| 1. |
- Gard, Anna, et al.
(författare)
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Quality of life of ice hockey players after retirement due to concussions
- 2020
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Ingår i: Concussion. - : Future Medicine. - 2056-3299. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sports-related concussion (SRC) is increasingly recognized as a potential health problem in ice hockey. Quality of life (QoL) in players retiring due to SRC has not been thoroughly addressed. Materials & methods: QoL using the Sports Concussion Assessment Tool 5th Edition, Impact of Event Scale-Revised and Short Form Health Survey was measured in Swedish ice hockey players who retired due to persistence of postconcussion symptoms or fear of attaining additional SRC. Results: A total of 76 players were assessed, on average of 5 years after their most recent SRC. Overall, retired players had a high burden of postconcussion symptoms and reduced QoL. Conclusion: Retired concussed ice hockey players have a reduced QoL, particularly those retiring due to postconcussion symptoms. Symptom burden should be continuously evaluated and guide the decision to retire.
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| 2. |
- Akner, Gunnar, 1953-, et al.
(författare)
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Vi står gärna bakom en utfallsbaserad vård
- 2017
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Ingår i: Dagens Samhälle. - 1652-6511.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Jörgen Nordenström försöker få det till att vår kritik av värdebaserad vård egentligen handlar om att vi vill ha mer resurser. Han har helt missuppfattat oss, skriver 26 specialistläkare i en replik.
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| 3. |
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| 4. |
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| 5. |
- Albers, Eva, 1966, et al.
(författare)
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Cellular response in fresh water microalgae to polluting compounds of flue gas when used as carbon source
- 2012
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Ingår i: 15th Workshop of International Study Group for Systems Biology (ISGSB), September 25-28, Ameland, The Netherlands.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Attention has lately been given to the use of microalgae as provider of valuable biomass or as production organism. To be able to use algae in industrial production, especially of biofuels, the cultivation procedures need to be improved in terms of efficiency and minimization of production costs. To reach these goals understanding of both process conditions as well as biological response to such conditions is needed for optimization of algal cultivation. Carbon dioxide, the carbon source during phototrophic growth, should be provided at high levels to result in the high biomass concentrations needed for a feasible production. Suitable high-level sources of CO2 are flue gases from industrial activities, which when used for algal cultivation will be a way of carbon capture reducing CO2 emissions. However, flue gases contain additional components that may affect cellular activity negatively. The aim of this research is to understand the physiological behavior of microalgae in industrial conditions to be able to optimize cellular performance. This initial project was launched to provide basic information about response of several types of microalgae that could grow in fresh water conditions to the main gaseous pollutants in flue gas, NO and SO2. This knowledge would guide the selection for a deeper characterization of effect-response relations and control of metabolism in algae in response to industrial conditions. Ten strains of fresh water species and one marine were selected based on reported fast growth and interesting composition such as high levels of lipids. The algae were screened for growth and cellular composition in cultivations with fresh water mineral medium. Artificially produced flue gas, mimicking effluents of pulp mills, consisting of 15% CO2 with 100 ppm NO and 10 ppm SO2 included for the last period of the cultivations was bubbled into the cultures. All strains tested were able to grow and two Scenedesmus strains, an isolated strain from a nearby lake, Chorella protothecoides and Chlamydomonas reinhardtii exhibited the highest specific growth rates. The highest levels of cellular macromolecules were found in Chlorella emersonii (45% carbohydrates), Nannochloropsis salina and the local isolate (65% proteins), and Botrycoccus braunii (57% lipids). It can be concluded that all strains tested were able to grow in cultures with flue gas as carbon source, also the marine species Nannochloropsis salina, and that the gaseous components decrease pH which needs to be monitored carefully to avoid that large drops in pH inhibit algal growth.
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| 6. |
- Albers, Eva, 1966, et al.
(författare)
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Influence of flue gas mimicking effluents of paper mills on growth and cellular composition of fresh water species of microalgae
- 2012
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Ingår i: 9th European Workshop on Biotechnology of Microalgae, 4-5 June, Nuthetal, Germany.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- To be able to use algae in industrial production, especially of biofuels, the cultivation procedures need to be improved in terms of efficiency and minimization of production costs. One important factor is to reach as high biomass concentrations as possible e.g. by using high levels of carbon dioxide provided by flue gas. The aim of this project was to study the influence of flue gas simulated to mimic effluents of pulp mills on growth and cellular composition of microalgae. Ten strains of fresh water species and one marine were selected based on reported fast growth and interesting composition such as high levels of lipids. The algae were screened in cultivations with fresh water mineral medium and artificially produced flue gas bubbled into the cultures consisting of 15% CO2 with 100 ppm NO and 10 ppm SO2 included for the last period of the cultivations. All strains tested were able to grow and two Scenedesmus strains, an isolated strain from a nearby lake, Chorella protothecoides and Chlamydomonas reinhardtii exhibited the highest specific growth rates. The highest levels of cellular macromolecules were found in Chlorella emersonii (45% of carbohydrates), Nannochloropsis salina and the local isolate (65% of proteins), and Botrycoccus braunii (57% of lipids). It can be concluded that all strains tested were able to grow in cultures with flue gas as carbon source, also the marine species Nannochloropsis salina, and that the gaseous components decrease pH which needs to be monitored carefully to avoid that large drops in pH inhibit algal growth.
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| 7. |
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| 8. |
- Andersson, Eva M., et al.
(författare)
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Is cadmium a risk factor for breast cancer - Results from a nested case-control study using data from the malmö diet and cancer study
- 2021
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Ingår i: Cancer Epidemiology Biomarkers and Prevention. - 1055-9965. ; 30:9, s. 1744-1752
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Tidskriftsartikel (refereegranskat)abstract
- Background: Some studies have shown that cadmium (Cd) is associated with breast cancer risk. One hypothesis is that Cd has estrogen-like properties. This case-control study investigated the association between breast cancer risk and blood Cd (BCd) levels. Methods: All breast cancers in the Malmö Diet and Cancer cohort were identified through linkage to the Swedish Cancer Registry, baseline (1991-1996) through 2014. Two controls per case were selected from the same cohort. BCd was analyzed at baseline. Associations were analyzed using logistic regression. Results: Mean BCd was 0.51 mg/L among 1, 274 cases and 0.46 among 2, 572 controls. There was an overall increased risk of breast cancer [OR, 1.18; 95% confidence interval (CI), 1.05-1.36] per mg/L of BCd. An increased risk was, however, only found at high BCd [OR, 1.34 (95% CI, 1.05-1.73)] for BCd more than 1.20 mg/L. The group with the highest BCd was mainly smokers. A spline indicated that at BCd less than 1.0 mg/L, the OR was not increased. The association with BCd was stronger in current smokers and at body mass index (BMI) above 25, while no modification due to receptor status was found. Conclusions: The results indicated increased risk of breast cancer only for high Cd exposure, which occurred mainly among smokers. This made it difficult to disentangle the effects of smoking and Cd, despite inclusion of smoking habits in the models. Impact: This study provides support for reducing Cd exposure through smoking cessation and dietary choice. On the population level, preventive measures against Cd pollution are warranted.
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| 9. |
- Barregård, Lars, 1948, et al.
(författare)
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Cadmium Exposure and Coronary Artery Atherosclerosis: A Cross-Sectional Population-Based Study of Swedish Middle-Aged Adults
- 2021
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Ingår i: Environmental health perspectives. - 1552-9924 .- 0091-6765. ; 129:6
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Tidskriftsartikel (refereegranskat)abstract
- The general population is ubiquitously exposed to the toxic metal cadmium through the diet and smoking. Cadmium exposure is associated with increased morbidity and mortality in myocardial infarction and stroke. Atherosclerosis is the main underlying mechanism of myocardial infarction. However, associations between cadmium and coronary artery atherosclerosis have not been examined.Our study sought to examine the hypothesis that blood cadmium (B-Cd) is positively associated with coronary artery calcification, as a measure of coronary artery atherosclerosis in the population-based Swedish SCAPIS study.Our analysis included 5,627 individuals (51% women), age 50-64 y, enrolled from 2013 to 2018. The coronary artery calcium score (CACS) was obtained from computed tomography. Blood cadmium was determined by inductively coupled plasma mass spectrometry (ICP-MS). Associations between B-Cd and coronary artery calcium score (CACS Agatston score) were evaluated using prevalence ratios (PRs) in models adjusted for sex, age, smoking, hypertension, diabetes, low-density cholesterol/high-density cholesterol ratio, and family history.The median B-Cd concentration was 0.24 μ g / L . The prevalence of positive coronary artery calcium ( CACS > 0 ) was 41% and the prevalence of CACS ≥ 100 was 13%. Relative to the lowest quartile (Q) of B-Cd ( < 0.16 μ g / L ), the highest quartile (median 0.63 μ g / L ) was associated with a small but significant increase in CACS > 0 (PR 1.1; 95% CI: 1.0, 1.3), and a greater relative increase in CACS ≥ 100 (PR 1.6; 95% CI: 1.3, 2.0). When restricted to 2,446 never-smokers, corresponding PRs were 1.1 (95% CI 0.9, 1.3) for CACS > 0 (63 cases in Q4) and 1.7 (95% CI 1.1, 2.7) for CACS ≥ 100 (17 cases in Q4).Blood cadmium in the highest quartile was associated with CACS in a general population sample with low to moderate cadmium exposure. This supports the hypothesis that atherosclerosis is an important mechanism underlying the associations between cadmium and incident cardiovascular disease. The findings suggest that public health measures to reduce cadmium exposure are warranted. https://doi.org/10.1289/EHP8523.
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| 10. |
- Bengtsson, Niklas, et al.
(författare)
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Control and Efficiency in the Nonprofit Sector : Evidence from a Randomized Policy Experiment
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Results in behavioral economics suggest that material incentives can crowd out motivation, if agents are mission-oriented rather than self-interested. We test this prediction on a sample of nonprot organizations in Sweden. Swedish nonprot organizations receive tax funds annually to promote human development issues through information campaigns. Traditionally, the contract with the main principal (the Swedish foreign aid agency) has been based on trust and self-regulation. We designed an experimental policy intervention, eectively replacing the trust-based contract with an increased level of monitoring from the principal, along with a threat to cut future funds if irregularities were detected. Our findings are inconsistent with (strong) motivational crowd-out. Overall, using both self-reported and observed measures of outreach, we find that the intervention improved eciency. Graphical analysis shows that non-monitored organizations exhibit a distinct tendency to maximize expenditure; in contrast, organizations in the treatment group are more likely to return unused grants to Sida. Additionally, we find no crowding out of private contributions and no evidence of a "discouraged NGO"-syndrome.
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| 11. |
- Bengtsson, Niklas, et al.
(författare)
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Replacing trust with control : a field test of motivation crowd out theory
- 2014
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Ingår i: Economic Journal. - : Oxford University Press (OUP). - 0013-0133 .- 1468-0297. ; 124:577, s. 833-858
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Tidskriftsartikel (refereegranskat)abstract
- Results in behavioural economics suggest that material incentives can crowd out motivation if agents are mission-oriented rather than self-interested. We test this prediction on a sample of non-profit organisations in Sweden. Traditionally, contracts with the main principal (the Swedish foreign aid agency) have been based on trust and self-regulation. We designed a randomised policy experiment, effectively replacing the trust-based contract with an increased level of monitoring from the principal. Overall, using both self-reported and observed measures of outreach, we find that the intervention increased outreach, reduced expenditures and reduced the number of financial irregularities.
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| 12. |
- Bengtsson, Stefan, 1961, et al.
(författare)
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Carbon-based nanoelectromechanical devices
- 2011
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Ingår i: International Journal of High Speed Electronics and Systems. - 1793-6438. ; 20:1, s. 195-204
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Tidskriftsartikel (refereegranskat)abstract
- Carbon-based nanoelectromechanical devices are approaching applications in electronics. Switches based on individual carbon nanotubes deliver record low off-state leakage currents. Arrays of vertically aligned carbon nanotubes or nanofibers can be fabricated to constitute varactors. Very porous, low density arrays of quasi-vertically aligned arrays of carbon nanotubes behave mechanically as a single unit with very unusual material properties.
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| 13. |
- Carroll, Christopher, et al.
(författare)
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Hypoxia Generated by Avian Embryo Growth Induces the HIF-α Response and Critical Vascularization
- 2021
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Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 9, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Cancer research has transformed our view on cellular mechanisms for oxygen sensing. It has been documented that these mechanisms are important for maintaining animal tissues and life in environments where oxygen (O2) concentrations fluctuate. In adult animals, oxygen sensing is governed by the Hypoxia Inducible Factors (HIFs) that are stabilized at low oxygen concentrations (hypoxia). However, the importance of hypoxia itself during development and for the onset of HIF-driven oxygen sensing remains poorly explored. Cellular responses to hypoxia associates with cell immaturity (stemness) and proper tissue and organ development. During mammalian development, the initial uterine environment is hypoxic. The oxygenation status during avian embryogenesis is more complex since O2 continuously equilibrates across the porous eggshell. Here, we investigate HIF dynamics and use microelectrodes to determine O2 concentrations within the egg and the embryo during the first four days of development. To determine the increased O2 consumption rates, we also obtain the O2 transport coefficient (DO2) of eggshell and associated inner and outer shell membranes, both directly (using microelectrodes in ovo for the first time) and indirectly (using water evaporation at 37.5°C for the first time). Our results demonstrate a distinct hypoxic phase (<5% O2) between day 1 and 2, concurring with the onset of HIF-α expression. This phase of hypoxia is demonstrably necessary for proper vascularization and survival. Our indirectly determined DO2 values are about 30% higher than those determined directly. A comparison with previously reported values indicates that this discrepancy may be real, reflecting that water vapor and O2 may be transported through the eggshell at different rates. Based on our obtained DO2 values, we demonstrate that increased O2 consumption of the growing embryo appears to generate the phase of hypoxia, which is also facilitated by the initially small gas cell and low membrane permeability. We infer that the phase of in ovo hypoxia facilitates correct avian development. These results support the view that hypoxic conditions, in which the animal clade evolved, remain functionally important during animal development. The study highlights that insights from the cancer field pertaining to the cellular capacities by which both somatic and cancer cells register and respond to fluctuations in O2 concentrations can broadly inform our exploration of animal development and success.
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| 14. |
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| 15. |
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| 16. |
- Dybjer, Elin, et al.
(författare)
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Polygenic risk of type 2 diabetes is associated with incident vascular dementia : a prospective cohort study
- 2023
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes and dementia are associated, but it is unclear whether the two diseases have common genetic risk markers that could partly explain their association. It is also unclear whether the association between the two diseases is of a causal nature. Furthermore, few studies on diabetes and dementia have validated dementia end-points with high diagnostic precision. We tested associations between polygenic risk scores for type 2 diabetes, fasting glucose, fasting insulin and haemoglobin A1c as exposure variables and dementia as outcome variables in 29 139 adults (mean age 55) followed for 20–23 years. Dementia diagnoses were validated by physicians through data from medical records, neuroimaging and biomarkers in cerebrospinal fluid. The dementia end-points included all-cause dementia, mixed dementia, Alzheimer’s disease and vascular dementia. We also tested causal associations between type 2 diabetes and dementia through two-sample Mendelian randomization analyses. Seven different polygenic risk scores including single-nucleotide polymorphisms with different significance thresholds for type 2 diabetes were tested. A polygenic risk score including 4891 single-nucleotide polymorphisms with a P-value of <5e-04 showed the strongest association with different outcomes, including all-cause dementia (hazard ratio 1.11; Bonferroni corrected P = 3.6e-03), mixed dementia (hazard ratio 1.18; Bonferroni corrected P = 3.3e-04) and vascular dementia cases (hazard ratio 1.28; Bonferroni corrected P = 9.6e-05). The associations were stronger for non-carriers of the Alzheimer’s disease risk gene APOE ϵ4. There was, however, no significant association between polygenic risk scores for type 2 diabetes and Alzheimer’s disease. Furthermore, two-sample Mendelian randomization analyses could not confirm a causal link between genetic risk markers of type 2 diabetes and dementia outcomes. In conclusion, polygenic risk of type 2 diabetes is associated with an increased risk of dementia, in particular vascular dementia. The findings imply that certain people with type 2 diabetes may, due to their genetic background, be more prone to develop diabetes-associated dementia. This knowledge could in the future lead to targeted preventive strategies in clinical practice.
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| 17. |
- Engström, Christian, et al.
(författare)
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Homogenization of the Maxwell equations using Floquet-Bloch decomposition
- 2003
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Ingår i: Mathematical and numerical waves 2003. - Berlin, Heidelberg : Springer. - 9783642558566 - 354040127X ; , s. 412-416
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Konferensbidrag (refereegranskat)abstract
- Using Bloch waves to represent the full solution of the Maxwell equations inperiodic media, we study the limit process where the material's period becomes much smaller than the wavelenght. it is seen that effective material parameters can be extracted and explicity represented in terms of the non-vanishing Bloch waves, providing an alternative means of homogenization.
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| 18. |
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| 19. |
- Engström, Niklas, 1985, et al.
(författare)
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Development of celiac-safe foods: prevention of transglutaminase 2 (TG2) deamidation of gluten in healthy non-celiac volunteers
- 2024
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Ingår i: Frontiers in Nutrition. - 2296-861X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Clinical trial registration: In celiac disease, intestinal transglutaminase (TG2) produces immunogenic peptides by deamidation of gluten proteins. These products drive the celiac immune response. We have previously identified an interaction between gliadin and a food additive, E304i, which prevents gliadin processing (both deamidation and transamidation) by TG2, in vitro. In this study, we investigated if E304i could prevent TG2 processing of gluten in flours and if the effect was evident after simulated gastrointestinal digestion. We also confirmed the outcome in vivo in a human cross-over intervention study in healthy non-celiac participants. TG2 transamidation experiments (in vitro) of digested wheat and rye flours supplemented with E304i at 30 mg/g indicated full prevention of TG2 processing. In the intervention study, participant serum levels of deamidated gliadin peptides (dGDPs) increased after the intake of reference wheat rolls (80 g per day for a week; 41% ± 4% compared to washout), while the intake of the intervention E304i/zinc sulfate wheat rolls generated a modest response (80 g per day for a week; 8 ± 10% of control). The difference between the groups (32.8 ± 15.6%) was significant (p = 0.00003, n = 9), confirming that E304i /zinc addition to wheat rolls prevented TG2 deamidation of gluten. In conclusion, this study shows that E304i /zinc addition to wheat rolls prevents TG2 deamidation of gluten in non-celiac participants. clinicaltrials.gov, identifier (NCT06005376).
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| 20. |
- Engström, Niklas, 1985, et al.
(författare)
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Development of celiac-safe foods: prevention of transglutaminase 2 (TG2) deamidation of gluten in healthy non-celiac volunteers
- 2024
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Ingår i: FRONTIERS IN NUTRITION. - 2296-861X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- In celiac disease, intestinal transglutaminase (TG2) produces immunogenic peptides by deamidation of gluten proteins. These products drive the celiac immune response. We have previously identified an interaction between gliadin and a food additive, E304i, which prevents gliadin processing (both deamidation and transamidation) by TG2, in vitro. In this study, we investigated if E304i could prevent TG2 processing of gluten in flours and if the effect was evident after simulated gastrointestinal digestion. We also confirmed the outcome in vivo in a human cross-over intervention study in healthy non-celiac participants. TG2 transamidation experiments (in vitro) of digested wheat and rye flours supplemented with E304i at 30 mg/g indicated full prevention of TG2 processing. In the intervention study, participant serum levels of deamidated gliadin peptides (dGDPs) increased after the intake of reference wheat rolls (80 g per day for a week; 41% +/- 4% compared to washout), while the intake of the intervention E304i/zinc sulfate wheat rolls generated a modest response (80 g per day for a week; 8 +/- 10% of control). The difference between the groups (32.8 +/- 15.6%) was significant (p = 0.00003, n = 9), confirming that E304i /zinc addition to wheat rolls prevented TG2 deamidation of gluten. In conclusion, this study shows that E304i /zinc addition to wheat rolls prevents TG2 deamidation of gluten in non-celiac participants.Clinical trial registration clinicaltrials.gov, identifier (NCT06005376).
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| 21. |
- Engström, Niklas, 1985, et al.
(författare)
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Sourdough fermentation of wheat flour does not prevent the interaction of transglutaminase 2 with α2-gliadin or gluten.
- 2015
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 7:4, s. 2134 - 2144
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Tidskriftsartikel (refereegranskat)abstract
- The enzyme transglutaminase 2 (TG2) plays a crucial role in the initiation of celiac disease by catalyzing the deamidation of gluten peptides. In susceptible individuals, the deamidated peptides initiate an immune response leading to celiac disease. Several studies have addressed lactic fermentation plus addition of enzymes as a means to degrade gluten in order to prevent adverse response in celiacs. Processing for complete gluten degradation is often harsh and is not likely to yield products that are of comparable characteristics as their gluten-containing counterparts. We are concerned that incomplete degradation of gluten may have adverse effects because it leads to more available TG2-binding sites on gluten peptides. Therefore, we have investigated how lactic acid fermentation affects the potential binding of TG2 to gluten protein in wheat flour by means of estimating TG2-mediated transamidation in addition to measuring the available TG2-binding motif QLP, in α2-gliadin. We show that lactic fermentation of wheat flour, as slurry or as part of sourdough bread, did not decrease the TG2-mediated transamidation, in the presence of a primary amine, to an efficient level (73%–102% of unfermented flour). Nor did the lactic fermentation decrease the available TG2 binding motif QLP in α2-gliadin to a sufficient extent in sourdough bread (73%–122% of unfermented control) to be useful for celiac safe food.
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| 22. |
- Engström, Niklas, 1985
(författare)
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Toward celiac-safe foods - Investigation of the interaction between transglutaminase 2 and gluten
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Celiac disease, a chronic autoimmune enteropathy, may develop in genetically predisposed individuals upon ingestion of gluten proteins found in wheat, barley, and rye. Overall prevalence of celiac disease is increasing and it currently affects around 1% of the population. The types and severity of symptoms of celiac disease show high variability, leading to many sufferers remaining undiagnosed. The only available treatment is to follow a strict gluten-free diet, but gluten-free alternatives are less available, more expensive, and often have lower nutritional and sensorial quality. This thesis work examined the interactions between the intestinal enzyme transglutaminase 2 and gluten peptides. Transglutaminase 2 plays a significant role in disease initiation and progression, and is the main autoimmune target in developed celiac disease. A method for measuring the interaction between transglutaminase 2 and gluten was developed and tested in studies on sourdough fermentation of wheat flour and bread. Transglutaminase 2-mediated transamidation of gluten was assayed and the extent of available binding motifs for transglutaminase 2 in α2-gliadin, considered the most immunogenic part of gluten, was assessed using an ELISA-based method. The results showed that lactic acid fermentation, which is not specifically tailored to degrade gluten, cannot sufficiently prevent transglutaminase 2 interaction with gluten or decrease the extent of available binding motifs for transglutaminase 2 on α2-gliadin. In studies investigating the possibility to block specific binding motifs for transglutaminase 2 on gluten peptides, using molecules suitable as food additives, binding to α2-gliadin was computationally simulated and promising candidates were identified. These candidates were analyzed in vitro for the ability to prevent transglutaminase 2-mediated transamidation and deamidation of gliadin. Ascorbyl palmitate was found to interact with α2-gliadin in computer simulations and effectively reduced gliadin interaction with transglutaminase 2 in vitro . The cytotoxicity profile of ascorbyl palmitate, in combination with gliadin, was evaluated in Caco-2 cell cultures by determining cell survival, direct cytotoxicity, inflammatory mediators, and cell layer integrity, and no negative effects were found. In ancillary studies of human ileostomy contents after ingestion of raw and extruded gluten-containing products, degradation products of α-gliadin were identified and the effect of extrusion on digestion was investigated. Preliminary results indicate that protein digestibility was decreased after intake of the extruded product, but the effect on α-gliadin digestion needs further evaluation. However, the majority of α-gliadin seems to be undigested after in vivo digestion in both products. The interaction between transglutaminase 2 and gluten is crucial for celiac disease and in this thesis work, several strategies for preventing this have been explored. Ascorbyl palmitate has been shown to effectively prevent this interaction in vitro and is thus a promising candidate for creating cereal-based foods potentially safe for celiacs.
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| 23. |
- Engström, Niklas, 1985, et al.
(författare)
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Towards Celiac-safe foods: Decreasing the affinity of transglutaminase 2 for gliadin by addition of ascorbyl palmitate and ZnCl2 as detoxifiers
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 7:77
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Tidskriftsartikel (refereegranskat)abstract
- Initiation of celiac disease is triggered in the gastrointestinal tract by transglutaminase 2 (TG2) assisted deamidation of gluten peptides. Deamidation is a side-reaction to transamidation and occurs if primary amines are absent. In contrast to deamidation, transamidation does not trigger an immune response. The aim of the study was to identify a suitable food additive that interacts with TG2 binding motives in gluten-derived peptides to prevent deamidation/transamidation. Homology modelling of alpha 2-gliadin and computational screening of compounds for their binding affinity to a common TG2 binding motive (P) QLP were done by using computational approaches followed by experimental testing of TG2 activity. A database containing 1174 potential food grade ligands was screened against the model of alpha 2-gliadin (27 out of 33 aa). Out of the five best ligands, ascorbyl palmitate, was observed to decrease TG2 transamidation of gliadin by 82% +/- 2%. To completely silence the transamidation, we added zinc chloride (ZnCl2), and thereby reached a 99% +/- 1% inhibition of TG2 activity. In addition, we conducted a pilot experiment in which ascorbyl palmitate was observed to decrease TG2 deamidation of gliadin completely. We propose ascorbyl palmitate in combination with ZnCl2 with the future perspective to become an additive in celiac-safe foods.
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| 24. |
- Engström, Olof
(författare)
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Carbohydrate dynamics and interactions studied by NMR spectroscopy
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The combination of NMR spectroscopy and molecular dynamics (MD) simulations are powerful tools in the studying of bioorganic molecules in solution. In this thesis two such studies are presented with focus on the NMR aspect. The caffeine association to sugars (D-glucose and sucrose) was investigated by NMR titrations and NOESY experiments in paper I. The observations from the NMR experiments confirmed MD simulations showing that the binding occurs by a face-to-face interaction between the aromatic surface of the caffeine and axial protons of the sugar ring. Different sugar molecules and residues have different preferences regarding which side of the sugar ring that are involved in the binding. The sucrose residues bind with only one ring face each whereas β-D-glucopyranose has two sides of similar binding probability and the α-D-glucopyranose has something in between. The MD simulations showed that the driving force of the binding is partly driven by hydration effects that favor the enthalpy of the system. A new approach to calculate NMR relaxation parameters (that is dependent on molecular motions) from computational simulations is presented in paper II. Each sugar residue is assumed to be a rigid unit connected by flexible joints in the approach, thus the name diffusive chain model (DCM). The simplified model together with a stochastic simulation approach lowers the computational cost which makes it possible to acquire long enough trajectories to the calculations of spin relaxation parameters. Two case studies with slightly different methodologies are presented. In one of them, spin relaxation parameters are reproduced for the human milk oligosaccharide LNF-1 in a feasible way by the use of Brownian dynamics.
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| 25. |
- Engström, Åsa, et al.
(författare)
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Losing the identity of a hockey player : the long-term effects of concussions
- 2020
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Ingår i: Concussion. - : Future Medicine. - 2056-3299. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To describe what suffering multiple concussions meant for former semi-professional or professional hockey players who were forced to end their career. Results: Nine former Swedish hockey players, who once played on national or professional teams were interviewed. The interviews were analyzed with reference to hermeneutic phenomenology to interpret and explain their experiences. The theme of losing one’s identity as a hockey player was constructed from five subthemes: being limited in everyday life, returning to the hockey stadium as soon as possible, forming a post career identity, lacking understanding and support, and preventing injuries by respecting other players. Conclusion: The former hockey players struggled with developing their off-the-ice identities and with finding other sources of meaning for their lives.Lay abstractDespite considerable attention to improving the initial management of concussions suffered by hockey players, few studies have examined their long-term effects. In response, the study reported here aimed to describe what suffering multiple concussions meant for former semi-professional or professional hockey players who were forced to end their career. Nine former Swedish hockey players, who once played on national or professional teams were interviewed and the interviews were analyzed in order to interpret and explain their experiences. The overall theme was formulated as losing one’s identity as a hockey player. In conclusion, the former hockey players seem to struggle with developing their off-the-ice identities and with finding other sources of meaning for their lives.
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| 26. |
- Fredlund, Elina, et al.
(författare)
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MOXD1 is a lineage-specific gene and a tumor suppressor in neuroblastoma
- 2024
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Ingår i: Science Advances. - 2375-2548. ; 10:25
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma is a childhood developmental cancer; however, its embryonic origins remain poorly understood. Moreover, in-depth studies of early tumor-driving events are limited because of the lack of appropriate models. Herein, we analyzed RNA sequencing data obtained from human neuroblastoma samples and found that loss of expression of trunk neural crest–enriched gene MOXD1 associates with advanced disease and worse outcome. Further, by using single-cell RNA sequencing data of human neuroblastoma cells and fetal adrenal glands and creating in vivo models of zebrafish, chick, and mouse, we show that MOXD1 is a determinate of tumor development. In addition, we found that MOXD1 expression is highly conserved and restricted to mesenchymal neuroblastoma cells and Schwann cell precursors during healthy development. Our findings identify MOXD1 as a lineage-restricted tumor-suppressor gene in neuroblastoma, potentiating further stratification of these tumors and development of novel therapeutic interventions.
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| 27. |
- Gambelunghe, A., et al.
(författare)
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Low-level exposure to lead, blood pressure, and hypertension in a population-based cohort
- 2016
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351. ; 149, s. 157-163
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Tidskriftsartikel (refereegranskat)abstract
- Background: Environmental lead exposure is a possible causative factor for increased blood pressure and hypertension, but large studies at low-level exposure are scarce, and results inconsistent. Objective: We aimed to examine the effects of environmental exposure to lead in a large population based sample. Methods: We assessed associations between blood lead and systolic/diastolic blood pressure and hypertension in 4452 individuals (46-67 years) living in Malmo, Sweden, in 1991-1994. Blood pressure was measured using a mercury sphygmomanometer after 10 min supine rest. Hypertension was defined as high systolic ( >= 140 mmHg) or diastolic ( >= 90 mmHg) blood pressure and/or current use of anti hypertensive medication. Blood lead was calculated from lead in erythrocytes and haematocrit. Multi variable associations between blood lead and blood pressure or hypertension were assessed by linear and logistic regression. Two-thirds of the cohort was re-examined 16 years later. Results: At baseline, mean blood pressure was 141/87 mmHg, 16% used antihypertensive medication, 63% had hypertension, and mean blood lead was 28 mu g/L. Blood lead in the fourth quartile was associated with significantly higher systolic and diastolic blood pressure (point estimates: 1-2 mmHg) and increased prevalence of hypertension (odds ratio: 1.3, 95% confidence interval: 1.1-1.5) versus the other quartiles after adjustment for sex, age, smoking, alcohol, waist circumference, and education. Associations were also significant with blood lead as a continuous variable. Blood lead at baseline, having a halflife of about one month, was not associated with antihypertensive treatment at the 16-year follow-up. Conclusions: Low-level lead exposure increases blood pressure and may increase the risk of hypertension.
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| 28. |
- Guldbrand, Carl, 1997, et al.
(författare)
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Low-level exposure to lead and atherosclerosis in the carotid arteries : Results from the Swedish population-based cohort SCAPIS
- 2024
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Ingår i: Environmental Research. - 0013-9351 .- 1096-0953. ; 244
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lead exposure is associated with cardiovascular disease. Atherosclerosis has been hypothesized to be one of the underlying mechanisms behind this association. Aim: To investigate whether lead exposure is associated with an increased risk of atherosclerosis in the carotid arteries in a large Swedish population-based cohort. Methods: We performed a cross-sectional study using data from the population-based Swedish CardioPulmonary bioImage Study (SCAPIS), including 5622 middle-aged men and women, enrolled 2013–2018. Blood lead (B–Pb), measured by inductively coupled plasma mass spectrometry, was used as exposure biomarker. The presence of atherosclerotic plaque in the carotid arteries (yes/no), total plaque area (mm2) and the presence of large plaques (>25 mm2) were determined by ultrasonography. Associations between B–Pb and the different outcomes were analysed using Poisson and linear regression models, adjusted for potential confounders. Results: Atherosclerotic plaque was present in 57% of the individuals, for whom the median total plaque area was 16 mm2 (range: 0.2–222). The median B–Pb concentration was 14 μg/L (range: 0.75–203). After adjusting for potential confounders, individuals in the fourth quartile of B–Pb (Q4) had a prevalence ratio (PR) for plaque of 1.08 (95% CI: 1.01, 1.16) when compared with the first quartile (Q1). A 10 μg/L increase in B–Pb concentrations was associated with an increase of 0.92 mm2 (95% CI: 0.14, 1.71) in total plaque area. The PR for large plaque was 1.09 (95% CI: 0.84, 1.42 for Q4 vs Q1). Conclusions: This study shows an association between B–Pb and atherosclerosis in the carotid arteries providing some support for the hypothesis that atherosclerosis is one of the mechanisms underlying the association between lead exposure and cardiovascular disease.
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| 29. |
- Harari, Florencia, 1986, et al.
(författare)
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Blood Lead Levels and Decreased Kidney Function in a Population-Based Cohort
- 2018
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Ingår i: American Journal of Kidney Diseases. - : Elsevier BV. - 0272-6386. ; 72:3, s. 381-389
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Tidskriftsartikel (refereegranskat)abstract
- Background: Environmental lead exposure has been associated with decreased kidney function, but evidence from large prospective cohort studies examining low exposure levels is scarce. We assessed the association of low levels of lead exposure with kidney function and kidney disease. Study Design: Prospective population-based cohort. Setting & Participants: 4,341 individuals aged 46 to 67 years enrolled into the Malmö Diet and Cancer Study-Cardiovascular Cohort (1991-1994) and 2,567 individuals subsequently followed up (2007-2012). Predictor: Blood lead concentrations in quartiles (Q1-Q4) at baseline. Outcomes: Change in estimated glomerular filtration rate (eGFR) between the baseline and follow-up visit based on serum creatinine level alone or in combination with cystatin C level. Chronic kidney disease (CKD) incidence (185 cases) through 2013 detected using a national registry. Measurements: Multivariable-adjusted linear regression models to assess associations between lead levels and eGFRs at baseline and follow-up and change in eGFRs over time. Cox regression was used to examine associations between lead levels and CKD incidence. Validation of 100 randomly selected CKD cases showed very good agreement between registry data and medical records and laboratory data. Results: At baseline, 60% of study participants were women, mean age was 57 years, and median lead level was 25 (range, 1.5-258) μg/L. After a mean of 16 years of follow-up, eGFR decreased on average by 6 mL/min/1.73 m2 (based on creatinine) and 24 mL/min/1.73 m2 (based on a combined creatinine and cystatin C equation). eGFR change was higher in Q3 and Q4 of blood lead levels compared with Q1 (P for trend = 0.001). The HR for incident CKD in Q4 was 1.49 (95% CI, 1.07-2.08) compared with Q1 to Q3 combined. Limitations: Lead level measured only at baseline, moderate number of CKD cases, potential unmeasured confounding. Conclusions: Low-level lead exposure was associated with decreased kidney function and incident CKD. Our findings suggest lead nephrotoxicity even at low levels of exposure.
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| 30. |
- Harari, Florencia, 1986, et al.
(författare)
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Blood lead levels and risk of atherosclerosis in the carotid artery : Results from a swedish cohort
- 2019
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Ingår i: Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 127:12, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lead exposure has been associated with increased incidence of adverse clinical cardiovascular outcomes. Atherosclerosis has been suggested as one of the underlying mechanisms, and findings from experimental studies support this, but human data are scarce. OBJECTIVES: Our objective was to determine the association between environmental lead exposure based on blood lead (B-Pb) concentrations and the prevalence of atherosclerotic plaque in the carotid artery. METHODS: We used cross-sectional data from the Malmö Diet and Cancer Study cardiovascular cohort (MDCS-CC; recruitment in 1991–1994) covering 4,172 middle-aged men and women. B-Pb at baseline, measured by inductively coupled plasma mass spectrometry, was used as the exposure biomarker. The presence of atherosclerotic plaque in the carotid artery was determined by B-mode ultrasonography. We used logistic regression to estimate odds ratios (ORs) for prevalence of plaque in the carotid artery according to B-Pb quartiles. RESULTS: The median B-Pb was 25 lg=L (range: 1.5–258), and 36% of the cohort had any atherosclerotic plaque. After controlling for confounders and known cardiovascular risk factors, the OR for prevalence of plaque in the highest quartile (Q4) of B-Pb compared with the lowest quartile (Q1) was 1.35 (95% CI: 1.09, 1.66) in the total group, 1.58 (95% CI: 1.20, 2.08) among women, and 1.18 (95% CI: 0.83, 1.69) among men. Among women, associations were limited to those who were postmenopausal [OR for Q4 vs. Q1 = 1.72 (95% CI: 1.26, 2.34) vs. OR = 0.96 (95% CI: 0.49, 1.89 in premenopausal women)]. Associations were weak and nonsignificant in never-smokers [OR for Q4 vs. Q1 = 1.14 (95% CI: 0.81, 1.61)]. DISCUSSION: Our study shows an association between B-Pb concentrations and occurrence of atherosclerotic plaque in the carotid artery, adding evidence for an underlying pro-atherogenic role of lead in cardiovascular disease. Associations appeared to be limited to postmenopausal (vs. premeno-pausal) women. https://doi.org/10.1289/EHP5057.
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| 31. |
- Hutchinson, Peter J, et al.
(författare)
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Consensus statement from the 2014 International Microdialysis Forum
- 2015
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 41:9, s. 1517-1528
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Tidskriftsartikel (refereegranskat)abstract
- Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.
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| 32. |
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| 33. |
- Kruse, Johan, et al.
(författare)
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Scrutinized with inadequate control and support : Interns' experiences communicating with and writing referrals to hospital radiology departments - A qualitative study
- 2016
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Ingår i: Radiography. - : Elsevier BV. - 1078-8174 .- 1532-2831. ; 22:4, s. 313-318
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Interns' experiences communicating with and writing referrals to hospital radiology departments are important for patient safety, image quality, and decision-making in the diagnostic process. Understanding roles within the department and in the diagnostic process is important for communication. This study aimed to describe interns' experiences communicating with and writing referrals to their hospital's radiology department. Method: A qualitative study design was used. Data was collected from focus discussions with ten interns in three focus groups in Northern Sweden during 2012. The data were subjected to qualitative content analysis. Results: One theme, "a feeling of being scrutinized and lacking control", was identified in the final categories. The interns experienced that the radiology department placed high demands on them and desired more diagnostic skills training, resources and feedback. The interns suggested the following improvements: enhanced dialogue and feedback, improved education, handy guidelines, and practice writing referrals. Conclusion: Interns need more feedback from, and dialogue with, members of the Department of Radiology. They also need more knowledge of referral guidelines, appropriateness criteria and more practice to develop their knowledge and skill for writing referrals. They describe feelings of inadequate support and feel scrutinized in demanding work conditions and need more collaboration. They also need more time and more control of radiology outcomes, and they are eager to learn.
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| 34. |
- Lestander, Örjan, et al.
(författare)
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Nursing students' perceptions of learning after High Fidelity simulation : Effects of a Three-step Post-Simulation Reflection Model
- 2016
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Ingår i: Nurse Education Today. - : Elsevier BV. - 0260-6917 .- 1532-2793. ; 40, s. 219-224
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Tidskriftsartikel (refereegranskat)abstract
- High-fidelity simulation (HFS) has become a bridge between theoretical knowledge and practical skills. A safe and realistic environment is commonly used in nursing education to improve cognitive, affective and psychomotor abilities. Debriefing following a simulation experience provides opportunities for students to analyse and begin to reflect upon their decisions, actions and results. The nursing literature highlights the need to promote the concept of reflective practice and to assist students in reflection, and research indicates the need to refine and develop debriefing strategies, which is the focus of the current paper.
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| 35. |
- Lynøe, Niels, et al.
(författare)
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Dödshjälp bakom okunskapens slöja
- 2018
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Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 115:24, s. 1020-1020
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Tidskriftsartikel (refereegranskat)
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| 36. |
- Lynøe, Niels, et al.
(författare)
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How to reveal disguised paternalism : version 2.0
- 2021
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Ingår i: BMC Medical Ethics. - : BioMed Central. - 1472-6939. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We aim to further develop an index for detecting disguised paternalism, which might influence physicians' evaluations of whether or not a patient is decision-competent at the end of life. Disguised paternalism can be actualized when physicians transform hard paternalism into soft paternalism by questioning the patient's decision-making competence.METHODS: A previously presented index, based on a cross-sectional study, was further developed to make it possible to distinguish between high and low degrees of disguised paternalism using the average index of the whole sample. We recalculated the results from a 2007 study for comparison to a new study conducted in 2020. Both studies are about physicians' attitudes towards, and arguments for or against, physician-assisted suicide.RESULTS: The 2020 study showed that geriatricians, palliativists, and middle-aged physicians (46-60 years old) had indices indicating disguised paternalism, in contrast with the results from the 2007 study, which showed that all specialties (apart from GPs and surgeons) had indices indicating high degrees of disguised paternalism.CONCLUSIONS: The proposed index for identifying disguised paternalism reflects the attitude of a group towards physician assisted suicide. The indices make it possible to compare the various medical specialties and age groups from the 2007 study with the 2020 study. Because disguised paternalism might have clinical consequences for the rights of competent patients to participate in decision-making, it is important to reveal disguised hard paternalism, which could masquerade as soft paternalism and thereby manifest in practice. Methods for improving measures of disguised paternalism are worthy of further development.
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| 37. |
- Lynøe, Niels, et al.
(författare)
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Rawlsian reasoning about fairness at the end of life
- 2023
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Ingår i: BMJ Supportive & Palliative Care. - : BMJ. - 2045-435X .- 2045-4368. ; 13:e3, s. e1398-e1404
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to discuss end-of-life care in the context of Rawls' and Daniels' philosophy of justice. The study is based on an empirical survey of Swedish physicians who were asked whether they would want the option of physician-assisted suicide (PAS) for themselves (hereafter called own preferences), what are their attitudes towards PAS in general and whether they were prepared to prescribe PAS drugs to eligible patients. The question is to what extent the physicians' answers are impartial and consistent in a Rawlsian sense.METHODS: The underlying indicator was the physicians' own preferences. Kappa score inter-rater agreement was measured between that response and that same physician's general attitude towards allowing PAS and preparedness to prescribe PAS drugs. The coherence of provided comments and arguments were analysed using content analysis.RESULTS: Palliative care physicians are the least willing to offer PAS, and surgeons and psychiatrist the most willing. There is a discrepancy between physicians' general attitudes about allowing PAS, their own wishes to be offered PAS at the end of life and the concrete action of prescribing PAS drugs. Arguments given for not prescribing PAS by those in favour of PAS are seemingly but not truly inconsistent.CONCLUSIONS: Those supporting PAS provided impartial and consistent arguments for their stances in a Rawlsian sense, while those against PAS provided partial arguments. Two specialties, psychiatrists and palliative care physicians, were coherent in their reasoning about PAS for themselves and their willingness to prescribe the needed drugs.
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| 38. |
- Lynøe, Niels, et al.
(författare)
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Trends in Swedish physicians’ attitudes towards physician-assisted suicide: a cross-sectional study
- 2021
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Ingår i: BMC Medical Ethics. - : BioMed Central. - 1472-6939. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To examine attitudes towards physician-assisted suicide (PAS) among physicians in Sweden and compare these with the results from a similar cross-sectional study performed in 2007.Participants: A random selection of 250 physicians from each of six specialties (general practice, geriatrics, internal medicine, oncology, surgery and psychiatry) and all 127 palliative care physicians in Sweden were invited to participate in this study.Setting: A postal questionnaire commissioned by the Swedish Medical Society in collaboration with Karolinska Institute in Stockholm.Results: The total response rate was 59.2%. Slightly fewer than half [47.1% (95% CI 43.7–50.5)] of the respondents from the six specialties accepted PAS, which is significantly more than accepted PAS in the 2007 study [34.9% (95% CI 31.5–38.3)]. Thirty-three percent of respondents were prepared to prescribe the needed drugs. When asked what would happen to the respondent’s own trust in healthcare, a majority [67.1% (95% CI 63.9–70.3)] stated that legalizing PAS would either not influence their own trust in healthcare, or that their trust would increase. This number is an increase compared to the 2007 survey, when just over half [51.9% (95% CI 48.0–55.2)] indicated that their own trust would either not be influenced, or would increase.Conclusions: The study reveals a shift towards a more accepting attitude concerning PAS among physicians in Sweden. Only a minority of the respondents stated that they were against PAS, and a considerable proportion reported being prepared to prescribe the needed drugs for patient self-administration if PAS were legalized.
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| 39. |
- Lynøe, Niels, et al.
(författare)
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Values at stake at the end of life : Analyses of personal preferences among Swedish physicians
- 2022
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Ingår i: Clinical Ethics. - : Sage Publications. - 1477-7509 .- 1758-101X. ; 18:2, s. 239-244
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Tidskriftsartikel (refereegranskat)abstract
- Background Physician-assisted suicide is a controversial issue and has sometimes raised emotion-laden reactions. Against this backdrop, we have analyzed how Swedish physicians are reasoning about physician-assisted suicide if it were to be legalized.Methods and participants We conducted a cross-sectional study and analyzed 819 randomly selected physicians’ responses from general practitioners, geriatricians, internists, oncologists, psychiatrists, surgeons, and all palliativists. Apart from the main questions about their attitude toward physician-assisted suicide, we also asked what would happen with the respondents’ own trust in healthcare if physician-assisted suicide were legalized. Response options were that trust would decrease, not be influenced, or would increase.Results We identified a strong statistical association between on the one hand those whose own trust would increase and who were pro physician-assisted suicide, and on the other hand those who were against physician-assisted suicide and whose own trust would decrease [relative risk: 16.7 (95% confidence interval: 10.2–27.2)]. Among those whose own trust would not be influenced (n = 456), 60% were pro pysician-assisted suicide, 16% were against, and 24% were undecided. Of those whose trust would increase or not be influenced, a large majority supported autonomy-based arguments, whereas those whose trust would decrease supported non-maleficence-based arguments.Conclusion Analyzing the answers after having divided respondents into those whose own trust in healthcare would decrease or increase and not be influenced brings about interesting results such as how the three groups prioritize arguments for and against physician-assisted suicide. This way of analyzing the data seems to be a promising strategy when identifying value-impregnated factual claims.
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| 40. |
- Marklund, Niklas, et al.
(författare)
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Monitoring of brain interstitial total tau and beta amyloid proteins by microdialysis in patients with traumatic brain injury.
- 2009
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Ingår i: Journal of neurosurgery. - 0022-3085 .- 1933-0693. ; 110:6, s. 1227-37
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Tidskriftsartikel (refereegranskat)abstract
- OBJECT: Damage to axons contributes to postinjury disabilities and is commonly observed following traumatic brain injury (TBI). Traumatic brain injury is an important environmental risk factor for the development of Alzheimer disease (AD). In the present feasibility study, the aim was to use intracerebral microdialysis catheters with a high molecular cutoff membrane (100 kD) to harvest interstitial total tau (T-tau) and amyloid beta 1-42 (Abeta42) proteins, which are important biomarkers for axonal injury and for AD, following moderate-to-severe TBI.METHODS: Eight patients (5 men and 3 women) were included in the study; 5 of the patients had a focal/mixed TBI and 3 had a diffuse axonal injury (DAI). Following the bedside analysis of the routinely measured energy metabolic markers (that is, glucose, lactate/pyruvate ratio, glycerol, and glutamate), the remaining dialysate was pooled and two 12-hour samples per day were used to analyze T-tau and Abeta42 by enzyme-linked immunosorbent assay from Day 1 up to 8 days postinjury.RESULTS: The results show high levels of interstitial T-tau and Abeta42 postinjury. Patients with a predominantly focal lesion had higher interstitial T-tau levels than in the DAI group from Days 1 to 3 postinjury (p < 0.05). In contrast, patients with DAI had consistently higher Abeta42 levels when compared with patients with focal injury.CONCLUSIONS: These results suggest that monitoring of interstitial T-tau and Abeta42 by using microdialysis may be an important tool when evaluating the presence and role of axonal injury following TBI.
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| 41. |
- Marklund, Niklas, et al.
(författare)
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Neurointensive care management of raised intracranial pressure caused by severe valproic acid intoxication
- 2007
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Ingår i: Neurocritical care. - : Springer Science and Business Media LLC. - 1541-6933 .- 1556-0961. ; 7:2, s. 160-164
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Tidskriftsartikel (refereegranskat)abstract
- Introduction We describe the neurointensive care (NIC) management of a patient with severe cerebral swelling and raised intracranial pressure (ICP) after severe sodium valproic acid (VPA) intoxication. A previously healthy 25-year old male with mild tonic-clonic epilepsy was found unconscious with serum VPA levels >10,000 mu mol/l. The patient deteriorated to Glasgow Motor Scale score (GMS) 2 and a CT scan showed signs of raised lCP. Early ICP was elevated, >50 mm Hg, and continuous EEG monitoring showed isoelectric readings. Methods The patient was treated with an ICP-guided protocol including mild hyperventilation, normovolemia, head elevation and intermittent doses of mannitol. Due to refractory elevations of ICP, high-dose pentobarbital infusion was initiated, and ICP gradually normalised. Results There were several systemic complications including coagulopathy, hypocalcemia and pancreatitis. The patient remained in a depressed level of consciousness for 2 months but gradually recovered, showing a good recovery with minor subjective cognitive deficits by 6 months. Conclusion We conclude that NIC may be an important treatment option in cases of severe intoxication causing cerebral swelling.
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| 42. |
- Morales Drissi, Natasha, et al.
(författare)
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Altered Brain Microstate Dynamics in Adolescents with Narcolepsy
- 2016
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Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin-1 producing neurons in the hypothalamus. Previous neuroimaging studies have investigated brain function in narcolepsy during rest using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In addition to hypothalamic and thalamic dysfunction they showed aberrant prefrontal perfusion and glucose metabolism in narcolepsy. Given these findings in brain structure and metabolism in narcolepsy, we anticipated that changes in functional magnetic resonance imaging (fMRI) resting state network (RSN) dynamics might also be apparent in patients with narcolepsy. The objective of this study was to investigate and describe brain microstate activity in adolescents with narcolepsy and correlate these to RSNs using simultaneous fMRI and electroencephalography (EEG). Sixteen adolescents (ages 13-20) with a confirmed diagnosis of narcolepsy were recruited and compared to age-matched healthy controls. Simultaneous EEG and fMRI data were collected during 10 min of wakeful rest. EEG data were analyzed for microstates, which are discrete epochs of stable global brain states obtained from topographical EEG analysis. Functional fMRI data were analyzed for RSNs. Data showed that narcolepsy patients were less likely than controls to spend time in a microstate which we found to be related to the default mode network and may suggest a disruption of this network that is disease specific. We concluded that adolescents with narcolepsy have altered resting state brain dynamics.
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| 43. |
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| 44. |
- Morales Drissi, Natasha, et al.
(författare)
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Structural anomaly in the reticular formation in narcolepsy type 1, suggesting lower levels of neuromelanin
- 2019
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Ingår i: NeuroImage: Clinical. - : Elsevier BV. - 2213-1582. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate structural changes in the brain stem of adolescents with narcolepsy, a disorder characterized by excessive daytime sleepiness, fragmented night-time sleep, and cataplexy. For this purpose, we used quantitative magnetic resonance imaging to obtain R1 and R2 relaxation rates, proton density, and myelin maps in adolescents with narcolepsy (n = 14) and healthy controls (n = 14). We also acquired resting state functional magnetic resonance imaging (fMRI) for brainstem connectivity analysis. We found a significantly lower R2 in the rostral reticular formation near the superior cerebellar peduncle in narcolepsy patients, family wise error corrected p = .010. Narcolepsy patients had a mean R2 value of 1.17 s−1 whereas healthy controls had a mean R2 of 1.31 s−1, which was a large effect size with Cohen d = 4.14. We did not observe any significant differences in R1 relaxation, proton density, or myelin content. The sensitivity of R2 to metal ions in tissue and the transition metal ion chelating property of neuromelanin indicate that the R2 deviant area is one of the neuromelanin containing nuclei of the brain stem. The close proximity and its demonstrated involvement in sleep-maintenance, specifically through orexin projections from the hypothalamus regulating sleep stability, as well as the results from the connectivity analysis, suggest that the observed deviant area could be the locus coeruleus or other neuromelanin containing nuclei in the proximity of the superior cerebellar peduncle. Hypothetically, the R2 differences described in this paper could be due to lower levels of neuromelanin in this area of narcolepsy patients. © 2019 The Authors
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| 45. |
- Morales Drissi, Natasha, et al.
(författare)
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Unexpected Fat Distribution in Adolescents With Narcolepsy
- 2018
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Narcolepsy type 1 is a chronic sleep disorder with significantly higher BMI reported in more than 50% of adolescent patients, putting them at a higher risk for metabolic syndrome in adulthood. Although well-documented, the body fat distribution and mechanisms behind weight gain in narcolepsy are still not fully understood but may be related to the loss of orexin associated with the disease. Orexin has been linked to the regulation of brown adipose tissue (BAT), a metabolically active fat involved in energy homeostasis. Previous studies have used BMI and waist circumference to characterize adipose tissue increases in narcolepsy but none have investigated its specific distribution. Here, we examine adipose tissue distribution in 19 adolescent patients with narcolepsy type 1 and compare them to 17 of their healthy peers using full body magnetic resonance imaging (MRI). In line with previous findings we saw that the narcolepsy patients had more overall fat than the healthy controls, but contrary to our expectations there were no group differences in supraclavicular BAT, suggesting that orexin may have no effect at all on BAT, at least under thermoneutral conditions. Also, in line with previous reports, we observed that patients had more total abdominal adipose tissue (TAAT), however, we found that they had a lower ratio between visceral adipose tissue (VAT) and TAAT indicating a relative increase of subcutaneous abdominal adipose tissue (ASAT). This relationship between VAT and ASAT has been associated with a lower risk for metabolic disease. We conclude that while weight gain in adolescents with narcolepsy matches that of central obesity, the lower VAT ratio may suggest a lower risk of developing metabolic disease.
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| 46. |
- Nordanstig, Joakim, et al.
(författare)
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Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease.
- 2020
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Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 1533-4406 .- 0028-4793. ; 383, s. 2538-46
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Tidskriftsartikel (refereegranskat)abstract
- The results of a recent meta-analysis aroused concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb endovascular interventions for symptomatic peripheral artery disease.We conducted an unplanned interim analysis of data from a multicenter, randomized, open-label, registry-based clinical trial. At the time of the analysis, 2289 patients had been randomly assigned to treatment with drug-coated devices (the drug-coated-device group, 1149 patients) or treatment with uncoated devices (the uncoated-device group, 1140 patients). Randomization was stratified according to disease severity on the basis of whether patients had chronic limb-threatening ischemia (1480 patients) or intermittent claudication (809 patients). The single end point for this interim analysis was all-cause mortality.No patients were lost to follow-up. Paclitaxel was used as the coating agent for all the drug-coated devices. During a mean follow-up of 2.49 years, 574 patients died, including 293 patients (25.5%) in the drug-coated-device group and 281 patients (24.6%) in the uncoated-device group (hazard ratio, 1.06; 95% confidence interval, 0.92 to 1.22). At 1 year, all-cause mortality was 10.2% (117 patients) in the drug-coated-device group and 9.9% (113 patients) in the uncoated-device group. During the entire follow-up period, there was no significant difference in the incidence of death between the treatment groups among patients with chronic limb-threatening ischemia (33.4% [249 patients] in the drug-coated-device group and 33.1% [243 patients] in the uncoated-device group) or among those with intermittent claudication (10.9% [44 patients] and 9.4% [38 patients], respectively).In this randomized trial in which patients with peripheral artery disease received treatment with paclitaxel-coated or uncoated endovascular devices, the results of an unplanned interim analysis of all-cause mortality did not show a difference between the groups in the incidence of death during 1 to 4 years of follow-up. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT02051088.).
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- Ofearghail, Fionn, 1994, et al.
(författare)
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A LCMS Metabolomic Workflow to Investigate Metabolic Patterns in Human Intestinal Cells Exposed to Hydrolyzed Crab Waste Materials
- 2021
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a LCMS metabolomic workflow to investigate metabolic patterns from human intestinal cells treated with simulated gastrointestinal-digested hydrolyzed crab waste materials. This workflow facilitates smart and reproducible comparisons of cell cultures exposed to different treatments. In this case the variable was the hydrolysis methods, also accounting for the GI digestion giving an output of direct correlation between cellular metabolic patterns caused by the treatments. In addition, we used the output from this workflow to select treatments for further evaluation of the Caco-2 cell response in terms of tentative anti-inflammatory activity in the hopes to find value in the crab waste materials to be used for food products. As hypothesized, the treatment identified to change the cellular metabolomic pattern most readily, was also found to cause the greatest effect in the cells, although the response was pro-inflammatory rather than anti-inflammatory, it proves that changes in cellular metabolic patterns are useful predictors of bioactivity. We conclude that the developed workflow allows for cost effective, rapid sample preparation as well as accurate and repeatable LCMS analysis and introduces a data pipeline specifically for probe the novel metabolite patterns created as a means to assess the performing treatments.
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