| 1. |
- 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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| 2. |
- Tschiderer, L., et al.
(författare)
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Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies
- 2023
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Ingår i: Journal of the American Heart Association (JAHA). - 2047-9980. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and ResultsWe undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I-2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I-2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I-2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). ConclusionsOur large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.
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| 3. |
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| 4. |
- Tschiderer, L., et al.
(författare)
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The Prospective Studies of Atherosclerosis (Proof-ATHERO) Consortium: Design and Rationale
- 2020
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Ingår i: Gerontology. - : S. Karger AG. - 0304-324X .- 1423-0003. ; 66:5, s. 447-459
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis - the pathophysiological mechanism shared by most cardiovascular diseases - can be directly or indirectly assessed by a variety of clinical tests including measurement of carotid intima-media thickness, carotid plaque, ankle-brachial index, pulse wave velocity, and coronary artery calcium. The Prospective Studies of Atherosclerosis (Proof-ATHERO) consortium (https://clinicalepi.i-med.ac.at/research/proof-athero/) collates de-identified individual-participant data of studies with information on atherosclerosis measures, risk factors for cardiovascular disease, and incidence of cardiovascular diseases. It currently comprises 74 studies that involve 106,846 participants from 25 countries and over 40 cities. In summary, 21 studies recruited participants from the general population (n = 67,784), 16 from high-risk populations (n = 22,677), and 37 as part of clinical trials (n = 16,385). Baseline years of contributing studies range from April 1980 to July 2014; the latest follow-up was until June 2019. Mean age at baseline was 59 years (standard deviation: 10) and 50% were female. Over a total of 830,619 person-years of follow-up, 17,270 incident cardiovascular events (including coronary heart disease and stroke) and 13,270 deaths were recorded, corresponding to cumulative incidences of 2.1% and 1.6% per annum, respectively. The consortium is coordinated by the Clinical Epidemiology Team at the Medical University of Innsbruck, Austria. Contributing studies undergo a detailed data cleaning and harmonisation procedure before being incorporated in the Proof-ATHERO central database. Statistical analyses are being conducted according to pre-defined analysis plans and use established methods for individual-participant data meta-analysis. Capitalising on its large sample size, the multi-institutional collaborative Proof-ATHERO consortium aims to better characterise, understand, and predict the development of atherosclerosis and its clinical consequences. (c) 2020 S. Karger AG, Basel
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| 5. |
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| 6. |
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| 7. |
- 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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| 8. |
- 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. |
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| 10. |
- Alvebratt, Caroline, et al.
(författare)
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In Vitro Performance and Chemical Stability of Lipid-Based Formulations Encapsulated in a Mesoporous Magnesium Carbonate Carrier
- 2020
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Lipid-based formulations can circumvent the low aqueous solubility of problematic drug compounds and increase their oral absorption. As these formulations are often physically unstable and costly to manufacture, solidification has been suggested as a way to minimize these issues. This study evaluated the physicochemical stability and in vitro performance of lipid-loaded mesoporous magnesium carbonate (MMC) particles with an average pore size of 20 nm. A medium chain lipid was loaded onto the MMC carrier via physical adsorption. A modified in vitro lipolysis setup was then used to study lipid release and digestion with 1H nuclear magnetic resonance spectroscopy. The lipid loading efficiency with different solidification techniques was also evaluated. The MMC, unlike more commonly used porous silicate carriers, dissolved during the lipolysis assay, providing a rapid release of encapsulated lipids into solution. The digestion of the dispersed lipid-loaded MMC therefore resembled that of a coarse dispersion of the lipid. The stability data demonstrated minor degradation of the lipid within the pores of the MMC particles, but storage for three months did not reveal extensive degradation. To conclude, lipids can be adsorbed onto MMC, creating a solid powder from which the lipid is readily released into the solution during in vitro digestion. The chemical stability of the formulation does however merit further attention.
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| 11. |
- Berg, Staffan, et al.
(författare)
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In Vitro and In Vivo Evaluation of 3D Printed Capsules with Pressure Triggered Release Mechanism for Oral Peptide Delivery
- 2021
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 110:1, s. 228-238
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Tidskriftsartikel (refereegranskat)abstract
- In this study a 3D printed capsule designed to break from the physiological pressures in the antropyloric region was evaluated for its ability to deliver the synthetic octapeptide octreotide in beagle dogs when co-formulated with the permeation enhancer sodium caprate. The pressure sensitive capsules were compared to traditional enteric coated hard gelatin capsules and enteric coated tablets. Paracetamol, which is completely absorbed in dogs, was included in the formulations and used as an absorption marker to give information about the in vivo performance of the dosage forms. The pressure sensitive capsules released drug in 50% of the dogs. In the cases where drug was released, there was no difference in octreotide bioavailability or C-max compared to the enteric coated dosage forms. When comparing all dosage forms, a correlation was seen between paracetamol C-max and octreotide bioavailability, suggesting that a high drug release rate may be beneficial for peptide absorption when delivered together with sodium caprate. (C) 2020 Published by Elsevier Inc.
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| 12. |
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| 13. |
- Lin, Audrey T., et al.
(författare)
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The history of Coast Salish "woolly dogs" revealed by ancient genomics and Indigenous Knowledge
- 2023
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Ingår i: Science. - 0036-8075 .- 1095-9203. ; 382:6676, s. 1303-1308
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Tidskriftsartikel (refereegranskat)abstract
- Ancestral Coast Salish societies in the Pacific Northwest kept long-haired woolly dogs that were bred and cared for over millennia. However, the dog wool-weaving tradition declined during the 19th century, and the population was lost. In this study, we analyzed genomic and isotopic data from a preserved woolly dog pelt from "Mutton", collected in 1859. Mutton is the only known example of an Indigenous North American dog with dominant precolonial ancestry postdating the onset of settler colonialism. We identified candidate genetic variants potentially linked with their distinct woolly phenotype. We integrated these data with interviews from Coast Salish Elders, Knowledge Keepers, and weavers about shared traditional knowledge and memories surrounding woolly dogs, their importance within Coast Salish societies, and how colonial policies led directly to their disappearance.
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| 14. |
- 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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| 15. |
- 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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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Andresen Bergström, Moa, 1978, et al.
(författare)
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Rethinking Drug Analysis in Health Care: High-Throughput Analysis of 71 Drugs of Abuse in Oral Fluid Using Ion Mobility-High-Resolution Mass Spectrometry
- 2022
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press (OUP). - 0146-4760 .- 1945-2403. ; 46:7, s. 765-775
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Tidskriftsartikel (refereegranskat)abstract
- We have identified a clinical need for a sensitive, specific, flexible, comprehensive and affordable analytical technology to efficiently detect polydrug use. In addition, the current standard practice of surveilled urine sampling is uncomfortable for the patient; hence, more patient-friendly sample collection methods are requested. To fill these needs, we have developed and validated a high-throughput liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method for the analysis of drugs of abuse (DoA) in oral fluid (OF). The method covers a panel of 71 substances including traditional DoA, prescription narcotics and new psychoactive substances (NPS), with a guaranteed limit of identification of <3 mu g/L for 87% of the analytes. Method validation showed high accuracy (>99.7%), sensitivity (>99.7%) and specificity (100%). Most analytes had a high process efficiency during the salting-out liquid-liquid extraction sample preparation and no or only a minor matrix effect during the analysis. We have implemented this method in clinical routine and present data from 18,579 OF samples collected during routine patient treatment in mainly psychiatric and addiction clinics in West Sweden between September 2020 and June 2021. Seventy-one percent of the samples were positive and a total of 41,472 DoA findings were detected. Amphetamine (27%), buprenorphine (25%), nordiazepam (18%) and alprazolam (16%) were most prevalent. New psychoactive substances were detected in 189 samples (1.0%). The occurrence of polydrug use was common; 34% of the positive samples contained three analytes or more and 12% six or more. To the best of our knowledge, this is the first method for comprehensive analysis of DoA in OF using LC-HRMS and the largest dataset published on the detection of DoA in OF. With the current complex and variable drug use pattern, this broad, cost-effective and reliable method has largely replaced immunoassay screening in urine in our laboratory.
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| 22. |
- Belgrano, Andrea, et al.
(författare)
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Mapping and Evaluating Marine Protected Areas and Ecosystem Services: A Transdisciplinary Delphi Forecasting Process Framework
- 2021
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Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Marine Protected Areas (MPAs) are an important tool for management and conservation and play an increasingly recognised role in societal and human well-being. However, the assessment of MPAs often lacks a simultaneous consideration of ecological and socio-economic outcomes, and this can lead to misconceptions on the effectiveness of MPAs. In this perspective, we present a transdisciplinary approach based on the Delphi method for mapping and evaluating Marine Protected Areas for their ability to protect biodiversity while providing Ecosystem Services (ES) and related human well-being benefits – i.e., the ecosystem outputs from which people benefit. We highlight the need to include the human dimensions of marine protection in such assessments, given that the effectiveness of MPAs over time is conditional on the social, cultural and institutional contexts in which MPAs evolve. Our approach supports Ecosystem-Based Management and highlights the importance of MPAs in achieving restoration, conservation, and sustainable development objectives in relation to EU Directives such as the Marine Strategy Framework Directive (MSFD), the Maritime Spatial Planning Directive (MSPD), and the Common Fisheries Policy (CFP).
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| 23. |
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| 24. |
- Bergström, Anders, et al.
(författare)
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Grey wolf genomic history reveals a dual ancestry of dogs
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 607:7918, s. 313-320
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Tidskriftsartikel (refereegranskat)abstract
- The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000–30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.
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| 25. |
- Bergström, Lena, et al.
(författare)
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Ekologisk kompensation i kustmiljön : Hur kan man uppväga förluster av biologisk mångfald och ekosystemtjänster i samband med mänsklig verksamhet i kustområdet?
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sveriges kustmiljöer är utsatta för olika typer av mänsklig påverkan, med negativa effekter på arter, livsmiljöer och ekosystemtjänster. Enligt skadelindringshierarkin ska negativa effekter från mänsklig verksamhet i första hand undvikas, minimeras eller avhjälpas. I de kvarstående fall där skada trots dessa åtgärder är oundviklig, kan ekologisk kompensation vara ett sätt att mildra effekterna i syfte att bibehålla eller öka biologisk mångfald och ekosystemtjänster.I projektet ECOCOA har vi undersökt om och hur ekologisk kompensation skulle kunna användas i förvaltningen av kustområden. Vår målsättning har varit att bidra till en vetenskapligt grundad syn på hur ekologisk kompensation skulle kunna medverka till att stoppa nettoförluster av biologisk mångfald och ekosystemtjänster. Eftersom kompensation kan beröra en mängd aktörer och sakägare med olika intressen och perspektiv är det viktigt med en transparent process som hanteras på ett jämförbart sätt mellan olika områden och fall. En viktig flaskhals idag är brist på praktisk erfarenhet hos aktörer om hur kompensationen ska kunna tillämpas. Vi har utvecklat ett ramverk utifrån de steg som man behöver beakta i en bedömning av skada och kompensationsbehov, med fokus på att öka förutsättningarna för en transparent bedömningsprocess. Det föreslagna ramverket bygger på fyra steg: 1) skadebedömning; 2) bedömning av kompensationsbehov; 3) val av kompensationsåtgärder; och 4) utvärdering av resultat. Ramverket baserar sig på att tydliggöra samband mellan ekosystemets strukturer och de nyttigheter dessa kan medföra för människan, där nyttigheter är beroende av ekosystemtjänster, ekosystemtjänster av funktioner, och funktioner av strukturer. Vi kopplar ramverket till en utvärdering av aktuellt kunskapsläge kring åtgärders effektivitet i kustområdet. Viktiga livsmiljöer som ingår är ålgräs, grunda vegetationsklädda mjukbottnar, naturligt vegetationsfria mjukbottnar, tångbälten, musselbankar, stenrev och kustnära våtmarker.Vi har med hjälp av ramverket utvärderat nuvarande och möjliga tillämpningar av ekologisk kompensation. Utvärderingen har gjorts dels genom ett fullständigt exempel som beskriver förlust av ålgräsängar och dels genom att undersöka befintliga fall och sammanhang där kompensation är eller skulle kunna bli relevant. Fallen bygger på i) domslut gällande tillståndspliktig vattenverksamhet, ii) dagens hantering av småskalig exploatering i kustområden, samt iii) tillämpningen av särskild fiskeavgift ur ett kompensationsperspektiv. Slutligen har vi utvecklat förslag på hur liknande tillämpningar skulle kunna se ut för ytterligare livsmiljöer i tillägg till ålgräs.Våra resultat visar det finns fortsatt stor osäkerhet kring hur kompensationsprocesser och kompensationsåtgärder fungerar i praktiken. Samtidigt är det en realitet att man idag i de allra flesta fall exploaterar utan kompensation, eller med otillräcklig kompensation. Detta innebär i praktiken att förluster värderas till noll, det vill säga att man accepterar förluster på biologisk mångfald, ekosystemtjänster och nyttigheter, och att de skador som uppstår inte uppmärksammas i form av åtgärdsbehov som ska täckas av den som orsakar skadan. Eftersom tillämpningen av vårt ramverk synliggör värdet av att förvalta biologisk mångfald och ekosystemtjänster tillsammans kan det även stödja förvaltningen av kustområden i enlighet med ekosystemansatsen på en mer generell nivå.Våra resultat synliggör vikten av att värna biologisk mångfald. Vår genomgång av potentiella kompensationsåtgärder, som redogörs för i rapporten, visar med tydlighet att det är kostsamt att först förstöra och sedan restaurera, i stället för att skydda och undvika skada i första hand. Vi ser dock ett utrymme och ett behov av att förbättra användningen av ekologisk kompensation som ett av många verktyg för att värna biologisk mångfald och ekosystemtjänster i svenska kustmiljöer i enlighet med miljöbalken. ECOCOAs ramverk tillsammans med kaskadmodeller för viktiga livsmiljöer och information om potentiella åtgärder, kunde här fungera som en gemensam utgångspunkt vid diskussioner, samrådsprocesser och bedömningar.
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| 26. |
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| 27. |
- Buer, A. L., et al.
(författare)
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Nitrogen and Phosphorous Content in Blue Mussels (Mytilus spp.) Across the Baltic Sea
- 2020
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To support the ongoing discussion about mussel farming and the potential to extract nutrients from the sea, this study investigated the phosphorus (P) and nitrogen (N) content of blue mussels (Mytilus spp.) under different abiotic and biotic parameters. The focus of this survey was on the highly eutrophied Baltic Sea, where salinity ranges from 4 to 27 psu, and is a major contributing factor to differential mussel growth. We observed that nutrient content was not linearly correlated to salinity, but if categorized, decreased at higher salinities. Chlorophyll-a and temperature did not significantly correlate with nutrient content, but season of harvest and mussel size did. Furthermore, habitat was a strong driver of nutrient content, indicating higher nutrient density if mussels are grown in mussel farms (i.e., in the water column) instead of on mussel culture beds or harvested from wild beds (on the sea bed). Values of N and P averaged 5.85% N and 0.83% P of tissue dry weight in mussels at the sea bed and 9.43% N and 0.96% P of tissue dry weight in mussels from longline cultivation. These results will be useful in refining estimations about mussel farming as a nutrient mitigation measure and the extraction potential, as well as related costs.
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| 28. |
- Cole, Scott, et al.
(författare)
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Environmental compensation for biodiversity and ecosystem services : A flexible framework that addresses human wellbeing
- 2021
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Ingår i: Ecosystem Services. - : Elsevier BV. - 2212-0416 .- 2212-0416. ; 50
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Tidskriftsartikel (refereegranskat)abstract
- Environmental compensation should address negative impacts from human activities on nature, including loss of biodiversity and ecosystem services. However, successful compensation, achieving no net loss, requires broad quantitative information on different types of losses and gains. We find that the scope of compensatory schemes varies in what is considered compensable, which makes it challenging to apply a conceptual approach consistently across schemes with different needs. We propose a flexible yet structured framework for determining which values should be compensated and how. Our framework focuses specifically on habitat deterioration and is illustrated with a case study involving loss of eelgrass habitat. The framework helps identify compensation needs and selects among suitable compensation options, merging science-based information with normative issues and local concerns. By integrating the ecosystem services cascade model, it encompasses aspects from biodiversity structure to human wellbeing. The framework prefers in-kind compensation because this targets the structure level and thus meets compensation needs in all subsequent levels of the cascade model; further, it is more likely to capture non-instrumental values (i.e. in nature) and reduce exposure to uncertainty. We highlight the importance of spatial aspects of ecosystem functions, services and their subsequent impacts on wellbeing. Although our selection hierarchy assumes a similar and nearby principle for habitat restoration (preference for in-kind/on-site), this criterion is not universal. We underscore the hierarchy's implicit normative assumptions and suggest that apparent disagreement about who should benefit may be traced to an unresolved conflict between egalitarianism and utilitarianism.
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| 29. |
- Faithfull, Carolyn
(författare)
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Ekosystemtjänstanalyser som stöd för en regional ekosystembaserad havsförvaltning : Erfarenheter från tre pilotområden: 8-fjordar, Stockholms skärgård och Södra Bottenhavet
- 2024
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Kartläggning och analys av ekosystemtjänster är viktiga verktyg för att synliggöra människans relation till och beroende av ekosystemet. De kan till exempel påvisa samband mellan processer i ekosystemet och samhället, och användas som underlag för att diskutera avvägningar mellan olika mål och intressen. I ekosystembaserad havsförvaltning kan diskussioner om ekosystemtjänster öka aktörers förståelse för ekosystemet som grund för vårt nyttjande av havet. De kan också stödja åtgärdsarbete och strategisk planering. Här presenterar vi analyser av ekosystemtjänster som tagits fram som underlag för en regional ekosystembaserad havsförvaltning i Södra Bottenhavet, Stockholms skärgård och området 8+fjordar i Bohuslän. Vi har dels använt två olika metoder för att kartlägga utbredningen av ekosystemtjänster och associerade nyttigheter i pilotområden - en naturbaserad metod som utgår från utbredningen av ekosystemkomponenter och en öppen GIS-metod för att samla in lokal kunskap om ekosystemtjänster från intressenter och allmänhet.Den naturbaserade kartläggningen gjordes för Södra Bottenhavet och Stockholms skärgård. Studien hade som mål att utveckla och testa en metod för att kartlägga kustnära ekosystemtjänster utifrån kartor av arter och livsmiljöer och utvärdera hur metoden kan användas för ekosystembaserad planering. Vi har gjort en bedömning av vilka ekosystemtjänster som är relevanta att kartlägga med metoden i dessa områden och vilka arter och livsmiljöer som främst kan förväntas bidra till dessa tjänster. För att lätt kunna dela resultaten har vi utvecklat en app som tillåter en användare att ta fram potentiella ekosystemtjänstkartor utifrån kartor över arter och livsmiljöer. Som nästa steg behöver appen utvärderas tillsammans med användare, för att testa användbarhet och vidare utvecklingsbehov.Öppen-GIS-analysen gjordes inom projektet 8+fjordar, där intressenter och allmänhet bjöds in till workshops för att beskriva sin syn på områdets värden och vad som påverkar miljön i området. De resulterande GIS-lagren ger en bild av hur användare av det lokala ekosystemet uppfattar sin närmiljö och vilka ekosystemtjänster de värdesätter och nyttjar. En initial utvärdering visar att resultaten kan användas till exempel för att identifiera platser där det finns konflikter mellan olika användningar av havet och peka ut behov av åtgärder för att lösa dessa konflikter. Processen att ta fram underlagen bidrog dessutom till ett gemensamt lärande inom projektet.Den tredje metoden som vi har använt är en enkät- och intervjustudie för att undersöka markägares attityder och preferenser i samband med åtgärdsarbete i Stockholms skärgård. Den här studien fokuserade på vilka ekosystemtjänster och nyttigheter markägare värdesätter i naturtypen grunda havsvikar. Resultatet kompletterar kunskapen om människans förhållande till denna naturtyp och lägger en viktig grund för att inkludera sociala mål och indikatorer i arbetet för att skydda och restaurera grunda havsvikar.Ekosystemtjänster är fortfarande ett abstrakt begrepp för många och rapporten syftar till att genom exempel synliggöra hur ekosystemtjänster kan användas för att stödja en långsiktigt hållbar förvaltning av kustområden. Att ta hänsyn till det komplexa samspelet mellan människa och natur är en central del av ekosystembaserad förvaltning. Våra tre exempel fyller delvis olika syften inom denna komplexitet. De kan användas individuellt för särskilda ändamål eller komplettera varandra. I samtliga fall är det viktigt att arbeta nära aktörer för att tydligt definiera behov, syften, och säkerställa att de slutliga resultaten blir lokalt användbara.
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| 30. |
- Hober, Sophia, Professor, 1965-, et al.
(författare)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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| 31. |
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| 32. |
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| 33. |
- Källmark, H., et al.
(författare)
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Serologic immunogenicity and safety of herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors
- 2023
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Ingår i: Rheumatology. - 1462-0324.
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Tidskriftsartikel (refereegranskat)abstract
- Objective Patients with RA treated with Janus kinase inhibitors (JAKis) are at increased risk of herpes zoster (HZ). The objective of this study was to investigate the serological immunogenicity and safety of the HZ subunit (HZ/su) vaccine in RA patients treated with JAKi, for which little is known.Methods RA patients treated with JAKi (n = 82) at the Department of Rheumatology, Skane University Hospital, Lund and Malmo, Sweden, and healthy controls (n = 51) received two doses of the HZ/su vaccine (Shingrix). Vaccine-specific antibody responses were analysed using indirect ELISA. Post-vaccination antibody levels were compared between patients and controls using analysis of covariance. Potential predictors for vaccine response were investigated using a multivariable linear regression analysis. Self-reported adverse events (AEs) and changes in RA disease activity were analysed.Results Following vaccination, vaccine-specific antibody levels increased significantly in both patients and controls (P < 0.0001). A total of 80.5% of patients and 98.0% of controls achieved a >= 4-fold increase in antibody levels. Post-vaccination antibody levels were lower in patients than controls [ratio 0.44 (95% CI 0.31, 0.63)] and lower in patients receiving JAKi + methotrexate than JAKi monotherapy [ratio 0.43 (95% CI 0.24, 0.79)]. AEs, mostly mild/moderate, were common. One patient developed HZ and six patients (6.5%) had increased RA disease activity following vaccination.Conclusion The HZ/su vaccine was serologically immunogenic in most RA patients treated with JAKi. Moreover, the vaccine had an acceptable safety profile. These results support recommendations for use of the HZ/su vaccine in this vulnerable population.Trial registration ClinicalTrials.gov (https://clinicaltrials.gov), NCT03886038.
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| 34. |
- Lakshmikanth, T., et al.
(författare)
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Human Immune System Variation during 1 Year
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 32:3
-
Tidskriftsartikel (refereegranskat)abstract
- The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components and the inference of global regulatory principles. Here, we present a longitudinal, systems-level analysis in 99 healthy adults 50 to 65 years of age and sampled every third month for 1 year. We describe the structure of interindividual variation and characterize extreme phenotypes along a principal cum. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited differences in markers of metabolic health suggestive of a possible link between metabolic and immunologic homeostatic regulation.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Simpson, David, 1961, et al.
(författare)
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GenChem v1.0-a chemical pre-processing and testing system for atmospheric modelling
- 2020
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 13:12, s. 6447-6465
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Tidskriftsartikel (refereegranskat)abstract
- This paper outlines the structure and usage of the GenChem system, which includes a chemical preprocessor GenChem.py) and a simple box model (box-Chem). GenChem provides scripts and input files for converting chemical equations into differential form for use in atmospheric chemical transport models (CTMs) and/or the boxChem system. Although GenChem is primarily intended for users of the Meteorological Synthesizing Centre - West of the European Monitoring and Evaluation Programme (EMEP MSC-W) CTM and related systems, boxChem can be run as a stand-alone chemical solver, enabling for example easy testing of chemical mechanisms against each other. This paper presents an outline of the usage of the GenChem system, explaining input and output files, and presents some examples of usage. The code needed to run GenChem is released as opensource code under the GNU license.
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| 41. |
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| 42. |
- Torén, Kjell, 1952, et al.
(författare)
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Chronic airflow limitation and its relation to respiratory symptoms among ever-smokers and never-smokers: a cross-sectional study
- 2020
-
Ingår i: Bmj Open Respiratory Research. - : BMJ. - 2052-4439. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background The diagnosis of chronic obstructive pulmonary disease is based on the presence of persistent respiratory symptoms and chronic airflow limitation (CAL). CAL is based on the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1:FVC) after bronchodilation, and FEV1:FVC less than the fifth percentile is often used as a cut-off for CAL. The aim was to investigate if increasing percentiles of FEV1:FVC were associated withany respiratory symptom(cough with phlegm, dyspnoea or wheezing) in a general population sample of never-smokers and ever-smokers. Methods In a cross-sectional study comprising 15 128 adults (50-64 years), 7120 never-smokers and 8008 ever-smokers completed a respiratory questionnaire and performed FEV(1)and FVC after bronchodilation. We calculated theirz-scores for FEV1:FVC and defined the fifth percentile using the Global Lung Function Initiative (GLI) reference value, GLI(5)and increasing percentiles up to GLI(25). We analysed the associations between different strata of percentiles and prevalence ofany respiratory symptomusing multivariable logistic regression for estimation of OR. Results Among all subjects, regardless of smoking habits, the odds ofany respiratory symptomwere elevated up to the GLI(15-20)strata. Among never-smokers, the odds ofany respiratory symptomwere elevated at GLI(<5)(OR 3.57, 95% CI 2.43 to 5.23) and at GLI(5-10)(OR 2.57, 95% CI 1.69 to 3.91), but not at higher percentiles. Among ever-smokers, the odds ofany respiratory symptomwere elevated from GLI(<5)(OR 4.64, 95% CI 3.79 to 5.68) up to GLI(>= 25)(OR 1.33, 95% CI 1.00 to 1.75). Conclusions The association between percentages of FEV1:FVC and respiratory symptoms differed depending on smoking history. Our results support a higher percentile cut-off for FEV1:FVC for never-smokers and, in particular, for ever-smokers.
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| 43. |
- Wright, Leah, et al.
(författare)
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A comparison of chitosan, mesoporous silica and poly(lactic-co-glycolic) acid nanocarriers for optimising intestinal uptake of oral protein therapeutics
- 2021
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 110:1, s. 217-227
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Tidskriftsartikel (refereegranskat)abstract
- Efficacious oral delivery of therapeutic proteins remains challenging and nanoparticulate approaches are gaining interest for enhancing their permeability. In this study, we explore the ability for three comparably sized nanocarriers, with diverse physicochemical properties (i.e., chitosan (CSNP), mesoporous silica nanoparticles (MSNP) and poly(lactic-co-glycolic) acid (PLGA-NP)), to successfully facilitate epithelial uptake of a model protein, ovalbumin (OVA). We report the effect of nanoparticle surface chemistry and nanostructure on protein release, cell toxicity and the uptake mechanism in a Madin Darby Canine Kidney (MDCK) cell model of the intestinal epithelium. All nanocarriers exhibited bi-phasic OVA release kinetics with sustained and incomplete release after 4 days, and more pronounced release from MSNP than either polymeric nanocarriers. CSNP and MSNP displayed the highest cellular uptake, however CSNP was prone to significant dose-dependent toxicity attributed to the cationic surface charge. Approximately 25% of MSNP uptake was governed by a clathrin-independent endocytic mechanism, while CSNP and PLGA-NP uptake was not controlled via any endocytic mechanisms investigated herein. Furthermore, endosomal localisation was observed for CSNP and MSNP, but not for PLGA-NP's. These findings may assist in the optimal choice and engineering of nanocarriers for specific intestinal permeation enhancement for oral protein delivery.
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| 44. |
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| 45. |
- 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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| 46. |
- Ansari, Shaquib Rahman, 1993-, et al.
(författare)
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Hyperthermia-Induced In Situ Drug Amorphization by Superparamagnetic Nanoparticles in Oral Dosage Forms
- 2022
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 14:19, s. 21978-21988
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Tidskriftsartikel (refereegranskat)abstract
- Superparamagnetic iron oxide nanoparticles (SPIONs) generate heat upon exposure to an alternating magnetic field (AMF), which has been studied for hyperthermia treatment and triggered drug release. This study introduces a novel application of magnetic hyperthermia to induce amorphization of a poorly aqueous soluble drug, celecoxib, in situ in tablets for oral administration. Poor aqueous solubility of many drug candidates is a major hurdle in oral drug development. A novel approach to overcome this challenge is in situ amorphization of crystalline drugs. This method facilitates amorphization by molecular dispersion of the drug in a polymeric network inside a tablet, circumventing the physical instability encountered during the manufacturing and storage of conventional amorphous solid dispersions. However, the current shortcomings of this approach include low drug loading, toxicity of excipients, and drug degradation. Here, doped SPIONs produced by flame spray pyrolysis are compacted with polyvinylpyrrolidone and celecoxib and exposed to an AMF in solid state. A design of experiments approach was used to investigate the effects of SPION composition (Zn0.5Fe2.5O4 and Mn0.5Fe2.5O4), doped SPION content (10–20 wt %), drug load (30–50 wt %), and duration of AMF (3–15 min) on the degree of drug amorphization. The degree of amorphization is strongly linked to the maximum tablet temperature achieved during the AMF exposure (r = 0.96), which depends on the SPION composition and content in the tablets. Complete amorphization is achieved with 20 wt % Mn0.5Fe2.5O4 and 30 wt % celecoxib in the tablets that reached the maximum temperature of 165.2 °C after 15 min of AMF exposure. Furthermore, manganese ferrite exhibits no toxicity in human intestinal Caco-2 cell lines. The resulting maximum solubility of in situ amorphized celecoxib is 5 times higher than that of crystalline celecoxib in biorelevant intestinal fluid. This demonstrates the promising capability of SPIONs as enabling excipients to magnetically induce amorphization in situ in oral dosage forms.
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| 47. |
- Asad, Shno, et al.
(författare)
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Proteomics-Informed Identification of Luminal Targets For In Situ Diagnosis of Inflammatory Bowel Disease
- 2021
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 110:1, s. 239-250
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory bowel disease (IBD) is a chronic condition resulting in impaired intestinal homeostasis. Current practices for diagnosis of IBD are challenged by invasive, demanding procedures. We hypothesized that proteomics analysis could provide a powerful tool for identifying clinical biomarkers for non-invasive IBD diagnosis. Here, the global intestinal proteomes from commonly used in vitro and in vivo models of IBD were analyzed to identify apical and luminal proteins that can be targeted by orally delivered diagnostic agents. Global proteomics analysis revealed upregulated plasma membrane proteins in intestinal segments of proximal- and distal colon from dextran sulfate sodium-treated mice and also in inflamed human intestinal Caco-2 cells pretreated with pro-inflammatory agents. The upregulated colon proteins in mice were compared to the proteome of the healthy ileum, to ensure targeting of diagnostic agents to the inflamed colon. Promising target proteins for future investigations of non-invasive diagnosis of IBD were found in both systems and included Tgm2/TGM2, Icam1/ICAM1, Ceacam1/CEACAM1, and Anxa1/ANXA1. Ultimately, these findings will guide the selection of appropriate antibodies for surface functionalization of imaging agents aimed to target inflammatory biomarkers in situ.
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| 48. |
- Axelsson, Magnus A. B., et al.
(författare)
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Retrospective identification of new psychoactive substances in patient samples submitted for clinical drug analysis
- 2022
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 131:5, s. 420-434
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Tidskriftsartikel (refereegranskat)abstract
- New psychoactive substances (NPS) are life threatening through unpredictable toxicity and limited analytical options for clinicians. We present the retrospective identification of NPS in raw data from a liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based multidrug panel analysis on 14 367 clinical oral fluid samples requested during 2019 mainly by psychiatric and addiction care clinics. Retrospectively analysed NPS included 48 notified originally in 2019 by the European Union Early Warning System (EU EWS) and 28 frequently reported in Sweden. Of 88 included NPS, 34 (mitragynine, flualprazolam, 3F/4F-α-P(i)HP, etizolam, 4F-MDMB-BINACA, cyproheptadine, 5F-MDMB-PICA, isotonitazene, isohexedrone, MDPEP, N-ethylpentedrone, tianeptine, flubromazolam, 4′-methylhexedrone, α-P(i)HP, eutylone, mephedrone, N-ethylhexedrone, 5F-MDMB-PINACA, ADB-BUTINACA, 3-methoxy PCP, 4F-furanylfentanyl, 4F-isobuturylfentanyl, acrylfentanyl, furanylfentanyl, clonazolam, norfludiazepam, 3F-phenmetrazine, 3-MMC, 4-methylpentedrone, BMDP, ethylphenidate, methylone and α-PVP) were identified as 219 findings in 84 patients. Eight NPS notified in 2019 were identified, five before EWS release. NPS occurred in 1.20% of all samples and 1.53% of samples containing traditional drugs, and in 1.87% of all patients and 2.88% of patients using traditional drugs. NPS use was more common in men and polydrug users. Legal (not scheduled) NPS were more used than comparable illegal ones. Retrospective identification could be useful when prioritizing NPS for clinical routine analysis and when studying NPS epidemiology. © 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.
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| 49. |
- 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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| 50. |
- Axen, Iben, et al.
(författare)
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Misinformation, chiropractic, and the COVID-19 pandemic
- 2020
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Ingår i: Chiropractic and Manual Therapies. - : BioMed Central (BMC). - 2045-709X. ; 28:1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: In March 2020, the World Health Organization elevated the coronavirus disease (COVID-19) epidemic to a pandemic and called for urgent and aggressive action worldwide. Public health experts have communicated clear and emphatic strategies to prevent the spread of COVID-19. Hygiene rules and social distancing practices have been implemented by entire populations, including 'stay-at-home' orders in many countries. The long-term health and economic consequences of the COVID-19 pandemic are not yet known.Main text: During this time of crisis, some chiropractors made claims on social media that chiropractic treatment can prevent or impact COVID-19. The rationale for these claims is that spinal manipulation can impact the nervous system and thus improve immunity. These beliefs often stem from nineteenth-century chiropractic concepts. We are aware of no clinically relevant scientific evidence to support such statements. We explored the internet and social media to collect examples of misinformation from Europe, North America, Australia and New Zealand regarding the impact of chiropractic treatment on immune function. We discuss the potential harm resulting from these claims and explore the role of chiropractors, teaching institutions, accrediting agencies, and legislative bodies.Conclusions: Members of the chiropractic profession share a collective responsibility to act in the best interests of patients and public health. We hope that all chiropractic stakeholders will view the COVID-19 pandemic as a call to action to eliminate the unethical and potentially dangerous claims made by chiropractors who practise outside the boundaries of scientific evidence.
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