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| 5. |
- Merid, Simon Kebede, et al.
(författare)
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Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
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Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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| 9. |
- Andreadis, Ioannis I., et al.
(författare)
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Exploring the use of modified in vitro digestion assays for the evaluation of ritonavir loaded solid lipid-based formulations
- 2023
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 189
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Tidskriftsartikel (refereegranskat)abstract
- Solid lipid-based formulations (sLBFs) have the potential to increase the oral bioavailability of drugs with poor solubility in water, while counteracting some of the disadvantages of liquid LBFs. The most common experimental set-up to study the performance of LBFs in vitro is the lipolysis assay, during which the LBFs are digested by lipases in an environment mimicking the human small intestine. However, this assay has failed in many cases to correctly predict the performance of LBFs in vivo, highlighting the need for new and improved in vitro assays to evaluate LBFs at the preclinical stage. In this study, the suitability of three different in vitro digestion assays for the evaluation of sLBFs was assessed; the classic one-step intestinal digestion assay, a two-step gastrointestinal digestion assay and a bicompartmental assay permitting the simultaneous monitoring of digestion and permeation of the active pharmaceutical ingredient (API) across an artificial membrane (Lecithin in Dodecane - LiDo). Three sLBFs (M1-M3) with varied composition and ritonavir as model drug were prepared and examined. When comparing the ability of these formulations to keep the drug solubilized in the aqueous phase, all three assays show that M1 performs better, while M3 presents poor performance. However, the classic in vitro intestinal digestion assay fails to provide a clear ranking of the three formulations, something that is more evident when using the two modified and more physiologically relevant assays. Also, the two modified assays provide additional information about the performance of the formulations including the performance in the gastric environment and intestinal flux of the drug. These modified in vitro digestion assays are valuable tools for the development and evaluation of sLBFs to make better informed decisions of which formulations to pursue for in vivo studies.
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| 10. |
- Axen, I., et al.
(författare)
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Interventions for common mental disorders in the occupational health service: a systematic review with a narrative synthesis
- 2020
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 93:7, s. 823-838
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Common mental disorders (CMD) are leading causes of decreased workability in Sweden and worldwide. Effective interventions to prevent or treat such disorders are important for public health. Objective To synthesize the research literature regarding occupational health service (OHS) interventions targeting prevention or reduction of CMD among employees. The effect on workability (sickness absence, return-to-work and self-reported workability) and on CMD symptoms was evaluated in a narrative analysis. Data sources The literature search was performed in four electronic databases in two searches, in 2014 and in 2017. Eligibility criteria (using PICO) Population: studies investigating employees at risk or diagnosed with CMD, as well as preventive workplace intervention targeting mental health. Intervention: studies where the recruitment or the intervention was delivered by the OHS or OHS personnel were included. Control: individuals or groups who did not receive the target intervention. Outcome: all types of outcomes concerning sickness absence and psychological health were included. Study quality was assessed using a Swedish AMSTAR-based checklist, and results from studies with low or medium risk of bias were narratively synthesized based on effect or absence thereof. Results Thirty-three studies were included and assessed for risk of bias. Twenty-one studies had low or medium risk of bias. In 18 studies, rehabilitation interventions were evaluated, 11 studies concerned interventions targeting employees at risk for developing CMD and four studies investigated preventive interventions. Work-focused cognitive behavioral therapy and problem-solving skill interventions decreased time to first return-to-work among employees on sick leave for CMD in comparison with treatment-as-usual. However, effect on return to full-time work was not consistent, and these interventions did not consistently improve CMD symptoms. Selective interventions targeting employees at risk of CMD and preventive interventions for employees were heterogeneous, so replication of these studies is necessary to evaluate effect. Limitations Other workplace interventions outside the OHS may have been missed by our search. There was considerable heterogeneity in the included studies, and most studies were investigating measures targeting the individual worker. Interventions at the workplace/organizational level were less common.
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| 11. |
- Bahls, M., et al.
(författare)
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Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium
- 2020
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 27:3
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. Methods and results: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. Conclusion: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints. © The European Society of Cardiology 2019.
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| 12. |
- Bake, Tina, et al.
(författare)
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Ghrelin Receptor Stimulation of the Lateral Parabrachial Nucleus in Rats Increases Food Intake but not Food Motivation
- 2020
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 28:8, s. 1503-1511
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Tidskriftsartikel (refereegranskat)abstract
- Objective The lateral parabrachial nucleus (lPBN) in the brainstem has emerged as a key area involved in feeding control that is targeted by several circulating anorexigenic hormones. Here, the objective was to determine whether the lPBN is also a relevant site for the orexigenic hormone ghrelin, inspired by studies in mice and rats showing that there is an abundance of ghrelin receptors in this area. Methods This study first explored whether iPBN cells respond to ghrelin involving Fos mapping and electrophysiological studies in rats. Next, rats were injected acutely with ghrelin, a ghrelin receptor antagonist, or vehicle into the lPBN to investigate feeding-linked behaviors. Results Curiously, ghrelin injection (intracerebroventricular or intravenous) increased Fos protein expression in the lPBN yet the predominant electrophysiological response was inhibitory. Intra-lPBN ghrelin injection increased chow or high-fat diet intake, whereas the antagonist decreased chow intake only. In a choice paradigm, intra-lPBN ghrelin increased intake of chow but not lard or sucrose. Intra-lPBN ghrelin did not alter progressive ratio lever pressing for sucrose or conditioned place preference for chocolate. Conclusions The lPBN is a novel locus from which ghrelin can alter consummatory behaviors (food intake and choice) but not appetitive behaviors (food reward and motivation).
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| 13. |
- Bergström, Anders, et al.
(författare)
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Origins and genetic legacy of prehistoric dogs
- 2020
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6516, s. 557-563
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Tidskriftsartikel (refereegranskat)abstract
- Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry.
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| 14. |
- Bergström, Anna, 1983-, et al.
(författare)
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The use of the PARIHS framework in implementation research and practice-a citation analysis of the literature
- 2020
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Ingår i: Implementation science : IS. - : Springer Science and Business Media LLC. - 1748-5908. ; 15:1
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: The Promoting Action on Research Implementation in Health Services (PARIHS) framework was developed two decades ago and conceptualizes successful implementation (SI) as a function (f) of the evidence (E) nature and type, context (C) quality, and the facilitation (F), [SI = f (E,C,F)]. Despite a growing number of citations of theoretical frameworks including PARIHS, details of how theoretical frameworks are used remains largely unknown. This review aimed to enhance the understanding of the breadth and depth of the use of the PARIHS framework. METHODS: This citation analysis commenced from four core articles representing the key stages of the framework's development. The citation search was performed in Web of Science and Scopus. After exclusion, we undertook an initial assessment aimed to identify articles using PARIHS and not only referencing any of the core articles. To assess this, all articles were read in full. Further data extraction included capturing information about where (country/countries and setting/s) PARIHS had been used, as well as categorizing how the framework was applied. Also, strengths and weaknesses, as well as efforts to validate the framework, were explored in detail. RESULTS: The citation search yielded 1613 articles. After applying exclusion criteria, 1475 articles were read in full, and the initial assessment yielded a total of 367 articles reported to have used the PARIHS framework. These articles were included for data extraction. The framework had been used in a variety of settings and in both high-, middle-, and low-income countries. With regard to types of use, 32% used PARIHS in planning and delivering an intervention, 50% in data analysis, 55% in the evaluation of study findings, and/or 37% in any other way. Further analysis showed that its actual application was frequently partial and generally not well elaborated. CONCLUSIONS: In line with previous citation analysis of the use of theoretical frameworks in implementation science, we also found a rather superficial description of the use of PARIHS. Thus, we propose the development and adoption of reporting guidelines on how framework(s) are used in implementation studies, with the expectation that this will enhance the maturity of implementation science.
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| 15. |
- Bergström, Sofia, et al.
(författare)
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Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease
- 2021
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 8:7, s. 1456-1470
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Decreased amyloid beta (A beta) 42 together with increased tau and phospho-tau in cerebrospinal fluid (CSF) is indicative of Alzheimer's disease (AD). However, the molecular pathophysiology underlying the slowly progressive cognitive decline observed in AD is not fully understood and it is not known what other CSF biomarkers may be altered in early disease stages. Methods: We utilized an antibody-based suspension bead array to analyze levels of 216 proteins in CSF from AD patients, patients with mild cognitive impairment (MCI), and controls from two independent cohorts collected within the AETIONOMY consortium. Two additional cohorts from Sweden were used for biological verification. Results: Six proteins, amphiphysin (AMPH), aquaporin 4 (AQP4), cAMP-regulated phosphoprotein 21 (ARPP21), growth-associated protein 43 (GAP43), neurofilament medium polypeptide (NEFM), and synuclein beta (SNCB) were found at increased levels in CSF from AD patients compared with controls. Next, we used CSF levels of A beta 42 and tau for the stratification of the MCI patients and observed increased levels of AMPH, AQP4, ARPP21, GAP43, and SNCB in the MCI subgroups with abnormal tau levels compared with controls. Further characterization revealed strong to moderate correlations between these five proteins and tau concentrations. Interpretation: In conclusion, we report six extensively replicated candidate biomarkers with the potential to reflect disease development. Continued evaluation of these proteins will determine to what extent they can aid in the discrimination of MCI patients with and without an underlying AD etiology, and if they have the potential to contribute to a better understanding of the AD continuum.
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| 16. |
- Bohlin, I, et al.
(författare)
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Mapping potential location for bilberry picking with remote sensing, local field data andphone application
- 2023
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the study was to create a practical method for identifying potential locations for bilberry picking with help of remote sensing, local field data and phone application to support the development of the local berry value chain. Local field data w as collected 2021 and 2022 and consisted 503 and 525 plots from a study area of circa 25x45km in Västerbotten, Sweden. The potential for bilberry production was evaluated by measuring the shrub cover and amount of raw berries. Wall to wall remote sensing d ata included a Sentinel 2 image from same summer, airborne laser scanning data from 2020 and other map products. We created classification models for bilberry shrub and yield using both logistic regression (2 classes) and ordinal regression (3 classes) mod els using 2021 data, and validated and calibrated models with 2022 data. Predictor variables consisted of spectral metrics from satellite data; structural metrics from laser data; existing raster maps of tree species, stand attributes, site index, soil moi sture and land use classes. The 2 class models performed better than three class models, delivering the AUC 0.73, overall accuracy 0.83 and kappa value 0.51 for best bilberry shrub model and 0.75, 0.77 and 0.50 respectively for best bilberry yield model. T he best models included both laser based structural metrics describing e.g canopy closure and spectral metrics, but also e.g. volume of pine, soil moisture and site index were found significant predictor variables. Calibration of the models improved annual predictions and the validation of the 2021 raster maps with 2022 data produced similar AUC, OA, and kappa values for bilberry yield (0.73, 0.74 and 0.46), but lower for bilberry shrub (0.61, 0.68 and 0.24). A dedicated phone application was developed duri ng the project, which was used both for collecting the field data and for presenting the potential locations of berry yields. Local berry maps can help berry pickers easier to find the berries in forest landscape and therefore support local berry value cha in. This study is part of the FAIRCHAIN project, which has received funding from the European Union’s funding programme H2020 research and innovation programme under grand agreement 101000723.
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| 18. |
- Dezfouli, Mahya, et al.
(författare)
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Newborn Screening for Presymptomatic Diagnosis of Complement and Phagocyte Deficiencies
- 2020
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The clinical outcomes of primary immunodeficiencies (PIDs) are greatly improved by accurate diagnosis early in life. However, it is not common to consider PIDs before the manifestation of severe clinical symptoms. Including PIDs in the nation-wide newborn screening programs will potentially improve survival and provide better disease management and preventive care in PID patients. This calls for the detection of disease biomarkers in blood and the use of dried blood spot samples, which is a part of routine newborn screening programs worldwide. Here, we developed a newborn screening method based on multiplex protein profiling for parallel diagnosis of 22 innate immunodeficiencies affecting the complement system and respiratory burst function in phagocytosis. The proposed method uses a small fraction of eluted blood from dried blood spots and is applicable for population-scale performance. The diagnosis method is validated through a retrospective screening of immunodeficient patient samples. This diagnostic approach can pave the way for an earlier, more comprehensive and accurate diagnosis of complement and phagocytic disorders, which ultimately lead to a healthy and active life for the PID patients.
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| 19. |
- Guimond, S. E., et al.
(författare)
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Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction
- 2022
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 8:5, s. 527-545
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein receptor binding domain and directly inhibits its binding to ACE2, consistent with molecular modeling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of SARS-CoV-2 virus show that pixatimod potently inhibits the infection of monkey Vero E6 cells and physiologically relevant human bronchial epithelial cells at safe therapeutic concentrations. Pixatimod also retained broad potency against variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, in a K18-hACE2 mouse model, pixatimod significantly reduced SARS-CoV-2 viral titers in the upper respiratory tract and virus-induced weight loss. This demonstration of potent anti-SARS-CoV-2 activity tolerant to emerging mutations establishes proof-of-concept for targeting the HS-Spike protein-ACE2 axis with synthetic HS mimetics and provides a strong rationale for clinical investigation of pixatimod as a potential multimodal therapeutic for COVID-19.
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| 20. |
- Hang, Trieu, et al.
(författare)
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Natural surface floaters in image-based river surface velocimetry: Insights from a case study
- 2024
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Ingår i: Flow Measurement and Instrumentation. - : Elsevier. - 0955-5986 .- 1873-6998. ; 96
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Tidskriftsartikel (refereegranskat)abstract
- This study focuses on utilizing image techniques for river velocity measurement, with a specific emphasis onnatural surface floating patterns. Employing a multi-camera system, we conducted 3D measurements on riversurfaces, including surface velocity and water surface reconstruction. A pattern-based tracking approach hasbeen adopted to improve the performance of image measurements on different types of natural floating tracers.The study employs the following approaches: 3D Lagrangian Pattern Tracking Velocimetry (3D-LPTV), 2DLagrangian Pattern Velocimetry (2D- LPTV), and Large-scale Particle Image Velocimetry (LSPIV), for surfacevelocity estimation. The outcomes revealed that all three approaches yielded consistent results in terms ofaveraged velocity. However, the LSPIV method produced about two times higher uncertainty in measured velocitiescompared to the other methods. A strategy to assess the quality of river surface patterns in velocityestimation is presented. Specifically, the sum of squared interrogation area intensity gradient (SSIAIG) was foundto be strongly correlated with measurement uncertainty. Additionally, a term related to the peak sidelobe ratio(PSR) of the cross-correlation map was found as an effective constraint, ensuring the image-tracking processachieves high reliability. The precision of measurements increases corresponding to the increase of image intensitygradient and PSR.
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| 21. |
- Hang, Trieu, et al.
(författare)
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Photogrammetry for Free Surface Flow Velocity Measurement : From Laboratory to Field Measurements
- 2021
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Ingår i: Water. - : MDPI. - 2073-4441. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- This study describes a multi-camera photogrammetric approach to measure the 3D velocityof free surface flow. The properties of the camera system and particle tracking velocimetry (PTV)algorithm were first investigated in a measurement of a laboratory open channel flow to prepare forfield measurements. The in situ camera calibration methods corresponding to the two measurementsituations were applied to mitigate the instability of the camera mechanism and camera geometry.There are two photogrammetry-based PTV algorithms presented in this study regarding differenttypes of surface particles employed on the water flow. While the first algorithm uses the particletracking method applied for individual particles, the second algorithm is based on correlation-basedparticle clustering tracking applied for clusters of small size particles. In the laboratory, referencedata are provided by particle image velocimetry (PIV) and laser Doppler velocimetry (LDV). Thedifferences in velocities measured by photogrammetry and PIV, photogrammetry and LDV are 0.1%and 3.6%, respectively. At a natural river, the change of discharges between two measurement timesis found to be 15%, and the corresponding value reported regarding mass flow through a nearbyhydropower plant is 20%. The outcomes reveal that the method can provide a reliable estimation of3D surface velocity with sufficient accuracy.
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| 23. |
- Jons, D., et al.
(författare)
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Increase in Epstein Barr virus serologies precedes neuroaxonal damage in pre-symptomatic multiple sclerosis
- 2022
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 28:Suppl. 3, s. 86-87
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Epstein-Barr virus (EBV) infection may be a pre-condition for the development of multiple sclerosis (MS). EBV antibodies, predominantly anti-EBNA1, develop in the presymp-tomatic phase of virtually all MS patients. Using material from a serum repository, studies in advance of MS onset indicated that EBV seropositivity preceded the first expression of incipient axonal lesions, serum Neurofilament Light (sNFL) .Objectives: To determine the onset and individual order of appearance of EBV seroreactivity and the serum neuroaxonal injury marker neurofilament light (sNfL) in a wide age spectrum of presymptomatic MS patients.Aims: To characterize the presymptomatic appearance of anti-bodies against an intranuclear (EBNA1) and a surface EBV anti-gen (gp350) and sNfL.Methods: A nested case-control study in 669 pre-symptomati-cally acquired blood samples from persons who later received an MS diagnosis, and from 1:1 matched control persons. Serum lev-els of EBNA1, VCA and gp350 IgG antibodies and sNFL (n=519) were measured in individual presymptomatic samples and expressed as delta scores with matched controls in relation to time until MS onset.Results: Serum levels expressed as delta scores for anti EBV and NfL IgG showed an incipient increase for anti EBNA1 and gp350 from 15-20 years before MS debut. Significant (p=0.001 and p=0.002) from 10-15 years, with consistent delta-scores succes-sively closer to MS onset. These findings contrasted to the level of sNfL which increasingly diverged from matched controls from 5-10 years before the onset of MS. None of the individual sam-ples negative for both EBNA1 and VCA IgG antibodies in the pre-MS group (n = 36) showed any elevation of the sNfL level.Conclusions: In a pre-MS material, the seroreactivity against EBNA1 was followed by VCA and gp350, before increased sNFL appeared, indicating incipient axonal injury. Together with its biological characteristics this temporal order confirms the role of EBV as a trigger of MS.
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| 24. |
- Karlsson, Ida, et al.
(författare)
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Exploring ethical issues arising from a problem-solving intervention in the Swedish Primary Care
- 2022
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Ingår i: European Journal of Public Health Vol.32 Issue Supplement 3. - : Oxford University Press (OUP). - 1101-1262.
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Konferensbidrag (refereegranskat)abstract
- Background Common mental disorders count for a large percentage of sick leave cases in Europe and in Sweden. Problem-solving with workplace involvement have shown promising results in reducing the number of sick leave days for employees on sick leave for these conditions. Engaging the workplace by for example including the first-line manager in the return-to-work process changes the usual role of the primary care. Hence, this study aims to explore ethical issues that potentially arise when introducing workplace involvement as part of a problem-solving intervention. Methods A qualitative study in the Swedish Primary Care using data from semi-structured interviews with rehabilitation coordinators (n = 6), employees on sick leave for common mental disorders (n = 13), and their first-line managers (n = 8). A theoretical framework for systematic identification of ethical aspects of healthcare technologies was used to guide the interviews and reporting of results. Content analysis was used to code the data, searching for latent content. Ethical issues related to the ethical values privacy, identity, autonomy, professional values, third party, equality and justice were identified and described. The analysis was concluded by a normative discussion. Results Ethical issues were identified such as difficulties for the employees to control personal information. A need to create an integrated role of a patient and an employee and for coordinators to act neutral instead of as a patient advocate. Managers needed to balance the needs of the organization with the needs of the employee. A pre-requisite for participation was agreeing to manager involvement which may affect the equality of the intervention. Conclusions A conversation about sharing of information, roles, responsibilities and expectations during the rehabilitation should be initiated early and be continuous. Managers need support in learning the “how to” when having an employee on sick leave due to a common mental disorder. Key messages The problem-solving intervention imposed ethical issues in regard to control over personal information and role shifting, which can be handled through discussions and awareness. By analysing ethical aspects and norms and values connected to the intervention, adaptations and solutions can be discussed and handled before full scale implementation.
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| 25. |
- Leinweber, Julia, et al.
(författare)
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Developing a woman-centered, inclusive definition of positive childbirth experiences : A discussion paper
- 2023
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Ingår i: Birth. - : John Wiley & Sons. - 0730-7659 .- 1523-536X. ; 50:2, s. 362-383
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Tidskriftsartikel (refereegranskat)abstract
- Introduction A positive childbirth experience promotes women’s health, both during and beyond the perinatal period. Understanding what constitutes a positive childbirth experience is thus critical to providing high-quality maternity care. Currently, there is no clear, inclusive, woman-centered definition of a positive childbirth experience to guide practice, education, and research.Aim To formulate an inclusive woman-centered definition of a positive childbirth experience.Methods A six-step process was undertaken: (a) Key concepts associated with a positive childbirth were derived from a rapid literature review; (b) The key concepts were used by interdisciplinary experts in the author group to create a draft definition; (c) The draft definition was presented to clinicians and researchers during a European research meeting on perinatal mental health; (d) The authors integrated the expert feedback to refine the working definition; (e) A revised definition was shared with women from consumer groups in six countries to confirm its face validity; and (f) A final definition was formulated based on the women’s feedback (n = 42).Results The following definition was formulated: “A positive childbirth experience refers to a woman’s experience of interactions and events directly related to childbirth that made her feel supported, in control, safe, and respected; a positive childbirth can make women feel joy, confident, and/or accomplished and may have short and/or long-term positive impacts on a woman’s psychosocial well-being.”Conclusions This inclusive, woman-centered definition highlights the importance of provider interactions for facilitating a positive childbirth experience. Feeling supported and having a sense of control, safety, and respect are central tenets. This definition could help to identify and validate positive childbirth experience(s), and to inform practice, education, research, advocacy, and policy-making.
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| 26. |
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| 27. |
- Lindberg, K., et al.
(författare)
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The HILUS-Trial—a Prospective Nordic Multicenter Phase 2 Study of Ultracentral Lung Tumors Treated With Stereotactic Body Radiotherapy
- 2021
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Ingår i: Journal of Thoracic Oncology. - : Elsevier BV. - 1556-0864. ; 16:7, s. 1200-1210
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Stereotactic body radiation therapy of thoracic tumors close to the central airways implies risk of severe toxicity. We report a prospective multicenter phase 2 trial for tumors located less than or equal to 1 cm from the proximal bronchial tree with primary end point of local control and secondary end point of toxicity. Methods: Stereotactic body radiation therapy with 7 Gy × 8 was prescribed to the 67% isodose encompassing the planning target volume. The patients were stratified to group A (tumors ≤ 1 cm from the main bronchi and trachea) or group B (all other tumors). Risk factors for treatment-related death were tested in univariate analysis, and a logistic regression model was developed for fatal bronchopulmonary bleeding versus dose to the main bronchi and trachea. Results: A total of 65 patients (group A/group B, n = 39/26) were evaluated. The median distance between the tumor and the proximal bronchial tree was 0 mm (0–10 mm). The 2-year local control was 83%. Grade 3 to 5 toxicity was noted in 22 patients, including 10 cases of treatment-related death (bronchopulmonary hemorrhage, n = 8; pneumonitis, n = 1; fistula, n = 1). Dose to the combined structure main bronchi and trachea and tumor distance to the main bronchi were important risk factors. Dose modeling revealed minimum dose to the “hottest” 0.2 cc to the structure main bronchi and trachea as the strongest predictor for lethal bronchopulmonary hemorrhage. Conclusions: On the basis of the presented data, 7 Gy × 8, prescribed to the planning target volume-encompassing isodose, should not be used for tumors located within 1 cm from the main bronchi and trachea. Group B-type tumors may be considered for the treatment on the basis of an individual risk-benefit assessment and a maximum dose to the main bronchi and trachea in the order of 70 to 80 Gy (equivalent dose in 2 Gy fractions). © 2021 International Association for the Study of Lung Cancer
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| 28. |
- Markaki, I., et al.
(författare)
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Cerebrospinal Fluid Levels of Kininogen-1 Indicate Early Cognitive Impairment in Parkinson’s Disease
- 2020
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Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cognitive impairment is common in patients with PD. Core markers of Alzheimer’s dementia have been related also to PD dementia, but no disease-specific signature to predict PD dementia exists to date. Objectives: The aim of this study was to investigate CSF markers associated with cognition in early PD. Methods: A high-throughput suspension bead array examined 216 proteins in CSF of 74 PD patients in the AETIONOMY project. Cognitive function was assessed with Repeatable Battery for the Assessment of the Neuropsychological Status, Montreal Cognitive Assessment, and Mini-Mental State Examination. Results: Of 69 patients with complete data, 34 had high (≥90) and 35 had low Repeatable Battery for the Assessment of the Neuropsychological Status total score (<90). Of 14 proteins in CSF that differed in levels between groups, increased kininogen-1, validated with several antibodies, was independently associated with lower Repeatable Battery for the Assessment of the Neuropsychological Status and Montreal Cognitive Assessment scores after adjustment for confounders. Conclusions: Kininogen-1 levels in CSF may serve as a marker of cognitive impairment in PD.
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| 29. |
- Mitselou, Niki, 1982-, et al.
(författare)
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Preterm birth and risk of IgE sensitization up to early adulthood : a population-based birth cohort study
- 2021
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:Suppl. 110, s. 397-399
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Immunoglobulin E (IgE) sensitization is associated with asthma and allergic diseases. Gestational age influences early immune system development, thereby potentially affecting the process of tolerance induction to allergens. We aimed to study IgE sensitization to common allergens by gestational age from childhood up to early adulthood. Method: Population-based birth cohort, data from the Swedish BAMSE study was used. Allergen-specific IgE to a mix of common food (fx5) and inhalant (Phadiatop) allergens were analysed at 4, 8, 16 and 24 years. Sensitization was defined as allergen-specific IgE ≥0.35 kU A /l to fx5 and/or Phadiatop at each time-point. Using logistic regression and generalized estimated equations, adjusted odds ratios (aORs) for sensitization in relation to gestational age were calculated. Replication was sought within the Swedish twin study STOPPA.Results: In BAMSE, 3523 participants were screened for IgE anti-bodies during follow-up; of these, 197 (5.6%) were born preterm (<37 gestational weeks), and 330 (9.4%) post-term (≥42 weeks). Preterm birth was inversely associated with sensitization to common food and/or inhalant allergens up to early adulthood; overall aOR = 0.71 (95% CI = 0.51- 0.98). An inverse association was also observed between preterm birth and sensitization to food allergens specifically; overall aOR = 0.59 (95% CI = 0.38- 0.95). No relation was found between post-term birth and IgE sensitization at any time-point. Replication analyses in STOPPA ( N = 675) showed similar risk estimates for sensitization to food and/or inhalant allergens (aOR = 0.76; 95% CI: 0.45- 1.26), which resulted in a combined meta-analysis aOR = 0.72 (95% CI: 0.55- 0.95). Conclusion: Our study suggests an inverse association between preterm birth and later IgE sensitization.
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| 30. |
- Persson Berg, Linn, 1984, et al.
(författare)
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Serum IgG levels to Epstein-Barr and measles viruses in patients with multiple sclerosis during natalizumab and interferon beta treatment
- 2022
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Ingår i: Bmj Neurology Open. - : BMJ. - 2632-6140. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with multiple sclerosis (MS) demonstrate higher seroprevalence of Epstein-Barr virus (EBV) and increased anti-EBV IgG levels in serum compared with healthy controls. Intrathecal antibody production to measles virus (MeV) is a common finding in patients with MS. Objective To measure serum IgG reactivity to EBV glycoprotein 350 (gp350) and MeV nucleocapsid protein (N-CORE) in patients with MS and healthy controls and to determine if reactivity changed in patients during interferon beta (IFN beta) and/or natalizumab (NAT) treatment. A secondary aim was to determine the seroprevalence of EBV in patients and controls. Methods Patients with MS (n=728) were included from the Swedish pharmacovigilance study for NAT. Paired serum samples from 714 patients drawn before and during NAT treatment and paired samples from 170 patients during prior IFN beta treatment were analysed. In total, 156 patients were included in both groups. Samples from 144 matched blood donors served as controls. Indirect ELISA was applied using recombinant EBVgp350 and MeV N-CORE as antigens. EBVgp350 IgG seronegative samples were also analysed using EBV nuclear antigen 1 and viral capsid antigen (VCA). Results Patients with MS showed higher serum levels of anti-EBVgp350 and anti-MeV N-CORE IgG compared with controls. During NAT treatment, the levels of anti-EBVgp350 and anti-MeV N-CORE IgG declined, compared with the relatively stable levels noted during prior IFN beta treatment. Ten patients failed to demonstrate anti-EBVgp350 IgG but did show detectable anti-VCA IgG, indicating EBV seropositivity. In contrast, 10/144 controls were EBV seronegative. Conclusions Treatment with NAT, which is considered a selective immunosuppressive agent with a compartmentalised effect on the central nervous system, appeared to be associated with a moderate decrease in circulating IgG levels to EBVgp350 and MeV N-CORE. All patients with MS were EBV IgG seropositive, supporting the potential role of EBV in the pathogenesis of MS.
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| 31. |
- Schulzen, Arne, et al.
(författare)
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Development and characterization of solid lipid-based formulations (sLBFs) of ritonavir utilizing a lipolysis and permeation assay
- 2024
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 196
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Tidskriftsartikel (refereegranskat)abstract
- As a high number of active pharmaceutical ingredients (APIs) under development belong to BCS classes II and IV, the need for improving bioavailability is critical. A powerful approach is the use of lipid-based formulations (LBFs) that usually consist of a combination of liquid lipids, cosolvents, and surfactants. In this study, ritonavir loaded solid LBFs (sLBFs) were prepared using solid lipid excipients to investigate whether sLBFs are also capable of improving solubility and permeability. Additionally, the influence of polymeric precipitation inhibitors (PVPVA and HPMC-AS) on lipolysis triggered supersaturation and precipitation was investigated. One step intestinal digestion and bicompartmental permeation studies using an artificial lecithin-in-dodecane (LiDo) membrane were performed for each formulation. All formulations presented significantly higher solubility (5 to >20-fold higher) during lipolysis and permeation studies compared to pure ritonavir. In the combined lipolysispermeation studies, the formulated ritonavir concentration increased 15 -fold in the donor compartment and the flux increased up to 71 % as compared to non-formulated ritonavir. The formulation with the highest surfactant concentration showed significantly higher ritonavir solubility compared to the formulation with the highest amount of lipids. However, the precipitation rates were comparable. The addition of precipitation inhibitors did not influence the lipolytic process and showed no significant benefit over the initial formulations with regards to precipitation. While all tested sLBFs increased the permeation rate, no statistically significant difference was noted between the formulations regardless of composition. To conclude, the different release profiles of the formulations were not correlated to the resulting flux through a permeation membrane, further supporting the importance of matring use of combined lipolysis-permeation assays when exploring LBFs.
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| 35. |
- Torén, Kjell, 1952, et al.
(författare)
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Occupational risks associated with severe COVID-19 disease and SARS-CoV-2 infection-a Swedish national case-control study conducted from October 2020 to December 2021
- 2023
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Ingår i: Scandinavian Journal of Work Environment & Health. - 0355-3140. ; 49:6, s. 386-394
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study aimed to investigate whether workplace factors and occupations are associated with SARSCoV-2 infection or severe COVID-19 in the later waves of the pandemic.Methods We studied 552 562 cases with a positive test for SARS-CoV-2 in the Swedish registry of communicable diseases, and 5985 cases with severe COVID-19 based on hospital admissions from October 2020 to December 2021. Four population controls were assigned the index dates of their corresponding cases. We linked job histories to job-exposure matrices to assess the odds for different transmission dimensions and different occupations. We used adjusted conditional logistic analyses to estimate odds ratios (OR) for severe COVID-19 and SARS-CoV-2 with 95% confidence intervals (CI).Results The highest OR for severe COVID-19 were for: regular contact with infected patients, (OR 1.37, 95% CI 1.23-1.54), close physical proximity (OR 1.47, 95% CI 1.34-1.61), and high exposure to diseases or infections (OR 1.72, 95% CI 1.52-1.96). Mostly working outside had lower OR (OR 0.77, 95% CI 0.57-1.06). The odds for SARS-CoV-2 when mostly working outside were similar (OR 0.83, 95% CI 0.80-0.86). The occupation with the highest OR for severe COVID-19 (compared with low-exposure occupations) was certified specialist physician (OR 2.05, 95% CI 1.31-3.21) among women and bus and tram drivers (OR 2.04, 95% CI 1.49-2.79) among men.Conclusions Contact with infected patients, close proximity and crowded workplaces increase the risks for severe COVID-19 and SARS-CoV-2 infection. Outdoor work is associated with decreased odds for SARS-CoV-2 infection and severe COVID-19.
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| 36. |
- Torén, Kjell, 1952, et al.
(författare)
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Occupational risks for infection with influenza A and B: a national case-control study covering 1 July 2006-31 December 2019
- 2023
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Ingår i: Occupational and Environmental Medicine. - 1351-0711 .- 1470-7926. ; 80:7, s. 377-383
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesWe investigated whether crowded workplaces, sharing surfaces and exposure to infections were factors associated with a positive test for influenza virus. MethodsWe studied 11 300 cases with a positive test for influenza A and 3671 cases of influenza B from Swedish registry of communicable diseases. Six controls for each case were selected from the population registry, with each control being assigned the index date of their corresponding case. We linked job histories to job-exposure matrices (JEMs), to assess different transmission dimensions of influenza and risks for different occupations compared with occupations that the JEM classifies as low exposed. We used adjusted conditional logistic analyses to estimate the ORs for influenza with 95% CI. ResultsThe highest odds were for influenza were: regular contact with infected patients (OR 1.64, 95% CI 1.54 to 1.73); never maintained social distance (OR 1.51, 95% CI 1.43 to 1.59); frequently sharing materials/surfaces with the general public (OR 1.41, 95% CI 1.34 to 1.48); close physical proximity (OR 1.54, 95% CI 1.45 to 1.62) and high exposure to diseases or infections (OR 1.54, 95% CI 1.44 to 1.64). There were small differences between influenza A and influenza B. The five occupations with the highest odds as compared with low exposed occupations were: primary care physicians, protective service workers, elementary workers, medical and laboratory technicians, and taxi drivers. ConclusionsContact with infected patients, low social distance and sharing surfaces are dimensions that increase risk for influenza A and B. Further safety measures are needed to diminish viral transmission in these contexts.
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| 44. |
- Yu, Z, et al.
(författare)
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Associations of improved air quality with lung function growth from childhood to adulthood: the BAMSE study
- 2023
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:5
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Tidskriftsartikel (refereegranskat)abstract
- The beneficial effect of improving air quality on lung function development remains understudied. We assessed associations of changes in ambient air pollution levels with lung function growth from childhood until young adulthood in a Swedish cohort study.MethodsIn the prospective birth cohort BAMSE (Children, Allergy, Environment, Stockholm, Epidemiology), spirometry was conducted at the 8-year (2002–2004), 16-year (2011–2013) and 24-year follow-ups (2016–2019). Participants with spirometry data at 8 years and at least one another measurement in subsequent follow-ups were included (1509 participants with 3837 spirometry measurements). Ambient air pollution levels (particulate matter≤2.5 μm [PM2.5], particulate matter≤10 μm [PM10], black carbon [BC] and nitrogen oxides [NOx]) at residential addresses were estimated using dispersion modelling. Linear mixed-effect models were used to estimate associations between air pollution exposure change and lung function development.ResultsOverall, air pollution levels decreased progressively during the study period. For example, the median (interquartile range, IQR) of PM2.5decreased from 8.24 (0.92) μg·m−3during 2002–2004 to 5.21 (0.67) μg·m−3during 2016–2019. At the individual level, for each IQR reduction of PM2.5the lung function growth rate increased by 4.63 ml year−1(95%CI:1.64–7.61, p<0.001) for FEV1and 9.38 ml year−1(95%CI: 4.76–14.00, p<0.001) for FVC. Similar associations were also observed for reductions of BC and NOx. Associations persisted after adjustment for potential confounders, and were not modified by asthma, allergic sensitization, overweight, early-life air pollution exposure or antioxidant dietary intake.ConclusionsLong-term reduction of air pollution is associated with positive lung function development from childhood to young adulthood.
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