| 1. |
- Karlsson, Hanna L., et al.
(författare)
-
Health hazards of particles in additive manufacturing : a cross-disciplinary study on reactivity, toxicity and occupational exposure to two nickel-based alloys
- 2023
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- The increasing use of additive manufacturing (AM) techniques (e.g., 3D-printing) offers many advantages but at the same time presents some challenges. One concern is the possible exposure and health risk related to metal containing particles of different sizes. Using the nickel-based alloys Hastelloy X (HX) and Inconel 939 (IN939) as a case, the aim of this cross-disciplinary study was to increase the understanding on possible health hazards and exposure. This was done by performing in-depth characterization of virgin, reused and condensate powders, testing in vitro toxicity (cytotoxicity, genotoxicity, oxidative stress), and measuring occupational airborne exposure. The results showed limited metal release from both HX and IN939, and slightly different surface composition of reused compared to virgin powders. No or small effects on the cultured lung cells were observed when tested up to 100 µg/mL. Particle background levels in the printing facilities were generally low, but high transient peaks were observed in relation to sieving. Furthermore, during post processing with grinding, high levels of nanoparticles (> 100,000 particles/cm3) were noted. Urine metal levels in AM operators did not exceed biomonitoring action limits. Future studies should focus on understanding the toxicity of the nanoparticles formed during printing and post-processing.
|
|
| 2. |
- Li, Hongzhe, et al.
(författare)
-
Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing
- 2023
-
Ingår i: eLife. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Hematopoiesis is regulated by the bone marrow (BM) stroma. However, cellular identities and functions of the different BM stromal elements in humans remain poorly defined. Based on single-cell RNA sequencing (scRNAseq), we systematically characterized the human non-hematopoietic BM stromal compartment and we investigated stromal cell regulation principles based on the RNA velocity analysis using scVelo and studied the interactions between the human BM stromal cells and hematopoietic cells based on ligand-receptor (LR) expression using CellPhoneDB. scRNAseq led to the identification of six transcriptionally and functionally distinct stromal cell populations. Stromal cell differentiation hierarchy was recapitulated based on RNA velocity analysis and in vitro proliferation capacities and differentiation potentials. Potential key factors that might govern the transition from stem and progenitor cells to fate-committed cells were identified. In situ localization analysis demonstrated that different stromal cells were localized in different niches in the bone marrow. In silico cell-cell communication analysis further predicted that different stromal cell types might regulate hematopoiesis through distinct mechanisms. These findings provide the basis for a comprehensive understanding of the cellular complexity of the human BM microenvironment and the intricate stroma-hematopoiesis crosstalk mechanisms, thus refining our current view on human hematopoietic niche organization.
|
|
| 3. |
- Liu, Yang, et al.
(författare)
-
Engineered human Diamond-Blackfan anemia disease model confirms therapeutic effects of clinically applicable lentiviral vector at single-cell resolution
- 2023
-
Ingår i: Haematologica. - 1592-8721. ; 108:11, s. 3095-3109
-
Tidskriftsartikel (refereegranskat)abstract
- Diamond-Blackfan anemia is a rare genetic bone marrow failure disorder which is usually caused by mutations in ribosomal protein genes. In the present study, we generated a traceable RPS19-deficient cell model using CRISPR-Cas9 and homology-directed repair to investigate the therapeutic effects of a clinically applicable lentiviral vector at single-cell resolution. We developed a gentle nanostraw delivery platform to edit RPS19 gene in primary human cord blood-derived CD34+ hematopoietic stem and progenitor cells. The edited cells showed expected impaired erythroid differentiation phenotype and a specific erythroid progenitor with abnormal cell cycle status accompanied by enrichment of TNFα/NF-κB and p53 signaling pathways was identified by single-cell RNA sequencing analysis. The therapeutic vector could rescue the abnormal erythropoiesis by activating cell cycle-related signaling pathways and promoted red blood cell production. Overall, these results establish nanostraws as a gentle option for CRISPR-Cas9-based gene editing in sensitive primary hematopoietic stem and progenitor cells, and provide support for future clinical investigations of the lentiviral gene therapy strategy.
|
|
| 4. |
- Woksepp, Hanna, et al.
(författare)
-
Dissemination of carbapenemase-producing Enterobacterales through wastewater and gulls at a wastewater treatment plant in Sweden
- 2023
-
Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 886
-
Tidskriftsartikel (refereegranskat)abstract
- Here we report the detection of carbapenemase-producing Enterobacterales (CPE) isolated from Swedish wastewater and gull faeces. CPE have not been detected in samples from animals in Sweden preceding this report. Sampling of wastewater treatment plant (WWTP) inlet and outlet, sedimentation basins, surface seawater from key aquatic bird habitats and freshly deposited gull faeces was done on six separate occasions during May to September 2021. Following broth enrichment, selective screening of putative CPE was performed on mSuperCarbaTM (CHROMagar). Species identification was done with MALDI-TOF. Antimicrobial susceptibility testing was performed according to EUCAST. In total, seventeen CPE were verified by genome sequencing carrying blaGES-5, blaIMI-3, blaOXA-181 or blaOXA-244. The blaGES-5 was carried on IncP plasmids in four different species; Escherichia coli ST10 isolated from WWTP outlet, Raoultella ornithinolytica isolated from WWTP inlet, outlet and sedimentation basins as well as gull faeces collected at the WWTP and Klebsiella spp. isolates from WWTP inlet and outlet. The genetic environment surrounding blaGES-5 was similar in two Citrobacter freundii causing human infections. The blaIMI-3 was carried on IncFII(Yp) plasmids in four Enterobacter ludwigii, isolated from WWTP outlet and gull faeces collected at a recreational city park 2 km from the WWTP. The blaOXA-181 was located on a COLKP3 plasmid found in an E. coli, while blaOXA-244 was chromosomally located in an E. coli ST10, both isolated from WWTP inlet. Phylogenetic analysis of R. ornithinolytica and E. ludwigii isolates indicate that the gulls carried strains related to those identified in the WWTP samples. The results thus add to the increasing evidence of WWTPs as anthropogenic reservoirs for mobile genetic elements with antibiotic-resistance functionality. Such environments could profoundly impact the dissemination and spread of such genetic elements via for example aquatic birds, thereby warranting further study and surveillance.
|
|
| 5. |
- Allard, Bert, 1945-, et al.
(författare)
-
Metal Exchangeability in the REE-Enriched Biogenic Mn Oxide Birnessite from Ytterby, Sweden
- 2023
-
Ingår i: Minerals. - : MDPI. - 2075-163X. ; 13:8
-
Tidskriftsartikel (refereegranskat)abstract
- A black substance exuding from fractures was observed in 2012 in Ytterby mine, Sweden, and identified in 2017 as birnessite with the composition Mx[Mn(III,IV)](2)O-4 center dot(H2O)n. M is usually calcium and sodium, with x around 0.5. The Ytterby birnessite is unique, with M being calcium, magnesium, and also rare earth elements (REEs) constituting up to 2% of the total metal content. The biogenic origin of the birnessite was established in 2018. Analysis of the microbial processes leading to the birnessite formation and the REE enrichment has continued since then. The process is fast and dynamic, as indicated by the depletion of manganese and of REE and other metals in the fracture water during the passage over the precipitation zone in the mine tunnel. Studies of the exchangeability of metals in the structure are the main objective of the present program. Exposure to solutions of sodium, calcium, lanthanum, and iron led to exchanges and altered distribution of the metals in the birnessite, however, generating phases with almost identical structures after the exchanges, and no new mineral phases were detected. Exchangeability was more efficient for trivalent elements (REE) over divalent (calcium) and monovalent (sodium) elements of a similar size (ionic radii 90-100 pm).
|
|
| 6. |
- Alriksson, Stina, 1971-, et al.
(författare)
-
Temporal risk assessment – 20th century Pb emissions to air and exposure via inhalation in the Swedish glass district
- 2023
-
Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 858:1
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of the present study was to assess historical emissions of Pb to air around a number of glassworks sites in southeastern Sweden, and the possible implications for human exposure. To do so, a four-step method was applied. First, emissions of Pb to air around 10 glassworks were modelled for the 20th century. Second, an assessment of the resulting exposure was made for a number of scenarios. Third, the number of people potentially exposed at different times was estimated, and fourth, measurements of “current” Pb concentrations in PM10 material from four sites were conducted in 2019. The results show that the highest emissions, and exposures, occurred from 1970 to1980. It coincides with the time period when the highest number of people resided in the villages. At this time, the average Pb concentration in air around the six largest factories was about 2.4 μg Pb/m3, i.e. 16 times the present US national ambient air quality standard (NAAQS) of 0.15 μg Pb/m3. By year 2000 the modelled average concentration had dropped to 0.05 μg Pb/m3, a level that is normal for urban regions today. The PM10 measurements from 2019 indicate a further decline, now with a mean value of about 0.02 μg Pb/m3. Over the entire study period, inhalation hazard quotients (HQs) exceeded the dietary HQ by many orders of magnitude, indicating that inhalation has been the most prevalent exposure pathway in the past. At present, both pathways are judged to be associated with low exposures. Even if only roughly approximated, a picture of the historical exposure can increase our understanding of the connection between exposure and disease, and can be valuable when risks are to be communicated to residents near contaminated areas.
|
|
| 7. |
- Andersson, Elin, et al.
(författare)
-
Quantification of chondroitin sulfate, hyaluronic acid and N-glycans in synovial fluid – A technical performance study
- 2023
-
Ingår i: Osteoarthritis and Cartilage Open. - 2665-9131. ; 5:3, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo validate a quantitative high performance liquid chromatography (HPLC) assay for chondroitin sulfate (CS) and hyaluronic acid (HA) in synovial fluid, and to analyze glycan-patterns in patient samples.DesignSynovial fluid from osteoarthritis (OA, n = 25) and knee-injury (n = 13) patients, a synovial fluid pool (SF-control) and purified aggrecan, were chondroitinase digested and together with CS- and HA-standards fluorophore labelled prior to quantitative HPLC analysis. N-glycan profiles of synovial fluid and aggrecan were assessed by mass spectrometry.ResultsUnsaturated uronic acid and sulfated-N-acetylgalactosamine (ΔUA-GalNAc4S and ΔUA-GalNAc6S) contributed to 95% of the total CS-signal in the SF-control sample. For HA and the CS variants in SF-control the intra- and inter-experiment coefficient of variation was between 3–12% and 11–19%, respectively; tenfold dilution gave recoveries between 74 and 122%, and biofluid stability test (room temperature storage and freeze-thaw cycles) showed recoveries between 81 and 140%. Synovial fluid concentrations of the CS variants ΔUA-GalNAc6S and ΔUA2S-GalNAc6S were three times higher in the recent injury group compared to the OA group, while HA was four times lower. Sixty-one different N-glycans were detected in the synovial fluid samples, but there were no differences in levels of N-glycan classes between patient groups. The CS-profile (levels of ΔUA-GalNAc4S and ΔUA-GalNAc6S) in synovial fluid resembled that of purified aggrecan from corresponding samples; the contribution to the N-glycan profile in synovial fluid from aggrecan was low.ConclusionsThe HPLC-assay is suitable for analyzing CS variants and HA in synovial fluid samples, and the GAG-pattern differs between OA and recently knee injured subjects.
|
|
| 8. |
- Andersson, Elin, et al.
(författare)
-
Quantification of chondroitin sulfate, hyaluronic acid and N-glycans in synovial fluid – A technical performance study
- 2023
-
Ingår i: Osteoarthritis and Cartilage Open. - 2665-9131. ; 5:3
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To validate a quantitative high performance liquid chromatography (HPLC) assay for chondroitin sulfate (CS) and hyaluronic acid (HA) in synovial fluid, and to analyze glycan-patterns in patient samples. Design: Synovial fluid from osteoarthritis (OA, n = 25) and knee-injury (n = 13) patients, a synovial fluid pool (SF-control) and purified aggrecan, were chondroitinase digested and together with CS- and HA-standards fluorophore labelled prior to quantitative HPLC analysis. N-glycan profiles of synovial fluid and aggrecan were assessed by mass spectrometry. Results: Unsaturated uronic acid and sulfated-N-acetylgalactosamine (ΔUA-GalNAc4S and ΔUA-GalNAc6S) contributed to 95% of the total CS-signal in the SF-control sample. For HA and the CS variants in SF-control the intra- and inter-experiment coefficient of variation was between 3–12% and 11–19%, respectively; tenfold dilution gave recoveries between 74 and 122%, and biofluid stability test (room temperature storage and freeze-thaw cycles) showed recoveries between 81 and 140%. Synovial fluid concentrations of the CS variants ΔUA-GalNAc6S and ΔUA2S-GalNAc6S were three times higher in the recent injury group compared to the OA group, while HA was four times lower. Sixty-one different N-glycans were detected in the synovial fluid samples, but there were no differences in levels of N-glycan classes between patient groups. The CS-profile (levels of ΔUA-GalNAc4S and ΔUA-GalNAc6S) in synovial fluid resembled that of purified aggrecan from corresponding samples; the contribution to the N-glycan profile in synovial fluid from aggrecan was low. Conclusions: The HPLC-assay is suitable for analyzing CS variants and HA in synovial fluid samples, and the GAG-pattern differs between OA and recently knee injured subjects.
|
|
| 9. |
- Assenhöj, Maria, et al.
(författare)
-
Occupational exposure and health surveys at metal additive manufacturing facilities
- 2023
-
Ingår i: Frontiers In Public Health. - : FRONTIERS MEDIA SA. - 2296-2565. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Additive manufacturing is a novel state-of-the art technology with significant economic and practical advantages, including the ability to produce complex structures on demand while reducing the need of stocking materials and products. Additive manufacturing is a technology that is here to stay; however, new technologies bring new challenges, not only technical but also from an occupational health and safety perspective. Herein, leading Swedish companies using metal additive manufacturing were studied with the aim of investigating occupational exposure and the utility of chosen exposure- and clinical markers as predictors of potential exposure-related health risks.Methods: Exposure levels were investigated by analysis of airborne dust and metals, alongside particle counting instruments measuring airborne particles in the range of 10 nm-10 mu m to identify dusty work tasks. Health examinations were performed on a total of 48 additive manufacturing workers and 39 controls. All participants completed a questionnaire, underwent spirometry, and blood and urine sampling. A subset underwent further lung function tests.Results: Exposure to inhalable dust and metals were low, but particle counting instruments identified specific work tasks with high particle emissions. Examined health parameters were well within reference values on a group level. However, statistical analysis implied an impact on workers kidney function and possible airway inflammation.Conclusion: The methodology was successful for investigating exposure-related health risks in additive manufacturing. However, most participants have been working <5 years. Therefore, long-term studies are needed before we can conclusively accept or reject the observed effects on health.
|
|
| 10. |
- Bartholomew, John G., et al.
(författare)
-
High-resolution spectroscopic techniques for studying rare-earth ions in nanoparticles
- 2023
-
Ingår i: Journal of Luminescence. - : Elsevier BV. - 0022-2313. ; 257
-
Tidskriftsartikel (refereegranskat)abstract
- Rare-earth doped nanoparticles can exhibit narrow optical and spin linewidths at low temperatures. These outstanding properties for nanomaterials make them attractive for quantum technologies based on optically addressable spins such as quantum memories and computers. Although accurate linewidth measurements have been reported using, for example, spectral hole burning or photon echo techniques, so far they have been mostly restricted to large ensembles of particles. Being able to extend linewidths measurements to few and single particles is particularly important in view of their integration in nanophotonic devices. In this paper, we present techniques for determining inhomogeneous and homogeneous linewidths of small ensembles of rare-earth ions in doped nanoparticles with high signal-to-noise ratios for convenient integration times. Using these techniques we have observed property variations for particles from the same synthesis, a first step towards their optimization for applications in quantum technologies.
|
|
