| 1. |
- Rolfö, Linda, et al.
(författare)
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Predictors of Preference for the Activity-based Flexible Office
- 2019
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Ingår i: Human Systems Engineering and Design. - Cham : Springer. - 9783030020521 - 9783030020538 ; 876, s. 547-553
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Konferensbidrag (refereegranskat)abstract
- Activity-based Flexible Offices (A-FOs) are implemented with varying degree of success. Employees relocate from cell or open-plan offices, from different organizational backgrounds, varying design and implementation processes, and have different types of work tasks. This study aims at investigating whether preference for the A-FO correlate with these preconditions. The results from Chi-square tests and Spearman’s non-parametric correlation of post-relocation questionnaires distributed to 11 A-FO sites, showed that a high preference for the A-FO correlated strongest with an A-FO preference prior to relocation, being a former open-plan office occupier and with frequent performance of innovation. Low preference for the A-FO correlated with frequent performance of concentration demanding tasks. Working with tasks with high confidentiality did not predict the preference ratings.
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| 2. |
- Ågerstrand, Marlene, et al.
(författare)
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Improving Environmental Risk Assessment of Human Pharmaceuticals
- 2015
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Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 49:9, s. 5336-5345
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents 10 recommendations for improving the European Medicines Agency's guidance for environmental risk assessment of human pharmaceutical products. The recommendations are based on up-to-date, available science in combination with experiences from other chemical frameworks such as the REACH-legislation for industrial chemicals. The recommendations concern: expanding the scope of the current guideline; requirements to assess the risk for development of antibiotic resistance; jointly performed assessments; refinement of the test proposal; mixture toxicity assessments on active pharmaceutical ingredients with similar modes of action; use of all available ecotoxicity studies; mandatory reviews; increased transparency; inclusion of emission data from production; and a risk management option. We believe that implementation of our recommendations would strengthen the protection of the environment and be beneficial to society. Legislation and guidance documents need to be updated at regular intervals in order to incorporate new knowledge from the scientific community. This is particularly important for regulatory documents concerning pharmaceuticals in the environment since this is a research field that has been growing substantially in the last decades.
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| 3. |
- Lind, Marcus, et al.
(författare)
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Thrombomodulin as a marker for bleeding complications during warfarin treatment
- 2009
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Ingår i: Archives of Internal Medicine. - : American Medical Association (AMA). - 0003-9926 .- 1538-3679. ; 169:13, s. 1210-1215
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The major adverse effect of warfarin treatment is hemorrhage. Several risk factors for bleeding complications are also risk factors for thromboembolic events, making the clinical decision to initiate or withhold anticoagulant treatment difficult. Specific markers that solely identify patients at high risk of bleeding would have great clinical impact. This study aimed to test if thrombomodulin (TM) concentrations were associated with bleeding complications, cardiovascular events, or mortality in long-term anticoagulant-treated patients. METHODS: In a longitudinal cohort study we followed up 719 patients receiving warfarin treatment for a mean duration of 4.2 years. All bleeding complications causing hospitalization were registered and classified. Soluble TM antigen (sTM) concentration in plasma was measured with an enzyme-linked immunosorbent assay method. RESULTS: During the follow-up time, 113 clinically relevant bleeding events and 73 major bleeding events occurred. Increased concentration of sTM was associated with both clinically relevant bleeding and major bleeding events after adjustment for age. In the multivariable models, hazard ratios for the highest tertiles compared with the lowest were 2.29 (95% confidence interval, 1.35-3.89) and 2.33 (95% confidence interval, 1.21-4.48), respectively. No association between sTM concentration and nonfatal ischemic cardiovascular events or all-cause mortality was found. CONCLUSIONS: Increased levels of sTM are associated with bleeding complications during warfarin treatment but not with cardiovascular events or all-cause mortality. Soluble TM antigen concentration has potential as a new specific marker to identify patients at high risk of bleeding during warfarin treatment.
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| 4. |
- Johansson, Åsa, et al.
(författare)
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Precision medicine in complex diseases - : Molecular subgrouping for improved prediction and treatment stratification
- 2023
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 1365-2796 .- 0954-6820. ; 294:4, s. 378-396
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Forskningsöversikt (refereegranskat)abstract
- Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease-both with regards to symptoms and underlying causal mechanisms-and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic-based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases-including psychiatric disorders and allergies-available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high-throughput molecular technologies, together with large collections of health data and novel data-driven approaches, offers promise toward improved individual health through precision medicine.
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| 5. |
- Gillman, Anna, et al.
(författare)
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Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
- 2015
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Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
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Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.
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| 6. |
- Norling, Karin, 1988, et al.
(författare)
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Gel Phase 1,2-Distearoyl-sn-glycero-3-phosphocholine-Based Liposomes Are Superior to Fluid Phase Liposomes at Augmenting Both Antigen Presentation on Major Histocompatibility Complex Class II and Costimulatory Molecule Display by Dendritic Cells in Vitro
- 2019
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Ingår i: ACS Infectious Diseases. - : American Chemical Society (ACS). - 2373-8227. ; 5:11, s. 1867-1878
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Tidskriftsartikel (refereegranskat)abstract
- Lipid-based nanoparticles have in recent years attracted increasing attention as pharmaceutical carriers. In particular, reports of them having inherent adjuvant properties combined with their ability to protect antigen from degradation make them suitable as vaccine vectors. However, the physicochemical profile of an ideal nanoparticle for vaccine delivery is still poorly defined. Here, we used an in vitro dendritic cell assay to assess the immunogenicity of a variety of liposome formulations as vaccine carriers and adjuvants. Using flow cytometry, we investigated liposome-assisted antigen presentation as well as the expression of relevant costimulatory molecules on the cell surface. Cytokine secretion was further evaluated with an enzyme-linked immunosorbent assay (ELISA). We show that liposomes can successfully enhance antigen presentation and maturation of dendritic cells, as compared to vaccine fusion protein (CTA1-3E alpha-DD) administered alone. In particular, the lipid phase state of the membrane was found to greatly influence the vaccine antigen processing by dendritic cells. As compared to their fluid phase counterparts, gel phase liposomes were more efficient at improving antigen presentation. They were also superior at upregulating the costimulatory molecules CD80 and CD86 as well as increasing the release of the cytokines IL-6 and IL-1 beta. Taken together, we demonstrate that gel phase liposomes, while nonimmunogenic on their own, significantly enhance the antigen-presenting ability of dendritic cells and appear to be a promising way forward to improve vaccine immunogenicity.
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| 7. |
- Leffler, Per, et al.
(författare)
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Toxicity and accumulation of trinitrotoluene (TNT) and its metabolites in atlantic salmon alevins exposed to an industrially polluted water
- 2014
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Ingår i: Journal of Toxicology and Environmental Health. - : Taylor & Francis Group. - 1528-7394 .- 1087-2620. ; 77:19, s. 1183-1191
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Tidskriftsartikel (refereegranskat)abstract
- A pond in an industrial area in Sweden was selected to study adverse effects on salmon alevins from 2,4,6-trinitrotoluene (TNT)-contaminated water. Chemical screening revealed heavy contamination of TNT and its degradation products, 2-amino-4,6-dinitrotoluene (2-ADNT) and 4-amino-2,6-dinitrotoluene (4-ADNT), ranging from 0.05 to 230 g/kg in the sediment (dry weight) within the water system. Pond water contained 3 mg/L TNT. A dilution series of pond water mixed with tap water revealed increased death frequency in alevins down to fivefold dilution (approximate 0.4 mg TNT/L). Uptake was concentration dependent, reaching 7, 9, and 22 μg/g tissue for TNT, 2-ADNT, and 4-ADNT at the highest test concentration. A time-dependent uptake of TNT and its degradation products was found at a water concentration of 0.08 mg TNT/L. Degradation products of TNT showed a more efficient uptake compared to native TNT, and accumulation of 4-ADNT was more pronounced during the late phase of the 40-d exposure study. Bioconcentration factors (BCF) (0.34, 52, and 134 ml/g for TNT, 2-ADNT, and 4-ADNT, respectively) demonstrated a significant uptake of the metabolite 4-ADNT in alevin tissue. Disturbed physiological conditions and delayed development in alevins were not studied, but may not be excluded even at 125-fold diluted pond water (0.016 mg TNT/L). BCF data indicated that bioaccumulation of TNT metabolites need to be considered in TNT chronic toxicity. Fish species and age differences in the accumulation of TNT metabolites need to be further studied.
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| 8. |
- Lupu, Diana, et al.
(författare)
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The ENDpoiNTs Project : Novel Testing Strategies for Endocrine Disruptors Linked to Developmental Neurotoxicity
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 21:11
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Tidskriftsartikel (refereegranskat)abstract
- Ubiquitous exposure to endocrine-disrupting chemicals (EDCs) has caused serious concerns about the ability of these chemicals to affect neurodevelopment, among others. Since endocrine disruption (ED)-induced developmental neurotoxicity (DNT) is hardly covered by the chemical testing tools that are currently in regulatory use, the Horizon 2020 research and innovation action ENDpoiNTs has been launched to fill the scientific and methodological gaps related to the assessment of this type of chemical toxicity. The ENDpoiNTs project will generate new knowledge about ED-induced DNT and aims to develop and improve in vitro, in vivo, and in silico models pertaining to ED-linked DNT outcomes for chemical testing. This will be achieved by establishing correlative and causal links between known and novel neurodevelopmental endpoints and endocrine pathways through integration of molecular, cellular, and organismal data from in vitro and in vivo models. Based on this knowledge, the project aims to provide adverse outcome pathways (AOPs) for ED-induced DNT and to develop and integrate new testing tools with high relevance for human health into European and international regulatory frameworks.
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| 9. |
- Brage, M, et al.
(författare)
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Different cysteine proteinases involved in bone resorption and osteoclast formation.
- 2005
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 76:6, s. 439-47
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Tidskriftsartikel (refereegranskat)abstract
- Cysteine proteinases, especially cathepsin K, play an important role in osteoclastic degradation of bone matrix proteins and the process can, consequently, be significantly inhibited by cysteine proteinase inhibitors. We have recently reported that cystatin C and other cysteine proteinase inhibitors also reduce osteoclast formation. However, it is not known which cysteine proteinase(s) are involved in osteoclast differentiation. In the present study, we compared the relative potencies of cystatins C and D as inhibitors of bone resorption in cultured mouse calvariae, osteoclastogenesis in mouse bone marrow cultures, and cathepsin K activity. Inhibition of cathepsin K activity was assessed by determining equilibrium constants for inhibitor complexes in fluorogenic substrate assays. The data demonstrate that whereas human cystatins C and D are equipotent as inhibitors of bone resorption, cystatin D is 10-fold less potent as an inhibitor of osteoclastogenesis and 200-fold less potent as an inhibitor of cathepsin K activity. A recombinant human cystatin C variant with Gly substitutions for residues Arg8, Leu9, Val10, and Trp106 did not inhibit bone resorption, had 1,000-fold decreased inhibitory effect on cathepsin K activity compared to wildtype cystatin C, but was equipotent with wildtype cystatin C as an inhibitor of osteoclastogenesis. It is concluded that (i) different cysteine proteinases are likely to be involved in bone resorption and osteoclast formation, (ii) cathepsin K may not be an exclusive target enzyme in any of the two systems, and (iii) the enzyme(s) involved in osteoclastogenesis might not be a typical papain-like cysteine proteinase.
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| 10. |
- Näslund, Johanna, et al.
(författare)
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Diclofenac affects kidney histology in the three-spined stickleback (Gasterosteus aculeatus) at low mu g/L concentrations
- 2017
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Ingår i: Aquatic Toxicology. - : Elsevier BV. - 0166-445X .- 1879-1514. ; 189, s. 87-96
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Tidskriftsartikel (refereegranskat)abstract
- Diclofenac, a commonly used non-steroidal anti-inflammatory drug, is considered for regulation under the European water framework directive. This is because effects on fish have been reported at concentrations around those regularly found in treated sewage effluents (similar to 1 mu g/L). However, a recent publication reports no effects on fish at 320 mu g/L. In this study, three-spined sticklebacks (Gasterosteus aculeatus) were exposed to 0, 4.6, 22, 82 and 271 mu g/L diclofenac in flow-through systems for 28 days using triplicate aquaria per concentration. At the highest concentration, significant mortalities were observed already after 21 days (no mortalities found up to 22 mu g/L). Histological analysis revealed a significant increase in the proportion of renal hematopoietic tissue (renal hematopoietic hyperplasia) after 28 days at the lowest concentration and at all higher concentrations, following a clear dose-response pattern. Skin ulcerations of the jaw were noted by macroscopic observations, primarily at the two highest concentrations. No histological changes were observed in the liver. There was an increase in the relative hepatic mRNA levels of c7 (complement component 7), a gene involved in the innate immune system, at 22 mu g/L and at all higher concentrations, again following a clear dose-response. The bio-concentration factor was stable across concentrations, but lower than reported for rainbow trout, suggesting lower internal exposure to the drug in the stickleback. In conclusion, this study demonstrates that diclofenac causes histological changes in the three-spined stickleback at low mu g/L concentrations, which cause concern for fish populations exposed to treated sewage effluents.
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