umu.sePublications
Change search
Refine search result
91011121314 551 - 600 of 665
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 551.
    Strömvall, Kerstin
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundholm, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Thysell, Elin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Highly aggressive rat prostate tumors rapidly precondition regional lymph nodes for subsequent metastatic growth2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 10, article id e0187086Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to examine in what ways MatLyLu (MLL) rat prostate tumors with high metastatic capacity influence regional lymph nodes prior to metastatic establishment compared to AT1 rat prostate tumors with low metastatic potential. MLL or AT1 tumor cells were injected into the ventral prostate of immunocompetent rats. Tumor and lymph node morphology, and lymph node mRNA expression of macrophage associated markers, T-cell associated markers, and cytokines were examined over time until the first microscopic signs of metastases (at day 14 for MLL- and at day 28 for AT1-tumors). Already at day 3 after tumor cell injection, when the tumors were extremely small and occupied less than 1% of the prostate volume, MLL- and AT1-tumors provoked different immune responses in both the prostate and the regional lymph nodes. MLL-tumors induced expression of immunosuppressive cytokines, suppressed T-cell accumulation, and directed T-cells towards an immunosuppressive phenotype. AT1-tumors caused a response more similar to that in vehicle-injected animals, with accumulation of T-cells in tumors and regional lymph nodes. Prostate tumors with high metastatic potential were able to precondition regional lymph nodes to subsequent metastatic growth in ways different from tumors with less metastatic potential. This may indicate the existence of a time-window when pre-metastatic changes in regional lymph nodes can aid in the prognostication of locally aggressive and potentially metastatic prostate cancer.

  • 552.
    Strömvall, Kerstin
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Thysell, Elin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Aggressive rat prostate tumors reprogram the benign parts of the prostate and regional lymph nodes prior to metastasis2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0176679Article in journal (Refereed)
    Abstract [en]

    In order to grow and spread tumors need to interact with adjacent tissues. We therefore hypothesized that small but aggressive prostate cancers influence the rest of the prostate and regional lymph nodes differently than tumors that are more indolent. Poorly metastatic (Dunning AT1) or highly metastatic (Dunning MLL) rat prostate tumor cells were injected into the ventral prostate lobe of immunocompetent rats. After 10 days-when the tumors occupied about 30% of the prostate lobe and lymph node metastases were undetectable- the global gene expression in tumors, benign parts of the prostate, and regional iliac lymph nodes were examined to define tumor-induced changes related to preparation for future metastasis. The tumors induced profound effects on the gene expression profiles in the benign parts of the prostate and these were strikingly different in the two tumor models. Gene ontology enrichment analysis suggested that tumors with high metastatic capacity were more successful than less metastatic tumors in inducing tumor-promoting changes and suppressing anti-tumor immune responses in the entire prostate. Some of these differences such as altered angiogenesis, nerve density, accumulation of T-cells and macrophages were verified by immunohistochemistry. Gene expression alterations in the regional lymph nodes suggested decreased quantity and activation of immune cells in MLL-lymph nodes that were also verified by immunostaining. In summary, even when small highly metastatic prostate tumors can affect the entire tumor-bearing organ and pre-metastatic lymph nodes differently than less metastatic tumors. When the kinetics of these extratumoral influences (by us named TINT = tumor instructed normal tissue) are more precisely defined they could potentially be used as markers of disease aggressiveness and become therapeutic targets.

  • 553.
    Suhr, Ole Bernt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lundgren, Hans-Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wijayatunga, Priyantha
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Westermark, Per
    Ihse, Elisabet
    Amyloid fibril composition within hereditary Val30Met (p. Val50Met) transthyretin amyloidosis families2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 2, article id e0211983Article in journal (Refereed)
    Abstract [en]

    Background: The amyloid fibril in hereditary transthyretin (TTR) Val30Met (pVal50Met) amyloid (ATTR Val30Met) amyloidosis is composed of either a mixture of full-length and TTR fragments (Type A) or of only full-length TTR (Type B). The type of amyloid fibril exerts an impact on the phenotype of the disease, and on the outcome of diagnostic procedures and therapy. The aim of the present study was to investigate if the type of amyloid fibril remains the same within ATTR Val30Met amyloidosis families. Methods: Fifteen families were identified in whom at least two first-degree relatives had their amyloid fibril composition determined. The type of ATTR was determined by Western blot in all but two patients. For these two patients a positive 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy indicated ATTR Type A. Results: In 14 of the 15 families, the same amyloid fibril composition was noted irrespective of differences in age at onset. In the one family, different ATTR fibril types was found in two brothers with similar ages at onset. Conclusions: Family predisposition appears to have an impact on amyloid fibril composition in members of the family irrespective of their age at onset of disease, but if genetically determined, the gene/genes are likely to be situated at another location than the TTR gene in the genome.

  • 554. Sun, Ruoxing
    et al.
    Kittichotirat, Weerayuth
    Wang, Justin
    Jan, Minnie
    Chen, Weizhen
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Department of Odontology.
    Bumgarner, Roger
    Chen, Casey
    Genomic stability of aggregatibacter actinomycetemcomitans during persistent oral infection in human2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, p. e66472-Article in journal (Refereed)
    Abstract [en]

    The genome of periodontal pathogen Aggregatibacter actinomycetemcomitans exhibits substantial variations in gene content among unrelated strains primarily due to the presence or absence of genomic islands. This study examined the genomic stability of A. actinomycetemcomitans during its persistent infection in the same host. Four pairs of A. actinomycetemcomitans strains, each pair isolated from an individual over time (0-10 years), were examined for their gains/losses of genes by whole genome sequencing, comparative genomic hybridization by microarray and PCR analysis. Possible effects due to genomic changes were further assessed by comparative transcriptome analysis using microarrays. The results showed that each pair of strains was clonally identical based on phylogenetic analysis of 150 core genes. A novel 24.1-Kb plasmid found in strain S23A was apparently lost in the sibling strain I23C. A 353-bp inversion affecting two essential genes of the serotype-specific gene cluster was found in the serotype antigen-nonexpressing strain I23C, while the same gene cluster was intact in the serotype-expressing sibling strain S23A. A 2,293-bp deletion affecting a gene encoding oxaloacetate decarboxylase and its neighbor region was found in strain SCC2302 but not in the sibling strain AAS4a. However, no evidence of gains or losses of genomic islands was found in the paired strains. Transcriptome profiles showed little or no difference in the paired strains. In conclusion, the genome of A. actinomycetemcomitans appears to be relatively stable during short-term infection. Several types of genomic changes were observed in the paired strains of A. actinomycetemcomitans recovered from the same subjects, including a mutation in serotype-specific gene cluster that may allow the bacteria to evade host immune response.

  • 555.
    Sundberg, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Nilsson, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evidence of disseminated intravascular coagulation in a hemorrhagic fever with renal syndrome-scoring models and severe illness2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 6, p. e21134-Article in journal (Refereed)
    Abstract [en]

    Background: Viral hemorrhagic fevers (VHF) are considered to be a serious threat to public health worldwide with up to 100 million cases annually. The general hypothesis is that disseminated intravascular coagulation (DIC) is an important part of the pathogenesis. The study objectives were to study the variability of DIC in consecutive patients with acute hemorrhagic fever with renal syndrome (HFRS), and to evaluate if different established DIC-scores can be used as a prognostic marker for a more severe illness.

    Method and Findings: In a prospective study 2006–2008, data from 106 patients with confirmed HFRS were analyzed and scored for the presence of DIC according to six different templates based on criteria from the International Society on Thrombosis and Haemostasis (ISTH). The DIC-scoring templates with a fibrinogen/CRP-ratio were most predictive, with predictions for moderate/severe illness (p<0.01) and bleeding of moderate/major importance (p<0.05). With these templates, 18.9–28.3% of the patients were diagnosed with DIC.

    Conclusions: DIC was found in about one fourth of the patients and correlated with a more severe disease. This supports that DIC is an important part of the pathogenesis in HFRS.

    ISTH-scores including fibrinogen/CRP-ratio outperform models without. The high negative predictive value could be a valuable tool for the clinician. We also believe that our findings could be relevant for other VHFs.

  • 556. Sundblad, Britt-Marie
    et al.
    Jansson, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Arvidsson, Peter
    Lundbäck, Bo
    Larsson, Kjell
    Chronic Obstructive Pulmonary Disease (COPD) During the Two Last Years of Life: A Retrospective Study of Decedents2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e84110Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Little is known about the management of patients suffering from chronic obstructive pulmonary disease (COPD) during the last years of life. The aim of the study was to describe how management of COPD is performed in Sweden during the last two years of life.

    METHODS: From the nationwide Cause of Death register all individuals with COPD as the underlying cause of death during two years were identified in one sparsely and one densely populated area of Sweden. Data were collected from medical records using a pre-defined protocol, especially developed for this purpose.

    RESULTS: Of 822 individuals with COPD as underlying cause of death, medical records from 729 were available. The COPD diagnosis was based on lung function measurements in approximately half of the patients and median age at COPD diagnosis was 74 years (range 34-95). Women died at younger age, median 78 years (range 52-96) than did men (80 years (51-99)). The median survival time from diagnosis to death was 6 years in men and women in both areas. Among women and men 8.3% and 4.3% were never smokers, respectively. The structure of COPD management differed between the two areas, with utilization of physiotherapists, dieticians and working therapists being more used in the northern area, likely because of differences in accessibility to care institutions.

    CONCLUSIONS: In Sweden COPD is mostly diagnosed late in life and often not verified by lung function measurements. Opposite to the general population, women with COPD die at a lower age than men.

  • 557.
    Sundqvist, Maja K.
    et al.
    Department of Forest Ecology and Management, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Giesler, Reiner
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Wardle, David A
    Department of Forest Ecology and Management, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Within- and across-species responses of plant traits and litter decomposition to elevation across contrasting vegetation types in subarctic tundra2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 10, p. e27056-Article in journal (Refereed)
    Abstract [en]

    Elevational gradients are increasingly recognized as a valuable tool for understanding how community and ecosystem properties respond to climatic factors, but little is known about how plant traits and their effects on ecosystem processes respond to elevation. We studied the response of plant leaf and litter traits, and litter decomposability across a gradient of elevation, and thus temperature, in subarctic tundra in northern Sweden for each of two contrasting vegetation types, heath and meadow, dominated by dwarf shrubs and herbaceous plants respectively. This was done at each of three levels; across species, within individual species, and the plant community using a community weighted average approach. Several leaf and litter traits shifted with increasing elevation in a manner consistent with greater conservation of nutrients at all three levels, and the most consistent response was an increase in tissue N to P ratio. However, litter decomposition was less directly responsive to elevation because the leaf and litter traits which were most responsive to elevation were not necessarily those responsible for driving decomposition. At the community level, the response to elevation of foliar and litter traits, and decomposability, varied greatly among the two vegetation types, highlighting the importance of vegetation type in determining ecological responses to climatic factors such as temperature. Finally our results highlight how understanding the responses of leaf and litter characteristics of functionally distinct vegetation types, and the processes that they drive, to temperature helps provide insights about how future climate change could affect tundra ecosystems.

  • 558. Sundstrom, Karin B.
    et al.
    Hoang, Anh Thu Nguyen
    Gupta, Shawon
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Svensson, Mattias
    Klingstrom, Jonas
    Andes Hantavirus-Infection of a 3D Human Lung Tissue Model Reveals a Late Peak in Progeny Virus Production Followed by Increased Levels of Proinflammatory Cytokines and VEGF-A2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 2, article id e0149354Article in journal (Refereed)
    Abstract [en]

    Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS), a severe acute disease with a 40% case fatality rate. Humans are infected via inhalation, and the lungs are severely affected during HPS, but little is known regarding the effects of ANDV-infection of the lung. Using a 3-dimensional air-exposed organotypic human lung tissue model, we analyzed progeny virus production and cytokine-responses after ANDV-infection. After a 7-10 day period of low progeny virus production, a sudden peak in progeny virus levels was observed during approximately one week. This peak in ANDV-production coincided in time with activation of innate immune responses, as shown by induction of type I and III interferons and ISG56. After the peak in ANDV production a low, but stable, level of ANDV progeny was observed until 39 days after infection. Compared to uninfected models, ANDV caused long-term elevated levels of eotaxin-1, IL-6, IL-8, IP-10, and VEGF-A that peaked 20-25 days after infection, i.e., after the observed peak in progeny virus production. Notably, eotaxin-1 was only detected in supernatants from infected models. In conclusion, these findings suggest that ANDV replication in lung tissue elicits a late proinflammatory immune response with possible long-term effects on the local lung cytokine milieu. The change from an innate to a proinflammatory response might be important for the transition from initial asymptomatic infection to severe clinical disease, HPS.

  • 559.
    Surowiec, Izabella
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ärlestig, Lisbeth
    Rantapää-Dahlqvist, Solbritt
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Metabolite and Lipid Profiling of Biobank Plasma Samples Collected Prior to Onset of Rheumatoid Arthritis2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 10, article id e0164196Article in journal (Refereed)
    Abstract [en]

    Objective: The early diagnosis of rheumatoid arthritis (RA) is desirable to install treatment to prevent disease progression and joint destruction. Autoantibodies and immunological markers pre-date the onset of symptoms by years albeit not all patients will present these factors, even at disease onset. Additional biomarkers would be of high value to improve early diagnosis and understanding of the process, leading to disease development. Methods: Plasma samples donated before the onset of RA were identified in the Biobank of Northern Sweden, a collection within national health survey programs. Thirty samples from pre-symptomatic individuals and nineteen from controls were subjected to liquid chromatography-mass spectrometry (LCMS) metabolite and lipid profiling. Lipid and metabolite profiles discriminating samples from pre-symptomatic individuals from controls were identified after univariate and multivariate OPLS-DA based analyses. Results: The OPLS-DA models including pre-symptomatic individuals and controls identified profiles differentiating between the groups that was characterized by lower levels of acyl-carnitines and fatty acids, with higher levels of lysophospatidylcholines (LPCs) and metabolites from tryptophan metabolism in pre-symptomatic individuals compared with controls. Lipid profiling showed that the majority of phospholipids and sphingomyelins were at higher levels in pre-symptomatic individuals in comparison with controls. Conclusions: Our LCMS based approach demonstrated that there are changes in small molecule and lipid profiles detectable in plasma samples collected from the pre-symptomatic individuals who subsequently developed RA, which point to an up-regulation of levels of lysophospatidylcholines, and of tryptophan metabolism, perturbation of fatty acid beta-oxidation and increased oxidative stress in pre-symptomatic individuals' years before onset of symptoms.

  • 560. Svanes, Oistein
    et al.
    Skorge, Trude Duelien
    Johannessen, Ane
    Bertelsen, Randi Jacobsen
    Bratveit, Magne
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Gislason, Thorarin
    Holm, Mathias
    Janson, Christer
    Joegi, Rain
    Macsali, Ferenc
    Norback, Dan
    Omenaas, Ernst Reidar
    Real, Francisco Gomez
    Schlunssen, Vivi
    Sigsgaard, Torben
    Wieslander, Gunilla
    Zock, Jan-Paul
    Aasen, Tor
    Dratva, Julia
    Svanes, Cecilie
    Respiratory Health in Cleaners in Northern Europe: Is Susceptibility Established in Early Life?2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 7, article id e0131959Article in journal (Refereed)
    Abstract [en]

    Rationale There is some evidence that maternal smoking increases susceptibility to personal smoking's detrimental effects. One might question whether early life disadvantage might influence susceptibility to occupational exposure. Objectives In this cross-sectional study we investigated respiratory symptoms, asthma and self-reported chronic obstructive pulmonary disease (COPD) as related to working as a cleaner in Northern European populations, and whether early life factors influenced susceptibility to occupational cleaning's unhealthy effects. Methods The RHINE III questionnaire study assessed occupational cleaning in 13,499 participants. Associations with respiratory symptoms, asthma and self-reported COPD were analysed with multiple logistic regressions, adjusting for sex, age, smoking, educational level, parent's educational level, BMI and participating centre. Interaction of occupational cleaning with early life disadvantage (maternal smoking, severe respiratory infection < 5 years, born during winter months, maternal age at birth > 35 years) was investigated. Main Results Among 2138 ever-cleaners the risks of wheeze (OR 1.4, 95% CI 1.3-1.6), adult-onset asthma (1.5 [1.2-1.8]) and self-reported COPD (1.7 [1.3-2.2]) were increased. The risk increased with years in occupational cleaning (adult-onset asthma: <= 1 year 0.9 [0.7-1.3]; 1-4 years 1.5 [1.1-2.0]; >= 4 years 1.6 [1.2-2.1]). The association of wheeze with cleaning activity >= 4 years was significantly stronger for those with early life disadvantage than in those without (1.8 [1.5-2.3] vs. 1.3 [0.96-1.8]; pinteraction 0.035). Conclusions Occupational cleaners had increased risk of asthma and self-reported COPD. Respiratory symptom risk was particularly increased in persons with factors suggestive of early life disadvantage. We hypothesize that early life disadvantage may increase airway vulnerability to harmful exposure from cleaning agents later in life.

  • 561. Svefors, Pernilla
    et al.
    Selling, Katarina Ekholm
    Shaheen, Rubina
    Khan, Ashraful Islam
    Persson, Lars-Ake
    Lindholm, Lars
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Cost-effectiveness of prenatal food and micronutrient interventions on under-five mortality and stunting: analysis of data from the MINIMat randomized trial, Bangladesh2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0191260Article in journal (Refereed)
    Abstract [en]

    Introduction Nutrition interventions may have favourable as well as unfavourable effects. The Maternal and Infant Nutrition Interventions in Matlab (MINIMat), with early prenatal food and micronutrient supplementation, reduced infant mortality and were reported to be very cost-effective. However, the multiple micronutrients (MMS) supplement was associated with an increased risk of stunted growth in infancy and early childhood. This unfavourable outcome was not included in the previous cost-effectiveness analysis. The aim of this study is to evaluate whether the MINIMat interventions remain cost-effective in view of both favourable (decreased under-five-years mortality) and unfavourable (increased stunting) outcomes. Method Pregnant women in rural Bangladesh, where food insecurity still is prevalent, were randomized to early (E) or usual (U) invitation to be given food supplementation and daily doses of 30 mg, or 60 mg iron with 400 mu g of folic acid, or MMS with 15 micronutrients including 30 mg iron and 400 mu g of folic acid. E reduced stunting at 4.5 years compared with U, MMS increased stunting at 4.5 years compared with Fe60, while the combination EMMS reduced infant mortality compared with UFe60. The outcome measure used was disability adjusted life years (DALYs), a measure of overall disease burden that combines years of life lost due to premature mortality (under five-year mortality) and years lived with disability (stunting). Incremental cost effectiveness ratios were calculated using cost data from already published studies. Results By incrementing UFe60 (standard practice) to EMMS, one DALY could be averted at a cost of US$24. Conclusion When both favourable and unfavourable outcomes were included in the analysis, early prenatal food and multiple micronutrient interventions remained highly cost effective and seem to be meaningful from a public health perspective.

  • 562.
    Svennerholm, Kristina
    et al.
    Anestesiologi, Sahlgrenska akademin, Göteborg.
    Bergh, Niklas
    Wallenberg lab, Sahlgrenska akademin, Göteborg.
    Larsson, Pia
    Wallenberg lab, Sahlgrenska akademin, Göteborg.
    Jern, Sverker
    Wallenberg lab, Sahlgrenska akademin, Göteborg.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, Björn
    Anestesiologi, Sahlgrenska akademin, Göteborg.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Histone Deacetylase Inhibitor Treatment Increases Coronary t-PA Release in a Porcine Ischemia Model2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 5, p. e97260-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The expression of the tissue plasminogen activator gene can be affected by histone deacetylation inhibition and thus appears to be under epigenetic control.

    OBJECTIVES: The study aimed to test if in vivo pharmacological intervention by valproic acid treatment would lead to increase in tissue plasminogen activator release capacity. METHODS: In an anaesthetized pig model, a controlled transient coronary occlusion was used to stimulate coronary tissue plasminogen activator release in a valproic acid treated (one week) and a non-treated group. Coronary venous blood samples from the ischemic region were collected, great cardiac vein thermodilution flow measurements were performed, and trans-coronary tissue plasminogen activator fluxes were calculated. Plasminogen activator inhibitor-1 was also measured.

    RESULTS: Adequate sampling from the affected area after the 10 minute ischemic period was confirmed by lactate measurements. Fluxes for tissue plasminogen activator at minutes 1, 3, 5, 7 and 10 were measured and then used to present cumulative net tissue plasminogen activator release for the whole measurement period for both groups. Area under the curve was higher for the valproic acid treated group at 10 minutes; 932+/-173 nanograms (n = 12) compared to the non-treated group, 451+/-78 nanograms (n = 10, p = 0.023). There was no difference in levels of plasminogen activator inhibitor-1 between groups.

    CONCLUSIONS: These findings support a proof of concept for histone deacetylation inhibition positive effect on tissue plasminogen activator expression in an in vivo setting. Further studies are needed to find an optimal way to implement histone deacetylation inhibition to achieve desired clinical changes in tissue plasminogen activator expression.

  • 563. Svennerholm, Kristina
    et al.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Biber, Björn
    Ulfhammer, Erik
    Saluveer, Ott
    Larsson, Pia
    Omerovic, Elmir
    Jern, Sverker
    Bergh, Niklas
    Histone Deacetylase Inhibition Enhances Tissue Plasminogen Activator Release Capacity in Atherosclerotic Man2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 3, article id e0121196Article in journal (Refereed)
    Abstract [en]

    The expression of the tissue plasminogen activator (t-PA) gene appears to be under epigenetic control and can be affected by histone deacetylation inhibition. The study aimed to test if histone deacetalyase inhibitor treatment lead to increased t-PA release or reduced exhaustion in t-PA release in response to stimulation, as well as change in plasminogen activator inhibitor-1 (PAI-1) in subjects with coronary disease. In this clinical study, 16 post-myocardial infarction subjects, the perfused forearm model was used with isoprenaline provocation during 20 minutes, to stimulate local t-PA release. Each subject was measured twice on the same day (repeated stimuli sequences) as well as on two different occasions, without treatment and after four weeks of treatment with valproic acid (500 mg, twice daily). Net forearm release for t-PA in response to isoprenaline at minutes 1.5, 3, 6, 9, 12, 15 and 18 was measured, allowing assessment of cumulative t-PA release. There was a reduction in the exhaustion of cumulative t-PA release during repeated and prolonged stimulation with valproic acid treatment compared to non-treatment. Plasma PAI-1 antigen was decreased following treatment compared to non-treatment (18.4 +/- 10.0 vs. 11.0 +/- 7.1 nano-grams/ml respectively, mean with 95% confidence interval). These findings demonstrate that histone deacetylation inhibition increases the capacity for endogenous t-PA release in subjects with vascular disease. Furthermore, the fibrinolytic balance is favored with suppressed PAI-1 levels. More studies are needed to establish the clinical relevance of these findings.

  • 564. Svennerholm, Kristina
    et al.
    Rodsand, Pouria
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lundholm, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ahrén, Dag
    Biber, Björn
    Ronquist, Gunnar
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    DNA content in extracellular vesicles isolated from porcine coronary venous blood directly after myocardial ischemic preconditioning2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 7, article id e0159105Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Extracellular vesicles (EV) are nano-sized membranous structures released from most cells. They have the capacity to carry bioactive molecules and gene expression signals between cells, thus mediating intercellular communication. It is believed that EV confer protection after ischemic preconditioning (IPC). We hypothesize that myocardial ischemic preconditioning will lead to rapid alteration of EV DNA content in EV collected from coronary venous effluent.

    MATERIALS AND METHODS: In a porcine myocardial ischemic preconditioning model, EV were isolated from coronary venous blood before and after IPC by differential centrifugation steps culminating in preparative ultracentrifugation combined with density gradient ultracentrifugation. The EV preparation was validated, the DNA was extracted and further characterized by DNA sequencing followed by bioinformatics analysis.

    RESULTS: Porcine genomic DNA fragments representing each chromosome, including mitochondrial DNA sequences, were detected in EV isolated before and after IPC. There was no difference detected in the number of sequenced gene fragments (reads) or in the genomic coverage of the sequenced DNA fragments in EV isolated before and after IPC. Gene ontology analysis showed an enrichment of genes coding for ion channels, enzymes and proteins for basal metabolism and vesicle biogenesis and specific cardiac proteins.

    CONCLUSIONS: This study demonstrates that porcine EV isolated from coronary venous blood plasma contain fragments of DNA from the entire genome, including the mitochondria. In this model we did not find specific qualitative or quantitative changes of the DNA content in EV collected immediately after an in vivo myocardial IPC provocation. This does not rule out the possibility that EV DNA content changes in response to myocardial IPC which could occur in a later time frame.

  • 565.
    Svenningsson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Falk, Eva
    Celius, Elisabeth G.
    Fuchs, Siegrid
    Schreiber, Karen
    Berko, Sara
    Sun, Jennifer
    Penner, Iris-Katharina
    Natalizumab Treatment Reduces Fatigue in Multiple Sclerosis: Results from the TYNERGY Trial: A Study in the Real Life Setting2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 3, p. e58643-Article in journal (Refereed)
    Abstract [en]

    Fatigue is a significant symptom in multiple sclerosis (MS) patients. First-generation disease modifying therapies (DMTs) are at best moderately effective to improve fatigue. Observations from small cohorts have indicated that natalizumab, an antibody targeting VLA-4, may reduce MS-related fatigue. The TYNERGY study aimed to further evaluate the effects of natalizumab treatment on MS-related fatigue. In this one-armed clinical trial including 195 MS patients, natalizumab was prescribed in a real-life setting, and a validated questionnaire, the Fatigue Scale for Motor and Cognitive functions (FSMC), was used both before and after 12 months of treatment to evaluate a possible change in the fatigue experienced by the patients. In the treated cohort all measured variables, that is, fatigue score, quality of life, sleepiness, depression, cognition, and disability progression were improved from baseline (all p values<0.0001). Walking speed as measured by the six-minute walk-test also increased at month 12 (p = 0.0016). All patients were aware of the nature of the treatment agent, and of the study outcomes.

    Conclusion: Natalizumab, as used in a real-life setting, might improve MS-related fatigue based on the results from this one-armed un-controlled stud. Also other parameters related to patients' quality of life seemed to improve with natalizumab treatment.

  • 566.
    Svenson, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Grönlund, Elisabeth
    Söderström, Ingegerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sitaram, Raviprakash T
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Telomere length in relation to immunological parameters in patients with renal cell carcinoma2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 2, article id e55543Article in journal (Refereed)
    Abstract [en]

    Over the last decade, telomere length (TL) has gained attention as a potential biomarker in cancer disease. We previously reported that long blood TL was associated with a poorer outcome in patients with breast cancer and renal cell carcinoma. Based on these findings, we hypothesized that certain immunological components may have an impact on TL dynamics in cancer patients. One aim of the present study was to investigate a possible association between serum cytokines and TL of peripheral blood cells, tumors and corresponding kidney cortex, in patients with clear cell renal cell carcinoma. For this purpose, a multiplex cytokine assay was used. Correlation analysis revealed significant positive correlations between tumor TL and peripheral levels of three cytokines (IL-7, IL-8 and IL-10). In a parallel patient group with various kidney tumors, TL was investigated in whole blood and in immune cell subsets in relation to peripheral levels of regulatory T cells (Tregs). A significant positive association was found between whole blood TL and Treg levels. However, the strongest correlation was found between Tregs and TL of the T lymphocyte fraction. Thus, patients with higher Treg levels displayed longer T cell telomeres, which might reflect a suppressed immune system with fewer cell divisions and hence less telomere shortening. These results are in line with our earlier observation that long blood TL is an unfavorable prognostic factor for cancer-specific survival. In summary, we here show that immunological components are associated with TL in patients with renal cell carcinoma, providing further insight into the field of telomere biology in cancer. 

  • 567.
    Svenson, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nordfjäll, Katarina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Baird, Duncan
    Roger, Laureline
    Osterman, Pia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hellenius, Mai-Lis
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Blood cell telomere length is a dynamic feature2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 6, p. e21485-Article in journal (Refereed)
    Abstract [en]

    There is a considerable heterogeneity in blood cell telomere length (TL) for individuals of similar age and recent studies have revealed that TL changes by time are dependent on TL at baseline. TL is partly inherited, but results from several studies indicate that e.g. life style and/or environmental factors can affect TL during life. Collectively, these studies imply that blood cell TL might fluctuate during a life time and that the actual TL at a defined time point is the result of potential regulatory mechanism(s) and environmental factors. We analyzed relative TL (RTL) in subsequent blood samples taken six months apart from 50 individuals and found significant associations between RTL changes and RTL at baseline. Individual RTL changes per month were more pronounced than the changes recorded in a previously studied population analyzed after 10 years' follow up. The data argues for an oscillating TL pattern which levels out at longer follow up times. In a separate group of five blood donors, a marked telomere loss was demonstrated within a six month period for one donor where after TL was stabilized. PCR determined RTL changes were verified by Southern blotting and STELA (single telomere elongation length analysis). The STELA demonstrated that for the donor with a marked telomere loss, the heterogeneity of the telomere distribution decreased considerably, with a noteworthy loss of the largest telomeres. In summary, the collected data support the concept that individual blood cell telomere length is a dynamic feature and this will be important to recognize in future studies of human telomere biology.

  • 568.
    Svensson, Kerstin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Division of CBRN Defense and Security, Swedish Defense Research Agency, Umeå, Sweden .
    Granberg, Malin
    Karlsson, Linda
    Neubauerova, Vera
    Forsman, Mats
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Division of CBRN Defense and Security, Swedish Defense Research Agency, Umeå, Sweden .
    A real-time PCR array for hierarchical identification of Francisella isolates2009In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, no 12, article id e8360Article in journal (Refereed)
    Abstract [en]

    A robust, rapid and flexible real-time PCR assay for hierarchical genetic typing of clinical and environmental isolates of Francisella is presented. Typing markers were found by multiple genome and gene comparisons, from which 23 canonical single nucleotide polymorphisms (canSNPs) and 11 canonical insertion-deletion mutations (canINDELs) were selected to provide phylogenetic guidelines for classification from genus to isolate level. The specificity of the developed assay, which uses 68 wells of a 96-well real-time PCR format with a detection limit of 100 pg DNA, was assessed using 62 Francisella isolates of diverse genetic and geographical origins. It was then successfully used for typing 14 F. tularensis subsp. holarctica isolates obtained from tularemia patients in Sweden in 2008 and five more genetically diverse Francisella isolates of global origins. When applied to human ulcer specimens for direct pathogen detection the results were incomplete due to scarcity of DNA, but sufficient markers were identified to detect fine-resolution differences among F. tularensis subsp. holarctica isolates causing infection in the patients. In contrast to other real-time PCR assays for Francisella, which are typically designed for specific detection of a species, subspecies, or strain, this type of assay can be easily tailored to provide appropriate phylogenetic and/or geographical resolution to meet the objectives of the analysis.

  • 569.
    Södergren, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Karp, Kjell
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Bengtsson, Christine
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology. Department of Rheumatology, Kristianstad Hospital, Kristianstad, Sweden.
    Möller, Bozena
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Wållberg-Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Biomarkers associated with cardiovascular disease in patients with early rheumatoid arthritis2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 8, article id e0220531Article in journal (Refereed)
    Abstract [en]

    Objectives: Patients with rheumatoid arthritis (RA) have an increased mortality and morbidity due to cardiovascular disease (CVD). In this prospective 5-year follow up of patients with RA, we analysed several biomarkers, known to be associated with atherosclerosis and/or inflammation in the general population. The aim of this study was to find out whether the RA-disease per se affect these biomarkers and if those could be associated with the progression of atherosclerosis, as measured by intima media thickness (IMT) among patients with early RA.

    Methods: Patients from northern Sweden diagnosed with early RA, are consecutively recruited into an ongoing prospective study on CVD comorbidity. A subgroup of patients, aged ≤60 years (n = 71) was included for ultrasound measurements of IMT at inclusion (T0) and after 5 years (T5) together with age-sex-matched controls (n = 40). The patients were clinically assessed. Blood was analysed for lipids, ESR and CRP and several biomarkers known to be associated with atherosclerosis in the general population.

    Results: At T0, the patients with RA had significantly lower levels of MIF and significantly higher levels of interleukin (IL)-18 and MIC-1 compared with controls. At T5, the patients with RA had significantly higher levels of pentraxin3, MIC-1, TNF-R2, ICAM-1, VCAM-1 and endostatin compared with controls. At T0 the levels of MPO correlated with DAS28, sCD40L with CRP and IL-18 with systolic blood pressure and Reynolds risk score. Using PLSR on a CVD-panel analysed with multiplex immunoassay, the patients with RA could be correctly classified into those who had a worsening in their IMT over the five years or not. Here, MMP3 was identified as influential.

    Conclusions: This study indicates that the RA disease itself could affect several of the biomarkers in this study, and possibly also the processes involved in the development of atherosclerosis.

  • 570. Taj, Tahir
    et al.
    Stroh, Emilie
    Åström, Daniel Oudin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Centre for Primary Health Care Research, Department of Clinical Science, Malmö, Lund University, Lund, Sweden.
    Jakobsson, Kristina
    Oudin, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Department of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Short-Term Fluctuations in Air Pollution and Asthma in Scania, Sweden: Is the Association Modified by Long-Term Concentrations?2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, article id e0166614Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Asthma is one of the most common respiratory diseases in the world. Research has shown that temporal increases in air pollution concentrations can aggravate asthma symptoms. The aim of this study was to assess whether individuals living in areas with higher air pollution concentrations responded differently to short-term temporal exposure to air pollution than those living in lower air pollution areas.

    METHOD: The study was designed as a case-crossover study in Scania, Sweden. Outcome data was visits to primary health care clinics with asthma as the main complaint during the years 2007 to 2010. Nitrogen dioxide levels were obtained from 21 different air pollution monitoring stations. Short-term exposure was defined as the average concentration four days prior to the visit. Data was pooled for areas above and below a two-year average NO2 concentration of 10 μg/m3, dispersion modelled with an emission database.

    RESULTS: The short-term association between NO2 and asthma visits seemed stronger in areas with NO2 levels below 10 μg/m3, with an odds ratio (OR) of 1.15 (95% confidence interval (CI): 1.08-1.23) associated with a 10 μg/m3 increase in NO2 compared to areas above 10 μg/m3 NO2 levels, where corresponding OR of 1.09 (95% CI: 1.02-1.17). However, this difference was not statistically significant. (p = 0.13).

    CONCLUSIONS: The study provided some evidence, although not statistically significant, that short-term associations between air pollution and asthma may depend on background air pollution levels. However, we cannot rule out that the association is due to other spatially dependent factors in Scania. The study should be reproduced in other study areas.

  • 571.
    Takaguchi, Taro
    et al.
    The University of Tokyo.
    Masuda, Naoki
    The University of Tokyo.
    Holme, Petter
    Umeå University, Faculty of Science and Technology, Department of Physics. Sungkyunkwan Univ, Dept Energy Sci, Suwon, South Korea ; Stockholm Univ, Dept Sociol, S-10691 Stockholm, Sweden.
    Bursty Communication Patterns Facilitate Spreading in a Threshold-Based Epidemic Dynamics2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 7, p. e68629-Article in journal (Refereed)
    Abstract [en]

    Records of social interactions provide us with new sources of data for understanding how interaction patterns affect collective dynamics. Such human activity patterns are often bursty,i.e., they consist of short periods of intense activity followed by long periods of silence. This burstiness has been shown to affect spreading phenomena; it accelerates epidemic spreading in some cases and slows it down in other cases. We investigate a model of history-dependent contagion. In our model, repeated interactions between susceptible and infected individuals in a short period of time is needed for a susceptible individual to contract infection. We carry out numerical simulations on real temporal network data to find that bursty activity patterns facilitate epidemic spreading in our model.

  • 572.
    te Beest, Mariska
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Community and Conservation Ecology Group, University of Groningen, Groningen, The Netherlands.
    Elschot, Kelly
    Olff, Han
    Etienne, Rampal S.
    Invasion success in a marginal habitat: an experimental test of competitive ability and drought tolerance in Chromolaena odorata2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 8, article id e68274Article in journal (Refereed)
    Abstract [en]

    Climatic niche models based on native-range climatic data accurately predict invasive-range distributions in the majority of species. However, these models often do not account for ecological and evolutionary processes, which limit the ability to predict future range expansion. This might be particularly problematic in the case of invaders that occupy environments that would be considered marginal relative to the climatic niche in the native range of the species. Here, we assess the potential for future range expansion in the shrub Chromolaena odorata that is currently invading mesic savannas (>650 mm MAP) in South Africa that are colder and drier than most habitats in its native range. In a greenhouse experiment we tested whether its current distribution in South Africa can be explained by increased competitive ability and/or differentiation in drought tolerance relative to the native population. We compared aboveground biomass, biomass allocation, water use efficiency and relative yields of native and invasive C. odorata and the resident grass Panicum maximum in wet and dry conditions. Surprisingly, we found little differentiation between ranges. Invasive C. odorata showed no increased competitive ability or superior drought tolerance compared to native C. odorata. Moreover we found that P. maximum was a better competitor than either native or invasive C. odorata. These results imply that C. odorata is unlikely to expand its future range towards more extreme, drier, habitats beyond the limits of its current climatic niche and that the species' invasiveness most likely depends on superior light interception when temporarily released from competition by disturbance. Our study highlights the fact that species can successfully invade habitats that are at the extreme end of their ranges and thereby contributes towards a better understanding of range expansion during species invasions.

  • 573.
    Tegern, Matthias
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy. Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Huddinge, Sweden.
    Aasa, Ulrika
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Ang, Bjorn O.
    Harms-Ringdahl, Karin
    Larsson, Helena
    Inter-rater and test-retest reliability of movement control tests for the neck, shoulder, thoracic, lumbar, and hip regions in military personnel2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 9, article id e0204552Article in journal (Refereed)
    Abstract [en]

    Strategies are needed to mitigate the high rates and related risks of musculoskeletal complaints and injuries (MSCI) in the military aviator community. Previous work on Swedish Armed Forces (SwAF) soldiers have shown that proper screening methods have been successful in reducing early discharge from military training. Research has pointed at the importance of optimal spinal movement control in military aviators. The aim of this work was to investigate the inter-rater and test-retest reliability of a battery of clinical tests for evaluating movement control in the neck, shoulders, thoracic, lumbar, and hip regions in a population of SwAF military personnel. Inter-rater and test-retest reliability of 15 movement control tests were assessed by crude and prevalence-adjusted kappa coefficient. The study included 37 (inter-rater) and 45 (test-retest) SwAF personnel and was performed with two physiotherapists simultaneously observing and rating the movements on the first occasion and repeated with one physiotherapist on the second occasion. For inter-rater reliability, the kappa coefficient ranged from .19 to .95. Seven tests showed substantial to almost perfect agreement (kappa > .60). With the adjusted kappa, three more tests reached the level of substantial agreement. The corresponding values for test-retest reliability ranged from .26 to .65. Substantial agreement was attained for two tests, three with adjusted kappa. The following tests can reliably be used when screening for biomechanically less advantageous movement patters in military aviators: Shoulder flexion, and rotation, Neck flexion in sitting and supine, Neck extension and rotation in sitting, Pelvic tilt, Forward lean and Single and Double knee extension tests. Grading criteria for tests in supine and quadruped positions need to be further elaborated.

  • 574.
    ter Beek, Josy
    et al.
    Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
    Krause, Nils
    Ädelroth, Pia
    Investigating the Proton Donor in the NO Reductase from Paracoccus denitrificans2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, article id e0152745Article in journal (Refereed)
    Abstract [en]

    Variant nomenclature: the variants were made in the NorB subunit if not indicated by the superscript(c), which are variants in the NorC subunit (e.g. E122A = exchange of Glu-122 in NorB for an Ala, E71(c)D; exchange of Glu-71 in NorC for an Asp). Bacterial NO reductases (NORs) are integral membrane proteins from the heme-copper oxidase superfamily. Most heme-copper oxidases are proton-pumping enzymes that reduce O-2 as the last step in the respiratory chain. With electrons from cytochrome c, NO reductase (cNOR) from Paracoccus (P.) denitrificans reduces NO to N2O via the following reaction: 2NO+2e(-)+2H(+) -> N2O+H2O. Although this reaction is as exergonic as O-2-reduction, cNOR does not contribute to the electrochemical gradient over the membrane. This means that cNOR does not pump protons and that the protons needed for the reaction are taken from the periplasmic side of the membrane (since the electrons are donated from this side). We previously showed that the P. denitrificans cNOR uses a single defined proton pathway with residues Glu-58 and Lys-54 from the NorC subunit at the entrance. Here we further strengthened the evidence in support of this pathway. Our further aim was to define the continuation of the pathway and the immediate proton donor for the active site. To this end, we investigated the region around the calcium-binding site and both propionates of heme b(3) by site directed mutagenesis. Changing single amino acids in these areas often had severe effects on cNOR function, with many variants having a perturbed active site, making detailed analysis of proton transfer properties difficult. Our data does however indicate that the calcium ligation sphere and the region around the heme b(3) propionates are important for proton transfer and presumably contain the proton donor. The possible evolutionary link between the area for the immediate donor in cNOR and the proton loading site (PLS) for pumped protons in oxygen-reducing heme-copper oxidases is discussed.

  • 575.
    Thay, Bernard
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Oscarsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Staphylococcus aureus alpha-toxin-dependent induction of host cell death by membrane-derived vesicles2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 1, article id e54661Article in journal (Refereed)
    Abstract [en]

    Staphylococcus aureus causes a wide spectrum of infections in humans, ranging from superficial cutaneous infections, infections in the circum-oral region, to life-threatening bacteremia. It was recently demonstrated that Gram-positive organisms such as S. aureus liberate membrane-derived vesicles (MVs), which analogously to outer membrane vesicles (OMVs) of Gram-negative bacteria can play a role in delivering virulence factors to host cells. In the present study we have shown that cholesterol-dependent fusion of S. aureus MVs with the plasma membrane represents a route for delivery of a key virulence factor, α-toxin (α-hemolysin; Hla) to human cells. Most S. aureus strains produce this 33-kDa pore-forming protein, which can lyse a wide range of human cells, and induce apoptosis in T-lymphocytes. Our results revealed a tight association of biologically active α-toxin with membrane-derived vesicles isolated from S. aureus strain 8325-4. Concomitantly, α-toxin contributed to HeLa cell cytotoxicity of MVs, and was the main vesicle-associated protein responsible for erythrocyte lysis. In contrast, MVs obtained from an isogenic hla mutant were significantly attenuated with regards to both causing lysis of erythrocytes and death of HeLa cells. This is to our knowledge the first recognition of an S. aureus MV-associated factor contributing to host cell cytotoxicity.

  • 576. Thein, Marcus
    et al.
    Bonde, Mari
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Bunikis, Ignas
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Denker, Katrin
    Sickmann, Albert
    Bergström, Sven
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Benz, Roland
    DipA, a Pore-Forming Protein in the Outer Membrane of Lyme Disease Spirochetes Exhibits Specificity for the Permeation of Dicarboxylates2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 5, p. e36523-Article in journal (Refereed)
    Abstract [en]

    Lyme disease Borreliae are highly dependent on the uptake of nutrients provided by their hosts. Our study describes the identification of a 36 kDa protein that functions as putative dicarboxylate-specific porin in the outer membrane of Lyme disease Borrelia. The protein was purified by hydroxyapatite chromatography from Borrelia burgdorferi B31 and designated as DipA, for dicarboxylate-specific porin A. DipA was partially sequenced, and corresponding genes were identified in the genomes of B. burgdorferi B31, Borrelia garinii PBi and Borrelia afzelii PKo. DipA exhibits high homology to the Oms38 porins of relapsing fever Borreliae. B. burgdorferi DipA was characterized using the black lipid bilayer assay. The protein has a single-channel conductance of 50 pS in 1 M KCl, is slightly selective for anions with a permeability ratio for cations over anions of 0.57 in KCl and is not voltage-dependent. The channel could be partly blocked by different di- and tricarboxylic anions. Particular high stability constants up to about 28,000 l/mol (in 0.1 M KCl) were obtained among the 11 tested anions for oxaloacetate, 2-oxoglutarate and citrate. The results imply that DipA forms a porin specific for dicarboxylates which may play an important role for the uptake of specific nutrients in different Borrelia species.

  • 577.
    Thors, Lina
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Persson, Emma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Egevad, Lars
    Granfors, Torvald
    Fowler, Christopher J
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Fatty acid amide hydrolase in prostate cancer: association with disease severity and outcome, CB1 receptor expression and regulation by IL-42010In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 8, p. e12275-Article in journal (Refereed)
    Abstract [en]

    Background

    Recent data have indicated that there may be a dysregulation of endocannabinoid metabolism in cancer. Here we have investigated the expression of the endocannabinoid metabolising enzyme fatty acid amide hydrolase (FAAH) in a well characterised tissue microarray from patients diagnosed with prostate cancer at transurethral resection for voiding problems.

    Methodology/Principal Findings

    FAAH immunoreactivity (FAAH-IR) was assessed in formalin-fixed paraffin-embedded non-malignant and tumour cores from 412 patients with prostate cancer. CB1 receptor immunoreactivity (CB1IR) scores were available for this dataset. FAAH-IR was seen in epithelial cells and blood vessel walls but not in the stroma. Tumour epithelial FAAH-IR was positively correlated with the disease severity at diagnosis (Gleason score, tumour stage, % of the specimen that contained tumour) for cases with mid-range CB1IR scores, but not for those with high CB1IR scores. For the 281 cases who only received palliative therapy at the end stages of the disease, a high tumour epithelial FAAH-IR was associated with a poor disease-specific survival. Multivariate Cox proportional-hazards regression analyses indicated that FAAH-IR gave additional prognostic information to that provided by CB1IR when a midrange, but not a high CB1IR cutoff value was used. Interleukin-4 (IL-4) receptor IR was found on tumour epithelial cells and incubation of prostate cancer PC-3 and R3327 AT1 cells with IL-4 increased their FAAH activity.

    Conclusions/Significance

    Tumour epithelial FAAH-IR is associated with prostate cancer severity and outcome at mid-range, but not high, CB1IR scores. The correlation with CB1IR in the tumour tissue may be related to a common local dysregulation by a component of the tumour microenvironment.

  • 578.
    Thorslund, Sara E
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Edgren, Tomas
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Pettersson, Jonas
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Nordfelth, Roland
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Sellin, Mikael E
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Ivanova, Ekaterina
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Francis, Matthew S
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Isaksson, Elin L
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Wolf-Watz, Hans
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Fällman, Maria
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    The RACK1 signaling scaffold protein selectively interacts with Yersinia pseudotuberculosis virulence function2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 2, p. e16784-Article in journal (Refereed)
    Abstract [en]

    Many Gram-negative bacteria use type III secretion systems to translocate effector proteins into host cells. These effectors interfere with cellular functions in a highly regulated manner resulting in effects that are beneficial for the bacteria. The pathogen Yersinia can resist phagocytosis by eukaryotic cells by translocating Yop effectors into the target cell cytoplasm. This is called antiphagocytosis, and constitutes an important virulence feature of this pathogen since it allows survival in immune cell rich lymphoid organs. We show here that the virulence protein YopK has a role in orchestrating effector translocation necessary for productive antiphagocytosis. We present data showing that YopK influences Yop effector translocation by modulating the ratio of the pore-forming proteins YopB and YopD in the target cell membrane. Further, we show that YopK that can interact with the translocators, is exposed inside target cells and binds to the eukaryotic signaling protein RACK1. This protein is engaged upon Y. pseudotuberculosis-mediated beta1-integrin activation and localizes to phagocytic cups. Cells with downregulated RACK1 levels are protected from antiphagocytosis. This resistance is not due to altered levels of translocated antiphagocytic effectors, and cells with reduced levels of RACK1 are still sensitive to the later occurring cytotoxic effect caused by the Yop effectors. Further, a yopK mutant unable to bind RACK1 shows an avirulent phenotype during mouse infection, suggesting that RACK1 targeting by YopK is a requirement for virulence. Together, our data imply that the local event of Yersinia-mediated antiphagocytosis involves a step where YopK, by binding RACK1, ensures an immediate specific spatial delivery of antiphagocytic effectors leading to productive inhibition of phagocytosis.

  • 579.
    Timby, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lif Holgerson, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lonnerdal, Bo
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Oral Microbiota in Infants Fed a Formula Supplemented with Bovine Milk Fat Globule Membranes: A Randomized Controlled Trial2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0169831Article in journal (Refereed)
    Abstract [en]

    Background In a recent study, supplementation of infant formula with milk fat globule membranes (MFGM) decreased the incidence of otitis media in infants <6 months of age. Objectives The aim of the present study was to characterize the oral microbiota in infants fed MFGM-supplemented formula and compare it to that of infants fed standard formula or breast milk.

    Methods In a prospective double-blinded randomized controlled trial, exclusively formula-fed infants <2 months of age were randomized to be fed experimental formula (EF, n = 80) with reduced energy and protein and supplemented with a bovine MFGM concentrate, or standard formula (SF, n = 80) until 6 months of age. A breast-fed reference (BFR, n = 80) group was also recruited. The oral microbiota was analyzed at 4 (n = 124) and 12 (n = 166) months of age using Illumina MiSeq multiplex sequencing and taxonomic resolution against the HOMD 16S rDNA database of oral bacteria.

    Results Species richness in the oral samples did not differ between the EF and SF groups, but partial least square modeling identified a few taxa that were significantly associated with being in either group, e.g. lower level of Moraxella catarrhalis in the EF group. Infants in the BFR group had significantly lower species richness at 4 months of age and their microbiota pattern differed markedly from the formula-fed groups.

    Conclusions Supplementation of infant formula with MFGM yielded moderate effects on the oral micro biome. Moraxella catarrhalis was less prevalent in infants fed EF than in those fed SF and may be associated with the decrease in otitis media seen in the same group.

  • 580.
    Timpka, Toomas
    et al.
    Östergötland County Council, Department of Public Health; Linköping University, Department of Medical and Health Sciences; Linköping University, Department of Computer and Information Science, Linköping University.
    Eriksson, Olle
    Linköping University, Department of Computer and Information Science .
    Spreco, Armin
    Linköping University, Department of Medical and Health Sciences; Linköping University, Department of Computer and Information Science.
    Gursky, Elin
    ANSER/Analytic Services Inc., National Strategies Support Directorate, Arlington, VA.
    Strömgren, Magnus
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History.
    Holm, Einar
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History.
    Ekberg, Joakim
    Östergötland County Council, Department of Public Health; Linköping University, Department of Medical and Health Sciences.
    Dahlström, Örjan
    Östergötland County Council, Department of Public Health; Linköping University, Department of Medical and Health Sciences; Linköping University, Department of Behavioural Sciences, Swedish Institute for Disability Research, Linnaeus Centre HEAD.
    Valter, Lars
    Östergötland County Council, Department of Public Health; Linköping University, Department of Medical and Health Sciences; Linköping University, Department of Computer and Information Science.
    Eriksson, Henrik
    Linköping University, Department of Computer and Information Science.
    Age as a determinant for dissemination of seasonal and pandemic influenza: An open cohort study of influenza outbreaks in Östergötland County, Sweden2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 2, p. e31746-Article in journal (Refereed)
    Abstract [en]

    An understanding of the occurrence and comparative timing of influenza infections in different age groups is important for developing community response and disease control measures. This study uses data from a Scandinavian county (population 427,000) to investigate whether age was a determinant for being diagnosed with influenza 2005–2010 and to examine if age was associated with case timing during outbreaks. Aggregated demographic data were collected from Statistics Sweden, while influenza case data were collected from a county-wide electronic health record system. A logistic regression analysis was used to explore whether case risk was associated with age and outbreak. An analysis of variance was used to explore whether day for diagnosis was also associated to age and outbreak. The clinical case data were validated against case data from microbiological laboratories during one control year. The proportion of cases from the age groups 10–19 (p<0.001) and 20–29 years old (p<0.01) were found to be larger during the A pH1N1 outbreak in 2009 than during the seasonal outbreaks. An interaction between age and outbreak was observed (p<0.001) indicating a difference in age effects between circulating virus types; this interaction persisted for seasonal outbreaks only (p<0.001). The outbreaks also differed regarding when the age groups received their diagnosis (p<0.001). A post-hoc analysis showed a tendency for the young age groups, in particular the group 10–19 year olds, led outbreaks with influenza type A H1 circulating, while A H3N2 outbreaks displayed little variations in timing. The validation analysis showed a strong correlation (r = 0.625; p<0.001) between the recorded numbers of clinically and microbiologically defined influenza cases. Our findings demonstrate the complexity of age effects underlying the emergence of local influenza outbreaks. Disentangling these effects on the causal pathways will require an integrated information infrastructure for data collection and repeated studies of well-defined communities.

  • 581. Timpka, Toomas
    et al.
    Spreco, Armin
    Gursky, Elin A
    Eriksson, Olle
    Dahlström, Örjan
    Strömgren, Magnus
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History, Economic and social geography.
    Ekberg, Joakim
    Pilemalm, Sofie
    Karlsson, David
    Hinkula, Jorma
    Holm, Einar
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History, Economic and social geography.
    Intentions to perform non-pharmaceutical protective behaviors during influenza outbreaks in Sweden: A cross-sectional study following a mass vaccination campaign2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 3, p. e91060-Article in journal (Refereed)
    Abstract [en]

    Failure to incorporate the beliefs and attitudes of the public into theoretical models of preparedness has been identified as a weakness in strategies to mitigate infectious disease outbreaks. We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. The interviewees were asked to make their appraisals for two scenarios: a) an influenza with low case fatality and mild lifestyle impact; b) severe influenza with high case fatality and serious disturbances of societal functions. Every second respondent (50.0%) reported high trust in official information about influenza. The proportion that reported intentions to take deliberate actions to improve personal hygiene during outbreaks ranged between 45–85%, while less than 25% said that they intended to increase social distancing. Multiple logistic regression models with coping appraisal as the explanatory factor most frequently contributing to the explanation of the variance in intentions showed strong discriminatory performance for staying home while not ill (mild outbreaks: Area under the curve [AUC] 0.85 (95% confidence interval 0.82;0.89), severe outbreaks AUC 0.82 (95% CI 0.77;0.85)) and acceptable performance with regard to avoiding public transportation (AUC 0.78 (0.74;0.82), AUC 0.77 (0.72;0.82)), using handwash products (AUC 0.70 (0.65;0.75), AUC 0.76 (0.71;0.80)), and frequently washing hands (AUC 0.71 (0.66;0.76), AUC 0.75 (0.71;0.80)). We conclude that coping appraisal was the explanatory factor most frequently included in statistical models explaining self-reported intentions to carry out non-pharmaceutical health actions in the Swedish outlined context, and that variations in threat appraisal played a smaller role in these models despite scientific uncertainties surrounding a recent mass vaccination campaign.

  • 582. Tkachuk, Artem
    et al.
    Kim, Maria
    Kravchuk, Oksana
    Savitsky, Mikhail
    A new powerful method for site-specific transgene stabilization based on chromosomal double-strand break repair.2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 10Article in journal (Refereed)
    Abstract [en]

    Transgenic insects are a promising tool in sterile insect techniques and population replacement strategies. Such transgenic insects can be created using nonautonomous transposons, which cannot be transferred without a transposase source. In biocontrol procedures where large numbers of insects are released, there is increased risk of transgene remobilization caused by external transposase sources that can alter the characteristics of the transgenic organisms lead horizontal transgene transfer to other species. Here we describe a novel, effective method for transgene stabilization based on the introduction of directed double-strand breaks (DSB) into a genome-integrated sequence and their subsequent repair by the single-strand annealing (SSA) pathway. Due to the construct's organization, the repair pathway is predictable, such that all transposon and marker sequences can be deleted, while preserving integration of exogenous DNA in the genome. The exceptional conservation of DNA repair pathways makes this method suitable for a broad range of organisms.

  • 583.
    Torell, Frida
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bennett, Kate
    Cereghini, Silvia
    Raennar, Stefan
    Lundstedt-Enkel, Katrin
    Moritz, Thomas
    Haumaitre, Cecile
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lundstedt, Torbjoern
    Multi-Organ Contribution to the Metabolic Plasma Profile Using Hierarchical Modelling2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, article id e0129260Article in journal (Refereed)
    Abstract [en]

    Hierarchical modelling was applied in order to identify the organs that contribute to the levels of metabolites in plasma. Plasma and organ samples from gut, kidney, liver, muscle and pancreas were obtained from mice. The samples were analysed using gas chromatography time-of-flight mass spectrometry (GC TOF-MS) at the Swedish Metabolomics centre, Umea University, Sweden. The multivariate analysis was performed by means of principal component analysis (PCA) and orthogonal projections to latent structures (OPLS). The main goal of this study was to investigate how each organ contributes to the metabolic plasma profile. This was performed using hierarchical modelling. Each organ was found to have a unique metabolic profile. The hierarchical modelling showed that the gut, kidney and liver demonstrated the greatest contribution to the metabolic pattern of plasma. For example, we found that metabolites were absorbed in the gut and transported to the plasma. The kidneys excrete branched chain amino acids (BCAAs) and fatty acids are transported in the plasma to the muscles and liver. Lactic acid was also found to be transported from the pancreas to plasma. The results indicated that hierarchical modelling can be utilized to identify the organ contribution of unknown metabolites to the metabolic profile of plasma.

  • 584.
    Tornevi, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Axelsson, Gösta
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Association between precipitation upstream of a drinking water utility and nurse advice calls relating to acute gastrointestinal illnesses2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 7, article id e69918Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The River Göta Älv is a source of fresh-water for the City of Gothenburg (Sweden). We recently identified a clear association between upstream precipitation and indicator bacteria concentrations in the river water outside the intake to the drinking water utility. This study aimed to determine if variation in the incidence of acute gastrointestinal illnesses is associated with upstream precipitation.

    METHODS: We acquired data, covering 1494 days, on the daily number of telephone calls to the nurse advice line from citizens in Gothenburg living in areas with Göta Älv as a fresh-water supply. We separated calls relating to gastrointestinal illnesses from other medical concerns, and analyzed their association with precipitation using a distributed lag non-linear Poisson regression model, adjusting for seasonal patterns and covariates. We used a 0-21-day lag period for precipitation to account for drinking water delivery times and incubation periods of waterborne pathogens.

    RESULTS: The study period contained 25,659 nurse advice calls relating to gastrointestinal illnesses. Heavy rainfall was associated with increased calls the same day and around 5-6 days later. Consecutive days of wet weather were also found to be associated with an increase in the daily number of gastrointestinal concerns. No associations were identified between precipitation and nurse advice calls relating to other medical concerns.

    CONCLUSION: An increase in nurse advice calls relating to gastrointestinal illnesses around 5-6 days after heavy rainfall is consistent with a hypothesis that the cause could be related to drinking water due to insufficient barriers in the drinking water production, suggesting the need for improved drinking water treatment.

  • 585.
    Tornevi, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Barregård, Lars
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Precipitation and primary health care visits for gastrointestinal illness in Gothenburg, Sweden2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0128487Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The river Göta Älv is a source of freshwater for the City of Gothenburg, Sweden, and we recently identified a clear influence of upstream precipitation on concentrations of indicator bacteria in the river water, as well as an association with the daily number of phone calls to the nurse advice line related to acute gastrointestinal illnesses (AGI calls). This study aimed to examine visits to primary health-care centers owing to similar symptoms (AGI visits) in the same area, to explore associations with precipitation, and to compare variability in AGI visits and AGI calls.

    METHODS: We obtained data covering six years (2007-2012) of daily AGI visits and studied their association with prior precipitation (0-28 days) using a distributed lag nonlinear Poisson regression model, adjusting for seasonal patterns and covariates. In addition, we studied the effects of prolonged wet and dry weather on AGI visits. We analyzed lagged short-term relations between AGI visits and AGI calls, and we studied differences in their seasonal patterns using a binomial regression model.

    RESULTS: The study period saw a total of 17,030 AGI visits, and the number of daily visits decreased on days when precipitation occurred. However, prolonged wet weather was associated with an elevated number of AGI visits. Differences in seasonality patterns were observed between AGI visits and AGI calls, as visits were relatively less frequent during winter and relatively more frequent in August, and only weak short-term relations were found.

    CONCLUSION: AGI visits and AGI calls seems to partly reflect different types of AGI illnesses, and the patients' choice of medical contact (in-person visits versus phone calls) appears to depend on current weather conditions. An association between prolonged wet weather and increased AGI visits supports the hypothesis that the drinking water is related to an increased risk of AGI illnesses.

  • 586.
    Tornevi, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Bergstedt, Olof
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Precipitation Effects on Microbial Pollution in a River: Lag Structures and Seasonal Effect Modification2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 5Article in journal (Refereed)
    Abstract [en]

    Background: The river Gota Alv is a source of freshwater for 0.7 million swedes. The river is subject to contamination from sewer systems discharge and runoff from agricultural lands. Climate models projects an increase in precipitation and heavy rainfall in this region. This study aimed to determine how daily rainfall causes variation in indicators of pathogen loads, to increase knowledge of variations in river water quality and discuss implications for risk management. Methods: Data covering 7 years of daily monitoring of river water turbidity and concentrations of E. coli, Clostridium and coliforms were obtained, and their short-term variations in relation with precipitation were analyzed with time series regression and non-linear distributed lag models. We studied how precipitation effects varied with season and compared different weather stations for predictive ability. Results: Generally, the lowest raw water quality occurs 2 days after rainfall, with poor raw water quality continuing for several more days. A rainfall event of >15 mm/24-h (local 95 percentile) was associated with a three-fold higher concentration of E. coli and 30% higher turbidity levels (lag 2). Rainfall was associated with exponential increases in concentrations of indicator bacteria while the effect on turbidity attenuated with very heavy rainfall. Clear associations were also observed between consecutive days of wet weather and decreased water quality. The precipitation effect on increased levels of indicator bacteria was significant in all seasons. Conclusions: Rainfall elevates microbial risks year-round in this river and freshwater source and acts as the main driver of varying water quality. Heavy rainfall appears to be a better predictor of fecal pollution than water turbidity. An increase of wet weather and extreme events with climate change will lower river water quality even more, indicating greater challenges for drinking water producers, and suggesting better control of sources of pollution.

  • 587. Torres-Espinola, Francisco J.
    et al.
    Berglund, Staffan K.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Centre of Excellence for Paediatric Research EURISTIKOS, University of Granada, Granada, Spain.
    Garcia, Salome
    Perez-Garcia, Miguel
    Catena, Andres
    Rueda, Ricardo
    Antonio Saez, Jose
    Campoy, Cristina
    Visual evoked potentials in offspring born to mothers with overweight, obesity and gestational diabetes2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 9, article id e0203754Article in journal (Refereed)
    Abstract [en]

    Background: Overweight, obesity, and gestational diabetes (GD) during pregnancy may negatively affect neurodevelopment in the offspring. However, the mechanisms are unclear and objective measures of neurodevelopment in infancy are scarce. We hypothesized that these maternal metabolic pathologies impair cortical visual evoked potentials (cVEPs), a proxy for visual and neuronal maturity.

    Design: The PREOBE study included 331 pregnant women stratified into four groups; normal weight (controls), overweight, obesity, and GD (the latter including mothers with normal weight, overweight and obesity). In a subsample of the offspring at 3 months (n = 157) and at 18 months (n = 136), we assessed the latencies and amplitudes of the P100 wave from cVEPs and calculated visual acuity.

    Results: At 3 months of age, visual acuity was significantly poorer in offspring born to GD mothers. At 18 months of age, there were no differences in visual acuity but infants born to GD mothers had significantly longer latencies of cVEPs when measured at 15', and 30' of arc. The group differences at 30' remained significant after confounder adjustment (mean [SD] 121.0 [16.0] vs. 112.6 [7.6] ms in controls, p = 0.007) and the most prolonged latencies were observed in offspring to GD mothers with concurrent overweight (128.9 [26.9] ms, p = 0.002) and obesity (118.5 [5.1] ms, p = 0.020).

    Conclusions: Infants born to mothers with GD, particularly those with concurrent overweight or obesity, have prolonged latencies of visual evoked potentials at 18 months of age, suggesting that this maternal metabolic profile have a long lasting, non-optimal, effect on infants' brain development.

  • 588. Torres-Espinola, Francisco J
    et al.
    Berglund, Staffan K
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    García-Valdés, Luz M
    Segura, M Teresa
    Jerez, Antonio
    Campos, Daniel
    Moreno-Torres, Rosario
    Rueda, Ricardo
    Catena, Andrés
    Peréz-García, Miguel
    Campoy, Cristina
    Maternal Obesity, Overweight and Gestational Diabetes Affect the Offspring Neurodevelopment at 6 and 18 Months of Age: A Follow Up from the PREOBE Cohort2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 7, article id e0133010Article in journal (Refereed)
    Abstract [en]

    Background: Brain development in fetal life and early infancy is critical to determine lifelong performance in various neuropsychological domains. Metabolic pathologies such as overweight, obesity, and gestational diabetes in pregnant women are prevalent and increasing risk factors that may adversely affect long-term brain development in their offspring. Objective: The objective of this research was to investigate the influence of maternal metabolic pathologies on the neurodevelopment of the offspring at 6 and 18 months of life. Design This was a prospective case-control study of 331 mother- and child pairs from Granada, Spain. The mothers were included during pregnancy into four groups according to their pre-gestational body mass index and their gestational diabetes status; overweight (n:56), obese (n:64), gestational diabetic (n:79), and healthy normal weight controls (n:132). At 6 months and 18 months we assessed the children with the Bayley III scales of neurodevelopment. Results: At 6 months (n=215), we found significant group differences in cognition composite language, and expressive language. Post hoc test revealed unexpectedly higher scores in the obese group compared to the normal weight group and a similar trend in overweight and diabetic group. The effects on language remained significant after adjusting for confounders with an adjusted odds ratio for a value above median in composite language score of 3.3 (95% CI: 1.1, 10.0; p=0.035) for children of obese mothers. At 18 month (n=197), the off-spring born to obese mothers had lost five points in language composite scores and the previous differences in language and cognition was replaced by a suggestive trend of lower gross motor scores in the overweight, obese, and diabetic groups. Conclusions: Infants of obese mothers had a temporary accelerated development of cognition and language, followed by a rapid deceleration until 18 months of age, particularly of language scores. This novel observation prompts further confirmative studies to explore possible placental and neurodevelopmental mechanisms involved.

  • 589. Tozan, Yesim
    et al.
    Ratanawong, Pitcha
    Louis, Valérie R
    Kittayapong, Pattamaporn
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Use of insecticide-treated school uniforms for prevention of dengue in schoolchildren: a cost-effectiveness analysis2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, article id e108017Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Dengue-related illness is a leading cause of hospitalization and death, particularly among children. Practical, acceptable and affordable measures are urgently needed to protect this age group. Schools where children spend most of their day is proposed as an ideal setting to implement preventive strategies against day-biting Aedes mosquitoes. The use of insecticide-treated school uniforms is a promising strategy currently under investigation.

    METHODS: Using a decision-analytic model, we evaluated the cost-effectiveness of the use of insecticide-treated school uniforms for prevention of dengue, compared with a "do-nothing" alternative, in schoolchildren from the societal perspective. We explored how the potential economic value of the intervention varied under various scenarios of intervention effectiveness and cost, as well as dengue infection risk in school-aged children, using data specific to Thailand.

    RESULTS: At an average dengue incidence rate of 5.8% per year in school-aged children, the intervention was cost-effective (ICER≤$16,440) in a variety of scenarios when the intervention cost per child was $5.3 or less and the intervention effectiveness was 50% or higher. In fact, the intervention was cost saving (ICER<0) in all scenarios in which the intervention cost per child was $2.9 or less per year and the intervention effectiveness was 50% or higher. The results suggested that this intervention would be of no interest to Thai policy makers when the intervention cost per child was $10.6 or higher per year regardless of intervention effectiveness (ICER>$16,440).

    CONCLUSIONS: Our results present the potential economic value of the use of insecticide-treated uniforms for prevention of dengue in schoolchildren in a typical dengue endemic setting and highlight the urgent need for additional research on this intervention.

  • 590. Tran, Seav-Ly
    et al.
    Puhar, Andrea
    Unité PMM, INSERM U786, Institut Pasteur, Paris, France, Universite de la Mediterranee, France.
    Ngo-Camus, Maud
    Ramarao, Nalini
    Trypan blue dye enters viable cells incubated with the pore-forming toxin HlyII of Bacillus cereus2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 9, article id e22876Article in journal (Refereed)
    Abstract [en]

    Trypan blue is a dye that has been widely used for selective staining of dead tissues or cells. Here, we show that the pore-forming toxin HlyII of Bacillus cereus allows trypan blue staining of macrophage cells, despite the cells remaining viable and metabolically active. These findings suggest that the dye enters viable cells through the pores. To our knowledge, this is the first demonstration that trypan blue may enter viable cells. Consequently, the use of trypan blue staining as a marker of vital status should be interpreted with caution. The blue coloration does not necessarily indicate cell lysis, but may rather indicate pore formation in the cell membranes and more generally increased membrane permeability.

  • 591.
    Trang, Phan Minh
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Giang, Kim Bao
    Kullgren, Gunnar
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Heatwaves and Hospital Admissions for Mental Disorders in Northern Vietnam2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, article id e0155609Article in journal (Refereed)
    Abstract [en]

    Studies in high-income countries have shown an association between heatwaves and hospital admissions for mental disorders. It is unknown whether such associations exist in subtropical nations like Vietnam. The study aim was to investigate whether hospital admissions for mental disorders may be triggered, or exacerbated, by heat exposure and heatwaves, in a low-and middle-income country, Vietnam. For this, we used data from the Hanoi Mental Hospital over five years (2008-2012) to estimate the effect of heatwaves on admissions for mental disorders. A zero-inflated negative binomial regression model accounting for seasonality, time trend, days of week, and mean humidity was used to analyse the relationship. Heatwave events were mainly studied as periods of three or seven consecutive days above the threshold of 35 degrees C daily maximum temperature (90th percentile). The study result showed heatwaves increased the risk for admission in the whole group of mental disorders (F00-79) for more persistent heatwaves of at least 3 days when compared with non-heatwave periods. The relative risks were estimated at 1.04 (0.95-1.13), 1.15 (1.005-1.31), and 1.36 (1-1.90) for a one-, three- and seven-day heatwave, respectively. Admissions for mental disorders increased among men, residents in rural communities, and the elderly population during heatwaves. The groups of organic mental disorders, including symptomatic illnesses (F0-9) and mental retardation (F70-79), had increased admissions during heatwaves. The findings are novel in their focus on heatwave impact on mental diseases in a population habituating in a subtropical low-and middle-income country characterized by rapid epidemiological transitions and environmental changes.

  • 592. Turunen, Merita
    et al.
    Hokkanen, Laura
    Backman, Lars
    Stigsdotter Neely, Anna
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Hanninen, Tuomo
    Paajanen, Teemu
    Soininen, Hilkka
    Kivipelto, Miia
    Ngandu, Tiia
    Computer-based cognitive training for older adults: Determinants of adherence2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 7, article id e0219541Article in journal (Refereed)
    Abstract [en]

    The possibilities of computer-based cognitive training (CCT) in postponing the onset of dementia are currently unclear, but promising. Our aim is to investigate older adults ' adherence to a long-term CCT program, and which participant characteristics are associated with adherence to the CCT. This study was part of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). Participants were 60-77-year-old individuals with increased dementia risk, recruited from previous population-based studies. The participants included in this study (n = 631) had been randomized to receive a multi-domain lifestyle intervention, including CCT. The measure of adherence was the number of completed CCT sessions (max = 144) as continuous measure. Due to a substantial proportion of participants with 0 sessions, the zero inflated negative binomial regression analyses were used to enable assessment of both predictors of starting the training and predictors of completing a higher number of training sessions. Several cognitive, demographic, lifestyle, and health-related variables were examined as potential predictors of adherence to CCT. Altogether, 63% of the participants participated in the CCT at least once, 20% completed at least half of the training, and 12% completed all sessions. Previous experience with computers, being married or cohabiting, better memory performance, and positive expectations toward the study predicted greater odds for starting CCT. Previous computer use was the only factor associated with a greater number of training sessions completed. Our study shows that there is a large variation in adherence to a long-lasting CCT among older adults with an increased risk of dementia. The results indicate that encouraging computer use, and taking into account the level of cognitive functioning, may help boost adherence to CCT.

  • 593.
    Tydén, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Department of Anaesthesiology and Intensive Care, Östersund Hospital, Östersund, Sweden.
    Herwald, Heiko
    Sjoberg, Folke
    Johansson, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Department of Surgical and Perioperative Sciences, Anaesthesiology and Intensive Care, Umeå University, Umeå, Sweden.
    Increased Plasma Levels of Heparin-Binding Protein on Admission to Intensive Care Are Associated with Respiratory and Circulatory Failure2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, article id e0152035Article in journal (Refereed)
    Abstract [en]

    Purpose: Heparin-binding protein (HBP) is released by granulocytes and has been shown to increase vascular permeability in experimental investigations. Increased vascular permeability in the lungs can lead to fluid accumulation in alveoli and respiratory failure. A generalized increase in vascular permeability leads to loss of circulating blood volume and circulatory failure. We hypothesized that plasma concentrations of HBP on admission to the intensive care unit (ICU) would be associated with decreased oxygenation or circulatory failure.

    Methods: This is a prospective, observational study in a mixed 8-bed ICU. We investigated concentrations of HBP in plasma at admission to the ICU from 278 patients. Simplified acute physiology score (SAPS) 3 was recorded on admission. Sequential organ failure assessment (SOFA) scores were recorded daily for three days.

    Results: Median SAPS 3 was 58.8 (48-70) and 30-day mortality 64/278 (23%). There was an association between high plasma concentrations of HBP on admission with decreased oxygenation (p<0.001) as well as with circulatory failure (p<0.001), after 48-72 hours in the ICU. There was an association between concentrations of HBP on admission and 30-day mortality (p = 0.002). ROC curves showed areas under the curve of 0,62 for decreased oxygenation, 0,65 for circulatory failure and 0,64 for mortality.

    Conclusions: A high concentration of HBP in plasma on admission to the ICU is associated with respiratory and circulatory failure later during the ICU care period. It is also associated with increased 30-day mortality. Despite being an interesting biomarker for the composite ICU population it's predictive value at the individual patient level is low.

  • 594.
    Tükenmez, Hasan
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Magnussen, Helge
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Kovermann, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Byström, Anders
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Wolf-Watz, Magnus
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Linkage between Fitness of Yeast Cells and Adenylate Kinase Catalysis2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 9, article id e0163115Article in journal (Refereed)
    Abstract [en]

    Enzymes have evolved with highly specific values of their catalytic parameters kcat and KM. This poses fundamental biological questions about the selection pressures responsible for evolutionary tuning of these parameters. Here we are address these questions for the enzyme adenylate kinase (Adk) in eukaryotic yeast cells. A plasmid shuffling system was developed to allow quantification of relative fitness (calculated from growth rates) of yeast in response to perturbations of Adk activity introduced through mutations. Biophysical characterization verified that all variants studied were properly folded and that the mutations did not cause any substantial differences to thermal stability. We found that cytosolic Adk is essential for yeast viability in our strain background and that viability could not be restored with a catalytically dead, although properly folded Adk variant. There exist a massive overcapacity of Adk catalytic activity and only 12% of the wild type kcat is required for optimal growth at the stress condition 20°C. In summary, the approach developed here has provided new insights into the evolutionary tuning of kcat for Adk in a eukaryotic organism. The developed methodology may also become useful for uncovering new aspects of active site dynamics and also in enzyme design since a large library of enzyme variants can be screened rapidly by identifying viable colonies.

  • 595.
    Uboni, Alessia
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Horstkotte, Tim
    Kaarlejärvi, Elina
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Plant Biology and Nature Management, Vrije Universiteit Brussel, Brussels, Belgium.
    Seveque, Anthony
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Stammler, Florian
    Olofsson, Johan
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Forbes, Bruce C.
    Moen, Jon
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Long-Term Trends and Role of Climate in the Population Dynamics of Eurasian Reindeer2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 6, article id e0158359Article in journal (Refereed)
    Abstract [en]

    Temperature is increasing in Arctic and sub-Arctic regions at a higher rate than anywhere else in the world. The frequency and nature of precipitation events are also predicted to change in the future. These changes in climate are expected, together with increasing human pressures, to have significant impacts on Arctic and sub-Arctic species and ecosystems. Due to the key role that reindeer play in those ecosystems, it is essential to understand how climate will affect the region's most important species. Our study assesses the role of climate on the dynamics of fourteen Eurasian reindeer (Rangifer tarandus) populations, using for the first time data on reindeer abundance collected over a 70-year period, including both wild and semi-domesticated reindeer, and covering more than half of the species' total range. We analyzed trends in population dynamics, investigated synchrony among population growth rates, and assessed the effects of climate on population growth rates. Trends in the population dynamics were remarkably heterogeneous. Synchrony was apparent only among some populations and was not correlated with distance among population ranges. Proxies of climate variability mostly failed to explain population growth rates and synchrony. For both wild and semi-domesticated populations, local weather, biotic pressures, loss of habitat and human disturbances appear to have been more important drivers of reindeer population dynamics than climate. In semi-domesticated populations, management strategies may have masked the effects of climate. Conservation efforts should aim to mitigate human disturbances, which could exacerbate the potentially negative effects of climate change on reindeer populations in the future. Special protection and support should be granted to those semi-domesticated populations that suffered the most because of the collapse of the Soviet Union, in order to protect the livelihood of indigenous peoples that depend on the species, and the multi-faceted role that reindeer exert in Arctic ecosystems.

  • 596. Umubyeyi, Aline
    et al.
    Persson, Margareta
    Umeå University, Faculty of Medicine, Department of Nursing.
    Mogren, Ingrid
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Krantz, Gunilla
    Gender Inequality Prevents Abused Women from Seeking Care Despite Protection Given in Gender-Based Violence Legislation: a Qualitative Study from Rwanda2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, article id e0154540Article in journal (Refereed)
    Abstract [en]

    Objective Despite its burden on a person's life, Intimate Partner Violence (IPV) is known to be poorly recognised and managed in most countries and communities. This study aimed to explore health care professionals' experiences of the health care seeking processes of women exposed to intimate partner violence in Rwanda. Methods Six focus group discussions were conducted in three district hospitals and three mental health units in Rwanda. A sample of 43 health care professionals with various professions and length of work experience, who regularly took care of patients subjected to IPV, was selected for focus group discussions. The analysis was performed using qualitative content analysis. Results The theme "Gendered norms and values defeat the violence legislation in women's health care seeking when women are abused" expressed the health care professionals' experiences of the double-faced situation which women exposed to IPV met in their help seeking process. Positive initiatives to protect women were identified, but the potential for abused women to seek help and support was reduced because of poverty, gender inequality with prevailing strong norms of male superiority, and the tendency to keep abuse as a private family matter. Conclusion Legislative measures have been instituted to protect women from abuse. Still many Rwandan women do not benefit from these efforts. The role of the health care services needs to be reinforced as an important and available resource for help and support for abused women but further legislative changes are also needed. Initiatives to further improve gender equality, and institutionalised collaboration between different sectors in society would contribute to protecting women from IPV.

  • 597.
    Vaezghasemi, Masoud
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Social Sciences, Umeå Centre for Gender Studies (UCGS).
    Öhman, Ann
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Social Sciences, Umeå Centre for Gender Studies (UCGS).
    Eriksson, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hakimi, Mohammad
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Kusnanto, Hari
    Ng, Nawi
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    The effect of gender and social capital on the dual burden of malnutrition: a multilevel study in indonesia2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 8, p. e103849-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The paradoxical phenomenon of the coexistence of overweight and underweight individuals in the same household, referred to as the "dual burden of malnutrition", is a growing nutrition dilemma in low- and middle-income countries (LMICs).

    AIMS: The objectives of this study were (i) to examine the extent of the dual burden of malnutrition across different provinces in Indonesia and (ii) to determine how gender, community social capital, place of residency and other socio-economic factors affect the prevalence of the dual burden of malnutrition.

    METHODS: The current study utilized data from the fourth wave of the Indonesian Family Life Survey (IFLS) conducted between November 2007 and April 2008. The dataset contains information from 12,048 households and 45,306 individuals of all ages. This study focused on households with individuals over two years old. To account for the multilevel nature of the data, a multilevel multiple logistic regression was conducted.

    RESULTS: Approximately one-fifth of all households in Indonesia exhibited the dual burden of malnutrition, which was more prevalent among male-headed households, households with a high Socio-economic status (SES), and households in urban areas. Minimal variation in the dual burden of malnutrition was explained by the community level differences (<4%). Living in households with a higher SES resulted in higher odds of the dual burden of malnutrition but not among female-headed households and communities with the highest social capital.

    CONCLUSION: To improve household health and reduce the inequality across different SES groups, this study emphasizes the inclusion of women's empowerment and community social capital into intervention programs addressing the dual burden of malnutrition.

  • 598.
    Vahid, Harandi M.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Susanne, Lindquist
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Shrikant, Shantilal Kolan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Thomas, Brännström
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jing-Xia, Liu
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Analysis of Neurotrophic Factors in Limb and Extraocular Muscles of Mouse Model of Amyotrophic Lateral Sclerosis2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 10, article id e109833Article in journal (Refereed)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is currently an incurable fatal motor neuron syndrome characterized by progressive weakness, muscle wasting and death ensuing 3–5 years after diagnosis. Neurotrophic factors (NTFs) are known to be important in both nervous system development and maintenance. However, the attempt to translate the potential of NTFs into the therapeutic options remains limited despite substantial number of approaches, which have been tested clinically. Using quantitative RT-PCR (qRT-PCR) technique, the present study investigated mRNA expression of four different NTFs: brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4) and glial cell line-derived neurotrophic factor (GDNF) in limb muscles and extraocular muscles (EOMs) from SOD1G93A transgenic mice at early and terminal stages of ALS. General morphological examination revealed that muscle fibres were well preserved in both limb muscles and EOMs in early stage ALS mice. However, in terminal ALS mice, most muscle fibres were either atrophied or hypertrophied in limb muscles but unaffected in EOMs. qRT-PCR analysis showed that in early stage ALS mice, NT-4 was significantly down-regulated in limb muscles whereas NT-3 and GDNF were markedly up-regulated in EOMs. In terminal ALS mice, only GDNF was significantly up-regulated in limb muscles. We concluded that the early down-regulation of NT-4 in limb muscles is closely associated with muscle dystrophy and dysfunction at late stage, whereas the early up-regulations of GDNF and NT-3 in EOMs are closely associated with the relatively well-preserved muscle morphology at late stage. Collectively, the data suggested that comparing NTFs expression between limb muscles and EOMs from different stages of ALS animal models is a useful method in revealing the patho-physiology and progression of ALS, and eventually rescuing motor neuron in ALS patients.

  • 599. Valentim, Felipe Leal
    et al.
    van Mourik, Simon
    Pose, David
    Kim, Min C
    Schmid, Markus
    Max Planck Institute for Developmental Biology, Department of Molecular Biology, Spemannstrasse 35, 72076 Tübingen, Germany.
    van Ham, Roeland C H J
    Busscher, Marco
    Sanchez-Perez, Gabino F
    Molenaar, Jaap
    Angenent, Gerco C
    Immink, Richard G H
    van Dijk, Aalt D J
    A Quantitative and Dynamic Model of the Arabidopsis Flowering Time Gene Regulatory Network2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 2, article id e0116973Article in journal (Refereed)
    Abstract [en]

    Various environmental signals integrate into a network of floral regulatory genes leading to the final decision on when to flower. Although a wealth of qualitative knowledge is available on how flowering time genes regulate each other, only a few studies incorporated this knowledge into predictive models. Such models are invaluable as they enable to investigate how various types of inputs are combined to give a quantitative readout. To investigate the effect of gene expression disturbances on flowering time, we developed a dynamic model for the regulation of flowering time in Arabidopsis thaliana. Model parameters were estimated based on expression time-courses for relevant genes, and a consistent set of flowering times for plants of various genetic backgrounds. Validation was performed by predicting changes in expression level in mutant backgrounds and comparing these predictions with independent expression data, and by comparison of predicted and experimental flowering times for several double mutants. Remarkably, the model predicts that a disturbance in a particular gene has not necessarily the largest impact on directly connected genes. For example, the model predicts that SUPPRESSOR OF OVEREXPRESSION OF CONSTANS (SOC1) mutation has a larger impact on APETALA1 (AP1), which is not directly regulated by SOC1, compared to its effect on LEAFY (LFY) which is under direct control of SOC1. This was confirmed by expression data. Another model prediction involves the importance of cooperativity in the regulation of APETALA1 (AP1) by LFY, a prediction supported by experimental evidence. Concluding, our model for flowering time gene regulation enables to address how different quantitative inputs are combined into one quantitative output, flowering time.

  • 600. van den Berg, Saskia W.
    et al.
    van der A, Daphne L.
    Spijkerman, Annemieke M. W.
    van Woudenbergh, Geertruida J.
    Tijhuis, Mariken J.
    Amiano, Pilar
    Ardanaz, Eva
    Beulens, Joline W. J.
    Boeing, Heiner
    Clavel-Chapelon, Francoise
    Crowe, Francesca L.
    de Lauzon-Guillain, Blandine
    Fagherazzi, Guy
    Franks, Paul W.
    Freisling, Heinz
    Gonzalez, Carlos
    Grioni, Sara
    Halkjaer, Jytte
    Maria Huerta, Jose
    Huybrechts, Inge
    Kaaks, Rudolf
    Khaw, Kay Tee
    Masala, Giovanna
    Nilsson, Peter M.
    Overvad, Kim
    Panico, Salvatore
    Ramon Quiros, J.
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Schulze, Matthias B.
    Slimani, Nadia
    Struijk, Ellen A.
    Tjonneland, Anne
    Tumino, Rosario
    Sharp, Stephen J.
    Langenberg, Claudia
    Forouhi, Nita G.
    Feskens, Edith J. M.
    Riboli, Elio
    Wareham, Nicholas J.
    The Association between Dietary Energy Density and Type 2 Diabetes in Europe: Results from the EPIC-InterAct Study2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 5, p. e59947-Article in journal (Refereed)
    Abstract [en]

    Background: Observational studies implicate higher dietary energy density (DED) as a potential risk factor for weight gain and obesity. It has been hypothesized that DED may also be associated with risk of type 2 diabetes (T2D), but limited evidence exists. Therefore, we investigated the association between DED and risk of T2D in a large prospective study with heterogeneity of dietary intake.

    Methodology/Principal Findings: A case-cohort study was nested within the European Prospective Investigation into Cancer (EPIC) study of 340,234 participants contributing 3.99 million person years of follow-up, identifying 12,403 incident diabetes cases and a random subcohort of 16,835 individuals from 8 European countries. DED was calculated as energy (kcal) from foods (except beverages) divided by the weight (gram) of foods estimated from dietary questionnaires. Prentice-weighted Cox proportional hazard regression models were fitted by country. Risk estimates were pooled by random effects meta-analysis and heterogeneity was evaluated. Estimated mean (sd) DED was 1.5 (0.3) kcal/g among cases and subcohort members, varying across countries (range 1.4-1.7 kcal/g). After adjustment for age, sex, smoking, physical activity, alcohol intake, energy intake from beverages and misreporting of dietary intake, no association was observed between DED and T2D (HR 1.02 (95% CI: 0.93-1.13), which was consistent across countries (l(2) = 2.9%).

    Conclusions/Significance: In this large European case-cohort study no association between DED of solid and semi-solid foods and risk of T2D was observed. However, despite the fact that there currently is no conclusive evidence for an association between DED and T2DM risk, choosing low energy dense foods should be promoted as they support current WHO recommendations to prevent chronic diseases.

91011121314 551 - 600 of 665
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf