| 1. |
- 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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| 2. |
- 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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| 3. |
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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
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| 9. |
- 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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| 10. |
- 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
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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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| 11. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
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Development and process evaluation of an educational intervention on person-centred communication targeting nurse assistants in home care
- 2020
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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.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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| 12. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
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Nurse assistants´ perceptions of developing person-centred communication
- 2021
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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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| 13. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
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Process evaluation of the ACTION programme : a strategy for implementing person‐centred communication in home care
- 2021
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Ingår i: BMC Nursing. - : Springer Nature. - 1472-6955. ; 20:1
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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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| 14. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
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‘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
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Ingår i: Nursing Open. - : John Wiley & Sons. - 2054-1058.
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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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| 15. |
- Gustafsson, Tanja, PhD student, 1980-, et al.
(författare)
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Walk a fine line between meaningfulness or discomfort : the complexity of emotional communication
- 2022
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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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| 16. |
- 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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| 17. |
- 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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| 18. |
- 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
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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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| 19. |
- 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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| 20. |
- 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
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Ingår i: BMC Geriatrics. - : BioMed Central (BMC). - 1471-2318. ; 23:1
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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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| 21. |
- 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
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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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| 22. |
- 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.
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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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| 23. |
- 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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| 24. |
- Larsson, Kjell, et al.
(författare)
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Behandling med läkemedel kan reducera mortaliteten vid KOL
- 2022
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Ingår i: Läkartidningen. - 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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| 25. |
- 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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| 26. |
- 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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| 27. |
- Mattisson, Jonas, 1994-, et al.
(författare)
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Loss of chromosome Y in regulatory T cells
- 2024
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Ingår i: BMC Genomics. - : BioMed Central (BMC). - 1471-2164. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMosaic loss of chromosome Y (LOY) in leukocytes is the most prevalent somatic aneuploidy in aging humans. Men with LOY have increased risks of all-cause mortality and the major causes of death, including many forms of cancer. It has been suggested that the association between LOY and disease risk depends on what type of leukocyte is affected with Y loss, with prostate cancer patients showing higher levels of LOY in CD4 + T lymphocytes. In previous studies, Y loss has however been observed at relatively low levels in this cell type. This motivated us to investigate whether specific subsets of CD4 + T lymphocytes are particularly affected by LOY. Publicly available, T lymphocyte enriched, single-cell RNA sequencing datasets from patients with liver, lung or colorectal cancer were used to study how LOY affects different subtypes of T lymphocyte. To validate the observations from the public data, we also generated a single-cell RNA sequencing dataset comprised of 23 PBMC samples and 32 CD4 + T lymphocytes enriched samples.ResultsRegulatory T cells had significantly more LOY than any other studied T lymphocytes subtype. Furthermore, LOY in regulatory T cells increased the ratio of regulatory T cells compared with other T lymphocyte subtypes, indicating an effect of Y loss on lymphocyte differentiation. This was supported by developmental trajectory analysis of CD4 + T lymphocytes culminating in the regulatory T cells cluster most heavily affected by LOY. Finally, we identify dysregulation of 465 genes in regulatory T cells with Y loss, many involved in the immunosuppressive functions and development of regulatory T cells.ConclusionsHere, we show that regulatory T cells are particularly affected by Y loss, resulting in an increased fraction of regulatory T cells and dysregulated immune functions. Considering that regulatory T cells plays a critical role in the process of immunosuppression; this enrichment for regulatory T cells with LOY might contribute to the increased risk for cancer observed among men with Y loss in leukocytes.
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| 28. |
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| 29. |
- Mezheyeuski, Artur, et al.
(författare)
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An immune score reflecting pro- and anti-tumoural balance of tumour microenvironment has major prognostic impact and predicts immunotherapy response in solid cancers
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 88
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression.Methods: Through a multiplex in situ analysis we evaluated 15 immune cell classes in 1481 tumour samples. Single-cell and bulk RNAseq data sets were used for functional analysis and validation of prognostic and predictive associations.Findings: By combining the prognostic information of anti-tumoural CD8+ lymphocytes and tumour supportive CD68+CD163+ macrophages in colorectal cancer we generated a signature of immune activation (SIA). The prognostic impact of SIA was independent of conventional parameters and comparable with the state-of-art immune score. The SIA was also associated with patient survival in oesophageal adenocarcinoma, bladder cancer, lung adenocarcinoma and melanoma, but not in endometrial, ovarian and squamous cell lung carcinoma. We identified CD68+CD163+ macrophages as the major producers of complement C1q, which could serve as a surrogate marker of this macrophage subset. Consequently, the RNA-based version of SIA (ratio of CD8A to C1QA) was predictive for survival in independent RNAseq data sets from these six cancer types. Finally, the CD8A/C1QA mRNA ratio was also predictive for the response to checkpoint inhibitor therapy.Interpretation: Our findings extend current concepts to procure prognostic information from the tumour immune microenvironment and provide an immune activation signature with high clinical potential in common human cancer types.
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| 30. |
- Moya Nunez, Alice, et al.
(författare)
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Influence of PbCl2 and KCl salt mixture on high temperature corrosion of alloy 625
- 2024
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Ingår i: Fuel. - : Elsevier Ltd. - 0016-2361 .- 1873-7153. ; 358
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Tidskriftsartikel (refereegranskat)abstract
- Aggressive corrosion can occur when firing waste or bio-based fuels, due to the presence of high concentrations of heavy metals, alkali metals, and chlorides. These deleterious compounds deposit on furnace walls and can form mixtures that can rapidly accelerate corrosion. The effect of salts containing lead had not been studied extensively at temperatures lower than 400 °C in nickel-based materials. This study investigates the effect of the individual salts PbCl2 and KCl and their mixture on the high temperature corrosion of alloy 625 at 340 °C and 380 °C. Samples of alloy 625 were covered with individual salts or a salt mixture and exposed to high temperatures in an atmosphere of synthetic air, 20-vol% H2O, and 100 ppm HCl. The results show that the presence of individual salts does not induce observable corrosion attack on alloy 625 after 168 h at any tested temperature. The salt mixture did cause a severe corrosion attack at 380 °C, observed after 24 h of exposure. It is suggested that the salt mixture induces the formation of lead chromates that may prevent or disrupt the formation of a protective chromia scale. It is believed that a key part of the mechanism is the formation of eutectic melts by the interaction of the scale with the salt mixture. Thermodynamic equilibria calculations show that the first melting temperature of PbCl2 and KCl salt mixture after reaction with oxygen can be as low as about 382 °C, and even lower (357 °C) if chromates are present.
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| 31. |
- Olsson, Tina M., et al.
(författare)
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Study protocol for a non-randomized controlled trial of the effects of internet-based parent training as a booster to the preschool edition of PATHS® : Universal edition of the Parent Web
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:4, s. e0284926-e0284926
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Tidskriftsartikel (refereegranskat)abstract
- Well implemented, universal parental support is often effective in families with younger children, but research on their effects on families with adolescent children is scarce. In this study, a trial of the universal parent training intervention “Parent Web” in early adolescence is added to the social emotional learning intervention Promoting Alternative Thinking Strategies (PATHS®), completed in early childhood. The Parent Web is a universal online parenting intervention based on social learning theory. The intervention aims to promote positive parenting and family interaction through five weekly modules completed over 6–8 weeks.The main hypothesis is that participants in the intervention group will exhibit significant pre to post- intervention-related benefits relative participants in the comparison group.The aims of this study are: 1) provide Parent Web as a booster aimed at improving parenting support and practices at the transition into adolescence to a cohort of parents whose children have previously participated in preschool PATHS, and 2) examine the effects of the universal edition of Parent Web. The study has a quasi-experimental design with pre- and post-testing.The incremental effects of this internet-delivered parent training intervention are tested in parents of early adolescents (11–13 years) who participated in PATHS when 4–5 years old compared to a matched sample of adolescents with no prior experience of PATHS. The primary outcomes are parent reported child behavior and family relationships. Secondary outcomes include self-reported parent health and stress. The proposed study is one of the few trials to test the effects of universal parental support in families of early adolescents and will therefore contribute to the understanding of how mental health in children and young people can be promoted across developmental periods through a continuum of universal measures.Trial registration: Clinical trials.gov (NCT05172297), prospectively registered on December 29, 2021.
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| 32. |
- Rudolph, Claudina, et al.
(författare)
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Scandinavian trial of uncomplicated aortic dissection therapy : study protocol for a randomized controlled trial
- 2023
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Ingår i: Trials. - : BioMed Central (BMC). - 1745-6215. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundContemporary management of uncomplicated type B aortic dissections (uTBAD) is based on the acuity and various morphological features. Medical therapy is mandatory, while the risks of early thoracic endovascular aortic repair (TEVAR) are balanced against the potential for rupture, complex surgery, and death. Improved aortic morphology following TEVAR is documented, but evidence for improved overall survival is lacking. The costs and impact on quality of life are also needed.MethodsThe trial is a randomized, open-label, superiority clinical trial with parallel assignment of subjects at 23 clinical sites in Denmark, Norway, Sweden, Finland, and Iceland. Eligibility includes patients aged ≥ 18 with uTBAD of < 4 weeks duration. Recruited subjects will be randomized to either standard medical therapy (SMT) or SMT + TEVAR, where TEVAR must be performed between 2–12 weeks from the onset of symptoms.DiscussionThis trial will evaluate the primary question of whether early TEVAR improves survival at 5 years among uTBAD patients. Moreover, the costs and the impact on quality of life should provide sorely needed data on other factors that play a role in treatment strategy decisions. The common Nordic healthcare model, with inclusion of all aortic centers, provides a favorable setting for carrying out this trial, while the robust healthcare registries ensure data validity.
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| 33. |
- Svebrant, Sofia, et al.
(författare)
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On-site pilot testing of hospital wastewater ozonation to reduce pharmaceutical residues and antibiotic-resistant bacteria
- 2021
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Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Hospital sewage constitutes an important point source for antibiotics and antibiotic-resistant bacteria due to the high antibiotic use. Antibiotic resistance can develop and cause problems in sewage systems within hospitals and municipal wastewater treatment plants, thus, interventions to treat hospital sewage on-site are important. Ozonation has proven effective in treating relatively clean wastewater, but the effect on untreated wastewater is unclear. Therefore, we piloted implementation of ozonation to treat wastewater in a tertiary hospital in Uppsala, Sweden. We measured active pharmaceutical ingredients (APIs) using liquid chromatography-mass spectrometry and antibiotic-resistant Enterobacteriaceae using selective culturing pre-and post-ozonation. Comparing low (1 m3 /h) and high (2 m3 /h) flow, we obtained a 'dose-dependent' effect of API reduction (significant reduction of 12/29 APIs using low and 2/29 APIs using high flow, and a mean reduction of antibiotics of 41% using low vs. 6% using high flow, 25% vs. 6% for all APIs). There was no significant difference in the amount of antibiotic-resistant Enterobacteiaceae pre-and post-ozonation. Our results demonstrate that ozonation of untreated wastewater can reduce API content. However, due to the moderate API decrease and numerous practical challenges in the on-site setting, this specific ozonation system is not suitable to implement at full scale in our hospital.
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| 34. |
- Tepper, Viktoria, et al.
(författare)
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Influenza A/H4N2 mallard infection experiments further indicate zanamivir as less prone to induce environmental resistance development than oseltamivir
- 2020
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 101:8, s. 816-824
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Tidskriftsartikel (refereegranskat)abstract
- Neuraminidase inhibitors (NAIs) are the gold standard treatment for influenza A virus (IAV). Oseltamivir is mostly used, followed by zanamivir (ZA). NAIs are not readily degraded in conventional wastewater treatment plants and can be detected in aquatic environments. Waterfowl are natural IAV hosts and replicating IAVs could thus be exposed to NAIs in the environment and develop resistance. Avian IAVs form the genetic basis for new human IAVs, and a resistant IAV with pandemic potential poses a serious public health threat, as NAIs constitute a pandemic preparedness cornerstone. Resistance development in waterfowl IAVs exposed to NAIs in the water environment has previously been investigated in an in vivo mallard model and resistance development was demonstrated in several avian IAVs after the exposure of infected ducks to oseltamivir, and in an H1N1 IAV after exposure to ZA. The N1 and N2 types of IAVs have different characteristics and resistance mutations, and so the present study investigated the exposure of an N2-type IAV (H4N2) in infected mallards to 1, 10 and 100 µg l−1 of ZA in the water environment. Two neuraminidase substitutions emerged, H274N (ZA IC50 increased 5.5-fold) and E119G (ZA IC50 increased 110-fold) at 10 and 100 µg l−1 of ZA, respectively. Reversion towards wild-type was observed for both substitutions in experiments with removed drug pressure, indicating reduced fitness of both resistant viruses. These results corroborate previous findings that the development of resistance to ZA in the environment seems less likely to occur than the development of resistance to oseltamivir, adding information that is useful in planning for prudent drug use and pandemic preparedness.
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