Het rapport 'God met ons ... Over de aard van het schriftgezag' van de Gereformeerde Kerken in Nederland

Dit rapport werd in Nimes aangekondigd. Op de vergadering van de Gereformeerde Oecumenische Synode, aldaar gehouden in juli 1980, vertelde Dr. H. B. Weijland dat in dit rapport een poging gedaan zou worden om op allerlei problemen die met het verstaan aan de Schrift samenhangen, in te gaan. Hij wekte niet de indruk dat met dit rapport alle problemen zouden worden opgelost

Controlling the activity of quorum sensing autoinducers with light

Bacteria use a communication system, called quorum sensing (QS), to organize into communities and synchronize gene expression to promote virulence and secure survival. Here we report on a proof-of-principle for externally interfering with this bacterial communication system, using light. By employing photoswitchable small molecules, we were able to photocontrol the QS-related bioluminescence in an Escherichia coli reporter strain, and the expression of target QS genes and pyocyanin production in Pseudomonas aeruginosa

Serum prolactin as a biomarker for the study of intracerebral dopamine effect in adult patients with phenylketonuria: a cross-sectional monocentric study

BACKGROUND: It has been previously postulated that high phenylalanine (Phe) might disturb intracerebral dopamine production, which is the main regulator of prolactin secretion in the pituitary gland. Previously, various associations between Phe and hyperprolactinemia were revealed in studies performed in phenylketonuria (PKU) children and adolescents. The aim of the present study was to clarify whether any relation between serum phenylalanine and prolactin levels can be found in adult PKU patients. PATIENTS AND METHODS: We conducted a cross-sectional, monocentric study including 158 adult patients (male n = 68, female n = 90) with PKU. All patients were diagnosed during newborn screening and were treated since birth. Serum Phe, tyrosine (Tyr), prolactin (PRL), and thyroid-stimulating hormone (TSH) levels were measured, and Phe/Tyr ratio was calculated. Males and females were analyzed separately because the serum prolactin level is gender-dependent. RESULTS: No significant correlations were found between serum phenylalanine, tyrosine, or the Phe/Tyr ratio and serum prolactin level either in the male or in the female group. CONCLUSIONS: In treated adult PKU patients, the serum prolactin level may not be significantly influenced by Phe or Tyr serum levels

Photoactivatable prodrugs of antimelanoma agent Vemurafenib

In this study, we report on novel photoactivatable caged prodrugs of vemurafenib. This kinase inhibitor was the first approved drug for the personalized treatment of BRAF-mutated melanoma and showed impressive results in clinical studies. However, the occurrence of severe side effects and drug resistance illustrates the urgent need for innovative therapeutic approaches. To conquer these limitations, we implemented photoremovable protecting groups into vemurafenib. In general, this caging concept provides spatial and temporal control over the activation of molecules triggered by ultraviolet light. Thus, higher inhibitor concentrations in tumor tissues might be reached with less systemic effects. Our study describes the first development of caged vemurafenib prodrugs useful as pharmacological tools. We investigated their photochemical characteristics and photoactivation. <i>In vitro</i> evaluation proved the intended loss-of-function and the light-dependent recovery of efficacy in kinase and cellular assays. The reported vemurafenib photo prodrugs represent a powerful biological tool for novel pharmacological approaches in cancer research

Caveolin-1 Influences Vascular Protease Activity and Is a Potential Stabilizing Factor in Human Atherosclerotic Disease

Caveolin-1 (Cav-1) is a regulatory protein of the arterial wall, but its role in human atherosclerosis remains unknown. We have studied the relationships between Cav-1 abundance, atherosclerotic plaque characteristics and clinical manisfestations of atherosclerotic disease.We determined Cav-1 expression by western blotting in atherosclerotic plaques harvested from 378 subjects that underwent carotid endarterectomy. Cav-1 levels were significantly lower in carotid plaques than non-atherosclerotic vascular specimens. Low Cav-1 expression was associated with features of plaque instability such as large lipid core, thrombus formation, macrophage infiltration, high IL-6, IL-8 levels and elevated MMP-9 activity. Clinically, a down-regulation of Cav-1 was observed in plaques obtained from men, patients with a history of myocardial infarction and restenotic lesions. Cav-1 levels above the median were associated with absence of new vascular events within 30 days after surgery [0% vs. 4%] and a trend towards lower incidence of new cardiovascular events during longer follow-up. Consistent with these clinical data, Cav-1 null mice revealed elevated intimal hyperplasia response following arterial injury that was significantly attenuated after MMP inhibition. Recombinant peptides mimicking Cav-1 scaffolding domain (Cavtratin) reduced gelatinase activity in cultured porcine arteries and impaired MMP-9 activity and COX-2 in LPS-challenged macrophages. Administration of Cavtratin strongly impaired flow-induced expansive remodeling in mice.This is the first study that identifies Cav-1 as a novel potential stabilizing factor in human atherosclerosis. Our findings support the hypothesis that local down-regulation of Cav-1 in atherosclerotic lesions contributes to plaque formation and/or instability accelerating the occurrence of adverse clinical outcomes. Therefore, given the large number of patients studied, we believe that Cav-1 may be considered as a novel target in the prevention of human atherosclerotic disease and the loss of Cav-1 may be a novel biomarker of vulnerable plaque with prognostic value

A prediction model for primary aldosteronism when the salt loading test is inconclusive

Objective: To develop a prediction model to confirm or exclude primary aldosteronism (PA) in patients with an inconclusive salt loading test (SLT). Context: Diagnosis in patients with a suspicion of PA can be confirmed using an SLT. In case of inconclusive test results the decision about how to manage the patient is usually based on contextual clinical data. Design: We included a retrospective cohort of 276 patients in the final analysis. Methods: All patients underwent an SLT between 2005 and 2016 in our university medical center. The SLT was inconclusive (post-infusion aldosterone levels 140–280 pmol/L) in 115 patients. An expert panel then used contextual clinical data to diagnose PA in 45 of them. Together with 101 patients with a positive SLT this resulted in a total of 146 patients with PA. A total of 11 variables were used in a multivariable logistic regression analysis. We assessed internal validity by bootstrapping techniques. Results: The following variables were independently associated with PA: more intense potassium supplementation, lower plasma potassium concentration, lower plasma renin concentration before SLT and higher plasma aldosterone concentration after SLT. The resulting prediction model had a sensitivity of 84.4% and a specificity of 94.3% in patients with an inconclusive SLT. The positive and negative predictive values were 90.5 and 90.4%, respectively. Conclusions: We developed a prediction model for the diagnosis of PA in patients with an inconclusive SLT that results in a diagnosis that was in high agreement with that of an expert panel

Factors Associated with High Prevalence of Intestinal Protozoan Infections among Patients in Sana'a City, Yemen

Intestinal protozoan diseases in Yemen are a significant health problem with prevalence ranging from 18% to 27%. The present study is a cross-sectional study aimed at determining the factors associated with the high prevalence of intestinal protozoan infections among patients seeking health care in Sana'a City, the capital of Yemen. (0.4%). Multivariate analysis using forward stepwise logistic regression based on intestinal protozoan infections showed that contact with animals (OR = 1.748, 95% CI = 1.168–2.617) and taking bath less than twice a week (OR = 1.820, 95% CI = 1.192–2.779) were significant risk factors of protozoan infections. infections being most common. Statistical analysis indicated that low personal hygiene and contact with animals were important predictors for intestinal protozoan infections. As highlighted in this study, in order to effectively reduce these infections, a multi-sectoral effort is needed. Preventive measures should include good hygienic practices, good animal husbandry practices, heightened provision of educational health programs, health services in all governorates including rural areas. Furthermore, it is also essential to find radical solutions to the recent water crises in Yemen

Evaluation of National Surgical Practice for Lateral Lymph Nodes in Rectal Cancer in an Untrained Setting

Background: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level. Methods: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either ‘node-picking’ (the removal of an individual LLN) or ‘partial regional node dissection’ (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those undergoing only rectal resection. Results: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7–3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2–2.5, p = 0.874). Conclusion: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.</p

Evidence and gap map of studies assessing the effectiveness of interventions for people with disabilities in low‐and middle‐income countries

Background: There are approximately 1 billion people in the world with some form of disability. This corresponds to approximately 15% of the world's population (World Report on Disability, 2011). The majority of people with disabilities (80%) live in low- and middle-income countries (LMICs), where disability has been shown to disproportionately affect the most disadvantaged sector of the population. Decision makers need to know what works, and what does not, to best invest limited resources aimed at improving the well-being of people with disabilities in LMICs. Systematic reviews and impact evaluations help answer this question. Improving the availability of existing evidence will help stakeholders to draw on current knowledge and to understand where new research investments can guide decision-making on appropriate use of resources. Evidence and gap maps (EGMs) contribute by showing what evidence there is, and supporting the prioritization of global evidence synthesis needs and primary data collection. Objectives: The aim of this EGM is to identify, map and describe existing evidence of effectiveness studies and highlight gaps in evidence base for people with disabilities in LMICs. The map helps identify priority evidence gaps for systematic reviews and impact evaluations. Methods: The EGM included impact evaluation and systematic reviews assessing the effect of interventions for people with disabilities and their families/carers. These interventions were categorized across the five components of community-based rehabilitation matrix; health, education, livelihood, social and empowerment. Included studies looked at outcomes such as, health, education, livelihoods, social inclusion and empowerment, and were published for LMICs from 2000 onwards until January 2018. The searches were conducted between February and March 2018. The EGM is presented as a matrix in which the rows are intervention categories (e.g., health) and subcategories (e.g., rehabilitation) and the column outcome domains (e.g., health) and subdomains (e.g., immunization). Each cell lists the studies for that intervention for those outcomes, with links to the available studies. Included studies were therefore mapped according to intervention and outcomes assessed and additional filters as region, population and study design were also coded. Critical appraisal of included systematic review was done using A Measurement Tool to Assess Systematic Reviews’ rating scale. We also quality-rated the impact evaluation using a quality assessment tool based on various approaches to risk of bias assessment. Results: The map includes 166 studies, of which 59 are systematic reviews and 107 impact evaluation. The included impact evaluation are predominantly quasiexperimental studies (47%). The numbers of studies published each year have increased steadily from the year 2000, with the largest number published in 2017.The studies are unevenly distributed across intervention areas. Health is the most heavily populated area of the map. A total of 118 studies of the 166 studies concern health interventions. Education is next most heavily populated with 40 studies in the education intervention/outcome sector. There are relatively few studies for livelihoods and social, and virtually none for empowerment. The most frequent outcome measures are health-related, including mental health and cognitive development (n = 93), rehabilitation (n = 32), mortality and morbidity (n = 23) and health check-up (n = 15). Very few studies measured access to assistive devices, nutrition and immunization. Over half (n = 49) the impact evaluation come from upper-middle income countries. There are also geographic gaps, most notably for low income countries (n = 9) and lower-middle income countries (n = 34). There is a fair amount of evidence from South Asia (n = 73) and Sub-Saharan Africa (n = 51). There is a significant gap with respect to study quality, especially with respect to impact evaluation. There appears to be a gap between the framing of the research, which is mostly within the medical model and not using the social model of disability. Conclusion: Investing in interventions to improve well-being of people with disabilities will be critical to achieving the 2030 agenda for sustainable development goals. The EGM summarized here provides a starting point for researchers, decision makers and programme managers to access the available research evidence on the effectiveness of interventions for people with disabilities in LMICs in order to guide policy and programme activity, and encourage a more strategic, policy-oriented approach to setting the future research agenda

Photoswitching Using Visible Light: A New Class of Organic Photochromic Molecules

A versatile new class of organic photochromic molecules that offers an unprecedented combination of physical properties including tunable photoswitching using visible light, excellent fatigue resistance, and large polarity changes is described. These unique features offer significant opportunities in diverse fields ranging from biosensors to targeted delivery systems while also allowing non-experts ready synthetic access to these materials