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2.
  • Fröling, Morgan, 1966-, et al. (författare)
  • Bio-CCS - a model based case study from the mid Sweden region
  • 2015
  • Ingår i: Proceedings of Global Cleaner Production and Sustainable Consumption, Sitges Barcelona, November 1-4, 2015.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • In its 2014 report, IPCC recommend Carbon Capture and Storage not only for fossil power plants but also for bioenergy to beable to meet the 2 degree target. In a case study, models for CCS applied to a combined heat and power (CHP) plant inÖstersund, Sweden, using wood chips as main fuel was assessed. The goal was to gain knowledge to be prepared to takemore rapid action if policy instruments are implemented in future. More "traditional" technology with absorption inmonoethanolamine (MEA) and subsequent underground storage uses a significant part of produced electricity, and in anenergy system perspective it is not necessarily the most efficient use of a limited wood resource. For processes withcomparatively low net climate impact, like bio-CHP, alternatives significantly more energy efficient per unit of capturedcarbon dioxide but only able to capture part of the total emitted carbon can be considered. One such alternative is to capturecarbon dioxide using microalgae. Key issues for assessment of processes in this case are how to store the carbon captured inthe algae biomass (e.g. in products) and for how long the carbon will be withdrawn from atmosphere with such storage.
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  • Kilpeläinen, Tuomas O, et al. (författare)
  • Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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  • Abu Hamdeh, Sami, et al. (författare)
  • Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury
  • 2018
  • Ingår i: Brain Pathology. - : Wiley. - 1015-6305 .- 1750-3639. ; 28:4, s. 451-462
  • Tidskriftsartikel (refereegranskat)abstract
    • Deposition of amyloid-β (Aβ) is central to Alzheimer's disease (AD) pathogenesis and associated with progressive neurodegeneration in traumatic brain injury (TBI). We analyzed predisposing factors for Aβ deposition including monomeric Aβ40, Aβ42 and Aβ oligomers/protofibrils, Aβ species with pronounced neurotoxic properties, following human TBI. Highly selective ELISAs were used to analyze N-terminally intact and truncated Aβ40 and Aβ42, as well as Aβ oligomers/protofibrils, in human brain tissue, surgically resected from severe TBI patients (n = 12; mean age 49.5 ± 19 years) due to life-threatening brain swelling/hemorrhage within one week post-injury. The TBI tissues were compared to post-mortem AD brains (n = 5), to post-mortem tissue of neurologically intact (NI) subjects (n = 4) and to cortical biopsies obtained at surgery for idiopathic normal pressure hydrocephalus patients (iNPH; n = 4). The levels of Aβ40 and Aβ42 were not elevated by TBI. The levels of Aβ oligomers/protofibrils in TBI were similar to those in the significantly older AD patients and increased compared to NI and iNPH controls (P < 0.05). Moreover, TBI patients carrying the AD risk genotype Apolipoprotein E epsilon3/4 (APOE ε3/4; n = 4) had increased levels of Aβ oligomers/protofibrils (P < 0.05) and of both N-terminally intact and truncated Aβ42 (P < 0.05) compared to APOE ε3/4-negative TBI patients (n = 8). Neuropathological analysis showed insoluble Aβ aggregates (commonly referred to as Aβ plaques) in three TBI patients, all of whom were APOE ε3/4 carriers. We conclude that soluble intermediary Aβ aggregates form rapidly after TBI, especially among APOE ε3/4 carriers. Further research is needed to determine whether these aggregates aggravate the clinical short- and long-term outcome in TBI.
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  • Almevall, Ariel, et al. (författare)
  • Self-rated health in old age, related factors and survival: A 20-Year longitudinal study within the Silver-MONICA cohort
  • 2024
  • Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier. - 0167-4943 .- 1872-6976. ; 122
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Self-rated health (SRH) offers insights into the evolving health demographics of an ageing population.Aim: To assess change in SRH from old age to very old age and their associations with health and well-being factors, and to investigate the association between SRH and survival.Methods: All participants in the MONICA 1999 re-examination born before 1940 (n = 1595) were included in the Silver-MONICA baseline cohort. The Silver-MONICA follow-up started in 2016 included participants in the Silver-MONICA baseline cohort aged 80 years or older. Data on SRH was available for 1561 participants at baseline with 446 of them also participating in the follow-up. The follow-up examination included a wide variety of measurements and tests.Findings: Most participants rated their health as "Quite good" (54.5 %) at baseline. Over the study period, 42.6 % had stable SRH, 40.6 % had declined, and 16.8 % had improved. Changes in SRH were at follow-up significantly associated with age, pain, nutrition, cognition, walking aid use, self-paced gait speed, lower extremity strength, independence in activities of daily living, weekly physical exercise, outdoor activity, participation in organized activities, visiting others, morale, and depressive symptoms. SRH at baseline was significantly associated with survival (p < 0.05).Conclusion: This study demonstrates associations between changes in SRH and a multitude of health- and wellbeing-related factors, as well as a relation between survival and SRH, accentuating their relevance within the ageing population.
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  • Benedict, Christian, et al. (författare)
  • Fat Mass and Obesity-Associated Gene (FTO) Is Linked to Higher Plasma Levels of the Hunger Hormone Ghrelin and Lower Serum Levels of the Satiety Hormone Leptin in Older Adults
  • 2014
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:11, s. 3955-3959
  • Tidskriftsartikel (refereegranskat)abstract
    • The mechanisms through which common polymorphisms in the fat mass and obesity-associated gene (FTO) drive the development of obesity in humans are poorly understood. Using cross-sectional data from 985 older people (50% females) who participated at age 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), circulating levels of ghrelin and leptin were measured after an overnight fast. In addition, subjects were genotyped for FTO rs17817449 (AA, n = 345 [35%]; AC/CA, n = 481 [48.8%]; CC, n = 159 [16.1%]). Linear regression analyses controlling for sex, selfreported physical activity level, fasting plasma glucose, and BMI were used. A positive relationship between the number of FTO C risk alleles and plasma ghrelin levels was found (P = 0.005; relative plasma ghrelin difference between CC and AA carriers = similar to 9%). In contrast, serum levels of the satiety-enhancing hormone leptin were inversely linked to the number of FTO C risk alleles (P = 0.001; relative serum leptin difference between CC and AA carriers = similar to 11%). These associations were also found when controlling for waist circumference. The present findings suggest that FTO may facilitate weight gain in humans by shifting the endocrine balance from the satiety hormone leptin toward the hunger-promoting hormone ghrelin.
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  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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11.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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12.
  • Bergström, Göran, 1964, et al. (författare)
  • Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS.
  • 2023
  • Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 373, s. 46-54
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS).The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p<0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women.Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.
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  • Bivehed, Erik, et al. (författare)
  • Flash-comet : Significantly improved speed and sensitivity of the comet assay through the introduction of lithium-based solutions and a more gentle lysis
  • 2020
  • Ingår i: Mutation research. Genetic toxicology and environmental mutagenesis. - : ELSEVIER. - 1383-5718 .- 1879-3592. ; 858
  • Tidskriftsartikel (refereegranskat)abstract
    • Evaluation of primary DNA-damage is one way to identify potential genotoxic agents and for this purpose the Comet assay has, for the last decades, been used to monitor DNA single strand and double strand breaks in individual cells. Various attempts have been made to modify the different steps in the in vitro protocol for the Comet assay in order to improve its sensitivity. However, to the best of our knowledge, nobody has tried to replace the traditionally used NaOH-based electrophoresis solution (pH > 13), with another type of solution. In the present paper, using TK-6 cells exposed to different concentrations of H2O2 or ionizing radiation, we present evidence clearly showing that a low-conductive LiOH-based electrophoresis solution at pH 12.5, and a more gentle lysis procedure, significantly improved both the speed and sensitivity of the assay. The new approach, which we call the Flash-comet, is based on a lysis buffer at pH 8.5, an unwinding time of 2.5 min in a LiOH solution without EDTA at pH 12.5, and an electrophoresis time of 1 min at 150 V (5 V/cm) using the same solution.
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  • Bivehed, Erik, et al. (författare)
  • Visualizing DNA single- and double-strand breaks in the Flash comet assay by DNA polymerase-assisted end-labelling
  • 2024
  • Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 52:4
  • Tidskriftsartikel (refereegranskat)abstract
    • In the comet assay, tails are formed after single-cell gel electrophoresis if the cells have been exposed to genotoxic agents. These tails include a mixture of both DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). However, these two types of strand breaks cannot be distinguished using comet assay protocols with conventional DNA stains. Since DSBs are more problematic for the cells, it would be useful if the SSBs and DSBs could be differentially identified in the same comet. In order to be able to distinguish between SSBs and DSBs, we designed a protocol for polymerase-assisted DNA damage analysis (PADDA) to be used in combination with the Flash comet protocol, or on fixed cells. By using DNA polymerase I to label SSBs and terminal deoxynucleotidyl transferase to label DSBs with fluorophore-labelled nucleotides. Herein, TK6-cells or HaCat cells were exposed to either hydrogen peroxide (H2O2), ionising radiation (X-rays) or DNA cutting enzymes, and then subjected to a comet protocol followed by PADDA. PADDA offers a wider detection range, unveiling previously undetected DNA strand breaks. Graphical Abstract
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  • Cornelis, Marilyn C, et al. (författare)
  • Targeted proteomic analysis of habitual coffee consumption
  • 2018
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 283:2, s. 200-211
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health.OBJECTIVE: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n=816) and followed-up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n=635) and EpiHealth (n=2418).METHODS: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records while a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay.RESULTS: Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR<5%, P<2.31×10(-3) ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), Tumor necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, -0.042 SD per cup of coffee, P=0.028) and EpiHealth (β, -0.025 SD per time of coffee, P=0.004). The negative coffee-CHI3L association replicated in EpiHealth (β, -0.07, P=1.15×10(-7) ), but not in ULSAM (β, -0.034, P=0.16).CONCLUSIONS: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee. 
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  • Dalin, Frida, 1984-, et al. (författare)
  • Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
  • 2017
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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  • Dieterich, Lothar C., et al. (författare)
  • Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGFβ2 in vascular abnormalization
  • 2012
  • Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 228:3, s. 378-390
  • Tidskriftsartikel (refereegranskat)abstract
    • Glioblastoma are aggressive astrocytic brain tumours characterized by microvascular proliferation and an abnormal vasculature, giving rise to brain oedema and increased patient morbidity. Here, we have characterized the transcriptome of tumour-associated blood vessels and describe a gene signature clearly associated with pleomorphic, pathologically altered vessels in human glioblastoma (grade IV glioma). We identified 95 genes differentially expressed in glioblastoma vessels, while no significant differences in gene expression were detected between vessels in non-malignant brain and grade II glioma. Differential vascular expression of ANGPT2, CD93, ESM1, ELTD1, FILIP1L and TENC1 in human glioblastoma was validated by immunohistochemistry, using a tissue microarray. Through qPCR analysis of gene induction in primary endothelial cells, we provide evidence that increased VEGF-A and TGFβ2 signalling in the tumour microenvironment is sufficient to invoke many of the changes in gene expression noted in glioblastoma vessels. Notably, we found an enrichment of Smad target genes within the distinct gene signature of glioblastoma vessels and a significant increase of Smad signalling complexes in the vasculature of human glioblastoma in situ. This indicates a key role of TGFβ signalling in regulating vascular phenotype and suggests that, in addition to VEGF-A, TGFβ2 may represent a new target for vascular normalization therapy.
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  • Dzabic, Mensur, et al. (författare)
  • Intragraft Cytomegalovirus Protein Expression Is Associated With Reduced Renal Allograft Survival
  • 2011
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 53:10, s. 969-976
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cytomegalovirus (CMV) infection is a risk factor for acute and chronic rejection of transplanted organs and is thought to mediate rejection indirectly. Methods: In this retrospective observational cohort study, early- and end-stage biopsies from renal allografts lost because of chronic allograft dysfunction (n = 29) were examined for CMV antigens and DNA using immunohistochemistry, in situ hybridization, and real-time polymerase chain reaction. Results: CMV immediate-early and late proteins were present in 27 (93%) of 29 of the end-stage chronic allograft dysfunction biopsies and in 64% of the corresponding early biopsies but not in pretransplant biopsies from CMV-seronegative donors (n = 3). Graft survival time was reduced in patients with moderate or high CMV levels in the graft soon after transplantation compared with that in patients with no or low CMV levels in the graft. No significant difference was observed in serum creatinine obtained at the time of early biopsies. Conclusions: We provide evidence that intragraft CMV protein expression is associated with end-stage chronic renal allograft dysfunction, that intragraft CMV levels increase as graft function deteriorates, and that CMV protein expression in the grafts soon after transplant is associated with reduced graft survival. Thus, CMV may have a pathological role in chronic renal allograft dysfunction.
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21.
  • Einarsdottir, Berglind Osk, 1979, et al. (författare)
  • A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
  • 2018
  • Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
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22.
  • Engström, Gunnar, et al. (författare)
  • Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
  • 2024
  • Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
  • Tidskriftsartikel (refereegranskat)abstract
    • Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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23.
  • Engström, Gunnar, et al. (författare)
  • The Swedish CArdioPulmonary BioImage Study : objectives and design
  • 2015
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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24.
  • Forsell, Erik, et al. (författare)
  • Internet delivered cognitive behavior therapy for antenatal depression : A randomised controlled trial
  • 2017
  • Ingår i: Journal of Affective Disorders. - Amsterdam, Netherlands : Elsevier. - 0165-0327 .- 1573-2517. ; 221, s. 56-64
  • Tidskriftsartikel (refereegranskat)abstract
    • Major depression occurs in 5-10% of pregnancies and is associated with many negative effects for mother and child, yet treatment options are scarce. To our knowledge, this is the first published randomised controlled trial on Internet delivered Cognitive Behavior Therapy (ICBT) for this group.Objective: To test the efficacy of a pregnancy adapted version of an existing 10-week ICBT-program for depression as well as assessing acceptability and adherence.Design: Randomised controlled trial.Setting: Online and telephone.Population or sample: Self-referred pregnant women (gestational week 10-28 at intake) currently suffering from major depressive disorder.Methods: 42 pregnant women (gestational week 12-28) with major depression were randomised to either treatment as usual (TAU) provided at their antenatal clinic or to ICBT as an add-on to usual care.Main outcome measures: The primary outcome was depressive symptoms measured with the Montgomery-Asberg depression rating scale-self report (MADRS-S). The Edinburgh Postnatal Depression Scale and measures of anxiety and sleep were used. Credibility, satisfaction, adherence and utilization were also assessed.Results: The ICBT group had significantly lower levels of depressive symptoms post treatment (p < 0.001, Hedges g = 1.21) and were more likely to be responders (i.e. achieve a statistically reliable improvement) (RR = 0.36; p = 0.004). Measures of treatment credibility, satisfaction, utilization, and adherence were comparable to implemented ICBT for depression.Limitations: Small sample size and no long-term evaluation.Conclusion: Pregnancy adapted ICBT for antenatal depression is feasible, acceptable and efficacious. These results need to be replicated in larger trials to validate these promising findings.
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26.
  • Gkanatsiou, Eleni, et al. (författare)
  • Characterization of monomeric and soluble aggregated Aβ in Down's syndrome and Alzheimer's disease brains.
  • 2021
  • Ingår i: Neuroscience letters. - : Elsevier BV. - 1872-7972 .- 0304-3940. ; 754
  • Tidskriftsartikel (refereegranskat)abstract
    • The major characteristics of Alzheimer's disease (AD) are amyloid plaques, consisting of aggregated beta amyloid (Aβ) peptides, together with tau pathology (tangles, neuropil treads and dystrophic neurites surrounding the plaques), in the brain. Down's syndrome (DS) individuals are at increased risk to develop AD-type pathology; most DS individuals have developed substantial pathology already at the age of 40. DS individuals have an extra copy of chromosome 21, harbouring the amyloid precursor protein gene (APP). Our aim was to investigate the Aβ peptide pattern in DS and AD brains to investigate differences in their amyloid deposition and aggregation, respectively. Cortical tissue from patients with DS (with amyloid pathology), sporadic AD and controls were homogenized and fractionated into TBS (water soluble) and formic acid (water insoluble) fractions. Immunoprecipitation (IP) was performed using a variety of antibodies targeting different Aβ species including oligomeric Aβ. Mass spectrometry was then used to evaluate the presence of Aβ species in the different patient groups. A large number of Aβ peptides were identified including Aβ1-X, 2-X, 3-X, 4-X, 5-X, 11-X, and Aβ peptides extended N terminally of the BACE1 cleavage site and ending at amino 15 in the Aβ sequence APP/Aβ(-X to 15), as well as peptides post-translationally modified by pyroglutamate formation. Most Aβ peptides had higher abundance in AD and DS compared to controls, except the APP/Aβ(-X to 15) peptides which were most abundant in DS followed by controls and AD. Furthermore, the abundancies of AβX-40 and AβX-34 were increased in DS compared with AD. Aβ1-40, Aβ1-42, and Aβ4-42 were identified as the main constitutes of protofibrils (IP'd using mAb158) and higher relative Aβ1-42 signals were obtained compared with samples IP'd with 6E10+4G8, indicating that the protofibrils/oligomers were enriched with peptides ending at amino acid 42. All Aβ peptides found in AD were also present in DS indicating similar pathways of Aβ peptide production, degradation and accumulation, except for APP/Aβ(-X to 15). Likewise, the Aβ peptides forming protofibrils/oligomers in both AD and DS were similar, implying the possibility that treatment with clinical benefit in sporadic AD might also be beneficial for subjects with DS.
  •  
27.
  • Gredmark-Russ, Sara, et al. (författare)
  • Active cytomegalovirus infection in aortic smooth muscle cells from patients with abdominal aortic aneurysm
  • 2009
  • Ingår i: Journal of Molecular Medicine. - : Springer Science and Business Media LLC. - 0946-2716 .- 1432-1440. ; 87:4, s. 347-356
  • Tidskriftsartikel (refereegranskat)abstract
    • Cytomegalovirus (CMV) is associated with atherosclerosis and transplant vascular sclerosis. The aim of this study was to explore the hypothesis that active CMV infection in the vessel wall could be associated with abdominal aortic aneurysm (AAA). We examined the prevalence of CMV in AAA specimens from 22 patients undergoing surgery and, in five cases, characterized the function of smooth muscle cells (SMCs) from the aneurysm in vitro. Twenty-one (95%) of the 22 AAA specimens were CMV positive by a polymerase chain reaction assay, in situ hybridization, or a highly sensitive immunohistochemical staining technique. No positive cells were found in aortas from three CMV-seronegative organ donor cadavers. CMV immediate-early and late antigens were expressed in SMCs in the lesions and were associated with 5-lipoxygenase (5-LO) expression. CMV-positive intimal SMCs migrated 6.6 +/- 1.5 times more efficiently than CMV-negative medial SMCs (p < 0.05). In vitro CMV infection of medial SMCs resulted in a 3.2 +/- 1.2 times increase in migration (p < 0.05). The intimal migration was significantly inhibited by antibodies against basic fibroblast growth factor (bFGF; p < 0.05) in a dose-dependent fashion. Antibodies against platelet-derived growth factor (PDGF)-AB, insulin-like growth factor 1, vascular endothelial growth factor (VEGF), RANTES, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha, or interleukin-1beta did not significantly affect intimal SMC migration. However, intimal and medial SMCs secreted similar amounts of bFGF, MCP-1, MIP-1alpha, RANTES, PDGF-AB, PDGF-BB, epidermal growth factor, and VEGF. CMV infection in vitro of intimal and medial cells did not result in significant changes of bFGF or MCP-1 secretion. Since CMV infection can affect several functional parameters in SMCs, including several key factors in infected SMCs, our findings provide support for the hypothesis that CMV contributes to the pathogenesis of abdominal aortic aneurysm.
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28.
  • Gustafsson, Stefan, et al. (författare)
  • Adiponectin and cardiac geometry and function in elderly : results from two community-based cohort studies
  • 2010
  • Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 162:3, s. 543-550
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Several smaller studies have indicated that adiponectin might be associated with left ventricular (LV) mass and function, but community-based studies with adequate sample size and adjustment for potential confounders are lacking. Our objective was to investigate such associations in two large community-based studies of elderly. DESIGN: Cross-sectional. METHODS: We evaluated cross-sectional relations between serum adiponectin and echocardiographic measures of cardiac geometry and function (LV mass index, LV relative wall thickness, LV end-diastolic diameter, left atrial diameter, ejection fraction, LV isovolumic relaxation time, and E/A ratio) in 954 70-year-old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), and in 427 71-year-old men from the Uppsala Longitudinal Study of Adult Men (ULSAM). RESULTS: In models adjusted for age, sex, body mass index, systolic blood pressure, antihypertensive treatment, antidiabetic treatment, lipid-lowering medication, fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, creatinine, and smoking, adiponectin was inversely associated with ejection fraction in men (beta, -1.62; 95% confidence interval (CI), -2.50, -0.75 in PIVUS; beta, -1.35; 95% CI, -2.41, -0.29 in ULSAM), but not in women. After additional adjustment for N-terminal pro-brain natriuretic peptide (NT-proBNP), the association between adiponectin and ejection fraction was attenuated (beta, -0.98; 95% CI, -1.86, -0.10 in PIVUS; beta, -0.75; 95% CI, -1.84, 0.35 in ULSAM). CONCLUSIONS: Serum adiponectin concentrations were associated with ejection fraction in men, and these associations were partially attenuated by NT-proBNP. Our results imply that adiponectin may be associated with systolic function through pathways that involve natriuretic peptides.
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29.
  • Gustafsson, Stefan, et al. (författare)
  • Associations of circulating adiponectin with measures of vascular function and morphology
  • 2010
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 95:6, s. 2927-2934
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Some previous studies have reported an association between circulating adiponectin and selected measures of vascular function and morphology, but most of these studies have been performed in small samples of patients with preexisting disease. OBJECTIVE: We aimed to evaluate associations between circulating adiponectin and comprehensive measures of vascular function and morphology in a large sample of individuals from the community. DESIGN, SETTINGS, AND PARTICIPANTS: We conducted a cross-sectional investigation of 981 70-yr-old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). MAIN OUTCOME MEASURES: Measures of outcome included vascular function [common carotid artery (CCA) distensibility, flow-mediated dilation, endothelium-dependent and endothelium-independent vasodilation using invasive methods] and vascular morphology [intima-media (IM) thickness, plaque presence, gray scale median (GSM) in the IM and plaques]. RESULTS: In age- and sex-adjusted models, adiponectin was positively associated with IM-GSM, plaque GSM, CCA distensibility, endothelium-dependent and endothelium-independent vasodilation. In multivariable models (with additional adjustment for body mass index; systolic blood pressure; antihypertensive, antidiabetic, and lipid-lowering medication; fasting blood glucose; total cholesterol; high-density lipoprotein cholesterol; creatinine; and smoking), adiponectin remained positively associated with IM-GSM [beta = 2.06; 95% confidence interval (CI), 0.54, 3.58], plaque GSM (beta = 3.11; 95% CI, 0.36, 5.86), and CCA distensibility (beta = 0.04; 95% CI, 0.00, 0.07). CONCLUSIONS: Serum levels of adiponectin were positively associated with IM-GSM and plaque GSM (indicating lower fat content in the IM and plaques) and CCA distensibility (indicating higher wall elasticity), independent of potential confounders. Our results imply that adiponectin is associated with less arterial pathology.
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30.
  • Gustafsson, Stefan, et al. (författare)
  • Oxidative Stress and Inflammatory Markers in Relation to Circulating Levels of Adiponectin
  • 2013
  • Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 21:7, s. 1467-1473
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Previous epidemiological studies together with animal studies have suggested an association between adiponectin and oxidative stress and inflammation, but community-based studies are lacking. Our objective was to investigate the relative importance of oxidative stress and inflammatory markers, representing different pathways in relation to adiponectin. Design and Methods: In a cross-sectional sample of 929 70-year-old individuals (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors study, relations between serum adiponectin and oxidative stress [conjugated dienes (CD), homocysteine, total antioxidant capacity, oxidized low-density lipoprotein (OxLDL), OxLDL antibodies, baseline CD of LDL, glutathione (GSH), total glutathione (TGSH), glutathione disulfide], circulation interleukins (IL-6, IL-8), other cytokines [tumor necrosis factor alpha, monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor], cell adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, P-selectin, L-selectin), and systemic inflammatory markers [C-reactive protein (CRP), leukocyte count] in separate models were investigated. Results: In age- and sex-adjusted, as well as multivariable-adjusted models, adiponectin was significantly and positively associated with GSH, log TGSH, whereas an inverse association was observed for CD and log EGF. An inverse association between adiponectin and MCP-1, log E-selectin, and log CRP was significant in age- and sex-adjusted models, but not in multivariable-adjusted models. Conclusions: Our results imply that higher levels of adiponectin are associated with a more beneficial oxidative stress profile, with higher levels of principal anti-oxidative GSH and total GSH together with lower levels of lipid peroxidation, possibly through shared pathways. Further studies are needed to investigate whether changes in the oxidative stress profile may be a mechanism linking adiponectin with type 2 diabetes and/or cardiovascular disease.
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31.
  • Hedling, Erik, et al. (författare)
  • Världsberömda filmsvenskar
  • 2005
  • Ingår i: Berömda svenskar: Tusen svenskar under tusen år. - 9197583251
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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32.
  • Henein, Mark, et al. (författare)
  • Left atrial strain rate estimates PCWP
  • 2013
  • Ingår i: International cardiovascular forum. - 2409-3424. ; :1, s. 25-30
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Raised left atrial (LA) pressure is a common pathway for many pathologies and is known for its complications. It has a direct effect on LA cavity size and potentially also its function. We hypothesized that raised LA pressure, as shown by pulmonary capillary wedge pressure (PCWP), correlates with severity of global LA deformation abnormalities during atrial systole (LASRa). DESIGN AND PATIENTS: We prospectively studied 46 consecutive patients, mean age 61 ±13 years, 17 males, of various etiologies who underwent right heart catheterization and simultaneous Doppler echocardiography using spectral, tissue Doppler and speckle tracking echocardiography techniques for assessing LA structure and function. RESULTS: PCWP correlated with direct measurements of LA structure and function: LA volume (r= 0.43, p<0.01) and LASRa (r=0.79, p<0.001). PCWP correlated also with other indirect measures of LA pressure such as E/A (r=0.65, p<0.001), E wave deceleration time (r=0.54, p<0.001), E/e’ (r=0.49, p<0.001) and LA systolic filling fraction (r=0.52, p<0.001). However, LASRa together with LA systolic filling fraction, had the highest areas under the curve (0.83 and 0.87, respectively) for identifying patients with PCWP > 15 mmHg. CONCLUSION: PCWP correlates with LA deformation rate during atrial systole and to a higher extent than conventional Doppler measures of raised LA pressures. These findings should have significant clinical implications in correctly identifying breathless patients due to raised LA pressure.
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33.
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34.
  • Henein, Michael Y., et al. (författare)
  • Can Doppler echocardiography estimate raised pulmonary capillary wedge pressure provoked by passive leg lifting in suspected heart failure?
  • 2019
  • Ingår i: Clinical Physiology and Functional Imaging. - : John Wiley & Sons. - 1475-0961 .- 1475-097X. ; 39:2, s. 128-134
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Non-invasive estimation of left ventricular filling pressure (LVFP) during stress is important for explaining exertional symptoms in patients with heart failure (HF). The aim of this study was to evaluate ability of Doppler echocardiographic measures of elevated LVFP with passive leg lifting (PLL) in patients with suspected HF.METHODS: Twenty-nine patients with clinical signs of HF who underwent simultaneous Doppler echocardiography and right heart catheterization (RHC) at rest and during PLL were consecutively investigated. Seventeen patients had normal PCWP (≤15 mmHg) at rest and during PLL and 12 with normal PCWP at rest but >15 mmHg with PLL. Conventional echo and 2D strain were used to assess early diastolic blood flow velocity (E), LV strain rate during early diastole (LVSRe), left atrial SR during atrial contraction (LASRa) and myocardial tissue Doppler velocities to assess lateral e' and further calculate E/e' and E/LVSRe and their relationship with PCWP, at rest and during PLL.RESULTS: Resting LAVI (β = 0·45, P = 0·009) and LASRa (β = -0·51, P = 0·004) were independently related to PCWP during PLL. Also, LASRa (β = -0·77, P<0·001), E/e' (β = 0·40, P = 0·04) and E/LVSRe (β = 0·47, P = 0·021) during PLL correlated with PCWP during PLL. Multiple regression analysis identified E/LVSRe (β = 0·46, P = 0·001) and LASRa (β = -0·58, P = 0·002) during PLL as being independently associated with PCWP during PLL.CONCLUSION: Left atrial volume and myocardial contraction (LASRa) at rest both predict unstable LV filling pressures measured as raised PCWP when provoked by PLL. Furthermore, LASRa at PLL seems to have the strongest association to PCWP during PLL.
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35.
  • Henein, Michael Y, et al. (författare)
  • Right and left heart dysfunction predict mortality in pulmonary hypertension
  • 2017
  • Ingår i: Clinical Physiology and Functional Imaging. - : Wiley-Blackwell. - 1475-0961 .- 1475-097X. ; 37:1, s. 45-51
  • Tidskriftsartikel (refereegranskat)abstract
    • In pulmonary hypertension (PH), the right heart dysfunction is a strong predictor of adverse clinical outcome, while the role of the left heart is not fully determined. The aim of this study was to identify predictors of mortality in precapillary PH including measures of both right and left heart function. We studied 34 patients (mean age 64 ± 13, range 31-82 years, 24 females) with precapillary PH, all of whom underwent detailed Doppler echocardiographic examination of the right and left heart function using conventional and speckle-tracking echocardiography. Patients were followed up for up to 8 years (mean 4·2 ± 1·9 years). At follow-up, 16 patients survived. Left ventricular (LV) filling time (P = 0·007), pulmonary artery acceleration time (P = 0·009), right atrial pressure (RAP) (P<0·001) and tricuspid regurgitation (TR) severity (P = 0·007) were worse in the deceased group. RV global longitudinal strain (GLS) (P = 0·001), RAP (P≤0·001), LV filling time (P<0·001) and TR severity (P<0·001) were the most accurate predictors, having the largest AUC (>0·65) and carried the highest risk for mortality (P<0·001 for all). The strongest predictors of mortality in precapillary PH indirectly reflect both left and right heart dysfunction including atrial structure and function disturbances. While an interaction pattern is observed, it needs to be confirmed in a larger cohort.
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36.
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37.
  • Hulander, Erik, et al. (författare)
  • Patients with radiographic axial spondylarthritis have an impaired dietary intake-a cross-sectional study with matched controls from northern Sweden.
  • 2023
  • Ingår i: Arthritis research & therapy. - : BioMed Central (BMC). - 1478-6362. ; 25:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Radiographic axial spondyloarthritis (r-axSpA) is one of the most common chronic inflammatory rheumatic diseases, affecting about 0.2% of the Swedish population. Adequate nutritional intake is essential for maintaining physiological functions. A poor diet increases the risk of developing conditions such as obesity, osteoporosis, and/or atherosclerosis. Diet quality is also theorized to affect systemic inflammation. Dietary habits in patients with r-axSpA are largely unknown. The aims of this study were to assess dietary nutrient intake in r-axSpA patients and examine whether it differs compared to persons without r-axSpA.r-axSpA patients (modified NY criteria) at the rheumatology clinic in Region Västerbotten, northern Sweden, were invited to take part in the Backbone study which investigates disease severity and comorbidities. In total, 155 patients were included. Nutritional intake was assessed by the semi-quantitative food frequency questionnaire MiniMeal-Q. Controls were collected from the Swedish CArdioPulmonary bioImage Study (n=30,154), a study that invited participants 50-64years of age by random selection from the Swedish population register. Out of the 155 r-axSpA patients, 81 were in the same age span. Four controls were identified for each patient, matched on age (±1year), sex, and geographic location. Data on dietary intake was available for 319 controls. Statistical comparisons of dietary intake between patients with r-axSpA and controls were done by exact conditional logistic regression analysis, adjusted for country of birth, educational level, single household, weight, smoking status, and energy intake.Patients had a comparatively significantly higher energy intake from carbohydrates, a lower fiber density, and a lower intake of marine omega-3 fatty acids. Furthermore, intake of vitamins D, E, and K as well as selenium, folate, calcium, magnesium, phosphorus, potassium, vitamin A, and β-carotene (a precursor of vitamin A and marker of vegetable and fruit intake) was significantly lower among patients compared to controls.Our results suggest that r-axSpA patients have an impaired dietary intake. Notably, intake was lower in several nutrients theorized to have anti-inflammatory properties (fiber density, marine-omega-3 fatty acids, vitamin D, and selenium). We further propose that nutrition screening might be incorporated into the management of r-axSpA patients.
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38.
  • Jason, Johan, et al. (författare)
  • Fiber-Optic Temperature Monitoring in Pulp Production
  • 2008
  • Ingår i: Transactions of the IWCS. - Eatontown, NJ : International Wire & Cable Symposium. ; , s. 7-16
  • Konferensbidrag (refereegranskat)abstract
    • A fiber-optic temperature sensor system for monitoring of the cooking process in pulp production has been developed. The sensor system is based on intensity modulation in mechanical fiber connections caused by the temperature dependent deflection of a bimetal strip. The sensor construction includes a fiber positioning device which eliminates the poor coupling efficiency otherwise experienced with coupling based sensors. An OTDR-based control unit monitors the changes in optical power at the sensor points, and the sensor network is realized with blown fiber. The total system is thus a very cost-effective solution. In this paper the development, testing, installation and operation of the sensor system is reported on, showing the system to be suitable for cooking process temperature monitoring.
  •  
39.
  • Jason, Johan, et al. (författare)
  • Fiber-Optic Temperature Monitoring in Pulp Production
  • 2006
  • Ingår i: Proceedings of the 55th IWCS/Focus Conference. - Eatontown, NJ : International Wire & Cable Symposium. ; , s. 41-49
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • A fiber-optic temperature sensor system has been developed and implemented in the monitoring of the cooking process in pulp production. The sensor system is based on intensity modulation in mechanical multimode fiber connections caused by the temperature dependent deflection of a bimetal strip. OTDR technology is used for monitoring the changes in optical power at the sensor points in the network, and a computer system takes care of calibration curves and the power-to-temperature conversion. Fiber segments between the sensor points and the control unit are realized with blown fiber. In this paper, the development and testing of the temperature monitoring system is reported on. Sensor performance, data readout, installation issues and measurement results are discussed. The system is shown to meet the requirements on precision and response time and to be a useful tool for the monitoring of the cooking process.
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40.
  • Johansson, Nils, et al. (författare)
  • Möjlighet till utrymning vid brand
  • 2012
  • Ingår i: Brandskyddshandboken - En handbok för projektering av brandskydd i byggnader. - 1402-3504. ; , s. 75-116
  • Bokkapitel (refereegranskat)
  •  
41.
  • Kain, Jaan-Henrik, 1960, et al. (författare)
  • Integration of complex knowledge
  • 2006
  • Ingår i: Malmqvist, Per-Arne et al (Eds.), Strategic Planning of Sustainable Urban Water Management; IWA Publishing: London.
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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42.
  •  
43.
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44.
  • Kain, Jaan-Henrik, 1960, et al. (författare)
  • Multi-Criteria Decision Aids for Sustainable Water Management
  • 2007
  • Ingår i: Proceedings of the Institution of Civil Engineers: Engineering Sustainability. - 1478-4629 .- 1751-7680. ; 160:2, s. 87-93
  • Tidskriftsartikel (refereegranskat)abstract
    • This article evaluates three multi-criteria decision aid (MCDA) methods—Regime, Novel Approach to Imprecise Assessment and Decision Environments (Naiade) and Strategic Advisor (Strad)—from a process facilitation perspective. This research shows that Strad has many advantages over the other tools regarding knowledge management, pluralism, functionality, transparency and participation. Concluding recommendations are as follows. (1) Agree explicit aims with stakeholder participation and if the aims change during the process, this is to be communicated. (2) Match methodology with the aims of the process since it is not always necessary to base the ranking on complex mathematical calculations. (3) Participatory processes should be conducted with care as they are resource consuming. Select cases thoughtfully and design them with a reflective attitude. The systematic structure of going through one criterion at a time is perceived as more important than software aggregation of multiple criteria at the end. It was further concluded that MCDAs have to be transparent and software must be flexible with an understandable user interface.
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45.
  • Kermpatsou, Despoina, et al. (författare)
  • Cellular responses to silencing of PDIA3 (protein disulphide-isomerase A3) : Effects on proliferation, migration, and genes in control of active vitamin D
  • 2024
  • Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier. - 0960-0760 .- 1879-1220. ; 240
  • Tidskriftsartikel (refereegranskat)abstract
    • The active form of vitamin D, 1,25-dihydroxyvitamin D3, is known to act via VDR (vitamin D receptor), affecting several physiological processes. In addition, PDIA3 (protein disulphide-isomerase A3) has been associated with some of the functions of 1,25-dihydroxyvitamin D3. In the present study we used siRNA-mediated silencing of PDIA3 in osteosarcoma and prostate carcinoma cell lines to examine the role(s) of PDIA3 for 1,25-dihydroxyvitamin D3-dependent responses. PDIA3 silencing affected VDR target genes and significantly altered the 1,25-dihydroxyvitamin D3-dependent induction of CYP24A1, essential for elimination of excess 1,25-dihydroxyvitamin D3. Also, PDIA3 silencing significantly altered migration and proliferation in prostate PC3 cells, independently of 1,25-dihydroxyvitamin D3. 1,25-Dihydroxyvitamin D3 increased thermostability of PDIA3 in cellular thermal shift assay, supporting functional interaction between PDIA3 and 1,25-dihydroxyvitamin D3-dependent pathways. In summary, our data link PDIA3 to 1,25-dihydroxyvitamin D3-mediated signalling, underline and extend its role in proliferation and reveal a novel function in maintenance of 1,25-dihydroxyvitamin D3 levels.
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46.
  • Kermpatsou, Despoina, et al. (författare)
  • Silencing of 1,25D3-MARRS (membrane-associated, rapid response steroid-binding) receptor in prostate cancer cell lines PC3 and DU145: effects on cellular responses
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • 1,25(OH)2-vitamin D3 has well-documented roles in a variety of cellular processes, including proliferation and differentiation. 1,25(OH)2-vitamin D3 signalling is largely mediated by vitamin D receptor (VDR), however, 1,25D3-MARRS (membrane-associated, rapid response steroid-binding) receptor has been investigated as a potential transducer of 1,25(OH)2-vitamin D3 membrane-initiated response. In this work we aimed to study the role of 1,25D3-MARRS in androgen-independent prostate carcinoma cell lines PC3 and DU145. Protein lysates from an array of cell lines were enriched for cytoplasmic and nuclear protein pools, in order to investigate the subcellular localisation of 1,25D3-MARRS and VDR. Further, we studied the effects of siRNA-mediated 1,25D3-MARRS depletion on cell proliferation and migration, as well as on gene expression of 1,25(OH)2-vitamin D3 metabolising enzymes and other genes of importance for 1,25(OH)2-vitamin D3-mediated signalling. The results of the present study indicate that depletion of 1,25D3-MARRS decreases proliferation in PC3 and DU145 prostate cancer cell lines, potentially via downregulation of c-Myc. 1,25D3-MARRS silencing also increased migration in PC3 cells, but not in DU145 cells, suggesting differential effects in different prostate cancer cell lines. In addition, significant effects of 1,25D3-MARRS silencing were found on CYP27B1 and CYP24A1, enzymes responsible for the regulation of cellular levels of 1,25(OH)2-vitamin D3. In summary, our data indicate that 1,25D3-MARRS can affect proliferation and/or migration in androgen-independent prostate cancer cells and may play a role for regulation and maintenance of adequate cellular 1,25(OH)2-vitamin D3 levels, either together with or independently of VDR.
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47.
  • Kjellström, Barbro, et al. (författare)
  • Five year risk assessment and treatment patterns in patients with chronic thromboembolic pulmonary hypertension
  • 2022
  • Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 9:5, s. 3264-3274
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Repeated risk assessments and treatment patterns over long time are sparsely studied in chronic thromboembolic pulmonary hypertension (CTEPH); thus, we aimed to investigate changes in risk status and treatment patterns in incident patients with CTEPH over a 5 year period.Methods and results: Descriptive and explorative study including 311 patients diagnosed with CTEPH 2008–2019 from the Swedish pulmonary hypertension registry, stratified by pulmonary endarterectomy surgery (PEA). Risk and PH-specific treatment were assessed in surgically treated (PEA) and medically treated (non-PEA) patients at diagnosis and up to 5 years follow-up. Data are presented as median (Q1–Q3), count or per cent. Prior to surgery, 63% in the PEA-group [n = 98, age 64 (51–71) years, 37% female] used PH-specific treatment and 20, 69, and 10% were assessed as low, intermediate or high risk, respectively. After 1 year post-surgery, 34% had no PH-specific treatment or follow-up visit registered despite being alive at 5 years. Of patients with a 5 year visit (n = 23), 46% were at low and 54% at intermediate risk, while 91% used PH-specific treatment. In the non-PEA group [n = 213, age 72 (65–77) years, 56% female], 28% were assessed as low, 61% as intermediate and 11% as high risk. All patients at high risk versus 50% at low risk used PH-specific treatment. The 1 year mortality was 6%, while the risk was unchanged in 57% of the patients; 14% improved from intermediate to low risk, and 1% from high to low risk. At 5 years, 27% had a registered visit and 28% had died. Of patients with a 5 year visit (n = 58), 38% were at low, 59% at intermediate and 1% at high risk, and 86% used PH-specific treatment.Conclusions: Risk status assessed pre-surgery did not foresee long-term post-PEA risk and pre-surgery PH-specific treatment did not foresee long-term post-PEA treatment. Medically treated CTEPH patients tend to remain at the same risk over time, suggesting a need for improved treatment strategies in this group.
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48.
  • Klingström, Tomas, et al. (författare)
  • Supporting the Development of Biobanks in Low and Medium Income Countries
  • 2016
  • Ingår i: 2016 IST-AFRICA WEEK CONFERENCE. - 9781905824557
  • Konferensbidrag (refereegranskat)abstract
    • Biobanks are an organized collection of biological material and associated data. They are a fundamental resource for life science research and contribute to the development of pharmaceutical drugs, diagnostic markers and to a deeper understanding of the genetics that regulate the development of all life on earth. Biobanks are well established in High Income Countries (HIC) and are rapidly emerging in Low and Middle Income Countries (LMIC). Surveys among biobanks operating in a LMIC setting indicate that limited resources and short term funding tied to specific projects threaten the sustainability of the biobanks. Fit-for-purpose biobanks targeting major societal challenges such as HIV and Malaria provide an excellent basis for integrating biobanks with the available research communities in LMIC regions. But to become sustainable for the future it is important that biobanks become an integrated part of local research communities. To achieve this, the cost of operating biobanks must be lowered, templates must be developed to support local ethics committees and researchers must be given the opportunity to build experience in successfully operating biobank based research projects. The B3Africa consortium is based on these conclusions and set up to support biobank based research by creating a cost efficient Laboratory Information Management System (LIMS) for developing biobanks and also contribute to the training and capacity building in the local research community. The technical platform called the eB3Kit is open source and consists of a LIMS and a bioinformatics module based on the eBiokit that allow researchers to take control over the analysis of their own data. Along with the technical platform the consortium will also contribute training and support for the associated infrastructures necessary to regulate the ethical and legal implications of biobank based research.
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49.
  • Kronschläger, Martin, et al. (författare)
  • Pharmacokinetics for topically applied caffeine in the rat
  • 2014
  • Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835 .- 1096-0007. ; 122, s. 94-101
  • Tidskriftsartikel (refereegranskat)abstract
    • Topically applied caffeine was recently identified as a promising candidate molecule for cataract prevention. Little is known about the pharmacokinetics for topically applied caffeine. Potential toxicity of 72 mM caffeine on the ocular surface and the lens was qualitatively monitored and no toxic effects were observed. The concentration of caffeine was measured in the lens and the blood after topical application of 72 mM caffeine to groups of 10 animals sacrificed at 30, 60, 90 and 120 min after topical application. The lens concentration decreased throughout the observation period while the blood concentration increased up to 120 min. Further, the concentration of caffeine in the lens and blood was measured 30 min after topical application of caffeine, the concentration of caffeine being 0.72, 3.34, 15.51 and 72 mM depending on group belonging, in groups of 10 animals. The caffeine concentration in lens and blood, respectively, increased proportionally to the caffeine concentration topically applied. The rat blood concentrations achieved were far below the equivalent threshold dose of FDA recommended daily dose for humans. This information is important for further development of caffeine eye drops for cataract prevention.
  •  
50.
  • Larsson, Erik, et al. (författare)
  • INTERNET OF THINGS AS A COMPLEMENT TO INCREASE SAFETY
  • 2020
  • Ingår i: Journal of the Belarusian State University. International Relations. - 2521-6848. ; 2020:1, s. 88-93
  • Tidskriftsartikel (refereegranskat)abstract
    • Safety evaluations made in the city Helsingborg indicate a decreased risk of being exposed to crime, but an increased feeling of unsafe. Damage in the form of scribbling (graffiti) is one of several indicators contributing to feeling unsafe. In this paper we investigate whether the use of Internet­-of-­things technology, where a sensor monitors a walking and cycling tunnel, makes it possible to reduce scribbling. The study shows a number of interesting results. When the sensor was in­ stalled, the public showed a great and positive interest. A short time after installation, the sensor was subjected to a qua­lified attack where heavy shocks were followed by an initiated way to determine if the sensor was damaged. A setting and tuning phase was used to empirically test different settings of the sensor to detect scribbling behavior. However, it became evident during the approximately 6­month long measurement period that we received many false alarms, which were, for example, that people took shelter in the tunnel in the rain and stood or walked slowly when using their mobile phone. Du­ ring the measurement period, two scribbles occurred where the sensor detected one of them. We observe that the amount of scribbling has decreased significantly. The number of error reports on scribbling dropped from an average of 3.33 per month before the sensor was in place to 0.75 cases per month after the sensor was in place.
  •  
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