The aim of our work was to assess the pollution-induced community tolerance (PICT) of isopod gut microbiota and pollution-induced isopod population tolerance (PIPT). Animals collected from a ...chronically Hg polluted and an unpolluted location were exposed for 14 days to 10
μg Hg/g dry food under laboratory conditions. The lysosomal membrane stability, hepatopancreas epithelium thickness, feeding activity and animal bacterial gut microbiota composition were determined. The results confirm the hypothesis that the response to short-term Hg exposure differs for animals from the Hg polluted and the unpolluted field locations. The animals and their gut microbiota from the Hg polluted location were less affected by Hg in a short-term feeding experiment than those from the unpolluted environment. We discuss the pollution-induced population tolerance of isopods and their gut microbiota as a measure of effects of long-term environmental pollution. The ecological consequences of such phenomena are also discussed.
Isopods (
Porcellio scaber) as well as their bacterial gut community from a mercury-polluted site are mercury tolerant.
Summary
The FIB/SEM system was satisfactorily used for scanning ion (SIM) and scanning electron microscopy (SEM) of gland epithelial cells of a terrestrial isopod Porcellio scaber (Isopoda, ...Crustacea). The interior of cells was exposed by site‐specific in situ focused ion beam (FIB) milling. Scanning ion (SI) imaging was an adequate substitution for scanning electron (SE) imaging when charging rendered SE imaging impossible. No significant differences in resolution between the SI and SE images were observed. The contrast on both the SI and SE images is a topographic. The consequences of SI imaging are, among others, introduction of Ga+ ions on/into the samples and destruction of the imaged surface. These two characteristics of SI imaging can be used advantageously. Introduction of Ga+ ions onto the specimen neutralizes the charge effect in the subsequent SE imaging. In addition, the destructive nature of SI imaging can be used as a tool for the gradual removal of the exposed layer of the imaged surface, uncovering the structures lying beneath. Alternative SEM and SIM in combination with site‐specific in situ FIB sample sectioning made it possible to image the submicrometre structures of gland epithelium cells with reproducibility, repeatability and in the same range of magnifications as in transmission electron microscopy (TEM). At the present state of technology, ultrastructural elements imaged by the FIB/SEM system cannot be directly identified by comparison with TEM images.
Abstract
Background
Background: Subcutaneous (SC) formulation of vedolizumab (VDZ), a gut selective integrin antagonist used for treatment of inflammatory bowel disease (IBD), has proven effective ...and safe in clinical trials after intravenous (IV) induction. However, it is not clear if patients can be effectively switched from IV maintenance treatment to SC. We aimed to assess real-world efficacy of switch from IV to SC formulation and to investigate if baseline maintenance regimen (every 8 weeks (q8) versus every 4 weeks(q4)) impacts outcome after switch.
Methods
Methods: In this observational study at a tertiary referral centre, we enrolled 126
prospectively followed consecutive adult patients with IBD who were switched to SC VDZ maintenance treatment. We included patients after IV induction (2 or 3 infusions) and patients who switched from IV maintenance treatment q8 and q4. SC VDZ dosing was 108 mg every 2 weeks regardless of the previous IV regimen. Clinical (Harvey Bradshaw index (HBI) for Crohn’s disease (CD) and partial Mayo score (pMayo) for ulcerative colitis (UC)) and biochemical disease activity (CRP, fecal calprotectin (FC)) were assessed at the time of switch and at first and second follow-up. HBI<5 and pMayo<2 were considered clinical remission. CRP <5mg/L and FC<150mg/kg were considered biomarker remission.
Results
Results: In total 126 patients (40% CD, 60% UC) were switched to SC vedolizumab. Demographics and baseline characteristics are presented in Table 1. Median time to 1st follow up (FU) was 14,5 weeks (IQR 12-26) and median time to 2nd FU was 40 (IQR 36-52) weeks. From all patients, 8/126 (6%) discontinued SC VDZ treatment, 5 of them due to endoscopically active disease (2 in IV induction group, 3 in q4 group), 1 had dysplasia and required surgery (IV induction group), two others (both q8 group) discontinued on their wish. In patients who continued SC treatment clinical and biomarker remission appears to be maintained at 1st and 2nd FU. Clinical and biomarker outcomes are presented in Table 1. Vedolizumab concentrations were 16.9, 24.6 and 13.0 at baseline, 27.0, 25.3 and 25.2 at 1st FU and 25.5, 34.6 and 22.1 at 2nd FU in the q8, q4 and IV induction group, respectively.
Conclusion
Conclusion: The results of this real-world study suggest maintenance of clinical and biomarker remission in patients switched from IV to SC vedolizumab. Baseline vedolizumab dosing regimen (every 4 weeks versus every 8 weeks) did not have an impact on outcomes.
Abstract
Background
The expanding therapeutic armamentarium for inflammatory bowel disease (IBD) has led to uncertainty about the optimal first-line biological therapy for a given patient. Given the ...paucity of dedicated head-to-head trials, treatment decisions can be supported by network meta-analyses or real-world data. Our aim was to assess the drug survival of first-line biologics by drug class (anti-tumour necrosis factor TNF agents, anti-integrin, anti-interleukin IL-12/23) and identify potential predictors for prolonged drug survival in our cohort of IBD patients, supported by the United Registries for Clinical Assessment and Research (UR-CARE).
Methods
We prospectively included all adult patients with IBD treated with biological drugs and at least one follow-up visit between October 2021 and August 2022 at our tertiary referral centre. Patient data were collected retrospectively from records and included demographics, disease characteristics and drug survival. Data were collected in UR-CARE with data lock on August 1, 2022. Cox regression was used to assess the association of patient and disease characteristics with drug survival of first-line biologic drugs by drug class.
Results
We included 1047 adult patients with IBD (644 Crohn’s disease CD, 403 ulcerative colitis UC) (Table 1). Among TNF antagonists, adalimumab was most frequently used in CD (280/644, 43.5%; infliximab: 241/644, 37.4%), infliximab was most frequently used in UC (169/403, 41.9%; adalimumab: 55/403, 13.6%; golimumab: 52/403, 12.9%). Unadjusted median drug survival of the first-line biologic did not differ by medication class in CD, but was significantly longer for vedolizumab than for anti-TNF agents in UC (hazard ratio HR for discontinuation 0.585, 95% confidence interval CI 0.41–0.84; P = 0.003) (Table 2). Disease duration and extent were not associated with drug survival. In CD, isolated ileal disease was associated with longer drug survival (HR 0.83, 95% CI 0.70–0.99; P = 0.04). Findings for both CD and UC were consistent in a sensitivity analysis of patients (CD 228, UC 202) started on biologics after January 1, 2019 when all three drug classes could be prescribed first line without limitations.
Conclusion
In our cohort of 1047 patients with IBD, the drug survival of first-line biologics was comparable regardless of drug class in CD. In UC, first-line vedolizumab was associated with longer drug survival. Disease location and duration did not impact drug survival.
The aim of this paper is to provide an insight into the past, current and future state of education in toxicology. Curricula in toxicology and environmental sciences at some European Universities are ...presented and discussed in the light of the 1999 Bologna reform. One of the key points in the Bologna reform is establishing a European Credit Transfer System (ECTS). An ECTS credit should reflect the expected learning outcomes of a student and should also be prospective of the value of lifelong learning. The Bologna reform encourages cooperation among institutions of higher education, recognition of variety of types of formal and informal education, implementation of lifelong education, joint programs and mobility. The other important point of Bologna reform is introduction of a new Master's level curricula for professional specialization which should be adapted to the specific skills demanded by the society. Such Master's level with competence based curriculum is a turning point in organizing toxicological education, which is necessary for the development of the profession. In addition, promotion of European cooperation and quality assurance within higher education could significantly benefit to toxicological education. The new Bologna education scheme appears to be suitable to direct toxicology toward a modern interdisciplinary profession capable of dealing with present and future challenges.
Significant hyperaccumulation of Zn, Cd and Pb in field samples of
Thlaspi praecox Wulf. collected from a heavy metal polluted area in Slovenia was found, with maximal shoot concentrations of 14 590
...mg
kg
−1 Zn, 5960
mg
kg
−1 Cd and 3500
mg
kg
−1 Pb. Shoot/root ratios of 9.6 for Zn and 5.6 for Cd show that the metals were preferentially transported to the shoots. Shoot bioaccumulation factors exceeded total soil Cd levels 75-fold and total soil Zn levels 20-fold, further supporting the hyperaccumulation of Cd and Zn. Eighty percent of Pb was retained in roots, thus indicating exclusion as a tolerance strategy for Pb. Low level colonisation with arbuscular mycorrhizal fungi (AMF) of a Paris type was observed at the polluted site, whereas at the non-polluted site Arum type colonisation was more common. To our knowledge this is the first report of Cd hyperaccumulation and AMF colonisation in metal hyperaccumulating
T. praecox.
Thlaspi praecox Wulf. (Brassicaceae) is a newly discovered Cd, Zn and Pb hyperaccumulator able to form symbiosis with arbuscular mycorrhizal fungi.
Developing safe and sustainable nanomaterials-based solutions to current global challenges including clean energy, sustainable food production and water security requires access to high quality data ...and appropriate analysis and modelling approaches. Achieving these challenges requires increased re-use of research data to accelerate progress and support development of new materials that are safe and sustainable for energy capture and storage, nano-agriculture and environmental remediation. The principles of Findability, Accessibility, Interoperability and Reusability (FAIR) provide a roadmap to enhanced data sharing and re-use, but require consensus within the nanosafety community on metadata, ontologies and persistent identifiers (among other things) and guidance to support implementation and achieve machine-readability. Here, we highlight the main focus of the AdvancedNano GO FAIR Implementation Network in supporting the nanosafety community with implementation of FAIR to maximize data-driven safe and sustainable application of nano- and advanced materials.
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•Environmental and human health safety assessment of nano- and advanced materials (NM and AdMa) is a necessity today to avoid devastating adverse effects from nanotechnology.•Safety assessment builds on data in findable, accessible, interoperable, and reusable (FAIR) formats.•The field of nanosafety has recently initiated implementation of the FAIR principles, however, clear rules for sustainable implementation and for active promotion of data reuse are still lacking. Ground-breaking steps need to be taken, especially in the areas of new approaches for hazard and risk assessment, including development and validation of machine-driven modelling approaches.•The AdvancedNano GO FAIR Implementation Network was launched to cover these needs, involving key players such as data generators, database developers, data(base) users and regulators/policy makers, to facilitate FAIRification of nanosafety data.•Overall, the network is a central component in the path towards a safe and sustainable future, built on transparent and effective data-driven risk assessment of NM and AdMa.
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