Proteomic analysis of differential protein expression in human atherosclerotic plaque progression

In this study, differential protein expression was assessed during human atherosclerotic plaque progression. A multifaceted approach was used in which differential protein expression was studied by two-dimensional (2D) gel electrophoresis and validated in individual patients using western blotting and immunohistochemistry. 2D profiles of whole-mount advanced stable lesions were compared to those of plaques containing a thrombus. Mass spectrometry analysis identified vinexin-beta and alpha1-antitrypsin (AAT) in the same spot that was differentially expressed in plaques with a thrombus. Immunohistochemistry and western blotting showed limited expression of both vinexin-beta and AAT in early lesions, whereas high expression of both proteins was found in advanced lesions. Differential expression of vinexin-beta in lesions with a thrombus compared to stable plaques could not be confirmed, indicating the importance of validation of proteomic analysis. For AAT, western blotting of 2D gels revealed expression of six isoforms in advanced plaques, one of which was confirmed to be solely expressed in thrombus-containing plaques. In conclusion, vinexin-beta is expressed in advanced human atherosclerotic plaques, but differential expression of this protein in lesions with a thrombus versus stable plaques could not be confirmed. However, this analysis revealed expression of six isoforms of AAT in advanced plaques, one of which was uniquely expressed in thrombus-containing plaques

[Neonatal screening for congenital hypothyroidism: more than 30 years of experience in the Netherlands].

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Neonatale screening op congenitale hypothyreoïdie : ruim 30 jaar ervaring in Nederland [Neonatal screening for congenital hypothyroidism: more than 30 years of experience in the Netherlands]

Doel Beschrijving van de Nederlandse neonatale screening op congenitale hypothyreoïdie (CH). Opzet Descriptief onderzoek. Methode We verzamelden gegevens over de neonatale screening op CH in de periode 1 januari 1981-31 december 2011 van de Dienst Vaccinvoorziening en Preventieprogramma’s van het RIVM, van laboratoria en van kinderartsen naar wie pasgeborenen met een afwijkende uitslag werden verwezen. De screeningsprocedure werd verscheidene keren bijgesteld. In de periode 1981-1994 werden bijvoorbeeld alleen de waarden van T4 en TSH bepaald uit het hielprikkaartje. Vanaf 1995 werd ook de waarde van thyroxinebindend globuline (TBG) meegenomen. Resultaten De deelname was 99,7%. Tot 1995 was de sensitiviteit 94%, de specificiteit 99,51% en de positief voorspellende waarde 6%; vanaf 1995 was dit respectievelijk 98%, 99,85% en 21%. De totale prevalentie van CH was 1:2670 (prevalentie CH van thyreoïdale oorsprong: 1:3100 en centrale CH: 1:21.600). De percentages kinderen met ernstige CH bij wie in de perioden 1981-1990, 1991-2000 en 2001-2011 vóór de 15e levensdag met thyroxinebehandeling werd gestart, waren respectievelijk 24 (63/263), 63 (170/269) en 96 (176/184). Conclusie De sensitiviteit en specificiteit van het screeningsprogramma is vanaf 1995 aanzienlijk hoger dan vóór 1995. In de recente jaren worden patiënten met ernstige CH aanzienlijk vroeger behandeld dan in de beginjaren. De neonatale screening op CH kan als een belangrijk succes van de openbare gezondheidszorg worden beschouwd

Development of carotid intraplaque hemorrhage demonstrated by serial magnetic resonance imaging

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Voedselcriminaliteit

ARTIKELEN: 1. K.E. Gussow en L.H. Kuiper - De bestrijding van voedselfraude in Nederland 2. S. van Ruth en W. Huisman - Kwetsbaarheid voor voedselfraude in de vleessector 3. D. Siegel en D.P. van Uhm - Zwarte kaviaar; over criminele netwerken, illegale handel en de bedreiging van de steur 4. Ch.I. Sambrook - Illegale pesticiden en voedselcriminaliteit 5. J.A. van den Akker en E.M.R. de Lange - Naar een Europese aanpak van voedselfraude 6. Ch. Vansteenkiste en T. Schotte - De rol van Europol in de strijd tegen voedselcriminaliteit 7. Internetsites. SAMENVATTING: Nederland en andere Europese landen zijn in de afgelopen periode opgeschrikt door verschillende voedselschandalen. Vooral in de vleessector is van alles mis, zoveel is duidelijk na de ontdekking van de paardenvleesfraude in 2013. In dit themanummer wordt het verband verkend tussen voedsel(on)veiligheid en criminaliteit, waarbij aansluiting wordt gezocht met criminologische theorieën over gelegenheidsstructuren, motivaties en organisatiecriminaliteit

Cost-effectiveness of newborn screening for cystic fibrosis determined with real-life data

Previous cost-effectiveness studies using data from the literature showed that newborn screening for cystic fibrosis (NBSCF) is a good economic option with positive health effects and longer survival.We used primary data to compare cost-effectiveness of four screening strategies for NBSCF, i.e. immunoreactive trypsinogen-testing followed by pancreatitis-associated protein-testing (IRT-PAP), IRT-DNA, IRT-DNA-sequencing, and IRT-PAP-DNA-sequencing, each compared to no-screening. A previously developed decision analysis model for NBSCF was fed with model parameters mainly based on a study evaluating two novel screening strategies among 145,499 newborns in The Netherlands.The four screening strategies had cost-effectiveness ratios varying from ?23,600 to ?29,200 per life-year gained. IRT-PAP had the most favourable cost-effectiveness ratio. Additional life-years can be gained by IRT-DNA but against higher costs. When treatment costs reduce with 5% due to early diagnosis, screening will lead to financial savings.NBSCF is as an economically justifiable public health initiative. Of the four strategies tested IRT-PAP is the most economic and this finding should be included in any decision making model, when considering implementation of newborn screening for CF. European Cystic Fibrosis Society. Published b

Implementing Individually Tailored Prescription of Physical Activity in Routine Clinical Care: Protocol of the Physicians Implement Exercise = Medicine (PIE=M) Development and Implementation Project.

Contains fulltext : 229883.pdf (publisher's version ) (Open Access)BACKGROUND: The prescription of physical activity (PA) in clinical care has been advocated worldwide. This "exercise is medicine" (E=M) concept can be used to prevent, manage, and cure various lifestyle-related chronic diseases. Due to several challenges, E=M is not yet routinely implemented in clinical care. OBJECTIVE: This paper describes the rationale and design of the Physicians Implement Exercise = Medicine (PIE=M) study, which aims to facilitate the implementation of E=M in hospital care. METHODS: PIE=M consists of 3 interrelated work packages. First, levels and determinants of PA in different patient and healthy populations will be investigated using existing cohort data. The current implementation status, facilitators, and barriers of E=M will also be investigated using a mixed-methods approach among clinicians of participating departments from 2 diverse university medical centers (both located in a city, but one serving an urban population and one serving a more rural population). Implementation strategies will be connected to these barriers and facilitators using a systematic implementation mapping approach. Second, a generic E=M tool will be developed that will provide tailored PA prescription and referral. Requirements for this tool will be investigated among clinicians and department managers. The tool will be developed using an iterative design process in which all stakeholders reflect on the design of the E=M tool. Third, we will pilot-implement the set of implementation strategies, including the E=M tool, to test its feasibility in routine care of clinicians in these 2 university medical centers. An extensive learning process evaluation will be performed among clinicians, department managers, lifestyle coaches, and patients using a mixed-methods design based on the RE-AIM framework. RESULTS: This project was approved and funded by the Dutch grant provider ZonMW in April 2018. The project started in September 2018 and continues until December 2020 (depending on the course of the COVID-19 crisis). All data from the first work package have been collected and analyzed and are expected to be published in 2021. Results of the second work package are described. The manuscript is expected to be published in 2021. The third work package is currently being conducted in clinical practice in 4 departments of 2 university medical hospitals among clinicians, lifestyle coaches, hospital managers, and patients. Results are expected to be published in 2021. CONCLUSIONS: The PIE=M project addresses the potential of providing patients with PA advice to prevent and manage chronic disease, improve recovery, and enable healthy ageing by developing E=M implementation strategies, including an E=M tool, in routine clinical care. The PIE=M project will result in a blueprint of implementation strategies, including an E=M screening and referral tool, which aims to improve E=M referral by clinicians to improve patients' health, while minimizing the burden on clinicians

Saccular Abdominal Aortic Aneurysms Patient Characteristics, Clinical Presentation, Treatment, and Outcomes in the Netherlands

Objective: The aim of this was to analyze differences between saccularshaped abdominal aortic aneurysms (SaAAAs) and fusiform abdominal aortic aneurysms (FuAAAs) regarding patient characteristics, treatment, and outcome, to advise a threshold for intervention for SaAAAs.Background: Based on the assumption that SaAAAs are more prone to rupture, guidelines suggest early elective treatment. However, little is known about the natural history of SaAAAs and the threshold for intervention is not substantiated.Methods: Observational study including primary repairs of degenerative AAAs in the Netherlands between 2016 and 2018 in which the shape was registered, registered in the Dutch Surgical Aneurysm Audit (DSAA). Patients were stratified by urgency of surgery; elective versus acute (symptomatic/ruptured). Patient characteristics, treatment, and outcome were compared between SaAAAs and FuAAAs.Results: A total of 7659 primary AAA-patients were included, 6.1% (n = 471) SaAAAs and 93.9% (n = 7188) FuAAAs. There were 5945 elective patients (6.5% SaAAA) and 1714 acute (4.8% SaAAA). Acute SaAAApatients were more often female (28.9% vs 17.2%, P = 0.007) compared with acute FuAAA-patients. SaAAAs had smaller diameters than FuAAAs, in elective (53.0mm vs 61 mm, P = 0.000) and acute (68mm vs 75 mm, P = 0.002) patients, even after adjusting for sex. In addition, 25.2% of acute SaAAA-patients presented with diameters <55mm and 8.4% <45 mm, versus 8.1% and 0.6% of acute FuAAA-patients (P = 0.000). Postoperative outcomes did not significantly differ between shapes in both elective and acute patients.Conclusions: SaAAAs become acute at smaller diameters than FuAAAs in DSAA patients. This study therefore supports the current idea that SaAAAs should be electively treated at smaller diameters than FuAAAs. The exact diameter threshold for elective treatment of SaAAAs is difficult to determine, but a diameter of 45mm seems to be an acceptable threshold.Vascular Surger