EUREGIO MRSA-net Twente/Munsterland - a Dutch-German cross-border network for the prevention and control of infections caused by methicillin-resistant Staphylococcus aureus

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Translational model of melphalan-induced gut toxicity reveals drug-host-microbe interactions that drive tissue injury and fever

Published: 20 April 2021PURPOSE: Conditioning therapy with high-dose melphalan (HDM) is associated with a high risk of gut toxicity, fever and infections in haematopoietic stem cell transplant (HSCT) recipients. However, validated preclinical models that adequately reflect clinical features of melphalan-induced toxicity are not available. We therefore aimed to develop a novel preclinical model of melphalan-induced toxicity that reflected well-defined clinical dynamics, as well as to identify targetable mechanisms that drive intestinal injury. METHODS: Male Wistar rats were treated with 4-8 mg/kg melphalan intravenously. The primary endpoint was plasma citrulline. Secondary endpoints included survival, weight loss, diarrhea, food/water intake, histopathology, body temperature, microbiota composition (16S sequencing) and bacterial translocation. RESULTS: Melphalan 5 mg/kg caused self-limiting intestinal injury, severe neutropenia and fever while impairing the microbial metabolome, prompting expansion of enteric pathogens. Intestinal inflammation was characterized by infiltration of polymorphic nuclear cells in the acute phases of mucosal injury, driving derangement of intestinal architecture. Ileal atrophy prevented bile acid reabsorption, exacerbating colonic injury via microbiota-dependent mechanisms. CONCLUSION: We developed a novel translational model of melphalan-induced toxicity, which has excellent homology with the well-known clinical features of HDM transplantation. Application of this model will accelerate fundamental and translational study of melphalan-induced toxicity, with the clinical parallels of this model ensuring a greater likelihood of clinical success.H. R. Wardill, C. E. M. de Mooij, A. R. da Silva Ferreira, I. P. van de Peppel, R. Havinga, H. J. M. Harmsen ... et al

Experiences of refugees and asylum seekers in general practice: a qualitative study

Background: There has been much debate regarding the refugee health situation in the UK. However most of the existing literature fails to take account of the opinions of refugees themselves. This study was established to determine the views of asylum seekers and refugees on their overall experiences in primary care and to suggest improvements to their care. Methods: Qualitative study of adult asylum seekers and refugees who had entered the UK in the last 10 years. The study was set in Barnet Refugee Walk in Service, London. 11 Semi structured interviews were conducted and analysed using framework analysis. Results: Access to GPs may be more difficult for failed asylum seekers and those without support from refugee agencies or family. There may be concerns amongst some in the refugee community regarding the access to and confidentiality of professional interpreters. Most participants stated their preference for GPs who offered advice rather than prescriptions. The stigma associated with refugee status in the UK may have led to some refugees altering their help seeking behaviour. Conclusion: The problem of poor access for those with inadequate support may be improved by better education and support for GPs in how to provide for refugees. Primary Care Trusts could also supply information to newly arrived refugees on how to access services. GPs should be aware that, in some situations, professional interpreters may not always be desired and that instead, it may be advisable to reach a consensus as to who should be used as an interpreter. A better doctor-patient experience resulting from improvements in access and communication may help to reduce the stigma associated with refugee status and lead to more appropriate help seeking behaviour. Given the small nature of our investigation, larger studies need to be conducted to confirm and to quantify these results

Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder

Contains fulltext : 167940.pdf (publisher's version ) (Open Access)Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD). In the present meta-analysis, we pooled randomized placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants' age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality. To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114-0.682), P=0.006, random-effects model). As an explanation for significant heterogeneity (I(2)=73.36, P<0.001), meta-regression showed that higher EPA dose (beta=0.00037 (0.00009-0.00065), P=0.009), higher percentage antidepressant users (beta=0.0058 (0.00017-0.01144), P=0.044) and earlier publication year (beta=-0.0735 (-0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed. In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants. Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential long-term biochemical side effects of high-dosed add-on EPA supplementation should be carefully monitored

Comparative prebiotic activity of mixtures of cereal grain polysaccharides

The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan. These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats. Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity. AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios. Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH). Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity. The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet. This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential

Uterine artery embolization versus surgical treatment in patients with symptomatic uterine fibroids: Protocol for a systematic review and meta-analysis of individual participant data.

OBJECTIVE: Uterine fibroids are the most common benign tumours in women of the reproductive age. Symptoms of heavy menstrual bleeding, abdominal discomfort and infertility may seriously affect a woman's quality of life. Uterine artery embolization is a safe and effective alternative treatment to hysterectomy or myomectomy for symptomatic uterine fibroids. Which treatment provides the highest quality of life, least complications, symptom reduction and least chance intervention, has not been established and might depend on strict patient selection. This study aims to identify which specific subgroups benefit most of each treatment by analyzing individual participant data derived from randomized controlled trials of women undergoing embolization or surgical treatment. This study will primarily assess the effectiveness of both treatment groups by evaluating the effect on quality of life of embolization in comparison to surgery on specific patient and fibroid characteristics and the possible need for re-intervention for fibroid-related symptoms. DATA SOURCES: PubMed/MEDLINE, Embase and The Cochrane Library were searched up to August 2020. STUDY ELIGIBILITY CRITERIA: We will collect individual participant data from randomized controlled trials that studied clinical and procedural outcomes of premenopausal women with symptomatic uterine fibroids, who were randomized between uterine artery embolization and surgery. STUDY APPRAISAL AND SYNTHESIS METHODS: Individual participant data from all eligible trials will be sought and analysed according to intention-to-treat principle. Risk of Bias will be done by using version 2 of the Cochrane tool for Risk of Bias in randomized trials. Subgroup analyses to explore the effect of e.g. age, fibroid characteristics and fibroid complaints will be performed, if data is available. This individual patient data meta-analysis will be analysed according to a one-stage model

First measurement of the Gerasimov-Drell-Hearn integral for Hydrogen from 200 to 800 MeV

A direct measurement of the helicity dependence of the total photoabsorption cross section on the proton was carried out at MAMI (Mainz) in the energy range 200 < E_gamma < 800 MeV. The experiment used a 4$\pi$ detection system, a circularly polarized tagged photon beam and a frozen spin target. The contributions to the Gerasimov-Drell-Hearn sum rule and to the forward spin polarizability $\gamma_0$ determined from the data are 226 \pm 5 (stat)\pm 12(sys) \mu b and -187 \pm 8 (stat)\pm 10(sys)10^{-6} fm^4, respectively, for 200 < E_\gamma < 800 MeV.Comment: 6 pages, 3 figures, 3 table