| 1. |
- Legradi, J. B., et al.
(författare)
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An ecotoxicological view on neurotoxicity assessment
- 2018
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Ingår i: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 30
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Forskningsöversikt (refereegranskat)abstract
- The numbers of potential neurotoxicants in the environment are raising and pose a great risk for humans and the environment. Currently neurotoxicity assessment is mostly performed to predict and prevent harm to human populations. Despite all the efforts invested in the last years in developing novel in vitro or in silico test systems, in vivo tests with rodents are still the only accepted test for neurotoxicity risk assessment in Europe. Despite an increasing number of reports of species showing altered behaviour, neurotoxicity assessment for species in the environment is not required and therefore mostly not performed. Considering the increasing numbers of environmental contaminants with potential neurotoxic potential, eco-neurotoxicity should be also considered in risk assessment. In order to do so novel test systems are needed that can cope with species differences within ecosystems. In the field, online-biomonitoring systems using behavioural information could be used to detect neurotoxic effects and effect-directed analyses could be applied to identify the neurotoxicants causing the effect. Additionally, toxic pressure calculations in combination with mixture modelling could use environmental chemical monitoring data to predict adverse effects and prioritize pollutants for laboratory testing. Cheminformatics based on computational toxicological data from in vitro and in vivo studies could help to identify potential neurotoxicants. An array of in vitro assays covering different modes of action could be applied to screen compounds for neurotoxicity. The selection of in vitro assays could be guided by AOPs relevant for eco-neurotoxicity. In order to be able to perform risk assessment for eco-neurotoxicity, methods need to focus on the most sensitive species in an ecosystem. A test battery using species from different trophic levels might be the best approach. To implement eco-neurotoxicity assessment into European risk assessment, cheminformatics and in vitro screening tests could be used as first approach to identify eco-neurotoxic pollutants. In a second step, a small species test battery could be applied to assess the risks of ecosystems.
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| 2. |
- van der Geest, A. M., et al.
(författare)
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Inadequate safety reporting in the publications of randomised clinical trials in irritable bowel syndrome : drug versus probiotic interventions
- 2022
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Ingår i: Beneficial Microbes. - : Wageningen Academic Publishers. - 1876-2883 .- 1876-2891. ; 13:3, s. 195-204
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Forskningsöversikt (refereegranskat)abstract
- Randomised controlled clinical trials (RCTs) offer a unique opportunity to obtain controlled efficacy and safety data to support clinical decisions. However, most RCT reporting has a stronger focus on efficacy rather than safety. This study aimed to identify the safety profile of both probiotic and drug interventions in irritable bowel syndrome (IBS). In connection to this paper, an accompanying paper was published in which a meta-analysis was conducted to evaluate the efficacy of probiotic interventions compared to that of drug interventions in IBS. Together, these two studies provide a first assessment regarding the feasibility to determine a burden to benefit ratio for both probiotic and drug interventions in IBS. RCTs including participants (>18 years old) with IBS and comparing probiotic or drugs interventions with control groups were identified by a systematic search of MEDLINE (January 2015 - Jan 2021). Reported safety profiles in drug studies were completer and more detailed as compared with studies on probiotics. Several inconsistencies in safety reporting were identified between and within drug and probiotic studies, such as: didn't report on safety; only reported adverse reactions (ARs) or adverse events (AEs) with a certain severity; didn't report the total number of AEs; didn't split in the control- or experimental arm; didn't specify AEs; and used different thresholds for 'common' AEs. Hence, it is difficult to compare safety data from drug and probiotic RCTs across and between different studies. On the current approaches to safety reporting, we could not establish an unambiguous safety profile for neither probiotic and drug interventions in IBS. These shortcomings hamper a critical comparison of the burden to benefit ratio for IBS intervention.
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| 3. |
- van der Geest, A. M., et al.
(författare)
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Comparing probiotic and drug interventions in irritable bowel syndrome : a meta-analysis of randomised controlled trials
- 2022
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Ingår i: Beneficial Microbes. - : Wageningen Academic Publishers. - 1876-2883 .- 1876-2891. ; 13:3, s. 183-194
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Forskningsöversikt (refereegranskat)abstract
- Clinical decisions made by health professionals to recommend either drug or probiotic interventions for irritable bowel syndrome (IBS) should be supported by proper knowledge of the efficacy rates of both types of interventions. In this article, we performed a systematic review and meta-analysis to examine the efficacy of both probiotic- and drug interventions in IBS. Medline was searched between January 2015 - January 2021. Randomised controlled trials (RCT) recruiting participants > 18 years old with IBS and examining the effect of probiotics or drugs were eligible for inclusion. The data of the primary outcome, i.e. the persistence of IBS symptoms (dichotomous symptom data), were pooled to obtain a relative risk (RR), with a 95% confidence interval (CI). Secondary outcomes, abdominal pain- and bloating scores (continuous data), were pooled using a standardised mean difference with a 95% CI. The search identified 269 citations of which 32 RCTs were eligible. Our meta-analysis indicated that both probiotic and drug interventions are able to improve the persistence of IBS symptoms (RR 0.60 [0.51; 0.92] versus 0.87 [0.81; 0.92], respectively) and abdominal pain scores (standardised mean difference (SMD) -0.35 [-0.56; -0.14] versus -0.10 [-0.20; 0.00], respectively). However, determining the overall efficacy of both intervention types is inherently complex and such results should be interpreted with care, due to the large diversity of probiotic- and drug types and doses, which is also complicated by variety in IBS subtypes. Hence, as a first step, more large scale randomised double blind placebo-controlled trials focussing on a specific IBS subtype targeted with specific probiotic strains or specific pharmaceutical modalities should be executed, enabling a more proper comparison between trials.
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| 4. |
- Reitsema, Rosanne D., 1994-, et al.
(författare)
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Aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumatica
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) are overlapping inflammatory diseases. Antigen-presenting cells (APCs), including monocytes and dendritic cells (DCs), are main contributors to the immunopathology of GCA and PMR. However, little is known about APC phenotypes in the peripheral blood at the time of GCA/PMR diagnosis.METHODS: APCs among peripheral blood mononuclear cells (PBMCs) of treatment-naive GCA and PMR patients were compared to those in age- and sex-matched healthy controls (HCs) using flow cytometry (n=15 in each group). We identified three monocyte subsets, and three DC subsets: plasmacytoid DCs (pDCs), CD141+ conventional DCs (cDC1) and CD1c+ conventional DCs (cDC2). Each of these subsets was analyzed for expression of pattern recognition receptors (TLR2, TLR4), immune checkpoints (CD86, PDL1, CD40) and activation markers (HLA-DR, CD11c).RESULTS: t-SNE plots revealed a differential clustering of APCs between GCA/PMR and HCs. Further analyses showed shifts in monocyte subsets and a lower proportion of the small population of cDC1 cells in GCA/PMR, whereas cDC2 proportions correlated negatively with CRP (r=-0.52). Classical monocytes of GCA/PMR patients show reduced expression of TLR2, HLA-DR, CD11c, which was in contrast to non-classical monocytes that showed higher marker expression. Additionally, single cell RNA sequencing in GCA patients identified a number of differentially expressed genes related to inflammation and metabolism in APCs.CONCLUSION: Circulating non-classical monocytes display an activated phenotype in GCA/PMR patients at diagnosis, whereas classical monocytes show reduced expression of activation markers. Whether these findings reflect APC migration patterns or the effects of long-term inflammation remains to be investigated.
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