| 1. |
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| 2. |
- Meister, Sebastian, et al.
(författare)
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An Affibody Molecule Is Actively Transported into the Cerebrospinal Fluid via Binding to the Transferrin Receptor
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:8, s. 2999-
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Tidskriftsartikel (refereegranskat)abstract
- Theuseofbiotherapeuticsforthetreatmentofdiseasesofthecentralnervoussystem(CNS) is typically impeded by insufficient transport across the blood–brain barrier. Here, we investigate a strategy to potentially increase the uptake into the CNS of an affibody molecule (ZSYM73) via binding to the transferrin receptor (TfR). ZSYM73 binds monomeric amyloid beta, a peptide involved in Alzheimer’s disease pathogenesis, with subnanomolar affinity. We generated a tri-specific fusion protein by genetically linking a single-chain variable fragment of the TfR-binding antibody 8D3 and an albumin-binding domain to the affibody molecule ZSYM73. Simultaneous tri-specific target engagementwasconfirmedinabiosensorexperimentandtheaffinityformurineTfRwasdetermined to 5 nM. Blockable binding to TfR on endothelial cells was demonstrated using flow cytometry and in a preclinical study we observed increased uptake of the tri-specific fusion protein into the cerebrospinal fluid 24 h after injection.
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| 3. |
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| 4. |
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| 5. |
- Axelsson, Malin, et al.
(författare)
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Differences in diagnostic patterns of obstructive airway disease between areas and sex in Sweden and Finland : The Nordic EpiLung Study
- 2021
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Ingår i: Journal of Asthma. - : Taylor & Francis. - 0277-0903 .- 1532-4303. ; 58:9, s. 1196-1207
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the current prevalence of physician-diagnosed obstructive airway diseases by respiratory symptoms and by sex in Sweden and Finland. Method: In 2016, a postal questionnaire was answered by 34,072 randomly selected adults in four study areas: Västra Götaland and Norrbotten in Sweden, and Seinäjoki-Vaasa and Helsinki in Finland. Results: The prevalence of asthma symptoms was higher in Norrbotten (13.2%), Seinäjoki-Vaasa (14.8%) and Helsinki (14.4%) than in Västra Götaland (10.7%), and physician-diagnosed asthma was highest in Norrbotten (13.0%) and least in Västra Götaland (10.1%). Chronic productive cough was most common in the Finnish areas (7.7-8.2 % versus 6.3-6.7 %) while the prevalence of physician-diagnosed chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD) varied between 1.7-2.7% in the four areas. Among individuals with respiratory symptoms, the prevalence of asthma was most common in Norrbotten, while a diagnosis of COPD or CB was most common in Västra Götaland and Seinäjoki-Vaasa. More women than men with respiratory symptoms reported a diagnosis of asthma in Sweden and Seinäjoki-Vaasa but there were no sex differences in Helsinki. In Sweden, more women than men with symptoms of cough or phlegm reported a diagnosis of CB or COPD, while in Finland the opposite was found. Conclusion: The prevalence of respiratory symptoms and corresponding diagnoses varied between and within the countries. The proportion reporting a diagnosis of obstructive airway disease among individuals with respiratory symptoms varied, indicating differences in diagnostic patterns both between areas and by sex.
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| 6. |
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| 7. |
- Bargholtz, Chr., et al.
(författare)
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Measurement of the eta -> pi(+)pi(-)e(+)e(-) decay branching ratio
- 2007
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 644:5-6, s. 299-303
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Tidskriftsartikel (refereegranskat)abstract
- The reaction pd -> He-3 eta at threshold was used to provide a clean source of eta mesons for decay studies with the WASA detector at CELSIUS. The branching ratio of the decay eta -> pi(+)pi(-)e(+)e(-) is measured to be (4.3 +/- 1.3 +/- 0.4) x 10(-4).
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| 8. |
- Bergström, Göran, 1964, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 9. |
- Bergström, Göran, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 10. |
- Boutajangout, Allal, et al.
(författare)
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Affibody-Mediated Sequestration of Amyloid beta Demonstrates Preventive Efficacy in a Transgenic Alzheimer's Disease Mouse Model
- 2019
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Different strategies for treatment and prevention of Alzheimer's disease (AD) are currently under investigation, including passive immunization with anti-amyloid beta (anti-A beta) monoclonal antibodies (mAbs). Here, we investigate the therapeutic potential of a novel type of A beta-targeting agent based on an affibody molecule with fundamentally different properties to mAbs. We generated a therapeutic candidate, denoted Z(SYM73)-albumin-binding domain (ABD; 16.8 kDa), by genetic linkage of the dimeric Z(SYM73) affibody for sequestering of monomeric A beta-peptides and an ABD for extension of its in vivo half-life. Amyloid precursor protein (APP)/PS1 transgenic AD mice were administered with Z(SYM73)-ABD, followed by behavioral examination and immunohistochemistry. Results demonstrated rescued cognitive functions and significantly lower amyloid burden in the treated animals compared to controls. No toxicological symptoms or immunology-related side-effects were observed. To our knowledge, this is the first reported in vivo investigation of a systemically delivered scaffold protein against monomeric A beta, demonstrating a therapeutic potential for prevention of AD.
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| 11. |
- Bäck, Hanna, et al.
(författare)
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Cabinets, Prime Ministers and Corruption. A Comparative Analysis of Parliamentary Governments in Post-War Europe
- 2016
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Why are some states more corrupt than others? Previous research explaining corruption suggests that multiparty governments are associated with higher levels of corruption since it is difficult for voters to hold parties in such cabinets accountable. Drawing on the literature on coalition governance, we suggest that a lack of government corruption has more to do with the ability of other key political actors to control the agents that have been delegated power in cabinet. We use a new dataset (Varieties of Democracy), giving us more specific measures on governmental corruption across a longer time-period. We show that corruption is significantly lower when the Prime Minister (PM) has strong constitutional powers, suggesting that the PM as a principal reduces agency problems.
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| 12. |
- Bäck, Hanna, et al.
(författare)
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Cabinets, Prime Ministers and Corruption. A Comparative Analysis of Parliamentary Governments in Post-war Europe
- 2019
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Ingår i: Political Studies. - : SAGE Publications. - 0032-3217 .- 1467-9248. ; 67:1, s. 149-170
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Tidskriftsartikel (refereegranskat)abstract
- Why are some states more corrupt than others? Drawing on the literature on governance in parliamentary democracies, we suggest that the degree of corruption depends on the ability of key political actors to control ministers who have been delegated power. We argue that the Prime Minister has incentives to limit corruption within the cabinet and has the ability to do so when there are certain “control mechanisms” at hand. One such mechanism is the PM’s ability to fire or demote ministers who are not behaving in accordance with his or her wishes. We hypothesize that governmental corruption will be lower in systems where the constitution grants the PM strong powers. Using a new dataset (Varieties of Democracy), which provides more specific measures on high-level corruption across a longer time period, we analyze corruption in 26 West and East European democracies over the post-war period and find support for our hypothesis.
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| 13. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 14. |
- Chen, Jiaxin, et al.
(författare)
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Microstructures of oxide films formed in alloy 182 BWR core shroud support leg cracks
- 2018
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Ingår i: Miner. Met. Mater. Ser.. - Cham : Springer International Publishing. - 9783319684536 ; Part F11, s. 417-431
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Konferensbidrag (refereegranskat)abstract
- This paper contributes to a TEM examination on the oxide films formed at three locations along a crack path in Alloy 182 weld from a BWR core shroud support leg, namely, the crack mouth, the midway between the mouth and the crack tip, and the crack tip. In the crack mouth the oxide film was approximately 1.6 μm in thickness and consisted of relatively pure NiO. The midway oxide film was mainly a nickel chromium oxide with a film thickness of 0.3 μm. At the crack tip the oxide film was a nickel chromium iron oxide with a film thickness of 30 nm. In all studied locations the main oxides had the similar rocksalt structure and the cracks were much wider than the thicknesses of the oxide films. It probably suggests that the corroded metal was largely dissolved into the coolant. The different dissolution rates of nickel, chromium and iron cations in the oxide films are clearly displayed with the compositions of the residual oxides. The oxide stability under different redox potentials along the crack path is briefly discussed.
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| 15. |
- Chen, Jiaxin, et al.
(författare)
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Microstructures of oxide films formed in alloy 182 bwr core shroud support leg cracks
- 2019
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Ingår i: Proceedings of the 18th International Conference on Environmental Degradation of Materials in Nuclear Power Systems – Water Reactors. - Cham : Springer International Publishing. - 9783030046385 - 9783030046392 - 9783319515403 - 9783319651354 - 9783319728520 - 9783319950211 ; , s. 1633-1647
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Konferensbidrag (refereegranskat)abstract
- This paper contributes to a TEM examination on the oxide films formed at three locations along a crack path in Alloy 182 weld from a BWR core shroud support leg, namely, the crack mouth, the midway between the mouth and the crack tip, and the crack tip. In the crack mouth the oxide film was approximately 1.6 μm in thickness and consisted of relatively pure NiO. The midway oxide film was mainly a nickel chromium oxide with a film thickness of 0.3 μm. At the crack tip the oxide film was a nickel chromium iron oxide with a film thickness of 30 nm. In all studied locations the main oxides had the similar rocksalt structure and the cracks were much wider than the thicknesses of the oxide films. It probably suggests that the corroded metal was largely dissolved into the coolant. The different dissolution rates of nickel, chromium and iron cations in the oxide films are clearly displayed with the compositions of the residual oxides. The oxide stability under different redox potentials along the crack path is briefly discussed.
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| 16. |
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| 17. |
- Ekebergh, Margaretha, et al.
(författare)
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The encounter between Caring Science and the Lifeworld
- 2012
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Scientific knowledge is characterized by abstract descriptions and structures which are not identical to the lived reality. Scientific knowledge cannot directly be applied on the lived existence, without being transformed and adjusted to the individual’s very complex lifeworld. Learning in caring contexts is an encounter between the scientific knowledge of caring and the learner’s lifeworld. This encounter needs a support that has the potential to bring caring science to life and to start an intertwining process with the lifeworld that creates embodied knowledge. Lifeworld didactics are built on an approach about learning as an individual process and that learning takes its point of departure in the learner’s previous experiences, which accompanies the learning process. The challenges within lifeworld didactics is to be open and sensitive to the learner’s lifeworld and with tact support the development of a reflective attitude in the learning process. Lifeworld didactics strategies are of crucial importance in different caring contexts. This paper presents three lifeworld led phenomenological research projects that have focused on acquiring caring science knowledge in caring contexts, more precisely it is the encounter between caring science and the lifeworld. The research is within the framework of lifeworld didactics, but the three projects each have a special focus. The first illustrates how the learning and caring processes merge and become an intertwined phenomenon in nursing students’ learning. The research is carried out in Dedicated Educational Units (DEU), within psychiatric and orthopedic care. Three perspectives are illustrated in the project; that of the students, the supervisors and the patients. The overall aim is to develop a supervision model that has the potential to support the students’ learning processes as well as the patients’ caring processes. The second illustrates how the concepts ‘patient perspective’ and ‘patient participation’ can be implemented in a clinical setting for elderly patients in order to improve the quality of care. This project is inspired by Participatory Action Research and is built on collaboration between the university and the health care services. The aim is to develop reflective educational material in terms of filmed drama episodes, based on the result of two studies about elderly patients’ participation in team meetings. The third illustrates the perspective of lifeworld didactics in two phenomenological studies that focus on Students` learning in an encounter with patients and Students` learning on the way to becoming professional - supported by supervision in pairs of students. The findings show patterns of essential meanings that have specific significance in the art of supporting students` learning in clinical education. These are; the significance of responsibility, its extent and shape in relation to the supervisor’s ability to adopt a reflective supervising attitude and to be supportive enough but at the same time to not assume the responsibility. The learning process shows to be a challenge for students, where safety in pairs of students has a great significance when coping with the challenge to learn and develop.
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| 18. |
- Ekebergh, Margaretha, et al.
(författare)
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The Encounter between Caring Sciences and the Lifeworld : The Art of Making Knowledge Alive and Embodied
- 2012
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Konferensbidrag (refereegranskat)abstract
- Scientific knowledge is characterized by abstract descriptions and structures, which are not identical to the lived reality. Scientific knowledge cannot directly be applied on the lived existence, without being transformed and adjusted to the individual’s very complex lifeworld. Learning in caring contexts is an encounter between the scientific knowledge of caring and the learner’s lifeworld. This encounter needs a support that has the potential to bring caring science to life and to start an intertwining process with the lifeworld that creates embodied knowledge. Lifeworld didactics are built on an approach about learning as an individual process and that learning takes its point of departure in the learner’s previous experiences, which accompanies the learning process. The challenges within lifeworld didactics are to be open and sensitive to the learner’s lifeworld and with tact support the development of a reflective attitude in the learning process. Lifeworld didactics strategies are of crucial importance in different caring contexts. This symposium presents three lifeworld led phenomenological research projects that have focused on acquiring caring science knowledge in caring contexts, more precisely it is the encounter between caring science and the lifeworld. The research is within the framework of lifeworld didactics, but the three projects each have a special focus.
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| 19. |
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| 20. |
- Faresjö, Rebecca, et al.
(författare)
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Transferrin Receptor Binding BBB-Shuttle Facilitates Brain Delivery of Anti-Aβ-Affibodies
- 2022
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Ingår i: Pharmaceutical research. - : Springer Nature. - 0724-8741 .- 1573-904X. ; 39:7, s. 1509-1521
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Tidskriftsartikel (refereegranskat)abstract
- Affibodies targeting amyloid-beta (Aβ) could potentially be used as therapeutic and diagnostic agents in Alzheimer’s disease (AD). Affibodies display suitable characteristics for imaging applications such as high stability and a short biological half-life. The aim of this study was to explore brain delivery and retention of Aβ protofibril-targeted affibodies in wild-type (WT) and AD transgenic mice and to evaluate their potential as imaging agents. Two affibodies, Z5 and Z1, were fused with the blood–brain barrier (BBB) shuttle single-chain variable fragment scFv8D3. In vitro binding of 125I-labeled affibodies with and without scFv8D3 was evaluated by ELISA and autoradiography. Brain uptake and retention of the affibodies at 2 h and 24 h post injection was studied ex vivo in WT and transgenic (tg-Swe and tg-ArcSwe) mice. At 2 h post injection, [125I]I-Z5 and [125I]I-Z1 displayed brain concentrations of 0.37 ± 0.09% and 0.46 ± 0.08% ID/g brain, respectively. [125I]I-scFv8D3-Z5 and [125I]I-scFv8D3-Z1 showed increased brain concentrations of 0.53 ± 0.16% and 1.20 ± 0.35%ID/g brain. At 24 h post injection, brain retention of [125I]I-Z1 and [125I]I-Z5 was low, while [125I]I-scFv8D3-Z1 and [125I]I-scFv8D3-Z5 showed moderate brain retention, with a tendency towards higher retention of [125I]I-scFv8D3-Z5 in AD transgenic mice. Nuclear track emulsion autoradiography showed greater parenchymal distribution of [125I]I-scFv8D3-Z5 and [125I]I-scFv8D3-Z1 compared with the affibodies without scFv8D3, but could not confirm specific affibody accumulation around Aβ deposits. Affibody-scFv8D3 fusions displayed increased brain and parenchymal delivery compared with the non-fused affibodies. However, fast brain washout and a suboptimal balance between Aβ and mTfR1 affinity resulted in low intrabrain retention around Aβ deposits.
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| 21. |
- Fick, Jerker, et al.
(författare)
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Contamination of surface, ground, and drinking water from pharmaceutical production
- 2009
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Ingår i: Environmental Toxicology and Chemistry. - : SETAC Journals. - 0730-7268 .- 1552-8618. ; 28:12, s. 2522-2527
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Tidskriftsartikel (refereegranskat)abstract
- Low levels of pharmaceuticals are detected in surface, ground, and drinking water worldwide. Usage and incorrect disposal have been considered the major environmental sources of these micro-contaminants. Recent publications, however, suggest that wastewater from drug production can potentially be a source of much higher concentrations in certain locations. We investigated the environmental fate of active pharmaceutical ingredients in a major production area for the global bulk-drug market. Water samples were taken from a common effluent treatment plant near Hyderabad, India, which receives process water from about 90 bulk drug manufacturers. Surface water was analyzed from the recipient stream and from two lakes that are not contaminated by the treatment plant. Water samples were also taken from wells in six nearby villages. The samples were analyzed for the presence of twelve pharmaceuticals with LC-MS/MS. All wells were determined to be contaminated with drugs. Ciprofloxacin, enoxacin, cetirizine, terbinafine and citalopram were detected at >1microg l-1 in several wells. Very high concentrations of ciprofloxacin (up to 14 mg L-1) and other pharmaceuticals (up to 2 mg L-1) were found in the effluent of the treatment plant and in the two lakes (up to 6.5 mg L-1). Thus, insufficient wastewater treatment in one of the world's largest centers for bulk drug production leads to unprecedented drug contamination of surface, ground, and drinking water. This raises serious concerns regarding the development of antibiotic resistance, and it creates a major challenge for producers and regulatory agencies to improve the situation.
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| 22. |
- Gillman, Anna, et al.
(författare)
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Resistance Mutation R292K Is Induced in Influenza A(H6N2) Virus by Exposure of Infected Mallards to Low Levels of Oseltamivir
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Resistance to neuraminidase inhibitors (NAIs) is problematic as these drugs constitute the major treatment option for severe influenza. Extensive use of the NAI oseltamivir (Tamiflu(R)) results in up to 865 ng/L of its active metabolite oseltamivir carboxylate (OC) in river water. There one of the natural reservoirs of influenza A, dabbling ducks, can be exposed. We previously demonstrated that an influenza A(H1N1) virus in mallards (Anas platyrhynchos) exposed to 1 mu g/L of OC developed oseltamivir resistance through the mutation H274Y (N2-numbering). In this study, we assessed the resistance development in an A(H6N2) virus, which belongs to the phylogenetic N2 group of neuraminidases with distinct functional and resistance characteristics. Mallards were infected with A(H6N2) while exposed to 120 ng/L, 1.2 mu g/L or 12 mu g/L of OC in their sole water source. After 4 days with 12 mu g/L of OC exposure, the resistance mutation R292K emerged and then persisted. Drug sensitivity was decreased approximate to 13,000-fold for OC and approximate to 7.8-fold for zanamivir. Viral shedding was similar when comparing R292K and wild-type virus indicating sustained replication and transmission. Reduced neuraminidase activity and decrease in recovered virus after propagation in embryonated hen eggs was observed in R292K viruses. The initial, but not the later R292K isolates reverted to wild-type during egg-propagation, suggesting a stabilization of the mutation, possibly through additional mutations in the neuraminidase (D113N or D141N) or hemagglutinin (E216K). Our results indicate a risk for OC resistance development also in a N2 group influenza virus and that exposure to one NAI can result in a decreased sensitivity to other NAIs as well. If established in influenza viruses circulating among wild birds, the resistance could spread to humans via re-assortment or direct transmission. This could potentially cause an oseltamivir-resistant pandemic; a serious health concern as preparedness plans rely heavily on oseltamivir before vaccines can be mass-produced.
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| 23. |
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| 24. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
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ACTION: A Person-centred Communication Intervention Targeting Nurse Assistants in Home Care for Older Persons
- 2019
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Konferensbidrag (refereegranskat)abstract
- Background: The aging population and the number of older persons living at home are increasing. Some have extensive needs for care, which leads to increased demands on professionals in home care settings. Professionals’ need to have sufficient competency to promote health and wellbeing among older persons. For sustainable care, there is a need for efficient educational efforts in the home care context. Person-centred communication may increase the quality of care and improve older persons independence.Aim: To develop, test and evaluate a web based educational intervention on person-centred communication targeting nurse assistants (NA) in home care setting.Method: A stepwise web based education, consisting of eight modules, was developed and tested. The education was evaluated using both quantitative and qualitative data.Results: In all, 23 NAs participated in the education. The majority of the NAs (n=21) participated in five or more modules. Overall, the education was experienced as feasible and accessible. Challenges emerged during the time of the intervention, such as time constrains, technical problems, and participants´ engagement.Conclusion: The web-based education was found to be a feasible way to offer education to home care staff, although successful implementation requires adaptations to the current context. Engagement from managers, especially considering the NAs motivation to complete the education is important for accomplishment by participants.Implications: This study can contribute to the knowledge regarding how to develop, test and evaluate an educational intervention, and considerations found to be important during the implementation process for success.
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| 25. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
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An educational intervention to improve communication skills in home care – a feasibility study
- 2022
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Konferensbidrag (refereegranskat)abstract
- An educational intervention to improve communication skills in home care – a feasibility studyBackgroundAn educational intervention focused on person-centred communication with older persons in home care was developed. Twenty-three nursing assistants (NAs) from two home care units were offered the intervention. This feasibility study was conducted to capture benefits and pit falls with study processes before large scale interventions, such as acceptability and appropriateness of evaluation methods.AimTo explore the feasibility of proposed methods for evaluating a novel educational intervention on person-centered communication for NAs in home care.MethodFeasibility study with pre- and post-assessments, including evaluation of data collection procedures, completion rates, and missing data for two questionnaires: Self-efficacy Questionnaire measuring communication skills and Measure of Job Satisfaction. Descriptive and statistical analysis was conducted. ResultsThe results showed a completion rate of 83% and 61% in pre- and post-assessment respectively, and a low proportion of missing data. The questionnaires were feasible and acceptable for NAs to complete and understand. Stress due to staff shortages and high workload negatively affected NAs’ participation in data collection. Overall, NAs rated their communication skills as high with a tendency towards higher communication self-efficacy after the intervention, however, this difference was not statistically significant. Job satisfaction remained unchanged pre- and post-intervention.ConclusionLow follow-up rates suggest that the data collection procedures need refinement. Although the outcomes are preliminary at this point, they indicate a ceiling effect in NAs’ self-efficacy ratings. The ceiling effect limits possibilities for improvement and suggests that studies with a larger sample is needed.Implications for caring in a changing worldIn a changing world, where a rapid aging population challenges home care services, there is a need for innovative interventions that support and strengthen health care professionals’ communication skills, aiming at improving older persons’ well-being This study contributes with knowledge to the complexity of developing and evaluating complex interventions on communication in home care.
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| 26. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
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Communication in home care—A feasibility study of an educational intervention in self‐efficacy and job satisfaction
- 2023
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Ingår i: Nursing Open. - : John Wiley & Sons. - 2054-1058. ; 10:3, s. 1375-1382
-
Tidskriftsartikel (refereegranskat)abstract
- AimTo explore the feasibility of evaluating a novel educational intervention on person-centered communication for nursing assistants (NAs) in home care.DesignA feasibility study with pre- and post-assessments.MethodsFeasibility was assessed pre- and post-intervention, including evaluation of data collection procedures, completion rates and missing data in two questionnaires: Self-efficacy Questionnaire measuring communication skills and Measure of Job Satisfaction, analysed descriptively and statistically.ResultsThe questionnaires were feasible and acceptable for the NAs to complete and understand. The pre- and post-assessments showed 83% and 61% completion rates, respectively, and a low proportion of missing data. Barriers for not participating in data collection were stress caused by staff shortages and high workload. Preliminary analysis of the questionnaires showed no significant difference pre- and post-intervention, even though an overall tendency of increased communication self-efficacy was observed. The NAs' self-efficacy ratings also revealed a ceiling effect.
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| 27. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
-
Development and process evaluation of an educational intervention on communication targeting nurse assistants in home care
- 2019
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Konferensbidrag (refereegranskat)abstract
- BackgroundPerson-centred communication is important to assure the quality of home care services and to promote older persons´ independence and influence over their lives. Previous research indicates challenges regarding communication between professionals and home care recipients, and how to deliver efficient educational efforts in the home care context.AimThe aim was to describe the development and process evaluation of a web-based education intervention in person-centred communication for nurse assistants (NA) in home care.MethodThe intervention consisted of a step-wise education, with eight modules that included short video based lectures and movies, one group supervision, and reflective assignments. The content was based on previous research on health care communication and person-centred care. Data were collected from multiple sources before, during and after the implementation, and analysed by a combination of quantitative and qualitative approaches.ResultsA complex intervention was conducted to improve the communication competency wanted for person-centred care. The intervention was offered to 23 nurse assistants (NA). Of those, 91% (n=21) participated, in total or in parts, in five or more modules. The findings address participants’ experiences of expectations and worries before the intervention, experiences from the implementation process, and their experiences from taking part of the intervention. During the implementation changes were made according to local circumstances. Overall, the education was experienced as feasible. The web-based design was found to be accessible and the content relevant.ConclusionFrom this study, it can be concluded that the key features for successful implementation of the intervention was the format, educational content, and technical facilities provided. In addition to this, participant involvement, resources and constructive practical circumstances for NAs to participate in the intervention are crucial.
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| 28. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
-
Development and process evaluation of an educational intervention on person-centred communication targeting nurse assistants in home care
- 2020
-
Konferensbidrag (refereegranskat)abstract
- BACKGROUNDPerson-centred communication is important to assure the quality of home care services and to promote older persons´ independence and influence over their lives. Previous research indicates challenges regarding communication between professionals and home care recipients, and how to deliver efficient educational efforts in the home care context.AIMThe aim was to describe the development and process evaluation of a web-based education intervention in person-centred communication for nurse assistants (NA) in home care.METHODSThe intervention consisted of a step-wise education, with eight modules that included short video based lectures and movies, one group supervision, and reflective assignments. The content was based on previous research on health care communication and person-centred care. Data were collected from multiple sources before, during and after the implementation, and analysed by a combination of quantitative and qualitative approaches.RESULTSA complex intervention was conducted to improve the communication competency wanted for person-centred care. The intervention was offered to 23 nurse assistants (NA). Of those, 91% (n=21) participated, in total or in parts, in five or more modules. The findings address participants’ experiences of expectations and worries before the intervention, experiences from the implementation process, and their experiences from taking part of the intervention. During the implementation changes were made according to local circumstances. Overall, the education was experienced as feasible. The web-based design was found to be accessible and the content relevant. CONCLUSIONOur findings show that the benefits of the web-based educational intervention included the short and focused lectures as well as its accessibility. Challenges with the implementation process included gaining access to the NAs and motivating and involving the NAs. This study emphasizes the environmental support needed to successfully conduct complex interventions, including physical, organizational and cultural aspects.
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| 29. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
-
Nurse assistants´ perceptions of developing person-centred communication
- 2021
-
Konferensbidrag (refereegranskat)abstract
- Background: Communication is important for nurse assistants (NAs) when caring for older persons. There is limited research about how to improve the communication competence of NAs in home care. The aim was to describe NAs perception on learning in relation to an educational intervention on person-centred communication.Methods: A qualitative descriptive study was conducted. Data consisted of four group interviews, five individual in-depth interviews and written reflection assignments from participants gathered during the web-based intervention. In total 23 NAs at two home care units participated. The data were analysed using a phenomenographic approach. This is a qualitative method for analysis developed from Nordic traditions of phenomenology. Phenomenography aims to describe individual perceptions of a certain phenomenon.Preliminary findings points to the nurse assistants perceiving that the education supported their development of person-centred communication. They pointed out self-reflections as important for their learning as well as to get confirmation on what was already known. The NAs described that the intervention added to their knowledge and skills. Even though, there was more to learn and challenges that remained regarding communication in challenging situations such as caring for persons in end-of-life and supporting their relatives, caring for persons being aggressive or violent.Preliminary implications of research: This study can provide knowledge on participants’ perspective on their learning process, which may be important to consider when conducting educational interventions in home care as well as other health care contexts.
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| 30. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
-
Process evaluation of the ACTION programme : a strategy for implementing person‐centred communication in home care
- 2021
-
Ingår i: BMC Nursing. - : Springer Nature. - 1472-6955. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is currently a strong emphasis on person-centred care (PCC) and communication; however, little research has been conducted on how to implement person-centred communication in home care settings. Therefore, the ACTION (A person-centred CommunicaTION) programme, which is a web-based education programme focusing on person-centred communication developed for nurse assistants (NAs) providing home care for older persons, was implemented. This paper reports on the process evaluation conducted with the aim to describe and evaluate the implementation of the ACTION programme. Methods: A descriptive design with a mixed method approach was used. Twenty-seven NAs from two units in Sweden were recruited, and 23 of them were offered the educational intervention. Quantitative and qualitative data were collected from multiple sources before, during and after the implementation. Quantitative data were used to analyse demographics, attendance and participation, while qualitative data were used to evaluate experiences of the implementation and contextual factors influencing the implementation. Results: The evaluation showed a high degree of NA participation in the first five education modules, and a decrease in the three remaining modules. Overall, the NAs perceived the web format to be easy to use and appreciated the flexibility and accessibility. The content was described as important. Challenges included time constraints; the heavy workload; and a lack of interaction, space and equipment to complete the programme. Conclusions: The results suggest that web-based education seems to be an appropriate strategy in home care settings; however, areas for improvement were identified. Our findings show that participants appreciated the web-based learning format in terms of accessibility and flexibility, as well as the face-to-face group discussions. The critical importance of organizational support and available resources are highlighted, such as management involvement and local facilitation. In addition, the findings report on the implementation challenges specific to the dynamic home care context. Trial registration: This intervention was implemented with nursing assistants, and the evaluation only involved nursing staff. Patients were not part of this study. According to the ICMJE, registration was not necessary (). © 2021, The Author(s).
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| 31. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
-
‘Sometimes you need an eye-opener’: A qualitative study on nursing assistants' experiences of developing communication skills through an educational intervention on person-centred communication
- 2023
-
Ingår i: Nursing Open. - : John Wiley & Sons. - 2054-1058.
-
Tidskriftsartikel (refereegranskat)abstract
- AimTo explore nursing assistants' (NAs') experiences of developing communication skills while participating in an educational intervention on person-centred communication.DesignA descriptive qualitative study was conducted.MethodsData were collected from interviews and written assignments before, during and after an educational intervention on person-centred communication targeting NAs in home care services. The data were analysed using a phenomenological approach. A total of 25 NAs participated in the study.ResultsThe findings describe NAs' experiences concerning the communication skills needed for building relationships with older persons and handling emotionally challenging situations. The educational intervention increased their knowledge and awareness of the importance of communication skills and how such skills are developed and refined.
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| 32. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
-
The Development and Process Evaluation of the ACTION Study. A Person-centred Communication Intervention Targeting Nursing Staff in Home Care for Older Persons
- 2019
-
Konferensbidrag (refereegranskat)abstract
- Background: Person-centred communication is important to assure the quality of home care services and to promote older persons independence and influence over their lives. Previous research indicates challenges regarding communication between professionals and home care recipients, and how to deliver efficient educational efforts in the home care context. Hitherto, research on design and implementation of this type of intervention is scarce.Aims and objectives: To describe the development and process evaluation of an education intervention in person-centred communication for nursing staff (NS) in home care.Method: The web-based education consisted of eight modules, including short video based lectures and movies, one group supervision, and reflective assignments. The content was based on previous research of health care communication and person-centred care. Data was collected from multiple sources (web analytics, interviews, evaluation forms, and field notes), before, during and after the implementation, and analysed by a combination of quantitative and qualitative approaches.Results: In all, 23 NS participated in the education. Initial analysis indicate that a majority of the participants completed six or more modules. Overall, the content was experienced as relevant and interesting. The flexibility and accessibility of the web-based format was appreciated, as well as the mix of lectures, short movies, reflective assignments and group supervision. Challenges included developing content relevant to work teams with diverse competence levels and individual differences (e.g. age, language, motivation). Furthermore, time constrains and structure of work emerged as barriers for implementing the education, in some cases adding stress and fragmentation to NS´ work.Conclusions: This type of intervention seems to be a feasible approach for flexible educations in person-centred communication for NS. Engagement and commitment from managers and team leaders may be key factors in succeeding, with impact on participants´ motivation to fulfil the education.
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| 33. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
-
Walk a fine line between meaningfulness or discomfort : the complexity of emotional communication
- 2022
-
Konferensbidrag (refereegranskat)abstract
- Background: The home care of older persons includes inter-personal interactions and communication needed to care for and respond to diverse needs of older people. Previous research has focused on emotional expressions of older persons and responses by nursing staff. Research on the meaning of the interaction in these sequences is sparse. Therefore, the aim of this study was to illuminate the meaning attached to sequences of emotional communication and the interaction during these sequences between older persons and nursing assistants during home care visits.Methods: A descriptive observational design was used. The data consisted of 44 audio recordings of real-life conversations between older persons and nursing assistants during home care visits. A hermeneutic phenomenological analysis was conducted.Findings: Preliminary results indicate sequences of emotional communication being a window of opportunities. The interaction that followed were linked to dual and sometimes incongruent meanings. Expressions being actively blocked or ignored could cause an increase of unpleasant emotions or distract away from negative feelings. Simultaneously, such conversations could both ease or add to the complexity of the interaction and communication. Conversations elaborating on the older persons’ emotions seemed to instill trust and create meaningfulness, at the same time as these situations contained unpleasant moments with sad or angry feelings. The risk for discomfort in these sequences could threaten the trust in the relationship.Discussion: Conversations on older persons worries can be complex: the findings point to a fine line between meaningfulness and distress in these sequences. Unpleasant emotions call for attention and caution, these may need to be noticed at the same time as they cannot be forced out.
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| 34. |
- Gyllenhammar, Irina, et al.
(författare)
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Clotrimazole exposure modulates aromatase activity in gonads and brain during gonadal differentiation in Xenopus tropicalis frogs
- 2009
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Ingår i: Aquatic Toxicology. - Amsterdam : Elsevier BV. - 0166-445X .- 1879-1514. ; 91:2, s. 102-109
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Tidskriftsartikel (refereegranskat)abstract
- Clotrimazole is a pharmaceutical used for treatment of fungal infections. It has been found in surface waters outside municipal wastewater treatment plants but data are scarce regarding its effects on aquatic organisms. It is known that clotrimazole and other imidazole fungicides are inhibitors of the enzyme aromatase (CYP 19). Aromatase converts androgens into estrogens and is suggested to be involved in the sex differentiation in amphibians. The aim of the present study was to evaluate effects of larval exposure to clotrimazole on aromatase activity in brain and gonads, and on gonadal differentiation in Xenopus tropicalis frogs. Another purpose was to determine if larval exposure to ethynylestradiol (EE(2)), at a concentration known to cause male-to-female sex reversal, affects aromatase activity in brain and gonads during gonadal differentiation. Tadpoles were exposed from shortly after hatching (Nieuwkoop and Faber developmental stages 47-48) until complete metamorphosis (NF stage 66) to 6, 41, and 375 nM clotrimazole or 100 nM (nominal) EE(2). Aromatase activity was measured in the brain and gonad/kidney complex of tadpoles during gonadal differentiation (NF stage 56) and, in the clotrimazole experiment, also at metamorphosis. In clotrimazole-exposed tadpoles gonadal aromatase activity increased over exposure time in the 41 and 375 nM groups but did not differ significantly from the control group. Gonadal aromatase activity was increased in both sexes exposed to 41 and 375 nM clotrimazole at metamorphosis. Brain aromatase activity was decreased in tadpoles (NF stage 56) exposed to 375 nM clotrimazole, but at metamorphosis no differences were seen between groups or between sexes. No effects of clotrimazole on sex ratio or gonadal histology were noted at completed metamorphosis. EE(2)-exposed tadpoles had a slightly decreased gonadal aromatase activity, though not significantly different from control group, and there was no effect of EE(2) on brain aromatase activity. All EE(2)-exposed tadpoles developed ovaries. These findings indicate that estrogen-induced ovarian differentiation is not paralleled by increased gonadal aromatase activity in X. tropicalis. Further studies are needed, especially on developmental reproductive toxicity, to assess the risk for endocrine disruption in wild amphibians posed by clotrimazole and other imidazole fungicides.
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| 35. |
- Gåfvels, Camilla, 1977-, et al.
(författare)
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Sy ihop : Kommunikativa resurser i olika (slöjd)bedömningshandlingar
- 2024
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Ingår i: Techne series. - 1238-9501 .- 1893-1774. ; 31:1, s. 82-100
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Tidskriftsartikel (refereegranskat)abstract
- This article explores assessment actions –as an aspect of classroom communication –and how they are expressed in sloyd teaching; with a formative aim centering on pupils’ learning and (the teacher’s) own teaching practice, respectively. In this context, the teacher holds a central role, mediating sloyd knowing through (communicative) verbal and physical actions, acting as an authoritative guidefor pupils’ learning, by making perceptually tacit knowing discernable thanks to pre-established confidence for the teacher in question. Besides authoritative guiding, another theoretical starting point of the article is sociomateriality; a perspective considering physical objects as resulting from connections and activity, hence influencing on the (more) social sphere of actions and activity. The method used is multimodal interaction analysis of three video-recorded sequences of teacher/pupil interaction in a sloyd-classroom setting. To sum up, the findings of the article display how formative assessment in the sloyd context consists of the teacher adapting questions posed to ascertain the knowing of the pupil, then waiting to see how/what/if the pupil performs, whilst being provided –gentle but ample –authoritative guiding to help in the process. The main contribution of the study is establishing the role of formative assessment within sloyd education. The research project has been conducted within the framework of Stockholm Teaching and Learning Studies (STLS), entailing the active involvement of the teacher in question as co-author of the article.
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| 36. |
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| 37. |
- Hjelm, Linnea C., 1993-, et al.
(författare)
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Affibody Molecules Intended for Receptor-Mediated Transcytosis via the Transferrin Receptor
- 2023
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Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 16:7
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Tidskriftsartikel (refereegranskat)abstract
- The development of biologics for diseases affecting the central nervous system has been less successful compared to other disease areas, in part due to the challenge of delivering drugs to the brain. The most well-investigated and successful strategy for increasing brain uptake of biological drugs is using receptor-mediated transcytosis over the blood-brain barrier and, in particular, targeting the transferrin receptor-1 (TfR). Here, affibody molecules are selected for TfR using phage display technology. The two most interesting candidates demonstrated binding to human TfR, cross-reactivity to the murine orthologue, non-competitive binding with human transferrin, and binding to TfR-expressing brain endothelial cell lines. Single amino acid mutagenesis of the affibody molecules revealed the binding contribution of individual residues and was used to develop second-generation variants with improved properties. The second-generation variants were further analyzed and showed an ability for transcytosis in an in vitro transwell assay. The new TfR-specific affibody molecules have the potential for the development of small brain shuttles for increasing the uptake of various compounds to the central nervous system and thus warrant further investigations.
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| 38. |
- Hjelm, Linnea C., et al.
(författare)
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Construction and Validation of a New Naive Sequestrin Library for Directed Evolution of Binders against Aggregation-Prone Peptides
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules are small affinity proteins that have excellent properties for many different applications, ranging from biotechnology to diagnostics and therapy. The relatively flat binding surface is typically resulting in high affinity and specificity when developing binding reagents for globular target proteins. For smaller unstructured peptides, the paratope of affibody molecules makes it more challenging to achieve a sufficiently large binding surface for high-affinity interactions. Here, we describe the development of a new type of protein scaffold based on a dimeric form of affibodies with a secondary structure content and mode of binding that is distinct from conventional affibody molecules. The interaction is characterized by encapsulation of the target peptide in a tunnel-like cavity upon binding. The new scaffold was used for construction of a high-complexity phage-displayed library and selections from the library against the amyloid beta peptide resulted in identification of high-affinity binders that effectively inhibited amyloid aggregation.
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| 39. |
- Hjelm, Linnea C., 1993-
(författare)
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Development of new affinity proteins for neurodegenerative disorders
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neurodegenerative disorders include a full spectrum of diagnoses, including dementias and other neuronal diseases, characterised by degradation of neurons in the brain occurring along with disease progression. Amongst the dementias, the most prevalent are Alzheimer’s (AD) and Parkinson’s disease (PD) that affect millions of people worldwide. During the last years, advancements in potential treatments have been made where the first two clinical antibodies have been approved by the US Food and Drug Administration (FDA) for a disease modifying effect on Alzheimer’s disease.As alternatives to antibodies, other types of affinity reagents that are based on non-immunoglobulin protein scaffolds are also investigated. Such alternative scaffolds often demonstrate distinct and complementary properties compared to antibodies. In this thesis, the development of a new type of affinity protein scaffold called sequestrin is described. Sequestrins are derived from the affibody molecule and comprise two heterogenic subunits with truncated N-terminals fused as a head-to-tail construct. Sequestrins undergo a structural rearrangement upon target binding and forms a stabile complex. The scaffold is designed for interactions with disease-related amyloidogenic peptides e.g. amyloid beta and alpha-synuclein involved in AD and PD, respectively. In the first paper, a sequestrin library was developed and its compatibility with phage display was investigated. Successful panning against the amyloid beta peptide resulted in binders with high affinity. Further on in paper II, the alpha-synuclein peptide was targeted and sequestrins with low nanomolar affinities were obtained. All sequestrins displayed structural rearrangement upon target engagement, which stabilized the interaction to the target peptides and further inhibited toxic aggregation, opening up for future studies of disease modifying effects in vivo.When targeting the brain, passage through the blood–brain barrier (BBB) is an obstacle that needs to be addressed to reach sufficiently high therapeutic concentrations. To overcome this barrier, brain shuttles have been developed with the capability to transport a cargo over the BBB. One such mechanism of transportation is by receptor-mediated transcytosis, which is utilized by e.g. the transferrin receptor (TfR). In paper III, a TfR-targeting shuttle was investigated for BBB passage when fused to a sequestrin targeting the amyloid beta peptide, resulting in a higher penetration through the BBB, and maintained functionality of the sequestrin.High-throughput in vitro methods would facilitate development of novel brain shuttles. Thus, in paper IV, a transwell system based on nanofibrillar silkmembranes with murine brain endothelial cells was developed. Evaluation of the method using a TfR-specific antibody demonstrated higher transfer over the barrier compared to an isotype control and the method has potential to facilitate screening of transcytosis capability of brain shuttles.In paper V, TfR-specific affibody-based brain shuttles were developed and investigated for transcytosis capability using the in vitro transcytosis assay. A panel of affibody molecules were evaluated, demonstrating both cross-species reactivity to murine and human TfR and active receptor-mediated transcytosis. These candidates could thus potentially be used in further development of CNS-targeting therapeutics.In conclusion, a new sequestrin scaffold was developed that can be utilised for targeting amyloidogenic peptides found in neurodegenerative disorders. An affibody-based brain shuttle was also developed, which showed transcytosis capability. In the future, the new brain shuttle might be combined with sequestrins to create multifunctional fusion proteins for facilitated delivery over the BBB, which hopefully can result in therapeutic concentrations in the brain even when administered with a lower dosage.
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| 40. |
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| 41. |
- Höglander, Jessica, et al.
(författare)
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Implementing A person-centred CommunicaTION (ACTION) educational intervention for in-home nursing assistants – a study protocol
- 2023
-
Ingår i: BMC Geriatrics. - : BioMed Central (BMC). - 1471-2318. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In this study, the focus is on how to support the competence development needed for nursing assistants in home care. Home care services for older persons can be challenging concerning the nature of the interpersonal interaction and communication needed to care for and respond to the diverse needs of older people who seek to live well in our communities. This implies a need to offer more person-centred care (PCC) to older persons. However, there is a lack of knowledge on how to develop such competence. We, therefore, developed A Person-centred CommunicaTION (ACTION) programme, which is a web-based educational intervention aimed at supporting competence development for nursing assistants. The research objective is to evaluate the ACTION programme with respect to participants’ responses to and the effect of the intervention. Methods: A multicentre case–control study with pre- and post-assessments was designed. The ACTION programme will be implemented at home care units, in two different geographic areas in Sweden. A total of 300 nursing assistants will be recruited: 150 for the intervention group and 150 for the control group. We will evaluate the impact measures and the process. Pre- and post-assessments will be performed with data collected via a) audio recordings of communication, b) a questionnaire on self-efficacy communication skills, PCC, empathy and job satisfaction, c) user data, evaluation forms, field notes and observations, and d) interviews. The data will be analysed with descriptive and analytic statistics and/or qualitative methods for meanings. Discussion: This study has the potential to contribute to the evidence supporting competence development required to offer person-centred and quality home care to older persons and to meet upcoming needs for flexible and easily accessible competence development. Trial registration: ISRCTN64890826. Registered 10 January 2022, https://www.isrctn.com/ISRCTN64890826
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| 42. |
- Johnsson, Natali, et al.
(författare)
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Delineating and clarifying the concept of self-care monitoring : a concept analysis
- 2023
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Ingår i: International Journal of Qualitative Studies on Health and Well-being. - : Taylor & Francis. - 1748-2623 .- 1748-2631. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- AimTo delineate and clarify the meaning of the concept of self-care monitoring from a patient perspective.MethodsA systematic search was performed in the databases ASSIA, CINAHL, PsycInfo, and PubMed (January 2016–September 2021). A selection of 46 peer-reviewed articles was included in the study and analysed using Rodgers’ Evolutionary Method for Concept Analysis.ResultsThe following four attributes were identified: Tracking symptoms, signs, and actions, Paying attention, Being confident, and Needing routines, creating a descriptive definition: “Self-care monitoring is an activity that means a person has to pay attention and be confident and needs routines for tracking symptoms, signs, and action.” The antecedents of the concept were shown to be Increased knowledge, Wish for independence, and Commitment. The concepts’ consequences were identified as Increased interaction, Perceived burden, and Enhanced well-being.ConclusionsThis concept analysis provides extensive understanding of self-care monitoring from a patient perspective. It was shown that the concept occurs when a person practices self-care monitoring at home either with or without devices. A descriptive definition was constructed and presented with exemplars to encourage practice of the concept in various healthcare settings and could be of relevance to people with chronic illnesses or other long-term conditions.
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| 43. |
- Johnsson, Natali, et al.
(författare)
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Supporting patients with venous leg ulcers in self-care monitoring : an interview study with primary health care professionals
- 2024
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Ingår i: Scandinavian Journal of Primary Health Care. - : Taylor & Francis Group. - 0281-3432 .- 1502-7724.
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThis study described the experiences and perceptions of how primary health care professionals (PHCPs) support patients with venous leg ulcers (VLUs) in self-care monitoring.DesignA qualitative approach with reflexive thematic analysis was used, with 24 individual qualitative open interviews.SettingPrimary health care clinics and community health care in four southern regions in Sweden.SubjectsRegistered nurses, district nurses and nurse assistants who had experience of caring for patients with VLUs. In total, 24 interviews were conducted with PHCPs in Sweden.ResultsPHCPs have a vital role in promoting patient independence and responsibility, identifying needs and adapting care strategies, while also recognising unmet needs in patients with VLUs.ConclusionPHCPs actively monitor patients' self-care and establish caring relationships. They see a need for a structured primary health care work routine for ulcer management. PHCPs described encouraging patients by identifying needs, adapting care and promoting self-care monitoring using various skills and strategies.PHCPs described unmet needs and insufficient care practices for patients with VLUs.PHCPs pointed out the importance of establishing caring relationships in order to involve patients in their VLU treatment.
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| 44. |
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| 45. |
- Larsson, Kjell, et al.
(författare)
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Behandling med läkemedel kan reducera mortaliteten vid KOL : [Pharmacological treatment reduces mortality in COPD]
- 2022
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Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 119
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 500 000 individuals in Sweden have chronic obstructive pulmonary disease (COPD). Co-morbid, especially cardiovascular, conditions are common in COPD and globally COPD is the third most common cause of mortality. Mortality in COPD is driven by dyspnea, exacerbations and comorbidities and is reduced by smoking cessation and lung rehabilitation. Also, pharmacological treatment, in particular inhaled corticosteroids, reduces mortality in COPD. The reduction in mortality that can be achieved by treatment with inhaled corticosteroids in combinations with long-acting bronchodilators is of the same order of magnitude as the effect on mortality by treatment of hyperlipidemia and hypertension.
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| 46. |
- Larsson, Kjell, et al.
(författare)
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Behandling med läkemedel kan reducera mortaliteten vid KOL
- 2022
-
Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 119
-
Tidskriftsartikel (refereegranskat)abstract
- Approximately 500 000 individuals in Sweden have chronic obstructive pulmonary disease (COPD). Co-morbid, especially cardiovascular, conditions are common in COPD and globally COPD is the third most common cause of mortality. Mortality in COPD is driven by dyspnea, exacerbations and comorbidities and is reduced by smoking cessation and lung rehabilitation. Also, pharmacological treatment, in particular inhaled corticosteroids, reduces mortality in COPD. The reduction in mortality that can be achieved by treatment with inhaled corticosteroids in combinations with long-acting bronchodilators is of the same order of magnitude as the effect on mortality by treatment of hyperlipidemia and hypertension.
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| 47. |
- Leitao, Charles Dahlsson, 1992-, et al.
(författare)
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Display of a naïve affibody library on staphylococci for selection of binders by means of flow cytometry sorting
- 2023
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 655, s. 75-81
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Tidskriftsartikel (refereegranskat)abstract
- Within the field of combinatorial protein engineering there is a great demand for robust high-throughput selection platforms that allow for unbiased protein library display, affinity-based screening, and amplification of selected clones. We have previously described the development of a staphylococcal display system used for displaying both alternative-scaffolds and antibody-derived pro-teins. In this study, the objective was to generate an improved expression vector for displaying and screening a high-complexity naive affibody library, and to facilitate downstream validation of isolated clones. A high-affinity normalization tag, consisting of two ABD-moieties, was introduced to simplify off-rate screening procedures. In addition, the vector was furnished with a TEV protease substrate recog-nition sequence upstream of the protein library which enables proteolytic processing of the displayed construct for improved binding signal. In the library design, 13 of the 58 surface-exposed amino acid positions were selected for full randomization (except proline and cysteine) using trinucleotide tech-nology. The genetic library was successfully transformed to Staphylococcus carnosus cells, generating a protein library exceeding 109 members. De novo selections against three target proteins (CD14, MAPK9 and the affibody ZEGFR:2377) were successfully performed using magnetic bead-based capture followed by flow-cytometric sorting, yielding affibody molecules binding their respective target with nanomolar affinity. Taken together, the results demonstrate the feasibility of the staphylococcal display system and the proposed selection procedure to generate new affibody molecules with high affinity.
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| 48. |
- Lindberg, Hanna, et al.
(författare)
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A truncated and dimeric format of an Affibody library on bacteria enables FACS-mediated isolation of amyloid-beta aggregation inhibitors with subnanomolar affinity
- 2015
-
Ingår i: Biotechnology Journal. - : Wiley. - 1860-6768 .- 1860-7314. ; 10:11, s. 1707-1718
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Tidskriftsartikel (refereegranskat)abstract
- The amyloid hypothesis suggests that accumulation of amyloid β (Aβ) peptides in the brain is involved in development of Alzheimer's disease. We previously generated a small dimeric affinity protein that inhibited Aβ aggregation by sequestering the aggregation prone parts of the peptide. The affinity protein is originally based on the Affibody scaffold, but is evolved to a distinct interaction mechanism involving complex structural rearrangement in both the Aβ peptide and the affinity proteins upon binding. The aim of this study was to decrease the size of the dimeric affinity protein and significantly improve its affinity for the Aβ peptide to increase its potential as a future therapeutic agent. We combined a rational design approach with combinatorial protein engineering to generate two different affinity maturation libraries. The libraries were displayed on staphylococcal cells and high-affinity Aβ-binding molecules were isolated using flow-cytometric sorting. The best performing candidate binds Aβ with a KD value of around 300 pM, corresponding to a 50-fold improvement in affinity relative to the first-generation binder. The new dimeric Affibody molecule was shown to capture Aβ1-42 peptides from spiked E. coli lysate. Altogether, our results demonstrate successful engineering of this complex binder for increased affinity to the Aβ peptide.
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- Lindberg, Hanna, et al.
(författare)
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Are Farming and Animal Exposure Risk Factors for the Development of Granulomatosis with Polyangiitis? Environmental Risk Factors Revisited : A Case-control Study
- 2021
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:6, s. 894-897
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate the possible association between animal exposure and risk for granulomatosis with polyangiitis (GPA).Methods. Patients with GPA at the Department of Rheumatology, Uppsala University Hospital, between January 1, 2011, and December 31, 2018, were consecutively included. All patients filled in a questionnaire on possible environmental exposures: occupation, hobbies, and animal contact. As controls we included 128 patients with rheumatoid arthritis (RA) and 248 population controls collected from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, matched for age, sex, and geographical area of residence. The controls filled out a questionnaire on current and past contact with farming and animals, at the time of the RA patient’s diagnosis.Results. A total of 62 patients with GPA, 128 patients with RA, and 248 population controls were included in the study. GPA was significantly associated with horse exposure, with a 2- to 3-fold increased risk compared with RA (OR 3.08, 95% CI 1.34–7.08) and population controls (OR 2.61, 95% CI 1.29–5.29). Borderline increased risks were found for any animal contact, but no association was found when analyzing contact with cats/dogs only. A significant association was found between GPA and farming compared to the population controls (OR 7.60, 95% CI 3.21–17.93).Conclusion. This study has identified for the first time, to our knowledge, a significant association between exposure to specific animals, namely horses, and the development of GPA. The results also support previous studies reporting an association between farming and GPA, underscoring the possibility of exogenous factors as initiators in the development of GPA.
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