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Sökning: WFRF:(Mattsson Linda)

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1.
  • Jansen, Willemijn J, et al. (författare)
  • Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
  • 2015
  • Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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  • Andersson, Linda, 1973, et al. (författare)
  • Deficiency in perilipin 5 reduces mitochondrial function and membrane depolarization in mouse hearts.
  • 2017
  • Ingår i: The international journal of biochemistry & cell biology. - : Elsevier BV. - 1878-5875 .- 1357-2725. ; 91:Pt A, s. 9-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Myocardial triglycerides stored in lipid droplets are important in regulating the intracellular delivery of fatty acids for energy generation in mitochondria, for membrane biosynthesis, and as agonists for intracellular signaling. Previously, we showed that deficiency in the lipid droplet protein perilipin 5 (Plin5) markedly reduces triglyceride storage in cardiomyocytes and increases the flux of fatty acids into phospholipids. Here, we investigated whether Plin5 deficiency in cardiomyocytes alters mitochondrial function. We found that Plin5 deficiency reduced mitochondrial oxidative capacity. Furthermore, in mitochondria from Plin5((-/)(-)) hearts, the fatty acyl composition of phospholipids in mitochondrial membranes was altered and mitochondrial membrane depolarization was markedly compromised. These findings suggest that mitochondria isolated from hearts deficient in Plin5, have specific functional defects.
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  • Bohman, Doris, et al. (författare)
  • Primary healthcare nurses' experiences of physical activity referrals : an interview study
  • 2015
  • Ingår i: Primary Health Care Research and Development. - : Cambridge University Press. - 1463-4236 .- 1477-1128. ; 16:3, s. 270-280
  • Tidskriftsartikel (refereegranskat)abstract
    • CONCLUSION: Our findings suggest that viewing the PAR as a complex intervention, with all that this entails, might be one approach to increasing the number of PARs being issued. Simpler systems, more time and the potential for testing the effectiveness of follow-ups could be possible ways of achieving this. AIM: The aim of this study is to illuminate primary health care (PHC) nurses' experiences of physical activity referrals (PARs). BACKGROUND: Despite extensive knowledge about the substantial health effects physical activities can produce, fewer and fewer people in our modern society regularly engage in physical activity. Within health care and, particularly, within the PHC arena, nurses meet people on a daily basis who need help to engage in a healthier lifestyle. The possibility of issuing written prescriptions for physical activities, often referred to as PARs, has been introduced as a tool to support such lifestyles. However, even though PHC nurses can prescribe physical activities, studies investigating their experience in this type of nursing intervention are rare. METHODS: For this study, 12 semi-structured interviews were conducted with PHC nurses, and the transcribed texts were analysed using a qualitative content analysis. FINDINGS: Two categories--PARs, an important nursing intervention, and PARs, the necessity of organisational support--reflected the nurses' experiences in using PARs.
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8.
  • Bridel, Claire, et al. (författare)
  • Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
  • 2019
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
  • Forskningsöversikt (refereegranskat)abstract
    • Importance  Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives  To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources  PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection  Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis  Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure  The cNfL levels adjusted for age and sex across diagnoses.Results  Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance  These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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9.
  • Drevinge, Christina, 1983, et al. (författare)
  • Perilipin 5 is protective in the ischemic heart
  • 2016
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 219, s. 446-454
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. Methods and results: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5(-/-) mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction. Conclusion: Our findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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10.
  • Ekerstad, Niklas, et al. (författare)
  • Clinical Frailty Scale classes are independently associated with 6-month mortality for patients after acute myocardial infarction
  • 2022
  • Ingår i: European Heart Journal. - : Oxford University Press. - 2048-8726 .- 2048-8734. ; 11:2, s. 89-98
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Data on the prognostic value of frailty to guide clinical decision-making for patients with myocardial infarction (MI) are scarce. To analyse the association between frailty classification, treatment patterns, in-hospital outcomes, and 6-month mortality in a large population of patients with MI.Methods and results: An observational, multicentre study with a retrospective analysis of prospectively collected data using the SWEDEHEART registry. In total, 3381 MI patients with a level of frailty assessed using the Clinical Frailty Scale (CFS-9) were included. Of these patients, 2509 (74.2%) were classified as non-vulnerable non-frail (CFS 1–3), 446 (13.2%) were vulnerable non-frail (CFS 4), and 426 (12.6%) were frail (CFS 5–9). Frailty and non-frail vulnerability were associated with worse in-hospital outcomes compared with non-frailty, i.e. higher rates of mortality (13.4% vs. 4.0% vs. 1.8%), cardiogenic shock (4.7% vs. 2.5% vs. 1.9%), and major bleeding (4.5% vs. 2.7% vs. 1.1%) (allP < 0.001), and less frequent use of evidence-based therapies. In Cox regression analyses, frailty was strongly and independently associated with 6-month mortality compared with non-frailty, after adjustment for age, sex, the GRACE risk score components, and other potential risk factors [hazard ratio (HR) 3.32, 95% confidence interval (CI) 2.30–4.79]. A similar pattern was seen for vulnerable non-frail patients (fully adjusted HR 2.07, 95% CI1.41–3.02).Conclusion: Frailty assessed with the CFS was independently and strongly associated with all-cause 6-month mortality, also after comprehensive adjustment for baseline differences in other risk factors. Similarly, non-frail vulnerability was independently associated with higher mortality compared with those with preserved functional ability.
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  • Enqvist, Jonas K, et al. (författare)
  • Energy turnover during 24 hours and 6 days of adventure racing.
  • 2010
  • Ingår i: Journal of Sports Sciences. - : Routledge. - 0264-0414 .- 1466-447X. ; 28:9, s. 947-955
  • Tidskriftsartikel (refereegranskat)abstract
    • Energy turnover was assessed in two conditions of mixed ultra-endurance exercise. In Study 1, energy expenditure and intake were measured in nine males in a laboratory over 24 h. In Study 2, energy expenditure was assessed in six males during an 800-km Adventure race (mean race time 152.5 h). Individual correlations between heart rate and oxygen uptake ([Vdot]O(2)) were established during pre-tests when kayaking, cycling, and running. During exercise, energy expenditure was estimated from continuous heart rate recordings. Heart rate and [Vdot]O(2) were measured regularly during fixed cycling work rates to correct energy expenditure for drift in oxygen pulse. Mean energy expenditure was 18,050 +/- 2,390 kcal (750 +/- 100 kcal . h(-1)) and 80,000 +/- 18,000 kcal (500 +/- 100 kcal . h(-1)) in Study 1 and Study 2 respectively, which is higher than previously reported. Energy intake in Study 1 was 8,450 +/- 1,160 kcal, resulting in an energy deficit of 9,590 +/- 770 kcal. Body mass decreased in Study 1 (-2.3 +/- 0.8 kg) but was unchanged in Study 2. Fat mass decreased in Study 2 (-2.3 +/- 1.5 kg). In Study 1, muscle glycogen content decreased by only 60%. Adventure racing requires a high energy expenditure, with large inter-individual variation. A large energy deficit is caused by inadequate energy intake, possibly due to suppressed appetite and gastrointestinal problems. The oxygen pulse, comparing start to 12 h of exercise and beyond, increased by 10% and 5% in Study 1 and Study 2 respectively. Hence, estimations of energy expenditure from heart rate recordings should be corrected according to this drift.
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  • Fernström, Maria, et al. (författare)
  • Reduced efficiency, but increased fat oxidation, in mitochondria from human skeletal muscle after 24-h ultraendurance exercise.
  • 2007
  • Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 102:5, s. 1844-1849
  • Tidskriftsartikel (refereegranskat)abstract
    • The hypothesis that ultraendurance exercise influences muscle mitochondrial function has been investigated. Athletes in ultraendurance performance performed running, kayaking, and cycling at 60% of their peak O(2) consumption for 24 h. Muscle biopsies were taken preexercise (Pre-Ex), postexercise (Post-Ex), and after 28 h of recovery (Rec). Respiration was analyzed in isolated mitochondria during state 3 (coupled to ATP synthesis) and state 4 (noncoupled respiration), with fatty acids alone [palmitoyl carnitine (PC)] or together with pyruvate (Pyr). Electron transport chain activity was measured with NADH in permeabilized mitochondria. State 3 respiration with PC increased Post-Ex by 39 and 41% (P < 0.05) when related to mitochondrial protein and to electron transport chain activity, respectively. State 3 respiration with Pyr was not changed (P > 0.05). State 4 respiration with PC increased Post-Ex but was lower than Pre-Ex at Rec (P < 0.05 vs. Pre-Ex). Mitochondrial efficiency [amount of added ADP divided by oxygen consumed during state 3 (P/O ratio)] decreased Post-Ex by 9 and 6% (P < 0.05) with PC and PC + Pyr, respectively. P/O ratio remained reduced at Rec. Muscle uncoupling protein 3, measured with Western blotting, was not changed Post-Ex but tended to decrease at Rec (P = 0.07 vs. Pre-Ex). In conclusion, extreme endurance exercise decreases mitochondrial efficiency. This will increase oxygen demand and may partly explain the observed elevation in whole body oxygen consumption during standardized exercise (+13%). The increased mitochondrial capacity for PC oxidation indicates plasticity in substrate oxidation at the mitochondrial level, which may be of advantage during prolonged exercise.
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  • Fernström, Maria, et al. (författare)
  • Skeletal muscle mitochondrial function and ROS production in response to extreme endurance exercise in athletes.
  • 2006
  • Ingår i: 14 European bioenergetic conference, Moscow, Russia, 22-27 July, 2006.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Although it is well known that endurance exercise induces oxidative stress (1) there is no evidence of deteriorated mitochondrial function after 1-2 hours intensive exercise (2). However, the effects of extreme endurance exercise on mitochondrial function and mitochondrial ROS production have not been investigated previously. Nine healthy well-trained men (age 27.1 ± 0.87 (mean ± SE), BMI 24.2 ± 0.64 and VO2 peak 62.5 ± 1.78 ml/kg. min) performed 24 hours exercise, consisting of equal parts running, cycling and paddling. Muscle biopsies were taken from vastus lateralis pre-exercise (PreEx), immediately post-exercise (PostEx) and after 28 hours of recovery (PostEx-28). Mitochondria were isolated and mitochondrial respiration was analyzed with palmitoyl-carnitine (PC) and pyruvate (Pyr). Mitochondrial H2O2 release was measured with the Amplex Red-horseradish peroxide method. The reaction was initiated by addition of succinate with following addition of antimycin A (reversed electron flow). UCP3 protein expression, evaluated with western blot technique, was not changed by exercise. Both state 3 (Pyr and PC) and state 4 (PC) rates of oxygen consumption (estimated per maximal ETC-activity) were increased PostEx (+29%, +11% and +18%). State 3 remained elevated PostEx-28, whereas state 4 (Pyr) decreased below that at PreEx (-18%). Mitochondrial efficiency (P/O) decreased PostEx (Pyr -8.9%, PC -6.1%) and remained reduced PostEx-28. The relative substrate oxidation (state 3 PC/Pyr) increased after exercise PreEx: (0.71 ± 0.06 vs. PostEx (0.90 ±0.04) and (0.77 ±0.06) PostEx-28. Mitochondrial H2O2 release (succinate) increased dramatically after exercise (+189 ± 64%). Treatment with Antimycin A resulted in a twofold-increased rate of mitochondrial H2O2 release PreEx but a decreased rate in PostEx samples. The exercise-induced changes in mitochondrial ROS production was totally abolished PostEx-28. In conclusion extreme endurance exercise decreases mitochondrial efficiency and increases mitochondrial ROS production. Both of these changes would increase the oxygen demand during exercise. Relative fatty acid oxidation as measured in isolated mitochondria increased after exercise indicating that the capacity to oxidize fat is improved during prolonged exercise.1. Mastaloudis, A., S.W. Leonard, and M.G. Traber, Oxidative stress in athletes during extreme endurance exercise. Free Radic Biol Med, 2001. 31(7): p. 911-22.2. Tonkonogi, M., et al., Mitochondrial function and antioxidative defence in human muscle: effects of endurance training and oxidative stress. J Physiol, 2000. 528 Pt 2: p. 379-88.
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  • Fogelstrand, Linda, 1974, et al. (författare)
  • Monocytic expression of CD14 and CD18, circulating adhesion molecules and inflammatory markers in women with diabetes mellitus and impaired glucose tolerance
  • 2004
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 47:11, s. 1948-52
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS/HYPOTHESIS: Type 2 diabetes is a major risk factor for cardiovascular disease. Monocyte recruitment and inflammatory activation are crucial steps in the development of atherosclerosis and several receptors are involved in these processes. The aim of this study was to investigate levels of CD14 and the beta(2)-integrin subunits CD11b and CD18 on monocytes from women with diabetes or impaired glucose tolerance. METHODS: A population-based sample of 112 Swedish women, who were aged 64 years and had diabetes mellitus or impaired or normal glucose tolerance, was investigated. Cell surface receptors were analysed with flow cytometry and serum inflammation markers and soluble adhesion molecules with enzyme-linked methods. RESULTS: The monocytic CD14 expression and serum levels of C-reactive protein, IL-6 and soluble adhesion molecules were higher in the diabetes group than in the group with normal glucose tolerance. Monocytic CD18 was elevated both in the diabetes and in the impaired glucose tolerance groups. The levels of monocytic surface markers correlated with BMI and to a lesser extent with glycaemic control. CONCLUSIONS/INTERPRETATION: The increased monocytic expression of important surface receptors together with elevated serum inflammation markers supports the concept of increased inflammation in type 2 diabetes and may be an important factor for the risk of atherosclerosis.
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  • Fredman, Peter, et al. (författare)
  • Economic values in the Swedish nature-based recreation sector : a synthesis
  • 2012
  • Ingår i: Tourism Economics. - London : IP Publishing. - 1354-8166 .- 2044-0375. ; 18:4, s. 903-910
  • Forskningsöversikt (refereegranskat)abstract
    • This research synthesis reports the main findings from a review of economic values associated with nature-based recreation in Sweden. The purpose of the work was to support policy and to identify areas for future research. Data came from over 150 scientific publications and other public sources. The authors find inter alia a lack of systematic data for several recreation activities (including naturebased tourism), a significant growth in the outdoor equipment industry and a relatively modest economic involvement by the public sector. The information is structured under different categories to illustrate the significance and range of different economic values. The authors conclude that there is a need for more comprehensive and systematically collected data, methodological development and interdisciplinary research.
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  • Gabrielsson, Linda, et al. (författare)
  • Palmitoylethanolamide for the treatment of pain : pharmacokinetics, safety and efficacy
  • 2016
  • Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 82:4, s. 932-942
  • Forskningsöversikt (refereegranskat)abstract
    • Palmitoylethanolamide (PEA) has been suggested to have useful analgesic properties and to be devoid of unwanted effects. Here, we have examined critically this contention, and discussed available data concerning the pharmacokinetics of PEA and its formulation. Sixteen clinical trials, six case reports/pilot studies and a meta-analysis of PEA as an analgesic have been published in the literature. For treatment times up to 49days, the current clinical data argue against serious adverse drug reactions (ADRs) at an incidence of 1/200 or greater. For treatment lasting more than 60days, the number of patients is insufficient to rule out a frequency of ADRs of less than 1/100. The six published randomized clinical trials are of variable quality. Presentation of data without information on data spread and nonreporting of data at times other than the final measurement were among issues that were identified. Further, there are no head-to-head clinical comparisons of unmicronized vs. micronized formulations of PEA, and so evidence for superiority of one formulation over the other is currently lacking. Nevertheless, the available clinical data support the contention that PEA has analgesic actions and motivate further study of this compound, particularly with respect to head-to-head comparisons of unmicronized vs. micronized formulations of PEA and comparisons with currently recommended treatments.
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18.
  • Isaksson, Johan, et al. (författare)
  • Highly elevated systemic inflammation is a strong independent predictor of early mortality in advanced non-small cell lung cancer
  • 2022
  • Ingår i: Cancer Treatment and Research Communications. - : Elsevier. - 2468-2942. ; 31
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAmple evidence support inflammation as a marker of outcome in non-small cell lung cancer (NSCLC). Here we explore the outcome for a subgroup of patients with advanced disease and substantially elevated systemic inflammatory activity.MethodsThe source cohort included consecutive patients diagnosed with NSCLC between January 2016 – May 2017 (n = 155). Patients with active infection were excluded. Blood parameters were examined individually, and cut-offs (ESR > 60 mm, CRP > 20 mg/L, WBC > 10 × 109, PLT > 400 × 109) were set to define the group of hyperinflamed patients. A score was developed by assigning one point for each parameter above cut-off (0–4 points).ResultsHigh systemic inflammation was associated with advanced stage and was seldom present in limited NSCLC. However, the one year survival of patients in stage IIIB-IV (n = 93) with an inflammation score of ≥2 was 0% compared to 33% and 50% among patients with a score of 1 and 0 respectively. The effect of a high inflammation score on overall survival remained significant in multi-variate analysis adjusted for confounding factors. The independent hazard ratio of an inflammation score ≥ 2 in multi-variate analysis (HR 3.43, CI 1.76–6.71) was comparable to a change in ECOG PS from 0 to 2 (HR 2.42, CI 1.13–5.18).ConclusionOur results show that high level systemic inflammation is a strong independent predictor of poor survival in advanced stage NSCLC. This observation may indicate a need to use hyperinflammation as an additional clinical parameter for stratification of patients in clinical studies and warrants further research on underlying mechanisms linked to tumor progression.
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19.
  • Jansen, Willemijn J, et al. (författare)
  • Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
  • 2018
  • Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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  • Johansson, Maria, et al. (författare)
  • Perceived outdoor lighting quality POLQ. A lighting assessment tool
  • 2014
  • Ingår i: Journal of Environmental Psychology. - : Elsevier BV. - 1522-9610 .- 0272-4944. ; 39, s. 14-21
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract in UndeterminedA shift towards more energy-efficient light sources for outdoor lighting such as light-emitting diodes (LEDs) is underway. Photometric measures are not sufficient to capture how users experience the light, so complementary tools are required. This study aimed to develop an observer-based environmental assessment tool, based on bipolar semantic differentials, for outdoor lighting in urban spaces. Exploratory (N = 130) and confirmatory (N = 117) factor analyses of observations of lighting installations made by laypersons on-site along pedestrian paths, resulted in two dimensions of high reliability: the Perceived Strength Quality (PSQ, Cronbach's alpha = 0.82–0.85) and the Perceived Comfort Quality (PCQ, Cronbach's alpha = 0.77–0.81). PSQ and PCQ differentiated between light sources of different illuminance level, colour temperature and colour rendering. Regression analyses showed that the perceived lighting qualities helped to explain the variance in visual accessibility, whereas PCQ helped to explain perceived danger in the environment. The perceived lighting qualities can add to the understanding of pedestrians' perception of outdoor lighting, and is proposed as a complementary tool for development of sustainable light designs in the urban environment
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22.
  • Johnson, Linda S, et al. (författare)
  • Serum Potassium Is Positively Associated With Stroke and Mortality in the Large, Population-Based Malmö Preventive Project Cohort
  • 2017
  • Ingår i: Stroke. - 1524-4628. ; 48:11, s. 2973-2978
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Low serum potassium is associated with stroke in populations with cardiovascular disease, hypertension, and diabetes mellitus but has not been studied in a mainly healthy population. We aimed to study the relation between serum potassium and incident stroke and mortality in the Malmö Preventive Project, a large cohort with screening in early mid-life and follow-up >25 years.METHODS: Serum potassium measurements and covariates were available in 21 353 individuals (79% men, mean age 44 years). Mean follow-up time was 26.9 years for stroke analyses and 29.3 years for mortality analyses. There were 2061 incident stroke events and 8709 deaths. Cox regression analyses adjusted for multiple stroke risk factors (age, sex, height, weight, systolic blood pressure, fasting blood glucose, serum sodium, current smoking, prevalent diabetes mellitus, prevalent coronary artery disease, and treatment for hypertension) were fitted.RESULTS: There was an independent, linear association between serum potassium, per mmol/L increase, and both stroke (hazard ratio, 1.33; 95% confidence interval, 1.17-1.52; P<0.0001) and mortality (hazard ratio, 1.20; 95% confidence interval, 1.13-1.28; P<0.0001). This was significant in subjects both older and younger than the median age (46.5 years), and there was evidence of an interaction with serum sodium. The association was positive and significant for both ischemic stroke and intracerebral hemorrhage and in both hypertensive and normotensive subjects.CONCLUSIONS: Serum potassium, measured in early mid-life, was linearly associated with both incidence of ischemic stroke and intracerebral hemorrhage and all-cause mortality. An interaction with serum sodium implies that factors related to electrolyte balance and incident hypertension may be mediating factors.
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23.
  • Karlsson, Linda, et al. (författare)
  • Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases.
  • 2024
  • Ingår i: Nature Communications. - 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer's disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.
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24.
  • Mattsson, C. Mikael, et al. (författare)
  • Reversed drift in heart rate but increased oxygen uptake at fixed work rate during 24 h ultra-endurance exercise.
  • 2010
  • Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 20:2, s. 298-304
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we report a reversed drift in heart rate (HR) but increased oxygen uptake (VO(2)) during ultra-endurance exercise. Nine well-trained male athletes performed 24-h exercise in a controlled laboratory setting, with alternating blocks of kayaking, running and cycling. Each block included 110 min of exercise and 10 min of rest, with an average work intensity of approximately 55% of respective VO(2peak). Blood samples were taken and HR and VO(2) measured every 6th hour during steady-state cycling at fixed work rate. As assumed HR was increased at 6 h by 15 +/- 6 beats/min compared with initial level (0 h). Thereafter the drift did not progress continuously, but instead unexpectedly returned toward initial values, although the plasma levels of catecholamines increased continuously during exercise. VO(2) was increased by 0.22 +/- 0.15 L/min (10%) at 6 h and 0.37 +/- 0.18 L/min (17%) at 12 h compared with 0 h, and thereafter remained stable. This implies an increased oxygen pulse (VO(2)/HR) by approximately 10% at the last half of the 24-h exercise compared with 0 h. Consequently, sole use of HR would give inaccurate estimates of exercise intensity and energy expenditure during endurance exercise lasting more than 6 h, and different patterns of cardiovascular drift need to be taken into account.
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25.
  • Mattsson, C. Mikael, et al. (författare)
  • Unexpected cardiovascular response during ultra-endurance exercise.
  • 2008
  • Ingår i: 13th Annual Congress of the European College of Sport Science (ECSS), Estoril, Lissabon, Portugal.. - 9789727351565 ; , s. 142-
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • During prolonged exercise at fixed work rate heart rate (HR) increases slowly with concomitant decrease in stroke volume (SV) in order to maintain cardiac output. Simultaneously, an increased oxygen uptake (VO2) occurs. In this paper we report an unexpected and previously not observed cardiovascular response to ultra-endurance exercise. Nine well-trained male athletes performed 24-h exercise in a controlled laboratory setting, with altering blocks of kayaking, running and cycling. Each block consisted of 110 min of exercise and 10 min of rest. Measurements (HR, VO2 and blood samples) were conducted during cycling at fixed work rate every 6th hour. The average work intensity was approximately 55 % of respective VO2peak. HR was increased at 6 h with 15 beats/min (13 %) compared to pre-exercise (Pre-Ex), but thereafter unexpectedly returned towards initial values. VO2 on the other hand was increased with 0.22 l/min (10 %) at 6 h and 0.37 l/min (17 %) at 12 h compared to Pre-Ex, and thereafter remained stable. This implies an increased oxygen pulse (VO2/HR) with approximately 10 % compared to Pre-Ex at the later half of the exercise. The cardiovascular drift did not progress continuously, but instead changed drastically when duration exceeded 6 hours. The changes in HR and VO2 might have different and complex explanations. HR drift might be explained mainly by central circulatory adaptation (e.g. desensitisation of cardiac adrenergic receptors) whereas drift in VO2 may depend upon peripheral changes (e.g. decreased mitochondrial efficiency). Consequently, using solely HR for determining exercise intensity and energy expenditure becomes invalid during ultra-endurance exercise, if the cardiovascular drift is not measured and taken into account.  
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26.
  • Mattsson-Carlgren, Niklas, et al. (författare)
  • Plasma Biomarker Strategy for Selecting Patients With Alzheimer Disease for Antiamyloid Immunotherapies
  • 2024
  • Ingår i: JAMA neurology. - 2168-6157 .- 2168-6149. ; 81:1, s. 69-78
  • Tidskriftsartikel (refereegranskat)abstract
    • Antiamyloid immunotherapies against Alzheimer disease (AD) are emerging. Scalable, cost-effective tools will be needed to identify amyloid β (Aβ)-positive patients without an advanced stage of tau pathology who are most likely to benefit from these therapies. Blood-based biomarkers might reduce the need to use cerebrospinal fluid (CSF) or positron emission tomography (PET) for this.To evaluate plasma biomarkers for identifying Aβ positivity and stage of tau accumulation.The cohort study (BioFINDER-2) was a prospective memory-clinic and population-based study. Participants with cognitive concerns were recruited from 2017 to 2022 and divided into a training set (80% of the data) and test set (20%).Baseline values for plasma phosphorylated tau 181 (p-tau181), p-tau217, p-tau231, N-terminal tau, glial fibrillary acidic protein, and neurofilament light chain.Performance to classify participants by Aβ status (defined by Aβ-PET or CSF Aβ42/40) and tau status (tau PET). Number of hypothetically saved PET scans in a plasma biomarker-guided workflow.Of a total 912 participants, there were 499 males (54.7%) and 413 females (45.3%), and the mean (SD) age was 71.1 (8.49) years. Among the biomarkers, plasma p-tau217 was most strongly associated with Aβ positivity (test-set area under the receiver operating characteristic curve [AUC]=0.94; 95% CI, 0.90-0.97). A 2-cut-point procedure was evaluated, where only participants with ambiguous plasma p-tau217 values (17.1% of the participants in the test set) underwent CSF or PET to assign definitive Aβ status. This procedure had an overall sensitivity of 0.94 (95% CI, 0.90-0.98) and a specificity of 0.86 (95% CI, 0.77-0.95). Next, plasma biomarkers were used to differentiate low-intermediate vs high tau-PET load among Aβ-positive participants. Plasma p-tau217 again performed best, with the test AUC=0.92 (95% CI, 0.86-0.97), without significant improvement when adding any of the other plasma biomarkers. At a false-negative rate less than 10%, the use of plasma p-tau217 could avoid 56.9% of tau-PET scans needed to identify high tau PET among Aβ-positive participants. The results were validated in an independent cohort (n=118).This study found that algorithms using plasma p-tau217 can accurately identify most Aβ-positive individuals, including those likely to have a high tau load who would require confirmatory tau-PET imaging. Plasma p-tau217 measurements may substantially reduce the number of invasive and costly confirmatory tests required to identify individuals who would likely benefit from antiamyloid therapies.
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27.
  • Mattsson, Hans, et al. (författare)
  • Gruvdammar och deras stabilitet
  • 2012
  • Ingår i: Bygg och Teknik. - 0281-658X .- 2002-8350. ; 104:1, s. 49-52
  • Tidskriftsartikel (populärvet., debatt m.m.)
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28.
  • Mattsson, Johan, et al. (författare)
  • Cholera toxin adjuvant promotes a balanced Th1/Th2/Th17 response independently of IL-12 and IL-17 by acting on Gsα in CD11b(+) DCs.
  • 2015
  • Ingår i: Mucosal immunology. - : Elsevier BV. - 1935-3456 .- 1933-0219. ; 8:4, s. 815-827
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite an extensive literature on the mechanism of action of cholera toxin (CT), we still lack critical information about how the toxin acts as an adjuvant and, especially, which dendritic cells (DCs) are the target cells. Although a T helper type 2 (Th2)-skewing effect of CT is most commonly reported, effective priming of Th17 cells as well as suppression of Th1 responses are well documented. However, the ability of CT to block interferon regulatory factor 8 (IRF8) function and interleukin (IL)-12 production in DCs, which blocks CD8α DC and Th1 cell development, is inconsistent with priming of Th1 and CD8 T cells in many other reports. This prompted us to investigate the adjuvant effect of CT in wild-type, IL-12p40-/-, Batf3-/-, and IL-17A-/- mice and in mice that selectively lack the Gsα target protein for CT adenosine diphosphate (ADP)-ribosylation in DCs. We found that CT promoted Th1 priming independently of IL-12, and whereas Th2 and also Th17 responses were augmented, the gut IgA responses did not require IL-17A. Adjuvanticity was intact in Batf3-/- mice, lacking CD8α(+) DCs, but completely lost in mice with Gsα-deficient CD11c cells. Thus, our data demonstrate that the adjuvant effect requires Gsα expression in CD11b(+) DCs, and that priming of mucosal IgA and CD4 T cells appears unbiased and is independent of IL-12 and IL-17A.Mucosal Immunology advance online publication, 26 November 2014; doi:10.1038/mi.2014.111.
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29.
  • Mattsson, Linda, 1973 (författare)
  • Demographics of self-selected participiants in mathematical tracks in Swedish Upper Secondary School
  • 2012
  • Ingår i: The Mathematics Enthusiast. - 1551-3440. ; 9:3, s. 271-302
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigates the three demographic factors gender, geographical origin and parents educational level among self-selected students in mathematical tracks in Swedish Upper Secondary School (n=147). Comparisons are made, through statistical tests of significance, with corresponding student distributions on the closely related Natural Science program (n = 1528). Data is obtained from Statistics Sweden. Results confirm that females are under-represented in mathematical tracks (p<0,01) and that parents of students in mathematical tracks have higher educational level than parents of students in the comparison group (p<0,05). Results do not show that students with foreign background are underrepresented in mathematical tracks, but raise questions about under-representation of Swedish students. Possible implications of these findings for these and similar programs are discussed.
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30.
  • Mattsson, Linda, 1973 (författare)
  • Demographics of self-selected participiants in mathematical tracks in Swedish Upper Secondary School
  • 2012
  • Ingår i: Mathematics Enthusiast. - 1551-3440. ; 9:3, s. 271-302
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigates the three demographic factors gender, geographical originand parents educational level among self-selected students in mathematical tracks in SwedishUpper Secondary School (n=147). Comparisons are made, through statistical tests ofsignificance, with corresponding student distributions on the closely related Natural Scienceprogram (n = 1528). Data is obtained from Statistics Sweden. Results confirm that femalesare under-represented in mathematical tracks (p
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31.
  • Mattsson, Linda, et al. (författare)
  • En helhetssyn på lärande via matematisk problemlösning
  • 2019
  • Rapport (populärvet., debatt m.m.)abstract
    • Syftet med kursen Matematisk problemlösningär att genom utmanande problemlösningfå studenter att träna på generellaarbets- och förhållningssätt som är hållbara ochvärdefulla för fortsatta (matematik)studier.Genom övnings- och examinationsuppgiftersom kräver kreativa matematiska resonemangtvingas studenter att fokusera på dematematiska komponenternas grunder vilketmöjliggör utveckling av högre matematiskakompetenser.* Vidare skapar kursuppläggetförutsättningar för utveckling av personligaoch professionella förmågor* väsentliga förlärande i tillämpningsämnen och utövande avframtida yrkesroll.
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32.
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33.
  • Mattsson, Linda, 1973, et al. (författare)
  • On track to gifted education in mathematics in Sweden
  • 2010
  • Ingår i: The Elements of Creativity and Giftedness in Mathematics (B. Sriraman and K.H. Lee; eds). - Rotterdam, the Netherlands : Sense Publishers. - 9789460914386 ; , s. 81-102
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • In this article we provide a description of the status of gifted education in mathematics in Sweden by highlighting the development of four components - a) national policies, b) advocacy groups, c) research, teacher education and curriculum development, and d) implementation in schools. All four of these components are important in the development of gifted education (Phillipson, Kaur & Phillipson, 2003.
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34.
  • Mattsson, Linda, 1973 (författare)
  • Tracking mathematical giftedness in an egalitarian context
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In three different studies upper secondary school head teachers’ characterization and identification of mathematical giftedness was investigated. A survey study (Paper II) explored the conceptions held by 36 randomly selected upper secondary school head teachers in mathematics. An interview study (Paper III) investigated the conceptions held by three purposively selected head teachers working at the longest running gifted programs in mathematics in Swedish upper secondary schools. A third study (Paper IV) looked for creativity, the characteristic head teachers’ most frequently associated with giftedness, in the admission tests used at the cutting-edge programs in mathematics in upper secondary school. As compared to theoretical models, results showed that the head teachers collectively expressed nuanced characterizations of mathematical giftedness and the identification thereof. This was especially demonstrated by the head teachers at the gifted mathematics programs. Still, for individual head teachers, there is a need to further their knowledge about the different abilities contributing to manifestations of mathematical giftedness. This would increase the possibility to identify and develop the mathematical abilities of an even greater number of mathematically promising students. Krutetskii’s (1976) structure of mathematical abilities manifested by capable mathematics students was used as a framework for the content analysis in the first two studies, and Lithner’s (2008) framework for creative and imitative reasoning was used in the third study. In a fourth study (Paper V) the representation of different student groups at five purposively selected gifted programs in upper secondary school was investigated. Findings from this comparative study of demographical factors – gender, geographical origin, and highest education of parents – were complemented by findings from the interview study where the cognitive, as well as personal and social, characteristics of students participating at three gifted programs were expressed. Results from the interview study indicated that students participating at the gifted programs showed signs of mathematical giftedness that are not necessarily connected to schoolhouse giftedness. Both mathematically gifted students who were individualists and reluctant to participate in traditional school mathematics, and those who were hardworking and ambitious, were recognized. Participating students had special needs, such as to approach mathematical tasks in their own way and learn how to communicate mathematics in written solutions, connected to their giftedness that call for special education. The demographical study showed that it is mostly males with highly educated parents who have found their way to gifted programs in mathematics. In sum, results indicate that the head teachers at the gifted programs acknowledge that there are gifted mathematics students with special educational needs at their gifted programs. There is also a call for the development of complementary educational activities to reach a greater number and variety of gifted students.
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35.
  • Mattsson, Niklas, et al. (författare)
  • Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimers disease
  • 2018
  • Ingår i: Alzheimer's & Dementia. - : ELSEVIER SCIENCE INC. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimers disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P amp;lt;.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimers Association. Published by Elsevier Inc. All rights reserved.
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36.
  • Mattsson, Niklas, et al. (författare)
  • Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
  • 2018
  • Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
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37.
  • Mattsson, Nick, et al. (författare)
  • Prognostic Impact of Mild Hypokalemia in Terms of Death and Stroke in the General Population - a Prospective Population Study
  • 2018
  • Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343. ; 131:3, s. 9-318
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Potassium supplementation reduces the risk of cardiovascular mortality and stroke in population studies; however, the prognostic impact of mild hypokalemia in the general population has not been thoroughly investigated. We aimed to investigate associations between mild hypokalemia and endpoints in the general population.METHODS: participants (48-76 year old) from the general population study "Copenhagen City Heart Study" (n=5916) were studied. Participants were divided into groups according to baseline-values of plasma-potassium (potassium); Hypokalemia (<3.7 mmol/L,n=758), normokalemia (3.7-4.5 mmol/L] n=4973, and high-potassium (>4.5 mmol/L,n=185). Hypokalemia was further divided in potassium<3.4 and 3.4-3.6 mmol/L. The primary endpoints were all-cause mortality and non-fatal validated ischemic stroke. Secondary endpoint was AMI. We adjusted for conventional risk factors, diuretics and atrial fibrillation (AF) at baseline.RESULTS: Mean potassium in the hypokalemic group was 3.5 mmol/L (range 2.6-3.6) and was associated (P<0.05) with increased systolic blood pressure, higher CHA2DS2-VASc-score, and increased use of diuretics as compared with normokalemia. Baseline AF was equally frequent across groups. Median follow-up-time was 11.9 years (Q1-Q3: 11.4-12.5 years). Hypokalemia was borderline associated with increased stroke-risk in a multivariable Cox model (including adjustment for competing risk) as compared with normokalemia (HR:1.40;95%CI:1.00-1.98). The subgroup with potassium<3.4 mmol/L had higher stroke- (HR:2.10;95%CI:1.19-3.73) and mortality-risk (HR:1.32;95%CI:1.01-1.74) as compared with normokalemia. Hypokalemia was not associated with AMI and no increased risk of mortality was seen with concomitant AMI and hypokalemia. No associations were seen with high-potassium.CONCLUSIONS: In a general population mild hypokalemia is associated with increased stroke-risk and to a lesser degree increased mortality-risk.
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38.
  • Mattsson, Nick, et al. (författare)
  • The Reply
  • 2018
  • Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343. ; 131:4, s. 169-169
  • Tidskriftsartikel (refereegranskat)
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39.
  •  
40.
  • Odqvist, Lina, et al. (författare)
  • Genetic variations in A20 DUB domain provide a genetic link to citrullination and neutrophil extracellular traps in systemic lupus erythematosus
  • 2019
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 78:10, s. 1363-1370
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Genetic variations in TNFAIP3 (A20) de-ubiquitinase (DUB) domain increase the risk of systemic lupus erythematosus (SLE) and rheumatoid arthritis. A20 is a negative regulator of NF-κB but the role of its DUB domain and related genetic variants remain unclear. We aimed to study the functional effects of A20 DUB-domain alterations in immune cells and understand its link to SLE pathogenesis. Methods: CRISPR/Cas9 was used to generate human U937 monocytes with A20 DUB-inactivating C103A knock-in (KI) mutation. Whole genome RNA-sequencing was used to identify differentially expressed genes between WT and C103A KI cells. Functional studies were performed in A20 C103A U937 cells and in immune cells from A20 C103A mice and genotyped healthy individuals with A20 DUB polymorphism rs2230926. Neutrophil extracellular trap (NET) formation was addressed ex vivo in neutrophils from A20 C103A mice and SLE-patients with rs2230926. Results: Genetic disruption of A20 DUB domain in human and murine myeloid cells did not give rise to enhanced NF-κB signalling. Instead, cells with C103A mutation or rs2230926 polymorphism presented an upregulated expression of PADI4, an enzyme regulating protein citrullination and NET formation, two key mechanisms in autoimmune pathology. A20 C103A cells exhibited enhanced protein citrullination and extracellular trap formation, which could be suppressed by selective PAD4 inhibition. Moreover, SLE-patients with rs2230926 showed increased NETs and increased frequency of autoantibodies to citrullinated epitopes. Conclusions: We propose that genetic alterations disrupting the A20 DUB domain mediate increased susceptibility to SLE through the upregulation of PADI4 with resultant protein citrullination and extracellular trap formation.
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41.
  • Ormann, Linda, et al. (författare)
  • Numerical analysis of curved embankment of an upstream tailings dam
  • 2011
  • Ingår i: Electronic Journal of Geotechnical Engineering. - : Mete Öner. - 1089-3032. ; 16:I, s. 931-944
  • Tidskriftsartikel (refereegranskat)abstract
    • A curved embankment (corner) of an upstream tailings dam was analyzed with the finite element method to identify possible zones of low compressive stresses susceptible to hydraulic fracturing that might initiate internal erosion. The embankment was also analyzed as a straight section, with the same cross section as in the corner, in order to compare compressive stresses in the corner and the straight section. The analysis showed that in comparison to the straight section of the dam, the compressive stresses in the corner were (i) much lower above the phreatic level, in the rockfill banks and the filter zones, and (ii) fairly lower below the phreatic level. The rockfill and the filter contain coarse materials, which are not sensitive to hydraulic fracturing and internal erosion. An increase in radius of the corner is proposed to avoid too low compressive stresses that may develop due to future raisings. The slope stability analysis showed that the corner is currently stable, but an additional rock fill bank on the downstream toe is required for future raisings.
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42.
  • Ormann, Linda, et al. (författare)
  • Numerical analysis of strengthening by rockfill embankments on an upstream tailings dam
  • 2013
  • Ingår i: Canadian geotechnical journal (Print). - : Canadian Science Publishing. - 0008-3674 .- 1208-6010. ; 50:4, s. 391-399
  • Tidskriftsartikel (refereegranskat)abstract
    • The consolidation process could be slow in an upstream tailings dam; therefore, the stability can reduce due to an increase in excess pore pressures when the dam is raised. The safety of the dam can be enhanced by constructing rockfill berms on the downstream side. This paper presents a case study on the strengthening of an upstream tailings dam with rockfill berms. The finite element analyses were performed for modelling the staged construction of the dam and for optimizing the volume of the rockfill berms. The dam was raised in 11 stages; each stage consisting of a raising phase and a consolidation phase. The study shows that the slope stability of the dam reduced due to an increase of excess pore pressures during the raising phase. The stability of the dam was successfully improved by utilizing rockfill berms as supports on the downstream side. A technique has been presented to minimize the volume of the rockfill berms so that the required stability can be achieved at minimum cost. This paper shows that the finite element method can be a useful tool for modelling the consolidation behaviour of an upstream tailings dam and minimizing the volume of the rockfill berms that may be needed to maintain the stability of the dam during staged construction.
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43.
  • Rankin, Linda, 1987- (författare)
  • Chronic pain : from the study of student attitudes and preferences to the in vitro investigation of a novel treatment strategy
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Chronic pain will affect one in five adults during their lifetime, and it exerts a heavy burden on society with major physiological, psychological, social, and economic impacts. The current chronic pain curriculum taught to medical students in most settings is fragmented, inconsistent and inadequate and a vast majority of general practitioners considered their undergraduate training in chronic pain incomplete. Attitudes and beliefs amongst health care personnel are important and have shown to have impact on clinical management. There is currently a knowledge gap that needs to be addressed in this matter. In this thesis, through an online survey, the attitudes and beliefs of medical students in Sweden and Australia were surveyed. Additionally, we explored which factors influence chronic pain management amongst medical students in Sweden and Australia and Swedish general practitioners. We found that Swedish final year students have a more positive attitude towards chronic pain patients compared to Australian students. Both student cohorts perceived chronic pain management education in need of improvement. Furthermore, we found that the relative importance of factors that influence treatment decisions are formed early during undergraduate training, which further underlines the importance of improving pain curricula during undergraduate medical education in order to give the emerging workforce appropriate tools to manage chronic pain.Management of chronic pain urgently requires novel, well-tolerated pharmacological treatment strategies. Palmitoylethanolamide (PEA) is a potential candidate for managing chronic pain. Its analgesic and anti-inflammatory effects have been observed in a range of experimental animal models and clinical trials. However, questions remain as to how PEA exerts its effects and how levels of PEA and its congeners are changed in states of pain and inflammatory disorders in humans. Treatment with PEA decreases cyclooxygenase 2 (COX-2) activity in animal models, but we found that PEA did not have direct effects upon the kinetic properties of COX-2 in a cell free system. However, COX-2 derived eicosanoid levels were reduced by PEA in lipopolysaccharide and interferon-g-stimulated RAW 264.7 cells. With respect to changes in PEA levels in a chronic inflammatory disorder, we investigated PEA levels, in addition to its synthesizing and hydrolysing enzymes in biopsies from patients with oral lichen planus (OLP). We found that the ratio of prostaglandins to PEA was increased in the OLP biopsy samples. Furthermore, PTGS2 mRNA levels (coding for COX-2) were increased in OLP-patients compared to controls relative to NAPEPLD mRNA levels (coding for a key enzyme in the synthesis of PEA). These results suggest that there is a relative deficit of PEA in OLP, raising the possibility that PEA might be useful for the treatment of this disorder.
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44.
  • Ryden, Petra, 1972-, et al. (författare)
  • Counting the cost of healthy eating : a Swedish comparison of Mediterranean-style and ordinary diets
  • 2008
  • Ingår i: International Journal of Consumer Studies. - : Wiley. - 1470-6423 .- 1470-6431. ; 32:2, s. 138-146
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this research was to examine the cost of a diet generally regarded as healthy, a Swedish version of the Mediterranean diet, and to compare it with the cost of an ordinary Swedish diet. A total of 30 individuals provided detailed dietary data collected in a randomized intervention study, examining the effect of dietary change to a Mediterranean-style diet in patients with rheumatoid arthritis (Mediterranean group, n = 16, control group, n = 14). The data, covering 1-month dietary intake, were examined with three different diet quality indicators to see whether the Mediterranean group consumed a healthier diet than the control group. All diet quality indicators showed that the Mediterranean group consumed a healthier diet than the control group. Consumer food prices were used to analyse the cost of the different diets. In immediate consumer cost terms, eating a healthier diet was more expensive when differences in energy intake were discounted. However, non-energy adjusted costs showed no significant difference between the groups. Hence, if one of the reasons for choosing a healthier diet is to achieve weight loss – by consuming less energy – it is possible that healthier eating is not more expensive.
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45.
  • Rydén, Petra, 1972- (författare)
  • Toward an understanding of the barriers to and facilitators of dietary change :
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Healthy dietary changes would be beneficial for society, as the economic burden of diet-related diseases is massive, and for the individual, who would reduce their risk of ill health. However, it is not easy to change dietary habits. Therefore, the aim of this thesis was to better understand dietary change, focusing on the barriers to and facilitators of healthy dietary change by i) examining changes in food choices when dietary change is imposed by a medical diagnosis, ii) examining experiences related to dietary change and its sustainability after participation in a study where healthy dietary changes were required, and iii) examining diet cost in relation to healthiness of the diet. Methods Eighty children aged 13 who were diagnosed with celiac disease (CD) by a screening study reported their food intake in a food frequency questionnaire before and 1,5 years after commencing a gluten-free diet. Changes in food intake and the healthiness of the diet were examined, controlling for societal changes through the use of an age- and sex-matched control group. Diet healthiness was assessed using the National Food Administration’s (NFA) food index and the Diet Quality Index-Swedish Nutritional Recommendations. Qualitative interviews were conducted with 14 individuals who participated in an intervention study five years earlier where they had been randomly selected to adhere to a Mediterranean-like diet for three months. Analyses of the transcribed interviews focused on their experiences of barriers to and facilitators of dietary change and its sustainability. The costs related to healthy diets were examined by comparing consumer food prices with dietary intake data collected in two separate studies. The first study collected dietary intake data through a diet history interview with participants who had been randomized to either a Mediterranean-like diet or to continue their normal diet. The second study collected dietary intake data from 4-, 8-, and 11-year-old children by means of food diaries and was conducted by the NFA. Diet healthiness was assessed using the Healthy Eating Index 2005. Results The screened CD group made relatively few changes to their diets. They decreased their intake of certain gluten-containing products, including pizza, chicken nuggets, fish sticks, and pastries. There were no changes in the healthiness of their diet. The narratives of the individuals changing their diets showed that social relationships were the main barrier to sustainability. Social relationships within the household were especially troublesome, and various coping strategies were required on an everyday basis. Dietary change also increased the burden of food work (e.g., planning, shopping, cooking), which was another major barrier to dietary change. Comparisons between consumer costs of healthy and less healthy diets showed that those consuming the healthier diets also had consumed more expensive diets. Conclusion More barriers to healthy dietary changes were found than facilitators of these transitions. For instance, the impact of social relationships on sustainability of dietary change was found to be high, indicating the importance of participation of other household members when dietary changes are implemented. The higher cost of the healthier diets may be another barrier for healthy dietary changes, especially for those with limited resources. Even though it is possible to eat healthily at a lower cost, such a diet would likely require both cooking skills and time, thus making the task more difficult. However, the finding that children diagnosed with CD only made minor changes in their consumption of, for instance, bread and pasta, indicates that one way of increasing the healthiness of a diet is to substitute healthier alternatives within the same food group for less healthy food items.
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46.
  • Sahlin, Kent, et al. (författare)
  • Ultra-endurance exercise increases the production of reactive oxygen species in isolated mitochondria from human skeletal muscle.
  • 2010
  • Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 108:4, s. 780-787
  • Tidskriftsartikel (refereegranskat)abstract
    • Exercise-induced oxidative stress is important for the muscular adaptation to training but may also cause muscle damage. We hypothesized that prolonged exercise would increase mitochondrial production of reactive oxygen species (ROS) measured in vitro and that this correlates with oxidative damage. Eight male athletes (24-32 years) performed ultra-endurance exercise (kayaking/running/cycling) with an average work intensity of 55% VO2peak for 24 h. Muscle biopsies were taken from vastus lateralis before exercise, immediately after exercise and after 28 h of recovery. The production of H2O2 was measured fluorometrically in isolated mitochondria with the Amplex red and peroxidase system. Succinate-supported mitochondrial H2O2 production was significantly increased after exercise (73% higher, P=0.025) but restored to the initial level at recovery. Plasma level of free fatty acids (FFA) increased 4-fold and exceeded 1.2 mmol l(-1) during the last 6 h of exercise. Plasma FFA at the end of exercise was significantly correlated to mitochondrial ROS production (r=0.74, P<0.05). Mitochondrial content of 4-hydroxy-nonenal-adducts (a marker of oxidative damage) was increased only after recovery and was not correlated with mitochondrial ROS production. Total thiol-group level and glutathione peroxidase activity were elevated after recovery. In conclusion: ultra-endurance exercise increases ROS production in isolated mitochondria but this is reversed after 28 h recovery. Mitochondrial ROS production was not correlated with oxidative damage of mitochondrial proteins, which was increased at recovery but not immediately after exercise. Key words: antioxidative defence, fatty acids, oxidative stress.
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  • Svensson, Linda, 1974, et al. (författare)
  • Inhibitory effects of N-acetylcysteine on scavenger receptor class A expression in human macrophages.
  • 2002
  • Ingår i: Journal of internal medicine. - 0954-6820. ; 251:5, s. 437-46
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The formation of foam cells from monocyte-derived macrophages involves the uptake of modified lipoproteins by scavenger receptors. Antioxidants inhibit lipoprotein oxidation and may also modulate gene expression. We investigated the effect of the antioxidant N-acetylcysteine on the expression of the class A scavenger receptor (SR-A) types I and II in human macrophages. DESIGN: Monocytes and macrophages from healthy blood donors and plaque-derived macrophages from patients undergoing carotid endarterectomy were used for experiments. SR-A mRNA was analysed with quantitative and semiquantitative reverse transcription-polymerase chain reaction, and ligand binding and uptake were assessed with 125I-labelled acetylated low-density lipoprotein (LDL). RESULTS: Incubation of monocytes and monocyte-derived macrophages with N-acetylcysteine decreased both SR-A I and II mRNA expression. N-Acetylcysteine also reduced SR-A mRNA in lesion-derived cells. Binding and uptake of 125I-acetylated LDL was decreased after brief incubation with N-acetylcysteine. After longer periods of incubation with N-acetylcysteine we observed an increased degradation of lipoproteins. CONCLUSIONS: Our results imply that N-acetylcysteine leads to a decrease in SR-A mRNA and initially also to an attenuated uptake of modified lipoproteins. This adds more to the knowledge about the cellular actions of this drug.
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