| 1. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 2. |
- Bry, Kristina, 1953, et al.
(författare)
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Communication skills training enhances nurses' ability to respond with empathy to parents' emotions in a neonatal intensive care unit
- 2016
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 105:4, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- AimWe quantitatively analysed the effect of a course in communication on the content of nurse-parent encounters and the ability of nurses to respond to the empathic needs of parents in a level III neonatal intensive care unit. MethodsWe evaluated 36 and 45 nurse-parent encounters audio recorded before and after 13 neonatal nurses attended a communication course. The number of empathic opportunities, the nurses' responses to these and the ways they involved parents in their infants' care were studied. ResultsBoth before and after the course, the nurses talked more than the parents during the conversations. This nurse-centredness decreased after the course. The use of empathic or exploring responses to empathic opportunities increased from 19.9 9.0% to 53.8 +/- 8.9% (p = 0.027), whereas ignoring the feelings of the parents or giving inadequate advice decreased from 63.0 +/- 10.0% to 27.5 +/- 8.4% (p = 0.043) after the course. Use of statements expressing caring for the parents and encouragement for parents to participate in the care of their infant increased after the course (p = 0.0034 and p = 0.043, respectively). The nurses felt the course was very useful for their profession. ConclusionA course in communication techniques improved nurses' ability to respond to parents' feelings with empathy.
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| 3. |
- Cappellini, Francesca, et al.
(författare)
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Mechanistic insight into reactivity and (geno)toxicity of well-characterized nanoparticles of cobalt metal and oxides
- 2018
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Ingår i: Nanotoxicology. - : Taylor & Francis. - 1743-5390 .- 1743-5404. ; 12:6, s. 602-620
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Tidskriftsartikel (refereegranskat)abstract
- An increasing use of cobalt (Co)-based nanoparticles (NPs) in different applications and exposures at occupational settings triggers the need for toxicity assessment. Improved understanding regarding the physiochemical characteristics of Co metal NPs and different oxides in combination with assessment of toxicity and mechanisms may facilitate decisions for grouping during risk assessment. The aim of this study was to gain mechanistic insights in the correlation between NP reactivity and toxicity of three different Co-based NPs (Co, CoO, and Co3O4) by using various tools for characterization, traditional toxicity assays, as well as six reporter cell lines (ToxTracker) for rapid detection of signaling pathways of relevance for carcinogenicity. The results showed cellular uptake of all NPs in lung cells and induction of DNA strand breaks and oxidative damage (comet assay) by Co and CoO NPs. In-depth studies on the ROS generation showed high reactivity of Co, lower for CoO, and no reactivity of Co3O4 NPs. The reactivity depended on the corrosion and transformation/dissolution properties of the particles and the media highlighting the role of the surface oxide and metal speciation as also confirmed by in silico modeling. By using ToxTracker, Co NPs were shown to be highly cytotoxic and induced reporters related to oxidative stress (Nrf2 signaling) and DNA strand breaks. Similar effects were observed for CoO NPs but at higher concentrations, whereas the Co3O4 NPs were inactive at all concentrations tested. In conclusion, our study suggests that Co and CoO NPs, but not Co3O4, may be grouped together for risk assessment.
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| 4. |
- Di Bucchianico, Sebastiano, et al.
(författare)
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Calcium-dependent cyto- and genotoxicity of nickel metal and nickel oxide nanoparticles in human lung cells
- 2018
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Ingår i: Particle and Fibre Toxicology. - : BMC. - 1743-8977. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genotoxicity is an important toxicological endpoint due to the link to diseases such as cancer. Therefore, an increased understanding regarding genotoxicity and underlying mechanisms is needed for assessing the risk with exposure to nanoparticles (NPs). The aim of this study was to perform an in-depth investigation regarding the genotoxicity of well-characterized Ni and NiO NPs in human bronchial epithelial BEAS-2B cells and to discern possible mechanisms. Comparisons were made with NiCl2 in order to elucidate effects of ionic Ni. Methods: BEAS-2B cells were exposed to Ni and NiO NPs, as well as NiCl2, and uptake and cellular dose were investigated by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS). The NPs were characterized in terms of surface composition (X-ray photoelectron spectroscopy), agglomeration (photon cross correlation spectroscopy) and nickel release in cell medium (ICP-MS). Cell death (necrosis/apoptosis) was investigated by Annexin VFITC/PI staining and genotoxicity by cytokinesis-block micronucleus (cytome) assay (OECD 487), chromosomal aberration (OECD 473) and comet assay. The involvement of intracellular reactive oxygen species (ROS) and calcium was explored using the fluorescent probes, DCFH-DA and Fluo-4. Results: NPs were efficiently taken up by the BEAS-2B cells. In contrast, no or minor uptake was observed for ionic Ni from NiCl2. Despite differences in uptake, all exposures (NiO, Ni NPs and NiCl2) caused chromosomal damage. Furthermore, NiO NPs were most potent in causing DNA strand breaks and generating intracellular ROS. An increase in intracellular calcium was observed and modulation of intracellular calcium by using inhibitors and chelators clearly prevented the chromosomal damage. Chelation of iron also protected against induced damage, particularly for NiO and NiCl2. Conclusions: This study has revealed chromosomal damage by Ni and NiO NPs as well as Ni ionic species and provides novel evidence for a calcium-dependent mechanism of cyto- and genotoxicity.
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| 5. |
- Gliga, Anda R., et al.
(författare)
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Cerium oxide nanoparticles inhibit differentiation of neural stem cells
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Cerium oxide nanoparticles (nanoceria) display antioxidant properties and have shown cytoprotective effects both in vitro and in vivo. Here, we explored the effects of nanoceria on neural progenitor cells using the C17.2 murine cell line as a model. First, we assessed the effects of nanoceria versus samarium (Sm) doped nanoceria on cell viability in the presence of the prooxidant, DMNQ. Both particles were taken up by cells and nanoceria, but not Sm-doped nanoceria, elicited a temporary cytoprotective effect upon exposure to DMNQ. Next, we employed RNA sequencing to explore the transcriptional responses induced by nanoceria or Sm-doped nanoceria during neuronal differentiation. Detailed computational analyses showed that nanoceria altered pathways and networks relevant for neuronal development, leading us to hypothesize that nanoceria inhibits neuronal differentiation, and that nanoceria and Sm-doped nanoceria both interfere with cytoskeletal organization. We confirmed that nanoceria reduced neuron specific beta 3-tubulin expression, a marker of neuronal differentiation, and GFAP, a neuroglial marker. Furthermore, using super-resolution microscopy approaches, we could show that both particles interfered with cytoskeletal organization and altered the structure of neural growth cones. Taken together, these results reveal that nanoceria may impact on neuronal differentiation, suggesting that nanoceria could pose a developmental neurotoxicity hazard.
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| 6. |
- Gliga, Anda R., et al.
(författare)
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RNA-sequencing reveals long-term effects of silver nanoparticles on human lung cells
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Despite a considerable focus on the adverse effects of silver nanoparticles (AgNPs) in recent years, studies on the potential long-term effects of AgNPs are scarce. The aim of this study was to explore the effects of AgNPs following repeated low-dose, long-term exposure of human bronchial epithelial cells. To this end, the human BEAS-2B cell line was exposed to 1 mu g/mL AgNPs (10 nm) for 6 weeks followed by RNA-sequencing (RNA-Seq) as well as genome-wide DNA methylation analysis. The transcriptomics analysis showed that a substantial number of genes (1717) were differentially expressed following AgNP exposure whereas only marginal effects on DNA methylation were observed. Downstream analysis of the transcriptomics data identified several affected pathways including the 'fibrosis' and 'epithelial-mesenchymal transition' (EMT) pathway. Subsequently, functional validation studies were performed using AgNPs of two different sizes (10 nm and 75 nm). Both NPs increased collagen deposition, indicative of fibrosis, and induced EMT, as evidenced by an increased invasion index, anchorage independent cell growth, as well as cadherin switching. In conclusion, using a combination of RNA-Seq and functional assays, our study revealed that repeated low-dose, long-term exposure of human BEAS-2B cells to AgNPs is pro-fibrotic, induces EMT and cell transformation.
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| 7. |
- Hedberg, Jonas, et al.
(författare)
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The importance of extracellular speciation and corrosion of copper nanoparticles on lung cell membrane integrity
- 2016
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Ingår i: Colloids and Surfaces B. - : Elsevier. - 0927-7765 .- 1873-4367. ; 141, s. 291-300
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Tidskriftsartikel (refereegranskat)abstract
- Copper nanoparticles (Cu NPs) are increasingly used in various biologically relevant applications and products, e.g., due to their antimicrobial and catalytic properties. This inevitably demands for an improved understanding on their interactions and potential toxic effects on humans. The aim of this study was to investigate the corrosion of copper nanoparticles in various biological media and to elucidate the speciation of released copper in solution. Furthermore, reactive oxygen species (ROS) generation and lung cell (A549 type II) membrane damage induced by Cu NPs in the various media were studied. The used biological media of different complexity are of relevance for nanotoxicological studies: Dulbecco's modified eagle medium (DMEM), DMEM+ (includes fetal bovine serum), phosphate buffered saline (PBS), and PBS + histidine. The results show that both copper release and corrosion are enhanced in DMEM+, DMEM, and PBS + histidine compared with PBS alone. Speciation results show that essentially no free copper ions are present in the released fraction of Cu NPs in neither DMEM+, DMEM nor histidine, while labile Cu complexes form in PBS. The Cu NPs were substantially more membrane reactive in PBS compared to the other media and the NPs caused larger effects compared to the same mass of Cu ions. Similarly, the Cu NPs caused much more ROS generation compared to the released fraction only. Taken together, the results suggest that membrane damage and ROS formation are stronger induced by Cu NPs and by free or labile Cu ions/complexes compared with Cu bound to biomolecules.
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| 8. |
- Hedberg, Yolanda, et al.
(författare)
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Surface passivity largely governs the bioaccessibility of nickel-based powder particles at human exposure conditions
- 2016
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 81, s. 162-170
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Tidskriftsartikel (refereegranskat)abstract
- The European chemical framework REACH requires that hazards and risks posed by chemicals, including alloys and metals, are identified and proven safe for humans and the environment. Therefore, differences in bioaccessibility in terms of released metals in synthetic biological fluids (different pH (1.5-7.4) and composition) that are relevant for different human exposure routes (inhalation, ingestion, and dermal contact) have been assessed for powder particles of an alloy containing high levels of nickel (Inconel 718, 57 wt% nickel). This powder is compared with the bioaccessibility of two nickel-containing stainless steel powders (AISI 316L, 10-12% nickel) and with powders representing their main pure alloy constituents: two nickel metal powders (100% nickel), two iron metal powders and two chromium metal powders. Xray photoelectron spectroscopy, microscopy, light scattering, and nitrogen absorption were employed for the particle and surface oxide characterization. Atomic absorption spectroscopy was used to quantify released amounts of metals in solution. Cytotoxicity (Alamar blue assay) and DNA damage (comet assay) of the Inconel powder were assessed following exposure of the human lung cell line A549, as well as its ability to generate reactive oxygen species (DCFH-DA assay). Despite its high nickel content, the Inconel alloy powder did not release any significant amounts of metals and did not induce any toxic response. It is concluded, that this is related to the high surface passivity of the Inconel powder governed by its chromium-rich surface oxide. Read-across from the pure metal constituents is hence not recommended either for this or any other passive alloy.
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| 9. |
- Karlsson, Hanna L., et al.
(författare)
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Toxicity of Metal and Metal Oxide Nanoparticles
- 2015
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Ingår i: Handbook on the Toxicology of Metals: Fourth Edition. - : Elsevier BV. ; , s. 75-112
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Engineered nanomaterials hold great potential in many sectors of society, not least in medicine. However, the increasing production and use of engineered nanomaterials also raises concerns about inadvertent exposure and the potential for adverse effects on human health and the environment. This chapter provides an overview of metal and metal oxide nanoparticles, their applications, and the potential for human exposure. This is followed by a discussion of general principles of nanoparticle-induced toxicity and methods for toxicity testing of nanomaterials. Careful assessment of the material properties is required for a full understanding of nanomaterial toxicity; a section of the chapter is therefore devoted to physicochemical characterization. This is followed by a detailed description of the current knowledge concerning 12 of the most important metal and metal oxide nanoparticles, with a systematic evaluation of invitro (cell culture) and invivo (animal) toxicity studies. Ecotoxicological effects are not discussed because the chapter is focused on implications for human health.
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| 10. |
- Latvala, Siiri, et al.
(författare)
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In vitro genotoxicity of airborne Ni-NP in air-liquid interface
- 2017
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Ingår i: Journal of Applied Toxicology. - : Wiley. - 0260-437X .- 1099-1263. ; 37:12, s. 1420-1427
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Tidskriftsartikel (refereegranskat)abstract
- Studies using advanced toxicological methods enabling in vitro conditions that are more realistic are currently needed for understanding the risks of pulmonary exposure to airborne nanoparticles. Owing to the carcinogenicity of certain nickel compounds, the increased production of nickel nanoparticles (Ni-NPs) raises occupational safety concerns. The aim of this study was to investigate the genotoxicity of airborne Ni-NPs using a recently developed air-liquid interface exposure system. The wild-type Chinese hamster lung fibroblast cell line (V79) was used and cytotoxicity, DNA damage and mutagenicity were studied by testing colony forming efficiency, alkaline DNA unwinding and HPRT mutation assays, respectively. Additionally, co-exposure to a PARP-1 inhibitor was performed to test possible involvement of base excision repair (BER) in repair of Ni-induced DNA damage. The results showed that cell viability was reduced significantly (to 45% and 46%) after 48hours Ni-NP exposure at concentrations of 0.15 and 0.32g cm(-2). DNA damage was significantly increased after Ni-NP exposure in the presence of the BER inhibitor indicating that Ni-NP-induced DNA damages are subsequently repaired by BER. Furthermore, there was no increased HPRT mutation frequency following Ni-NP exposure. In conclusion, this study shows that Ni-NP treatment of lung fibroblasts in an air-liquid interface system that mimics real-life exposure, results in increased DNA strand breaks and reduced cellular viability. These DNA lesions were repaired with BER in an error-free manner without resulting in mutations. This study also underlines the importance of appropriate quantification of the actual exposure concentrations during air-liquid interface exposure studies. The aim of this study was to investigate the genotoxicity of airborne Ni nanoparticles using a recently developed air-liquid interface exposure system that mimics real-life exposure. Cytotoxicity, DNA damage and mutagenicity were in the V79 cell line. Ni nanoparticle exposure of the cells in the air-liquid interface resulted in increased DNA strand breaks and reduced cellular viability at concentrations of 0.15 and 0.32 g cm (-2). These DNA lesions were repaired with BER in an error-free manner without resulting in mutations
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| 11. |
- Latvala, Siiri, et al.
(författare)
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Nickel release, ROS generation and toxicity of Ni and NiO micro- and nanoparticles
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Occupational exposure to airborne nickel is associated with an elevated risk for respiratory tract diseases including lung cancer. Therefore, the increased production of Ni-containing nanoparticles necessitates a thorough assessment of their physical, chemical, as well as toxicological properties. The aim of this study was to investigate and compare the characteristics of nickel metal (Ni) and nickel oxide (NiO) particles with a focus on Ni release, reactive oxygen species (ROS) generation, cellular uptake, cytotoxicity and genotoxicity. Four Ni-containing particles of both nano-size (Ni-n and NiO-n) and micron-size (Ni-m1 and Ni-m2) were tested. The released amount of Ni in solution was notably higher in artificial lysosomal fluid (e.g. 80–100 wt% for metallic Ni) than in cell medium after 24h (ca. 1–3 wt% for all particles). Each of the particles was taken up by the cells within 4 h and they remained in the cells to a high extent after 24 h post-incubation. Thus, the high dissolution in ALF appeared not to reflect the particle dissolution in the cells. Ni-m1 showed the most pronounced effect on cell viability after 48 h (alamar blue assay) whereas all particles showed increased cytotoxicity in the highest doses (20–40 μg cm2) when assessed by colony forming efficiency (CFE). Interestingly an increased CFE, suggesting higher proliferation, was observed for all particles in low doses (0.1 or 1 μg cm-2). Ni-m1 and NiO-n were the most potent in causing acellular ROS and DNA damage. However, no intracellular ROS was detected for any of the particles. Taken together, micron-sized Ni (Ni-m1) was more reactive and toxic compared to the nano-sized Ni. Furthermore, this study underlines that the low dose effect in terms of increased proliferation observed for all particles should be further investigated in future studies.
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| 12. |
- Lebedova, Jana, et al.
(författare)
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Size-dependent genotoxicity of silver, gold and platinum nanoparticles studied using the mini-gel comet assay and micronucleus scoring with flow cytometry
- 2018
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Ingår i: Mutagenesis. - : OXFORD UNIV PRESS. - 0267-8357 .- 1464-3804. ; 33:1, s. 77-85
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Tidskriftsartikel (refereegranskat)abstract
- Metallic nanoparticles (NPs) are promising nanomaterials used in different technological solutions as well as in consumer products. Silver (Ag), gold (Au) and platinum (Pt) represent three metallic NPs with current or suggested use in different applications. Pt is also used as vehicle exhaust catalyst leading to a possible exposure via inhalation. Despite their use, there is limited data on their genotoxic potential and possible size-dependent effects, particularly for Pt NPs. The aim of this study was to explore size-dependent genotoxicity of these NPs (5 and 50 nm) following exposure of human bronchial epithelial cells. We characterised the NPs and assessed the viability (Alamar blue assay), formation of DNA strand breaks (mini-gel comet assay) and induction of micronucleus (MN) analysed using flow cytometry (in vitro microflow kit). The results confirmed the primary size (5 and 50 nm) but showed agglomeration of all NPs in the serum free medium used. Slight reduced cell viability (tested up to 50 mu g/ml) was observed following exposure to the Ag NPs of both particle sizes as well as to the smallest (5 nm) Au NPs. Similarly, at non-cytotoxic concentrations, both 5 and 50 nm-sized Ag NPs, as well as 5 nm-sized Au NPs, increased DNA strand breaks whereas for Pt NPs only the 50 nm size caused a slight increase in DNA damage. No clear induction of MN was observed in any of the doses tested (up to 20 mu g/ml). Taken together, by using the comet assay our study shows DNA strand breaks induced by Ag NPs, without any obvious differences in size, whereas effects from Au and Pt NPs were size-dependent in the sense that the 5 nm-sized Au NPs and 50 nm-sized Pt NPs particles were active. No clear induction of MN was observed for the NPs.
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| 13. |
- McCarrick, Sarah, et al.
(författare)
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High variability in toxicity of welding fume nanoparticles from stainless steel in lung cells and reporter cell lines : the role of particle reactivity and solubility
- 2019
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Ingår i: Nanotoxicology. - : TAYLOR & FRANCIS LTD. - 1743-5390 .- 1743-5404.
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Tidskriftsartikel (refereegranskat)abstract
- Millions of people in the world perform welding as their primary occupation resulting in exposure to metal-containing nanoparticles in the fumes generated. Even though health effects including airway diseases are well-known, there is currently a lack of studies investigating how different welding set-ups and conditions affect the toxicity of generated nanoparticles of the welding fume. The aim of this study was to investigate the toxicity of nine types of welding fume particles generated via active gas shielded metal arc welding (GMAW) of chromium-containing stainless steel under different conditions and, furthermore, to correlate the toxicity to the particle characteristics. Toxicological endpoints investigated were generation of reactive oxygen species (ROS), cytotoxicity, genotoxicity and activation of ToxTracker reporter cell lines. The results clearly underline that the choice of filler material has a large influence on the toxic potential. Fume particles generated by welding with the tested flux-cored wire (FCW) were found to be more cytotoxic compared to particles generated by welding with solid wire or metal-cored wire (MCW). FCW fume particles were also the most potent in causing ROS and DNA damage and they furthermore activated reporters related to DNA double- strand breaks and p53 signaling. Interestingly, the FCW fume particles were the most soluble in PBS, releasing more chromium in the hexavalent form and manganese compared to the other fumes. These results emphasize the importance of solubility of different metal constituents of the fume particles, rather than the total metal content, for their acute toxic potential.
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| 14. |
- Noh, Hyun Ji, et al.
(författare)
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Integrating evolutionary and regulatory information with multispecies approach implicates genes and pathways in obsessive-compulsive disorder
- 2017
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Obsessive-compulsive disorder is a severe psychiatric disorder linked to abnormalities in glutamate signaling and the cortico-striatal circuit. We sequenced coding and regulatory elements for 608 genes potentially involved in obsessive-compulsive disorder in human, dog, and mouse. Using a new method that prioritizes likely functional variants, we compared 592 cases to 560 controls and found four strongly associated genes, validated in a larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains. CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are enriched for regulatory variants, of which at least six (35%) alter transcription factor-DNA binding in neuroblastoma cells. NRXN1 achieves genome-wide significance (p = 6.37 x 10(-11)) when we include 33,370 population-matched controls. Our findings suggest synaptic adhesion as a key component in compulsive behaviors, and show that targeted sequencing plus functional annotation can identify potentially causative variants, even when genomic data are limited.
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| 15. |
- Palmér, Hanna, 1974-, et al.
(författare)
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Teaching for entrepreneurial and mathematical competences : teachers stepping out of their comfort zone
- 2018
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Ingår i: Students' and Teachers' Values, Attitudes, Feelings and Beliefs in Mathematics Classrooms. - Cham : Springer International Publishing. - 9783319702438 - 9783319702445 ; , s. 13-23
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Konferensbidrag (refereegranskat)abstract
- This paper reports on an educational design research study exploring the potential in combining the teaching of entrepreneurial and mathematical competences in Swedish primary schools. The focus in this paper, however, is not on the wholeness of this study but on changes in the teacher role when entrepreneurial and mathematical competences are to be combined in teaching – as expressed by the teachers themselves. Two of these expressed changes are “saying less” and “daring to let go of control”. In the paper, these two changes are explored in relation to how they seem to influence these teachers’ teaching of mathematics, and some implications are drawn regarding how their students’ possibilities to learn mathematics may have been influenced.
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| 16. |
- Åkerlund, Emma, et al.
(författare)
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Genotoxic and mutagenic properties of Ni and NiO nanoparticles investigated by comet assay,-H2AX staining, Hprt mutation assay and ToxTracker reporter cell lines
- 2018
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Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 0893-6692 .- 1098-2280. ; 59:3, s. 211-222
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Tidskriftsartikel (refereegranskat)abstract
- Nickel (Ni) compounds are classified as carcinogenic to humans but the underlying mechanisms are still poorly understood. Furthermore, effects related to nanoparticles (NPs) of Ni have not been fully elucidated. The aim of this study was to investigate genotoxicity and mutagenicity of Ni and NiO NPs and compare the effect to soluble Ni from NiCl2. We employed different models; i.e., exposure of (1) human bronchial epithelial cells (HBEC) followed by DNA strand break analysis (comet assay and -H2AX staining); (2) six different mouse embryonic stem (mES) reporter cell lines (ToxTracker) that are constructed to exhibit fluorescence upon the induction of various pathways of relevance for (geno)toxicity and cancer; and (3) mES cells followed by mutagenicity testing (Hprt assay). The results showed increased DNA strand breaks (comet assay) for the NiO NPs and at higher doses also for the Ni NPs whereas no effects were observed for Ni ions/complexes from NiCl2. By employing the reporter cell lines, oxidative stress was observed as the main toxic mechanism and protein unfolding occurred at cytotoxic doses for all three Ni-containing materials. Oxidative stress was also detected in the HBEC cells following NP-exposure. None of these materials induced the reporter related to direct DNA damage and stalled replication forks. A small but statistically significant increase in Hprt mutations was observed for NiO but only at one dose. We conclude that Ni and NiO NPs show more pronounced (geno)toxic effects compared to Ni ions/complexes, indicating more serious health concerns. Environ. Mol. Mutagen. 59:211-222, 2018.
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| 17. |
- Åkerlund, Emma, et al.
(författare)
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Inflammation and (secondary) genotoxicity of Ni and NiO nanoparticles
- 2019
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Ingår i: Nanotoxicology. - : Taylor & Francis. - 1743-5390 .- 1743-5404. ; 13:8, s. 1060-1072
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticle-induced genotoxicity can arise through different mechanisms, and generally, primary and secondary genotoxicity can be distinguished where the secondary is driven by an inflammatory response. It is, however, yet unclear how a secondary genotoxicity can be detected using in vitro methods. The aim of this study was to investigate inflammation and genotoxicity caused by agglomerated nickel (Ni) and nickel oxide (NiO) nanoparticles and, furthermore, to explore the possibility to test secondary (inflammation-driven) genotoxicity in vitro. As a benchmark particle to compare with, we used crystalline silica (quartz). A proteome profiler antibody array was used to screen for changes in release of 105 different cytokines and the results showed an increased secretion of various cytokines including vascular endothelial growth factor (VEGF) following exposure of macrophages (differentiated THP-1 cells). Both Ni and NiO caused DNA damage (comet assay) following exposure of human bronchial epithelial cells (HBEC) and interestingly conditioned media (CM) from exposed macrophages also resulted in DNA damage (2- and 3-fold increase for Ni and NiO, respectively). Similar results were also found when using a co-culture system of macrophages and epithelial cells. In conclusion, this study shows that it is possible to detect a secondary genotoxicity in lung epithelial cells by using in vitro methods based on conditioned media or co-cultures. Further investigation is needed in order to find out what factors that are causing this secondary genotoxicity and whether such effects are caused by numerous nanoparticles.
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