liu.seSearch for publications in DiVA
Change search
Refine search result
1234567 51 - 100 of 888
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 51.
    Appelgren, Daniel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Marginal-Zone B-Cells Are Main Producers of IgM in Humans, and Are Reduced in Patients With Autoimmune Vasculitis2018In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 2242Article in journal (Refereed)
    Abstract [en]

    In mice, B1 and marginal zone (MZ) B-cells play an important role in prevention of autoimmunity through production of regulatory cytokines and natural antibodies. There is limited knowledge about the human counterparts of these cells. We therefore investigated functions of MZ-like B-cells and the frequency of circulating MZ-like and Bl-like B-cells in healthy controls (HC), as well as in patients with autoimmune vasculitis to learn more about the role of these cells in autoimmune disease. After stimulation with CpG oligodeoxynucleotides (ODN) of class B in vitro, MZ-like B-cells were the main producers of IgM whereas switched memory B-cells primarily produced IgG and IgA. TNF and IL-10 were produced by both MZ-like and switched memory B-cells. Neither antibody nor TNF/IL-10 production by the B-cell subsets differed between patients and HC. Patients with autoimmune vasculitis, irrespective of disease activity, had lower percentage and absolute numbers of circulating MZ-like B-cells, and lower absolute numbers of B1-like B-cells. The percentage of B1-like B-cells was reduced during active disease. These findings remained significant when the analysis was confined to active treatment-naive patients (disease onset).Our results suggest that human innate-like B-cells might have a physiological role in prevention of autoimmunity.

  • 52.
    Arapovic-Johansson, Bozana
    et al.
    Unit of Intervention and Implementation Research for Worker Health, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Wåhlin, Charlotte
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Unit of Intervention and Implementation Research for Worker Health, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Hagberg, Jan
    Unit of Intervention and Implementation Research for Worker Health, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Kwak, Lydia
    Unit of Intervention and Implementation Research for Worker Health, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Björklund, Christina
    Unit of Intervention and Implementation Research for Worker Health, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Jensen, Irene
    Unit of Intervention and Implementation Research for Worker Health, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Participatory work place intervention for stress prevention in primary health care. A randomized controlled trial2018In: European Journal of Work and Organizational Psychology, ISSN 1359-432X, E-ISSN 1464-0643, Vol. 27, no 2, p. 219-234Article in journal (Refereed)
    Abstract [en]

    The aim of this study is to explore whether a participatory, organizational intervention can reduce work-related risk factors, and thereby prevent stress-related ill health. We build on the job demand-control and effort-reward imbalance models of stress. It is a two-armed randomized trial, with one primary health care unit receiving the intervention and a two-unit control group. Validated questionnaires for the assessment of psychosocial work environment and health were administered, at the baseline and at 6 and 12-month follow up. The primary outcome was job strain. Secondary outcomes were effort-reward imbalance, exhaustion, sleep, and recovery. Group-level objective data on workload and data about relevant processes during the study were continuously collected. The changes in the intervention group with regard to job strain, effort-reward imbalance, exhaustion, sleep and recovery were not statistically different from changes in the control group. For the non-exhausted employees though, reward was significantly higher at follow up compared to baseline, but only in the intervention group. An important piece of information is that the objective workload was statistically significantly higher in the intervention group throughout the study. Not all the components of the intervention were implemented as intended. Context and process information, such as objective data and implementation fidelity are necessary for a valid interpretation of the results.

  • 53.
    Archer, Brent
    et al.
    University of Louisiana at Lafayette, PO Box 43170, Lafayette, LA 70504-3170, USA.
    Müller, Nicole
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Penn, Claire
    University of the Witwatersrand, Johannesburg, 1 Jan Smuts Avenue, Braamfontein, Gauteng 2000, South Africa.
    Facilitation effects of cueing techniques in two Sesotho speakers with anomia2016In: Speech, Language and Hearing, ISSN 2050-571X, Vol. 19, no 3, p. 140-152Article in journal (Refereed)
    Abstract [en]

    Aphasiologists developing treatments for anomia should closely align therapy methods with the typological and morphological characteristics of the language in question. The lead author initiated this study to develop more defensible interventions for speakers of Sesotho, a South African language. Prefix-based cueing (our alternative name for initial phoneme cueing that describes these cues in Sesotho-oriented terms) was compared to a novel technique, root-based cueing (RBC). While prefix-based cues are described in the literature, we hypothesized root-based cues would be more appropriate in this context since they were thought to be more consonant with the linguistic parameters of Sesotho. Two speakers with aphasia, who demonstrated significant anomic symptoms, served as participants. We used a multiple-baseline, single case study design. Two 144-item word lists were developed with every item represented by a photograph. Each of the two word lists was associated with one of the two cueing techniques investigated. After baseline measurements were obtained, each participant attended eight facilitation sessions for each cueing condition, resulting in eight data points per condition and participant. For both participants, RBC resulted in greater naming performance than cueing by means of initial phonemes. Our explanation of these results is based on the Interactive Lexical Network model of lexical access; root-based cues may be more effective because they more efficiently constrain the number of lemmas activated after a cue is provided. We argue that a confluence of factors (word-retrieval processes and the character of Sesotho morphosyntax) gave rise to the noted differences in naming facilitation.

  • 54.
    Arkema, Elizabeth V
    et al.
    1Clinical Epidemiology Unit, Department of Medicine, Solna Karolinska Institute, Stockholm.
    Jönsen, Andreas
    Department of Clinical Sciences, Lund University, Lund.
    Rönnblom, Lars
    Department of Medical Sciences, Science for Life Laboratories, Uppsala University, Uppsala.
    Svenungsson, Elisabet
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Simard, Julia F
    Clinical Epidemiology Unit, Department of Medicine, Solna Karolinska Institute, Stockholm.
    Case definitions in Swedish register data to identify systemic lupus erythematosus2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 1Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To develop and investigate the utility of several different case definitions for systemic lupus erythematosus (SLE) using national register data in Sweden.

    METHODS: The reference standard consisted of clinically confirmed SLE cases pooled from four major clinical centres in Sweden (n=929), and a sample of non-SLE comparators randomly selected from the National Population Register (n=24 267). Demographics, comorbidities, prescriptions and autoimmune disease family history were obtained from multiple registers and linked to the reference standard. We first used previously published SLE definitions to create algorithms for SLE. We also used modern data mining techniques (penalised least absolute shrinkage and selection operator logistic regression, elastic net regression and classification trees) to objectively create data-driven case definitions. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the case definitions identified.

    RESULTS: Defining SLE by using only hospitalisation data resulted in the lowest sensitivity (0.79). When SLE codes from the outpatient register were included, sensitivity and PPV increased (PPV between 0.97 and 0.98, sensitivity between 0.97 and 0.99). Addition of medication information did not greatly improve the algorithm's performance. The application of data mining methods did not yield different case definitions.

    CONCLUSIONS: The use of SLE International Classification of Diseases (ICD) codes in outpatient clinics increased the accuracy for identifying individuals with SLE using Swedish registry data. This study implies that it is possible to use ICD codes from national registers to create a cohort of individuals with SLE.

  • 55.
    Arkema, Elizabeth V
    et al.
    Karolinska Institute, Stockholm, Sweden.
    Palmsten, Kristin
    University of California, San Diego, USA.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Svenungsson, Elisabet
    Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Salmon, Jane E
    Weill Cornell Medical College, New York, New York.
    Simard, Julia F
    Stanford School of Medicine, Stanford, California, USA ;Karolinska Institute, Stockholm, Sweden.
    What to Expect When Expecting With Systemic Lupus Erythematosus (SLE): A Population-Based Study of Maternal and Fetal Outcomes in SLE and Pre-SLE.2016In: Arthritis care & research, ISSN 2151-464X, E-ISSN 2151-4658, Vol. 68, no 7Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess maternal and fetal outcomes associated with subclinical (pre-systemic lupus erythematosus [SLE] and SLE presenting up to 5 years postpartum) and prevalent maternal SLE during pregnancy compared with the general population.

    METHODS: This prospective cohort study used population-based Swedish registers to identify 13,598 women with first singleton pregnancies registered in the Medical Birth Register (551 prevalent SLE, 65 pre-SLE within 0-2 years, 133 pre-SLE within 2-5 years, and 12,847 general population). SLE was defined as ≥2 SLE-coded discharge diagnoses in the patient register with ≥1 diagnosis from a specialist. Unadjusted risks of adverse pregnancy or birth outcomes were calculated by SLE status, and Cochran-Armitage tests evaluated trend across exposure groups.

    RESULTS: Maternal outcomes such as preeclampsia, hypothyroidism, stroke, and infection were more common among women with SLE. Sixteen percent of prevalent-SLE pregnancies were diagnosed with preeclampsia compared with 5% of those from the general population. Among the pre-SLE women, preeclampsia was found in 26% of those with SLE within 2 years postpartum and 13% in those with SLE within 2-5 years postpartum. Similarly, infant outcomes, such as preterm birth, infection, and mortality, were worse among those born to mothers with prevalent SLE and pre-SLE during pregnancy. The test for trend was significant for most outcomes.

    CONCLUSION: Our data demonstrate that adverse maternal and fetal outcomes are more common in SLE pregnancies. Furthermore, these unfavorable outcomes are observed in pregnancies occurring prior to the diagnosis of SLE. Thus, the underlying immunologic profile of SLE and alterations preceding clinical SLE may contribute to these pregnancy complications.

  • 56.
    Arkema, Elizabeth V
    et al.
    Clinical Epidemiology Unit, Karolinska Institutet, Stockholm.
    Rossides, Marios
    Clinical Epidemiology Unit, Karolinska Institutet, Stockholm.
    Von Euler, Mia
    Karolinska Institutet, Stockholm, Sweden.
    Svenungsson, Elisabet
    Rheumatology Unit, Karolinska Institutet, Stockholm.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Simard, Julia F
    Karolinska Institutet, Stockholm, Sweden, Stanford School of Medicine, Stanford, California, USA.
    Response to 'Increased stroke incidence in systemic lupus erythematosus patients"2018In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, no 10, article id UNSP e72Article in journal (Refereed)
  • 57.
    Arkema, Elizabeth V.
    et al.
    Karolinska Institute, Sweden.
    Svenungsson, Elisabet
    Karolinska Institute, Sweden.
    Von Euler, Mia
    Karolinska Institute, Sweden.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Simard, Julia F.
    Karolinska Institute, Sweden; Stanford School Med, CA USA; Stanford School Med, CA USA.
    Stroke in systemic lupus erythematosus: a Swedish population-based cohort study2017In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, no 9, p. 1544-1549Article in journal (Refereed)
    Abstract [en]

    Objective To study the occurrence of ischaemic and haemorrhagic stroke in systemic lupus erythematosus (SLE) compared with the general population by age, sex and time since SLE diagnosis Methods Adults with incident SLE were identified from the Swedish National Patient Register (NPR, n=3390) and general population comparators from the Total Population Register were matched on age, sex and county (n=16730). Individuals were followed prospectively until first of death, December 2013, emigration or incident stroke (identified from the NPR, Cause of Death Register and the Stroke Register). Incidence rates, rate differences and HR were estimated comparing SLE with non-SLE. Estimates were stratified by sex, age and time since diagnosis. Results We observed 126 strokes in SLE and 304 in the general population. Individuals with SLE had a twofold increased rate of ischaemic stroke compared with the general population (HR 2.2; 95% CI 1.7 to 2.8). The HR for intracerebral haemorrhage was 1.4 (95% CI 0.7 to 2.8). There was effect modification by sex and age, with the highest HRs for females and individuals amp;lt;50 years old. The HR for ischaemic stroke was highest in the first year of follow-up (3.7; 95% CI 2.1 to 6.5). Conclusions The relative risk of ischaemic stroke in SLE was more than doubled compared with the general population, and importantly, the highest relative risks were observed within the first year after SLE diagnosis. Thus, the first encounter with patients presents an opportunity for rheumatologists to screen for risk factors and intervene.

  • 58.
    Arlinger, Stig
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Nordqvist, Peter
    Royal Institute Technology, Sweden.
    Öberg, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    International Outcome Inventory for Hearing Aids: Data From a Large Swedish Quality Register Database2017In: American Journal of Audiology, ISSN 1059-0889, E-ISSN 1558-9137, Vol. 26, no 3, p. 443-450Article in journal (Refereed)
    Abstract [en]

    Purpose: The purpose of this study was to analyze a database of completed International Outcome Inventory for Hearing Aids (IOI-HA) questionnaires obtained from over 100,000 clients fitted with new hearing aids in Sweden during the period of 2012-2016. Mean IOI-HA total scores were correlated with degree of hearing loss, unilateral versus bilateral fitting, first-time versus return clients, gender, and variation among dispensing clinics. The correlations with expectations, service quality, and technical functioning of the hearing aids were also analyzed. Method: Questionnaires containing the 7 IOI-HA items as well as questions concerning some additional issues were mailed to clients 3-6 months after fitting of new hearing aids. The questionnaires were returned to and analyzed by an independent research institute. Results: More than 100 dispensing clinics nationwide take part in this project. A response rate of 52.6% resulted in 106,631 data sets after excluding incomplete questionnaires. Forty-six percent of the responders were women, and 54% were men. The largest difference in mean score (0.66) was found for the IOI-HA item "use" between return clients and first-time users. Women reported significantly higher (better) scores for the item "impact on others" compared with men. The bilaterally fitted subgroup reported significantly higher scores for all 7 items compared with the unilaterally fitted subgroup. Experienced users produced higher scores on benefit and satisfaction items, whereas first-time users gave higher scores for residual problems. No correlation was found between mean IOI-HA total score and average hearing threshold level (pure-tone average [ PTA]). Mean IOI-HA total scores were found to correlate significantly with perceived service quality of the dispensing center and with the technical functionality of the hearing aids. Conclusions: When comparing mean IOI-HA total scores from different studies or between groups, differences with regard to hearing aid experience, gender, and unilateral versus bilateral fitting have to be considered. No correlation was found between mean IOI-HA total score and degree of hearing loss in terms of PTA. Thus, PTA is not a reliable predictor of benefit and satisfaction of hearing aid provision as represented by the IOI-HA items. Identification of a specific lower fence in PTA for hearing aid candidacy is therefore to be avoided. Large differences were found in mean IOI-HA total scores related to different dispensing centers.

  • 59.
    Asp, Filip
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Mäki-Torkko, Elina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Karltorp, Eva
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Harder, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Hergils, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Eskilsson, Gunnar
    Karolinska University Hospital, Sweden.
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    A longitudinal study of the bilateral benefit in children with bilateral cochlear implants2015In: International Journal of Audiology, ISSN 1499-2027, E-ISSN 1708-8186, Vol. 54, no 2, p. 77-88Article in journal (Refereed)
    Abstract [en]

    Objective: To study the development of the bilateral benefit in children using bilateral cochlear implants by measurements of speech recognition and sound localization. Design: Bilateral and unilateral speech recognition in quiet, in multi-source noise, and horizontal sound localization was measured at three occasions during a two-year period, without controlling for age or implant experience. Longitudinal and cross-sectional analyses were performed. Results were compared to cross-sectional data from children with normal hearing. Study sample: Seventy-eight children aged 5.1-11.9 years, with a mean bilateral cochlear implant experience of 3.3 years and a mean age of 7.8 years, at inclusion in the study. Thirty children with normal hearing aged 4.8-9.0 years provided normative data. Results: For children with cochlear implants, bilateral and unilateral speech recognition in quiet was comparable whereas a bilateral benefit for speech recognition in noise and sound localization was found at all three test occasions. Absolute performance was lower than in children with normal hearing. Early bilateral implantation facilitated sound localization. Conclusions: A bilateral benefit for speech recognition in noise and sound localization continues to exist over time for children with bilateral cochlear implants, but no relative improvement is found after three years of bilateral cochlear implant experience.

  • 60.
    Atikuzzaman, Mohammad
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Bhai Mehta, Ratnesh
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Fogelholm, Jesper
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Wright, Dominic
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Mating induces the expression of immune- and pH-regulatory genes in the utero-vaginal junction containing mucosal sperm-storage tubuli of hens2015In: Reproduction, Vol. 150, no 6, p. 473-483Article in journal (Refereed)
    Abstract [en]

    The female chicken, as with other species with internal fertilization, can tolerate the presence of spermatozoa within specialized sperm-storage tubuli (SST) located in the mucosa of the utero-vaginal junction (UVJ) for days or weeks, without eliciting an immune response. To determine if the oviduct alters its gene expression in response to sperm entry, segments from the oviduct (UVJ, uterus, isthmus, magnum and infundibulum) of mated and unmated (control) hens, derived from an advanced inter-cross line between Red Junglefowl and White Leghorn, were explored 24 h after mating using cDNA microarray analysis. Mating shifted the expression of fifteen genes in the UVJ (53.33% immune-modulatory and 20.00% pH-regulatory) and seven genes in the uterus, none of the genes in the latter segment overlapping the former (with the differentially expressed genes themselves being less related to immune-modulatory function). The other oviductal segments did not show any significant changes. These findings suggest sperm deposition causes a shift in expression in the UVJ (containing mucosal SST) and the uterus for genes involved in immune-modulatory and pH-regulatory functions, both relevant for sperm survival in the hen's oviduct.

  • 61.
    Augier, Eric
    et al.
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Dulman, Russell S.
    NIAAA, MD USA.
    Rauffenbart, Caroline
    NIAAA, MD USA.
    Augier, Gaelle
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Cross, Alan J.
    AstraZeneca Neurosci, MA USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    The mGluR2 Positive Allosteric Modulator, AZD8529, and Cue-Induced Relapse to Alcohol Seeking in Rats2016In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 41, no 12, p. 2932-2940Article in journal (Refereed)
    Abstract [en]

    Group II metabotropic glutamate receptors (mGluR2 and mGluR3) may control relapse of alcohol seeking, but previously available Group II agonists were unable to discriminate between mGluR2 and mGluR3. Here we use AZD8529, a novel positive allosteric mGluR2 modulator, to determine the role of this receptor for alcohol-related behaviors in rats. We assessed the effects of AZD8529 (20 and 40 mg/kg s.c.) on male Wistar rats trained to self-administer 20% alcohol and determined the effects of AZD8529 on self-administration, as well as stress-induced and cue-induced reinstatement of alcohol seeking. The on-target nature of findings was evaluated in Indiana P-rats, a line recently shown to carry a mutation that disrupts the gene encoding mGluR2. The behavioral specificity of AZD8529 was assessed using self-administration of 0.2% saccharin and locomotor activity tests. AZD8529 marginally decreased alcohol self-administration at doses that neither affected 0.2% saccharin self-administration nor locomotor activity. More importantly, cue- but not stress-induced alcohol seeking was blocked by the mGluR2 positive allosteric modulator. This effect of AZD8529 was completely absent in P rats lacking functional mGluR2s, demonstrating the receptor specificity of this effect. Our findings provide evidence fora causal role of mGluR2 in cue induced relapse to alcohol seeking. They contribute support for the notion that positive allosteric modulators of mGluR2 block relapse-like behavior across different drug categories.

  • 62.
    Augustsson, Anna
    et al.
    Department of Biology and Environmental Science, Linnaeus University, Kalmar, Sweden.
    Uddh-Söderberg, Terese
    Department of Biology and Environmental Science, Linnaeus University, Kalmar, Sweden.
    Filipsson, Monika
    Department of Biology and Environmental Science, Linnaeus University, Kalmar, Sweden.
    Helmfrid, Ingela
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Berglund, Marika
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Hogmalm, Johan
    Department of Earth Sciences, University of Gothenburg, Gothenburg, Sweden.
    Karlsson, Andreas
    Department of Earth Sciences, University of Gothenburg, Gothenburg, Sweden.
    Alriksson, Stina
    Department of Biology and Environmental Science, Linnaeus University, Kalmar, Sweden.
    Challenges in assessing the health risks of consuming vegetables in metal-contaminated environments2018In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 113, p. 269-280, article id S0160-4120(17)31204-7Article in journal (Refereed)
    Abstract [en]

    A great deal of research has been devoted to the characterization of metal exposure due to the consumption of vegetables from urban or industrialized areas. It may seem comforting that concentrations in crops, as well as estimated exposure levels, are often found to be below permissible limits. However, we show that even a moderate increase in metal accumulation in crops may result in a significant increase in exposure. We also highlight the importance of assessing exposure levels in relation to a regional baseline. We have analyzed metal (Pb, Cd, As) concentrations in nearly 700 samples from 23 different vegetables, fruits, berries and mushrooms, collected near 21 highly contaminated industrial sites and from reference sites. Metal concentrations generally complied with permissible levels in commercial food and only Pb showed overall higher concentrations around the contaminated sites. Nevertheless, probabilistic exposure assessments revealed that the exposure to all three metals was significantly higher in the population residing around the contaminated sites, for both low-, median- and high consumers. The exposure was about twice as high for Pb and Cd, and four to six times as high for As. Since vegetable consumption alone did not result in exposure above tolerable intakes, it would have been easy to conclude that there is no risk associated with consuming vegetables grown near the contaminated sites. However, when the increase in exposure is quantified, its potential significance is harder to dismiss - especially when considering that exposure via other routes may be elevated in a similar way.

  • 63.
    Aziz, Abdul Maruf Asif
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Brothers, Shaun
    University of Miami Health System, University of Miami, Miami, USA.
    Sartor, Gregory
    University of Miami Health System, University of Miami, Miami, USA.
    Holm, Lovisa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Wahlestedt, Claes
    University of Miami Health System, University of Miami, Miami, USA.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    The nociceptin/orphanin FQ receptor agonist SR-8993 as a candidate therapeutic for alcohol use disorders: validation in rat models2016In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 233, no 19-20, p. 3553-3563Article in journal (Refereed)
    Abstract [en]

    RATIONALE: Alcoholism is a complex disorder in which diverse pathophysiological processes contribute to initiation and progression, resulting in a high degree of heterogeneity among patients. Few pharmacotherapies are presently available, and patient responses to these are variable. The nociceptin/orphanin FQ (NOP) receptor has been suggested to play a role both in alcohol reward and in negatively reinforced alcohol seeking. Previous studies have shown that NOP-receptor activation reduces alcohol intake in genetically selected alcohol-preferring as well as alcohol-dependent rats. NOP activation also blocks stress- and cue-induced reinstatement of alcohol-seeking behavior.

    OBJECTIVES: Here, we aimed to examine a novel, potent, and brain-penetrant small-molecule NOP-receptor agonist, SR-8993, in animal models of alcohol- as well as anxiety-related behavior using male Wistar rats.

    RESULTS: SR-8993 was mildly anxiolytic when given to naïve animals and potently reversed acute alcohol withdrawal-induced ("hangover") anxiety. SR-8993 reduced both home-cage limited access drinking, operant responding for alcohol, and escalation induced through prolonged intermittent access to alcohol. SR-8993 further attenuated stress- as well as cue-induced relapse to alcohol seeking. For the effective dose (1.0 mg/kg), non-specific effects such as sedation may be limited, since a range of control behaviors were unaffected, and this dose did not interact with alcohol elimination.

    CONCLUSION: These findings provide further support for NOP-receptor agonism as a promising candidate treatment for alcoholism and establish SR-8993 or related molecules as suitable for further development as therapeutics.

  • 64.
    Backman, Sofia
    et al.
    Skane Univ Hosp, Sweden.
    Rosen, Ingmar
    Skane Univ Hosp, Sweden.
    Blennow, Mats
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Andersson, Thomas
    Karolinska Univ Hosp, Sweden.
    Englund, Marita
    Karolinska Univ Hosp, Sweden.
    Flink, Roland
    Uppsala Univ Hosp, Sweden.
    Hallberg, Boubou
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Liedholm, Lars-Johan
    Umea Univ Hosp, Sweden.
    Norman, Elisabeth
    Lund Univ, Sweden.
    Sailer, Alexandra
    Umea Univ Hosp, Sweden.
    Thordstein, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Swedish consensus reached on recording, interpretation and reporting of neonatal continuous simplified electroencephalography that is supported by amplitude-integrated trend analysis2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 10, p. 1702-1709Article in journal (Refereed)
    Abstract [en]

    Continuous monitoring of electroencephalography (EEG), with a focus on amplitude-integrated EEG (aEEG), has been used in neonatal intensive care for decades. A number of systems have been suggested for describing and quantifying aEEG patterns. Extensive full-montage EEG monitoring is used in specialised intensive care units. The American Clinical Neurophysiology Society published recommendations for defining and reporting EEG findings in critically ill adults and infants. Swedish neonatologists and clinical neurophysiologists collaborated to optimise simplified neonatal continuous aEEG and EEG recordings based on these American documents. Conclusion: This paper describes the Swedish consensus document produced by those meetings.

  • 65.
    Ball, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    How many rhotic phonemes does modern Welsh have?2015In: Representations and Interpretations in Celtic Studies / [ed] Tomasz Czerniak, Maciej Czerniakowski, Krzysztof Jaskuła, Lublin: John Paul II Catholic University of Lublin , 2015, p. 49-61Chapter in book (Other academic)
  • 66.
    Ball, Martin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Is there phonology without meaning?2015Conference paper (Refereed)
  • 67.
    Ball, Martin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Multilingualism and acquired neurogenic speech disorders. Plenary presentation.2015Conference paper (Refereed)
  • 68.
    Ball, Martin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    The Establishment of DisorderedSpeechBank: A digital archive of disordered speech across languages2016Conference paper (Refereed)
  • 69.
    Ball, Martin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Isaksson, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, Elias
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Müller, Nicole
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Dysarthria in Swedish2016Conference paper (Other academic)
  • 70.
    Ball, Martin J.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Multilingualism and acquired neurogenic speech disorders2015In: Proceedings of the International Symposium on Monolingual and Bilingual Speech 2015 / [ed] Elena Babatsouli, David Ingram, Chania, Crete: Institute of Monolingual and Bilingual Speech , 2015, p. 40-46Chapter in book (Other academic)
    Abstract [en]

    Acquired neurogenic communication disorders can affect language, speech, or both. Although neurogenic speech disorders have been researched for a considerable time, much of this work has been restricted to a few languages (mainly English, with German, French, Japanese and Chinese also represented). Further, the work has concentrated on monolingual speakers. In this account, I aim to outline the main acquired speech disorders, and give examples of research into multilingual aspects of this topic. The various types of acquired neurogenic speech disorders support a tripartite analysis of normal speech production. Dysarthria (of varying sub - types) is a disorder of the neural pathways and muscle activity: the implementation of the motor plans for speech. Apraxia of speech on the other hand is a disorder of compilation of those motor plans (seen through the fact that novel utterances are disordered, while often formulaic utterances are not). Aphasia (at least when it affects speech rather than just language) manifests as a disorder at the phonological level; for example, paraphasias disrupt the normal ordering of segments, and jargon aphasias affect both speech sound inventories and the link between sound and meaning. I will illustrate examples of various acquired neurogenic speech dis orders in multilingual speakers drawn from recent literature. We will conclude by considering an example of jargon aphasia produced by a previously bilingual speaker (that is, bilingual before the acquired neurological damage). This example consists of non - perseverative non - word jargon, produced by a Louisiana French - English bilingual woman with aphasia. The client’s jargon has internal systematicity and these systematic properties show overlaps with both the French and English phonological system and structure. Therefore, while she does not have access to the lexicon of either language, it would seem that she accesses both the French and English phonological systems.

  • 71.
    Ball, Martin J.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Principles of clinical phonology: theoretical approaches2016 (ed. 1)Book (Refereed)
    Abstract [en]

    Those working on the description of disordered speech are bound to be also involved with clinical phonology to some extent. This is because interpreting the speech signal is only the first step to an analysis. Describing the organization and function of a speech system is the next step. However, it is here that phonologists differ in their descriptions, as there are many current approaches in modern linguistics to undertaking phonological analyses of both normal and disordered speech.

    Much of the work in theoretical phonology of the last fifty years or so is of little use in either describing disordered speech or explaining it. This is because the dominant theoretical approach in linguists as a whole attempts elegant descriptions of linguistic data, not a psycholinguistic model of what speakers do when they speak. The latter is what is needed in clinical phonology. In this text, Martin J. Ball addresses these issues in an investigation of what principles should underlie a clinical phonology. This is not, however, simply another manual on how to do phonological analyses of disordered speech data, though examples of the application of various models of phonology to such data are provided. Nor is this a guide on how to do therapy, though a chapter on applications is included. Rather, this is an exploration of what theoretical underpinnings are best suited to describing, classifying, and treating the wide range of developmental and acquired speech disorders encountered in the speech-language pathology clinic.

  • 72.
    Ball, Martin J.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Representations and Interpretations in Celtic Studies2015In: How many rhotic phonemes does modern Welsh have? / [ed] Tomasz Paweł Czerniak, Maciej Czerniakowski, Krzysztof Jaskuła; Katolicki Uniwersytet Lubelski Jana Pawła II. Wydawnictwo, Lublin: John Paul II Catholic University of Lublin , 2015, 1, p. 49-61Chapter in book (Refereed)
  • 73.
    Ball, Martin J.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Howard, Sara
    Esling, John
    Dickson, Craig
    Revisions to the extIPA and VoQS symbol sets.2016Conference paper (Refereed)
  • 74.
    Ball, Martin J.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Muller, Nicole
    The phonemic status of the rhotics in Modern Standard Welsh.2016Conference paper (Refereed)
  • 75.
    Ball, Martin J
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences.
    Müller, Nicole
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences.
    Editorial Material: Special Issue: Selected Papers from ICPLA 2014 in CLINICAL LINGUISTICS and PHONETICS, vol 29, issue 4, pp 247-2482015In: Clinical Linguistics & Phonetics, ISSN 0269-9206, E-ISSN 1464-5076, Vol. 29, no 4, p. 247-248Article in journal (Other academic)
    Abstract [en]

    n/a

  • 76.
    Barbier, Estelle
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Tapocik, Jenica D.
    NIAAA, MD 20892 USA.
    Juergens, Nathan
    NIAAA, MD 20892 USA.
    Pitcairn, Caleb
    NIAAA, MD 20892 USA.
    Borich, Abbey
    NIAAA, MD 20892 USA.
    Schank, Jesse R.
    NIAAA, MD 20892 USA.
    Sun, Hui
    NIAAA, MD 20892 USA.
    Schuebel, Kornel
    NIAAA, MD 20892 USA.
    Zhou, Zhifeng
    NIAAA, MD 20892 USA.
    Yuan, Qiaoping
    NIAAA, MD 20892 USA.
    Vendruscolo, Leandro F.
    NIDA, MD 21224 USA.
    Goldman, David
    NIAAA, MD 20892 USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    DNA Methylation in the Medial Prefrontal Cortex Regulates Alcohol-Induced Behavior and Plasticity2015In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 35, no 15, p. 6153-6164Article in journal (Refereed)
    Abstract [en]

    Recent studies have suggested an association between alcoholism and DNA methylation, a mechanism that can mediate long-lasting changes in gene transcription. Here, we examined the contribution of DNA methylation to the long-term behavioral and molecular changes induced by a history of alcohol dependence. In search of mechanisms underlying persistent rather than acute dependence-induced neuroadaptations, we studied the role of DNA methylation regulating medial prefrontal cortex (mPFC) gene expression and alcohol-related behaviors in rats 3 weeks into abstinence following alcohol dependence. Postdependent rats showed escalated alcohol intake, which was associated with increased DNA methylation as well as decreased expression of genes encoding synaptic proteins involved in neurotransmitter release in the mPFC. Infusion of the DNA methyltransferase inhibitor RG108 prevented both escalation of alcohol consumption and dependence-induced downregulation of 4 of the 7 transcripts modified in postdependent rats. Specifically, RG108 treatment directly reversed both downregulation of synaptotagmin 2 (Syt2) gene expression and hypermethylation on CpG#5 of its first exon. Lentiviral inhibition of Syt2 expression in the mPFC increased aversion-resistant alcohol drinking, supporting a mechanistic role of Syt2 in compulsive-like behavior. Our findings identified a functional role of DNA methylation in alcohol dependence-like behavioral phenotypes and a candidate gene network that may mediate its effects. Together, these data provide novel evidence for DNA methyltransferases as potential therapeutic targets in alcoholism.

  • 77.
    Barns, Angela
    et al.
    Curtin University, Perth, Western Australia, Australia.
    Svanholm, Frida
    Linköping University, Department of Medical and Health Sciences.
    Kjellberg, Anette
    Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Linköping University, Faculty of Medicine and Health Sciences.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin University, Perth, Western Australia, Australia.
    Living in the present: Women's everyday experiences of living with rheumatoid arthritis2015In: SAGE Open, ISSN 2158-2440, E-ISSN 2158-2440, Vol. 5, no 4, p. 1-13Article in journal (Refereed)
    Abstract [en]

    This article presents the findings from a qualitative research project exploring eight women’s experiences of living with rheumatoid arthritis (RA). Through semistructured interviews, the women provided insights into the physical, emotional, and social impacts of RA and the “work” involved in negotiating its influence in the everyday life. In narrating their experiences of adapting to RA, the women express a common desire for “normalcy,” to return to a time and space before the disruption of RA. The women’s accounts also emphasized the interrelatedness between bodily experience and constructions of self, highlighting the corporeal nature of RA and the constant shaping and reshaping of personal meanings and values.

  • 78.
    Bartek, Jiri Jr.
    et al.
    Copenhagen Univ Hosp, Denmark; Karolinska Univ Hosp, Sweden.
    Laugesen, Christian
    Copenhagen Univ Hosp, Denmark.
    Mirza, Sadia
    Karolinska Univ Hosp, Sweden.
    Forsse, Axel
    Odense Univ Hosp, Denmark.
    Petersen, Michael Anders
    Odense Univ Hosp, Denmark.
    Corell, Alba
    Sahlgrens Univ Hosp, Sweden.
    Dyhrfort, Philip Wilhelm
    Uppsala Univ Hosp, Sweden.
    Redebrandt, Henrietta Nittby
    Lund Univ Hosp, Sweden.
    Reen, Linus
    Lund Univ Hosp, Sweden.
    Zolfaghari, Shaian
    Lund Univ Hosp, Sweden.
    Tobieson, Lovisa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Carlsvärd, Björn
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Bergholt, Bo
    Arhus Univ Hosp, Denmark.
    Bashir, Asma
    Arhus Univ Hosp, Denmark.
    Soerensen, Preben
    Alborg Univ Hosp, Denmark.
    Bilgin, Arzu
    Alborg Univ Hosp, Denmark.
    Johansson, Conny
    Umea Univ Hosp, Sweden.
    Lindvall, Peter
    Umea Univ Hosp, Sweden.
    Forander, Petter
    Uppsala Univ Hosp, Sweden.
    Bellander, Bo-Michael
    Karolinska Univ Hosp, Sweden.
    Springborg, Jacob B.
    Copenhagen Univ Hosp, Denmark.
    Jakola, Asgeir S.
    Sahlgrens Univ Hosp, Sweden; Sahlgrens Acad, Sweden.
    Scandinavian Multicenter Acute Subdural Hematoma (SMASH) Study: Study Protocol for a Multinational Population-Based Consecutive Cohort2019In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 84, no 3, p. 799-803Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Traumatic acute subdural hematomas (ASDHs) are associated with high rate of morbidity and mortality, especially in elderly individuals. However, recent reports indicate that the morbidity and mortality rates might have improved. OBJECTIVE To evaluate postoperative (30-d) mortality in younger vs elderly (70 yr) patients with ASDH. Comparing younger and elderly patients, the secondary objectives are morbidity patterns of care and 6 mo outcome according to Glasgow outcome scale (GOS). Finally, in patients with traumatic ASDH, we aim to provide prognostic variables. METHODS This is a large-scale population-based Scandinavian study including all neurosurgical departments in Denmark and Sweden. All adult (18 yr) patients surgically treated between 2010 and 2014 for a traumatic ASDH in Denmark and Sweden will be included. Identification at clinicaltrials.gov is NCT03284190. EXPECTED OUTCOMES We expect to provide data on potential differences between younger vs elderly patients in terms of mortality and morbidity. We hypothesize that elderly patients selected for surgery have a similar pattern of care as compared with younger patients. We will provide functional outcome in terms of GOS at 6 mo in younger vs elderly patients undergoing ASDH evacuation. Finally, clinical useful prognostic factors for favorable (GOS 4-5) vs unfavorable (GOS 1-3) will be identified. DISCUSSION An improved understanding of the clinical outcome, treatment and resource allocation, clinical course, and the prognostic factors of traumatic ASDH will allow neurosurgeons to make better treatment decisions.

  • 79.
    Bay-Richter, Cecilie
    et al.
    Aarhus University, Denmark.
    Linderholm, Klas R.
    Karolinska Institute, Sweden.
    Lim, Chai K.
    Macquarie University, Australia.
    Samuelsson, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. Linköping University, Faculty of Medicine and Health Sciences.
    Traskman-Bendz, Lil
    Lund University, Sweden.
    Guillemin, Gilles J.
    Macquarie University, Australia.
    Erhardt, Sophie
    Karolinska Institute, Sweden.
    Brundin, Lena
    Michigan State University, MI USA; Van Andel Research Institute, MI USA.
    A role for inflammatory metabolites as modulators of the glutamate N-methyl-D-aspartate receptor in depression and suicidality2015In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 43, p. 110-117Article in journal (Refereed)
    Abstract [en]

    Background: Patients with depression and suicidality suffer from low-grade neuroinflammation. Proinflammatory cytokines activate indoleamine 2,3-dioxygenase, an initial enzyme of the kynurenine pathway. This pathway produces neuroactive metabolites, including quinolinic- and kynurenic acid, binding to the glutamate N-methyl-D-aspartate-receptor, which is hypothesized to be part of the neural mechanisms underlying symptoms of depression. We therefore hypothesized that symptoms of depression and suicidality would fluctuate over time in patients prone to suicidal behavior, depending on the degree of inflammation and kynurenine metabolite levels in the cerebrospinal fluid (CSF). Methods: We measured cytokines and kynurenine metabolites in CSF, collected from suicide attempters at repeated occasions over 2 years (total patient samples n = 143, individuals n = 30) and healthy controls (n = 36). The association between the markers and psychiatric symptoms was assessed using the Montgomery Asberg Depression Rating Scale and the Suicide Assessment Scale. Results: Quinolinic acid was increased and kynurenic acid decreased over time in suicidal patients versus healthy controls. Furthermore, we found a significant association between low kynurenic acid and severe depressive symptoms, as well as between high interleukin-6 levels and more severe suicidal symptoms. Conclusions: We demonstrate a long-term dysregulation of the kynurenine pathway in the central nervous system of suicide attempters. An increased load of inflammatory cytokines was coupled to more severe symptoms. We therefore suggest that patients with a dysregulated kynurenine pathway are vulnerable to develop depressive symptoms upon inflammatory conditions, as a result the excess production of the NMDA-receptor agonist quinolinic acid. This study provides a neurobiological framework supporting the use of NMDA-receptor antagonists in the treatment of suicidality and depression. (C) 2014 Elsevier Inc. All rights reserved.

  • 80.
    Bednarska, Olga
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Icenhour, Adriane
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
    Tapper, Sofie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Witt, Suzanne Tyson
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Elsenbruch, Sigrid
    Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome2019In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 160, no 9, p. 2004-2012Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a visceral pain condition with psychological comorbidity. Brain imaging studies in IBS demonstratealtered function in anterior insula (aINS), a key hub for integration of interoceptive, affective, and cognitive processes. However,alterations in aINS excitatory and inhibitory neurotransmission as putative biochemical underpinnings of these functional changesremain elusive. Using quantitative magnetic resonance spectroscopy, we compared women with IBS and healthy women (healthycontrols [HC]) with respect to aINS glutamate 1 glutamine (Glx) and g-aminobutyric acid (GABA1) concentrations and addressedpossible associations with symptoms. Thirty-nine women with IBS and 21 HC underwent quantitative magnetic resonancespectroscopy of bilateral aINS to assess Glx and GABA1 concentrations. Questionnaire data from all participants and prospectivesymptom-diary data from patients were obtained for regression analyses of neurotransmitter concentrations with IBS-related andpsychological parameters. Concentrations of Glx were lower in IBS compared with HC (left aINS P , 0.05, right aINS P , 0.001),whereas no group differences were detected for GABA1concentrations. Lower right-lateralized Glx concentrations in patients weresubstantially predicted by longer pain duration, while less frequent use of adaptive pain‐coping predicted lower Glx in left aINS. Ourfindings provide first evidence for reduced excitatory but unaltered inhibitory neurotransmitter levels in aINS in IBS. The results alsoindicate a functional lateralization of aINS with a stronger involvement of the right hemisphere in perception of abdominal pain and ofthe left aINS in cognitive pain regulation. Our findings suggest that glutaminergic deficiency may play a role in pain processing in IBS.

  • 81.
    Bednarska, Olga
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Tapper, Sofie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Lowén, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Neurotransmittor Concentration in Pregenual ACC in Stool Consistency Patient Subgroups With IBS2014Conference paper (Refereed)
    Abstract [en]

    Introduction

    The Anterior Cingulate Cortex (ACC) is a key region of the central autonomic brain network. Irritable Bowel Syndrome (IBS) is characterized abdominal pain and bowel habit disturbances. Autonomic dysregulation has been reported in IBS as well as altered ACC activation in pregenual ACC during visceral stimulation 1 2. Glutamate is the major excitatory and Gamma-aminobutyric acid (GABA) the major inhibitory neurotransmitter in the brain.

    Aim & Methods

    We aimed to measure neurotransmitter concentration in the pregenual ACC, in stool consistency subgroups with IBS by using quantitative neurotransmitter Magnetic Resonance Spectroscopy (qMRS)Seven patients with IBS-mixed (6 women) and five patients with IBS -diarrhea (4 women) according to Rome 3 were included. Mean age was 34.2 years (SD 5.3) with no significant difference between subgroups.  Patients completed symptom severity score (IBS-SSS). Quantitative MRS was measured in a 3T MRI scanner. A water-suppressed MEGA-PRESS sequence (TR 2.0 s, TE 68 ms) was used with the editing pulses placed at 1.90 ppm (‘ON-dynamics’) and at 7.46 ppm (‘OFF-dynamics’) with a voxel (3x3x3 cm3) placed in the pACC. Each MEGA-PRESS measurement resulted in a sequence of 40 OFF- and ON-dynamics, where each was computed by 8 phase cycles. Directly after each water-suppressed MEGA-PRESS measurement, a shorter 2-dynamic unsuppressed water MEGA-PRESS measurement was performed within the same voxel, which was used to obtain the concentrations in physically well-defined units of [mM]. The GABA concentrations were computed by averaging the difference spectra obtained by subtracting each OFF-dynamic from subsequent ON-dynamic and using LCModel (Version 6.3) for the final quantification. The Glutamate concentrations were obtained by only averaging the OFF-dynamics, which were not affected by the editing pulses. Additionally, all dynamics were phase and frequency corrected prior to the averaging. For group comparison unpaired T-tests were used.

    Results

    Patients had moderate to severe symptoms with IBS-SSS of 367 (SD 79.7). There was no significant difference between IBS subgroups in terms of IBS-SSS. Mean pACC GABA concentration was 1.66 (SD 0.17) mM in IBS-M and 1.65 (SD 0.27) mM in IBS-D. There was no significant difference between groups (p=0.9). Mean pACC Glutamate concentration was 4.54 (0.35) mM in IBS-M and 5.13 (SD 0.64) mM in IBS-D. There was no significant difference between groups, although a trend with p=0.06 was observed.

    Conclusion

    Further qMRS data have to be collected in IBS patients as well as healthy controls to evaluate if IBS subgroups demonstrate alterations in pACC glutamate and GABA concentrations

  • 82.
    Bednarska, Olga
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Casado-Bedmar, Maite
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Salvo-Romero, Eloisa
    University of Autonoma Barcelona, Spain.
    Vicario, Maria
    University of Autonoma Barcelona, Spain.
    Mayer, Emeran A.
    University of Calif Los Angeles, CA 90095 USA.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome2017In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 153, no 4, p. 948-+Article in journal (Refereed)
    Abstract [en]

    BACKGROUND amp; AIMS: Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis and symptoms of IBS develop following gastroenteritis. We aimed to study the passage of live bacteria through the colonic epithelium, and determine the role of mast cells (MCs) and vasoactive intestinal polypeptide (VIP) in barrier regulation in IBS and healthy individuals. METHODS: Colon biopsies from 32 women with IBS and 15 age-matched healthy women (controls) were mounted in Ussing chambers; we measured numbers of fluorescently labeled Escherichia coli HS and Salmonella typhimurium that passed through from the mucosal side to the serosal side of the tissue. Some biopsies were exposed to agents that block the VIP receptors (VPAC1 and VPAC2) or MCs. Levels of VIP and tryptase were measured in plasma and biopsy lysates. Number of MCs and MCs that express VIP or VIP receptors were quantified by immunofluorescence. Biopsies from an additional 5 patients with IBS and 4 controls were mounted in chambers and Salmonella were added; we studied passage routes through the epithelium by transmission electron microscopy and expression of tight junctions by confocal microscopy. RESULTS: In colon biopsies from patients with IBS, larger numbers of E coli HS and S typhimurium passed through the epithelium than in biopsies from controls (P amp;lt;.0005). In transmission electron microscopy analyses, bacteria were found to cross the epithelium via only the transcellular route. Bacterial passage was reduced in biopsies from patients with IBS and controls after addition of antibodies against VPACs or ketotifen, which inhibits MCs. Plasma samples from patients with IBS had higher levels of VIP than plasma samples from controls. Biopsies from patients with IBS had higher levels of tryptase, larger numbers of MCs, and a higher percentage of MCs that express VPAC1 than biopsies from controls. In biopsies from patients with IBS, addition of Salmonella significantly reduced levels of occludin; subsequent addition of ketotifen significantly reversed this effect. CONCLUSIONS: We found that colonic epithelium tissues from patients with IBS have increased translocation of commensal and pathogenic live bacteria compared with controls. The mechanisms of increased translocation include MCs and VIP.

  • 83.
    Bendas, Johanna
    et al.
    Technical University of Dresden, Germany.
    Georgiadis, Janniko R.
    University of Medical Centre Groningen, Netherlands.
    Ritschel, Gerhard
    Technical University of Dresden, Germany.
    Olausson, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Weidner, Kerstin
    Technical University of Dresden, Germany.
    Croy, Ilona
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Technical University of Dresden, Germany.
    C-Tactile Mediated Erotic Touch Perception Relates to Sexual Desire and Performance in a Gender-Specific Way2017In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 14, no 5, p. 645-653Article in journal (Refereed)
    Abstract [en]

    Background: Unmyelinated low-threshold mechanoreceptors-the so-called C-tactile (CT) afferents-play a crucial role in the perception and conduction of caressing and pleasant touch sensations and significantly contribute to the concept of erotic touch perception. Aim: To investigate the relations between sexual desire and sexual performance and the perception of touch mediated by CT afferents. Methods: Seventy healthy participants (28 men, 42 women; mean age+/-SD = 24.84+/-4.08 years, range = 18-36 years) underwent standardized and highly controlled stroking stimulation that varied in the amount of CT fiber stimulation by changing stroking velocity (CT optimal = 1, 3 and 10 cm/s; CT suboptimal = 0.1, 0.3, and 30 cm/s). Participants rated the perceived pleasantness, eroticism, and intensity of the applied tactile stimulation on a visual analog scale, completed the Sexual Desire Inventory, and answered questions about sexual performance. Outcomes: Ratings of perceived eroticism of touch were related to self-report levels of sexual desire and sexual performance. Results: Pleasantness and eroticism ratings showed similar dependence on stroking velocity that aligned with the activity of CT afferents. Erotic touch perception was related to sexual desire and sexual performance in a gender-specific way. In women, differences in eroticism ratings between CT optimal and suboptimal velocities correlated positively with desire for sexual interaction. In contrast, in men, this difference correlated to a decreased frequency and longer duration of partnered sexual activities. Clinical Implications: The present results lay the foundation for future research assessing these relations in patients with specific impairments of sexual functioning (eg, hypoactive sexual desire disorder). Strengths and Limitations: The strength of the study is the combination of standardized neurophysiologic methods and behavioral data. A clear limitation of the study design is the exclusion of exact data on the female menstrual cycle and the recruitment of an inhomogeneous sample concerning sexual orientation. Conclusion: The present results provide further evidence that unmyelinated CT afferents play a role in the complex mechanism of erotic touch perception. The ability to differentiate between CT optimal and suboptimal stimuli relates to sexual desire and performance in a gender-specific way. Copyright (C) 2017, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  • 84.
    Bengtsson, Ewert
    et al.
    Uppsala University, Sweden.
    Danielsen, Havard
    Oslo University Hospital, Norway.
    Treanor, Darren
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. University of Leeds, England; Leeds Teaching Hospital NHS Trust, England.
    Gurcan, Metin N.
    Ohio State University, OH 43210 USA.
    MacAulay, Calum
    British Columbia Cancer Research Centre, Canada.
    Molnar, Bela
    Semmelweis University, Hungary.
    Computer-aided diagnostics in digital pathology2017In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 91, no 6, p. 551-554Article in journal (Other academic)
    Abstract [en]

    n/a

  • 85.
    Bentow, C.
    et al.
    Inova Diagnost, CA USA.
    Lakos, G.
    Inova Diagnost, CA USA.
    Martis, P.
    Inova Diagnost, CA USA.
    Wahl, E.
    Inova Diagnost, CA USA.
    Garcia, M.
    Hospital Clin Barcelona, Spain.
    Vinas, O.
    Hospital Clin Barcelona, Spain.
    Espinosa, G.
    Hospital Clin Barcelona, Spain.
    Cervera, R.
    Hospital Clin Barcelona, Spain.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Carmona-Fernandes, D.
    University of Lisbon, Portugal.
    Santos, M. J.
    University of Lisbon, Portugal.
    Hanly, J. G.
    Dalhousie University, Canada.
    Mahler, M.
    Inova Diagnost, CA USA.
    International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies2016In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 25, no 8, p. 864-872Article in journal (Refereed)
    Abstract [en]

    Objective: Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). Patients and methods: A total of 1431 samples (SLE, n=843; disease controls, n=588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n=566). The SLEDAI-2K scores were available for 805 SLE patients and a cut-off ofamp;gt;4 was used to define active disease. Results: QUANTA Flash dsDNA had a sensitivity of 54.3% for the diagnosis of SLE, combined with 89.8% specificity. Anti-dsDNA antibody levels were significantly higher (pamp;lt;0.0001) in active SLE (SLEDAI-2Kamp;gt;4; n=232; median value 83.0IU/mL) versus the inactive patients (n=573; median value 22.3IU/mL), and the SLEDAI-2K scoring correlated with their dsDNA antibody levels (Spearmans rho=0.44, pamp;lt;0.0001). Similar but less pronounced findings were also found for the ELISA, in relation to disease activity. Conclusions: The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity.

  • 86.
    Bergamino, Maurizio
    et al.
    Laureate Institute Brain Research, OK, USA.
    Pasternak, Ofer
    Harvard University, MA, USA.
    Farmer, Madison
    Laureate Institute Brain Research, OK, USA.
    Shenton, Martha E.
    Harvard University, MA, USA; VA Boston Healthcare Syst, MA USA.
    Hamilton, Paul
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Laureate Institute Brain Research, OK, USA.
    Applying a free-water correction to diffusion imaging data uncovers stress-related neural pathology in depression2016In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 10, p. 336-342Article in journal (Refereed)
    Abstract [en]

    Diffusion tensor imaging (DTI) holds promise for developing our understanding of white-matter pathology in major depressive disorder (MDD). Variable findings in DTI-based investigations ofMDD, however, have thwarted development of this literature. Effects of extra-cellular free-water on the sensitivity of DTI metrics could account for some of this inconsistency. Here we investigated whether applying a free-water correction algorithm to DTI data could improve the sensitivity to detect clinical effects using DTI metrics. Only after applying this correction, we found: a) significantly decreased fractional anisotropy and axial diffusivity (AD) in the left inferior frontooccipital fasciculus (IFOF) in MDD; and b) increased self-reported stress that significantly correlated with decreased IFOF AD in depression. We estimated and confirmed the robustness of differences observed between free-water corrected and uncorrected approaches using bootstrapping. We conclude that applying a free-water correction to DTI data increases the sensitivity of DTI-based metrics to detect clinical effects in MDD. (C) 2015 The Authors. Published by Elsevier Inc.

  • 87.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Bich Hoang, Ngoc Thi
    Vietnam Natl Childrens Hosp, Vietnam.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Kien Le, Ngai
    Vietnam Natl Childrens Hosp, Vietnam.
    Svartström, Olov
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Khanh Khu, Dung Thi
    Vietnam Natl Childrens Hosp, Vietnam.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Thanh Le, Hai
    Vietnam Natl Childrens Hosp, Vietnam.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Olson, Linus
    TRAC, Sweden; TRAC, Vietnam; Karolinska Inst, Sweden.
    Larsson, Mattias
    TRAC, Sweden; TRAC, Vietnam; Karolinska Inst, Sweden.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. TRAC, Sweden; TRAC, Vietnam.
    Insertion sequence transpositions and point mutations in mgrB causing colistin resistance in a clinical strain of carbapenem-resistant Klebsiella pneumoniae from Vietnam2018In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 51, no 5, p. 789-793Article in journal (Refereed)
    Abstract [en]

    Resistance among Klebsiella pneumoniae to the last-resort antibiotics carbapenems and colistin is increasing worldwide. In this study, whole-genome sequencing was used to determine the colistin resistance mechanisms in clinical isolates of carbapenem-and colistin-resistant K. pneumoniae from Vietnam. Alterations in the regulatory gene mgrB, via mutations and insertion sequence transpositions, were found in 30 of 31 isolates, emphasising the importance of this resistance mechanism in colistin-resistant K. pneumoniae. (c) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  • 88.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Chen, Baoli
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sun, Qiang
    Shandong Univ, Peoples R China.
    Xu, Liuchen
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Li, Yan
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Bi, Zhenwang
    Shandong Ctr Dis Control and Prevent, Peoples R China.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Characterization of extended-spectrum -lactamase-producing Escherichia coli harboring mcr-1 and toxin genes from human fecal samples from China2018In: FUTURE COMPUTING ... the ... International Conference on Future Computational Technologies and Applications, ISSN 1746-0913, E-ISSN 1999-5903, Vol. 13, no 15, p. 1647-1656Article in journal (Refereed)
    Abstract [en]

    Aim: To characterize extended-spectrum -lactamase-producing Escherichia coli harboring the colistin resistance gene mcr-1 from human fecal samples collected in 2012 in a rural area of Shandong province, PR China. Materials amp; methods: Whole-genome sequencing and antimicrobial susceptibility testing was performed on 25 mcr-1-positive isolates to determine carriage of antibiotic resistance and virulence genes, diversity and antibiotic resistance profiles. Results: The isolates were highly genetically diverse and carried a large variety of different antibiotic resistance genes. The multidrug-resistance rate was high (96%). Virulence genes associated with intestinal pathogenic E. coli were carried by 32% of the isolates. Conclusion: Further monitoring of the epidemiological situation is necessary to ensure a preparedness for potential emergence of novel, difficult-to-treat strains and awareness of available treatment options.

  • 89.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hoang, Ngoc Thi Bich
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Le, Ngai Kien
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Welander, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Khu, Dung Thi Khanh
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Nilsson, Lennart E.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Olson, Linus
    The Karolinska Institute, Stockholm, Sweden.
    Le, Hai Thanh
    National Hospital of Pediatrics, Hanoi, Vietnam.
    Larsson, Mattias
    The Karolinska Institute, Stockholm, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Colistin- and carbapenem-resistant Klebsiella pneumoniae carrying mcr-1 and bla(OXA-48) isolated at a paediatric hospital in Vietnam2018In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 73, no 4, p. 1100-1102Article in journal (Other academic)
    Abstract [en]

    n/a

  • 90.
    Bergström, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Lundberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jönsson, Simon
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sarndahl, Eva
    Örebro University, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Annexin A1 in blood mononuclear cells from patients with coronary artery disease: Its association with inflammatory status and glucocorticoid sensitivity2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174177Article in journal (Refereed)
    Abstract [en]

    Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of glucocorticoid actions. In atherosclerotic tissue, increased expression of AnxA1 has been associated with protective plaque-stabilizing effects. Here, we investigated the expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Blood was collected from 57 patients with stable CAD (SCAD) and 41 healthy controls. We also included a minor group (n = 10) with acute coronary syndrome (ACS). AnxA1 mRNA was measured in PBMCs. Expression of AnxA1 protein (total and surface-bound) and glucocorticoid receptors (GR) were detected in PBMC subsets by flow cytometry. Also, salivary cortisol, interleukin(IL)-6 and IL-10 in plasma, and LPS-induced cytokine secretion from PBMCs, with or without dexamethasone, were assessed. AnxA1 mRNA was found to be slightly increased in PBMCs from SCAD patients compared with controls. However, protein expression of AnxA1 or GRs in PBMC subsets did not differ between SCAD patients and controls, despite SCAD patients showing a more proinflammatory cytokine profile ex vivo. Only surface expression of AnxA1 on monocytes correlated with dexamethasone-mediated suppression of cytokines. In ACS patients, a marked activation of AnxA1 was seen involving both gene expression and translocation of protein to cell surface probably reflecting a rapid glucocorticoid action modulating the acute inflammatory response in ACS. To conclude, surface expression of AnxA1 on monocytes may reflect the degree of glucocorticoid sensitivity. Speculatively, "normal" surface expression of AnxA1 indicates that anti-inflammatory capacity is impaired in SCAD patients.

  • 91.
    Bergström, Maria
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Linköping University, Faculty of Medicine and Health Sciences.
    Ahlstrand, Inger
    Jönköping University, Sweden.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Jonköping University, Sweden; Curtin University, Australia.
    Börsbo, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Björk, Mathilda
    Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Like the worst toothache you've had - How people with rheumatoid arthritis describe and manage pain2017In: Scandinavian Journal of Occupational Therapy, ISSN 1103-8128, E-ISSN 1651-2014, Vol. 24, no 6, p. 468-476Article in journal (Refereed)
    Abstract [en]

    Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease often associated with disability. Despite new treatments, pain and activity limitations are still present. Objectives: To describe how persons with RA experience and manage pain in their daily life. Methods: Seven semi-structured focus groups (FGs) were conducted and analyzed using content analysis. Results: The analysis revealed four categories: 1) Pain expresses itself in different ways referred to pain as overwhelming, aching or as a feeling of stiffness. 2) Mitigating pain referred to the use of heat, cold, medications and activities as distractions from the pain. 3) Adapting to pain referred to strategies employed as coping mechanisms for the pain, e.g. planning and adjustment of daily activities, and use of assistive devices. 4) Pain in a social context referred to the participants social environment as being both supportive and uncomprehending, the latter causing patients to hide their pain. Conclusions: Pain in RA is experienced in different ways. This emphasizes the multi-professional team to address this spectrum of experiences and to find pain management directed to the individual experience that also include the persons social environment.

  • 92.
    Berlin, Gösta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Cherif, Honar
    Akademiska sjukhuset - Hematologiska kliniken Uppsala, Sweden Akademiska sjukhuset - Hematologiska kliniken Uppsala, Sweden.
    Knutson, Folke
    Akademiska sjukhuset - Klinisk immunologi och transfusionsmedicin Uppsala, Sweden Akademiska sjukhuset - Klinisk immunologi och transfusionsmedicin Uppsala, Sweden.
    Mattsson, Jonas
    Karolinska Universitetssjukhuset - Centrum för allogen stamcellstransplantation Stockholm, Sweden .
    Axdorph Nygell, Ulla
    Karolinska Universitetssjukhuset - Klinisk immunologi och transfusionsmedicin Stockholm, Sweden .
    Granulocyttransfusion bör övervägas vid neutropeni och allvarlig infektion [Granulocyte transfusion – when and how should it be used?]2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, article id EXUUArticle, review/survey (Refereed)
    Abstract [en]

    There are no randomized controlled trials proving the clinical benefit of granulocyte transfusions. However, clinical experience and a number of case studies suggest that granulocyte transfusions may be life-saving in certain situations. In our opinion granulocyte transfusions should be considered for patients with profound neutropenia and severe, life-threatening infection not responding to antibiotic or antifungal therapy. Since the clinical effect seems to be dose-dependent, the granulocyte concentrate should contain a large number of cells, which usually means that the donor should be mobilized with steroids and G-CSF. Regular blood donors as well as relatives to the patient can be used for granulocyte donations with apheresis technique after information of the process. Granulocyte transfusion should be given daily as long as the indication remains. The clinical efficacy of the transfusions should be evaluated daily.

  • 93.
    Berlin, Gösta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Cherif, Honar
    Akademiska sjukhuset - Hematologiska kliniken Uppsala, Sweden Akademiska sjukhuset - Hematologiska kliniken Uppsala, Sweden.
    Knutson, Folke
    Akademiska sjukhuset - Klinisk immunologi och transfusionsmedicin Uppsala, Sweden Akademiska sjukhuset - Klinisk immunologi och transfusionsmedicin Uppsala, Sweden.
    Mattsson, Jonas
    Karolinska Universitetssjukhuset - Centrum för allogen stamcellstransplantation Stockholm, Sweden Karolinska Universitetssjukhuset - Centrum för allogen stamcellstransplantation Stockholm, Sweden.
    Axdorph Nygell, Ulla
    Karolinska Universitetssjukhuset - Klinisk immunologi och transfusionsmedicin Stockholm, Sweden Karolinska Universitetssjukhuset - Klinisk immunologi och transfusionsmedicin Stockholm, Sweden.
    Replik gällande granulocyttransfusion: Rekommendationerna är väl underbyggda2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Article in journal (Refereed)
  • 94.
    Berlin, Gösta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Tapper, Linus
    Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Tynngård, Nahreen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Effects of age, gender and menstrual cycle on platelet function assessed by impedance aggregometry2019In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 30, no 4, p. 473-479Article in journal (Refereed)
    Abstract [en]

    Platelets are needed to prevent or arrest bleeding and aggregate at the site of injury upon vascular damage. Platelets express receptors for estrogens which might affect the function of the platelets and their hemostatic ability. The aim was to identify possible differences in platelet function related to age, gender, and phases of the menstrual cycle by use of impedance aggregometry with Multiplate. In the first part of the study, platelet function was assessed in 60 healthy individuals (30 men and 30 women) in each of three age groups (20-25, 40-45, and 60-65 years). In the second part of the study, the platelet function was analyzed on four occasions during the menstrual cycle in women without oral contraceptives (OCs) (n = 17) and compared to 19 women on OCs and 18 men of similar age (20-40 years). For the women on OCs, aggregation was analyzed once during the tablet-free week and once late during the period with OCs. The men were sampled once. Women of younger age (amp;lt;45 years) had significantly higher agonist-induced aggregation response than both men and post-menopausal women (60-65 years). The agonist-induced aggregation response did not differ between phases of the menstrual cycle or OC use. The results suggest that estradiol and/or progesterone affect spontaneous aggregation since it was found to be lowest in the mid-luteal phase. Spontaneous aggregation was significantly lower in women on OCs than in both men and women without OCs. Our findings indicate that fertile age is associated with higher aggregation response capacity of the platelets, possibly to prevent excessive bleeding during menstruation, but this response capacity is not altered during the menstrual cycle or by use of OCs.

  • 95.
    Bernardi, R. E.
    et al.
    Heidelberg University, Germany.
    Zohsel, K.
    Heidelberg University, Germany.
    Hirth, N.
    Heidelberg University, Germany.
    Treutlein, J.
    Heidelberg University, Germany.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Laucht, M.
    Heidelberg University, Germany.
    Spanagel, R.
    Heidelberg University, Germany.
    Sommer, W. H.
    Heidelberg University, Germany.
    A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology2016In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 6, no e861Article in journal (Refereed)
    Abstract [en]

    It has been proposed that vulnerability to nicotine addiction is moderated by variation at the mu-opioid receptor locus (OPRM1), but results from human studies vary and prospective studies based on genotype are lacking. We have developed a humanized mouse model of the most common functional OPRM1 polymorphism rs1799971_A4G (A118G). Here we use this model system together with a cohort of German youth to examine the role of the OPRM1 A118G variation on nicotine reward. Nicotine reinforcement was examined in the humanized mouse model using i.v. self-administration. Male (n = 17) and female (n = 26) mice homozygous either for the major human A allele (AA) or the minor G allele (GG) underwent eight daily 2 h sessions of nicotine self-administration. Furthermore, male (n = 104) and female (n = 118) subjects homozygous for the A allele or carrying the G allele from the Mannheim Study of Children at Risk were evaluated for pleasurable and unpleasant experiences during their initial smoking experience. A significant sex-by-genotype effect was observed for nicotine self-administration. Male 118GG mice demonstrated higher nicotine intake than male 118AA mice, suggesting increased nicotine reinforcement. In contrast, there was no genotype effect in female mice. Human male G allele carriers reported increased pleasurable effects from their first smoking experience, as compared to male homozygous A, female G and female homozygous A allele carriers. The 118G allele appears to confer greater sensitivity to nicotine reinforcement in males, but not females.

  • 96.
    Bernstein, Joshua G. W.
    et al.
    Walter Reed National Mil Medical Centre, MD 20889 USA.
    Danielsson, Henrik
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Hällgren, Mathias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Stenfelt, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rönnberg, Jerker
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Lunner, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Oticon AS, Denmark.
    Spectrotemporal Modulation Sensitivity as a Predictor of Speech-Reception Performance in Noise With Hearing Aids2016In: TRENDS IN HEARING, ISSN 2331-2165, Vol. 20, article id 2331216516670387Article in journal (Refereed)
    Abstract [en]

    The audiogram predicts amp;lt;30% of the variance in speech-reception thresholds (SRTs) for hearing-impaired (HI) listeners fitted with individualized frequency-dependent gain. The remaining variance could reflect suprathreshold distortion in the auditory pathways or nonauditory factors such as cognitive processing. The relationship between a measure of suprathreshold auditory function-spectrotemporal modulation (STM) sensitivity-and SRTs in noise was examined for 154 HI listeners fitted with individualized frequency-specific gain. SRTs were measured for 65-dB SPL sentences presented in speech-weighted noise or four-talker babble to an individually programmed master hearing aid, with the output of an ear-simulating coupler played through insert earphones. Modulation-depth detection thresholds were measured over headphones for STM (2cycles/octave density, 4-Hz rate) applied to an 85-dB SPL, 2-kHz lowpass-filtered pink-noise carrier. SRTs were correlated with both the high-frequency (2-6 kHz) pure-tone average (HFA; R-2 = .31) and STM sensitivity (R-2 = .28). Combined with the HFA, STM sensitivity significantly improved the SRT prediction (Delta R-2 = .13; total R-2 = .44). The remaining unaccounted variance might be attributable to variability in cognitive function and other dimensions of suprathreshold distortion. STM sensitivity was most critical in predicting SRTs for listenersamp;lt;65 years old or with HFA amp;lt;53 dB HL. Results are discussed in the context of previous work suggesting that STM sensitivity for low rates and low-frequency carriers is impaired by a reduced ability to use temporal fine-structure information to detect dynamic spectra. STM detection is a fast test of suprathreshold auditory function for frequencies amp;lt;2 kHz that complements the HFA to predict variability in hearing-aid outcomes for speech perception in noise.

  • 97.
    Berntsson, S. G.
    et al.
    Uppsala Univ, Sweden.
    Kristoffersson, A.
    Uppsala Univ, Sweden; Motala Gen Hosp, Sweden.
    Boström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Feresiadou, A.
    Uppsala Univ, Sweden.
    Burman, J.
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala Univ, Sweden; Motala Gen Hosp, Sweden.
    Rapidly increasing off-label use of rituximab in multiple sclerosis in Sweden Outlier or predecessor?2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 4, p. 327-331Article in journal (Refereed)
    Abstract [en]

    ObjectivesOff-label use of rituximab to treat MS patients in Sweden is high, and the need for long-term safety data may not be met. Our objectives were to assess the rate of rituximab prescription in patients with multiple sclerosis in Sweden and, in addition, to evaluate the safety of rituximab in a single centre for patients with multiple sclerosis. Material and MethodsReview of the Swedish MS register was performed to study the number of MS patients treated with rituximab during the last 6years. Investigation also included a retrospective review of medical files in search for possible side effects/adverse events in all adult patients with MS treated with rituximab at Uppsala University Hospital. ResultsPresently, in Sweden the rate of rituximab prescriptions in relation to other annually started of disease- modifying drugs in MS is 53.5%. ConclusionsThe share of MS patients in Sweden who are treated with rituximab is very high, and also rapidly increasing. Taken into account the off-label use, cases with adverse medical conditions that could possibly be related to rituximab use should be reported thoroughly.

  • 98.
    Berntsson, Shala G.
    et al.
    Uppsala Univ, Sweden.
    Gauffin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Melberg, Atle
    Uppsala Univ, Sweden.
    Holtz, Anders
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala Univ, Sweden.
    Inherited Ataxia and Intrathecal Baclofen for the Treatment of Spasticity and Painful Spasms2019In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 97, no 1, p. 18-23Article in journal (Refereed)
    Abstract [en]

    Background: Intrathecal baclofen (ITB) treatment is considered a powerful tool in the management of severe spasticity in neurological conditions such as multiple sclerosis, cerebral palsy, and traumatic spinal cord and brain injury. 

    Objectives: The objective of this study was to assess the effectiveness of the ITB in patients with inherited ataxia suffering from severe painful spasms and/or spasticity. 

    Method: A total of 5 patients with spinocerebellar ataxia 3 or 7 or Friedreich’s ataxia were included in this observational multicenter study. The patients were interviewed and completed outcome measures assessing pain (The Brief Pain Inventory), fatigue (Fatigue Severity Scale), and life satisfaction (LiSAT-9) before and 1 year after the treatment. Spasticity (Modified Ashworth Scale) and spasm frequency (SPFS) were measured objectively for each patient. 

    Results: The mean treatment time was 1.9 years. Evaluation of established standard forms revealed symptomatic relief from spasticity, spasms, pain, and fatigue in addition to improved body posture, sleep, and life satisfaction after ITB treatment. 

    Conclusions: We report the potential beneficial effects of ITB treatment in patients with inherited ataxia who also suffer from spasticity/spasms. ITB treatment indication in neurological disorders allows for extension to the treatment of spasticity/ spasms in patients with hereditary ataxia.

  • 99.
    Bilbao, Ainhoa
    et al.
    University of Heidelberg, Mannheim, Germany.
    Robinson, J Elliott
    Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Malanga, C J
    Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
    Spanagel, Rainer
    University of Heidelberg, Mannheim, Germany.
    Sommer, Wolfgang H
    University of Heidelberg, Mannheim, Germany.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    A Pharmacogenetic Determinant of Mu-Opioid Receptor Antagonist Effects on Alcohol Reward and Consumption: Evidence from Humanized Mice.2015In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 77, no 10, p. 850-858Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It has been proposed that therapeutic responses to naltrexone in alcoholism are moderated by variation at the mu-opioid receptor gene locus (OPRM1). This remains controversial because human results vary and no prospectively genotyped studies have been reported. We generated humanized mice carrying the respective human OPRM1 A118G alleles. Here, we used this model system to examine the role of OPRM1 A118G variation for opioid antagonist effects on alcohol responses.

    METHODS: Effects of naltrexone on alcohol reward were examined using intracranial self-stimulation. Effects of naltrexone or nalmefene on alcohol intake were examined in continuous access home cage two-bottle free-choice drinking and operant alcohol self-administration paradigms.

    RESULTS: Alcohol lowered brain stimulation reward thresholds in 118GG mice in a manner characteristic of rewarding drugs, and this effect was blocked by naltrexone. Brain stimulation reward thresholds were unchanged by alcohol or naltrexone in 118AA mice. In the home cage, increased alcohol intake emerged in 118GG mice with increasing alcohol concentrations and was 33% higher at 17% alcohol. At this concentration, naltrexone selectively suppressed alcohol intake in 118GG animals to a level virtually identical to that of 118AA mice. No effect of naltrexone was found in the latter group. Similarly, both naltrexone and nalmefene were more effective in suppressing operant alcohol self-administration in 118GG mice.

    CONCLUSIONS: In a model that allows close experimental control, OPRM1 A118G variation robustly moderates effects of opioid antagonism on alcohol reward and consumption. These findings strongly support a personalized medicine approach to alcoholism treatment that takes into account OPRM1 genotype.

  • 100.
    Bivik Eding, Cecilia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Domer, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wäster, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Jerhammar, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases2015In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, no 7, p. 792-797Article in journal (Refereed)
    Abstract [en]

    Ultraviolet (UV) irradiation is a risk factor for development of malignant melanoma. UVA-induced lysosomal exocytosis and subsequent cell growth enhancement was studied in malignant melanoma cell lines and human skin melanocytes. UVA irradiation caused plasma membrane damage that was rapidly repaired by calcium-dependent lysosomal exocytosis. Lysosomal content was released into the culture medium directly after irradiation and such conditioned media stimulated the growth of non-irradiated cell cultures. By comparing melanocytes and melanoma cells, it was found that only the melanoma cells spontaneously secreted cathepsins into the surrounding medium. Melanoma cells from a primary tumour showed pronounced invasion ability, which was prevented by addition of inhibitors of cathepsins B, D and L. Proliferation was reduced by cathepsin L inhibition in all melanoma cell lines, but did not affect melanocyte growth. In conclusion, UVA-induced release of cathepsins outside cells may be an important factor that promotes melanoma growth and progression.

1234567 51 - 100 of 888
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf