct relevance for disease prediction. New research is needed to ascertain if differences in circulating levels, expression or activity of factor H protein explain the genetic association.

Age-related macular degeneration (ARMD) is the leading cause of irreversible visual loss in the Western world, affecting approximately 25 million people worldwide. The pathogenesis is complex and missense mutations in FBLN5 have been reported in association with ARMD. We have investigated the role of fibulin 5 in ARMD by completing the first European study of the gene FBLN5 in ARMD (using 2 European cohorts of 805 ARMD patients and 279 controls) and by determining the functional effects of the missense mutations on fibulin 5 expression. We also correlated the FBLN5 genotype with the ARMD phenotype. We found two novel sequence changes in ARMD patients that were absent in controls and expressed these and the other nine reported FBLN5 mutations associated with ARMD and two associated with the autosomal recessive disease cutis laxa. Fibulin 5 secretion was significantly reduced (P<0.001) for four ARMD (p.G412E, p.G267S, p.I169 T, and p.Q124P) and two cutis laxa (p.S227P, p.C217R) mutations. These results suggest that some missense mutations associated with ARMD lead to decreased fibulin 5 secretion with a possible corresponding reduction in elastinogenesis. This study confirms the previous work identifying an association between FBLN5 mutations and ARMD and for the first time suggests a functional mechanism by which these mutations can lead to ARMD. It further demonstrates that FBLN5 mutations can be associated with different phenotypes of ARMD (not limited to the previously described cuticular drusen type). Such knowledge may ultimately lead to the development of novel therapies for this common disease.

Platelet-rich plasma (PRP) is a fraction of blood with a platelet concentration above baseline. When platelets get activated, growth factors involved in wound healing are released. The application of PRP has shown good results in wound care, however, up to date no substantial research has been performed on the effect of PRP in burn treatment. This randomized double blind intra-patient controlled study investigates the effect of autologous PRP on wound healing in burns that require surgery with a meshed split skin graft (SSG). Fifty-two patients with various areas of deep dermal to full thickness burns, receiving surgery with a SSG were included after informed consent. Comparable study areas A and B (intra-patient) were appointed, randomized and either treated with a SSG and PRP or with a SSG alone. At day 5 to 7 postoperative, the epithelialization and graft take rate were assessed. Three, six, and twelve months postoperative, follow-up measurements were performed in the form of POSAS-questionnaires, DermoSpectroMeter, and Cutometer measurements. There was no statistically significant difference between the mean take rate nor the mean epithelialization rate at day 5-7 between the PRP-treated and control areas. However, PRP-treated wound areas showed more often better or equal epithelialization and take rates at day 5-7 than the standard treated areas. Minor effects were also seen in the reoperated and early operated subgroups. At 3, 6, and 12 months postoperative, POSAS scores from the patients and the observers, Dermaspectro-, and Cutometer measurements did not depict a significant difference between the PRP and standard treated areas. Concluding, the addition of PRP in the treatment of burn wounds did not result in improved graft take and epithelialization, nor could we demonstrate better scar quality. There was, however, a considerable variation in our clinical population.

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Laboratory-based surveillance, one of the pillars of monitoring infectious disease trends, relies on data produced in clinical and/or public health laboratories. Currently, diagnostic laboratories worldwide submit strains or samples to a relatively small number of reference laboratories for characterisation and typing. However, with the introduction of molecular diagnostic methods and sequencing in most of the larger diagnostic and university hospital centres in highincome countries, the distinction between diagnostic and reference/public health laboratory functions has become less clear-cut. Given these developments, new ways of networking and data sharing are needed. Assuming that clinical and public health laboratories may be able to use the same data for their own purposes when sequence-based testing and typing are used, we explored ways to develop a collaborative approach and a jointly owned database (TYPENED) in the Netherlands. The rationale was that sequence data-whether produced to support clinical care or for surveillance-can be aggregated to meet both needs. Here we describe the development of the TYPENED approach and supporting infrastructure, and the implementation of a pilot laboratory network sharing enterovirus sequences and metadata.

Objective-To investigate the association between variants in the complement component 5 (C5) gene and age-related macular degeneration (AMD).Design-Separate and combined data from three large AMD case-control studies and a prospective population-based study (The Rotterdam Study).Participants-A total of 2599 AMD cases and 3458 ethnically matched controls.Methods-Fifteen single nucleotide polymorphisms (SNPs) spanning the C5 gene were initially genotyped in 375 cases and 199 controls from the Netherlands (The AMRO-NL study population). Replication testing of selected SNPs was performed in the Rotterdam Study (NL) and study populations from Southampton, United Kingdom (UK) and New York, United States (US).Main Outcome Measures-Early and late stages of prevalent and incident AMD, graded according to (a modification of) the international grading and classification system of AMD. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptOphthalmology. Author manuscript; available in PMC 2011 March 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptResults-Significant allelic or genotypic associations between eight C5 SNPs and AMD were found in the AMRO-NL study and this risk appeared independently of CFH Y402H, LOC387715 A69S, age and gender. None of these findings could be confirmed consistently in three replication populations.Conclusions-Although the complement pathway, including C5, plays a crucial role in AMD, and the C5 protein is present in drusen, no consistent significant associations between C5 SNPs and AMD were found in all studies. The implications for genetic screening of AMD are discussed.

Outbreaks of foodborne hepatitis A are rarely recognized as such. Detection of these infections is challenging because of the infection’s long incubation period and patients’ recall bias. Nevertheless, the complex food market might lead to reemergence of hepatitis A virus outside of disease-endemic areas. To assess the role of food as a source of infection, we combined routine surveillance with real-time strain sequencing in the Netherlands during 2008–2010. Virus RNA from serum of 248 (59%) of 421 reported case-patients could be sequenced. Without typing, foodborne transmission was suspected for only 4% of reported case-patients. With typing, foodborne transmission increased to being the most probable source of infection for 16%. We recommend routine implementation of an enhanced surveillance system that includes prompt forwarding and typing of hepatitis A virus RNA isolated from serum, standard use of questionnaires, data sharing, and centralized interpretation of data.