| 1. |
- Byman, Elin, et al.
(författare)
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Alpha-amylase 1A copy number variants and the association with memory performance and Alzheimer's dementia
- 2020
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Previous studies have shown that copy number variation (CNV) in the alpha (alpha)-amylase gene (AMY1A) is associated with body mass index, insulin resistance, and blood glucose levels, factors also shown to increase the risk of Alzheimer's dementia (AD). We have previously demonstrated the presence of alpha-amylase in healthy neuronal dendritic spines and a reduction of the same in AD patients. In the current study, we investigate the relationship between AMY1A copy number and AD, memory performance, and brain alpha-amylase activity. Methods and materials The association between AMY1A copy number and development of AD was analyzed in 5422 individuals (mean age at baseline 57.5 +/- 5.9, females 58.2%) from the Malmo diet and cancer study genotyped for AMY1A copy number, whereof 247 where diagnosed with AD during a mean follow-up of 20 years. Associations between AMY1A copy number and cognitive performance where analyzed in 791 individuals (mean age at baseline 54.7 +/- 6.3, females 63%), who performed Montreal Cognitive Assessment (MoCA) test. Correlation analysis between alpha-amylase activity or alpha-amylase gene expression and AMY1A copy number in post-mortem hippocampal tissue from on demented controls (n = 8) and AD patients (n = 10) was also performed. Results Individuals with very high ( >= 10) AMY1A copy number had a significantly lower hazard ratio of AD (HR = 0.62, 95% CI 0.41-0.94) and performed significantly better on MoCA delayed word recall test, compared to the reference group with AMY1A copy number 6. A trend to lower hazard ratio of AD was also found among individuals with low AMY1A copy number (1-5) (HR = 0.74, 95% CI 0.53-1.02). A tendency towards a positive correlation between brain alpha-amylase activity and AMY1A copy number was found, and females showed higher brain alpha-amylase activity compared to males. Conclusion Our study suggests that the degree of alpha-amylase activity in the brain is affected by AMY1A copy number and gender, in addition to AD pathology. The study further suggests that very high AMY1A copy number is associated with a decreased hazard ratio of AD and we speculate that this effect is mediated via a beneficial impact of AMY1A copy number on episodic memory performance.
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| 2. |
- Dahlgren, Anna, et al.
(författare)
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Intensive longitudinal study of newly graduated nurses' quick returns and self-rated stress
- 2021
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 47:5, s. 404-407
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Tidskriftsartikel (refereegranskat)abstract
- Objective Little is known about the relationship between quick returns (QR) - shift combinations that result in inter-shift rest periods <11 hours) and stress. The current study examined whether variations in the frequency of QR, both between and within individuals, were associated with changes in self-rated stress.Methods A questionnaire was sent weekly to newly graduated nurses during the first 12 weeks of work. Stress was measured with four items from the Stress-Energy Questionnaire on a scale from 1 not at all to 5 very much [mean 2.65, standard deviation (SD) 1.08]. Shifts worked in the past week were reported and QR were identified by evening-morning shift combinations (mean 0.98, SD 0.90 per week). In total, 350 persons were included in the analysis (3556 observations). Data were analyzed with a multilevel residual dynamic structural equation model (RDSEM) using Bayesian estimation procedures.Results There was no between-person effect of QR on stress averaged across measurement occasions (0.181, 95% CI -0.060-0.415). However, there was a small within-person effect of QR (0.031, 95% CI 0.001-0.062), meaning that more QR during a given week, compared to that person's average, was associated with an increase in their level of stress during that week.Conclusions Nurses were likely to report increased stress during weeks in which they worked more QR. Intervention studies are needed to determine whether the relationship is causal.
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| 3. |
- Eklund, Elin, 1992, et al.
(författare)
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Quasi-experimental evaluation of municipal ice cleat distribution programmes for older adults in Sweden
- 2023
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Ingår i: Injury Prevention. - : BMJ Publishing Group Ltd. - 1353-8047 .- 1475-5785. ; 29:5, s. 378-83
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionFall injuries caused by icy road conditions are a prevalent public health problem during winters in Sweden, especially in older populations. To combat this problem, many Swedish municipalities have distributed ice cleats to older adults. While previous research has shown promising results, there is a lack of comprehensive empirical data on the effectiveness of ice cleat distribution. We address this gap by investigating the impact of these distribution programmes on ice-related fall injuries among older adults. MethodsWe combined survey data on ice cleat distribution in Swedish municipalities with injury data from the Swedish National Patient Register (NPR). The survey was used to identify municipalities that have distributed ice cleats to older adults at some point between 2001 and 2019. Data from NPR were used to identify municipality-level data on patients who have been treated for injuries related to snow and ice. We used a triple differences design-a generalisation of difference in differences-that compared ice-related fall injury rates before and after intervention in 73 treatment and 200 control municipalities, with unexposed age groups serving as within-municipality controls. ResultsWe estimate that the average ice cleat distribution programmes reduced ice-related fall injury rates by -0.24 (95% CI -0.49 to 0.02) per 1000 person-winters. The impact estimate was larger in municipalities that distributed more ice cleats (-0.38 (95% CI -0.76 to -0.09)). No similar patterns were found for fall injuries unrelated to snow and ice. ConclusionOur results suggest that ice cleat distribution can decrease the incidence of ice-related injuries among older adults.
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| 4. |
- Frögéli, Elin, et al.
(författare)
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Preventing Stress-Related Ill Health Among New Registered Nurses by Supporting Engagement in Proactive Behaviors : A Randomized Controlled Trial
- 2020
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Ingår i: Worldviews on Evidence-Based Nursing. - : Wiley. - 1545-102X .- 1741-6787. ; 17:3, s. 202-212
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: New registered nurses (RNs) are at risk of developing symptoms of stress-related ill health.OBJECTIVES: To evaluate the effect of a 3 × 3 hour group intervention aiming to prevent symptoms of stress-related ill health among new RNs by increasing engagement in proactive behaviors. The intervention involves discussions and models of newcomer experiences and stress and the behavior change techniques reinforcing approach behaviors, systematic exposure, and action planning.DESIGN: A randomized parallel group trial with an active control condition.PARTICIPANTS: The study sample consisted of 239 new RNs participating in a transition-to-practice program for new RNs in a large county in Sweden.METHODS: Participants were randomized to either the experimental intervention or a control intervention. Data on experiences of stress, avoidance of proactive behaviors, engagement in leisure activities, role clarity, task mastery, and social acceptance were collected before and after the intervention. Effects were evaluated using multilevel model analysis and regression analysis. Missing data were imputed using multiple imputation.RESULTS: The control group experienced a statistically significant increase in experiences of stress during the period of the study (t(194.13) = 1.98, p = .049), whereas the level in the experimental group remained stable. Greater adherence to the intervention predicted a greater effect on experiences of stress (β = -0.15, p = .039) and social acceptance (β = 0.16, p = .027).LINKING EVIDENCE TO ACTION: Transition-to-practice programs may benefit from adding an intervention that specifically addresses new RNs' experiences of stress to further support them as they adjust to their new professional role. However, replication studies with larger samples, more reliable measures, and longer periods of follow-up are needed.
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| 5. |
- Frögéli, Elin, et al.
(författare)
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The Importance of Effective Organizational Socialization for Preventing Stress, Strain, and Early Career Burnout : An Intensive Longitudinal Study of New Professionals
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 19:12, s. 7356-7356
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Tidskriftsartikel (refereegranskat)abstract
- Burnout was originally conceptualized based on experiences of new professionals. Role clarity, task mastery, and social acceptance are recognized as key resources enabling new professionals’ management of the challenges of the new profession. However, relations between these resources and stress, strain, and burnout have not yet been thoroughly investigated at professional entry. Increased understanding of these relations could have implications for strategies to prevent burnout. The aim of the study was to investigate within- and between-individual effects over the first months and relations to burnout at one-year post-entry. Data (n = 322) was collected weekly over the first 13 weeks and again 9 months later. Relationships were modelled using a multilevel regression model and correlation analysis. Results showed that on weeks when participants experienced higher role clarity, task mastery, and social acceptance, they reported significantly less stress, and that participants who experienced higher levels of the resources in general, reported significantly less strain. Levels of the resources at three months were related to symptoms of burnout at 12 months. The study findings provide support of the role of task mastery, role clarity, and social acceptance as resources buffering the impact of demands at professional entry on experiences of stress, strain, and burnout.
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| 6. |
- Gustavsson, Tobias, et al.
(författare)
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Long-term effects of immunotherapy with a brain penetrating Aβ antibody in a mouse model of Alzheimer's disease
- 2023
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central (BMC). - 1758-9193. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBrain-directed immunotherapy is a promising strategy to target amyloid-β (Aβ) deposits in Alzheimer’s disease (AD). In the present study, we compared the therapeutic efficacy of the Aβ protofibril targeting antibody RmAb158 with its bispecific variant RmAb158-scFv8D3, which enters the brain by transferrin receptor-mediated transcytosis.MethodsAppNL−G−F knock-in mice received RmAb158, RmAb158-scFv8D3, or PBS in three treatment regimens. First, to assess the acute therapeutic effect, a single antibody dose was given to 5 months old AppNL−G−F mice, with evaluation after 3 days. Second, to assess the antibodies’ ability to halt the progression of Aβ pathology, 3 months old AppNL−G−F mice received three doses during a week, with evaluation after 2 months. Reduction of RmAb158-scFv8D3 immunogenicity was explored by introducing mutations in the antibody or by depletion of CD4+ T cells. Third, to study the effects of chronic treatment, 7-month-old AppNL−G−F mice were CD4+ T cell depleted and treated with weekly antibody injections for 8 weeks, including a final diagnostic dose of [125I]RmAb158-scFv8D3, to determine its brain uptake ex vivo. Soluble Aβ aggregates and total Aβ42 were quantified with ELISA and immunostaining.ResultsNeither RmAb158-scFv8D3 nor RmAb158 reduced soluble Aβ protofibrils or insoluble Aβ1-42 after a single injection treatment. After three successive injections, Aβ1-42 was reduced in mice treated with RmAb158, with a similar trend in RmAb158-scFv8D3-treated mice. Bispecific antibody immunogenicity was somewhat reduced by directed mutations, but CD4+ T cell depletion was used for long-term therapy. CD4+ T cell-depleted mice, chronically treated with RmAb158-scFv8D3, showed a dose-dependent increase in blood concentration of the diagnostic [125I]RmAb158-scFv8D3, while concentration was low in plasma and brain. Chronic treatment did not affect soluble Aβ aggregates, but a reduction in total Aβ42 was seen in the cortex of mice treated with both antibodies.ConclusionsBoth RmAb158 and its bispecific variant RmAb158-scFv8D3 achieved positive effects of long-term treatment. Despite its ability to efficiently enter the brain, the benefit of using the bispecific antibody in chronic treatment was limited by its reduced plasma exposure, which may be a result of interactions with TfR or the immune system. Future research will focus in new antibody formats to further improve Aβ immunotherapy.
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| 7. |
- Modin, Oskar, 1980, et al.
(författare)
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A relationship between phages and organic carbon in wastewater treatment plant effluents
- 2022
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Ingår i: Water Research X. - : Elsevier BV. - 2589-9147. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- With stringent effluent requirements and the implementation of new processes for micropollutant removal, it is increasingly important for wastewater treatment plants (WWTPs) to understand the factors affecting effluent quality. Phages (viruses infecting prokaryotes) are abundant in the biological treatment processes. They can contribute to organic carbon in the treated effluent both because they are organic in nature and occur in the effluent and because they cause lysis of microorganisms. Today very little is known about the effects of phages on effluent quality. The goal of this study was, therefore, to determine the relationship between phages and organic carbon in WWTP effluents. We also examined the diversity, taxonomy, and host-association of DNA phages using metagenomics. Effluent samples were collected from four WWTPs treating municipal wastewater. Significant differences in both organic carbon and virus-like particle concentrations were observed between the plants and there was a linear relationship between the two parameters. The phage communities were diverse with many members being taxonomically unclassified. Putative hosts were dominated by bacteria known to be abundant in activated sludge systems such as Comamonadaceae. The composition of phages differed between the WWTPs, suggesting that local conditions shape the communities. Overall, our findings suggest that the abundance and composition of phages are related to effluent quality. Thus, there is a need for further research clarifying the association between phage dynamics and WWTP function.
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| 8. |
- Ossiansson, Elin, 1983, et al.
(författare)
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Primary filtration of municipal wastewater with sludge fermentation – Impacts on biological nutrient removal
- 2023
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Ingår i: Science of the Total Environment. - 0048-9697 .- 1879-1026. ; 902
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Tidskriftsartikel (refereegranskat)abstract
- Primary filtration is a compact pre-treatment process for municipal wastewater, which can lead to high removal of total suspended solids (TSS) if polymer is added prior to filtration. Extensive carbon removal with rotating belt filter (RBF) can be combined with filter primary sludge fermentation at ambient temperature, in order to produce volatile fatty acids (VFAs) as carbon source for biological nutrient removal (BNR). This process was implemented at large pilot-scale and operated for more than a year. The results showed that the RBF efficiently removed particles >10 μm, and that the TSS removal had a strong linear correlation to the influent TSS concentration. Fermentation of the sludge at ambient temperature and five days retention time and addition of the fermentate to the wastewater could nearly double the VFA concentration in the wastewater by adding 31 ± 9 mg VFA-COD/L. Meanwhile, an increase of 2 mg/L of ammonium nitrogen, and 0.7 mg /L of phosphate phosphorus would be added to the wastewater with the fermentate. Adding the fermented sludge to the wastewater stream and removing the particles with RBF makes it possible to utilize nearly all the produced VFAs for BNR, and the feasibility of this configuration was shown at pilot-scale. According to simulations of subsequent BNR, the pre-treatment would lead to lower effluent total nitrogen concentrations. Alternatively, the required BNR volume could be reduced by 11–18 %. The estimated total biogas production was similar for pre-treatment with primary settler and RBF with fermentation. RBF without fermentation gave the most favourable energy balance, but did not reach the same low effluent value for total nitrogen as RBF with fermentation.
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| 9. |
- Ossiansson, Elin, 1983, et al.
(författare)
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Seasonal variations in acidogenic fermentation of filter primary sludge
- 2023
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Ingår i: Water Research. - 0043-1354 .- 1879-2448. ; 242
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Tidskriftsartikel (refereegranskat)abstract
- Primary treatment of municipal wastewater by rotating belt filtration followed by hydrolysis and acidogenic fermentation of the filter primary sludge (FPS) at ambient temperature was studied at pilot-scale during one year. The seasonal variations of volatile fatty acids (VFAs), nutrient release and soluble COD production as well as microbial community assembly were assessed, leading to novel findings for fermentation at ambient temperature. The reproducibility of VFA production performance was first established by operating the two fermentation reactors under the same conditions, showing similar results regarding VFA production and microbial community structure. One year of operation at 5 d retention time (RT) and 16–29 °C resulted in an average VFA yield of 180±35 mg COD/g VSin and soluble COD yield of 242±40 mg COD/g VSin. The VFA formation was temperature-dependent, with ϴ=1.033±0.005 (r=r20·Θ(T−20∘C)). The seasonal variations of the acetic and propionic acid productions were pronounced, whereas the productions of VFAs with longer chains were more stable regardless of temperature. The community structure of the reactor microbiomes was also clearly affected by season and temperature and linked with the production spectrum of VFAs. The ammonium and phosphate releases were stable during the year, leading to a decrease in ratios of soluble COD to NH4+-N and PO43−-P during winter. The soluble COD yield was 11% and 27% higher at 5 d RT compared to 3 and 2 d RT respectively, but the corresponding volumetric productivities were lower. The dissimilarities between microbiomes in influent FPS and fermenters were significant even at a short RT of 2 d, and increased with longer RT of 3 and 5 d, primarily caused by selection of bacteria within Bacteroidota in the fermentation reactors.
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| 10. |
- Rendo, Verónica, et al.
(författare)
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Exploiting loss of heterozygosity for allele-selective colorectal cancer chemotherapy
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Allelic losses occurring in cancer cells have been suggested as potential targets for therapy. Here, the authors show how recurring loss of heterozygosity of a drug metabolic gene in colorectal cancers can be exploited using a low molecular weight compound. Cancer chemotherapy targeting frequent loss of heterozygosity events is an attractive concept, since tumor cells may lack enzymatic activities present in normal constitutional cells. To find exploitable targets, we map prevalent genetic polymorphisms to protein structures and identify 45 nsSNVs (non-synonymous small nucleotide variations) near the catalytic sites of 17 enzymes frequently lost in cancer. For proof of concept, we select the gastrointestinal drug metabolic enzyme NAT2 at 8p22, which is frequently lost in colorectal cancers and has a common variant with 10-fold reduced activity. Small molecule screening results in a cytotoxic kinase inhibitor that impairs growth of cells with slow NAT2 and decreases the growth of tumors with slow NAT2 by half as compared to those with wild-type NAT2. Most of the patient-derived CRC cells expressing slow NAT2 also show sensitivity to 6-(4-aminophenyl)-N-(3,4,5-trimethoxyphenyl)pyrazin-2-amine (APA) treatment. These findings indicate that the therapeutic index of anti-cancer drugs can be altered by bystander mutations affecting drug metabolic genes.
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