umu.sePublikationer
Ändra sökning
Avgränsa sökresultatet
1234567 151 - 200 av 665
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 151.
    Engdahl, Cecilia
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Knutsson, Sofie
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Fredriksson, Sten-Åke
    Linusson, Anna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bucht, Göran
    Ekström, Fredrik
    Acetylcholinesterases from the Disease Vectors Aedes aegypti and Anopheles gambiae: Functional Characterization and Comparisons with Vertebrate Orthologues2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 10, artikel-id e0138598Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mosquitoes of the Anopheles (An.) and Aedes (Ae.) genus are principal vectors of human diseases including malaria, dengue and yellow fever. Insecticide-based vector control is an established and important way of preventing transmission of such infections. Currently used insecticides can efficiently control mosquito populations, but there are growing concerns about emerging resistance, off-target toxicity and their ability to alter ecosystems. A potential target for the development of insecticides with reduced off-target toxicity is the cholinergic enzyme acetylcholinesterase (AChE). Herein, we report cloning, baculoviral expression and functional characterization of the wild-type AChE genes (ace-1) from An. gambiae and Ae. aegypti, including a naturally occurring insecticide-resistant (G119S) mutant of An. gambiae. Using enzymatic digestion and liquid chromatography-tandem mass spectrometry we found that the secreted proteins were post-translationally modified. The Michaelis-Menten constants and turnover numbers of the mosquito enzymes were lower than those of the orthologous AChEs from Mus musculus and Homo sapiens. We also found that the G119S substitution reduced the turnover rate of substrates and the potency of selected covalent inhibitors. Furthermore, non-covalent inhibitors were less sensitive to the G119S substitution and differentiate the mosquito enzymes from corresponding vertebrate enzymes. Our findings indicate that it may be possible to develop selective non-covalent inhibitors that effectively target both the wild-type and insecticide resistant mutants of mosquito AChE.

  • 152. Engvall, Gunn
    et al.
    Ångström-Brännström, Charlotte
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Mullaney, Tara
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Designhögskolan vid Umeå universitet.
    Nilsson, Kristina
    Wickart-Johansson, Gun
    Svärd, Anna-Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nyholm, Tufve
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Lindh, Jack
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Lindh, Viveca
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    It Is Tough and Tiring but It Works - Children's Experiences of Undergoing Radiotherapy2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 4, artikel-id e0153029Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Approximately 300 children ages 0 to 18 are diagnosed with cancer in Sweden every year, and 80 to 90 of them undergo radiotherapy treatment. The aim was to describe children's experiences of preparing for and undergoing radiotherapy, and furthermore to describe children's suggestions for improvement. Thirteen children between the ages of 5 and 15 with various cancer diagnoses were interviewed. Data was analyzed using qualitative content analysis. The findings revealed five categories: positive and negative experiences with hospital stays and practical arrangements; age-appropriate information, communication, and guidance to various degrees; struggle with emotions; use of distraction and other suitable coping strategies; and children's suggestions for improvement during radiotherapy. An overarching theme emerged: "It is tough and tiring but it works". Some key areas were: explanatory visits, the need for information and communication, being afraid, discomfort and suffering, the need for media distraction, dealing with emotions, and the need for support. A systematic, family-centered preparation program could possible help families prepare and individualized distraction during radiotherapy could contribute to reducing distress. Further studies with interventions could clarify successful programs.

  • 153.
    Eremenko, Ekaterina
    et al.
    Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
    Ben-Zvi, Anat
    National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
    Morozova-Roche, Ludmilla A.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Raveh, Dina
    Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
    Aggregation of Human S100A8 and S100A9 Amyloidogenic Proteins Perturbs Proteostasis in a Yeast Model2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 3, s. e58218-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Amyloid aggregates of the calcium-binding EF-hand proteins, S100A8 and S100A9, have been found in the corpora amylacea of patients with prostate cancer and may play a role in carcinogenesis. Here we present a novel model system using the yeast Saccharomyces cerevisiae to study human S100A8 and S100A9 aggregation and toxicity. We found that S100A8, S100A9 and S100A8/9 cotransfomants form SDS-resistant non-toxic aggregates in yeast cells. Using fluorescently tagged proteins, we showed that S100A8 and S100A9 accumulate in foci. After prolonged induction, S100A8 foci localized to the cell vacuole, whereas the S100A9 foci remained in the cytoplasm when present alone, but entered the vacuole in cotransformants. Biochemical analysis of the proteins indicated that S100A8 and S100A9 alone or coexpressed together form amyloid-like aggregates in yeast. Expression of S100A8 and S100A9 in wild type yeast did not affect cell viability, but these proteins were toxic when expressed on a background of unrelated metastable temperature-sensitive mutant proteins, Cdc53-1p, Cdc34-2p, Srp1-31p and Sec27-1p. This finding suggests that the expression and aggregation of S100A8 and S100A9 may limit the capacity of the cellular proteostasis machinery. To test this hypothesis, we screened a set of chaperone deletion mutants and found that reducing the levels of the heat-shock proteins Hsp104p and Hsp70p was sufficient to induce S100A8 and S100A9 toxicity. This result indicates that the chaperone activity of the Hsp104/Hsp70 bi-chaperone system in wild type cells is sufficient to reduce S100A8 and S100A9 amyloid toxicity and preserve cellular proteostasis. Expression of human S100A8 and S100A9 in yeast thus provides a novel model system for the study of the interaction of amyloid deposits with the proteostasis machinery.

  • 154.
    Eriksson, Margareta K.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Sjukgymnastik.
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    A 3-year randomized trial of lifestyle intervention for cardiovascular risk reduction in the primary care setting: the Swedish Björknäs study2009Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, nr 4, s. e5195-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Successfully transferring the findings of expensive and tightly controlled programmes of intensive lifestyle modification to the primary care setting is necessary if such knowledge is to be of clinical utility. The objective of this study was to test whether intensive lifestyle modification, shown previously in tightly-controlled clinical trials to be efficacious for diabetes risk-reduction among high-risk individuals, can reduce cardiovascular risk factor levels in the primary care setting. 

    Methodology / Principal Findings The Swedish Björknäs study was a randomized controlled trial conducted from 2003 to 2006 with follow-up on cardiovascular risk factors at 3, 12, 24 and 36 months. A total of 151 middle-aged men and women at moderate- to high-risk of cardiovascular disease from northern Sweden were randomly assigned to either an intensive lifestyle intervention (n=75) or control (n=76) group. The intervention was based broadly on the protocol of the Diabetes Prevention Program. The three-month intervention period was administered in the primary care setting and consisted of supervised exercise sessions and diet counselling, followed by regular group meetings during three years. The control group was given general advice about diet and exercise and received standard clinical care. Outcomes were changes in anthropometrics, aerobic fitness, self-reported physical activity, blood pressure, and metabolic traits. At 36 months post-randomisation, intensive lifestyle modification reduced waist circumference (–2.2cm: p=0.001), waist-hip ratio (–0.02: p<0.0001), systolic blood pressure (–4.9mmHg: p=0.036), and diastolic blood pressure (–1.6mmHg: p=0.005), and improved aerobic fitness (5%; p=0.038). Changes in lipid or glucose values did not differ statistically between groups. At 36 months, self-reported time spent exercising and total physical activity had increased more in the intervention group than in the control group (p<0.001).

    Conclusion / Significance  A program of intensive lifestyle modification undertaken in the primary health care setting can favourably influence cardiovascular risk-factor profiles in high-risk individuals.

  • 155.
    Eriksson Sörman, Daniel
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Marsh, John Everett
    Hansson, Patrik
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Ljungberg, Jessica K.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Longitudinal effects of bilingualism on dual-tasking2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 12, artikel-id e0189299Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An ongoing debate surrounds whether bilinguals outperform monolinguals in tests of executive processing. The aim of this study was to investigate if there are long-term (10 year) bilingual advantages in executive processing, as indexed by dual-task performance, in a sample that were 40-65 years at baseline. The bilingual (n = 24) and monolingual (n = 24) participants were matched on age, sex, education, fluid intelligence, and study sample. Participants performed free-recall for a 12-item list in three dual-task settings wherein they sorted cards either during encoding, retrieval, or during both encoding and retrieval of the word-list. Free recall without card sorting was used as a reference to compute dual-task costs. The results showed that bilinguals significantly outperformed monolinguals when they performed card-sorting during both encoding and retrieval of the word-list, the condition that presumably placed the highest demands on executive functioning. However, dual-task costs increased over time for bilinguals relative to monolinguals, a finding that is possibly influenced by retirement age and limited use of second language in the bilingual group.

  • 156.
    Erttmann, Saskia F.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Gekara, Nelson O.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Fällman, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Bacteria Induce Prolonged PMN Survival via a Phosphatidylcholine-Specific Phospholipase C- and Protein Kinase C-Dependent Mechanism2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 1, s. e87859-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Polymorphonuclear leukocytes (PMNs) are essential for the human innate immune defense, limiting expansion of invading microorganisms. PMN turnover is controlled by apoptosis, but the regulating signaling pathways remain elusive, largely due to inherent differences between mice and humans that undermine use of mouse models for understanding human PMN biology. Here, we aim to elucidate signal transduction mediating survival of human peripheral blood PMNs in response to bacteria, such as Yersinia pseudotuberculosis, an enteropathogen that causes the gastro-intestinal disease yersiniosis, as well as Escherichia coli and Staphylococcus aureus. Determinations of cell death reveal that uninfected control cells undergo apoptosis, while PMNs infected with either Gram-positive or -negative bacteria show profoundly increased survival. Infected cells exhibit decreased caspase 3 and 8 activities, increased mitochondrial integrity and are resistant to apoptosis induced by a death receptor ligand. This bacteria-induced response is accompanied by pro-inflammatory cytokine production including interleukin-8 and tumor necrosis factor-a competent to attract additional PMNs. Using agonists and pharmacological inhibitors, we show participation of Toll-like receptor 2 and 4, and interestingly, that protein kinase C (PKC) and phosphatidylcholine-specific phospholipase C (PC-PLC), but not tyrosine kinases or phosphatidylinositol-specific phospholipase C (PI-PLC) are key players in this dual PMN response. Our findings indicate the importance of prolonged PMN survival in response to bacteria, where general signaling pathways ensure complete exploitation of PMN anti-microbial capacity.

  • 157.
    Esberg, Anders
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Moqtaderi, Zarmik
    Fan, Xiaochun
    Lu, Jian
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Struhl, Kevin
    Byström, Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Iwr1 protein is important for preinitiation complex formation by all three nuclear RNA polymerases in Saccharomyces cerevisiae2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 6, s. e20829-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Iwr1, a protein conserved throughout eukaryotes, was originally identified by its physical interaction with RNA polymerase (Pol) II.

    PRINCIPAL FINDINGS: Here, we identify Iwr1 in a genetic screen designed to uncover proteins involved in Pol III transcription in S. cerevisiae. Iwr1 is important for Pol III transcription, because an iwr1 mutant strain shows reduced association of TBP and Pol III at Pol III promoters, a decreased rate of Pol III transcription, and lower steady-state levels of Pol III transcripts. Interestingly, an iwr1 mutant strain also displays reduced association of TBP to Pol I-transcribed genes and of both TBP and Pol II to Pol II-transcribed promoters. Despite this, rRNA and mRNA levels are virtually unaffected, suggesting a post-transcriptional mechanism compensating for the occupancy defect.

    CONCLUSIONS: Thus, Iwr1 plays an important role in preinitiation complex formation by all three nuclear RNA polymerases.

  • 158.
    Esberg, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Muller, Ludo A. H.
    McCusker, John H.
    Genomic structure of and genome-wide recombination in the saccharomyces cerevisiae S288C progenitor isolate EM932011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 9, s. e25211-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The diploid isolate EM93 is the main ancestor to the widely used Saccharomyces cerevisiae haploid laboratory strain, S288C. In this study, we generate a high-resolution overview of the genetic differences between EM93 and S288C. We show that EM93 is heterozygous for >45,000 polymorphisms, including large sequence polymorphisms, such as deletions and a Saccharomyces paradoxus introgression. We also find that many large sequence polymorphisms (LSPs) are associated with Ty-elements and sub-telomeric regions. We identified 2,965 genetic markers, which we then used to genotype 120 EM93 tetrads. In addition to deducing the structures of all EM93 chromosomes, we estimate that the average EM93 meiosis produces 144 detectable recombination events, consisting of 87 crossover and 31 non-crossover gene conversion events. Of the 50 polymorphisms showing the highest levels of non-crossover gene conversions, only three deviated from parity, all of which were near heterozygous LSPs. We find that non-telomeric heterozygous LSPs significantly reduce meiotic recombination in adjacent intervals, while sub-telomeric LSPs have no discernable effect on recombination. We identified 203 recombination hotspots, relatively few of which are hot for both non-crossover gene conversions and crossovers. Strikingly, we find that recombination hotspots show limited conservation. Some novel hotspots are found adjacent to heterozygous LSPs that eliminate other hotspots, suggesting that hotspots may appear and disappear relatively rapidly.

  • 159. Everitt, Aaron R
    et al.
    Clare, Simon
    McDonald, Jacqueline U
    Kane, Leanne
    Harcourt, Katherine
    Ahras, Malika
    Lall, Amar
    Hale, Christine
    Rodgers, Angela
    Young, Douglas B
    Haque, Ashraful
    Billker, Oliver
    Tregoning, John S
    Dougan, Gordon
    Kellam, Paul
    Defining the range of pathogens susceptible to Ifitm3 restriction using a knockout mouse model2013Ingår i: PLoS ONE, E-ISSN 1932-6203, Vol. 8, nr 11, s. e80723-e80723Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The interferon-inducible transmembrane (IFITM) family of proteins has been shown to restrict a broad range of viruses in vitro and in vivo by halting progress through the late endosomal pathway. Further, single nucleotide polymorphisms (SNPs) in its sequence have been linked with risk of developing severe influenza virus infections in humans. The number of viruses restricted by this host protein has continued to grow since it was first demonstrated as playing an antiviral role; all of which enter cells via the endosomal pathway. We therefore sought to test the limits of antimicrobial restriction by Ifitm3 using a knockout mouse model. We showed that Ifitm3 does not impact on the restriction or pathogenesis of bacterial (Salmonella typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis) or protozoan (Plasmodium berghei) pathogens, despite in vitro evidence. However, Ifitm3 is capable of restricting respiratory syncytial virus (RSV) in vivo either through directly restricting RSV cell infection, or by exerting a previously uncharacterised function controlling disease pathogenesis. This represents the first demonstration of a virus that enters directly through the plasma membrane, without the need for the endosomal pathway, being restricted by the IFITM family; therefore further defining the role of these antiviral proteins.

  • 160. Fallath, Thorya
    et al.
    Kidd, Brendan N.
    Stiller, Jiri
    Davoine, Celine
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Björklund, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Manners, John M.
    Kazan, Kemal
    Schenk, Peer M.
    MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 4, artikel-id e0176022Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The conserved protein complex known as Mediator conveys transcriptional signals by acting as an intermediary between transcription factors and RNA polymerase II. As a result, Mediator subunits play multiple roles in regulating developmental as well as abiotic and biotic stress pathways. In this report we identify the head domain subunits MEDIATOR18 and MEDIATOR20 as important susceptibility factors for Fusarium oxysporum infection in Arabidopsis thaliana. Mutants of MED18 and MED20 display down-regulation of genes associated with jasmonate signaling and biosynthesis while up-regulation of salicylic acid associated pathogenesis related genes and reactive oxygen producing and scavenging genes. We propose that MED18 and MED20 form a sub-domain within Mediator that controls the balance of salicylic acid and jasmonate associated defense pathways.

  • 161.
    Farooqi, Aijaz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Adamsson, M
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Serenius, F.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hägglöf, Bruno
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Executive Functioning and Learning Skills of Adolescent Children Born at Fewer than 26 Weeks of Gestation2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 3, artikel-id e0151819Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims To assess the cognitive and behavioral aspects of executive functioning (EF) and learning skills in extremely preterm (EPT) children compared with term control children aged 10 to 15 years. Methods A total of 132 of 134 (98% of all eligible survivors) EPT children born at the 2 Swedish regional tertiary care centers from 1992 to 1998 (mean age = 12 years, mean birth weight = 718 g, and mean gestational age = 24.4 weeks) and 103 matched term controls were assessed. General intelligence was assessed using the Wechsler Intelligence Scale for Children (WISC-III-R), and cognitive aspects of EF were analyzed using EF-sensitive sub-scales of the WISC-III-R and Tower test of the Delis-Kaplan Executive Function Scale (D-KEFS). Behaviors related to EF and learning skills were assessed using the Five to Fifteen questionnaire, which is a validated parent and teacher instrument. Academic performance in school was assessed by teachers' responses on Achenbach's Teachers Report Form. Analyses performed included multivariate analyses of covariance (ANCOVA and MANCOVA) and logistic regression analyses. Results The EPT children displayed significant deficits in cognitive aspects of EF compared with the controls, exhibiting decreases on the order of 0.9 SD to 1.2 SD for tasks of verbal conceptual reasoning, verbal and non-verbal working memory, processing speed and planning ability (P < 0.001 for all). After excluding the children with major neurosensory impairment (NSI) or a Full Scale intelligence quotient (FSIQ) of < 70, significant differences were observed on all tests. Compared with controls, parents and teachers of EPT children reported significantly more EF-related behavioral problems. MANCOVA of teacher-reported learning skills in children with FSIQ > 70 and without major NSI revealed no interactions, but significant main effects were observed for the behavioral composite executive function score, group status (EPT vs control) and FSIQ, for which all effect sizes were medium to large. The corresponding findings of MANCOVA of the parent-reported learning skills were very similar. According to the teachers' ratings, the EPT children were less well adjusted to the school environment. Conclusion EPT children born in the 1990s who received active perinatal care are at an increased risk of executive dysfunction, even after excluding children with significant neurodevelopmental disabilities. Even mild to moderate executive dysfunctions has a significant impact on learning skills. These findings suggest the need for timely interventions that address specific cognitive vulnerabilities and executive dysfunctions.

  • 162. Feitosa, Mary F.
    et al.
    Kraja, Aldi T.
    Chasman, Daniel I.
    Sung, Yun J.
    Winkler, Thomas W.
    Ntalla, Ioanna
    Guo, Xiuqing
    Franceschini, Nora
    Cheng, Ching-Yu
    Sim, Xueling
    Vojinovic, Dina
    Marten, Jonathan
    Musani, Solomon K.
    Li, Changwei
    Bentley, Amy R.
    Brown, Michael R.
    Schwander, Karen
    Richard, Melissa A.
    Noordam, Raymond
    Aschard, Hugues
    Bartz, Traci M.
    Bielak, Lawrence F.
    Dorajoo, Rajkumar
    Fisher, Virginia
    Hartwig, Fernando P.
    Horimoto, Andrea R. V. R.
    Lohman, Kurt K.
    Manning, Alisa K.
    Rankinen, Tuomo
    Smith, Albert V.
    Tajuddin, Salman M.
    Wojczynski, Mary K.
    Alver, Maris
    Boissel, Mathilde
    Cai, Qiuyin
    Campbell, Archie
    Chai, Jin Fang
    Chen, Xu
    Divers, Jasmin
    Gao, Chuan
    Goel, Anuj
    Hagemeijer, Yanick
    Harris, Sarah E.
    He, Meian
    Hsu, Fang-Chi
    Jackson, Anne U.
    Kahonen, Mika
    Kasturiratne, Anuradhani
    Komulainen, Pirjo
    Kuhnel, Brigitte
    Laguzzi, Federica
    Luan, Jian'an
    Matoba, Nana
    Nolte, Ilja M.
    Padmanabhan, Sandosh
    Riaz, Muhammad
    Rueedi, Rico
    Robino, Antonietta
    Said, M. Abdullah
    Scott, Robert A.
    Sofer, Tamar
    Stancakova, Alena
    Takeuchi, Fumihiko
    Tayo, Bamidele O.
    van der Most, Peter J.
    Varga, Tibor V.
    Vitart, Veronique
    Wang, Yajuan
    Ware, Erin B.
    Warren, Helen R.
    Weiss, Stefan
    Wen, Wanqing
    Yanek, Lisa R.
    Zhang, Weihua
    Zhao, Jing Hua
    Afaq, Saima
    Amin, Najaf
    Amini, Marzyeh
    Arking, Dan E.
    Aung, Tin
    Boerwinkle, Eric
    Borecki, Ingrid
    Broeckel, Ulrich
    Brown, Morris
    Brumat, Marco
    Burke, Gregory L.
    Canouil, Mickael
    Chakravarti, Aravinda
    Charumathi, Sabanayagam
    Chen, Yii-Der Ida
    Connell, John M.
    Correa, Adolfo
    Fuentes, Lisa de las
    de Mutsert, Renee
    de Silva, H. Janaka
    Deng, Xuan
    Ding, Jingzhong
    Duan, Qing
    Eaton, Charles B.
    Ehret, Georg
    Eppinga, Ruben N.
    Evangelou, Evangelos
    Fau, Jessica D.
    Felix, Stephan B.
    Forouhi, Nita G.
    Forrester, Terrence
    Franco, Oscar H.
    Friedlander, Yechiel
    Gandin, Ilaria
    Gao, He
    Ghanbari, Mohsen
    Gigante, Bruna
    Gu, C. Charles
    Gu, Dongfeng
    Hagenaars, Saskia P.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Harris, Tamara B.
    He, Jiang
    Heikkinen, Sami
    Heng, Chew-Kiat
    Hirata, Makoto
    Howard, Barbara V.
    Ikram, M. Arfan
    John, Ulrich
    Katsuya, Tomohiro
    Khor, Chiea Chuen
    Kilpelainen, Tuomas O.
    Koh, Woon-Puay
    Krieger, Jose E.
    Kritchevsky, Stephen B.
    Kubo, Michiaki
    Kuusisto, Johanna
    Lakka, Timo A.
    Langefeld, Carl D.
    Langenberg, Claudia
    Launer, Lenore J.
    Lehne, Benjamin
    Lewis, Cora E.
    Li, Yize
    Lin, Shiow
    Liu, Jianjun
    Liu, Jingmin
    Loh, Marie
    Louie, Tin
    Magi, Reedik
    McKenzie, Colin A.
    Meitinger, Thomas
    Metspalu, Andres
    Milaneschi, Yuri
    Milani, Lili
    Mohlke, Karen L.
    Momozawa, Yukihide
    Nalls, Mike A.
    Nelson, Christopher P.
    Sotoodehnia, NelsonNona
    Norris, Jill M.
    O'Connell, Jeff R.
    Palmer, Nicholette D.
    Perls, Thomas
    Pedersen, Nancy L.
    Peters, Annette
    Peyser, Patricia A.
    Poulter, Neil
    Raffel, Leslie J.
    Raitakari, Olli T.
    Roll, Kathryn
    Rose, Lynda M.
    Rosendaal, Frits R.
    Rotter, Jerome I.
    Schmidt, Carsten O.
    Schreiner, Pamela J.
    Schupf, Nicole
    Scott, William R.
    Sever, Peter S.
    Shi, Yuan
    Sidney, Stephen
    Sims, Mario
    Sitlani, Colleen M.
    Smith, Jennifer A.
    Snieder, Harold
    Starr, John M.
    Strauch, Konstantin
    Stringham, Heather M.
    Tan, Nicholas Y. Q.
    Tang, Hua
    Taylor, Kent D.
    Teo, Yik Ying
    Tham, Yih Chung
    Turner, Stephen T.
    Uitterlinden, Andre G.
    Vollenweider, Peter
    Waldenberger, Melanie
    Wang, Lihua
    Wang, Ya Xing
    Bin Wei, Wen
    Williams, Christine
    Yao, Jie
    Yu, Caizheng
    Yuan, Jian-Min
    Zhao, Wei
    Zonderman, Alan B.
    Becker, Diane M.
    Boehnke, Michael
    Bowden, Donald W.
    Chambers, John C.
    Deary, Ian J.
    Esko, Tonu
    Farrall, Martin
    Franks, Paul W.
    Freedman, Barry I.
    Froguel, Philippe
    Gasparini, Paolo
    Gieger, Christian
    Jonas, Jost Bruno
    Kamatani, Yoichiro
    Kato, Norihiro
    Kooner, Jaspal S.
    Kutalik, Zoltan
    Laakso, Markku
    Laurie, Cathy C.
    Leander, Karin
    Lehtimaki, Terho
    Study, Lifelines Cohort
    Magnusson, Patrik K. E.
    Oldehinkel, Albertine J.
    Penninx, Brenda W. J. H.
    Poiasek, Ozren
    Porteous, David J.
    Rauramaa, Rainer
    Samani, Nilesh J.
    Scott, James
    Shu, Xiao-Ou
    van der Harst, Pim
    Wagenknecht, Lynne E.
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wickremasinghe, Ananda R.
    Wu, Tangchun
    Zheng, Wei
    Bouchard, Claude
    Christensen, Kaare
    Evans, Michele K.
    Gudnason, Vilmundur
    Horta, Bernardo L.
    Kardia, Sharon L. R.
    Liu, Yongmei
    Pereira, Alexandre C.
    Psaty, Bruce M.
    Ridker, Paul M.
    van Dam, Rob M.
    Gauderman, W. James
    Zhu, Xiaofeng
    Mook-Kanamori, Dennis O.
    Fornage, Myriam
    Rotimi, Charles N.
    Cupples, L. Adrienne
    Kelly, Tanika N.
    Fox, Ervin R.
    Hayward, Caroline
    van Duijn, Cornelia M.
    Tai, E. Shyong
    Wong, Tien Yin
    Kooperberg, Charles
    Palmas, Walter
    Rice, Kenneth
    Morrison, Alanna C.
    Elliott, Paul
    Caulfield, Mark J.
    Munroe, Patricia B.
    Rao, Dabeeru C.
    Province, Michael A.
    Levy, Daniel
    Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 6, artikel-id e0198166Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

  • 163.
    Fick, Jerker
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lindberg, Richard
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Tysklind, Mats
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Haemig, Paul D
    Waldenström, Jonas
    Olsen, Björn
    Antiviral oseltamivir is not removed or degraded in normal sewage water treatment: implications for development of resistance by influenza A virus2007Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 2, nr 10Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Oseltamivir is the main antiviral for treatment and prevention of pandemic influenza. The increase in oseltamivir resistance reported recently has therefore sparked a debate on how to use oseltamivir in non pandemic influenza and the risks associated with wide spread use during a pandemic. Several questions have been asked about the fate of oseltamivir in the sewage treatment plants and in the environment. We have assessed the fate of oseltamivir and discuss the implications of environmental residues of oseltamivir regarding the occurrence of resistance. A series of batch experiments that simulated normal sewage treatment with oseltamivir present was conducted and the UV-spectra of oseltamivir were recorded. Findings: Our experiments show that the active moiety of oseltamivir is not removed in normal sewage water treatments and is not degraded substantially by UV light radiation, and that the active substance is released in waste water leaving the plant. Our conclusion is that a ubiquitous use of oseltamivir may result in selection pressures in the environment that favor development of drug-resistance.

  • 164. Finnbjornsdottir, Ragnhildur Gudrun
    et al.
    Carlsen, Hanne Krage
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Centre of Public Health Sciences, University of Iceland, Stapi, v/Hringbraut, 101 Reykjavik, Iceland.
    Thorsteinsson, Throstur
    Oudin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Lund, Sigrun Helga
    Gislason, Thorarinn
    Rafnsson, Vilhjalmur
    Association between Daily Hydrogen Sulfide Exposure and Incidence of Emergency Hospital Visits: A Population-Based Study2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 5, artikel-id e0154946Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The adverse health effects of high concentrations of hydrogen sulfide (H2S) exposure are well known, though the possible effects of low concentrations have not been thoroughly studied. The aim was to study short-term associations between modelled ambient low-level concentrations of intermittent hydrogen sulfide (H2S) and emergency hospital visits with heart diseases (HD), respiratory diseases, and stroke as primary diagnosis.

    METHODS: The study is population-based, using data from patient-, and population-registers from the only acute care institution in the Reykjavik capital area, between 1 January, 2007 and 30 June, 2014. The study population was individuals (≥18yr) living in the Reykjavik capital area. The H2S emission originates from a geothermal power plant in the vicinity. A model was used to estimate H2S exposure in different sections of the area. A generalized linear model assuming Poisson distribution was used to investigate the association between emergency hospital visits and H2S exposure. Distributed lag models were adjusted for seasonality, gender, age, traffic zones, and other relevant factors. Lag days from 0 to 4 were considered.

    RESULTS: The total number of emergency hospital visits was 32961 with a mean age of 70 years. In fully adjusted un-stratified models, H2S concentrations exceeding 7.00μg/m3 were associated with increases in emergency hospital visits with HD as primary diagnosis at lag 0 risk ratio (RR): 1.067; 95% confidence interval (CI): 1.024-1.111, lag 2 RR: 1.049; 95%CI: 1.005-1.095, and lag 4 RR: 1.046; 95%CI: 1.004-1.089. Among males an association was found between H2S concentrations exceeding 7.00μg/m3, and HD at lag 0 RR: 1.087; 95%CI: 1.032-1.146 and lag 4 RR: 1080; 95%CI: 1.025-1.138; and among those 73 years and older at lag 0 RR: 1.075; 95%CI: 1.014-1.140 and lag 3 RR: 1.072; 95%CI: 1.009-1.139. No associations were found with other diseases.

    CONCLUSIONS: The study showed an association between emergency hospital visits with HD as primary diagnosis and same day H2S concentrations exceeding 7.00μg/m3, more pronounced among males and those 73 years and older than among females and younger individuals.

  • 165.
    Fjellman-Wiklund, Anncristine
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Nordin, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Skelton, Dawn A.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi. School of Health and Life Sciences, Institute of Applied Health Research, Glasgow Caledonian University, Glasgow, United Kingdom.
    Lundin-Olsson, Lillemor
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Reach the Person behind the Dementia Physical Therapists' Reflections and Strategies when Composing Physical Training2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 12, artikel-id e0166686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dementia is a disease characterized by cognitive impairment and physical decline that worsens over time. Exercise is one lifestyle factor that has been identified as a potential means of reducing or delaying progression of the symptoms of dementia, maximizing function and independence. The purpose of this study was to explore physical therapists' (PTs) experiences and reflections on facilitating high-intensity functional exercise with older people living with dementia, in residential care home settings. The study used a qualitative design based on interviews, individually or in small groups, with seven PTs engaged as leaders in the training of older people with dementia. The interviews were analyzed with a modified Grounded Theory method with focus on constant comparisons. To increase trustworthiness the study used triangulation within investigators and member checking. The core category "Discover and act in the moment-learn over time" reflects how the PTs continuously developed their own learning in an iterative process. They built on previous knowledge to communicate with residents and staff and to tailor the high intensity training in relation to each individual at that time point. The category "Be on your toes" highlights how the PTs searched for sufficient information about each individual, before and during training, by eliciting the person's current status from staff and by interpreting the person's body language. The category "Build a bond with a palette of strategies" describes the importance of confirmation to build up trust and the use of group members and the room to create an interplay between exercise and social interaction. These findings highlight the continuous iterative process of building on existing knowledge, sharing and reflecting, being alert to any alterations needed for individuals that day, communication skills (both with residents and staff) and building a relationship and trust with residents in the effective delivery of high intensity functional exercise to older people living with dementia in care settings.

  • 166.
    Fong, Gloria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada.
    Backman, Ludvig J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin.
    Scott, Alex
    Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada.
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    The Effects of Substance P and Acetylcholine on Human Tenocyte Proliferation Converge Mechanistically via TGF-β12017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 3, artikel-id e0174101Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous in vitro studies on human tendon cells (tenocytes) have demonstrated that the exogenous administration of substance P (SP) and acetylcholine (ACh) independently result in tenocyte proliferation, which is a prominent feature of tendinosis. Interestingly, the possible link between SP and ACh has not yet been explored in human tenocytes. Recent studies in other cell types demonstrate that both SP and ACh independently upregulate TGF-β1 expression via their respective receptors, the neurokinin 1 receptor (NK-1R) and muscarinic ACh receptors (mAChRs). Furthermore, TGF-β1 has been shown to downregulate NK-1R expression in human keratocytes. The aim of this study was to examine if TGF-β1 is the intermediary player involved in mediating the proliferative pathway shared by SP and ACh in human tenocytes. The results showed that exogenous administration of SP and ACh both caused significant upregulation of TGF-β1 at the mRNA and protein levels. Exposing cells to TGF-β1 resulted in increased cell viability of tenocytes, which was blocked in the presence of the TGFβRI/II kinase inhibitor. In addition, the proliferative effects of SP and ACh on tenocytes were reduced by the TGFβRI/II kinase inhibitor; this supports the hypothesis that the proliferative effects of these signal substances are mediated via the TGF-β axis. Furthermore, exogenous TGF-β1 downregulated NK-1R and mAChRs expression at both the mRNA and protein levels, and these effects were negated by simultaneous exposure to the TGFβRI/II kinase inhibitor, suggesting a negative feedback loop. In conclusion, the results indicate that TGF-β1 is the intermediary player through which the proliferative actions of both SP and ACh converge mechanistically.

  • 167.
    Forsberg, Karin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Jonsson, P Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Bergemalm, Daniel
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Graffmo, Karin S
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hultdin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Jacobsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Rosquist, Roland
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Novel antibodies reveal inclusions containing non-native SOD1 in sporadic ALS patients2010Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, nr 7, s. e11552-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mutations in CuZn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) and are found in 6% of ALS patients. Non-native and aggregation-prone forms of mutant SOD1s are thought to trigger the disease. Two sets of novel antibodies, raised in rabbits and chicken, against peptides spaced along the human SOD1 sequence, were by enzyme-linked immunosorbent assay and an immunocapture method shown to be specific for denatured SOD1. These were used to examine SOD1 in spinal cords of ALS patients lacking mutations in the enzyme. Small granular SOD1-immunoreactive inclusions were found in spinal motoneurons of all 37 sporadic and familial ALS patients studied, but only sparsely in 3 of 28 neurodegenerative and 2 of 19 non-neurological control patients. The granular inclusions were by confocal microscopy found to partly colocalize with markers for lysosomes but not with inclusions containing TAR DNA binding protein-43, ubiquitin or markers for endoplasmic reticulum, autophagosomes or mitochondria. Granular inclusions were also found in carriers of SOD1 mutations and in spinobulbar muscular atrophy (SBMA) patients and they were the major type of inclusion detected in ALS patients homozygous for the wild type-like D90A mutation. The findings suggest that SOD1 may be involved in ALS pathogenesis in patients lacking mutations in the enzyme.

  • 168.
    Fottrell, Edward
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Kahn, Kathleen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Tollman, Stephen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Byass, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Probabilistic methods for verbal autopsy interpretation: InterVA robustness in relation to variations in a priori probabilities2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 11, s. e27200-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: InterVA is a probabilistic method for interpreting verbal autopsy (VA) data. It uses a priori approximations of probabilities relating to diseases and symptoms to calculate the probability of specific causes of death given reported symptoms recorded in a VA interview. The extent to which InterVA's ability to characterise a population's mortality composition might be sensitive to variations in these a priori probabilities was investigated.

    Methods: A priori InterVA probabilities were changed by 1, 2 or 3 steps on the logarithmic scale on which the original probabilities were based. These changes were made to a random selection of 25% and 50% of the original probabilities, giving six model variants. A random sample of 1,000 VAs from South Africa, were used as a basis for experimentation and were processed using the original InterVA model and 20 random instances of each of the six InterVA model variants. Rank order of cause of death and cause-specific mortality fractions (CSMFs) from the original InterVA model and the mean, maximum and minimum results from the 20 randomly modified InterVA models for each of the six variants were compared.

    Results: CSMFs were functionally similar between the original InterVA model and the models with modified a priori probabilities such that even the CSMFs based on the InterVA model with the greatest degree of variation in the a priori probabilities would not lead to substantially different public health conclusions. The rank order of causes were also similar between all versions of InterVA.

    Conclusion: InterVA is a robust model for interpreting VA data and even relatively large variations in a priori probabilities do not affect InterVA-derived results to a great degree. The original physician-derived a priori probabilities are likely to be sufficient for the global application of InterVA in settings without routine death certification.

  • 169.
    Fowler, Christopher J
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Hammarsten, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Tumour cannabinoid CB(1) receptor and phosphorylated epidermal growth factor receptor expression are additive prognostic markers for prostate cancer2010Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, nr 12, s. e15205-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    These data indicate that a high tumour CB(1) receptor expression at diagnosis augments the deleterious effects of a high pEGFR expression upon disease-specific survival.

  • 170. Fransen-Pettersson, Nina
    et al.
    Duarte, Nadia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik. nstituto Gulbenkian de Sciencia, Oeiras, 2780–156 Oeiras, Portugal.
    Nilsson, Julia
    Lundholm, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Mayans, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Larefalk, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Hannibal, Tine D.
    Hansen, Lisbeth
    Schmidt-Christensen, Anja
    Ivars, Fredrik
    Cardell, Susanna
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Rozell, Bjoern
    Holmberg, Dan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik. EMV Immunology, BMC, Lund University, Lund, Sweden; ISIM- Immunology, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark.
    A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 7, artikel-id e0159850Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF) mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT) induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders.

  • 171. Fritz, Helena K.
    et al.
    Gustafsson, Anna
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Ceder, Yvonne
    Axelson, Hakan
    Dahlback, Bjorn
    The Axl-Regulating Tumor Suppressor miR-34a Is Increased in ccRCC but Does Not Correlate with Axl mRNA or Axl Protein Levels2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 8, artikel-id e0135991Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High expression of the receptor tyrosine kinase Axl is associated with poor prognosis in patients with Renal Cell Carcinoma (RCC), the most common malignancy of the kidney. The miR-34a has been shown to directly regulate Axl in cancer cells. The miR-34a is a mediator of p53-dependent tumor suppression, and low expression of miR-34a has been associated with worse prognosis in several cancers. Our aim was to elucidate whether miR-34a or the other members of the miR-34 family (miR-34b/c) regulate Axl in RCC.

  • 172.
    Frost, Stefan
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Ho, Oanh
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Login, Frédéric H
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Weise, Christoph F
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wolf-Watz, Hans
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Wolf-Watz, Magnus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Autoproteolysis and Intramolecular Dissociation of Yersinia YscU Precedes Secretion of Its C-Terminal Polypeptide YscU CC2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 11, artikel-id e49349Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Type III secretion system mediated secretion and translocation of Yop-effector proteins across the eukaryotic target cell membrane by pathogenic Yersinia is highly organized and is dependent on a switching event from secretion of early structural substrates to late effector substrates (Yops). Substrate switching can be mimicked in vitro by modulating the calcium levels in the growth medium. YscU that is essential for regulation of this switch undergoes autoproteolysis at a conserved N↑PTH motif, resulting in a 10 kDa C-terminal polypeptide fragment denoted YscUCC. Here we show that depletion of calcium induces intramolecular dissociation of YscUCC from YscU followed by secretion of the YscUCC polypeptide. Thus, YscUCC behaved in vivo as a Yop protein with respect to secretion properties. Further, destabilized yscU mutants displayed increased rates of dissociation of YscUCC in vitro resulting in enhanced Yop secretion in vivo at 30°C relative to the wild-type strain.These findings provide strong support to the relevance of YscUCC dissociation for Yop secretion. We propose that YscUCC orchestrates a block in the secretion channel that is eliminated by calcium depletion. Further, the striking homology between different members of the YscU/FlhB family suggests that this protein family possess regulatory functions also in other bacteria using comparable mechanisms.

  • 173. Gabrielsen, Mads
    et al.
    Beckham, Katherine S H
    Feher, Victoria A
    Zetterström, Caroline E
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Wang, Dai
    Müller, Sylke
    Elofsson, Mikael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Amaro, Rommie E
    Byron, Olwyn
    Roe, Andrew J
    Structural Characterisation of Tpx from Yersinia pseudotuberculosis Reveals Insights into the Binding of Salicylidene Acylhydrazide Compounds2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 2, s. e32217-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Thiol peroxidase, Tpx, has been shown to be a target protein of the salicylidene acylhydrazide class of antivirulence compounds. In this study we present the crystal structures of Tpx from Y. pseudotuberculosis (ypTpx) in the oxidised and reduced states, together with the structure of the C61S mutant. The structures solved are consistent with previously solved atypical 2-Cys thiol peroxidases, including that for “forced” reduced states using the C61S mutant. In addition, by investigating the solution structure of ypTpx using small angle X-ray scattering (SAXS), we have confirmed that reduced state ypTpx in solution is a homodimer. The solution structure also reveals flexibility around the dimer interface. Notably, the conformational changes observed between the redox states at the catalytic triad and at the dimer interface have implications for substrate and inhibitor binding. The structural data were used to model the binding of two salicylidene acylhydrazide compounds to the oxidised structure of ypTpx. Overall, the study provides insights into the binding of the salicylidene acylhydrazides to ypTpx, aiding our long-term strategy to understand the mode of action of this class of compounds.

  • 174. Gallo, Valentina
    et al.
    Mackenbach, Johan P.
    Ezzati, Majid
    Menvielle, Gwenn
    Kunst, Anton E.
    Rohrmann, Sabine
    Kaaks, Rudolf
    Teucher, Birgit
    Boeing, Heiner
    Bergmann, Manuela M.
    Tjonneland, Anne
    Dalton, Susanne O.
    Overvad, Kim
    Redondo, Maria-Luisa
    Agudo, Antonio
    Daponte, Antonio
    Arriola, Larraitz
    Navarro, Carmen
    Barricante Gurrea, Aurelio
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Tim
    Naska, Androniki
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Masala, Giovanna
    Panico, Salvatore
    Contiero, Paolo
    Tumino, Rosario
    Bueno-de-Mesquita, H. Bas
    Siersema, Peter D.
    Peeters, Petra P.
    Zackrisson, Sophia
    Almquist, Martin
    Eriksson, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Skeie, Guri
    Braaten, Tonje
    Lund, Eiliv
    Illner, Anne-Kathrin
    Mouw, Traci
    Riboli, Elio
    Vineis, Paolo
    Social Inequalities and Mortality in Europe: Results from a Large Multi-National Cohort2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 7, s. e39013-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Socio-economic inequalities in mortality are observed at the country level in both North America and Europe. The purpose of this work is to investigate the contribution of specific risk factors to social inequalities in cause-specific mortality using a large multi-country cohort of Europeans. Methods: A total of 3,456,689 person/years follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of subjects coming from 9 European countries was recorded as proxy for socioeconomic status (SES). Cox proportional hazard model's with a step-wise inclusion of explanatory variables were used to explore the association between SES and mortality; a Relative Index of Inequality (RII) was calculated as measure of relative inequality. Results: Total mortality among men with the highest education level is reduced by 43% compared to men with the lowest (HR 0.57, 95% C.I. 0.52-0.61); among women by 29% (HR 0.71, 95% C.I. 0.64-0.78). The risk reduction was attenuated by 7% in men and 3% in women by the introduction of smoking and to a lesser extent (2% in men and 3% in women) by introducing body mass index and additional explanatory variables (alcohol consumption, leisure physical activity, fruit and vegetable intake) (3% in men and 5% in women). Social inequalities were highly statistically significant for all causes of death examined in men. In women, social inequalities were less strong, but statistically significant for all causes of death except for cancer-related mortality and injuries. Discussion: In this European study, substantial social inequalities in mortality among European men and women which cannot be fully explained away by accounting for known common risk factors for chronic diseases are reported.

  • 175. Garenne, Michel
    et al.
    Kahn, Kathleen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Collinson, Mark
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Gomez-Olive, Xavier
    Tollman, Stephen
    Protective Effect of Pregnancy in Rural South Africa: Questioning the Concept of "Indirect Cause'' of Maternal Death2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 5, s. e64414-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Measurement of the level and composition of maternal mortality depends on the definition used, with inconsistencies leading to inflated rates and invalid comparisons across settings. This study investigates the differences in risk of death for women in their reproductive years during and outside the maternal risk period (pregnancy, delivery, puerperium), focusing on specific causes of infectious, non-communicable and external causes of death after separating out direct obstetrical causes. Methods: Data on all deaths of women aged 15-49 years that occurred in the Agincourt sub-district between 1992 and 2010 were obtained from the Agincourt health and socio-demographic surveillance system (HDSS) located in rural South Africa. Causes of death were assessed using a validated verbal autopsy instrument. Analysis included 2170 deaths, of which 137 occurred during the maternal risk period. Findings: Overall, women had significantly lower mortality during the maternal risk period than outside it (age-standardized RR = 0.75; 95% CI = 0.63-0.89). This was true in most age groups with the exception of adolescents aged 15-19 years where the risk of death was higher. Mortality from most causes, other than obstetric causes, was lower during the maternal risk period except for malaria, cardiovascular diseases and violence where there were no differences. Lower mortality was significant for HIV/AIDS (RR = 0.29, P<0.0001), cancers (RR = 0.10, P<0.023), and accidents (RR = 0, P<0.0001). Interpretation: In this rural setting typical of much of Southern Africa, pregnancy was largely protective against the risk of death, most likely because of a strong selection effect amongst those women who conceived successfully. The concept of indirect cause of maternal death needs to be re-examined.

  • 176.
    Gebrehiwot, Tesfay Gebregzabher
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Department of Public Health, College of Health Sciences, Mekelle University, Mekelle, Ethiopia.
    San Sebastian, Miguel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Edin, Kerstin
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Goicolea, Isabel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    The Health Extension Program and Its Association with Change in Utilization of Selected Maternal Health Services in Tigray Region, Ethiopia: A Segmented Linear Regression Analysis2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 7, artikel-id e0131195Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: In 2003, the Ethiopian Ministry of Health established the Health Extension Program (HEP), with the goal of improving access to health care and health promotion activities in rural areas of the country. This paper aims to assess the association of the HEP with improved utilization of maternal health services in Northern Ethiopia using institution-based retrospective data.

    METHODS: Average quarterly total attendances for antenatal care (ANC), delivery care (DC) and post-natal care (PNC) at health posts and health care centres were studied from 2002 to 2012. Regression analysis was applied to two models to assess whether trends were statistically significant. One model was used to estimate the level and trend changes associated with the immediate period of intervention, while changes related to the post-intervention period were estimated by the other.

    RESULTS: The total number of consultations for ANC, DC and PNC increased constantly, particularly after the late-intervention period. Increases were higher for ANC and PNC at health post level and for DC at health centres. A positive statistically significant upward trend was found for DC and PNC in all facilities (p<0.01). The positive trend was also present in ANC at health centres (p = 0.04), but not at health posts.

    CONCLUSION: Our findings revealed an increase in the use of antenatal, delivery and post-natal care after the introduction of the HEP. We are aware that other factors, that we could not control for, might be explaining that increase. The figures for DC and PNC are however low and more needs to be done in order to increase the access to the health care system as well as the demand for these services by the population. Strengthening of the health information system in the region needs also to be prioritized.

  • 177.
    Ghafouri, Nazdar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Ghafouri, Bijar
    Larsson, Britt
    Turkina, Maria V
    Karlsson, Linn
    Fowler, Christopher J
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Gerdle, Björn
    High levels of N-palmitoylethanolamide and N-stearoylethanolamide in microdialysate samples from myalgic trapezius muscle in women2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 11, s. e27257-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: N-acylethanolamines (NAEs) are endogenous compounds that regulate inflammation and pain. These include the cannabinoid ligand anandamide (AEA) and the peroxisome proliferator-activated receptor-a ligand palmitoylethanolamide (PEA). Little is known as to the levels of NAEs in pain states in human, particularly in the skeletal muscle. The aim of this study was to investigate the levels of these lipid mediators in muscle dialysate from women with chronic neck-/shoulder pain compared to healthy controls.

    Methods: Eleven women with chronic neck-/shoulder pain and eleven healthy women participated in this study. All participants went through microdialysis procedures in the trapezius muscle. Muscle dialysate samples were collected during four hours and analysed by nano liquid chromatography tandem mass spectrometry (nLC-MS/MS).

    Results: We were able to detect AEA, PEA, N-stearoylethanolamine (SEA) and 2-arachidonoylglycerol (2-AG) in a single chromatographic run. Of the NAEs studied, PEA and SEA were clearly detectable in the muscle microdialysate samples. The muscle dialysate levels of PEA and SEA were significantly higher in myalgic subjects compared to healthy controls.

    Conclusion: This study demonstrates that microdialysis in combination with mass spectrometry can be used for analysing NAE's in human muscle tissue regularly over time. Furthermore the significant group differences in the concentration of PEA and SEA in this study might fill an important gap in our knowledge of mechanisms in chronic myalgia in humans. In the long run this expanded understanding of nociceptive and anitinociceptive processes in the muscle may provide a base for ameliorating treatment and rehabilitation of pain.

  • 178. Gillman, Anna
    et al.
    Muradrasoli, Shaman
    Mardnas, Andreas
    Söderstrom, Hanna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Fedorova, Ganna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Vodnany, University of South Bohemia in Ceske Budejovice, Czech Republic.
    Lowenthal, Max
    Wille, Michelle
    Daggfeldt, Annika
    Jarhult, Josef D.
    Oseltamivir Resistance in Influenza A(H6N2) Caused by an R292K Substitution in Neuraminidase Is Not Maintained in Mallards without Drug Pressure2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 9, artikel-id e0139415Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Wild waterfowl is the natural reservoir of influenza A virus (IAV); hosted viruses are very variable and provide a source for genetic segments which can reassort with poultry or mammalian adapted IAVs to generate novel species crossing viruses. Additionally, wild waterfowl act as a reservoir for highly pathogenic IAVs. Exposure of wild birds to the antiviral drug oseltamivir may occur in the environment as its active metabolite can be released from sewage treatment plants to river water. Resistance to oseltamivir, or to other neuraminidase inhibitors (NAIs), in IAVs of wild waterfowl has not been extensively studied. Aim and Methods In a previous in vivo Mallard experiment, an influenza A(H6N2) virus developed oseltamivir resistance by the R292K substitution in the neuraminidase (NA), when the birds were exposed to oseltamivir. In this study we tested if the resistance could be maintained in Mallards without drug exposure. Three variants of resistant H6N2/R292K virus were each propagated during 17 days in five successive pairs of naive Mallards, while oseltamivir exposure was decreased and removed. Daily fecal samples were analyzed for viral presence, genotype and phenotype. Results and Conclusion Within three days without drug exposure no resistant viruses could be detected by NA sequencing, which was confirmed by functional NAI sensitivity testing. We conclude that this resistant N2 virus could not compete in fitness with wild type subpopulations without oseltamivir drug pressure, and thus has no potential to circulate among wild birds. The results of this study contrast to previous observations of drug induced resistance in an avian H1N1 virus, which was maintained also without drug exposure in Mallards. Experimental observations on persistence of NAI resistance in avian IAVs resemble NAI resistance seen in human IAVs, in which resistant N2 subtypes do not circulate, while N1 subtypes with permissive mutations can circulate without drug pressure. We speculate that the phylogenetic group N1 NAs may easier compensate for NAI resistance than group N2 NAs, though further studies are needed to confirm such conclusions.

  • 179. Godefay, Hagos
    et al.
    Byass, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Institute of Applied Health Sciences, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, United Kingdom; MRC/Wits Rural Public Health and Health Transitions Research Unit, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
    Graham, Wendy J
    Kinsman, John
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Mulugeta, Afework
    Risk Factors for Maternal Mortality in Rural Tigray, Northern Ethiopia: A Case-Control Study2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 12, artikel-id e0144975Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Maternal mortality continues to have devastating impacts in many societies, where it constitutes a leading cause of death, and thus remains a core issue in international development. Nevertheless, individual determinants of maternal mortality are often unclear and subject to local variation. This study aims to characterise individual risk factors for maternal mortality in Tigray, Ethiopia. Methods: A community-based case-control study was conducted, with 62 cases and 248 controls from six randomly-selected rural districts. All maternal deaths between May 2012 and September 2013 were recruited as cases and a random sample of mothers who delivered in the same communities within the same time period were taken as controls. Multiple logistic regression was used to identify independent determinants of maternal mortality. Results: Four independent individual risk factors, significantly associated with maternal death, emerged. Women who were not members of the voluntary Women's Development Army were more likely to experience maternal death (OR 2.07, 95% CI 1.04-4.11), as were women whose husbands or partners had below-median scores for involvement during pregnancy (OR 2.19, 95% CI 1.14-4.18). Women with a pre-existing history of other illness were also at increased risk (OR 5.58, 95% CI 2.17-14.30), as were those who had never used contraceptives (OR 2.58, 95% CI 1.37-4.85). Previous pregnancy complications, a below-median number of antenatal care visits and a woman's lack of involvement in health care decision making were significant bivariable risks that were not significant in the multivariable model. Conclusions: The findings suggest that interventions aimed at reducing maternal mortality need to focus on encouraging membership of the Women's Development Army, enhancing husbands' involvement in maternal health services, improving linkages between maternity care and other disease-specific programmes and ensuring that women with previous illnesses or non-users of contraceptive services are identified and followed-up as being at increased risk during pregnancy and childbirth.

  • 180.
    Goicolea, Isabel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Grupo de Investigación de Salud Pública, Universidad de Alicante, Spain.
    Vives-Cases, Carmen
    Hurtig, Anna-Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Marchal, Bruno
    Briones-Vozmediano, Erica
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Grupo de Investigación de Salud Pública, Universidad de Alicante, Spain ; .
    Otero-Garcia, Laura
    Garca-Quinto, Marta
    Sebastian, Miguel San
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Mechanisms that Trigger a Good Health-Care Response to Intimate Partner Violence in Spain. Combining Realist Evaluation and Qualitative Comparative Analysis Approaches2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 8, artikel-id e0135167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Health care professionals, especially those working in primary health-care services, can play a key role in preventing and responding to intimate partner violence. However, there are huge variations in the way health care professionals and primary health care teams respond to intimate partner violence. In this study we tested a previously developed programme theory on 15 primary health care center teams located in four different Spanish regions: Murcia, C Valenciana, Castilla-León and Cantabria. The aim was to identify the key combinations of contextual factors and mechanisms that trigger a good primary health care center team response to intimate partner violence.

    Methods

    A multiple case-study design was used. Qualitative and quantitative information was collected from each of the 15 centers (cases). In order to handle the large amount of information without losing familiarity with each case, qualitative comparative analysis was undertaken. Conditions (context and mechanisms) and outcomes, were identified and assessed for each of the 15 cases, and solution formulae were calculated using qualitative comparative analysis software.

    Results

    The emerging programme theory highlighted the importance of the combination of each team’s self-efficacy, perceived preparation and women-centredness in generating a good team response to intimate partner violence. The use of the protocol and accumulated experience in primary health care were the most relevant contextual/intervention conditions to trigger a good response. However in order to achieve this, they must be combined with other conditions, such as an enabling team climate, having a champion social worker and having staff with training in intimate partner violence.

    Conclusions

    Interventions to improve primary health care teams’ response to intimate partner violence should focus on strengthening team’s self-efficacy, perceived preparation and the implementation of a woman-centred approach. The use of the protocol combined with a large working experience in primary health care, and other factors such as training, a good team climate, and having a champion social worker on the team, also played a key role. Measures to sustain such interventions and promote these contextual factors should be encouraged.

  • 181.
    Golovlev, Igor
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Twine, Susan M.
    Shen, Hua
    Sjöstedt, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Conlan, Wayne
    A Delta clpB Mutant of Francisella tularensis Subspecies holarctica Strain, FSC200, Is a More Effective Live Vaccine than F. tularensis LVS in a Mouse Respiratory Challenge Model of Tularemia2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 11, s. e78671-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Francisella tularensis subsp. tularensis is a highly virulent pathogen for humans especially if inhaled. Consequently, it is considered to be a potential biothreat agent. An experimental vaccine, F. tularensis live vaccine strain, derived from the less virulent subsp. holarctica, was developed more than 50 years ago, but remains unlicensed. Previously, we developed a novel live vaccine strain, by deleting the chaperonin clpB gene from F. tularensis subsp. tularensis strain, SCHU S4. SCHU S4 Delta clpB was less virulent for mice than LVS and a more effective vaccine against respiratory challenge with wild type SCHU S4. In the current study, we were interested to determine whether a similar mutant on the less virulent subsp. holarctica background would also outperform LVS in terms of safety and efficacy. To this end, clpB was deleted from clinical holarctica strain, FSC200. FSC200 Delta clpB had a significantly higher intranasal LD50 than LVS for BALB/c mice, but replicated to higher numbers at foci of infection after dermal inoculation. Moreover, FSC200 Delta clpB killed SCID mice more rapidly than LVS. However, dermal vaccination of BALB/c mice with the former versus the latter induced greater protection against respiratory challenge with SCHU S4. This increased efficacy was associated with enhanced production of pulmonary IL-17 after SCHU S4 challenge.

  • 182. Golubic, Rajna
    et al.
    May, Anne M.
    Borch, Kristin Benjaminsen
    Overvad, Kim
    Charles, Marie-Aline
    Tormo Diaz, Maria Jose
    Amiano, Pilar
    Palli, Domenico
    Valanou, Elisavet
    Vigl, Matthaeus
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wareham, Nicholas
    Ekelund, Ulf
    Brage, Soren
    Validity of Electronically Administered Recent Physical Activity Questionnaire (RPAQ) in Ten European Countries2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 3, s. e92829-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To examine the validity of the Recent Physical Activity Questionnaire (RPAQ) which assesses physical activity (PA) in 4 domains (leisure, work, commuting, home) during past month. Methods: 580 men and 1343 women from 10 European countries attended 2 visits at which PA energy expenditure (PAEE), time at moderate-to-vigorous PA (MVPA) and sedentary time were measured using individually-calibrated combined heart-rate and movement sensing. At the second visit, RPAQ was administered electronically. Validity was assessed using agreement analysis. Results: RPAQ significantly underestimated PAEE in women [median(IQR) 34.1 (22.1, 52.2) vs. 40.6 (32.4, 50.9) kJ/kg/day, 95%LoA: -44.4, 63.4 kJ/kg/day) and in men (43.7 (29.0, 69.0) vs. 45.5 (34.1, 57.6) kJ/kg/day, 95%LoA: -47.2, 101.3 kJ/kg/day]. Using individualised definition of 1MET, RPAQ significantly underestimated MVPA in women [median(IQR): 62.1 (29.4, 124.3) vs. 73.6 (47.8, 107.2) min/day, 95%LoA: -130.5, 305.3 min/day] and men [82.7 (38.8, 185.6) vs. 83.3 (55.1, 125.0) min/day, 95%LoA: -136.4, 400.1 min/day]. Correlations (95%CI) between subjective and objective estimates were statistically significant [PAEE: women, rho = 0.20 (0.15-0.26); men, rho = 0.37 (0.30-0.44); MVPA: women, rho = 0.18 (0.13-0.23); men, rho = 0.31 (0.24-0.39)]. When using non-individualised definition of 1MET (3.5 mlO(2)/kg/min), MVPA was substantially overestimated (similar to 30 min/day). Revisiting occupational intensity assumptions in questionnaire estimation algorithms with occupational group-level empirical distributions reduced median PAEE-bias in manual (25.1 kJ/kg/day vs. 29.0 kJ/kg/day, p<0.001) and heavy manual workers (64.1 vs. -4.6 kJ/kg/day, p<0.001) in an independent hold-out sample. Conclusion: Relative validity of RPAQ-derived PAEE and MVPA is comparable to previous studies but underestimation of PAEE is smaller. Electronic RPAQ may be used in large-scale epidemiological studies including surveys, providing information on all domains of PA.

  • 183. Gordts, Philip L S M
    et al.
    Bartelt, Alexander
    Nilsson, Stefan K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Annaert, Wim
    Christoffersen, Christina
    Nielsen, Lars Bo
    Heeren, Joerg
    Roebroek, Anton J M
    Impaired LDL Receptor-Related Protein 1 Translocation Correlates with Improved Dyslipidemia and Atherosclerosis in apoE-Deficient Mice2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 6, s. e38330-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Determination of the in vivo significance of LDL receptor-related protein 1 (LRP1) dysfunction on lipid metabolism and atherosclerosis development in absence of its main ligand apoE.

    METHODS AND RESULTS: LRP1 knock-in mice carrying an inactivating mutation in the NPxYxxL motif were crossed with apoE-deficient mice. In the absence of apoE, relative to LRP1 wild-type animals, LRP1 mutated mice showed an increased clearance of postprandial lipids despite a compromised LRP1 endocytosis rate and inefficient insulin-mediated translocation of the receptor to the plasma membrane, likely due to inefficient slow recycling of the mutated receptor. Postprandial lipoprotein improvement was explained by increased hepatic clearance of triglyceride-rich remnant lipoproteins and accompanied by a compensatory 1.6-fold upregulation of LDLR expression in hepatocytes. One year-old apoE-deficient mice having the dysfunctional LRP1 revealed a 3-fold decrease in spontaneous atherosclerosis development and a 2-fold reduction in LDL-cholesterol levels.

    CONCLUSION: These findings demonstrate that the NPxYxxL motif in LRP1 is important for insulin-mediated translocation and slow perinuclear endosomal recycling. These LRP1 impairments correlated with reduced atherogenesis and cholesterol levels in apoE-deficient mice, likely via compensatory LDLR upregulation.

  • 184.
    Gouveia-Figueira, Sandra
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Karlsson, Jessica
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Deplano, Alessandro
    Hashemian, Sanaz
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Svensson, Mona
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Fredriksson Sundbom, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Congiu, Cenzo
    Onnis, Valentina
    Fowler, Christopher J.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Characterisation of (R)-2-(2-Fluorobiphenyl-4-yl)-N-(3-Methylpyridin-2-yl)Propanamide as a Dual Fatty Acid Amide Hydrolase: Cyclooxygenase Inhibitor2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 9, artikel-id e0139212Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Increased endocannabinoid tonus by dual-action fatty acid amide hydrolase (FAAH) and substrate selective cyclooxygenase (COX-2) inhibitors is a promising approach for pain-relief. One such compound with this profile is 2-(2-fluorobiphenyl-4-yl)-N-(3-methylpyridin-2-yl)propanamide (Flu-AM1). These activities are shown by Flu-AM1 racemate, but it is not known whether its two single enantiomers behave differently, as is the case towards COX-2 for the parent flurbiprofen enantiomers. Further, the effects of the compound upon COX-2-derived lipids in intact cells are not known. Methodology/Principal Findings COX inhibition was determined using an oxygraphic method with arachidonic acid and 2-arachidonoylglycerol (2-AG) as substrates. FAAH was assayed in mouse brain homogenates using anandamide (AEA) as substrate. Lipidomic analysis was conducted in unstimulated and lipopolysaccharide + interferon gamma-stimulated RAW 264.7 macrophage cells. Both enantiomers inhibited COX-2 in a substrate-selective and time-dependent manner, with IC50 values in the absence of a preincubation phase of: (R)-Flu-AM1, COX-1 (arachidonic acid) 6 mu M; COX-2 (arachidonic acid) 20 mu M; COX-2 (2-AG) 1 mu M; (S)-Flu-AM1, COX-1 (arachidonic acid) 3 mu M; COX-2 (arachidonic acid) 10 mu M; COX-2 (2-AG) 0.7 mu M. The compounds showed no enantiomeric selectivity in their FAAH inhibitory properties. (R)-Flu-AM1 (10 mu M) greatly inhibited the production of prostaglandin D2 and E2 in both unstimulated and lipopolysaccharide + interferon.-stimulated RAW 264.7 macrophage cells. Levels of 2-AG were not affected either by (R)-Flu-AM1 or by 10 mu M flurbiprofen, either alone or in combination with the FAAH inhibitor URB597 (1 mu M). Conclusions/Significance Both enantiomers of Flu-AM1 are more potent inhibitors of 2-AG compared to arachidonic acid oxygenation by COX-2. Inhibition of COX in lipopolysaccharide + interferon.-stimulated RAW 264.7 cells is insufficient to affect 2-AG levels despite the large induction of COX-2 produced by this treatment.

  • 185.
    Gouveia-Figueira, Sandra
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Gaida, Jamie E.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Alfredson, Hakan
    Fowler, Christopher J.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Serum Levels of Oxylipins in Achilles Tendinopathy: An Exploratory Study2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 4, artikel-id e0123114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Linoleic acid-derived oxidation products are found in experimental pain models. However, little is known about the levels of such oxylipins in human pain. In consequence, in the present study, we have undertaken a lipidomic profiling of oxylipins in blood serum from patients with Achilles tendinopathy and controls.

    Methodology/Principal findings: A total of 34 oxylipins were analysed in the serum samples. At a significance level of P<0.00147 (<0.05/34), two linoleic acid-derived oxylipins, 13-hydroxy-10E,12Z-octadecadienoic (13-HODE) and 12(13)-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME) were present at significantly higher levels in the Achilles tendinopathy samples. This difference remained significant when the dataset was controlled for age, gender and body-mass index. In contrast, 0/21 of the arachidonic acid- and 0/4 of the dihomo-γ-linolenic acid, eicosapentaenoic acid or docosahenaenoic acid-derived oxylipins were higher in the patient samples at this level of significance. The area under the Receiver-Operator Characteristic (ROC) curve for 12,13-DiHOME was 0.91 (P<0.0001). Levels of four N-acylethanolamines were also analysed and found not to be significantly different between the controls and the patients at the level of P<0.0125 (<0.05/4).

    Conclusions/Significance: It is concluded from this exploratory study that abnormal levels of linoleic acid-derived oxylipins are seen in blood serum from patients with Achilles tendinopathy. Given the ability of two of these, 9- and 13-HODE to activate transient receptor potential vanilloid 1, it is possible that these changes may contribute to the symptoms seen in Achilles tendinopathy.

  • 186.
    Gouveia-Figueira, Sandra
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Späth, Jana
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Zivkovic, Angela M.
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Profiling the Oxylipin and Endocannabinoid Metabolome by UPLC-ESI-MS/MS in Human Plasma to Monitor Postprandial Inflammation2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 7, artikel-id e0132042Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bioactive lipids, including oxylipins, endocannabinoids, and related compounds may function as specific biochemical markers of certain aspects of inflammation. However, the postprandial responsiveness of these compounds is largely unknown; therefore, changes in the circulating oxylipin and endocannabinoid metabolome in response to a challenge meal were investigated at six occasions in a subject who freely modified her usual diet. The dietary change, and especially the challenge meal itself, represented a modification of precursor fatty acid status, with expectedly subtle effects on bioactive lipid levels. To detect even the slightest alteration, highly sensitive ultra-performance liquid chromatography (UPLC) coupled to electrospray ionization (ESI) tandem mass spectrometry (MS/MS) methods for bioactive lipid profiling was employed. A previously validated UPLC-ESI-MS/MS method for profiling the endocannabinoid metabolome was used, while validation of an UPLC-ESI-MS/MS method for oxylipin analysis was performed with acceptable outcomes for a majority of the parameters according to the US Food and Drug Administration guidelines for linearity (0.9938 < R-2 < 0.9996), limit of detection (0.0005-2.1 pg on column), limit of quantification (0.0005-4.2 pg on column), inter-and intraday accuracy (85-115%) and precision (<5%), recovery (40-109%) and stability (40-105%). Forty-seven of fifty-two bioactive lipids were detected in plasma samples at fasting and in the postprandial state (0.5, 1, and 3 hours after the meal). Multivariate analysis showed a significant shift of bioactive lipid profiles in the postprandial state due to inclusion of dairy products in the diet, which was in line with univariate analysis revealing seven compounds (NAGly, 9-HODE, 13-oxo-ODE, 9(10)-EpOME, 12(13)-EpOME, 20-HETE, and 11,12-DHET) that were significantly different between background diets in the postprandial state (but not at fasting). The only change in baseline levels at fasting was displayed by TXB2. Furthermore, postprandial responsiveness was detected for seven compounds (POEA, SEA, 9(10)-DiHOME, 12(13)-DiHOME, 13-oxo-ODE, 9-HODE, and 13-HODE). Hence, the data confirm that the UPLC-ESI-MS/MS method performance was sufficient to detect i) a shift, in the current case most notably in the postprandial bioactive lipid metabolome, caused by changes in diet and ii) responsiveness to a challenge meal for a subset of the oxylipin and endocannabinoid metabolome. To summarize, we have shown proof-of-concept of our UPLC-ESI-MS/MS bioactive lipid protocols for the purpose of monitoring subtle shifts, and thereby useful to address lipid-mediated postprandial inflammation.

  • 187.
    Granlund, Irene
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Hall, Michael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Kieselbach, Thomas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Schröder, Wolfgang P
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Light induced changes in protein expression and uniform regulation of transcription in the thylakoid lumen of Arabidopsis thaliana2009Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, nr 5, s. e5649-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In plants oxygenic photosynthesis is performed by large protein complexes found in the thylakoid membranes of chloroplasts. The soluble thylakoid lumen space is a narrow and compressed region within the thylakoid membrane which contains 80-200 proteins. Because the thylakoid lumen proteins are in close proximity to the protein complexes of photosynthesis, it is reasonable to assume that the lumen proteins are highly influenced by the presence of light. To identify light regulated proteins in the thylakoid lumen of Arabidopsis thaliana we developed a faster thylakoid preparation and combined this with difference gel electrophoresis (DIGE) of dark-adapted and light-adapted lumen proteomes. The DIGE experiments revealed that 19 lumen proteins exhibit increased relative protein levels after eight hour light exposure. Among the proteins showing increased abundance were the PsbP and PsbQ subunits of Photosystem II, major plastocyanin and several other proteins of known or unknown function. In addition, co-expression analysis of publicly available transcriptomic data showed that the co-regulation of lumen protein expression is not limited to light but rather that lumen protein genes exhibit a high uniformity of expression. The large proportion of thylakoid lumen proteins displaying increased abundance in light-adapted plants, taken together with the observed uniform regulation of transcription, implies that the majority of thylakoid lumen proteins have functions that are related to photosynthetic activity. This is the first time that an analysis of the differences in protein level during a normal day/night cycle has been performed and it shows that even a normal cycle of light significantly influences the thylakoid lumen proteome. In this study we also show for the first time, using co-expression analysis, that the prevalent lumenal chloroplast proteins are very similarly regulated at the level of transcription.

  • 188. Gray, Sarah
    et al.
    Axelsson, Bertil
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Östersunds sjukhus.
    The prevalence of deranged C-reactive protein and albumin in patients with incurable cancer approaching death2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 3, artikel-id e0193693Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Amongst patients with incurable cancer approaching death, cachexia is common and associated with adverse outcomes. The term cachexia lacks a universally accepted definition and there is no consensus regarding which variables are to be measured. Furthermore, an elevated C-reactive protein is a common clinical challenge in this patient group. This study aims to add to the ongoing discussion regarding the definition of cancer cachexia and to study the role of C-reactive protein and s-albumin in this context.

    Material and methods A 1-year cohort, consisting of 155 cancer patients enrolled in a specialized palliative home care team in the city of Ostersund, Sweden, that were deceased during the year of 2015 was studied. Laboratory measures were studied within 0-30 and 31-60 days prior to death. C-reactive protein >10 mg/L and coinciding s-albumin <30 g/L was referred to as "laboratory cachexia". Also, the number of days from the first found "laboratory cachexia" until death was noted.

    Results The prevalence of "laboratory cachexia" was 85% 0-30 days prior to death compared to 66% 31-60 days prior to death (p<0.01). The majority of patients (75%) had an onset of "laboratory cachexia" within 0-120 days prior to death, with a median of 47 days. The median values for C-reactive protein and s-albumin within 0-30 days prior to death were 84mg/L and 23g/L respectively.

    Discussion Could markedly deranged values of C-reactive protein and s-albumin, such as found in this study, signal a relatively short remaining survival time in patients with incurable cancer and no clinical signs of ongoing infection? The role of "laboratory cachexia" in this context as well as the cut off values for the laboratory measures included may be further discussed.

  • 189.
    Grip, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    Tengman, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    Liebermann, Dario G
    Häger, Charlotte
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    Kinematic analyses including finite helical axes of drop jump landings demonstrate decreased knee control long after anterior cruciate ligament injury2019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 10, artikel-id e0224261Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The purpose was to evaluate the dynamic knee control during a drop jump test following injury of the anterior cruciate ligament injury (ACL) using finite helical axes. Persons injured 17-28 years ago, treated with either physiotherapy (ACLPT, n = 23) or reconstruction and physiotherapy (ACLR, n = 28) and asymptomatic controls (CTRL, n = 22) performed a drop jump test, while kinematics were registered by motion capture. We analysed the Preparation phase (from maximal knee extension during flight until 50 ms post-touchdown) followed by an Action phase (until maximal knee flexion post-touchdown). Range of knee motion (RoM), and the length of each phase (Duration) were computed. The finite knee helical axis was analysed for momentary intervals of ~15° of knee motion by its intersection (ΔAP position) and inclination (ΔAP Inclination) with the knee's Anterior-Posterior (AP) axis. Static knee laxity (KT100) and self-reported knee function (Lysholm score) were also assessed. The results showed that both phases were shorter for the ACL groups compared to controls (CTRL-ACLR: Duration 35±8 ms, p = 0.000, CTRL-ACLPT: 33±9 ms, p = 0.000) and involved less knee flexion (CTRL-ACLR: RoM 6.6±1.9°, p = 0.002, CTRL-ACLR: 7.5 ±2.0°, p = 0.001). Low RoM and Duration correlated significantly with worse knee function according to Lysholm and higher knee laxity according to KT-1000. Three finite helical axes were analysed. The ΔAP position for the first axis was most anterior in ACLPT compared to ACLR (ΔAP position -1, ACLPT-ACLR: 13±3 mm, p = 0.004), with correlations to KT-1000 (rho 0.316, p = 0.008), while the ΔAP inclination for the third axis was smaller in the ACLPT group compared to controls (ΔAP inclination -3 ACLPT-CTRL: -13±5°, p = 0.004) and showed a significant side difference in ACL injured groups during Action (Injured-Non-injured: 8±2.7°, p = 0.006). Small ΔAP inclination -3 correlated with low Lysholm (rho 0.391, p = 0.002) and high KT-1000 (rho -0.450, p = 0.001). Conclusions Compensatory movement strategies seem to be used to protect the injured knee during landing. A decreased ΔAP inclination in injured knees during Action suggests that the dynamic knee control may remain compromised even long after injury.

  • 190. Guerra, Lina
    et al.
    Albihn, Ami
    Tronnersjö, Susanna
    Yan, Qinzi
    Guidi, Riccardo
    Stenerlöw, Bo
    Sterzenbach, Torsten
    Josenhans, Christine
    Fox, James G
    Schauer, David B
    Thelestam, Monica
    Larsson, Lars-Gunnar
    Henriksson, Marie
    Frisan, Teresa
    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
    Myc is required for activation of the ATM-dependent checkpoints in response to DNA damage2010Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, nr 1, artikel-id e8924Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The MYC protein controls cellular functions such as differentiation, proliferation, and apoptosis. In response to genotoxic agents, cells overexpressing MYC undergo apoptosis. However, the MYC-regulated effectors acting upstream of the mitochondrial apoptotic pathway are still unknown.

    PRINCIPAL FINDINGS: In this study, we demonstrate that expression of Myc is required to activate the Ataxia telangiectasia mutated (ATM)-dependent DNA damage checkpoint responses in rat cell lines exposed to ionizing radiation (IR) or the bacterial cytolethal distending toxin (CDT). Phosphorylation of the ATM kinase and its downstream effectors, such as histone H2AX, were impaired in the myc null cell line HO15.19, compared to the myc positive TGR-1 and HOmyc3 cells. Nuclear foci formation of the Nijmegen Breakage Syndrome (Nbs) 1 protein, essential for efficient ATM activation, was also reduced in absence of myc. Knock down of the endogenous levels of MYC by siRNA in the human cell line HCT116 resulted in decreased ATM and CHK2 phosphorylation in response to irradiation. Conversely, cell death induced by UV irradiation, known to activate the ATR-dependent checkpoint, was similar in all the cell lines, independently of the myc status.

    CONCLUSION: These data demonstrate that MYC contributes to the activation of the ATM-dependent checkpoint responses, leading to cell death in response to specific genotoxic stimuli.

  • 191.
    Guillemot, Vincent
    et al.
    Bioinformatics and Biostatistics Hub, Institut Pasteur, Paris, France.
    Beaton, Derek
    The Rotman Research Institute, Institution at Baycrest, Toronto, Canada.
    Gloaguen, Arnaud
    L2S, UMR CNRS 8506, CNRS–Centrale Supélec–Université Paris-Sud, Université Paris-Saclay, 3 rue Joliot-Curie, 91192 Gif-sur-Yvette, France.
    Löfstedt, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Levine, Brian
    The Rotman Research Institute, Institution at Baycrest, Toronto, Canada.
    Raymond, Nicolas
    IRMAR, UMR 6625, Université de Rennes, Rennes, France.
    Tenenhaus, Arthur
    L2S, UMR CNRS 8506, CNRS–Centrale Supélec–Université Paris-Sud, Université Paris-Saclay, 3 rue Joliot-Curie, Gif-sur-Yvette, France.
    Abdi, Hervé
    School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, United States of America.
    A constrained singular value decomposition method that integrates sparsity and orthogonality2019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 3, artikel-id e0211463Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We propose a new sparsification method for the singular value decomposition—called the constrained singular value decomposition (CSVD)—that can incorporate multiple constraints such as sparsification and orthogonality for the left and right singular vectors. The CSVD can combine different constraints because it implements each constraint as a projection onto a convex set, and because it integrates these constraints as projections onto the intersection of multiple convex sets. We show that, with appropriate sparsification constants, the algorithm is guaranteed to converge to a stable point. We also propose and analyze the convergence of an efficient algorithm for the specific case of the projection onto the balls defined by the norms L1 and L2. We illustrate the CSVD and compare it to the standard singular value decomposition and to a non-orthogonal related sparsification method with: 1) a simulated example, 2) a small set of face images (corresponding to a configuration with a number of variables much larger than the number of observations), and 3) a psychometric application with a large number of observations and a small number of variables. The companion R-package, csvd, that implements the algorithms described in this paper, along with reproducible examples, are available for download from https://github.com/vguillemot/csvd.

  • 192.
    Guo, Yong-Zhi
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Li, Jinan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Hagstrom, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ny, Tor
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Beneficial and detrimental effects of plasmin(ogen) during infection and sepsis in mice2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 9, s. e24774-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Plasmin has been proposed to be an important mediator during inflammation/infection. In this study, by using mice lacking genes for plasminogen, tissue-type plasminogen activator (tPA), and urokinase-type PA (uPA), we have investigated the functional roles of active plasmin in infection and sepsis. Two models were used: an infection model by intravenous injection of 1x10(7) CFU of S. aureus, and a sepsis model by intravenous injection of 1.6x10(8) CFU of S. aureus. We found that in the infection model, wild-type (WT) mice showed significantly higher survival rates than plasminogen-deficient (plg(-/-)) mice. However, in the sepsis model, plg(-/-) or tPA(-/-)/uPA(-/-) mice showed the highest survival rate whereas WT and tPA(+/-)/uPA(+/-) mice showed the lowest survival rate, and plg(+/-), tPA(-/-), and uPA(-/-) mice had an intermediate survival rate. These results indicate that the levels of active plasmin are critical in determining the survival rate in the sepsis, partly through high levels of inflammatory cytokines and enhanced STAT3 activation. We conclude that plasmin is beneficial in infection but promotes the production of inflammatory cytokines in sepsis that may cause tissue destruction, diminished neutrophil function, and an impaired capacity to kill bacteria which eventually causes death of these mice.

  • 193.
    Gustafsson, Per E.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Janlert, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Theorell, Tores
    Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Westerlund, Hugo
    Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Hammarström, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Do peer relations in adolescence influence health in adulthood?: Peer problems in the school setting and the metabolic syndrome in middle-age2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 6, s. e39385-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    While the importance of social relations for health has been demonstrated in childhood, adolescence and adulthood, few studies have examined the prospective importance of peer relations for adult health. The aim of this study was to examine whether peer problems in the school setting in adolescence relates to the metabolic syndrome in middle-age. Participants came from the Northern Swedish Cohort, a 27-year cohort study of school leavers (effective n = 881, 82% of the original cohort). A score of peer problems was operationalized through form teachers' assessment of each student's isolation and popularity among school peers at age 16 years, and the metabolic syndrome was measured by clinical measures at age 43 according to established criteria. Additional information on health, health behaviors, achievement and social circumstances were collected from teacher interviews, school records, clinical measurements and self-administered questionnaires. Logistic regression was used as the main statistical method. Results showed a dose-response relationship between peer problems in adolescence and metabolic syndrome in middle-age, corresponding to 36% higher odds for the metabolic syndrome at age 43 for each SD higher peer problems score at age 16. The association remained significant after adjustment for health, health behaviors, school adjustment or family circumstances in adolescence, and for psychological distress, health behaviors or social circumstances in adulthood. In analyses stratified by sex, the results were significant only in women after adjustment for covariates. Peer problems were significantly related to all individual components of the metabolic syndrome. These results suggest that unsuccessful adaption to the school peer group can have enduring consequences for metabolic health.

  • 194.
    Gustafsson, Per E
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    San Sebastian, Miguel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    When does hardship matter for health? Neighborhood and individual disadvantages and functional somatic symptoms from adolescence to mid-life in the Northern Swedish Cohort.2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 6, s. e99558-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A large body of research has shown that health is influenced by disadvantaged living conditions, including both personal and neighborhood conditions. Little is however known to what degree the health impact of different forms of disadvantage differ along the life course. The present study aims to examine when, during the life course, neighborhood and individual disadvantages relate to functional somatic symptoms. Participants (n = 992) came from The Northern Swedish Cohort and followed from age 16, 21, 30 until 42 years. Functional somatic symptoms, socioeconomic disadvantage, and social and material adversity were measured through questionnaires and linked to register data on neighborhood disadvantage. Data was analyzed with longitudinal and cross-sectional multilevel models. Results showed that neighborhood disadvantage, social and material adversity and gender all contributed independently to overall levels of symptoms across the life course. Cross-sectional analyses also suggested that the impact of disadvantage differed between life course periods; neighborhood disadvantage was most important in young adulthood, and the relative importance of material versus social adversity increased as participants grew older. In summary, the study suggests that disadvantages from different contextual sources may affect functional somatic health across the life course, but also through life course specific patterns.

  • 195.
    Gustafsson, Per E.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    San Sebastian, Miguel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Janlert, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Theorell, Töres
    Westerlund, Hugo
    Hammarström, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Residential Selection across the Life Course: Adolescent Contextual and Individual Determinants of Neighborhood Disadvantage in Mid-Adulthood.2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 11, artikel-id e80241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Numerous cross-sectional studies have examined neighborhood effects on health. Residential selection in adulthood has been stressed as an important cause of selection bias but has received little empirical attention, particularly its determinants from the earlier life course. The present study aims to examine whether neighborhood, family, school, health behaviors and health in adolescence are related to socioeconomic disadvantage of one's neighborhood of residence in adulthood.

    METHODS: Based on the prospective Northern Swedish Cohort (analytical N = 971, 90.6% retention rate), information was collected at age 16 years concerning family circumstances, school adjustment, health behaviors and mental and physical health. Neighborhood register data was linked to the cohort and used to operationalize aggregated measures of neighborhood disadvantage (ND) at age 16 and 42. Data was analyzed with linear mixed models, with ND in adulthood regressed on adolescent predictors and neighborhood of residence in adolescence as the level-2 unit.

    RESULTS: Neighborhood disadvantage in adulthood was clustered by neighborhood of residence in adolescence (ICC = 8.6%). The clustering was completely explained by ND in adolescence. Of the adolescent predictors, ND (b = .14 (95% credible interval = .07-.22)), final school marks (b = -.18 (-.26--.10)), socioeconomic disadvantage (b = .07 (.01-.14)), and, with borderline significance, school peer problems (b = .07 (-.00-.13)), were independently related to adulthood ND in the final adjusted model. In sex-stratified analyses, the most important predictors were school marks (b = -.21 (-.32--.09)) in women, and neighborhood of residence (ICC = 15.5%) and ND (b = .20 (.09-.31)) in men.

    CONCLUSIONS: These findings show that factors from adolescence - which also may impact on adult health - could influence the neighborhood context in which one will live in adulthood. This indicates that residential selection bias in neighborhood effects on health research may have its sources in early life.

  • 196.
    Gustafsson, Sofia B
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Henriksson, Maria L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Dahlin, Anna M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Edin, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Jacobsson, Stig OP
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Öberg, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Fowler, Christopher J
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    High tumour cannabinoid CB(1) receptor immunoreactivity negatively impacts disease-specific survival in stage II microsatellite stable colorectal cancer2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 8, s. 1-11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There is good evidence in the literature that the cannabinoid system is disturbed in colorectal cancer. In the present study, we have investigated whether CB(1) receptor immunoreactive intensity (CB(1)IR intensity) is associated with disease severity and outcome.

    Methodology/Principal Findings: CB(1)IR was assessed in formalin-fixed, paraffin-embedded specimens collected with a consecutive intent during primary tumour surgical resection from a series of cases diagnosed with colorectal cancer. Tumour centre (n = 483) and invasive front (n = 486) CB(1)IR was scored from 0 (absent) to 3 (intense staining) and the data was analysed as a median split i.e. CB(1)IR <2 and >= 2. In microsatellite stable, but not microsatellite instable tumours (as adjudged on the basis of immunohistochemical determination of four mismatch repair proteins), there was a significant positive association of the tumour grade with the CB1IR intensity. The difference between the microsatellite stable and instable tumours for this association of CB(1)IR was related to the CpG island methylation status of the cases. Cox proportional hazards regression analyses indicated a significant contribution of CB(1)IR to disease-specific survival in the microsatellite stable tumours when adjusting for tumour stage. For the cases with stage II microsatellite stable tumours, there was a significant effect of both tumour centre and front CB(1)IR upon disease specific survival. The 5 year probabilities of event-free survival were: 8565 and 66+/-8%; tumour interior, 86+/-4% and 63+/-8% for the CB(1)IR<2 and CB(1)IR >= 2 groups, respectively.

    Conclusions/Significance: The level of CB(1) receptor expression in colorectal cancer is associated with the tumour grade in a manner dependent upon the degree of CpG hypermethylation. A high CB(1)IR is indicative of a poorer prognosis in stage II microsatellite stable tumour patients.

  • 197.
    Gómez Real, Francisco
    et al.
    Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
    Pérez Barrionuevo, Laura
    Department of Clinical Science, University of Bergen, Bergen, Norway.
    Franklin, Karl
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lindberg, Eva
    Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
    Jacobsen Bertelsen, Randi
    Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway.
    Benediktsdóttir, Bryndís
    University of Iceland, Faculty of Medicine, Reykjavik, Iceland.
    Forsberg, Bertil
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Gislason, Thorarinn
    University of Iceland, Faculty of Medicine, Reykjavik, Iceland.
    Jögi, Rain
    Lung Clinic, Tartu University Clinics, Tartu, Estonia.
    Johannessen, Ane
    Department of Clinical Science, University of Bergen, Bergen, Norway; Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway .
    Omenaas, Ernst
    Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway.
    Saure, Eirunn
    Department of Clinical Science, University of Bergen, Bergen, Norway.
    Schlünssen, Vivi
    Department of Public Health, Section for Environment, Occupation and Health, Aarhus University, Aarhus, Denmark.
    Skorge, Trude Duelien
    Department of Clinical Science, University of Bergen, Bergen, Norway.
    Torén, Kjell
    Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Pérez Saavedra, Antonio
    Clinica Dental Pérez Saveedra, Málaga, Spain.
    Svanes, Øistein
    Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway.
    Nordrehaug Åstrøm, Anne
    Department of Clinical Dentistry, University of Bergen, Bergen Norway.
    Janson, Christer
    Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway.
    Svanes, Cecilie
    Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway.
    The Association of Gum Bleeding with Respiratory Health in a Population Based Study from Northern Europe2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 1, artikel-id e0147518Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: There is little knowledge about how oral and respiratory health is interrelated even though the mucosa of the oral cavity and airways constitutes a continuum and the exposures to these are partly similar.

    AIMS: To investigate whether gum bleeding is related to asthma, respiratory symptoms and self-reported COPD.

    METHODS: A postal questionnaire including questions about respiratory and oral health was sent to general population samples in seven Northern European centres. In 13,409 responders, gum bleeding when brushing teeth was reported always/often by 4% and sometimes by 20%. Logistic regressions accounted for age, smoking, educational level, centre and gender. Effects of BMI, cardio-metabolic diseases, early life factors, gastro-oesophageal reflux, dental hygiene, nasal congestion, and asthma medication were addressed.

    RESULTS: Gum bleeding always/often was significantly associated with ≥3 asthma symptoms (OR 2.58, 95% CI 2.10-3.18), asthma (1.62 [1.23-2.14]) and self-reported COPD (2.02 [1.28-3.18]). There was a dose-response relationship between respiratory outcomes and gum bleeding frequency (≥3 symptoms: gum bleeding sometimes 1.42 [1.25-1.60], often/always 2.58 [2.10-3.18]), and there was no heterogeneity between centres (pheterogeneity = 0.49). None of the investigated risk factors explained the associations. The observed associations were significantly stronger among current smokers (pinteraction = 0.004).

    CONCLUSIONS: A consistent link between gum bleeding and obstructive airways disease was observed, not explained by common risk factors or metabolic factors. We speculate that oral pathogens might have unfavourable impact on the airways, and that the direct continuity of the mucosa of the oral cavity and the airways reflects a pathway that might provide novel opportunities for interventions.

  • 198.
    Habayeb, Mazen S
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Ekström, Jens-Ola
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Hultmark, Dan
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Nora virus persistent infections are not affected by the RNAi machinery.2009Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, nr 5, s. e5731-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Drosophila melanogaster is widely used to decipher the innate immune system in response to various pathogens. The innate immune response towards persistent virus infections is among the least studied in this model system. We recently discovered a picorna-like virus, the Nora virus which gives rise to persistent and essentially symptom-free infections in Drosophila melanogaster. Here, we have used this virus to study the interaction with its host and with some of the known Drosophila antiviral immune pathways. First, we find a striking variability in the course of the infection, even between flies of the same inbred stock. Some flies are able to clear the Nora virus but not others. This phenomenon seems to be threshold-dependent; flies with a high-titer infection establish stable persistent infections, whereas flies with a lower level of infection are able to clear the virus. Surprisingly, we find that both the clearance of low-level Nora virus infections and the stability of persistent infections are unaffected by mutations in the RNAi pathways. Nora virus infections are also unaffected by mutations in the Toll and Jak-Stat pathways. In these respects, the Nora virus differs from other studied Drosophila RNA viruses.

  • 199.
    Hadrévi, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Ghafouri, Bijar
    Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University and Pain and Rehabilitation Centre, County Council of Östergötland, SE 581 85 Linköping, Sweden.
    Larsson, Britt
    Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University.
    Gerdle, Björn
    Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University.
    Hellström, Fredrik
    Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, Faculty of Health and Occupational Studies , University of Gävle, Umeå, Sweden.
    Multivariate Modeling of Proteins Related to Trapezius Myalgia, a Comparative Study of Female Cleaners with or without Pain2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 9, s. e73285-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The prevalence of chronic trapezius myalgia is high in women with high exposure to awkward working positions, repetitive movements and movements with high precision demands. The mechanisms behind chronic trapezius myalgia are not fully understood. The purpose of this study was to explore the differences in protein content between healthy and myalgic trapezius muscle using proteomics. Muscle biopsies from 12 female cleaners with work-related trapezius myalgia and 12 pain free female cleaners were obtained from the descending part of the trapezius. Proteins were separated with two-dimensional differential gel electrophoresis (2D-DIGE) and selected proteins were identified with mass spectrometry. In order to discriminate the two groups, quantified proteins were fitted to a multivariate analysis: partial least square discriminate analysis. The model separated 28 unique proteins which were related to glycolysis, the tricaboxylic acid cycle, to the contractile apparatus, the cytoskeleton and to acute response proteins. The results suggest altered metabolism, a higher abundance of proteins related to inflammation in myalgic cleaners compared to healthy, and a possible alteration of the contractile apparatus. This explorative proteomic screening of proteins related to chronic pain in the trapezius muscle provides new important aspects of the pathophysiology behind chronic trapezius myalgia.

  • 200.
    Halin Bergström, Sofia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Nilsson, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Adamo, Hanibal
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Thysell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Jernberg, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Extratumoral Heme Oxygenase-1 (HO-1) Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 6, artikel-id e0157280Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aggressive tumors induce tumor-supporting changes in the benign parts of the prostate. One factor that has increased expression outside prostate tumors is hemoxygenase-1 (HO-1). To investigate HO-1 expression in more detail, we analyzed samples of tumor tissue and peritumoral normal prostate tissue from rats carrying cancers with different metastatic capacity, and human prostate cancer tissue samples from primary tumors and bone metastases. In rat prostate tumor samples, immunohistochemistry and quantitative RTPCR showed that the main site of HO-1 synthesis was HO-1(+) macrophages that accumulated in the tumor-bearing organ, and at the tumor-invasive front. Small metastatic tumors were considerably more effective in attracting HO-1(+) macrophages than larger non-metastatic ones. In clinical samples, accumulation of HO-1(+) macrophages was seen at the tumor invasive front, almost exclusively in high-grade tumors, and it correlated with the presence of bone metastases. HO-1(+) macrophages, located at the tumor invasive front, were more abundant in bone metastases than in primary tumors. HO-1 expression in bone metastases was variable, and positively correlated with the expression of macrophage markers but negatively correlated with androgen receptor expression, suggesting that elevated HO-1 could be a marker for a subgroup of bone metastases. Together with another recent observation showing that selective knockout of HO-1 in macrophages reduced prostate tumor growth and metastatic capacity in animals, the results of this study suggest that extratumoral HO-1(+) macrophages may have an important role in prostate cancer.

1234567 151 - 200 av 665
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf