Gut mucosal gene expression in inflammatory bowel disease:the heterogeneous nature of inflammation

This thesis entitled “Gut mucosal gene expression in inflammatory bowel disease - the heterogeneous nature of inflammation” describes the molecular basis of inflammatory bowel disease (IBD), which has a prevalence of 8:1000 in the Netherlands. IBD is marked by episodes of intestinal inflammation, and may manifest in other organs. Despite a large variety of treatment options, a substantial part of patients remains difficult to treat, and has to try out various (expensive) medications hoping to find one that works. This is a clinical and societal problem, requiring a solution. Within this thesis, the cause of IBD is sought and new opportunities for medical therapy are explored. One of the projects reveals 190 unique DNA variants that affect gut mucosal gene expression, depending of inflammation status. These findings support the theory that a patient-specific genetic background of IBD exists. Using a new technique, ‘single cell sequencing’, gut mucosal cells of IBD patients are investigated. There, it was found that specific cell types are expressing risk genes for IBD. These cells could be specifically targeted using currently available medication. Lastly, the gut mucosal cells of IBD patients are compared with a specific subgroup of IBD patients that has concomitant primary sclerosing cholangitis, a bile duct inflammation disease. Functional differences in inflammatory cells are found that may indicate differences in pathogenesis for this subgroup of the disease. In conclusion, this thesis describes molecular differences between patients with IBD, which may be key to personalized treatment of the disease

Trustrecht en bewind:rechtsvergelijkende beschouwingen met betrekking tot het Anglo-Amerikaanse trustrecht in verband met het bewind, de executele en andere parallelfiguren in het Nederlandse recht

This book contains a comparative study of Anglo~American trust law. It is inspired by the proposition that this ..greatest and most distinctive achievement of Anglo~American law" 1 might hold some elements which could be useful or even in~ dispensable for the growth of Dutch law. The background of this proposition is revealed in Chapter I: there exists in Dutch law a number of trust~like schemes which cannot satisfactorily be explained on the basis of the ordinary Civil Law concepts. So there are the devices of executele and bewind, the former comparable to executorship, the latter generally to a spendthrift trust, and sometimes to an ordinary trust to secure future in~ terests. There are trustees acting for bondholders and committees doing the same. There are, furthermore, the devices of the administratie van effecten, often comparable to the voting trust, and of the effectendepot, comparable to the investment trust in its strict trust~form. There is also the transfer of copyrights, com~ monly performed by composers, in order that the transferee may exercise those rights for the benefit of the transferring composer. And finally a device may be mentioned, that is comparable to a common~law assignment for the benefit of creditors ... Zie: Brief accoun

Hartrevalidatie : over het bepalen en voorspellen van herstel

Jaarlijks worden in Nederland ongeveer 26.000 patienten opgenomen in een ziekenhuis wegens een hartinfart, of voor het ondergaan van een hartoperatie. Een derde van deze patienten volgt een hartrevalidatieprogramma. Ret gaat hierbij om poliklinische hartrevalidatie. Weliswaar wordt in bijna aile (Nederlandse) ziekenhuizen tijdens de opname van hartpatienten aandacht besteed aan actieve mobilisatie, reactivering en/of training van de normale dagelijkse activiteiten, maar deze vroege klinische revalidatie-activiteiten worden gerekend tot de standaardzorg van het ziekenhuis voor alle patienten. Daarnaast bestaan echter mogelijkheden om na de klinische fase deel te nemen aan een afzonderlijk programma, dat in Nederland doorgaans poliklinisch plaatsvindt in speciale hartrevalidatiecentra. Dit hoek beperkt zich tot de poliklinische hartrevalidatie, omdat dit een extra interventie is, die iets toevoegt aan de standaardzorg en niet aan alle patienten wordt aangeboden. Naar het oordeel van de Nederlandse Hartstichting komen in beginsel aile hartpatienten voor hartrevalidatie in aanmerking. Ret feit dat zowel binnen als buiten Nederland grate aantallen patienten door behandelend artsen worden doorverwezen naar hartrevalidatiecentra, wettigt het vermoeden dat ook bij vele behandelend artsen de verwachting leeft dat hartrevalidatie herstel bevordert.Many studies on cardiac rehabilitation have preceded the one described in this thesis. However, they have not yet led to the scientific recognition of the value of cardiac rehabilitation. A review of the literature forces us to draw the conclusion that cardiac rehabilitation has reached an impasse. Cardiac rehabilitation programmes have largely been developed on the basis of clinical practise. The programmes therefore differ in nature, form and content and consequently are almost impossible to compare. This situation makes it difficult to draw scientific conclusions on the value of cardia

Understanding human gut diseases at single-cell resolution

Our understanding of gut functioning and pathophysiology has grown considerably in the past decades, and advancing technologies enable us to deepen this understanding. Single-cell RNA sequencing (scRNA-seq) has opened a new realm of cellular diversity and transcriptional variation in the human gut at a high, single-cell resolution. ScRNA-seq has pushed the science of the digestive system forward by characterizing the function of distinct cell types within complex intestinal cellular environments, by illuminating the heterogeneity within specific cell populations, and by identifying novel cell types in the human gut that could contribute to a variety of intestinal diseases. In this review, we highlight recent discoveries made with scRNA-seq that significantly advance our understanding of the human gut both in health and across the spectrum of gut diseases, including inflammatory bowel disease, colorectal carcinoma and celiac disease

Jaw thrust versus the use of a boil-and-bite mandibular advancement device as a screening tool during drug-induced sleep endoscopy

STUDY OBJECTIVES: The objectives of this study were to analyze agreement in degree of obstruction and configuration of the upper airway between jaw thrust and an oral device in situ during drug-induced sleep endoscopy and to evaluate clinical decision making using jaw thrust or a boil-and-bite mandibular advancement device (MAD; the MyTAP). METHODS: This was a single-center prospective cohort study in patients with obstructive sleep apnea who underwent drug-induced sleep endoscopy between January and July 2019. RESULTS: Sixty-three patients were included. Agreement among observations in the supine position for degree of obstruction was 60% (n = 36, κ = 0.41) at the level of the velum, 68.3% (n = 41, κ = 0.35) for oropharynx, 58.3% (n = 35, κ = 0.28) for tongue base, and 56.7% (n = 34, κ = 0.14) for epiglottis; agreement among observations in the lateral position were 81.7% (n = 49, κ = 0.32), 71.7% (n = 43, κ = 0.36), 90.0% (n = 54, κ = 0.23), and 96.7% (n = 58, κ = could not be determined), respectively. In the supine position, agreement for configuration of obstruction at the level of the velum was found in 20 of 29 patients (69.0%, κ = 0.41) and in the lateral position was 100%. Thirty patients would have been prescribed a MAD using jaw thrust and 34 using the boil-and-bite MAD as a screening instrument. The main reason for being labeled as nonsuitable was complete residual retropalatal collapse during jaw thrust. Using the boil-and-bite MAD, this was caused by complete retropalatal or hypopharyngeal collapse. CONCLUSIONS: There is only slight to moderate agreement in degree of obstruction for jaw thrust and a new-generation boil-and-bite MAD during drug-induced sleep endoscopy. Greater improvement of upper airway patency at the hypopharyngeal level was observed during jaw thrust, but this maneuver was less effective in improving upper airway obstruction at the retropalatal level. CITATION: Vonk PE, Uniken Venema JAM, Hoekema A, Ravesloot MJL, van de Velde–Muusers JA, de Vries N. Jaw thrust versus the use of a boil-and-bite mandibular advancement device as a screening tool during drug-induced sleep endoscopy. J Clin Sleep Med. 2020;16(7):1021–1027

Long-term Obstructive Sleep Apnea Therapy; a 10-Year Follow-up of Mandibular Advancement Device and Continuous Positive Airway Pressure

Study Objectives: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder, commonly managed by either continuous positive airway pressure (CPAP) or a mandibular advancement device (MAD). Long-term follow-up and comparison regarding efficacy of these therapies is scarce. In this study the results of treatment, patient adherence, and satisfaction over a 10-year follow-up of these therapies are reported. Methods: This is a longitudinal follow-up study taken from a subset of patients initially enrolled in a randomized controlled clinical trial of 103 patients with OSA (51 and 52 patients randomized for MAD and CPAP, respectively). After a 10-year follow-up period, 14 patients using MAD and 17 patients using CPAP could be evaluated for this longitudinal follow-up study. Data were analyzed at baseline, after 3 months and at 1-, 2-, and 10-year follow-up. All 31 patients with OSA underwent polysomnography and self-reported measurements. Results: Polysomnography results showed a favorable outcome of both therapies at 10-year follow-up. At baseline, included patients in both groups did not significantly differ in apnea-hypopnea index (AHI) values. At 10-year follow-up, both the MAD and CPAP groups showed a significant reduction in AHI. At baseline the mean AHI in the MAD group was 31.7 ± 20.6 events/h whereas in the CPAP group it was 49.2 ± 26.1 events/h. At 10-year follow-up the mean AHI in the MAD group was 9.9 ± 10.3 events/h and in the CPAP group it was 3.4 ± 5.4 events/h. Both therapies resulted in a substantial improvement in self-reported neurobehavioral outcomes at 10-year follow-up. Conclusions: Both CPAP and MAD therapy demonstrate good and stable treatment effects after a 10-year follow-up period. Therefore, when indicated, both therapies are appropriate modalities for the long-term management of OSA