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  • 251.
    Feldman Barrett, Lisa
    et al.
    Northeastern University, MA 02115 USA; Massachusetts Gen Hospital, MA 02129 USA; Harvard Medical Sch, MA 02129 USA; Massachusetts Gen Hospital, MA 02114 USA; Harvard Medical Sch, MA 02115 USA.
    Quigley, Karen S.
    Northeastern University, MA 02115 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).
    An active inference theory of allostasis and interoception in depression2016In: Philosophical Transactions of the Royal Society of London. Biological Sciences, ISSN 0962-8436, E-ISSN 1471-2970, Vol. 371, no 1708, article id 20160011Article in journal (Refereed)
    Abstract [en]

    In this paper, we integrate recent theoretical and empirical developments in predictive coding and active inference accounts of interoception (including the Embodied Predictive Interoception Coding model) with working hypotheses from the theory of constructed emotion to propose a biologically plausible unified theory of the mind that places metabolism and energy regulation (i.e. allostasis), as well as the sensory consequences of that regulation (i.e. interoception), at its core. We then consider the implications of this approach for understanding depression. We speculate that depression is a disorder of allostasis, whose myriad symptoms result from a locked in brain that is relatively insensitive to its sensory context. We conclude with a brief discussion of the ways our approach might reveal new insights for the treatment of depression. This article is part of the themed issue Interoception beyond homeostasis: affect, cognition and mental health.

  • 252.
    Fletcher, Paul
    et al.
    University College Cork, Ireland.
    Ball, MartinLinköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.Crystal, DavidUniversity of Bangor, UK.
    Profiling grammar: more languages of LARSP2016Collection (editor) (Other academic)
    Abstract [en]

    This book brings together twelve previously unpublished language profiles based on the original Language Assessment, Remediation and Screening Procedure (LARSP). The languages featured are: Afrikaans, Bulgarian, Cantonese, Finnish, Greek, Hindi, Hungarian, Japanese, Kannada, Korean, Malay and Swedish. Each chapter includes a grammatical sketch of the language, details of typical language development in speakers of the language, as well as a description of and justification for the profile itself. The book will be an invaluable resource for speech-language pathologists and others wishing to analyse the grammatical abilities of individuals speaking one of these languages. This new collection complements a previous book in this series on the same theme: Assessing Grammar: The Languages of LARSP (Ball et al., 2012,).

  • 253.
    Flodin, Ulf
    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, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Paues, Jakob
    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.
    Åkerlind, Britt
    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 Business support and Development, Department of Communicable Disease and Infection Control.
    Leanderson, 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, Occupational and Environmental Medicine Center.
    Sjögren, Bengt
    Karolinska Institutet, Arbetsmiljötoxikologi, Institutet för miljömedicin Stockholm, Sweden Institutet för miljömedicin, Karolinska Institutet - Arbetsmiljötoxikologi Stockholm, Sweden.
    Svetsare – en riskgrupp för septisk pneumoni [Welders - a risk group for septic pneumonia]: Vaccination mot pneumokocker kan vara motiverat för yrkesgruppen2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 6Article in journal (Refereed)
  • 254.
    Flodin, Ulf
    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, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Rolander, B.
    Jonkoping Univ, Sweden; Futurum, Sweden.
    Lofgren, H.
    Ryhov Hosp, Sweden.
    Krapi, Blerim
    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.
    Nyqvist, Fredrik
    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.
    Wåhlin, Charlotte
    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. Linköping University, Faculty of Medicine and Health Sciences. Unit of Intervention and Implementation Research, Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Risk factors for neck pain among forklift truck operators: a retrospective cohort study2018In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 19, article id 44Article in journal (Refereed)
    Abstract [en]

    Background

    No previous research has been performed into neck pain among forklift operators. This is a common complaint among these workers, who number around 150,000 in Sweden and six million in Europe. The aim of the study was to examine long-term exposure to unnatural neck positions among forklift operators as a risk factor for neck pain.

    Methods

    A retrospective cohort study was conducted of all eligible employees at a high-level warehouse. Forklift operators and office workers answered an 18-page questionnaire comprising questions about joint pain, work tasks, work postures and year of start for all items. By using person years in the exposed and less-exposed groups before start of neck pain we were able to calculate Incident Rate ratios for various exposures.

    Results

    Forty nine percent of the forklift operators reported having experienced neck pain compared to 30 % of office workers. Being a forklift operator was associated with an increased risk of neck pain (OR = 5.1, 95% CI 1.4–18.2). Holding the head in an unnatural position resulted in significantly increased risks for neck pain, irrespective of type of position. The risks for neck pain remained after taking other ergonomic exposures and psychosocial aspects into consideration.

    Conclusions

    This is the first published study showing that forklift operators have an increased risk of neck pain. The results are therefore of significance for improving work schedules, the adjustment of work tasks for these workers and the design of the vehicles.

  • 255.
    Forsberg, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Immunomodulatory effects of probiotic supplementation during pregnancy and infancy in allergy prevention studies2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The incidence of allergic diseases is increasing, possibly due to a reduced intensity and diversity of microbial stimulation. More knowledge is needed on the immunological mechanisms underlying the eczema preventive effect of pre- and postnatal probiotic supplementation. The pregnancy period seems to be of essential importance, since both epidemiological and experimental animal studies show the importance of microbial exposure during gestation on allergy prevention.

    We have performed a study where the probiotic lactic acid producing bacteria Lactobacillus reuteri was supplemented to pregnant women, at risk of having an allergic infant. The pregnant mothers received the study product from gestational week 36 until delivery, and the infants then continued with the same product until one year of age. The probiotic, as compared with placebo, supplemented infants had less IgE-associated eczema at two years of age.

    In order to investigate how the supplementation affected the immune system peripheral blood was collected and immune cells were stimulated with common allergens and TLR ligands. The probiotic treated group responded with a more regulated response to allergens and TLR2 ligands in comparison to the placebo supplemented group. We also investigated how the probiotic supplementation affected the epigenetic methylation pattern in circulating T helper cells during infancy, observing the most pronounced effects at birth.

    In a follow up study, supplementation was started earlier to possibly gain a stronger allergy preventive effect via changes in maternal immune regulation. Supplementation with Lactobacillus reuteri and ω-3 fatty acids started at gestational week 20 and throughout pregnancy. After 20 weeks of supplementation, some immunomodulatory effects among circulating activated regulatory T cells and a subpopulation of monocytes were noted. Several systemic immune modifying effects of pregnancy were observed.

    In summary, probiotics show several immunomodulatory effects in infants and pregnant women. However, more research is needed to better understand the effects of the probiotic supplementation to aid future identification of more efficacious allergy preventive strategies.

    List of papers
    1. Pre- and post-natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy
    Open this publication in new window or tab >>Pre- and post-natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy
    2013 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 43, no 4, p. 434-442Article in journal (Refereed) Published
    Abstract [en]

    Background

    We have previously shown that Lactobacillus reuteri supplementation from pregnancy week 36 and to the infant through the first year of life decreased the prevalence of IgE-associated eczema at 2 years. The underlying immunological mechanisms are unknown, however.

    Objective

    To investigate the immunomodulatory effect of probiotic supplementation on allergen- and mitogen-induced immune responses in children until 2 years of age.

    Methods

    Blood mononuclear cells were collected at birth, 6, 12 and 24 months from 61 children (29 probiotic and 32 placebo treated) and cultured with ovalbumin, birch and cat extract and Phytohaemagglutinin (PHA). Cytokine and chemokine secretion was determined using an in-house multiplexed Luminex assay and ELISA. Real-time PCR was performed to investigate the Ebi3, Foxp3, GATA-3 and T-bet mRNA expression.

    Results

    Probiotic treatment was associated with low cat-induced Th2-like responses at 6 months (IL-5, P = 0.01, and IL-13, P = 0.009), with a similar trend for IL-5 at 12 months (P = 0.09). Cat-induced IFN-γ responses were also lower after probiotic than after placebo treatment at 24 months (P = 0.007), with similar findings for the anti-inflammatory IL-10 at birth (P = 0.001) and at 12 months (P = 0.009). At 24 months, Th2-associated CCL22 levels were lower in the probiotic than in the placebo group after birch stimulation (P = 0.02), with a similar trend after ovalbumin stimulation (P = 0.07). Lower CCL22 levels were recorded at 12 and 24 months (P = 0.03 and P = 0.01) after PHA stimulation.

    Conclusion and Clinical Relevance

    Lactobacillus reuteri supplementation decreases allergen responsiveness and may enhance immunoregulatory capacity during infancy. L. reuteri supplementation from week 36 and during the first year of life significantly decreases IgE-associated eczema and lowers allergen and mitogen responsiveness.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2013
    Keywords
    allergen, allergy, chemokine, cytokine, eczema, Foxp3, infancy, Lactobacillus reuteri, probiotics, sensitization
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-91537 (URN)10.1111/cea.12082 (DOI)000316623800008 ()
    Note

    Funding Agencies|Swedish Research Council|K2011-56X-21854-01-06|Ekhaga Foundation||Olle Engkvist Foundation||Heart and Lung foundation||Research Council for the South-East Sweden|F2000-106|Swedish Asthma and Allergy Association||Cancer and Allergy Association||BioGaia AB, Stockholm, Sweden||University Hospital of Linkoping, Sweden||

    Available from: 2013-04-26 Created: 2013-04-26 Last updated: 2017-12-06
    2. Pre- and postnatal administration of Lactobacillus reuteri decreases TLR2 responses in infants.
    Open this publication in new window or tab >>Pre- and postnatal administration of Lactobacillus reuteri decreases TLR2 responses in infants.
    2014 (English)In: Clinical and translational allergy, ISSN 2045-7022, Vol. 4, p. 1-7Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Mice models indicate that intact Toll like receptor (TLR) signaling may be essential for the allergy protective effects of diverse bacterial exposure observed in clinical trials and epidemiological studies. Probiotic supplementation with Lactobacillus reuteri from pregnancy week 36 and to the infant through the first year of life decreased the prevalence of IgE-associated eczema at two years (ClinicalTrials.gov NCT01285830). The effect of this supplementation on innate immune responses to bacterial products and the expression of associated TLRs were explored.

    METHODS: Blood mononuclear cells were collected at birth, 6, 12 and 24 months from 61 infants and cultured with TLR2, 4 and 9 ligands. Cytokine and chemokine secretion was determined as well as TLR2, 4 and 9 mRNA expression.

    RESULTS: Probiotic supplementation was associated with decreased LTA (lipoteichoic acid) induced CCL4, CXCL8, IL-1β and IL-6 responses at 12 months and decreased CCL4 and IL-1β secretion at 24 months. TLR2 mRNA expression was not affected by probiotic treatment.

    CONCLUSIONS: Decreased responses to TLR2, the main receptor for LTA from Gram positive bacteria, in probiotic treated children seem to be dependent on factors downstream of TLR mRNA expression.

    Keywords
    Angina pectoris; Coronary ostial stenosis; Takayasu
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-111347 (URN)10.1186/2045-7022-4-21 (DOI)25002964 (PubMedID)
    Available from: 2014-11-18 Created: 2014-10-15 Last updated: 2017-10-26
  • 256.
    Forsberg, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    West, C. E.
    World University of Network, Sweden; Umeå University, Sweden.
    Prescott, S. L.
    World University of Network, Sweden; University of Western Australia, Australia; Princess Margaret Hospital Children, Australia.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. World University of Network, Sweden.
    Pre- and probiotics for allergy prevention: time to revisit recommendations?2016In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, no 12, p. 1506-1521Article, review/survey (Refereed)
    Abstract [en]

    Reduced intensity and diversity of microbial exposure is considered a major factor driving abnormal postnatal immune maturation and increasing allergy prevalence, particularly in more affluent regions. Quantitatively, the largest important source of early immunemicrobial interaction, the gut microbiota, is of particular interest in this context, with variations in composition and diversity in the first months of life associated with subsequent allergy development. Attempting to restore the health consequences of the ` dysbiotic drift in modern society, interventions modulating gut microbiota for allergy prevention have been evaluated in several randomized placebo-controlled trials. In this review, we provide an overview of these trials and discuss recommendations from international expert bodies regarding prebiotic, probiotic and synbiotic interventions. Recent guidelines from the World Allergy Organization recommend the use of probiotics for the primary prevention of eczema in pregnant and breastfeeding mothers of infants at high risk for developing allergy and in high-risk infants. It is however stressed that these recommendations are conditional, based on very low-quality evidence and great heterogeneity between studies, which also impedes specific and practical advice to consumers on the most effective regimens. We discuss how the choice of probiotic strains, timing and duration of administration can critically influence the outcome due to different effects on immune modulation and gut microbiota composition. Furthermore, we propose strategies to potentially improve allergy-preventive effects and enable future evidence-based implementation.

  • 257.
    Fostad, Ida G.
    et al.
    University of Oslo, Norway; Norwegian Dry Eye Clin, Norway.
    Eidet, Jon R.
    Norwegian Dry Eye Clin, Norway; Oslo University Hospital, Norway.
    Lagali, Neil
    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 Ophthalmology in Linköping.
    Dartt, Darlene A.
    Harvard Medical Sch, MA 02114 USA.
    Raeder, Sten
    Norwegian Dry Eye Clin, Norway.
    Messelt, Edvard B.
    University of Oslo, Norway.
    Utheim, Tor P.
    University of Oslo, Norway; Norwegian Dry Eye Clin, Norway; Oslo University Hospital, Norway; Vestre Viken Hospital Trust, Norway.
    Identification of Objective Morphometric Markers of Xerostomia in the Oral Mucosa Epithelium with In Vivo Confocal Microscopy2017In: Microscopy and Microanalysis, ISSN 1431-9276, E-ISSN 1435-8115, Vol. 23, no 1, p. 88-96Article in journal (Refereed)
    Abstract [en]

    The purpose of this work was to determine whether the morphology of the oral mucosa epithelium (OME) of patients with xerostomia differ from patients without xerostomia. In total, 34 patients with dry eye disease (DED) with or without xerostomia were examined at The Norwegian Dry Eye Disease Clinic with in vivo confocal microscopy of the lower lip. In addition, age- and gender-matched healthy controls (HC) were included. DED patients with xerostomia had a higher superficial to deep backscatter ratio compared with DED patients without xerostomia (p=0.002) and HC (p=0.001). Regression analysis demonstrated that this ratio was related to xerostomia independently of gender and age (pamp;lt;0.001). Sensitivity and specificity of detecting xerostomia were 0.78 and 0.85, respectively, when using a superficial to deep backscatter ratio cut-off value of 0.995 (p=0.004). The mean nucleus to cytosol backscatter ratio in the superficial OME was lower in patients with xerostomia than in those without xerostomia (p=0.034). In vivo confocal microscopy is a potential tool for evaluating the oral cavity and to assess changes in the OME associated with xerostomia, objectively and quantitatively. The cause of the increased backscatter in the superficial OME in xerostomia, however, remains to be elucidated.

  • 258.
    Fostad, Ida G.
    et al.
    University of Oslo, Norway; Norwegian Dry Eye Clin, Norway.
    Eidet, Jon R.
    Norwegian Dry Eye Clin, Norway; Oslo University Hospital, Norway.
    Utheim, Tor P.
    University of Oslo, Norway; Norwegian Dry Eye Clin, Norway; Oslo University Hospital, Norway; Vestre Viken Hospital Trust, Norway; Buskerud and Vestfold University of Coll, Norway.
    Raeder, Sten
    Norwegian Dry Eye Clin, Norway.
    Lagali, Neil
    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 Ophthalmology in Linköping.
    Messelt, Edvard B.
    University of Oslo, Norway.
    Dartt, Darlene A.
    Harvard University, MA USA.
    Dry Eye Disease Patients with Xerostomia Report Higher Symptom Load and Have Poorer Meibum Expressibility2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, p. e0155214-Article in journal (Refereed)
    Abstract [en]

    The purpose of the study was to investigate if xerostomia (dry mouth) is associated with symptoms and signs of dry eye disease (DED). At the Norwegian Dry Eye Clinic, patients with symptomatic DED with different etiologies were consecutively included in the study. The patients underwent a comprehensive ophthalmological work-up and completed self-questionnaires on symptoms of ocular dryness (Ocular Surface Disease Index [OSDI] and McMonnies Dry Eye Questionnaire) and the Sjogrens syndrome (SS) questionnaire (SSQ). Three hundred and eighteen patients (52% women and 48% men) with DED were included. Patient demographics were: 0 to 19 years (1%), 20 to 39 (25%), 40 to 59 (34%), 60 to 79 (35%) and 80 to 99 (5%). Xerostomia, defined as "daily symptoms of dry mouth the last three months" (as presented in SSQ) was reported by 23% of the patients. Female sex was more common among patients with xerostomia (81%) than among non-xerostomia patients (44%; Pamp;lt; 0.001). Patients with xerostomia (60 +/- 15 years) were older than those without xerostomia (51 +/- 17; Pamp;lt; 0.001). The use of prescription drugs was more prevalent among xerostomia patients (65%) than among non-xerostomia patients (35%; Pamp;lt; 0.021; adjusted for age and sex). Patients with xerostomia had a higher OSDI score (19.0 +/- 10.0) than those without xerostomia (12.9 +/- 8.0; Pamp;lt; 0.001). Moreover, xerostomia patients had more pathological meibum expressibility (0.9 +/- 0.7) than those without xerostomia (0.7 +/- 0.8; P = 0.046). Comparisons of OSDI and ocular signs were performed after controlling for the effects of sex, age and the number of systemic prescription drugs used. In conclusion, xerostomia patients demonstrated a higher DED symptom load and had poorer meibum expressibility than non-xerostomia patients.

  • 259.
    Fridell, Sara
    et al.
    Region Östergötland, Public Dental Health Care, Center for Oral Rehabilitation Linköping.
    Ström, Edvin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Agebratt, Christian
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Leanderson, 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, Occupational and Environmental Medicine Center.
    Guldbrand, Hans
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Nyström, Fredrik H.
    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 Endocrinology.
    A randomised study in young subjects of the effects of eating extra fruit or nuts on periodontal inflammation2018In: BDJ open, ISSN 2056-807X, Vol. 3, article id 17022Article in journal (Refereed)
    Abstract [en]

    Objectives/Aims:

    Fruit is often advocated as a healthy source of nutrients and vitamins. However, the high contents of sugars in many fruits could potentially counteract positive effects on the teeth.

    Materials and methods:

    We recruited 30 healthy non-obese participants who were randomised to either supplement their diet with extra fruits or nuts, each at +7 kcal/kg body weight/day, for 2 months.

    Results:

    Fructose intake increased from 9.1±6.0 to 25.6±9.6 g/day, P<0.0001, in the fruit group and was reduced from 12.4±5.7 to 6.5±5.3 g/day, P=0.007, in the nut group. Serum-vitamin C increased in both groups (fruit: P=0.017; nuts: P=0.009). α-Tocopherol/cholesterol ratio increased in the fruit group (P=0.0033) while β-carotene/cholesterol decreased in the nut group (P<0.0001). The amount of subjects with probing pocket depths ⩾4 mm in the fruit group was reduced (P=0.045) according to blinded examinations, and the difference in the changes in probing pockets ⩾4 mm was also statistically significant between the food groups (P=0.010).

    Conclusion:

    A large increase of fruit intake, compared with nuts, had a favourable effect on periodontal status in some respects, despite the high sugar contents. To search for potential protective micronutrients in fruit that protect the teeth could be an aim for further research.

  • 260.
    Fritz, Michael
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Klawonn, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Kumar Singh, Anand
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Zajdel, Joanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Wilhelms, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Lazarus, Michael
    University of Tsukuba, Japan.
    Löfberg, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Jaarola, Maarit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Örtegren Kugelberg, Unn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Billiar, Timothy R.
    University of Pittsburgh, PA USA.
    Hackam, David J.
    Johns Hopkins University, MD USA.
    Sodhi, Chhinder P.
    Johns Hopkins University, MD USA.
    Breyer, Matthew D.
    Lilly Research Labs, IN USA.
    Jakobsson, Johan
    Lund University, Sweden; Lund University, Sweden.
    Schwaninger, Markus
    University of Lubeck, Germany.
    Schuetz, Gunther
    German Cancer Research Centre, Germany.
    Rodriguez Parkitna, Jan
    Polish Academic Science, Poland.
    Saper, Clifford B.
    Beth Israel Deaconess Medical Centre, MA 02215 USA; Harvard University, MA USA.
    Blomqvist, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Prostaglandin-dependent modulation of dopaminergic neurotransmission elicits inflammation-induced aversion in mice2016In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 126, no 2, p. 695-705Article in journal (Refereed)
    Abstract [en]

    Systemic inflammation causes malaise and general feelings of discomfort. This fundamental aspect of the sickness response reduces the quality of life for people suffering from chronic inflammatory diseases and is a nuisance during mild infections like common colds or the flu. To investigate how inflammation is perceived as unpleasant and causes negative affect, we used a behavioral test in which mice avoid an environment that they have learned to associate with inflammation-induced discomfort. Using a combination of cell-type-specific gene deletions, pharmacology, and chemogenetics, we found that systemic inflammation triggered aversion through MyD88-dependent activation of the brain endothelium followed by COX1-mediated cerebral prostaglandin E-2 (PGE(2)) synthesis. Further, we showed that inflammation-induced PGE(2) targeted EP1 receptors on striatal dopamine D1 receptor-expressing neurons and that this signaling sequence induced aversion through GABA-mediated inhibition of dopaminergic cells. Finally, we demonstrated that inflammation-induced aversion was not an indirect consequence of fever or anorexia but that it constituted an independent inflammatory symptom triggered by a unique molecular mechanism. Collectively, these findings demonstrate that PGE(2)-mediated modulation of the dopaminergic motivational circuitry is a key mechanism underlying the negative affect induced by inflammation.

  • 261.
    Frodlund, Jonas
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    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.
    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.
    Ledin, Torbjörn
    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.
    Vestibular Function After Cochlear Implantation: A Comparison of Three Types of Electrodes2016In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 37, no 10, p. 1535-1540Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the vestibular function after cochlear implantation with different types of electrode arrays. Study Design: Retrospective cohort study. Setting: Academic tertiary referral center. Materials and Methods: Forty three adults underwent first cochlear implantation. Three consecutive series of patients: Group 1 (n = 13) implanted with a precurved electrode, Group 2 (n = 15) implanted with a straight electrode, Group 3 (n = 15) implanted with a flexible electrode. Patients vestibular functions were assessed with pre-and postoperative caloric testing using videonystagmography (VNG). The postoperative reduction of the maximum slow phase velocity (MSPV) in the implanted ear was evaluated. Medical charts were reviewed to evaluate the occurrence of late onset of postoperative vestibular symptoms. Results: Mean reduction of MSPV was 7.6/s (standard deviation [SD] 8.0) in Group 1, 23.1/s (SD 16.6) in Group 2, and 0.1/s (SD 18.5) in Group 3. Significant difference was found between Group 1 and 2 (p amp;lt; 0.030) and between Group 2 and 3 (p amp;lt; 0.001). Group 2 showed a higher prevalence of late onset of clinical vertigo (28.6%) than Group 1 (7.7%) and 3 (6.7%). Conclusion: In this prospective study, significantly larger reductions of caloric responses were found in subjects implanted with a straight electrode compared with subjects implanted with a precurved or flexible electrode. These findings seem to correlate to a higher prevalence of postoperative vertigo.

  • 262.
    Frodlund, Martina
    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, Heart and Medicine Center, Department of Rheumatology.
    Reid, S.
    Uppsala Univ, Sweden.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Dahlström, Örjan
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    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.
    Leonard, D.
    Uppsala Univ, Sweden.
    The majority of Swedish systemic lupus erythematosus patients are still affected by irreversible organ impairment: factors related to damage accrual in two regional cohorts2019In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, article id UNSP 0961203319860198Article in journal (Refereed)
    Abstract [en]

    Background Although the survival of patients with systemic lupus erythematosus (SLE) has improved, irreversible organ damage remains a critical concern. We aimed to characterize damage accrual and its clinical associations and causes of death in Swedish patients. Methods Accumulation of damage was evaluated in 543 consecutively recruited and well-characterized cases during 1998-2017. The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology damage index (SDI) was used to estimate damage. Results Organ damage (SDI amp;gt;= 1) was observed in 59%, and extensive damage (SDI amp;gt;= 3) in 25% of cases. SDI amp;gt;= 1 was significantly associated with higher age at onset, SLE duration, the number of fulfilled SLICC criteria, neurologic disorder, antiphospholipid antibody syndrome (APS), hypertension, hyperlipidemia, depression and secondary Sjogrens syndrome (SS). In addition, SDI amp;gt;= 3 was associated with serositis, renal and haematological disorders and interstitial lung disease. A multiple regression model identified not only well-known risk factors like APS, antihypertensives and corticosteroids, but pericarditis, haemolytic anaemia, lymphopenia and myositis as being linked to SDI. Malignancy, infection and cardiovascular disease were the leading causes of death. Conclusions After a mean SLE duration of 17 years, the majority of todays Swedish SLE patients have accrued damage. We confirm previous observations and report some novel findings regarding disease phenotypes and damage accrual.

  • 263.
    Frodlund, Martina
    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, Heart and Medicine Center, Department of Rheumatology.
    Vikerfors, A.
    Karolinska Univ Hosp, Sweden; Swedish Med Prod Agcy, Sweden.
    Grosso, G.
    Karolinska Univ Hosp, Sweden.
    Skogh, Thomas
    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.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Elvin, K.
    Karolinska Inst, Sweden.
    Gunnarsson, I.
    Karolinska Univ Hosp, Sweden.
    Kastbom, Alf
    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.
    Dahlström, Örjan
    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.
    Ronnelid, J.
    Uppsala Univ, Sweden.
    Svenungsson, E.
    Karolinska Univ Hosp, 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.
    Immunoglobulin A anti-phospholipid antibodies in Swedish cases of systemic lupus erythematosus: associations with disease phenotypes, vascular events and damage accrual2018In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 194, no 1, p. 27-38Article in journal (Refereed)
    Abstract [en]

    Immunoglobulin (Ig) G- and IgM-class anti-cardiolipin antibodies (aCL) and lupus anti-coagulant (LA) are included in the 1997 update of the American College of Rheumatology (ACR-97) systemic lupus erythematosus (SLE) criteria. Despite limited evidence, IgA-aCL and IgA anti-(2)-glycoprotein-I (anti-(2)GPI) were included in the 2012 Systemic Lupus International Collaborating Clinics criteria. The present study aimed to evaluate IgG-/IgA-/IgM-aCL and anti-(2)GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy, anti-phospholipid syndrome (APS) and organ damage among 526 Swedish SLE patients meeting ACR-97. Patients with rheumatoid arthritis (n=100), primary Sjogrens syndrome (n=50) and blood donors (n=507) served as controls. Anti-phospholipid antibodies (aPL) were analysed by fluoroenzyme-immunoassays detecting aCL/anti-(2)GPI. Seventy-six (14%) SLE cases fulfilled the Sydney APS-criteria, and 1 aCL/anti-(2)GPI isotype (IgG/IgA/IgM) occurred in 138 SLE patients (26%). Forty-five (9%) of the SLE cases had IgA-aCL, 20 of whom (4%) lacked IgG-/IgM-aCL. Seventy-four (14%) tested positive for IgA anti-(2)GPI, 34 (6%) being seronegative regarding IgG/IgM anti-(2)GPI. Six (1%) had APS manifestations but were seropositive regarding IgA-aCL and/or IgA anti-(2)GPI in the absence of IgG/IgM-aPL and LA. Positive LA and IgG-aPL tests were associated with most APS-related events and organ damage. Exclusive IgA anti-(2)GPI occurrence associated inversely with Caucasian ethnicity [odds ratio (OR)=021, 95% confidence interval (CI)=006-072) and photosensitivity (OR=019, 95% CI=005-072). Nephritis, smoking, LA-positivity and statin/corticosteroid-medication associated strongly with organ damage, whereas hydroxychloroquine-medication was protective. In conclusion, IgA-aPL is not rare in SLE (16%) and IgA-aPL analysis may have additional value among SLE cases with suspected APS testing negative for other isotypes of aPL and LA.

  • 264.
    From, Asa
    et al.
    Blekingesjukhuset, Sweden.
    Sundström, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Samuelsson, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Differences in phonologic and prosodic abilities in children with phonological language impairment and phonological-grammatical language impairment assessed with non-word repetition2016In: Logopedics, Phoniatrics, Vocology, ISSN 1401-5439, E-ISSN 1651-2022, Vol. 41, no 2, p. 66-76Article in journal (Refereed)
    Abstract [en]

    Prosody can be described as the rhythmic, dynamic, and melodic aspects of language. Swedish has a relatively complex prosodic system compared to, for example, English. A large percentage of Swedish children with language impairment show prosodic problems to some extent. In the present study, non-word repetition was used to assess the phonological and prosodic abilities in children with phonological language impairment and children with phonological-grammatical language impairment. In the study, 10 children with phonological language impairment and 14 children with phonological-grammatical language impairment from 4;3 to 6;2 years of age participated. All children heard the same recorded non-words and words. The group with phonological language impairment received higher scores in all variables, compared to the group with phonological-grammatical language impairment. The results showed significant differences between the groups regarding production of vowels correct in words and production of phonemes correct in non-words as well as production of unstressed syllables in non-words and production of correct stress in non-words. Percent correctly produced vowels in words, but not in non-words, correlated significantly with grammatical ability.

  • 265.
    Frost Bellgowan, Julie
    et al.
    Laureate Institute Brain Research, OK USA.
    Molfese, Peter
    Haskins Labs Inc, CT USA.
    Marx, Michael
    Stanford University, CA 94305 USA.
    Thomason, Moriah
    Wayne State University, MI USA.
    Glen, Daniel
    NIMH, MD 20892 USA.
    Santiago, Jessica
    Laureate Institute Brain Research, OK USA.
    Gotlib, Ian H.
    Stanford University, CA 94305 USA.
    Drevets, Wayne C.
    Laureate Institute Brain Research, OK USA; Janssen Pharmaceut, Belgium.
    Hamilton, Paul J.
    Linköping University, Center for Social and Affective Neuroscience (CSAN). Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Laureate Institute Brain Research, OK USA.
    A Neural Substrate for Behavioral Inhibition in the Risk for Major Depressive Disorder2015In: Journal of the American Academy of Child and Adolescent Psychiatry, ISSN 0890-8567, E-ISSN 1527-5418, Vol. 54, no 10, p. 841-848Article in journal (Refereed)
    Abstract [en]

    Objective: Behavioral inhibition (BI) is an early developing trait associated with cautiousness and development of clinical depression and anxiety. Little is known about the neural basis of BI and its predictive importance concerning risk for internalizing disorders. We looked at functional connectivity of the default-mode network (DMN) and salience network (SN), given their respective roles in self-relational and threat processing, in the risk for internalizing disorders, with an emphasis on determining the functional significance of these networks for BI. Method: We used functional magnetic resonance imaging to scan, during the resting state, children and adolescents 8 to 17 years of age who were either at high familial risk (HR; n = 16) or low familial risk (LR; n = 18) for developing clinical depression and/or anxiety. Whole-brain DMN and SN functional connectivity were estimated for each participant and compared across groups. We also compared the LR and HR groups on levels of BI and anxiety, and incorporated these data into follow-up neurobehavioral correlation analyses. Results: The HR group, relative to the LR group, showed significantly decreased DMN connectivity with the ventral striatum and bilateral sensorimotor cortices. Within the HR group, trait BI increased as DMN connectivity with the ventral striatum and sensorimotor cortex decreased. The HR and LR groups did not differ with respect to SN connectivity. Conclusion: Our findings show, in the risk for internalizing disorders, a negative functional relation between brain regions supporting self-relational processes and reward prediction. These findings represent a potential neural substrate for behavioral inhibition in the risk for clinical depression and anxiety.

  • 266.
    Furmark, Tomas
    et al.
    Uppsala University, Sweden.
    Marteinsdottir, Ina
    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.
    Frick, Andreas
    Uppsala University, Sweden.
    Heurling, Kerstin
    Uppsala University, Sweden.
    Tillfors, Maria
    University of Örebro, Sweden.
    Appel, Lieuwe
    Uppsala University, Sweden.
    Antoni, Gunnar
    Uppsala University, Sweden.
    Hartvig, Per
    University of Copenhagen, Denmark.
    Fischer, Hakan
    Stockholm University, Sweden.
    Langstrom, Bengt
    Uppsala University, Sweden; Southern Denmark University, Denmark.
    Eriksson, Elias
    Gothenburg University, Sweden.
    Fredrikson, Mats
    Uppsala University, Sweden; Karolinska Institute, Sweden.
    Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder2016In: Journal of Psychopharmacology, ISSN 0269-8811, E-ISSN 1461-7285, Vol. 30, no 10, p. 1028-1035Article in journal (Refereed)
    Abstract [en]

    It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[ -C-11]tryptophan, [C-11]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [C-11]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder patients compared with controls in the hippocampus and basal ganglia nuclei and, at a more lenient (uncorrected) statistical threshold, in the amygdala and anterior cingulate cortex. In patients, the serotonin synthesis rate in the amygdala and anterior cingulate cortex was significantly elevated in TPH2 T carriers in comparison with GG homozygotes. Our results support that social anxiety disorder entails an overactive presynaptic serotonergic system that, in turn, seems functionally influenced by the TPH2 G-703T polymorphism in emotionally relevant brain regions.

  • 267.
    Fytagoridis, Anders
    et al.
    Karolinska Institute, Sweden; Umeå University, Sweden; University of Queensland, Australia.
    Heard, Tomas
    University of Queensland, Australia.
    Samuelsson, Jennifer
    Umeå University, Sweden; Sahlgrens University Hospital, Sweden.
    Zsigmond, Peter
    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.
    Jiltsova, Elena
    University of Uppsala Hospital, Sweden.
    Skyrman, Simon
    Karolinska Institute, Sweden.
    Skoglund, Thomas
    Sahlgrens University Hospital, Sweden.
    Coyne, Terry
    University of Queensland, Australia; Brizbrain and Spine, Australia.
    Silburn, Peter
    University of Queensland, Australia.
    Blomstedt, Patric
    Umeå University, Sweden.
    Surgical Replacement of Implantable Pulse Generator in Deep Brain Stimulation: Adverse Events and Risk Factors in a Multicenter Cohort2016In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 94, no 4, p. 235-239Article in journal (Refereed)
    Abstract [en]

    Background: Deep brain stimulation (DBS) is a growing treatment modality, and most DBS systems require replacement of the implantable pulse generator (IPG) every few years. The literature regarding the potential impact of adverse events of IPG replacement on the longevity of DBS treatments is rather scarce. Objective: To investigate the incidence of adverse events, including postoperative infections, associated with IPG replacements in a multicenter cohort. Methods: The medical records of 808 patients from one Australian and five Swedish DBS centers with a total of 1,293 IPG replacements were audited. A logistic regression model was used to ascertain the influence of possible predictors on the incidence of adverse events. Results: The overall incidence of major infections was 2.3% per procedure, 3.7% per patient and 1.7% per replaced IPG. For 28 of 30 patients this resulted in partial or complete DBS system removal. There was an increased risk of infection for males (OR 3.6, p = 0.026), and the risk of infection increased with the number of prior IPG replacements (OR 1.6, p amp;lt; 0.005). Conclusions: The risk of postoperative infection with DBS IPG replacement increases with the number of previous procedures. There is a need to reduce the frequency of IPG replacements. (C) 2016 S. Karger AG, Basel

  • 268.
    Fällman, Katarina
    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, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Lundgren, Lina
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Geriatric Medicine in Norrköping.
    Wressle, Ewa
    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 Acute Internal Medicine and Geriatrics.
    Marcusson, 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, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Classon, Elisabet
    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 Acute Internal Medicine and Geriatrics. Linköping University, The Swedish Institute for Disability Research.
    Normative data for the oldest old: Trail Making Test A, Symbol Digit Modalities Test, Victoria Stroop Test and Parallel Serial Mental Operations2019In: Aging, Neuropsychology and Cognition, ISSN 1382-5585, E-ISSN 1744-4128Article in journal (Refereed)
    Abstract [en]

    Normative data for evaluating cognitive function in the oldest old, aged 85 years and above, are currently sparse. The normative values used in clinical practice are often derived from younger old persons, from small sample sizes or from broad age spans (e.g. amp;gt;75 years) resulting in a risk of misjudgment in assessments of cognitive decline. This longitudinal study presents normative values for the Trail Making Test A (TMT-A), the Symbol Digit Modalities Test (SDMT), the Victoria Stroop Test (VST) and the Parallel Serial Mental Operations (PaSMO) from cognitively intact Swedes aged 85 years and above. 207 participants, born in 1922, were tested at 85, 90 (n = 68) and 93 (n = 35) years of age with a cognitive screening test battery. The participants were originally recruited for participation in the Elderly in Linkoping Screening Assessment. Normative values are presented as mean values and standard deviations, with and without adjustment for education. There were no clinically important differences between genders, but education had a significant effect on test results for the 85-year-olds. Age effects emerged in analyses of those participants who completed the entire study and were evident for TMT-A, SDMT, VST1 and PaSMO. When comparisons can be made, our results are in accordance with previous data for TMT-A, SDMT and VST, and we present new normative values for PaSMO.

  • 269.
    Garcia-Etxebarria, Koldo
    et al.
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden.
    Zheng, Tenghao
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Bonfiglio, Ferdinando
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden.
    Bujanda, Luis
    Biodonostia Hlth Res Inst, Spain; Univ Basque Country, Spain.
    Dlugosz, Aldona
    Karolinska Inst, Sweden.
    Lindberg, Greger
    Karolinska Inst, Sweden.
    Schmidt, Peter T.
    Univ Basque Country, Spain.
    Karling, Pontus
    Umea Univ, Sweden.
    Ohlsson, Bodil
    Lund Univ, Sweden.
    Simren, Magnus
    Univ Gothenburg, Sweden.
    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.
    Nardone, Gerardo
    University Federico II, Naples, Italy.
    Cuomo, Rosario
    Federico II Univ Hosp, Italy.
    Usai-Satta, Paolo
    Azienda Osped G Brotzu, Italy.
    Galeazzi, Francesca
    Padova Univ Hosp, Italy.
    Neri, Matteo
    G DAnnunzio Univ and Fdn, Italy.
    Portincasa, Piero
    G DAnnunzio Univ and Fdn, Italy.
    Bellini, Massimo
    Univ Bari, Italy.
    Barbara, Giovanni
    Univ Pisa, Italy.
    Jonkers, Daisy
    Univ Bologna, Italy.
    Eswaran, Shanti
    Univ Michigan, MI USA.
    Chey, William D.
    Univ Michigan, MI USA.
    Kashyap, Purna
    Mayo Clin, MN USA.
    Chang, Lin
    Univ Calif Los Angeles, CA 90095 USA.
    Mayer, Emeran A.
    Univ Calif Los Angeles, CA 90095 USA.
    Wouters, Mira M.
    Katholieke Univ Leuven, Belgium.
    Boeckxstaens, Guy
    Katholieke Univ Leuven, Belgium.
    Camilleri, Michael
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Franke, Andre
    Maastricht Univ, Netherlands; Christian Albrechts Univ Kiel, Germany.
    DAmato, Mauro
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden; Karolinska Inst, Sweden; Basque Sci Fdn, Spain.
    Increased Prevalence of Rare Sucrase-isomaltase Pathogenic Variants in Irritable Bowel Syndrome Patients2018In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 16, no 10, p. 1673-1676Article in journal (Refereed)
    Abstract [en]

    n/a

  • 270.
    Garvin, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Evalill
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    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.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    The joint subclinical elevation of CRP and IL-6 is associated with lower health-related quality of life in comparison with no elevation or elevation of only one of the biomarkers2016In: Quality of Life Research, ISSN 0962-9343, E-ISSN 1573-2649, Vol. 25, no 1, p. 213-221Article in journal (Refereed)
    Abstract [en]

    Measures of health-related quality of life (HRQoL), like the Short Form (SF)-36, have been suggested to correlate with inflammatory biomarkers. It is, however, unclear whether a joint measure of two inflammatory biomarkers would bring additional information in comparison with evaluation of one inflammatory biomarker. To evaluate associations between SF-36 and low-grade inflammation in a Swedish population, with emphasis on a combined measure of C-reactive protein (CRP) and interleukin-6 (IL-6) as a proxy for low-grade inflammation. In a randomly selected sample of a middle-aged Swedish general population (n = 905; aged 45-69 years, 50 % women), relations between SF-36 parameters and the biomarkers were tested. Regression and correlation analyses were adjusted for sex, age, presence of disease, lifestyle, and psychological factors. After adjustment for sex and age, HRQoL was significantly lower in the group with a joint elevation of CRP and IL-6 in comparison with either the group with no elevation or the groups showing elevation of one of the two biomarkers. Also after full adjustments, the combined measure of elevated CRP and IL-6, with few exceptions, was associated with significantly lower HRQoL in comparison with elevations in one of them, difference ranging from 4 (Mental Health scale) to 18 scale steps (Role-Physical scale). This study confirms that there is a relationship between HRQoL and low-grade inflammation. In particular, SF-36 scores are significantly lower in a group with joint elevation of IL-6 and CRP, in comparison with elevation of either one of them.

  • 271.
    Garvin, Stina
    et al.
    Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics. 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.
    Tiefenböck, Katharina
    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.
    Farnebo, 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 Otorhinolaryngology in Linköping.
    Thunell, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Farnebo, Marianne
    Karolinska Institute, Sweden.
    Roberg, Karin
    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.
    Nuclear expression of WRAP53 beta is associated with a positive response to radiotherapy and improved overall survival in patients with head and neck squamous cell carcinoma2015In: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 51, no 1, p. 24-30Article in journal (Refereed)
    Abstract [en]

    Objectives: Today there are no reliable predictive markers for radiotherapy response in head and neck squamous cell carcinoma (HNSCC), leading to both under-and over-treatment of patients, personal suffering, and negative socioeconomic effects. Inherited mutation in WRAP53 beta (WD40 encoding RNA Antisense to p53), a protein involved in intracellular trafficking, dramatically increases the risk of developing HNSCC. The purpose of this study was to investigate whether WRAP53 beta can predict response to radiotherapy in patients with HNSCC. Materials and methods: Tumor biopsies from patients with HNSCC classified as responders or non-responders to radiotherapy were examined for the expression of the WRAP53 beta protein and single nucleotide polymorphisms in the corresponding gene employing immunohistochemistry and allelic discrimination, respectively. In addition, the effect of RNAi-mediated downregulation of WRAP53 beta on the intrinsic radiosensitivity of two HNSCC cell lines was assed using crystal violet and clonogenic assays. Results: Nuclear expression of WRAP53 beta was significantly associated with better response to radiotherapy and improved patient survival. Downregulation of WRAP53 beta with siRNA in vitro enhanced cellular resistance to radiation. Conclusions: Our findings suggest that nuclear expression of WRAP53 beta promotes tumor cell death in response to radiotherapy and is a promising predictor of radiotherapy response in patients with HNSCC.

  • 272.
    Gawel, Danuta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Serra-Musach, Jordi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lilja, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Aagesen, Jesper
    Reg Jonkoping Cty, Sweden.
    Arenas, Alex
    Univ Rovira and Virgili, Spain.
    Asking, Bengt
    Reg Jonkoping Cty, Sweden.
    Bengner, Malin
    Reg Jonkoping Cty, Sweden.
    Bjorkander, Janne
    Reg Jonkoping Cty, Sweden.
    Biggs, Sophie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Hjortswang, Henrik
    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 Gastroentorology.
    Karlsson, Jan-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Köpsén, Mattias
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Jung Lee, Eun Jung
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Yonsei Univ, South Korea.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Xinxiu
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Magnusson, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Martinez, David
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Matussek, Andreas
    Reg Jonkoping Cty, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Schafer, Samuel
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Sonmez, Ceylan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Stjernman, Henrik
    Reg Jonkoping Cty, Sweden.
    Tjärnberg, Andreas
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Wu, Simon
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Shalek, Alex K.
    MIT, MA 02139 USA; Broad Inst MIT and Harvard, MA 02142 USA; Ragon Inst MGH MIT and Harvard, MA USA.
    Stenmarker, Margaretha
    Reg Jonkoping Cty, Sweden; Inst Clin Sci, Sweden.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Benson, Mikael
    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, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases2019In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 11, article id 47Article in journal (Refereed)
    Abstract [en]

    Background

    Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs.

    Methods

    The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs.

    Results

    We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model.

    Conclusions

    Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.

  • 273.
    Ge, Changrong
    et al.
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
    Tong, Dongmei
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Southern Medical University, Guangzhou, China..
    Liang, Bibo
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm,Southern Medical University, Guangzhou, China.
    Lönnblom, Erik
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm.
    Schneider, Nadine
    University Hospital Frankfurt Goethe University, Frankfurt, Germany.
    Hagert, Cecilia
    University of Turku, Finland.
    Viljanen, Johan
    Biomedicinskt centrum, Uppsala University, Uppsala, Sweden.
    Ayoglu, Burcu
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Stawikowska, Roma
    Florida Atlantic University, Jupiter, Florida, USA.
    Nilsson, Peter
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Fields, Gregg B
    Florida Atlantic University, Jupiter, Florida, USA.
    Skogh, Thomas
    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.
    Kastbom, Alf
    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.
    Kihlberg, Jan
    Uppsala University, Uppsala, Sweden.
    Burkhardt, Harald
    University Hospital Frankfurt Goethe University, Frankfurt, Germany.
    Dobritzsch, Doreen
    Uppsala University, Uppsala, Sweden.
    Holmdahl, Rikard
    Karolinska Institutet, Stockholm, Sweden; University of Turku, Turku, Finland, Southern Medical University, Guangzhou, China.
    Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage2017In: JCI insight, ISSN 2379-3708, Vol. 2, no 13, article id 93688Article in journal (Refereed)
    Abstract [en]

    Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis.

  • 274.
    Ge, Changrong
    et al.
    Karolinska Inst, Sweden.
    Xu, Bingze
    Karolinska Inst, Sweden.
    Liang, Bibo
    Karolinska Inst, Sweden; Southern Med Univ, Peoples R China.
    Lonnblom, Erik
    Karolinska Inst, Sweden.
    Lundstrom, Susanna L.
    Karolinska Inst, Sweden.
    Zubarev, Roman A.
    Karolinska Inst, Sweden.
    Ayoglu, Burcu
    KTH Royal Inst Technol, Sweden.
    Nilsson, Peter
    KTH Royal Inst Technol, Sweden.
    Skogh, Thomas
    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.
    Kastbom, Alf
    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.
    Malmstrom, Vivianne
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Klareskog, Lars
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Toes, Rene E. M.
    Leiden Univ, Netherlands.
    Rispens, Theo
    Univ Amsterdam, Netherlands.
    Dobritzsch, Doreen
    Uppsala Univ, Sweden.
    Holmdahl, Rikard
    Karolinska Inst, Sweden; Southern Med Univ, Peoples R China.
    Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies2019In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 71, no 2, p. 210-221Article in journal (Refereed)
    Abstract [en]

    Objective Anti-citrullinated protein antibodies (ACPAs) develop many years before the clinical onset of rheumatoid arthritis (RA). This study was undertaken to address the molecular basis of the specificity and cross-reactivity of ACPAs from patients with RA. Methods Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross-reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen-binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x-ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients. Results Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity-determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recognized by high titers of serum autoantibodies in 2 large cohorts of RA patients. Conclusion These data show, for the first time, how ACPAs derived from human RA serum recognize citrulline. The specific citrulline recognition and backbone-mediated interactions provide a structural explanation for the promiscuous recognition of citrullinated peptides by RA-specific ACPAs.

  • 275.
    Geetha, Duvuru
    et al.
    Johns Hopkins University, Baltimore, MD, USA.
    Hruskova, Zdenka
    Charles University, Prague, Czech Republic .
    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.
    Hogan, Jonathan
    Hospital of the University of Pennsylvania, Philadelphia, USA.
    Morgan, Matthew D
    University of Birmingham, UK .
    Cavero, Teresa
    Hospital 12 de Octubre, Madrid, Spain .
    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.
    Seo, Philip
    John Hopkins University, Baltimore, USA.
    Manno, Rebecca L
    John Hopkins University, Baltimore, USA.
    Dale, Jessica
    University of Birmingham, Birmingham, UK.
    Harper, Lorraine
    University of Birmingham, UK.
    Tesar, Vladimir
    Charles University, Prague, Czech Republic .
    Jayne, David Rw
    Addenbrooke's Hospital, Cambridge, UK .
    Rituximab for treatment of severe renal disease in ANCA associated vasculitis2016In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 29, no 2, p. 195-201Article in journal (Refereed)
    Abstract [en]

    Background

    Rituximab (RTX) is approved for remission induction in ANCA associated vasculitis (AAV). However, data on use of RTX in patients with severe renal disease is lacking.

    Methods

    We conducted a retrospective multi-center study to evaluate the efficacy and safety of RTX with glucocorticoids (GC) with and without use of concomitant cyclophosphamide (CYC) for remission induction in patients presenting with e GFR less than 20 ml/min/1.73 m2. We evaluated outcomes of remission at 6 months (6 M), renal recovery after acute dialysis at diagnosis, e-GFR rise at 6 M, patient and renal survival and adverse events.

    Results

    A total 37 patients met the inclusion criteria. The median age was 61 years. (55–73), 62 % were males, 78 % had new diagnosis and 59 % were MPO ANCA positive. The median (IQR) e-GFR at diagnosis was 13 ml/min/1.73 m2 (7–16) and 15 required acute dialysis. Eleven (30 %) had alveolar hemorrhage. Twelve (32 %) received RTX with GC, 25 (68 %) received RTX with GC and CYC and seventeen (46 %) received plasma exchange. The median (IQR) follow up was 973 (200–1656) days. Thirty two of 33 patients (97 %) achieved remission at 6 M and 10 of 15 patients (67 %) requiring dialysis recovered renal function. The median prednisone dose at 6 M was 6 mg/day. The mean (SD) increase in e-GFR at 6 months was 14.5 (22) ml/min/m2. Twelve patients developed ESRD during follow up. There were 3 deaths in the first 6 months. When stratified by use of concomitant CYC, there were no differences in baseline e GFR, use of plasmapheresis, RTX dosing regimen or median follow up days between the groups. No differences in remission, renal recovery ESRD or death were observed.

    Conclusions

    This study of AAV patients with severe renal disease demonstrates that the outcomes appear equivalent when treated with RTX and GC with or without concomitant CYC.

  • 276.
    Gentile, Giovanni
    et al.
    Karolinska Institute, Sweden.
    Åberg, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Petkova, Valeria I.
    Karolinska Institute, Sweden.
    Abdulkarim, Zakaryah
    Karolinska Institute, Sweden.
    Henrik Ehrsson, H.
    Karolinska Institute, Sweden.
    Patterns of neural activity in the human ventral premotor cortex reflect a whole-body multisensory percept2015In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 109, p. 328-340Article in journal (Refereed)
    Abstract [en]

    Previous research has shown that the integration of multisensory signals from the body in fronto-parietal association areas underlies the perception of a body part as belonging to ones physical self. What are the neural mechanisms that enable the perception of ones entire body as a unified entity? In one behavioral and one fMRI multivoxel pattern analysis experiment, we used a full-body illusion to investigate how congruent visuo-tactile signals from a single body part facilitate the emergence of the sense of ownership of the entire body. To elicit this illusion, participants viewed the body of a mannequin from the first-person perspective via head-mounted displays while synchronous touches were applied to the hand, abdomen, or leg of the bodies of the participant and the mannequin; asynchronous visuo-tactile stimuli served as controls. The psychometric data indicated that the participants perceived ownership of the entire artificial body regardless of the body segment that received the synchronous visuo-tactile stimuli. Based on multivoxel pattern analysis, we found that the neural responses in the left ventral premotor cortex displayed illusion-specific activity patterns that generalized across all tested pairs of body parts. Crucially, a tripartite generalization analysis revealed the whole-body specificity of these premotor activity patterns. Finally, we also identified multivoxel patterns in the premotor, intraparietal, and lateral occipital cortices and in the putamen that reflected multisensory responses specific to individual body parts. Based on these results, we propose that the dynamic formation of a whole-body percept may be mediated by neuronal populations in the ventral premotor cortex that contain visuo-tactile receptive fields encompassing multiple body segments.

  • 277.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Davidsson, Anette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engström, Maria
    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).
    Larsson, Elna-Marie
    Uppsala University, Sweden.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Dizdar (Dizdar Segrell), Nil
    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.
    The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes2015In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 262, no 9, p. 2154-2163Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to compare the efficacy of olfactory testing and presynaptic dopamine imaging in diagnosing Parkinsons disease (PD) and atypical parkinsonian syndromes (APS); to evaluate if the combination of these two diagnostic tools can improve their diagnostic value. A prospective investigation of 24 PD patients, 16 APS patients and 15 patients with non-parkinsonian syndromes was performed during an 18-month period. Single photon emission computed tomography with the presynaptic radioligand I-123-FP-CIT (DaTSCAN (R)) and olfactory testing with the Brief 12-item Smell Identification Test (B-SIT) were performed in all patients. DaTSCAN was analysed semi-quantitatively, by calculating two different striatal uptake ratios, and visually according to a predefined ranking scale. B-SIT score was significantly lower for PD patients, but not significantly different between APS and non-parkinsonism. The visual assessment of DaTSCAN had higher sensitivity, specificity and diagnostic accuracy compared to olfactory testing. Most PD patients (75 %) had visually predominant dopamine depletion in putamen, while most APS patients (56 %) had visually severe dopamine depletion both in putamen and in caudate nucleus. The combination of DaTSCAN and B-SIT led to a higher rate of correctly classified patients. Olfactory testing can distinguish PD from non-parkinsonism, but not PD from APS or APS from non-parkinsonism. DaTSCAN is more efficient than olfactory testing and can be valuable in differentiating PD from APS. However, combining olfactory testing and DaTSCAN imaging has a higher predictive value than these two methods separately.

  • 278.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Warntjes, Marcel Jan Bertus
    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 Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). SyntheticMR AB, Linkoping, Sweden.
    Dizdar Segrell, Nil
    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.
    Zachrisson, Helene
    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 Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    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).
    Haller, Sven
    Affidea CDRC Centre Diagnost Radiol Carouge SA, Switzerland; Uppsala University, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Sweden.
    Olfactory Impairment in Parkinsons Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging2017In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, no 2, p. 301-311Article in journal (Refereed)
    Abstract [en]

    Background: Olfactory impairment is an early manifestation of Parkinsons disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter. Objective: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT. Methods: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions. Results: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls. Conclusions: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.

  • 279.
    Georgiopoulos, Charalampos
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Witt, Suzanne Tyson
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Haller, Sven
    Affidea CDRC Ctr Diagnost Radiol Carouge SA, Switzerland; Uppsala Univ, Sweden.
    Dizdar Segrell, Nil
    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.
    Zachrisson, Helene
    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 Clinical Physiology in Linköping.
    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).
    Larsson, Elna-Marie
    Uppsala Univ, Sweden.
    Olfactory fMRI: Implications of Stimulation Length and Repetition Time2018In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 43, no 6, p. 389-398Article in journal (Refereed)
    Abstract [en]

    Studying olfaction with functional magnetic resonance imaging (fMRI) poses various methodological challenges. This study aimed to investigate the effects of stimulation length and repetition time (TR) on the activation pattern of 4 olfactory brain regions: the anterior and the posterior piriform cortex, the orbitofrontal cortex, and the insula. Twenty-two healthy participants with normal olfaction were examined with fMRI, with 2 stimulation lengths (6 s and 15 s) and 2 TRs (0.901 s and 1.34 s). Data were analyzed using General Linear Model (GLM), Tensorial Independent Component Analysis (TICA), and by plotting the event-related time course of brain activation in the 4 olfactory regions of interest. The statistical analysis of the time courses revealed that short TR was associated with more pronounced signal increase and short stimulation was associated with shorter time to peak signal. Additionally, both long stimulation and short TR were associated with oscillatory time courses, whereas both short stimulation and short TR resulted in more typical time courses. GLM analysis showed that the combination of short stimulation and short TR could result in visually larger activation within these olfactory areas. TICA validated that the tested paradigm was spatially and temporally associated with a functionally connected network that included all 4 olfactory regions. In conclusion, the combination of short stimulation and short TR is associated with higher signal increase and shorter time to peak, making it more amenable to standard GLM-type analyses than long stimulation and long TR, and it should, thus, be preferable for olfactory fMRI.

  • 280.
    Gerdin, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Department of Surgery, Höglandssjukhuset, Eksjö, Sweden.
    Eriksson, Anders S.
    Sahlgrens University Hospital, Sweden.
    Olaison, Gunnar
    Northern Hospital Zeeland, Denmark.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Faculty of Medicine and Health Sciences.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    The Swedish Crohn Trial: A Prematurely Terminated Randomized Controlled Trial of Thiopurines or Open Surgery for Primary Treatment of Ileocaecal Crohns Disease2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 1, p. 50-54Article in journal (Refereed)
    Abstract [en]

    Background and aims: The importance of efficient and safe treatment of Crohns disease is highlighted by its chronicity. Both medical and surgical treatments have shown good results in the symptomatic control of limited ileocaecal Crohns disease. The aim of this study was to compare medical treatment with surgical treatment of ileocaecal Crohns disease. Methods: Thirty-six patients from seven hospitals with primary ileocaecal Crohns disease were randomized to either medical or surgical treatment. The medical treatment was induction of remission with budesonide and thereafter maintenance treatment with azathioprine. The surgical treatment was open ileocaecal resection. Crohns disease activity index over time, expressed as area under the curve at 1, 3 and 5 years, was the primary endpoint. Subjective health measured with the 36-item Short Form Survey Instrument (SF36) and a visual analogue scale (VAS) were secondary endpoints. Results: There were no differences between the treatment groups in Crohns disease activity index over time. General health, measured as SF36 score, was higher in patients receiving surgical treatment than in those receiving medical treatment at 1 year, but there was no corresponding difference in VAS. Due to the slow inclusion rate and changes in clinical practice, the study was t = erminated prematurely. Conclusion: The study ended up being underpowered and should be interpreted with caution, but there was no clinically significant difference between the two treatment arms. Further studies are needed to address this important clinical question.

  • 281.
    Ghaderi Berntsson, Shala
    et al.
    Uppsala University, 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 University, Sweden.
    Flensner, Gullvi
    University of West, Sweden.
    Cerebellar ataxia and intrathecal baclofen therapy: Focus on patients experiences2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, article id e0180054Article in journal (Refereed)
    Abstract [en]

    Elucidating patients A experiences of living with chronic progressive hereditary ataxia and the symptomatic treatment with intrathecal baclofen (ITB) is the objective of the current study. A multicenter qualitative study with four patients included due to the rare combination of hereditary ataxia and ITB therapy was designed to elucidate participants experiences through semi-structured interviews. The transcribed text was analyzed according to content analysis guidelines. Overall we identified living in the present/taking one day at a time as the main theme covering the following categories: 1) Uncertainty about the future as a consequence of living with a hereditary disease; The disease; 2) Impact on life as a whole, 3) Influence on personal life in terms of feeling forced to terminate employment, 4) Limiting daily activities, and 5) ITB therapy, advantages, and disadvantages. Uncertainty about the future was the category that affected participants personal life, employment, and daily activities. The participants experience of receiving ITB therapy was expressed in terms of improved quality of life due to better body position and movement as well as better sleep and pain relief.

  • 282.
    Ghafouri, Bijar
    et al.
    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.
    Carlsson, Anders
    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.
    Holmberg, Sara
    Department Research and Dev, Sweden.
    Thelin, Anders
    Uppsala University, Sweden.
    Tagesson, Christer
    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.
    Biomarkers of lsystemic inflammation in farmers with musculoskeletal disorders; a plasma proteomic study2016In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, no 206Article in journal (Refereed)
    Abstract [en]

    Background: Farmers have an increased risk for musculoskeletal disorders (MSD) such as osteoarthritis of the hip, low back pain, and neck and upper limb complaints. The underlying mechanisms are not fully understood. Workrelated exposures and inflammatory responses might be involved. Our objective was to identify plasma proteins that differentiated farmers with MSD from rural referents. Methods: Plasma samples from 13 farmers with MSD and rural referents were included in the investigation. Gel based proteomics was used for protein analysis and proteins that differed significantly between the groups were identified by mass spectrometry. Results: In total, 15 proteins differed significantly between the groups. The levels of leucine-rich alpha-2-glycoprotein, haptoglobin, complement factor B, serotransferrin, one isoform of kininogen, one isoform of alpha-1-antitrypsin, and two isoforms of hemopexin were higher in farmers with MSD than in referents. On the other hand, the levels of alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, vitamin D-binding protein, apolipoprotein A1, antithrombin, one isoform of kininogen, and one isoform of alpha-1-antitrypsin were lower in farmers than in referents. Many of the identified proteins are known to be involved in inflammation. Conclusions: Farmers with MSD had altered plasma levels of protein biomarkers compared to the referents, indicating that farmers with MSD may be subject to a more systemic inflammation. It is possible that the identified differences of proteins may give clues to the biochemical changes occurring during the development and progression of MSD in farmers, and that one or several of these protein biomarkers might eventually be used to identify and prevent work-related MSD.

  • 283.
    Giles, Kagmeni
    et al.
    University Teaching Hospital Yaoundé (UTHY), Cameroon(1);University of Yaoundé I, Faculty of Medicine and Biomedical Sciences, Cameroon.
    Christelle, Domngang
    Mountains University Banganté, Cameroon.
    Yannick, Bilong
    University of Yaoundé I, Faculty of Medicine and Biomedical Sciences, Cameroon.
    Fricke, Otto Herrmann
    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 Ophthalmology in Linköping.
    Wiedemann, Peter
    Eye Hospital of Leipzig University, Germany.
    Cataract surgery with intraocular lens implantation in children aged 5-15 in local anaesthesia: visual outcomes and complications.2016In: Pan African Medical Journal, ISSN 1937-8688, E-ISSN 1937-8688, Vol. 24, p. 6article id 200Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to report feasibility, the visual outcomes and complications of pediatric cataract surgery with primary intraocular lens implantation in children aged 5 to15 years in local anesthesia. This retrospective interventional case series included 62 eyes from 50 children who underwent pediatrc cataract surgery with primary intraocular lens implantation at the Mana eye Clinic Nkongsamba between 2006 and 2015 Main outcome measures were: best-corrected post operative visual acuity, and intraoperative and postoperative complications. Mean age at surgery was 10.18 ± 3.21 years. Mean follow up length was 15.75 ± 3.36 weeks. Etiology included: 10 congenital cataracs (16.12%). 35 developmental cataracts (56.45%) and 17 traumatic cataracts (27.41%). The mean preoperative BCVA was logMAR 1.19 ± 0.33. (range 0.6-2.3). After cycloplegia refraction 2 weeks after surgery, the mean postoperative BCVA was log MAR 0.58 ± 0.88 (range 0.5-1.8). The mean implanted IOL power was 22.01 ±3.16 D. IOL was succefuly implanted in 54 eyes (87.07%). Eight eyes (9.67%) were left aphakic. Increase in BCVA of 4 logMAR lines and above was recorded in 27 patients (43.55%). Intraoperative complications included: 4 posterior capsule holes with vitrous lost, 3 lenses subluxation and 1 case of iris dialyse. Late postoperative complications included: posterior capsular opacity which occurred in 16 patients, 3 posterior synechia, 2 retinal detachment. Peribulbar anaesthesia can be considered as a viable option in selected patients presenting developmental cataract undergoing cataract surgery in developing countries. Effort should be made to improve the early identification of congenital cataract and its early surgical intervention and prompt optical rehabilitation to prevent amblyopia. [ABSTRACT FROM AUTHOR]

  • 284.
    Gowin, Joshua L.
    et al.
    NIAAA, MD USA.
    Vatsalya, Vatsalya
    NIAAA, MD USA; University of Louisville, KY 40292 USA; Robley Rex VAMC, KY USA.
    Westman, Jonathan G.
    NIAAA, MD USA.
    Schwandt, Melanie L.
    NIAAA, MD 20892 USA.
    Bartlett, Selena
    Queensland University of Technology, Australia.
    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.
    Momenan, Reza
    NIAAA, MD USA.
    Ramchandani, Vijay A.
    NIAAA, MD USA.
    The Effect of Varenicline on the Neural Processing of Fearful Faces and the Subjective Effects of Alcohol in Heavy Drinkers2016In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 40, no 5, p. 979-987Article in journal (Refereed)
    Abstract [en]

    Background: Pharmacotherapies for alcohol use disorder have been shown to reduce hazardous drinking and improve overall health. The effect sizes for the effectiveness of these medications, however, are small, underscoring the need to expand the range of therapeutics and develop personalized treatment approaches. Recent studies have suggested that varenicline, an 42-nicotinic partial agonist widely used for smoking cessation, can help alcoholics reduce drinking, but the neurocognitive underpinnings of its effectiveness remain largely unexplored. Methods: In this double-blind study, 32 heavy drinkers were randomized to receive varenicline (2 mg/d) or placebo. After 2 weeks of dosing, participants underwent functional MRI scans, during which they viewed images of faces with either neutral or fearful expressions at baseline and following an intravenous alcohol infusion to a target breath alcohol concentration of 80 mg%. Blood oxygen level-dependent (BOLD) response was analyzed with Analysis of Functional Neuroimaging software. Linear mixed-effects models were used to examine the effects of facial expression (fearful vs. neutral) and medication (placebo vs. varenicline) on BOLD response. The effect of medication on measures of subjective response to alcohol was also examined. Results: Results indicated a significant facial expression-by-medication interaction in the left amygdala. The groups showed equivalent activation to neutral faces, but, whereas the placebo group showed increased activation to fearful faces, the varenicline group showed no change in activation. Amygdala activation to fearful faces correlated with number of drinks in the previous 90 days and Obsessive Compulsive Drinking Scale scores. There was no effect of varenicline on subjective response to alcohol. Conclusions: Our results indicate that varenicline may disrupt amygdala response to fearful faces in heavy drinkers. Further, amygdala activation correlated with alcohol consumption, suggesting that the effects of varenicline may be related to aspects of drinking behavior. These results suggest that amygdala response to fearful faces may be developed as a biomarker of the effectiveness of medications being developed for the treatment of alcohol use disorder.

  • 285.
    Graff, Pal
    et al.
    Orebro Univ, Sweden; Natl Inst Occupat Hlth STAMI, Norway.
    Bryngelsson, Ing-Liss
    Orebro Univ, Sweden.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Flodin, Ulf
    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.
    Adult onset asthma in non-allergic women working in dampness damaged buildings: A retrospective cohort study2019In: American Journal of Industrial Medicine, ISSN 0271-3586, E-ISSN 1097-0274, Vol. 62, no 4, p. 357-363Article in journal (Refereed)
    Abstract [en]

    Background There is still no consensus about the association between working in dampness-damaged buildings and new onset of asthma among adults. The purpose of this study was to assess asthma in the staff of two psychiatric clinics where some premises were suffering from dampness. Methods A 20-year retrospective cohort study was performed using questionnaires. Results Incidence rate ratios (IRR) for asthma were non-significantly elevated (IRR = 2.3) among exposed individuals. The risk was greater among females (IRR = 3.5, 95% CI 1.0-16). IRR for non-atopic women was 8.8 (95% CI 1.4-196). Adjusting for smoking habits weakened the risks marginally (IRR = 7.3, 95% CI 1.1-167). The number of male participants was too low to draw conclusion regarding the risk for men. Conclusion The results suggest that working in dampness-damaged buildings might be a possible health hazard. This finding is most pronounced in non-atopic females.

  • 286.
    Graff, Pål
    et al.
    Örebro University, Örebro , Sweden.
    Ståhlbom, Bengt
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Faculty of Medicine and Health Sciences.
    Nordenberg, Eva
    Siemens Industrial Turbomachinery, Finspång, Sweden.
    Graichen, Andreas
    Siemens Industrial Turbomachinery, Finspång, Sweden.
    Johansson, Pontus
    Siemens Industrial Turbomachinery, Finspång, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Faculty of Medicine and Health Sciences.
    Evaluating Measuring Techniques for Occupational Exposure during Additive Manufacturing of Metals: A Pilot Study2017In: Journal of Industrial Ecology, ISSN 1088-1980, E-ISSN 1530-9290, Vol. 21, p. 120-129Article in journal (Refereed)
    Abstract [en]

    Additive manufacturing that creates three-dimensional objects by adding layer uponlayer of material is a new technique that has proven to be an excellent tool for themanufacturing of complex structures for a variety of industrial sectors. Today, knowl-edge regarding particle emissions and potential exposure-related health hazards forthe operators is limited. The current study has focused on particle numbers, masses,sizes, and identities present in the air during additive manufacturing of metals. Mea-surements were performed during manufacturing with metal powder consisting es-sentially of chromium, nickel, and cobalt. Instruments used were Nanotracer (10 to300 nanometers [nm]), Lighthouse (300 nm to 10 micrometers), and traditional filter-basedparticle mass estimation followed by inductively coupled plasma mass spectrometry. Resultsshowed that there is a risk of particle exposure at certain operations and that particle sizestended to be smaller in recycled metal powder compared to new. In summary, nanosizedparticles were present in the additive manufacturing environment and the operators wereexposed specifically while handling the metal powder. For the workers’ safety, improvedpowder handling systems and measurement techniques for nanosized particles will possiblyhave to be developed and then translated into work environment regulations. Until then,relevant protective equipment and regular metal analyses of urine is recommended

  • 287.
    Granqvist, Mathias
    et al.
    Karolinska Inst, Sweden.
    Burman, Joachim
    Uppsala Univ, Sweden.
    Gunnarsson, Martin
    Orebro Univ, Sweden.
    Lycke, Jan
    Sahlgrens Univ Hosp, Sweden.
    Nilsson, Petra
    University Hospital, Lund, Sweden.
    Olsson, Tomas
    Karolinska Inst, Sweden.
    Sundstrom, Peter
    Skane Univ Hosp, Sweden; Umea Univ, Sweden.
    Svenningsson, Anders
    Karolinska Inst, Sweden.
    Vrethem, 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, Local Health Care Services in Central Östergötland, Department of Neurology.
    Frisell, Thomas
    Karolinska Inst, Sweden.
    Piehl, Fredrik
    Karolinska Inst, Sweden.
    Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS2019In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, article id UNSP 1352458519866600Article in journal (Refereed)
    Abstract [en]

    Background: Population-based real-world evidence studies of the effectiveness and tolerability of dimethyl fumarate in relation to common treatment alternatives are still limited. Objective: To evaluate the clinical effectiveness and tolerability of dimethyl fumarate (DMF) as the initial and secondary treatment for relapsing-remitting multiple sclerosis (RRMS) patients compared with common treatment alternatives in Sweden. Methods: We conducted a nationwide retrospective observational cohort study of all RRMS patients identified through the Swedish MS registry initiating DMF (n = 641) or interferons/glatiramer acetate (IFN/GA; n = 555) as the initial therapy, or DMF (n = 703) or fingolimod (FGL; n = 194) after switch from IFN/GA between 1 January 2014 and 31 December 2016. Results: The discontinuation rate was lower with DMF as the initial treatment than IFN/GA (adjusted hazard rate (HR): 0.46, 95% confidence interval (CI): 0.37-0.58, p amp;lt; 0.001), but higher than FGL as the secondary treatment (HR: 1.51, CI: 1.08-2.09, p amp;lt; 0.05). Annualized relapse rate (ARR) was lower with DMF compared to IFN/GA (0.04, CI: 0.03-0.06 vs 0.10, CI: 0.07-0.13; p amp;lt; 0.05), but not FGL (0.03, CI: 0.02-0.05 vs 0.02, CI: 0.01-0.04; p = 0.41). Finally, time to first relapse (TTFR) was longer with DMF as the initial, but not secondary, therapy (p amp;lt; 0.05 and p = 0.20, respectively). Conclusion: Our findings indicate that DMF performs better than IFN/GA as the initial treatment for RRMS. Compared to FGL, DMF displayed a lower tolerability, but largely similar effectiveness outcomes.

  • 288.
    Griffith, May
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Lee, Chyan-Jang
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Buznyk, Oleksiy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Filatov Inst Eye Dis and Tissue Therapy, Ukraine.
    Artificial Corneas, and Reinforced Composite Implants for High Risk Donor Cornea Transplantation2017In: The Stem Cell Microenvironment and its Role in Regenerative Medicine and Cancer Pathogenesis, RIVER PUBLISHERS , 2017, Vol. 7, p. 93-102Conference paper (Refereed)
    Abstract [en]

    Here, we review examples of artificial corneas that have been developed as alternatives to donor cornea transplantation. These consist of artificial corneas developed as prostheses and regenerative scaffolds. Examples of reinforced and composite implants developed within our group are profiled.

  • 289.
    Grodzinsky, Ewa
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    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.
    Viktorsson, Lisa
    Carlsson, Ann-Kristin
    Jones, Michael P.
    Macquarie University, Australia.
    Olsen Faresjö, Ashild
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    More negative self-esteem and inferior coping strategies among patients diagnosed with IBS compared with patients without IBS - a case-control study in primary care2015In: BMC Family Practice, ISSN 1471-2296, E-ISSN 1471-2296, Vol. 16, no 6Article in journal (Refereed)
    Abstract [en]

    Background

    Irritable Bowel Syndrome (IBS) is a chronic, relapsing gastrointestinal disorder,that affects approximately 10% of the general population and the majority are diagnosed  in primary care. IBS has been reported to be associated with altered psychological and cognitive functioning such as mood disturbances, somatization, catastrophizing or altered visceral interoception by negative emotions and stress. The aim was to  investigate the psychosocial constructs of self-esteem and sense of coherence among IBS patients compared to non-IBS patients in primary care.     

    Methods

    A case–control study in primary care setting among IBS patients meeting the ROME III         criteria (n = 140) compared to controls i.e. non-IBS patients (n = 213) without any         present or previous gastrointestinal complaints. The data were collected through self-reportedquestionnaires of psychosocial factors.     

    Results

    IBS-patients reported significantly more negative self-esteem (p < 0.001), lower scores         for positive self-esteem (p < 0.001), and lower sense of coherence (p < 0.001) than the controls. The IBS-cases were also less likely to report ‘good’ health status (p < 0.001) and less likely to report a positive belief in the future (p < 0.001). After controlling for relevant confounding factors in multiple regressions, the elevation  in negative self-esteem among IBS patients remained statistically significant (p =0.02), as did the lower scores for sense of coherence among IBS cases (p = 0.04).     

    Conclusions

    The more frequently reported negative self-esteem and inferior coping strategies among         IBS patients found in this study suggest the possibility that psychological therapies         might be helpful for these patients. However these data do not indicate the causal         direction of the observed associations. More research is therefore warranted to determine whether these psychosocial constructs are more frequent in IBS patients.

  • 290.
    Gron, Kathrine Lederballe
    et al.
    Rigshosp, Denmark; Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Arkema, Elizabeth V.
    Karolinska Inst, Sweden.
    Glintborg, Bente
    Rigshosp, Denmark; Rigshosp, Denmark; Copenhagen Univ Hosp, Denmark.
    Mehnert, Frank
    Aarhus Univ Hosp, Denmark.
    Ostergaard, Mikkel
    Rigshosp, Denmark; Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Dreyer, Lene
    Aalborg Univ Hosp, Denmark.
    Norgaard, Mette
    Aarhus Univ Hosp, Denmark.
    Krogh, Niels Steen
    ZiteLab ApS, Denmark.
    Askling, Johan
    Karolinska Inst, Sweden.
    Hetland, Merete Lund
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Askling, Johan
    Karolinska Inst, Sweden.
    Klareskog, Lars
    Karolinska Inst, Sweden.
    Feltelius, Nils
    Karolinska Inst, Sweden.
    Baecklund, Eva
    Uppsala Univ, 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.
    Rantapaa-Dahlqvist, Solbritt
    Umea Univ, Sweden.
    Forsblad-dElia, Helena
    Umea Univ, Sweden.
    Jacobsson, Lennart
    Sahlgrens Acad, Sweden.
    Turesson, Carl
    Lund Univ, Sweden.
    Lindqvist, Elisabet
    Lund Univ, Sweden.
    Nisell, Ralph
    Swedish Rheumatol Qual Register, Sweden.
    Risk of serious infections in patients with rheumatoid arthritis treated in routine care with abatacept, rituximab and tocilizumab in Denmark and Sweden2019In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, no 3, p. 320-327Article in journal (Refereed)
    Abstract [en]

    Objective To estimate (1) crude and age-and gender-adjusted incidence rates (IRs) of serious infections (SI) and (2) relative risks (RR) of SI in patients with rheumatoid arthritis (RA) initiating treatment with abatacept, rituximab or tocilizumab in routine care. Methods This is an observational cohort study conducted in parallel in Denmark and Sweden including patients with RA in Denmark (DANBIO) and Sweden (Anti-Rheumatic Treatment in Sweden Register/Swedish Rheumatology Quality Register) who started abatacept/rituximab/tocilizumab in 2010-2015. Patients could contribute to more than one treatment course. Incident SI (hospitalisations listing infection) and potential confounders were identified through linkage to national registries. Age-and gender-adjusted IRs of SI per 100 person years and additionally adjusted RRs of SI during 0-12 and 0-24 months since start of treatment were assessed (Poisson regression). Country-specific RRs were pooled using inverse variance weighting. Results We identified 8987 treatment courses (abatacept: 2725; rituximab: 3363; tocilizumab: 2899). At treatment start, rituximab-treated patients were older, had longer disease duration and more previous malignancies; tocilizumab-treated patients had higher C reactive protein. During 0-12 and 0-24 months of follow-up, 456 and 639 SI events were identified, respectively. The following were the age-and gender-adjusted 12-month IRs for abatacept/rituximab/tocilizumab: 7.1/8.1/6.1 for Denmark and 6.0/6.4/4.7 for Sweden. The 24-month IRs were 6.1/7.5/5.2 for Denmark and 5.6/5.8/4.3 for Sweden. Adjusted 12-month RRs for tocilizumab versus rituximab were 0.82 (0.50 to 1.36) for Denmark and 0.76 (0.57 to 1.02) for Sweden, pooled 0.78 (0.61 to 1.01); for abatacept versus rituximab 0.94 (0.55 to 1.60) for Denmark and 0.86 (0.66 to 1.13) for Sweden, pooled 0.88 (0.69 to 1.12); and for abatacept versus tocilizumab 1.15 (0.69 to 1.90) for Denmark and 1.14 (0.83 to 1.55) for Sweden, pooled 1.13 (0.91 to 1.42). The adjusted RRs for 0-24 months were similar. Conclusion For patients starting abatacept, rituximab or tocilizumab, differences in baseline characteristics were seen. Numerical differences in IR of SI between drugs were observed. RRs seemed to vary with drug (tocilizumab amp;lt; abatacept amp;lt; rituximab) but should be interpreted with caution due to few events and risk of residual confounding.

  • 291.
    Guendouzi, Jacqueline
    et al.
    Southeastern Louisiana University, USA.
    Meaux, A.
    Southeastern Louisiana University, 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.
    Avoiding interactional conflict in dementia: the influence of gender styles on interactions.2016In: Journal of Language Aggression and Conflict, ISSN 2213-1272, Vol. 4, no 1, p. 9-35Article in journal (Refereed)
    Abstract [en]

    Sociolinguistic research in the general population has established the existence of gender differences in the social use of language. In particular, it has been noted that women use more markers of politeness, small talk and structural devices (e.g. minimal responses, tag questions) to help maintain their conversations. Analysis of interactions involving people with dementia (PWD) suggests that these gender based differences were still present in the face of dementia. Furthermore, the use of these forms of language helped the women with dementia to avoid conflict and extend the length of their interactions. This study investigated whether the use of such language helped or hindered women with dementia in maintaining conversational satisfaction.

  • 292.
    Guldbrand, Hans
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Dizdar, B.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Bunjaku, B.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences.
    Bachrach-Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    In type 2 diabetes, randomisation to advice to follow a low-carbohydrate diet transiently improves glycaemic control compared with advice to follow a low-fat diet producing a similar weight loss2012In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 55, no 8, p. 2118-2127Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: The study aimed to compare the effects of a 2 year intervention with a low-fat diet (LFD) or a low-carbohydrate diet (LCD), based on four group meetings to achieve compliance. METHODS: This was a prospective randomised parallel trial involving 61 adults with type 2 diabetes consecutively recruited in primary care and randomised by drawing ballots. Patients that did not speak Swedish could not be recruited. The primary outcomes in this non-blinded study were weight and HbA(1c). Patients on the LFD aimed for 55-60 energy per cent (E%) and those on LCD for 20 E% from carbohydrate. RESULTS: The mean BMI and HbA(1c) of the participants were 32.7 ± 5.4 kg/m(2) and 57.0 ± 9.2 mmol/mol, respectively. No patients were lost to follow-up. Weight loss did not differ between groups and was maximal at 6 months: LFD -3.99 ± 4.1 kg (n = 31); LCD -4.31 ± 3.6 kg (n = 30); p < 0.001 within groups. At 24 months, patients on the LFD had lost -2.97 ± 4.9 kg and those on LCD -2.34 ± 5.1 kg compared with baseline (p = 0.002 and p = 0.020 within groups, respectively). HbA(1c) fell in the LCD group only (LCD at 6 months -4.8 ± 8.3 mmol/mol, p = 0.004, at 12 months -2.2 ± 7.7 mmol/mol, p = 0.12; LFD at 6 months -0.9 ± 8.8 mmol/mol, p = 0.56). At 6 months, HDL-cholesterol had increased with the LCD (from 1.13 ± 0.33 mmol/l to 1.25 ± 0.47 mmol/l, p = 0.018) while LDL-cholesterol did not differ between groups. Insulin doses were reduced in the LCD group (0 months, LCD 42 ± 65 E, LFD 39 ± 51 E; 6 months, LCD 30 ± 47 E, LFD 38 ± 48 E; p = 0.046 for between-group change). CONCLUSIONS/INTERPRETATION: Weight changes did not differ between the diet groups, while insulin doses were reduced significantly more with the LCD at 6 months, when compliance was good. Thus, aiming for 20% of energy intake from carbohydrates is safe with respect to cardiovascular risk compared with the traditional LFD and this approach could constitute a treatment alternative. TRIAL REGISTRATION: ClinicalTrials.gov NCT01005498 FUNDING: University Hospital of Linköping Research Funds, Linköping University, the County Council of Östergötland, and the Diabetes Research Centre of Linköping University.

  • 293.
    Gustafsson, Greta
    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, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Broström, Anders
    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. Department of Nursing Science, School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Ulander, Martin
    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.
    Vrethem, 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, Local Health Care Services in Central Östergötland, Department of Neurology.
    Svanborg, Eva
    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.
    Occurrence of epileptiform discharges and sleep during EEG recordings in children after melatonin intake versus sleep-deprivation2015In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 126, no 8, p. 1493-1497Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To determine if melatonin is equally efficient as partial sleep deprivation in inducing sleep without interfering with epileptiform discharges in EEG recordings in children 1-16years old.

    METHODS:

    We retrospectively analysed 129 EEGs recorded after melatonin intake and 113 EEGs recorded after partial sleep deprivation. Comparisons were made concerning occurrence of epileptiform discharges, the number of children who fell asleep and the technical quality of EEG recordings. Comparison between different age groups was also made.

    RESULTS:

    No significant differences were found regarding occurrence of epileptiform discharges (33% after melatonin intake, 36% after sleep deprivation), or proportion of unsuccessful EEGs (8% and 10%, respectively). Melatonin and sleep deprivation were equally efficient in inducing sleep (70% in both groups). Significantly more children aged 1-4years obtained sleep after melatonin intake in comparison to sleep deprivation (82% vs. 58%, p⩽0.01), and in comparison to older children with melatonin induced sleep (58-67%, p⩽0.05). Sleep deprived children 9-12years old had higher percentage of epileptiform discharges (62%, p⩽0.05) compared to younger sleep deprived children.

    CONCLUSION:

    Melatonin is equally efficient as partial sleep deprivation to induce sleep and does not affect the occurrence of epileptiform discharges in the EEG recording. Sleep deprivation could still be preferable in older children as melatonin probably has less sleep inducing effect.

    SIGNIFICANCE:

    Melatonin induced sleep have advantages, especially in younger children as they fall asleep easier than after sleep deprivation. The procedure is easier for the parents than keeping a young child awake for half the night.

  • 294.
    Gustafsson, Håkan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Biomedical Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Hallbeck, Martin
    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 Pathology and Clinical Genetics.
    Lindgren, Mikael
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology. Norwegian University of Science and Technology, Norway.
    Kolbun, Natallia
    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).
    Jonson, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Engström, Maria
    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).
    de Muinck, Ebo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Visualization of oxidative stress in ex vivo biopsies using electron paramagnetic resonance imaging2015In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 73, no 4, p. 1682-1691Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies.

    METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections.

    RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques.

    CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.

  • 295.
    Gustafsson, Håkan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Norrköping/Finspång. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Kale, Ajay
    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.
    Dasu, Alexandru
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. The Skandion Clinic, Uppsala, Sweden.
    Lund, Anders
    Linköping University, Department of Physics, Chemistry and Biology, Chemical Physics. Linköping University, Faculty of Science & Engineering.
    Edqvist, Per-Henrik
    Uppsala University, Uppsala, Sweden.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    EPR oximetry of cetuximab-treated head-and-neck tumours in a mouse model2017In: Cell Biochemistry and Biophysics, ISSN 1085-9195, E-ISSN 1559-0283, Vol. 75, no 3-4, p. 299-309Article in journal (Refereed)
    Abstract [en]

    Head and neck squamous cell carcinoma (HNSCC) tumours are associated with high mortality despite advances in therapy. The monoclonal antibody cetuximab (Erbitux®) has been approved for the treatment of advanced HNSCC. However, only a subset of HNSC patients receiving cetuximab actually responds to treatment, underlining the need for a means to tailor treatments of individual patients. The aim of the present study was to investigate the effect of cetuximab treatment on tumour growth, on tumour partial oxygen pressure as measured by LiPc electron paramagnetic resonance oximetry and on the expression of proteins involved in tumour growth, metabolism and hypoxia. Two HNSCC cell lines, UT-SCC-2 and UT-SCC-14, were used to generate xenografts on female BALB/c (nu/nu) nude mice. Mice with xenografts were given three injections of intraperitoneal cetuximab or phosphate-buffered saline, and the tumour volume was recorded continuously. After treatment the tumour partial oxygen pressure was measured by LiPc electron paramagnetic resonance oximetry and the expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, Ki-67, MCT1, MCT4, GLUT1, CAIX and HIF-1α were investigated by immunohistochemistry. In xenografts from both cell lines (UT-SCC-2 and UT-SCC-14) cetuximab had effect on the tumour volume but the effect was more pronounced on UT-SCC-14 xenografts. A higher tumour oxygenation was measured in cetuximab-treated tumours from both cell lines compared to untreated controls. Immunocytochemical staining after cetuximab treatment shows a significantly decreased expression of EGFR, pEGFR, Ki67, CAIX and nuclear HIF-1α in UT-SCC-14 tumours compared to untreated controls. MCT1 and GLUT1 were significantly decreased in tumours from both cell lines but more pronounced in UT-SCC-14 tumours. Taken together, our results show that cetuximab treatment decreases the tumour growth and increases the tumour partial oxygen pressure of HNSCC xenografts. Furthermore we found a potential connection between the partial oxygen pressure of the tumours and the expression of proteins involved in tumour growth, metabolism and hypoxia.

  • 296.
    Gustafsson, Mika
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Alfredsson, Lars
    Karolinska Institute, Sweden.
    Baranzini, Sergio
    University of Calif San Francisco, CA, USA.
    Bjorkander, Janne
    County Council Jonköping, Sweden.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hellberg, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Eklund, Daniel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Kockum, Ingrid
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Konstantinell, Aelita
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Arctic University of Norway, Norway.
    Lahesmaa, Riita
    University of Turku, Finland; Abo Akad University, Finland.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Liljenström, H. Robert I.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Mattson, Lina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Matussek, Andreas
    County Council Jonköping, Sweden.
    Mellergård, Johan
    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.
    Mendez, Melissa
    University of Peruana Cayetano Heredia, Peru.
    Olsson, Tomas
    Karolinska Institute, Sweden; Centre Molecular Med, Sweden.
    Pujana, Miguel A.
    Catalan Institute Oncol, Spain.
    Rasool, Omid
    University of Turku, Finland; Abo Akad University, Finland.
    Serra-Musach, Jordi
    Catalan Institute Oncol, Spain.
    Stenmarker, Margaretha
    County Council Jonköping, Sweden.
    Tripathi, Subhash
    University of Turku, Finland; Abo Akad University, Finland.
    Viitala, Miro
    University of Turku, Finland; Abo Akad University, Finland.
    Wang, Hui
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nestor, Colm
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases2015In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 7, no 313, article id 313ra178Article in journal (Refereed)
    Abstract [en]

    Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development.

  • 297.
    Gustafsson, Mikael
    et al.
    Linköping University, Department of Medical and Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    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.
    Absolut kvantifiering av metaboliter i hjärnans vita substans hos patienter med MS och normal magnetkamerundersökning2000Conference paper (Other academic)
  • 298.
    Gutefeldt, Kerstin
    et al.
    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 Infectious Diseases.
    Hedman, Christina A
    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 Endocrinology.
    Thyberg, Ingrid S M
    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.
    Bachrach-Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Arnqvist, Hans
    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 Endocrinology.
    Spångeus, Anna
    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 Endocrinology.
    Upper extremity impairments in type 1 diabetes with long duration: common problems with great impact on daily life2019In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 41, no 6, p. 633-640Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the prevalence, activity limitations and potential risk factors of upper extremity impairments in type 1 diabetes in comparison to controls.

    METHODS: In a cross-sectional population-based study in the southeast of Sweden, patients with type 1 diabetes <35 years at onset, duration ≥20 years, <67 years old and matched controls were invited to answer a questionnaire on upper extremity impairments and activity limitations and to take blood samples.

    RESULTS: Seven hundred and seventy-three patients (ages 50 ± 10 years, diabetes duration 35 ± 10 years) and 708 controls (ages 54 ± 9 years) were included. Shoulder pain and stiffness, hand paraesthesia and finger impairments were common in patients with a prevalence of 28-48%, which was 2-4-folds higher than in controls. Compared to controls, the patients had more bilateral impairments, often had coexistence of several upper extremity impairments, and in the presence of impairments, reported more pronounced activity limitations. Female gender (1.72 (1.066-2.272), p = 0.014), longer duration (1.046 (1.015-1.077), p = 0.003), higher body mass index (1.08 (1.017-1.147), p = 0.013) and HbA1c (1.029 (1.008-1.05), p = 0.007) were associated with upper extremity impairments.

    CONCLUSIONS: Compared to controls, patients with type 1 diabetes have a high prevalence of upper extremity impairments, often bilateral, which are strongly associated with activity limitations. Recognising these in clinical practise is crucial, and improved preventative, therapeutic and rehabilitative interventions are needed. Implications for rehabilitation Upper extremity impairments affecting the shoulder, hand and fingers are common in patients with type 1 diabetes, the prevalence being 2-4-fold higher compared to non-diabetic persons. Patients with diabetes type 1 with upper extremity impairments have more pronounced limitations in daily activities compared to controls with similar impairments. Recognising upper extremity impairments and activity limitations are important and improved preventive, therapeutic and rehabilitation methods are needed.

  • 299.
    Gutefeldt, Kerstin
    et al.
    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 Endocrinology.
    Hedman, Christina
    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 Endocrinology.
    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.
    Bachrach Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Spångeus, Anna
    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 Endocrinology.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Dysregulated growth hormone-insulin-like growth factor-1 axis in adult type 1 diabetes with long duration2018In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 89, no 4, p. 424-430Article in journal (Refereed)
    Abstract [en]

    ContextIn type 1 diabetes (T1D), dysregulation of the GH-IGF-1 axis has been reported. Whether this is related to upper extremity impairments (UEI) is unknown. ObjectiveExamine differences in GH-IGF-1 axis between T1D on subcutaneous insulin treatment and matched controls without diabetes and possible associations between GH-IGF-1 axis and UEI. DesignCross-sectional population-based study. Patients with T1D, onset amp;lt;35years, duration 20years, amp;lt;67years old and controls were invited to answer questionnaires and take blood samples. SubjectsA total of 605 patients with T1D and 533 controls accepted to participate. OutcomesFasting levels of IGF-1, IGF-1 Z-score, IGFBP-1, IGFBP-3, C-peptide, GH and UEI. ResultsPatients with T1D had lower IGF-1 and IGFBP-3 and higher IGFBP-1 and GH than controls. The difference in IGF-1 persisted with age. Insulin dose was associated with increasing IGF-1 Z-score but even at a very high insulin dose (amp;gt;1U/kg) IGF-1 Z-score was subnormal compared to controls. IGF-1 Z-score was unaffected by glycaemic control (HbA1c) but increased with residual insulin secretion, (C-peptide 1-99 pmol/L). IGFBP-1 was associated with fasting blood glucose, negatively in controls and positively in patients with T1D probably reflecting insulin resistance and insulin deficiency, respectively. There was no association between lower IGF-1 Z-score and UEI in T1D. ConclusionIn adult T1D with fair glycaemic control, the GH-IGF-1 axis is dysregulated exhibiting GH resistance, low IGF-1 and elevated IGFBP-1. Subcutaneous insulin cannot normalize these changes while endogenous insulin secretion has marked effects on IGF-1 pointing to a role of portal insulin.

  • 300.
    Guterstam, Arvid
    et al.
    Karolinska Institute, Sweden.
    Björnsdotter Åberg, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Bergouignan, Loretxu
    Karolinska Institute, Sweden; Basque Centre Cognit Brain and Language, Spain.
    Gentile, Giovanni
    Karolinska Institute, Sweden; CALTECH, CA 91125 USA.
    Li, Tie-Qiang
    Karolinska University, Sweden.
    Henrik Ehrsson, H.
    Karolinska Institute, Sweden.
    Decoding illusory self-location from activity in the human hippocampus2015In: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 9, no 412Article in journal (Refereed)
    Abstract [en]

    Decades of research have demonstrated a role for the hippocampus in spatial navigation and episodic and spatial memory. However, empirical evidence linking hippocampal activity to the perceptual experience of being physically located at a particular place in the environment is lacking. In this study, we used a multisensory out-of-body illusion to perceptually teleport six healthy participants between two different locations in the scanner room during high-resolution functional magnetic resonance imaging (fMRI). The participants were fitted with MRI-compatible head-mounted displays that changed their first-person visual perspective to that of a pair of cameras placed in one of two corners of the scanner room. To elicit the illusion of being physically located in this position, we delivered synchronous visuo-tactile stimulation in the form of an object moving toward the cameras coupled with touches applied to the participants chest. Asynchronous visuo-tactile stimulation did not induce the illusion and served as a control condition. We found that illusory self-location could be successfully decoded from patterns of activity in the hippocampus in all of the participants in the synchronous (P less than 0.05) but not in the asynchronous condition (Pgreater than 0.05). At the group-level, the decoding accuracy was significantly higher in the synchronous than in the asynchronous condition (P = 0.012). These findings associate hippocampal activity with the perceived location of the bodily self in space, which suggests that the human hippocampus is involved not only in spatial navigation and memory but also in the construction of our sense of bodily self-location.

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