Filaggrin loss-of-function mutations and atopic dermatitis as risk factors for hand eczema in apprentice nurses:part II of a prospective cohort study

BACKGROUND/OBJECTIVES: Environmental exposure and personal susceptibility both contribute to the development of hand eczema. In this study, we investigated the effect of loss-of-function mutations in the filaggrin gene (FLG), atopic dermatitis and wet work exposure on the development of hand eczema in apprentice nurses. METHODS: Dutch apprentice nurses were genotyped for the four most common FLG mutations; atopic dermatitis and hand eczema history were assessed by questionnaire. Exposure and hand eczema during traineeships were assessed with diary cards. RESULTS: The prevalence of hand eczema during traineeships was higher among subjects with a history of hand eczema reported at inclusion. Hand washing during traineeships and at home increased the risk of hand eczema. After adjustment for the effects of exposure and FLG mutations, an odds ratio of 2.5 (90% confidence interval 1.7–3.7) was found for a history of atopic dermatitis. In this study, an increased risk of hand eczema conferred by FLG mutations could not be shown, but subjects with concomitant FLG mutations and atopic dermatitis showed the highest risk of hand eczema during traineeships. CONCLUSION: A history of atopic dermatitis, a history of hand eczema and wet work exposure were the most important factors increasing the risk of hand eczema during traineeships

Transcription-coupled and global genome repair differentially influence UV-B-induced acute skin effects and syste

Exposure to UV-B radiation impairs immune responses in mammals by inhibiting especially Th1-mediated contact hypersensitivity and delayed-type hypersensitivity. Immunomodulation is not restricted to the exposed skin, but is also observed at distant sites, indicating the existence of mediating factors such as products from exposed skin cells or photoactivated factors present in the superficial layers. DNA damage appears to play a key role, because enhanced nucleotide excision repair (NER) strongly counteracts immunosuppression. To determine the effects of the type and genomic location of UV-induced DNA damage on immunosuppression and acute skin reactions (edema and erythema) four congenic mouse strains carrying different defects in NER were compared: CSB and XPC mice lacking transcription-coupled or global genome NER, respectively, as well as XPA and TTD/XPD mice carrying complete or partial defects in both NER subpathways, respectively. The major conclusions are that 1) transcription-coupled DNA repair is the dominant determinant in protection against acute skin effects; 2) systemic immunomodulation is only affected when both NER subpathways are compromised; and 3) sunburn is not related to UV-B-induced immunosuppression

Technology and Society in Equilibrium:

This sector portrait of the design engineering sciences describes the common denominator of the various design disciplines in the Netherlands. In a future sector plan, the above investment areas will be further explored and purposefully developed. The implementation of technological innovations aligned to societal issues encompasses a design challenge. This increasingly demands science-based design methodologies. The broad Dutch design landscape can fulfil the role of connector well in this regard. In order to optimally strengthen this bridging function, three areas for further investment have been identified: Research More research and research funding are needed to meet the design challenges posed by Dutch societal missions, as well as for the further development of Key Enabling Methodologies (KEMs) as the basis for effective design. Educational Capacity Expanded teaching capacity and further development of design-driven didactics are needed to meet the growing demand for designers, This demand stems from the emerging need for design approaches in new research programmes within Horizon Europe and the Dutch Research Council (NWO). Access to Technology Continuous access to the rapidly evolving technological disciplines must be guaranteed for professionals who can both understand the technology and meet the investigative design challenge

A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals

Background: The decision to attempt or refrain from resuscitation is preferably based on prognostic factors for outcome and subsequently communicated with patients. Both patients and physicians consider good communication important, however little is known about patient involvement in and understanding of cardiopulmonary resuscitation (CPR) directives. Aim: To determine the prevalence of Do No

Ranking of Fuzzy Similar Faces Using Relevance Matrix and Aggregation Operators

AbstractIn perception based imaging, Sketching With Words (SWW) is a well-established methodology in which the objects of computation are fuzzy geometric objects (f-objects).The problem of facial imaging of criminal on the basis of onlooker statement is not lack of method and measures but the modeling of onlooker(s) mind set. Because the onlooker has to give statements about different human face parts like forehead, eyes, nose, and chin etc.The concept of fuzzy similarity (f-similarity) and proper aggregation of components of face may provide more flexibility to onlooker(s). In proposed work onlooker(s) statement is recorded. Thereafter it is compared with existing statements. The f-similarity with different faces in database is estimated by using ‘as many as possible’ linguistic quantifier. Three types of constraints over size of parts of face ‘small’, ‘medium’, and ‘large’ are considered. Possibilistic constraints with linguistic hedges and negation operator like ‘very long’, ‘not long’, ‘not very long’ etc. are used. Moreover we have generated ranking of alike faces in decreasing order by using the concepts of f-similarity and relevance matrix

Fluid hydration to prevent post-ERCP pancreatitis in average- to high-risk patients receiving prophylactic rectal NSAIDs (FLUYT trial): Study protocol for a randomized controlled trial

Background: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP and may run a severe course. Evidence suggests that vigorous periprocedural hydration can prevent PEP, but studies to date have significant methodological drawbacks. Importantly, evidence for its added value in patients already receiving prophylactic rectal non-steroidal anti-inflammatory drugs (NSAIDs) is lacking and the cost-effectiveness of the approach has not been investigated. We hypothesize that combination therapy of rectal NSAIDs and periprocedural hydration would significantly lower the incidence of post-ERCP pancreatitis compared to rectal NSAIDs alone in moderate- to high-risk patients undergoing ERCP. Methods: The FLUYT trial is a multicenter, parallel group, open label, superiority randomized controlled trial. A total of 826 moderate- to high-risk patients undergoing ERCP that receive prophylactic rectal NSAIDs will be randomized to a control group (no fluids or normal saline with a maximum of 1.5 mL/kg/h and 3 L/24 h) or intervention group (lactated Ringer's solution with 20 mL/kg over 60 min at start of ERCP, followed by 3 mL/kg/h for 8 h thereafter). The primary endpoint is the incidence of post-ERCP pancreatitis. Secondary endpoints include PEP severity, hydration-related complications, and cost-effectiveness. Discussion: The FLUYT trial design, including hydration schedule, fluid type, and sample size, maximize its power of identifying a potential difference in post-ERCP pancreatitis incidence in patients receiving prophylactic rectal NSAIDs

Impact of the lockdown on acute stroke treatments during the first surge of the COVID-19 outbreak in the Netherlands

INTRODUCTION: We investigated the impact of the Corona Virus Disease 2019 (COVID-19) pandemic and the resulting lockdown on reperfusion treatments and door-to-treatment times during the first surge in Dutch comprehensive stroke centers. Furthermore, we studied the association between COVID-19-status and treatment times. METHODS: We included all patients receiving reperfusion treatment in 17 Dutch stroke centers from May 11th, 2017, until May 11th, 2020. We collected baseline characteristics, National Institutes of Health Stroke Scale (NIHSS) at admission, onset-to-door time (ODT), door-to-needle time (DNT), door-to-groin time (DGT) and COVID-19-status at admission. Parameters during the lockdown (March 15th, 2020 until May 11th, 2020) were compared with those in the same period in 2019, and between groups stratified by COVID-19-status. We used nationwide data and extrapolated our findings to the increasing trend of EVT numbers since May 2017. RESULTS: A decline of 14% was seen in reperfusion treatments during lockdown, with a decline in both IVT and EVT delivery. DGT increased by 12 min (50 to 62 min, p-value of < 0.001). Furthermore, median NIHSS-scores were higher in COVID-19 - suspected or positive patients (7 to 11, p-value of 0.004), door-to-treatment times did not differ significantly when stratified for COVID-19-status. CONCLUSIONS: During the first surge of the COVID-19 pandemic, a decline in acute reperfusion treatments and a delay in DGT was seen, which indicates a target for attention. It also appeared that COVID-19-positive or -suspected patients had more severe neurologic symptoms, whereas their EVT-workflow was not affected. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12883-021-02539-4

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus