Favourable effects of consuming a Palaeolithic-type diet on characteristics of the metabolic syndrome:a randomized controlled pilot-study

Background: The main goal of this randomized controlled single-blinded pilot study was to study whether, independent of weight loss, a Palaeolithic-type diet alters characteristics of the metabolic syndrome. Next we searched for outcome variables that might become favourably influenced by a Paleolithic-type diet and may provide new insights in the pathophysiological mechanisms underlying the metabolic syndrome. In addition, more information on feasibility and designing an innovative dietary research program on the basis of a Palaeolithic-type diet was obtained.Methods: Thirty-four subjects, with at least two characteristics of the metabolic syndrome, were randomized to a two weeks Palaeolithic-type diet (n = 18) or an isoenergetic healthy reference diet, based on the guidelines of the Dutch Health Council (n = 14). Thirty-two subjects completed the study. Measures were taken to keep bodyweight stable. As primary outcomes oral glucose tolerance and characteristics of the metabolic syndrome (abdominal circumference, blood pressure, glucose, lipids) were measured. Secondary outcomes were intestinal permeability, inflammation and salivary cortisol. Data were collected at baseline and after the intervention.Results: Subjects were 53.5 (SD9.7) year old men (n = 9) and women (n = 25) with mean BMI of 31.8 (SD5.7) kg/m(2). The Palaeolithic-type diet resulted in lower systolic blood pressure (-9.1 mmHg; P = 0.015), diastolic blood pressure (-5.2 mmHg; P = 0.038), total cholesterol (-0.52 mmol/l; P = 0.037), triglycerides (-0.89 mmol/l; P = 0.001) and higher HDL-cholesterol (+0.15 mmol/l; P = 0.013), compared to reference. The number of characteristics of the metabolic syndrome decreased with 1.07 (P = 0.010) upon the Palaeolithic-type diet, compared to reference. Despite efforts to keep bodyweight stable, it decreased in the Palaeolithic group compared to reference (-1.32 kg; P = 0.012). However, favourable effects remained after post-hoc adjustments for this unintended weight loss. No changes were observed for intestinal permeability, inflammation and salivary cortisol.Conclusions: We conclude that consuming a Palaeolithic-type diet for two weeks improved several cardiovascular risk factors compared to a healthy reference diet in subjects with the metabolic syndrome.</p

Rapid in vitro generation of bona fide exhausted CD8+ T cells is accompanied by Tcf7 promotor methylation

Exhaustion is a dysfunctional state of cytotoxic CD8+ T cells (CTL) observed in chronic infection and cancer. Current in vivo models of CTL exhaustion using chronic viral infections or cancer yield very few exhausted CTL, limiting the analysis that can be done on these cells. Establishing an in vitro system that rapidly induces CTL exhaustion would therefore greatly facilitate the study of this phenotype, identify the truly exhaustion-associated changes and allow the testing of novel approaches to reverse or prevent exhaustion. Here we show that repeat stimulation of purified TCR transgenic OT-I CTL with their specific peptide induces all the functional (reduced cytokine production and polyfunctionality, decreased in vivo expansion capacity) and phenotypic (increased inhibitory receptors expression and transcription factor changes) characteristics of exhaustion. Importantly, in vitro exhausted cells shared the transcriptomic characteristics of the gold standard of exhaustion, CTL from LCMV cl13 infections. Gene expression of both in vitro and in vivo exhausted CTL was distinct from T cells anergy. Using this system, we show that Tcf7 promoter DNA methylation contributes to TCF1 downregulation in exhausted CTL. Thus this novel in vitro system can be used to identify genes and signaling pathways involved in exhaustion and will facilitate the screening of reagents that prevent/reverse CTL exhaustion

Citrus/Cydonia comp. Subcutaneous Injections Versus Nasal Spray for Seasonal Allergic Rhinitis: a Randomized Controlled Trial on Efficacy and Safety

Background. Clinical experiences in vitro and clinical studies have demonstrated the curative potency and safety of Citrus/Cydonia compositum in seasonal allergic rhinitis treatment. Objectives. To compare the efficacy and safety of two routes of administration (nasal spray versus subcutaneous injections). Methodology: Design. a national, randomised, comparative clinical trial with two parallel groups. Participants. 23 patients fulfilled the study requirements. Intervention. after a one- or two-week wash-out period, 23 patients were randomized, to a 6-week treatment period. Outcomes. immunological and symptom severity changes and safety. Immunologic outcome assessments were blinded to group assignment. 23 patients were randomized and from 22/23 patients (11 in each group) blood samples were analyzed before and after treatment. Conclusion. Both routes of administration demonstrate immunological and clinical effects, with larger inflammatory and innate immunological effects of the nasal spray route and larger allergen-specific clinical effects of the subcutaneous route, and are safe

Development of an evidence-based decision aid on complementary and alternative medicine (CAM) and pain for parents of children with cancer

Purpose: To develop an evidence-based decision aid for parents of children with cancer and to help guide them in the use ofcomplementary and alternative medicine (CAM) for cancer care. Methods: This study had a mixed research design. The needs of parents were investigated by survey and focus group. Asystematic review and meta-analysis were performed on the effectiveness of CAM using Grading of RecommendationsAssessment, Development and Evaluation (GRADE). Clinical experts were interviewed and a decision aid on CAM treatmentfor pain was developed. Results: Parents emphasized the importance of reliable information on CAM, focusing primarily on communication and a broadspectrum of complaints related to cancer treatment. The decision aid on CAM for pain included five modalities based on 11randomized control trials (RCTs): hypnotherapy, mind-body techniques, massage, healing touch, and music therapy. Metaanalysis could be performed on hypnotherapy, which significantly reduced cancer-related procedural pain compared withstandard care (MD, − 1.37; 95% CI, − 1.60, − 1.15; P &lt; 0.00001) and attention control (MD, − 1.13; 95% CI, − 1.34, − 0.94;P &lt; 0.00001), and massage, demonstrating no effect on pain compared with standard care (MD, − 0.77; 95% CI, − 1.82, 0.28;P = 0.15). Research evidence and supplementary information from clinical practice and patient were incorporated in a websitebased decision aid. Conclusions: An evidence-based decision aid was developed to support parents of children with cancer in making decisions aboutCAM for pain management. Next steps will be to expand the website to include additional childhood cancer-related complaintsand to evaluate its use in practiceThis article is distributed under the terms of the CreativeCommons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)</p

Rapid in vitro generation of bona fide exhausted CD8+ T cells is accompanied by Tcf7 promotor methylation

Exhaustion is a dysfunctional state of cytotoxic CD8+ T cells (CTL) observed in chronic infection and cancer. Current in vivo models of CTL exhaustion using chronic viral infections or cancer yield very few exhausted CTL, limiting the analysis that can be done on these cells. Establishing an in vitro system that rapidly induces CTL exhaustion would therefore greatly facilitate the study of this phenotype, identify the truly exhaustion-associated changes and allow the testing of novel approaches to reverse or prevent exhaustion. Here we show that repeat stimulation of purified TCR transgenic OT-I CTL with their specific peptide induces all the functional (reduced cytokine production and polyfunctionality, decreased in vivo expansion capacity) and phenotypic (increased inhibitory receptors expression and transcription factor changes) characteristics of exhaustion. Importantly, in vitro exhausted cells shared the transcriptomic characteristics of the gold standard of exhaustion, CTL from LCMV cl13 infections. Gene expression of both in vitro and in vivo exhausted CTL was distinct from T cells anergy. Using this system, we show that Tcf7 promoter DNA methylation contributes to TCF1 downregulation in exhausted CTL. Thus this novel in vitro system can be used to identify genes and signaling pathways involved in exhaustion and will facilitate the screening of reagents that prevent/reverse CTL exhaustion

Europees Refentiekader voor Talen : Gebarentalen

Het onderliggende document is een overzicht van het Europees Referentiekader (ERK) zoals aangepast voor gebarentalen. Het bevat een kort overzicht van het ERK met een aantal punten waar specifiek aandacht aan besteed is zodat de richtlijnen van het RK (ook) van toepassing zijn op het leren van gebarentalen als tweede taal en het meten van de gebarentaalvaardigheden. Voorts worden descriptoren uitgebreid beschreven, waarbij het vaak letterlijke teksten van de Nederlandse versie van de Nederlandse Taalunie (2008) zijn overgenomen en/of aangepast (met toestemming). Bij het aanpassen is tevens gebruik gemaakt van een Ierse versie van het ERK voor gebarentalen (Leeson & Byrne-Dunne, 200

Cardiovascular risk management in rheumatoid arthritis patients still suboptimal: the Implementation of Cardiovascular Risk Management in Rheumatoid Arthritis project

To assess the 10-year cardiovascular (CV) risk score and to identify treatment and undertreatment of CV risk factors in patients with established RA. Demographics, CV risk factors and prevalence of cardiovascular disease (CVD) were assessed by questionnaire. To calculate the 10-year CV risk score according to the Dutch CV risk management guideline, systolic blood pressure was measured and cholesterol levels were determined from fasting blood samples. Patients were categorized into four groups: indication for treatment but not treated; inadequately treated, so not meeting goals (systolic blood pressure ⩽140 mmHg and/or low-density lipoprotein ⩽2.5 mmol/l); adequately treated; or no treatment necessary. A total of 720 consecutive RA patients were included, 375 from Reade and 345 from the Antonius Hospital. The mean age of patients was 59 years (s.d. 12) and 73% were female. Seventeen per cent of the patients had a low 10-year CV risk ( <10%), 21% had an intermediate risk (10-19%), 53% a high risk (⩾20%) and 9% had CVD. In total, 69% had an indication for preventive treatment (cholesterol-lowering or antihypertensive drugs). Of those, 42% received inadequate treatment and 40% received no treatment at all. Optimal CV risk management remains a major challenge and better awareness and management are urgently needed to reduce the high risk of CVD in the RA populatio