| 1. |
- Vicari, Marco, et al.
(författare)
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Spatial multimodal analysis of transcriptomes and metabolomes in tissues
- 2024
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Ingår i: Nature Biotechnology. - : Nature Research. - 1087-0156 .- 1546-1696. ; 42:7, s. 1046-1050
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Tidskriftsartikel (refereegranskat)abstract
- We present a spatial omics approach that combines histology, mass spectrometry imaging and spatial transcriptomics to facilitate precise measurements of mRNA transcripts and low-molecular-weight metabolites across tissue regions. The workflow is compatible with commercially available Visium glass slides. We demonstrate the potential of our method using mouse and human brain samples in the context of dopamine and Parkinson’s disease.
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| 2. |
- Rung, Emilia, 1974, et al.
(författare)
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Progesterone-receptor antagonists and statins decrease de novo cholesterol synthesis and increase apoptosis in rat and human periovulatory granulosa cells in vitro
- 2005
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Ingår i: Biology of reproduction. - : Oxford University Press (OUP). - 0006-3363 .- 1529-7268. ; 72:3, s. 538-45
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Tidskriftsartikel (refereegranskat)abstract
- Progesterone-receptor (PR) stimulation promotes survival in rat and human periovulatory granulosa cells. To investigate the mechanisms involved, periovulatory rat granulosa cells were incubated in vitro with or without the PR-antagonist Org 31710. Org 31710 caused the expected increase in apoptosis, and expression profiling using cDNA microarray analysis revealed regulation of several groups of genes with functional and/or metabolic connections. This regulation included decreased expression of genes involved in follicular rupture, increased stress responses, decreased angiogenesis, and decreased cholesterol synthesis. A decreased cholesterol synthesis was verified in experiments with both rat and human periovulatory granulosa cells treated with the PR-antagonists Org 31710 or RU 486 by measuring incorporation of [14C]acetate into cholesterol, cholesterol ester, and progesterone. Correspondingly, specific inhibition of cholesterol synthesis in periovulatory rat granulosa cells using 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (lovastatin, mevastatin, or simvastatin) increased apoptosis, measured as DNA fragmentation and caspase-3/7 activity. The increase in apoptosis caused by simvastatin was reversed by addition of the cholesterol synthesis-intermediary mevalonic acid. These results show that PR antagonists reduce cholesterol synthesis in periovulatory granulosa cells and that cholesterol synthesis is important for granulosa cell survival.
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| 3. |
- Vicari, Marco, et al.
(författare)
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Spatial multimodal analysis of transcriptomes and metabolomes in tissues
- 2023
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Ingår i: Nature Biotechnology. - 1087-0156 .- 1546-1696.
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Tidskriftsartikel (refereegranskat)abstract
- We present a spatial omics approach that combines histology, mass spectrometry imaging and spatial transcriptomics to facilitate precise measurements of mRNA transcripts and low-molecular-weight metabolites across tissue regions. The workflow is compatible with commercially available Visium glass slides. We demonstrate the potential of our method using mouse and human brain samples in the context of dopamine and Parkinson’s disease.
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| 4. |
- Ahlin, Sofie, 1985, et al.
(författare)
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Fracture risk after three bariatric surgery procedures in Swedish obese subjects : up to 26 years follow-up of a controlled intervention study
- 2020
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:5, s. 546-557
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have reported an increased fracture risk after bariatric surgery. Objective: To investigate the association between different bariatric surgery procedures and fracture risk. Methods: Incidence rates and hazard ratios for fracture events were analysed in the Swedish Obese Subjects study; an ongoing, nonrandomized, prospective, controlled intervention study. Hazard ratios were adjusted for risk factors for osteoporosis and year of inclusion. Information on fracture events were captured from the Swedish National Patient Register. The current analysis includes 2007 patients treated with bariatric surgery (13.3% gastric bypass, 18.7% gastric banding, and 68.0% vertical banded gastroplasty) and 2040 control patients with obesity matched on group level based on 18 variables. Median follow-up was between 15.1 and 17.9 years for the different treatment groups. Results: During follow-up, the highest incidence rate for first-time fracture was observed in the gastric bypass group (22.9 per 1000 person-years). The corresponding incidence rates were 10.4, 10.7 and 9.3 per 1000 person-years for the vertical banded gastroplasty, gastric banding and control groups, respectively. The risk of fracture was increased in the gastric bypass group compared with the control group (adjusted hazard ratio [adjHR] 2.58; 95% confidence interval [CI] 2.02–3.31; P < 0.001), the gastric banding group (adjHR 1.99; 95%CI 1.41–2.82; P < 0.001), and the vertical banded gastroplasty group (adjHR 2.15; 95% CI 1.66–2.79; P < 0.001). Conclusions: The risk of fracture is increased after gastric bypass surgery. Our findings highlight the need for long-term follow-up of bone health for patients undergoing this treatment.
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| 5. |
- Amin, Khabat, et al.
(författare)
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Analysis of road safety trends 2020 : Management by objectives for road safety work towards the 2020 interim targets
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The Swedish road safety management is based on the Vision Zero and designated interim targets to track progress towards its achievement. 2020 was the final year for achieving the interim target of halving the number of fatalities between 2007 and 2020, i.e., a maximum of 220 fatalities in 2020. The interim target also specifies that the number of seriously injured in road traffic must be reduced by a quarter. This report describes and analyses the current road safety trends in terms of road safety performance indicators and the numbers of fatalities and seriously injured. As this report is the last for the 2007-2020 interim target period, it can be seen as a final summary of how well the targets were achieved for fatalities and seriously injured and for the safety performance indicators. However, it is also important to remember that the year 2020 coincided with the COVID-19 pandemic, which had a profound impact on virtually the entire society. This affected travel in a number of different ways, and consequently it is impossible to estimate the impact this has had on the outcome in 2020, although it probably has led to a slightly lower outcome. The table below shows starting and final values together with an overview of whether the safety performance indicators have met the 2020 targets.
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| 6. |
- Bernhardsson, Susanne, 1958, et al.
(författare)
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Clinical practice in line with evidence? A survey among primary care physiotherapists in western Sweden
- 2015
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Ingår i: Journal of Evaluation in Clinical Practice. - : Wiley. - 1356-1294 .- 1365-2753. ; 21:6, s. 1169-1177
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Tidskriftsartikel (refereegranskat)abstract
- Rationale, aims and objectives Evidence-based practice is becoming increasingly important in primary care physiotherapy. Clinical practice needs to reflect current best evidence and be concordant with evidence-based clinical guidelines. There is limited knowledge about therapeutic interventions used in primary care physiotherapy in Sweden. The objectives were to examine preferred treatment interventions reported by publicly employed physiotherapists in primary care for three common musculoskeletal disorders (low back pain, neck pain and subacromial pain), the extent to which these interventions were supported by evidence, and associations with demographic variables. Methods 419 physiotherapists in primary care in western Sweden were surveyed using a validated web-based questionnaire. Results The survey was completed by 271 respondents (65%). Median number of interventions reported was 7 (range 1-16). The most common treatment interventions across the three conditions were advice on posture (reported by 82-94%), advice to stay active (86-92%), and different types of exercise (65-92%). Most of these interventions were supported by evidence. However, interventions with insufficient evidence, such as advice on posture, TENS and aquatic exercise, were also used by 29-96%. Modalities such as laser therapy and ultrasound were sparingly used (< 5%), which is in line with evidence. For neck pain, use of evidence-based interventions was associated with gender and for subacromial pain, with work experience. Conclusions Advice and exercise therapy were the interventions most frequently reported across the three diagnoses, illustrating an active treatment strategy. While most reported interventions are supported by evidence, interventions with unclear or no evidence of effect were also used to a high extent.
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| 7. |
- Bernhardsson, Susanne, 1958, et al.
(författare)
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Determinants of Guideline Use in Primary Care Physical Therapy: A Cross-Sectional Survey of Attitudes, Knowledge, and Behavior
- 2014
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Ingår i: Physical Therapy. - : Oxford University Press (OUP). - 0031-9023 .- 1538-6724. ; 94:3, s. 343-354
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Tidskriftsartikel (refereegranskat)abstract
- Background. Understanding of attitudes, knowledge, and behavior related to evidence-based practice (ESP) and use of evidence-based clinical practice guidelines in primary care physical therapy is limited. Objectives. The objectives of this study were: (1) to investigate self-reported attitudes, knowledge, behavior, prerequisites, and barriers related to EBP and guideline use among physical therapists in primary care and (2) to explore associations of self-reported use of guidelines with these social cognitive factors 'along with demographic and workplace characteristics. Methods. A web-based survey of 419 physical therapists in primary care in western Sweden was performed. Multiple logistic regression analysis was performed to examine factors associated with guideline use. Results. The response rate was 64.7%. Most respondents had positive attitudes toward EBP and guidelines: 90% considered EBP necessary, and 96% considered guidelines important. Approximately two thirds reported confidence in finding and using evidence. One third reported being aware of guidelines. Thirteen percent knew where to find guidelines, and only 9% reported having easy access to guidelines. Fewer than half reported using guidelines frequently. The most important barriers to using guidelines were lack of time, poor availability, and limited access to guidelines. Young age and brief work experience were associated with positive attitudes toward EBP. A postgraduate degree was associated with higher application of EBP. Positive attitudes, awareness of guidelines, considering guidelines to facilitate practice, and knowing how to integrate patient preferences with guideline use were associated with frequent use of guidelines. Limitations. Data were self-reported, which may have increased the risk of social.desirability bias. Conclusions. Use of guidelines was not as frequent as could be expected in view of the positive attitudes toward EBP and guidelines among physical therapists. Awareness of and perceived access to guidelines were limited. The identified determinants can be addressed when developing 'guideline implementation strategies.
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| 8. |
- Bernhardsson, Susanne, 1958, et al.
(författare)
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Evaluation of a tailored, multi-component intervention for implementation of evidence-based clinical practice guidelines in primary care physical therapy: a non-randomized controlled trial
- 2014
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background Clinical practice guidelines are important for transmitting research findings into practice and facilitating the application of evidence-based practice (EBP). There is a paucity of knowledge about the impact of guideline implementation strategies in primary care physical therapy. The aim of this study was to evaluate the effect of a guideline implementation intervention in primary care physical therapy in western Sweden. Methods An implementation strategy based on theory and current evidence was developed. A tailored, multi-component implementation intervention, addressing earlier identified determinants, was carried out in three areas comprising 28 physical therapy practices including 277 physical therapists (PTs) (intervention group). In two adjacent areas, 171 PTs at 32 practices received no intervention (control group). The core component of the intervention was an implementation seminar with group discussions. Among other components were a website and email reminders. Data were collected at baseline and follow-up with a web-based questionnaire. Primary outcomes were the self-reported awareness of, knowledge of, access to, and use of guidelines. Secondary outcomes were self-reported attitudes toward EBP and guidelines. Analyses were performed using Pearson’s χ2 test and approximative z-test. Results 168 PTs (60.6%) in the intervention group and 88 PTs (51.5%) in the control group responded to the follow-up questionnaire. 186/277 PTs (67.1%) participated in the implementation seminars, of which 97 (52.2%) responded. The proportions of PTs reporting awareness of (absolute difference in change 20.6%, p = 0.023), knowledge where to find (20.4%, p = 0.007), access to (21.7%, p < 0.001), and frequent use of (9.5%, NS) guidelines increased more in the intervention group than in the control group. The proportion of PTs reporting frequent guideline use after participation in the implementation seminar was 15.2% (p = 0.043) higher than the proportion in the control group. A higher proportion considered EBP helpful in decision making (p = 0.018). There were no other significant differences in secondary outcomes. Conclusions A tailored, theory- and evidence-informed, multi-component intervention for the implementation of clinical practice guidelines had a modest, positive effect on awareness of, knowledge of, access to, and use of guidelines, among PTs in primary care in western Sweden. In general, attitudes to EBP and guidelines were not affected.
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| 9. |
- Bernhardsson, Susanne, 1958, et al.
(författare)
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Implementation of physical activity on prescription for children with obesity in paediatric health care (IMPA): protocol for a feasibility and evaluation study using quantitative and qualitative methods
- 2022
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Ingår i: Pilot and Feasibility Studies. - : Springer Science and Business Media LLC. - 2055-5784. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Physical inactivity is a main cause of childhood obesity which tracks into adulthood obesity, making it important to address early in life. Physical activity on prescription (PAP) is an evidence-based intervention that has shown good effect on physical activity levels in adults, but has not been evaluated in children with obesity. This project aims to evaluate the prerequisites, determinants, and feasibility of implementing PAP adapted to children with obesity and to explore children's, parents', and healthcare providers' experiences of PAP. Methods: In the first phase of the project, healthcare providers and managers from 26 paediatric clinics in Region Vastra Gotaland, Sweden, will be invited to participate in a web-based survey and a subset of this sample for a focus group study. Findings from these two data collections will form the basis for adaptation of PAP to the target group and context. In a second phase, this adapted PAP intervention will be evaluated in a clinical study in a sample of approximately 60 children with obesity (ISO-BMI > 30) between 6 and 12 years of age and one of their parents/legal guardians. Implementation process and clinical outcomes will be assessed pre- and post-intervention and at 8 and 12 months' follow-up. Implementation outcomes are the four core constructs of the Normalization Process Theory; coherence, cognitive participation, collective action, and reflexive monitoring; and appropriateness, acceptability, and feasibility of the PAP intervention. Additional implementation process outcomes are recruitment and attrition rates, intervention fidelity, dose, and adherence. Clinical outcomes are physical activity pattern, BMI, metabolic risk factors, health-related quality of life, sleep, and self-efficacy and motivation for physical activity. Lastly, we will explore the perspectives of children and parents in semi-structured interviews. Design and analysis of the included studies are guided by the Normalization Process Theory. Discussion: This project will provide new knowledge regarding the feasibility of PAP for children with obesity and about whether and how an evidence-based intervention can be fitted and adapted to new contexts and populations. The results may inform a larger scale trial and future implementation and may enhance the role of PAP in the management of obesity in paediatric health care in Sweden.
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| 10. |
- Bourgard, Catarina, 1985, et al.
(författare)
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Development of Dicationic Bisguanidine-Arylfuran Derivatives as Potent Agents against Gram-Negative Bacteria.
- 2022
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Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance among bacteria is a growing global challenge. A major reason for this is the limited progress in developing new classes of antibiotics active against Gram-negative bacteria. Here, we investigate the antibacterial activity of a dicationic bisguanidine-arylfuran, originally developed as an antitrypanosomal agent, and new derivatives thereof. The compounds showed good activity (EC50 2-20 µM) against antibiotic-resistant isolates of the Gram-negative members of the ESKAPE group (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) and Escherichia coli with different antibiotic susceptibility patterns, including ESBL isolates. Cytotoxicity was moderate, and several of the new derivatives were less cytotoxic than the lead molecule, offering better selectivity indices (40-80 for several ESKAPE isolates). The molecular mechanism for the antibacterial activity of these molecules is unknown, but sensitivity profiling against human ESKAPE isolates and E. coli collections with known susceptibility patterns against established antibiotics indicates that it is distinct from lactam and quinolone antibiotics.
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