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  • 101.
    Berlin, Gösta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Hammar, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Tapper, Linus
    Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Tynngård, Nahreen
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Effects of age, gender and menstrual cycle on platelet function assessed by impedance aggregometry2019Inngår i: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 30, nr 4, s. 473-479Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 102.
    Bernardi, R. E.
    et al.
    Heidelberg University, Germany.
    Zohsel, K.
    Heidelberg University, Germany.
    Hirth, N.
    Heidelberg University, Germany.
    Treutlein, J.
    Heidelberg University, Germany.
    Heilig, Markus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för social och affektiv neurovetenskap (CSAN). Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Laucht, M.
    Heidelberg University, Germany.
    Spanagel, R.
    Heidelberg University, Germany.
    Sommer, W. H.
    Heidelberg University, Germany.
    A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology2016Inngår i: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 6, nr e861Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 103.
    Bernstein, Joshua G. W.
    et al.
    Walter Reed National Mil Medical Centre, MD 20889 USA.
    Danielsson, Henrik
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutet för handikappvetenskap (IHV).
    Hällgren, Mathias
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Öron- näsa- och halskliniken US.
    Stenfelt, Stefan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Rönnberg, Jerker
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutet för handikappvetenskap (IHV).
    Lunner, Thomas
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutet för handikappvetenskap (IHV). Oticon AS, Denmark.
    Spectrotemporal Modulation Sensitivity as a Predictor of Speech-Reception Performance in Noise With Hearing Aids2016Inngår i: TRENDS IN HEARING, ISSN 2331-2165, Vol. 20, artikkel-id 2331216516670387Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 104.
    Berntsson, S. G.
    et al.
    Uppsala Univ, Sweden.
    Kristoffersson, A.
    Uppsala Univ, Sweden; Motala Gen Hosp, Sweden.
    Boström, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Feresiadou, A.
    Uppsala Univ, Sweden.
    Burman, J.
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Uppsala Univ, Sweden; Motala Gen Hosp, Sweden.
    Rapidly increasing off-label use of rituximab in multiple sclerosis in Sweden Outlier or predecessor?2018Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, nr 4, s. 327-331Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 105.
    Berntsson, Shala G.
    et al.
    Uppsala Univ, Sweden.
    Gauffin, Helena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Melberg, Atle
    Uppsala Univ, Sweden.
    Holtz, Anders
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Uppsala Univ, Sweden.
    Inherited Ataxia and Intrathecal Baclofen for the Treatment of Spasticity and Painful Spasms2019Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 97, nr 1, s. 18-23Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

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

  • 106.
    Bilbao, Ainhoa
    et al.
    University of Heidelberg, Mannheim, Germany.
    Robinson, J Elliott
    Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
    Heilig, Markus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Malanga, C J
    Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
    Spanagel, Rainer
    University of Heidelberg, Mannheim, Germany.
    Sommer, Wolfgang H
    University of Heidelberg, Mannheim, Germany.
    Thorsell, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    A Pharmacogenetic Determinant of Mu-Opioid Receptor Antagonist Effects on Alcohol Reward and Consumption: Evidence from Humanized Mice.2015Inngår i: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 77, nr 10, s. 850-858Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

  • 107.
    Bivik Eding, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Domer, Jakob
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Wäster, Petra
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Jerhammar, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Rosdahl, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Öllinger, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases2015Inngår i: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, nr 7, s. 792-797Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 108.
    Björk, Karl
    et al.
    Karolinska Institute, Stockholm, Sweden .
    Tronci, Valeria
    Psychobiology Section, NIDA, National Institutes of Health, Baltimore, MD, USA .
    Thorsell, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Tanda, Gianluigi
    Psychobiology Section, NIDA, National Institutes of Health, Baltimore, MD, USA .
    Hirth, Natalie
    University of Heidelberg, Mannheim, Germany .
    Heilig, Markus
    Laboratory of Clinical and Translational Studies, NIAAA, National Institutes of Health, Bethesda, MD, USA .
    Hansson, Anita C.
    Laboratory of Clinical and Translational Studies, NIAAA, National Institutes of Health, Bethesda, MD, USA.
    Sommer, Wolfgang H
    Laboratory of Clinical and Translational Studies, NIAAA, National Institutes of Health, Bethesda, MD, USA.
    β-Arrestin 2 knockout mice exhibit sensitized dopamine release and increased reward in response to a low dose of alcohol2013Inngår i: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 230, nr 3, s. 439-449Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rationale

    The rewarding effects of alcohol have been attributed to interactions between opioid and dopaminergic system within the mesolimbic reward pathway. We have previously shown that ablation of β-arrestin 2 (Arrb2), a crucial regulator of μ-opioid receptor function, attenuates alcohol-induced hyperlocomotion and c-fos activation in the nucleus accumbens.

    Objectives

    Here, we further investigated the role of Arrb2 in modulating alcohol-induced dopamine (DA) release and conditioned place preference (CPP). We also assessed the functional importance of Arrb2 for μ-opioid receptor surface expression and signaling following an acute alcohol challenge.

    Methods

    Alcohol-evoked (0.375, 0.75, and 1.5 g/kg intraperitoneally) DA release was measured by in vivo microdialysis in the shell of nucleus accumbens. Reward was assessed by the CPP paradigm. Receptor function was assessed by μ-receptor binding and [35S]GTP-γ-S autoradiography.

    Results

    In Arrb2 knockout mice accumbal DA levels reach maximum response at a lower dose compared to wild-type (wt) animals. In line with these results, Arrb2 knockout mice display increased CPP for alcohol as compared to wt mice. Finally, Arrb2 mutant mice display increased μ-opioid receptor signaling in the ventral and dorsal striatum and amygdala in response to a low dose of alcohol, indicating impaired desensitization mechanisms in these mice.

    Conclusions

    Our results show that Arrb2 modulates the response to low doses of alcohol on various levels including μ-opioid receptor signaling, DA release, and reward. They also reveal a clear dissociation between the effects of Arrb2 on psychomotor and reward behaviors.

  • 109.
    Björk, Mathilda
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Rehabenheten. Jonköping University, Sweden.
    Dahlström, Örjan
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutet för handikappvetenskap (IHV).
    Wetterö, Jonas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Sjöwall, Christoffer
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Quality of life and acquired organ damage are intimately related to activity limitations in patients with systemic lupus erythematosus2015Inngår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 16, nr 188Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Systemic lupus erythematosus (SLE) is an autoimmune multi-organ disease, characterized by episodes of disease flares and remissions over time, which may restrain affected patients ability to perform daily activities. The purpose of the present study was to characterize variation in activity limitations among well-defined SLE patients, and to describe disease phenotypes, acquired organ damage and their relations to activity limitation and self-reported health, respectively. Methods: The disease phenotypes were organized into 4 different clinical groups and logistic regression analyses were used to identify how an elevated health assessment questionnaire (HAQ) score was related to disease variables such as phenotypes, disease activity and damage accrual. Correlation and multiple linear regression analyses were used to examine the association between each group of variables - background variables, disease variables and self-reported measurements - and the degree of elevated HAQ. Results: We found a higher proportion of activity limitation in patients with skin and joint involvement compared to others. The presence of activity limitation, as detected by the HAQ instrument, was significantly associated with quality of life (EuroQol-5D) and accrual of organ damage using the Systemic Lupus International Collaborative Clinics/ACR damage index. Conclusions: The findings highlight the differing requirements of the multi-professional rehabilitation interventions for the various SLE phenotypes in order to optimize the clinical care of the patients.

  • 110.
    Björk, Mathilda
    et al.
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för arbetsterapi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Thyberg, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Valtersson, Eva
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Rörelse och Hälsa.
    Stenström, Birgitta
    Reumatologförbundet, Sweden.
    Sverker, Annette
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Socialt arbete. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Rörelse och Hälsa.
    Disability in the feet related to participation in daily life in patients with early RA: – an interview study in the Swedish TIRA project2017Konferansepaper (Fagfellevurdert)
  • 111.
    Björk, Mathilda
    et al.
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för arbetsterapi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Thyberg, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Valtersson, Eva
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Rörelse och Hälsa.
    Östlund, Gunnel
    School of Health Care and Social Welfare, Mälardalen University, Eskilstuna, Sweden.
    Stenström, Birgitta
    Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Sverker, Annette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Rörelse och Hälsa.
    Foot barriers in patients with early rheumatoid arthritis: an interview study among Swedish women and men2018Inngår i: Arthritis care & research, ISSN 2151-464X, E-ISSN 2151-4658, Vol. 70, nr 9, s. 1348-1354Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Foot impairments are related to reduced mobility and participation restrictions in daily activities in patients with established rheumatoid arthritis (RA). The new biological medications are effective and reduce disease activity, but not disability to the same extent. Foot impairments are assumed to be related to participation restrictions also in patients with early RA, diagnosed after the introduction of biological medications. The knowledge of foot impairments needs to be more explored after the introduction of biological disease-modifying drugs (bDMARDs). The aim of this study was to explore the patients' perspective of foot impairments related to early RA.

    METHODS: The sample included 59 patients (20-63 years) who were interviewed about participation dilemmas in daily life using the Critical Incident Technique. The interviews were audio-recorded and transcribed. Data related to foot impairments were extracted and analyzed thematically. A research partner validated the analysis. The study was approved by the Regional Ethics Committee.

    RESULTS: Patients with early RA described a variety of participation restrictions related to foot impairments: 1) foot hindrances in domestic life, 2) foot impairments influencing work, 3) leisure activities restricted by one's feet 4) struggling to be mobile 5) foot impairments as an early sign of rheumatic disease.

    CONCLUSION: There is a need to focus on foot impairments related to early RA, and for health care professionals to understand these signs. A suggestion for future research is to conduct a longitudinal follow-up of foot impairment related to medication, disease activity and disability in patients diagnosed after the introduction of bDMARDs. This article is protected by copyright. All rights reserved.

  • 112.
    Björnevik, Kjetil
    et al.
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Riise, Trond
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Boström, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Casetta, Ilaria
    University of Ferrara, Italy.
    Cortese, Marianna
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Granieri, Enrico
    University of Ferrara, Italy.
    Holmoy, Trygve
    University of Oslo, Norway; Akershus University Hospital, Norway.
    Kampman, Margitta T.
    University Hospital North Norway, Norway.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Uppsala University, Sweden.
    Magalhaes, Sandra
    McGill University, Canada.
    Pugliatti, Maura
    University of Bergen, Norway; University of Ferrara, Italy.
    Wolfson, Christina
    McGill University, Canada; McGill University, Canada.
    Myhr, Kjell-Morten
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Negative interaction between smoking and EBV in the risk of multiple sclerosis: The EnvIMS study2017Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, nr 7, s. 1018-1024Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Results from previous studies on a possible interaction between smoking and Epstein-Barr virus (EBV) in the risk of multiple sclerosis (MS) are conflicting. Objectives: To examine the interaction between smoking and infectious mononucleosis (IM) in the risk of MS. Methods: Within the case-control study on Environmental Factors In Multiple Sclerosis (EnvIMS), 1904 MS patients and 3694 population-based frequency-matched healthy controls from Norway, Italy, and Sweden reported on prior exposure to smoking and history of IM. We examined the interaction between the two exposures on the additive and multiplicative scale. Results: Smoking and IM were each found to be associated with an increased MS risk in all three countries, and there was a negative multiplicative interaction between the two exposures in each country separately as well as in the pooled analysis (p=0.001). Among those who reported IM, there was no increased risk associated with smoking (odds ratio (OR): 0.95, 95% confidence interval (CI): 0.66-1.37). The direction of the estimated interactions on the additive scale was consistent with a negative interaction in all three countries (relative excess risk due to interaction (RERI): -0.98, 95% CI: -2.05-0.15, p=0.09). Conclusion: Our findings indicate competing antagonism, where the two exposures compete to affect the outcome.

  • 113.
    Björnsdotter Åberg, Malin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. University of Gothenburg, Sweden.
    Wang, Nancy
    Yale School Med, CT USA.
    Pelphrey, Kevin
    George Washington University, DC USA; Childrens National Medical Centre, DC 20010 USA.
    Kaiser, Martha D.
    Yale School Med, CT USA.
    Evaluation of Quantified Social Perception Circuit Activity as a Neurobiological Marker of Autism Spectrum Disorder2016Inngår i: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 73, nr 6, s. 614-621Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    IMPORTANCE Autism spectrum disorder (ASD) is marked by social disability and is associated with dysfunction in brain circuits supporting social cue perception. The degree to which neural functioning reflects individual-level behavioral phenotype is unclear, slowing the search for functional neuroimaging biomarkers of ASD. OBJECTIVE To examine whether quantified neural function in social perception circuits may serve as an individual-level marker of ASD in children and adolescents. DESIGN, SETTING, AND PARTICIPANTS The cohort study was conducted at the Yale Child Study Center and involved children and adolescents diagnosed as having ASD and typically developing participants. Participants included a discovery cohort and a larger replication cohort. Individual-level social perception circuit functioning was assessed as functional magnetic resonance imaging brain responses to point-light displays of coherent vs scrambled human motion. MAIN OUTCOMES AND MEASURES Outcome measures included performance of quantified brain responses in affected male and female participants in terms of area under the receiver operating characteristic curve (AUC), sensitivity and specificity, and correlations between brain responses and social behavior. RESULTS Of the 39 participants in the discovery cohort aged 4 to 17 years, 22 had ASD and 30 were boys. Of the 75 participants in the replication cohort aged 7 to 20 years, 37 had ASD and 52 were boys. A relative reduction in social perception circuit responses was identified in discovery cohort boys with ASD at an AUC of 0.75 (95% CI, 0.52-0.89; P = .01); however, typically developing girls and girls with ASD could not be distinguished (P = .54). The results were confirmed in the replication cohort, where brain responses were identified in boys with ASD at an AUC of 0.79 (95% CI, 0.64-0.91; P amp;lt; .001) and failed to distinguish affected and unaffected girls (P = .82). Across both cohorts, boys were identified at an AUC of 0.77 (95% CI, 0.64-0.86) with corresponding sensitivity and specificity of 76% each. Additionally, brain responses were associated with social behavior in boys but not in girls. CONCLUSIONS AND RELEVANCE Quantified social perception circuit activity is a promising individual-level candidate neural marker of the male ASD behavioral phenotype. Our findings highlight the need to better understand effects of sex on social perception processing in relation to ASD phenotype manifestations.

  • 114.
    Björnsson, Bergthor
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Bojmar, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Sundqvist, Tommy
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Sandström, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Nitrite, a novel method to decrease ischemia/reperfusion injury in the rat liver2015Inngår i: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, nr 6, s. 1775-1783Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: To investigate whether nitrite administered prior to ischemia/reperfusion (I/R) reduces liver injury.

    METHODS: Thirty-six male Sprague-Dawley rats were randomized to 3 groups, including sham operated (n = 8), 45-min segmental ischemia of the left liver lobe (IR, n = 14) and ischemia/reperfusion (I/R) preceded by the administration of 480 nmol of nitrite (n = 14). Serum transaminases were measured after 4 h of reperfusion. Liver microdialysate (MD) was sampled in 30-min intervals and analyzed for glucose, lactate, pyruvate and glycerol as well as the total nitrite and nitrate (NOx). The NOx was measured in serum.

    RESULTS: Aspartate aminotransferase (AST) at the end of reperfusion was higher in the IR group than in the nitrite group (40 ± 6.8 μkat/L vs 22 ± 2.6 μkat/L, P = 0.022). Similarly, alanine aminotransferase (ALT) was also higher in the I/R group than in the nitrite group (34 ± 6 μkat vs 14 ± 1.5 μkat, P = 0.0045). The NOx in MD was significantly higher in the nitrite group than in the I/R group (10.1 ± 2.9 μM vs 3.2 ± 0.9 μM, P = 0.031) after the administration of nitrite. During ischemia, the levels decreased in both groups and then increased again during reperfusion. At the end of reperfusion, there was a tendency towards a higher NOx in the I/R group than in the nitrite group (11.6 ± 0.7 μM vs 9.2 ± 1.1 μM, P = 0.067). Lactate in MD was significantly higher in the IR group than in the nitrite group (3.37 ± 0.18 mM vs 2.8 ± 0.12 mM, P = 0.01) during ischemia and the first 30 min of reperfusion. During the same period, glycerol was also higher in the IRI group than in the nitrite group (464 ± 38 μM vs 367 ± 31 μM, P = 0.049). With respect to histology, there were more signs of tissue damage in the I/R group than in the nitrite group, and 29% of the animals in the I/R group exhibited necrosis compared with none in the nitrite group. Inducible nitric oxide synthase (iNOS) transcription increased between early ischemia (t = 15) and the end of reperfusion in both groups.

    CONCLUSION: Nitrite administered before liver ischemia in the rat liver reduces anaerobic metabolism and cell necrosis, which could be important in the clinical setting.

  • 115.
    Blomgran, Parmis
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Blomgran, Robert
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    A possible link between loading, inflammation and healing: Immune cell populations during tendon healing in the rat2016Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, nr 29824Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Loading influences tendon healing, and so does inflammation. We hypothesized that the two are connected. 48 rats underwent Achilles tendon transection. Half of the rats received Botox injections into calf muscles to reduce mechanical loading. Cells from the regenerating tissue were analyzed by flow cytometry. In the loaded group, the regenerating tissue contained 83% leukocytes (CD45(+)) day 1, and 23% day 10. The M1/M2 macrophage ratio (CCR7/CD206) peaked at day 3, while T helper (CD3(+)CD4(+)) and T-reg cells (CD25(+) Foxp3(+)) increased over time. With Botox, markers associated with down-regulation of inflammation were more common day 5 (CD163, CD206, CD25, Foxp3), and M1 or M2 macrophages and T-reg cells were virtually absent day 10, while still present with full loading. The primary variable, CCR7/CD206 ratio day 5, was higher with full loading (p = 0.001) and the T-reg cell fraction was lower (p amp;lt; 0.001). Free cage activity loading is known to increase size and strength of the tendon in this model compared to Botox. Loading now appeared to delay the switch to an M2 type of inflammation with more T-reg cells. It seems a prolonged M1 phase due to loading might make the tendon regenerate bigger.

  • 116.
    Blomgran, Parmis
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Blomgran, Robert
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Cox-2 inhibition and the composition of inflammatory cell populations during early and mid-time tendon healing2017Inngår i: Muscles, ligaments and Tendons journal, ISSN 2240-4554, Vol. 7, nr 2, s. 223-229Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: During early tendon healing, the cells within the regenerating tissue are, to a large part, inflammatory leukocytes (CD45+). In a rat Achilles tendon healing model, the inflammation resolves between 5 and 10 days. In the same model, Cox inhibitors (NSAIDs) impair healing when given during the first 5 days, but have a positive effect if given later. We tested the hypothesis that a Cox inhibitor would exert these effects by influencing inflammation, and thereby the composition of the inflammatory cell subpopulations.Methods: Achilles tendon transection was performed in 44 animals. Animals were randomized to either parecoxib or saline injections. Healing was evaluated by mechanical testing day 7 after surgery and by flow cytometry day 3 and 10.Results: Cross-sectional area, peak force and stiffness were reduced by parecoxib 31, 33, and 25% respectively (p=0.005, p=0.002, and p=0.005). By flow cytometry, there was a strong effect of time (p<0.001) on virtually all inflammatory cell subpopulations (CD45, CD11b, CD68, CCR7, CD163, CD206, CD3, CD4), but no significant effect of parecoxib at any time point.Conclusion: The results suggest that the negative effects of Cox inhibitors on tendon healing might be exerted mainly via mechanisms not directly related to inflammatory cells.

  • 117.
    Blystad, Ida
    et al.
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper.
    Håkansson, Irene
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Tisell, Anders
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Smedby, Örjan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Lundberg, Peter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Larsson, Elna-Marie
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Uppsala University, Sweden.
    Quantitative MRI for Analysis of Active Multiple Sclerosis Lesions without Gadolinium-Based Contrast Agent2016Inngår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 37, nr 1, s. 94-100Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND PURPOSE: Contrast-enhancing MS lesions are important markers of active inflammation in the diagnostic work-up of MS and in disease monitoring with MR imaging. Because intravenous contrast agents involve an expense and a potential risk of adverse events, it would be desirable to identify active lesions without using a contrast agent. The purpose of this study was to evaluate whether pre-contrast injection tissue-relaxation rates and proton density of MS lesions, by using a new quantitative MR imaging sequence, can identify active lesions. MATERIALS AND METHODS: Forty-four patients with a clinical suspicion of MS were studied. MR imaging with a standard clinical MS protocol and a quantitative MR imaging sequence was performed at inclusion (baseline) and after 1 year. ROIs were placed in MS lesions, classified as nonenhancing or enhancing. Longitudinal and transverse relaxation rates, as well as proton density were obtained from the quantitative MR imaging sequence. Statistical analyses of ROI values were performed by using a mixed linear model, logistic regression, and receiver operating characteristic analysis. RESULTS: Enhancing lesions had a significantly (P &lt; .001) higher mean longitudinal relaxation rate (1.22 0.36 versus 0.89 +/- 0.24), a higher mean transverse relaxation rate (9.8 +/- 2.6 versus 7.4 +/- 1.9), and a lower mean proton density (77 +/- 11.2 versus 90 +/- 8.4) than nonenhancing lesions. An area under the receiver operating characteristic curve value of 0.832 was obtained. CONCLUSIONS: Contrast-enhancing MS lesions often have proton density and relaxation times that differ from those in nonenhancing lesions, with lower proton density and shorter relaxation times in enhancing lesions compared with nonenhancing lesions.

  • 118.
    Boij, Roland
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Aspects of inflammation, angiogenesis and coagulation in preeclampsia2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Preeclampsia is a major challenge to obstetricians, due to its impact on maternal and fetal morbidity and mortality and the lack of preventive and treatment strategies. The overall aim of this thesis is to increase the knowledge of the pathogenesis of preeclampsia including the role of inflammation, angiogenesis and coagulation, both locally at the fetomaternal interface and in the maternal circulation. Uncompensated maternal endothelial inflammatory responses to factors from stressed trophoblasts seem to be a major contributor to the syndrome, together with an imbalance in angiogenesis and an activated coagulation system. An increasing amount of data indicates an involvement of the immune system with defect tolerance to the conceptus as an integral part of the pathogenesis, at least in early-onset preeclampsia (EOP).

    We showed that a single administration of human preeclampsia serum in pregnant IL-10−/− mice induced the full spectrum of preeclampsia-like symptoms including hypoxic injury in uteroplacental tissues and endotheliosis in maternal kidneys. Importantly, preeclampsia serum, as early as 12 to 14 weeks of gestation, disrupted cross talk between trophoblasts and endothelial cells in an in vitro model of endovascular activity (Tube formation test). These results indicate that preeclamptic sera can be used to better understand the pathophysiology and to predict the disorder. Preeclampsia has been associated with increased inflammation, aberrant angiogenesis and activated coagulation, but their correlation and relative contribution are unknown. We found that markers for all these mechanisms were independently associated with preeclampsia. Cytokines, chemokines, and complement factors seem all to be part of a Th1-associated inflammatory reaction in preeclampsia, more pronounced in EOP than in late-onset preeclampsia (LOP), in line with a more homogeneous pathogenesis in EOP as based on placental pathology. In women with intrauterine growth restriction (IUGR), with an anticipated pathologic placentation, only differences in levels for sFlt-1 and PlGF were found in comparison with mothers without IUGR. Thus, sFlt-1 and PlGF seem to be indicators of placental pathology, while other biomarkers might also reflect maternal endothelial pathology. Chemokines, in contrast to cytokines, may prove to be useful markers in preeclampsia.

    A deficiency in regulatory T (Treg) cells causing reduced immune regulatory capacity has been proposed in preeclampsia. Utilizing recent advances in flow cytometry phenotyping, we found no major alterations in circulating Treg numbers in preeclamptic women compared with normal pregnant and non-pregnant women. However, preeclampsia was associated with increased fractions of CTLA-4+ and CCR4+ cells within Treg subpopulations, which is in line with a migratory defect of Treg cells, and potentially associated with a reduced number of suppressive Treg cells at the fetomaternal interface. As we found that corticosteroid treatment affected the results, it should be accounted for in studies of EOP. Chemokines are supposed to be part of the immune adaptation in pregnancy. We found a decreased expression of CCL18  (Th2/Tregassociated), in trophoblasts from preeclamptic compared to normal pregnant women, indicating a local regulatory defect in preeclampsia, in line with our finding of a possible migratory defect of circulating Treg cells. Due to increased expression of CCL20 (Th17) and CCL22 (Th2) in first trimester placenta and increased circulating levels of CXCL10 (Th1) and CCL20 (Th17) in third trimester preeclamptic women, we suggest that CCL20 and CCL22 may be important for implantation and early placentation while in third trimester of a preeclamptic pregnancy CXCL10 and CCL20 mainly mirror maternal increased endothelial inflammation and aberrant angiogenesis. In summary, we found that preeclampsia is associated with increased inflammation, aberrant angiogenesis and activated coagulation, caused by placental factors in maternal peripheral circulation, more pronounced in the early-onset form of preeclampsia. It also appears that there is a defective modulation of the immune system in preeclamptic pregnancies. The results provide a better understanding of the pathogenesis of preeclampsia and have given suggestions to predictive markers for preeclampsia in the future.

    Delarbeid
    1. Sera from Preeclampsia Patients Elicit Symptoms of Human Disease in Mice and Provide a Basis for an in Vitro Predictive Assay
    Åpne denne publikasjonen i ny fane eller vindu >>Sera from Preeclampsia Patients Elicit Symptoms of Human Disease in Mice and Provide a Basis for an in Vitro Predictive Assay
    Vise andre…
    2010 (engelsk)Inngår i: AMERICAN JOURNAL OF PATHOLOGY, ISSN 0002-9440, Vol. 177, nr 5, s. 2387-2398Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Early diagnosis and treatment of preeclampsia would significantly reduce maternal and fetal morbidity and mortality. However, its etiology and prediction have remained elusive. Based on the hypothesis that sera from patients with preeclampsia could function as a "blueprint" of causative factors, we describe a serum-based pregnancy-specific mouse model that closely mirrors the human condition as well as an in vitro predictive assay. We show that a single administration of human preeclampsia serum in pregnant IL-10(-/-) mice induced the full spectrum of preeclampsia-like symptoms, caused hypoxic injury in uteroplacental tissues, and elevated soluble fins-like tyrosine kinase 1 and soluble endoglin, markers thought to be related to the disease. The same serum sample(s) induced a partial preeclampsia phenotype in wild-type mice. Importantly, preeclampsia serum disrupted cross talk between trophoblasts and endothelial cells in an in vitro model of endovascular activity. Disruption of endovascular activity could be documented in serum samples as early as 12 to 14 weeks of gestation from patients who subsequently developed preeclampsia. These results indicate that preeclampsia patient sera can be used to understand the pregnancy-specific disease pathology in mice and can predict the disorder.

    sted, utgiver, år, opplag, sider
    American Society for Investigative Pathology (ASIP), 2010
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-62755 (URN)10.2353/ajpath.2010.100475 (DOI)000284182900026 ()
    Tilgjengelig fra: 2010-12-03 Laget: 2010-12-03 Sist oppdatert: 2016-11-11
    2. Biomarkers of Coagulation, Inflammation, and Angiogenesis are Independently Associated with Preeclampsia
    Åpne denne publikasjonen i ny fane eller vindu >>Biomarkers of Coagulation, Inflammation, and Angiogenesis are Independently Associated with Preeclampsia
    Vise andre…
    2012 (engelsk)Inngår i: AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, ISSN 1046-7408, Vol. 68, nr 3, s. 258-270Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Problem Although preeclampsia has been associated with inflammation, coagulation, and angiogenesis, their correlation and relative contribution are unknown. Method of Study About 114 women with preeclampsia, 31 with early onset (EOP) and 83 with late onset preeclampsia (LOP), and 100 normal pregnant controls were included. A broad panel of 32 biomarkers reflecting coagulation, inflammation, and angiogenesis was analyzed. Results Preeclampsia was associated with decreased antithrombin, IL-4 and placental growth factor levels and with increased C3a, pentraxin-3, and sFlt-1 levels, with more marked differences in the EOP group. The Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in the preeclampsia and EOP group than in controls, respectively. No correlations between the biomarkers were found in preeclampsia. Multivariate logistic regression tests confirmed the results. Conclusions Cytokines, chemokines and complement activation seem to be part of a Th1-like inflammatory reaction in preeclampsia, most pronounced in EOP, where chemokines may be more useful than cytokines as biomarkers. Biomarkers were not correlated suggesting partly independent or in time separated mechanisms.

    sted, utgiver, år, opplag, sider
    John Wiley and Sons, 2012
    Emneord
    preeclampsia, coagulation, inflammation, angiogenesis, chemokines, cytokines and early onset preeclampsia
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-81815 (URN)10.1111/j.1600-0897.2012.01158.x (DOI)000307440300012 ()
    Merknad

    Funding Agencies|FORSS (Medical Research Council of Southeast Sweden)||Futurum (the Research department of County of Jonkoping)||Swedish Research Council|2007-15809-48800-58|Linneaus University (Sweden)||

    Tilgjengelig fra: 2012-09-26 Laget: 2012-09-24 Sist oppdatert: 2020-01-16
    3. Regulatory T-cell Subpopulations in Severe or Early-onset Preeclampsia
    Åpne denne publikasjonen i ny fane eller vindu >>Regulatory T-cell Subpopulations in Severe or Early-onset Preeclampsia
    Vise andre…
    2015 (engelsk)Inngår i: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 74, nr 4, s. 368-378Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Problem A deficiency in regulatory T (Treg) cells causing reduced immune regulatory capacity has been proposed in preeclampsia. Objective Utilizing recent advances in flow cytometry phenotyping, we aimed to assess whether a deficiency of Treg subpopulations occurs in preeclampsia. Method of study Six-color flow cytometry was used for Treg phenotyping in 18 preeclamptic women (one early-onset, one severe and 16 both), 20 women with normal pregnancy, and 20 non-pregnant controls. Results No differences were found in major Treg populations including CD127(low)CD25(+)/CD127(ow)FOXP3(+), resting (FOXP3(dim)CD45RA(+)), and activated (FOXP3(bright)CD45RA(-)) Treg cells, whereas preeclamptic women showed increased CTLA-4(+) and CCR4(+) proportions within resting/activated Treg populations. Corticosteroid treatment prior to blood sampling (n = 10) affected the distribution of Treg populations. Conclusions Although we found no major alterations in circulating Treg frequencies, differences in CTLA-4(+) and CCR4(+) frequencies suggest a migratory defect of Treg cells in preeclampsia. Corticosteroid treatment should be taken into account when evaluating Treg cells.

    sted, utgiver, år, opplag, sider
    WILEY-BLACKWELL, 2015
    Emneord
    Early-onset preeclampsia; preeclampsia; pregnancy; regulatory T cells
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-122528 (URN)10.1111/aji.12410 (DOI)000362664200009 ()26118401 (PubMedID)
    Merknad

    Funding Agencies|FORSS (Medical Research Council of Southeast Sweden); Futurum, academy for Health and Care Jonkoping County Council, Sweden

    Tilgjengelig fra: 2015-11-09 Laget: 2015-11-06 Sist oppdatert: 2020-01-16
  • 119.
    Boij, Roland
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. County Hospital Ryhov, Sweden.
    Mjosberg, Jenny
    Karolinska Institute, Sweden.
    Svensson Arvelund, Judit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Hjorth, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Matthiesen, Leif
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Helsingborg Hospital, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Regulatory T-cell Subpopulations in Severe or Early-onset Preeclampsia2015Inngår i: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 74, nr 4, s. 368-378Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Problem A deficiency in regulatory T (Treg) cells causing reduced immune regulatory capacity has been proposed in preeclampsia. Objective Utilizing recent advances in flow cytometry phenotyping, we aimed to assess whether a deficiency of Treg subpopulations occurs in preeclampsia. Method of study Six-color flow cytometry was used for Treg phenotyping in 18 preeclamptic women (one early-onset, one severe and 16 both), 20 women with normal pregnancy, and 20 non-pregnant controls. Results No differences were found in major Treg populations including CD127(low)CD25(+)/CD127(ow)FOXP3(+), resting (FOXP3(dim)CD45RA(+)), and activated (FOXP3(bright)CD45RA(-)) Treg cells, whereas preeclamptic women showed increased CTLA-4(+) and CCR4(+) proportions within resting/activated Treg populations. Corticosteroid treatment prior to blood sampling (n = 10) affected the distribution of Treg populations. Conclusions Although we found no major alterations in circulating Treg frequencies, differences in CTLA-4(+) and CCR4(+) frequencies suggest a migratory defect of Treg cells in preeclampsia. Corticosteroid treatment should be taken into account when evaluating Treg cells.

  • 120.
    Bojmar, Linda
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Zhang, Haiying
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Costa da Silva, Bruno
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Karlsson, Elin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Vincent, Theresa
    Departments of Physiology and Biophysics and Cell and Developmental Biology, Weill Cornell Medical College, New York, USA / Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Lyden, David
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Sandström, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome2015Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The ultimate cause of death for many cancer patients is the spread of the cancer via metastasis. Even so, there are still a lack of knowledge regarding the metastasis process. This study was performed to investigate the role of metastamirs in exosomes and their metastatic patterns. We used the well-established isogeneic murine cancer model of low metastatic 67NR cells, mimicking luminal/basal breast tumors, and highly metastatic 4T1 cells with characteristics of basal breast  tumors. We studied the exosomal properties and pre-metastatic effects in this metastasis model and compared human materials and exosomes of several other tumor types. Our data clearly demonstrated that exosomes from the highly metastatic cells home to the metastatic organs of their parental cells whereas exosomes from cells with low metastatic potential mostly located to lymph nodes. The exosome protein cargos also resembled their parental cells and potentially affects their target organs, and cells, differently. Furthermore, the exosomes from the highly metastatic cells had a more pronounced effect on tumor growth and pre-metastatic changes than the low metastatic exosomes. The microRNA-18a, a predictor of metastasis, was present to a higher extent in metastatic exosomes as compared to low metastatic exosomes, and altered the tumor progressive properties. Our findings support the role of exomirs as important players in the metastatic process, the value as biomarkers and potential therapeutic targets.

  • 121.
    Bolin, K.
    et al.
    University of Gothenburg, Sweden.
    Berggren, F.
    UCB Pharma, Denmark.
    Berling, P.
    UCB Pharma, Denmark.
    Morberg, S.
    UCB Pharma, Denmark.
    Gauffin, Helena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Region Östergötland, Närsjukvården i västra Östergötland, Medicinska specialistkliniken. Uppsala University, Sweden.
    Patterns of antiepileptic drug prescription in Sweden: A register-based approach2017Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 136, nr 5, s. 521-527Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To determine drug utilization pathways from the incident healthcare visit due to epilepsy and three years onward. Material and methods: Anti-epileptic drug utilization was calculated using individual information on inpatient- and outpatient care utilization and drug sales. Throughout, we used national register information pertaining to pharmaceutical sales linked to diagnosis-related healthcare utilization. Information on pharmaceutical sales was collected for the 2007-2013 period. Results: For the entire studied period, a majority of new patients with epilepsy were initiated on anti-epileptic drug treatment with a monotherapy (98%); most of these patients remained on that first treatment (64%). The three most frequently prescribed drugs accounted for 72% of the initiated AED treatments. Patients with epilepsy (ICD-10: G40/41) were most commonly prescribed carbamazepine, lamotrigine and valproate. The most common second-line monotherapy was levetiracetam. About 12% of new patients with epilepsy who were initiated on AED treatment during the period eventually switched to an add-on therapy. The proportion of patients who were initiated on treatment with carbamazepine or valproate decreased, and the proportion of patients who remained on their initial monotherapy increased between 2007 and 2013. Conclusions: A limited number of anti-epileptic drugs accounted for the treatment of a majority of new patients with epilepsy (carbamazepine, lamotrigine and valproate accounted for more than 70%). Add-on therapies showed the same pattern, as the most frequently prescribed add-on regimens were the same ones that accounted for most of the monotherapies. There was a tendency towards fewer patients being initiated on AED treatment with either carbamazepine or valproate.

  • 122.
    Bolin, K.
    et al.
    University of Gothenburg, Sweden; University of Gothenburg, Sweden.
    Berggren, F.
    UCB Pharma, Denmark.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Prevalence and cost of epilepsy in Sweden - a register-based approach2015Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 131, nr 1, s. 37-44Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    ObjectivesTo estimate the prevalence of epilepsy, costs associated with in- and outpatient care, drug utilization and productivity losses due to epilepsy in Sweden for the years 2005 and 2011. MethodsCost components were calculated using registry data on inpatient- and outpatient-care utilization, drug sales and early pensions granted due to permanent disability and mortality. Moreover, by cross-identification of information in healthcare and pharmaceutical registries, we were able to distinguish between pharmaceuticals prescribed for epilepsy and non-epilepsy indications. ResultsThe prevalence of epilepsy was estimated at 0.62% in 2005 and 0.88% in 2011. The total cost of epilepsy increased during the same period, while the per-patient cost decreased from Euro2929 to Euro1729. Direct medical costs accounted for about 36% of the estimated total cost in 2005 and 60% in 2011. The estimated healthcare cost due to epilepsy as a share of total healthcare costs for all illnesses was about the same in 2005 as in 2011 (0.2%), while the corresponding pharmaceutical cost increased from about 0.5% in 2005 to almost 1% in 2011. ConclusionsThe per-patient cost of epilepsy is substantial, implying a significant aggregated cost incurred on society (despite a prevalenceless than1%). Our results suggest that the per-patient pharmaceutical utilization increased, while the per-patient physician visits and hospitalizations decreased, between 2005 and 2011. Moreover, we demonstrate that the 2005 prevalence measure was underestimated the true prevalence in 2005.

  • 123.
    Boman, Andrea
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Janefjord, Camilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. CBD Solutions, Stockholm, Sweden.
    Halliday, Glenda
    Neuroscience Research Australia and University of New South Wales, Sydney, Australia.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden / UCL Institute of Neurology, Queen Square, London, United Kingdom.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden.
    Garner, Brett
    Illawarra Health and Medical Research Institute, Wollongong, Australia / School of Biological Sciences, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, Australia.
    Miller, Bruce
    Memory and Aging Center, University of California, San Francisco, United States.
    Saftig, Paul
    Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
    Kågedal, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    The role of LAMP-2 in AβPP processing and Aβ degradation; implications for Alzheimer’s Disease2015Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Dysfunction in the lysosomal network, i.e., the endosomal, lysosomal and autophagy systems, are implicated in the pathways in Alzheimer’s disease brain pathology. This dysfunction is mirrored in the cerebrospinal fluid where a specific subset of lysosomal network proteins are found at elevated levels, lysosomal associated membrane protein-2 (LAMP-2) being one of the identified lysosomal proteins. Here we report that hippocampus and frontal cortex in Alzheimer’s disease cases have increased mRNA and protein expression of LAMP-2, and thus these brain areas are likely involved in the increased LAMP-2 levels seen in cerebrospinal fluid from Alzheimer’s disease patients. The increased LAMP-2 levels correlated with increased levels of β-amyloid1-42 (Aβ1-42). Oligomeric Aβ1-42 caused an upregulation of intracellular LAMP-2 in neuroblastoma cells, but did not trigger the release of LAMP-2 to the extracellular milieu, indicating that other cell types or mechanisms are responsible for the LAMP-2 release seen in cerebrospinal fluid. Overexpression of LAMP-2 in neuroblastoma cells caused a trend of reduction of secreted Aβ1-42 and changed the processing pattern of the Aβ precursor protein. These results indicate that Aβ1-42 mediated increase of LAMP-2 expression can act as a regulator of Aβ generation and secretion. LAMP-2 overexpression did not change the cellular uptake of extracellularly added Aβ1-42, but caused a delayed clearance of Aβ1-42. Whether the prolonged intracellular localization of Aβ1-42 in LAMP-2 overexpressing cells can change the transmission or degradation of Aβ remains to be investigated.

  • 124.
    Bonfiglio, Ferdinando
    et al.
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden.
    Zheng, Tenghao
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Garcia-Etxebarria, Koldo
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden.
    Hadizadeh, Fatemeh
    Karolinska Inst, Sweden.
    Bujanda, Luis
    Biodonostia Hlth Res Inst, Spain; Univ Basque Country, Spain.
    Bresso, Francesca
    Karolinska Univ Hosp, Sweden.
    Agreus, Lars
    Karolinska Inst, Sweden.
    Andreasson, Anna
    Karolinska Inst, Sweden; Stockholm Univ, Sweden.
    Dlugosz, Aldona
    Karolinska Inst, Sweden.
    Lindberg, Greger
    Karolinska Inst, Sweden.
    Schmidt, Peter T.
    Karolinska Inst, Sweden.
    Karling, Pontus
    Umea Univ, Sweden.
    Ohlsson, Bodil
    Lund Univ, Sweden.
    Simren, Magnus
    Univ Gothenburg, Sweden.
    Walter, Susanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Nardone, Gerardo
    Univ Federico II, 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; G DAnnunzio Univ and Fdn, Italy.
    Portincasa, Piero
    Univ Bari, Italy.
    Bellini, Massimo
    Univ Pisa, Italy.
    Barbara, Giovanni
    Univ Bologna, Italy.
    Latiano, Anna
    Casa Sollievo Sofferenza Hosp, Italy.
    Huebenthal, Matthias
    Christian Albrechts Univ Kiel, Germany.
    Thijs, Vincent
    Florey Inst Neurosci and Mental Hlth, Australia.
    Netea, Mihai G.
    Radboud Univ Nijmegen, Netherlands; Radboud Univ Nijmegen, Netherlands; Univ Bonn, Germany.
    Jonkers, Daisy
    Maastricht Univ, Netherlands.
    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
    Christian Albrechts Univ Kiel, Germany.
    Zhernakova, Alexandra
    Univ Med Ctr Groningen, Netherlands.
    DAmato, Mauro
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden; Karolinska Inst, Sweden; Ikerbasque, Spain.
    Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome2018Inngår i: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 155, nr 1, s. 168-179Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND amp; AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctors diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 x 10(-8)) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P amp;lt; 5.0 x 10(-6)). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 x 10(-10) in UK Biobank) and also [GRAPHICS] associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKB-KAP), which is mutated in patients with familial dysautonomia. CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.

  • 125.
    Borch Petersen, Eline
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Eriksholm Research Centre, Snekkersten, Denmark,.
    Lunner, Thomas
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Eriksholm Research Centre, Snekkersten, Denmark,.
    Vestergaard, Martin
    University of Cambridge, Centre for the Neural Basis of Hearing.
    Sundewall Thorén, Elisabet
    Eriksholm Research Centre, Snekkersten, Denmark,.
    Danish Reading Span data from 283 hearing-aid users, including a sub-group analysis of their relationship to speech-in-noise performance2016Inngår i: International Journal of Audiology, ISSN 1499-2027, E-ISSN 1708-8186, Vol. 55, nr 4, s. 254-261Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: This study provides descriptive statistics of the Danish reading span (RS) test for hearing-impaired adults. The combined effect of hearing loss, RS score, and age on speech-in-noise performance in different spatial settings was evaluated in a subset of participants. Design: Data from published and unpublished studies were re-analysed. Data regarding speech-in-noise performance with co-located or spatially separated sound sources were available for a subset of participants. Study sample: RS scores from 283 hearing-impaired participants were extracted from past studies, and 239 of these participants had completed a speech-in-noise test. Results: RS scores (mean = 41.91%, standard deviation = 11.29%) were related to age (p <0.01), but not pure-tone average (PTA) (p = 0.29). Speech-in-noise performance for co-located sound sources was related to PTA and RS score (both p < 0.01, adjusted R-squared = 0.226). Performance for spatially separated sounds was related to PTA (p < 0.01, adjusted R-squared = 0.10) but not RS score (p = 0.484). We found no differences between the standardized coefficients of the two regression models. Conclusions: The distribution of RS scores indicated a high test difficulty. We found that age should be controlled when RS scores are compared across populations. The experimental setup of the speech-in-noise test may influence the relationship between performance and RS score.

  • 126.
    Borch Petersen, Eline
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Snekkersten, Eriksholm Research Centre.
    Lunner, Thomas
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutet för handikappvetenskap (IHV). Snekkersten, Oticon A/S, Eriksholm Research Centre.
    Vestergaard, Martin
    University of Cambridge, Centre for the Neural Basis of Hearing.
    Sundewall Thorén, Elisabet
    Snekkersten, Eriksholm Research Centre.
    Normative Reading Span Data from 283 Hearing Aid Users and the Relationship to Performance in Speech-in-Noise Test2014Inngår i: International Journal of Audiology, ISSN 1499-2027, E-ISSN 1708-8186Artikkel i tidsskrift (Fagfellevurdert)
  • 127.
    Bostner, Josefine
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Karlsson, Elin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Bivik Eding, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Perez-Tenorio, Gizeh
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Franzén, Hanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Konstantinell, Aelita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Fornander, Tommy
    Karolinska University Hospital, Sweden.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    S6 kinase signaling: tamoxifen response and prognostic indication in two breast cancer cohorts2015Inngår i: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 22, nr 3, s. 331-343Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Detection of signals in the mammalian target of rapamycin (mTOR) and the estrogen receptor (ER) pathways may be a future clinical tool for the prediction of adjuvant treatment response in primary breast cancer. Using immunohistological staining, we investigated the value of the mTOR targets p70-S6 kinase (S6K) 1 and 2 as biomarkers for tamoxifen benefit in two independent clinical trials comparing adjuvant tamoxifen with no tamoxifen or 5 years versus 2 years of tamoxifen treatment. In addition, the prognostic value of the S6Ks was evaluated. We found that S6K1 correlated with proliferation, HER2 status, and cytoplasmic AKT activity, whereas high protein expression levels of S6K2 and phosphorylated (p) S6K were more common in ER-positive, and low-proliferative tumors with pAKT-s473 localized to the nucelus. Nuclear accumulation of S6K1 was indicative of a reduced tamoxifen effect (hazard ratio (HR): 1.07, 95% CI: 0.53-2.81, P=0.84), compared with a significant benefit from tamoxifen treatment in patients without tumor S6K1 nuclear accumulation (HR: 0.42, 95% CI: 0.29-0.62, Pless than0.00001). Also S6K1 and S6K2 activation, indicated by pS6K-t389 expression, was associated with low benefit from tamoxifen (HR: 0.97, 95% CI: 0.50-1.87, P=0.92). In addition, high protein expression of S6K1, independent of localization, predicted worse prognosis in a multivariate analysis, P=0.00041 (cytoplasm), P=0.016 (nucleus). In conclusion, the mTOR-activated kinases S6K1 and S6K2 interfere with proliferation and response to tamoxifen. Monitoring their activity and intracellular localization may provide biomarkers for breast cancer treatment, allowing the identification of a group of patients less likely to benefit from tamoxifen and thus in need of an alternative or additional targeted treatment.

  • 128.
    Boström, A.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping. Linköpings universitet, Medicinska fakulteten.
    Thulin, K.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Norrköping.
    Fredriksson, Mats
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap.
    Reese, D.
    IFK Norrköping, Norrköping, Sweden.
    Rockborn, Peter
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Norrköping. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper.
    Hammar, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Risk factors for acute and overuse sport injuries in Swedish children 11 to 15 years old: What about resistance training with weights?2016Inngår i: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 26, nr 3, s. 317-323Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To determine the 1-year self-reported incidence of overuse and traumatic sport injuries and risk factors for injuries in children participating in a summer sports camp representing seven different sports. 4363 children, 11 to 15 years old participating in a summer camp in seven different sports answered a questionnaire. Injury in this cross-sectional study was defined as a sport-related trauma or overload leading to pain and dysfunction preventing the person from participation in training or competition for at least 1 week. A number of risk factors for injury were investigated such as sex, age, number of hours spent on training in general, and on resistance training with weights. Nearly half [49%, 95% confidence interval (CI) 48–51%] of the participants had been injured as a result of participation in a sport during the preceding year, significantly more boys than girls (53%, 95% CI 50–55% vs 46%, 95% CI 43–48%; P < 0.001). Three factors contributed to increased incidence of sport injuries: age, sex, and resistance training with weights. Time spent on resistance training with weights was significantly associated with sport injuries in a logistic regression analysis. In children age 11 to 15 years, the risk of having a sport-related injury increased with age and occurred more often in boys than in girls. Weight training was the only modifiable risk factor that contributed to a significant increase in the incidence of sport injuries.

  • 129.
    Boström, Inger
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Linköpings universitet, Hälsouniversitetet.
    Landtblom, Anne-Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken. Uppsala University, Sweden.
    Does the changing sex ratio of multiple sclerosis give opportunities for intervention?2015Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 132, s. 42-45Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    In several international studies, an increasing women-to-men (w/m) ratio in patients with multiple sclerosis (MS) has been reported. Such sex ratios have been analysed by year of onset or by year of birth. In a Swedish study, data from the Swedish MS register (SMSreg) were used to analyse the w/m ratio in Sweden. The sex ratio was analysed both by year of birth (8834 patients) and by year of onset (9098 patients). No increased w/m ratio was seen in this study. The age-specific sex ratio did not demonstrate any significant changes. However, a new investigation of the sex ratio in Sweden, based on data from all available data sources (19,510 patients), showed a significantly increased w/m ratio of MS in Sweden from 1.70 to 2.67. Environmental factors such as cigarette smoking, hormonal factors and nutrition are of interest in this context, but the cause of the increasing w/m ratio in MS is yet not possible to explain.

  • 130.
    Bouma, Gerd
    et al.
    Vrije University, Netherlands.
    Münch, Andreas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Microscopic Colitis2015Inngår i: Digestive Diseases, ISSN 0257-2753, E-ISSN 1421-9875, Vol. 33, nr 2, s. 208-214Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Microscopic colitis (MC) is the common denominator for lymphocytic and collagenous colitis (CC). It is now recognized as a relatively frequent cause of diarrhea that equals the prevalence of inflammatory bowel disease. Patients are typically middle-aged women, but disease may occur at every age. Patients with MC report watery, non-bloody diarrhea in the absence of endoscopic and radiologic abnormalities. Lymphocytic colitis is characterized by an increased number of intraepithelial lymphocytes, and CC by a thickened subepithelial collagen band, whereas in both an increased mononuclear infiltration of the lamina propria is found. The pathogenesis of MC is largely unknown, but may relate to autoimmunity, adverse reactions to drugs or (bacterial) toxins, and abnormal collagen metabolism in the case of CC. Budesonide is so far the only drug that has proven efficacy in randomized controlled trials both for the induction and maintenance of remission. Patients who are nonresponsive, dependent or who experience side effects on budesonide may benefit from thiopurine or anti-TNF treatment, but these options are still experimental. The long-term prognosis of MC is good; it does not appear to predispose to malignancies and can in some cases be self-limiting. Further research and randomized clinical trials are required to expand our understanding of the natural course and the pathogenesis of MC.

  • 131.
    Bragde, Hanna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Ryhov Cty Hosp, Sweden.
    Jansson, Ulf
    Ryhov Cty Hosp, Sweden.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Grodzinsky, Ewa
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Division of Forensic Genetics & Forensic Toxicology National Board of Forensic Medicine Linköping, Sweden.
    Söderman, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Ryhov Cty Hosp, Sweden.
    Celiac disease biomarkers identified by transcriptome analysis of small intestinal biopsies2018Inngår i: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 75, nr 23, s. 4385-4401Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Establishing a celiac disease (CD) diagnosis can be difficult, such as when CD-specific antibody levels are just above cutoff or when small intestinal biopsies show low-grade injuries. To investigate the biological pathways involved in CD and select potential biomarkers to aid in CD diagnosis, RNA sequencing of duodenal biopsies from subjects with either confirmed Active CD (n=20) or without any signs of CD (n=20) was performed. Gene enrichment and pathway analysis highlighted contexts, such as immune response, microbial infection, phagocytosis, intestinal barrier function, metabolism, and transportation. Twenty-nine potential CD biomarkers were selected based on differential expression and biological context. The biomarkers were validated by real-time polymerase chain reaction of eight RNA sequencing study subjects, and further investigated using an independent study group (n=43) consisting of subjects not affected by CD, with a clear diagnosis of CD on either a gluten-containing or a gluten-free diet, or with low-grade intestinal injury. Selected biomarkers were able to classify subjects with clear CD/non-CD status, and a subset of the biomarkers (CXCL10, GBP5, IFI27, IFNG, and UBD) showed differential expression in biopsies from subjects with no or low-grade intestinal injury that received a CD diagnosis based on biopsies taken at a later time point. A large number of pathways are involved in CD pathogenesis, and gene expression is affected in CD mucosa already in low-grade intestinal injuries. RNA sequencing of low-grade intestinal injuries might discover pathways and biomarkers involved in early stages of CD pathogenesis.

  • 132.
    Brohede, Sabina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Wingren, Gun
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Hälsouniversitetet.
    Wijma, Barbro
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Wijma, Klaas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Prevalence of body dysmorphic disorder among Swedish women: A population-based study2015Inngår i: Comprehensive Psychiatry, ISSN 0010-440X, E-ISSN 1532-8384, Vol. 58, s. 108-115Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Body dysmorphic disorder (BDD) is characterized by a highly distressing and impairing preoccupation with nonexistent or slight defects in appearance. Patients with BDD present to both psychiatric and non-psychiatric physicians. A few studies have assessed BDD prevalence in representative samples of the general population and have demonstrated that this disorder is relatively common. Our primary objective was to assess the prevalence of BDD in the Swedish population because no data are currently available. Methods: In the current cross-sectional study, 2891 randomly selected Swedish women aged 18-60 years participated. The occurrence of BDD was assessed using the Body Dysmorphic Disorder Questionnaire (BDDQ), which is a validated self-report measure derived from the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for BDD. In addition, symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Results: The prevalence of BDD among Swedish women was 2.1%. The women with BDD had significantly more symptoms of depression and anxiety than the women without BDD. Depression (HADS depression score greater than= 8) and anxiety (HADS anxiety score greater than= 8) were reported by 42% and 72% of the women with BDD, respectively. Conclusions: The results of the present study indicate that BDD is relatively common among Swedish women (2.1%) and that it is associated with significant morbidity.

  • 133.
    Brohede, Sabina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Wyon, Yvonne
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Wingren, Gun
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Wijma, Barbro
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Wijma, Klaas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Body dysmorphic disorder in female Swedish dermatology patients2017Inngår i: International Journal of Dermatology, ISSN 0011-9059, E-ISSN 1365-4632, Vol. 56, nr 12, s. 1387-1394Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BackgroundIndividuals with body dysmorphic disorder (BDD) are highly distressed and impaired owing to perceived defects in their physical appearance that are not noticeable to others. They are frequently concerned about their skin and often present to dermatologists rather than psychiatrists. However, BDD patients attending dermatology clinics may be at risk of not receiving an appropriate assessment and beneficial treatment. The aims of this study were to estimate the BDD prevalence rate among Swedish female dermatology patients and to assess the psychological condition of BDD patients compared to that of other dermatology patients. MethodsThe occurrence of BDD was estimated using the Body Dysmorphic Disorder Questionnaire (BDDQ), a validated self-report measure for BDD. Symptoms of depression and anxiety were measured by the Hospital Anxiety and Depression Scale (HADS), and quality of life was assessed using the Dermatology Life Quality Index (DLQI). ResultsThe prevalence rate of BDD among female Swedish dermatology patients was 4.9% (95% CI 3.2-7.4). Anxiety (HADS A11) was 4-fold more commonly reported by patients with positive BDD screening (48% vs. 11%), and depression (HADS D11) was over 10-fold more common in patients with positive BDD screening (19% vs. 1.8%) (Pamp;lt;0.001). The median DLQI score was 18 in the BDD group, compared to a score of 4 in the non-BDD group (Pamp;lt;0.001). ConclusionsOur results indicate that BDD is fairly common among female Swedish dermatology patients (4.9%) and that BDD patients have high levels of depression and anxiety and severely impaired quality of life.

  • 134.
    Broström, Anders
    et al.
    Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US. Jönköping University, Sweden.
    Fridlund, Bengt
    Jönköping University, Sweden.
    Hedberg, Berith
    Jönköping Academic Qual Improvement and Leadership Heatlh, Sweden.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Ulander, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US.
    Communication between patients with obstructive sleep apnoea syndrome and healthcare personnel during the initial visit to a continuous positive airway pressure clinic2017Inngår i: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 26, nr 3-4, s. 568-577Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims and objectives. To describe facilitators and barriers from a patient perspective in communications between patients with obstructive sleep apnoea syndrome and healthcare personnel during the first meeting when continuous positive airway pressure is initiated. Background. Adherence to continuous positive airway pressure treatment tends to be poor, especially at the initial phase of treatment. Communication between the patient and healthcare personnel has not been studied from the patient perspective, as either a barrier or facilitator for adherence. Methods. A descriptive design using qualitative content analysis was used. Interviews with 25 patients with obstructive sleep apnoea syndrome took place after their initial visit at four continuous positive airway pressure clinics. A deductive analysis based on The 4 Habits Model (i.e. emphasise the importance of investing in the beginning of the consultation, elicit the patients perspective, demonstrate empathy and invest in the end of the consultation) was conducted. Results. Building confidence (i.e. structure building, information transfer, commitment) or hindering confidence (i.e. organisational insufficiency, stress behaviour, interaction deficit) was associated with investing in the beginning. Motivating (i.e. situational insight, knowledge transfer, practical training) or demotivating (i.e. expectations, dominance and power asymmetry, barriers) was associated with eliciting the patients perspective. Building hope (i.e. awareness, sensitivity, demonstration of understanding) or hindering hope (i.e. unprepared, uncommitted, incomprehension) was associated with showing empathy. Agreement (i.e. confirmation, responsibilities, comprehensive information) or disagreement (i.e. structural obscurity, irresponsibility, absent-mindedness) was associated with investing in the end. Conclusions. Understanding of facilitators and barriers, as described by patients, can be used to improve contextual conditions and communication skills among healthcare personnel. Relevance to clinical practice. A patient-centred communication technique should be used in relation to all stages of The 4 Habits Model to facilitate shared decision-making and improve adherence to continuous positive airway pressure treatment.

  • 135.
    Broström, Anders
    et al.
    Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US. Department of Nursing, School of Health and Welfare, Sweden.
    Pakpour, A. H.
    Department of Nursing, School of Health and Welfare, Sweden; Social Determinants of Health Research Center Qazvin, Iran.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Fridlund, B.
    CICE Linneus University, Sweden.
    Ulander, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US.
    Psychometric properties of the Ethos Brief Index (EBI) using factorial structure and Rasch Analysis among patients with obstructive sleep apnea before and after CPAP treatment is initiated.2019Inngår i: Sleep and Breathing, ISSN 1520-9512, E-ISSN 1522-1709, Vol. 23, nr 3, s. 761-768Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Continuous positive airway treatment (CPAP) is the recommended treatment for patients with obstructive sleep apnea (OSA). Outcome measures often focus on clinical and/or self-rated variables related to the medical condition. However, a brief validated instrument focusing on the whole life situation (i.e., ethos) suitable for clinical practice is missing. The aim of this study was to investigate factorial structure, categorical functioning of the response scale, and differential item functioning across sub-populations of the Ethos Brief Index (EBI) among patients with obstructive sleep apnea (OSA) before and after initiation of continuous positive airway pressure (CPAP).

    METHODS: A prospective design, including 193 patients with OSA (68% men, 59.66 years, SD 11.51) from two CPAP clinics, was used. Clinical assessment and overnight respiratory polygraphy were used to diagnose patients. Questionnaires administered before and after 6 months of CPAP treatment included EBI, Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scale, and global perceived health (initial item in SF-36). The validity and reliability of the EBI were investigated using Rasch and confirmatory factor analysis models. Measurement invariance, unidimensionality, and differential item functioning across gender groups, Apnea-Hypopnea Index, and ESS groups were assessed.

    RESULTS: The reliability of the EBI was confirmed using composite reliability and Cronbach's alpha. The results supported unidimensionality of the EBI in confirmatory factor analysis and the Rasch model. No differential item functioning was found. A latent profile analysis yielded two profiles of patients with low (n = 42) and high (n = 151) ethos. Patients in the low ethos group were younger and had higher depression scores, lower perceived health, and higher body mass index.

    CONCLUSIONS: The EBI is a valid tool with robust psychometric properties suitable for use among patients with OSA before and after treatment with CPAP is initiated. Future studies should focus on its predictive validity.

  • 136.
    Broström, Anders
    et al.
    Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US. Jonkoping Univ, Sweden.
    Pakpour, Amir H.
    Jonkoping Univ, Sweden; Qazvin Univ Med Sci, Iran.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Gardner, Benjamin
    Kings Coll London, England.
    Ulander, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US.
    Promoting CPAP adherence in clinical practice: A survey of Swedish and Norwegian CPAP practitioners beliefs and practices2018Inngår i: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 27, nr 6, artikkel-id UNSP e12675Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The benefits of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea are well established, but adherence tends to be low. Research exploring CPAP practitioners beliefs around determinants of CPAP adherence, and the actions they use in clinical practice to promote CPAP adherence is lacking. This study aimed to: (i) develop and validate a questionnaire to assess beliefs and current practices among CPAP practitioners; (ii) explore practitioners beliefs regarding the main determinants of patient adherence, and the actions practitioners most commonly use to promote CPAP adherence; and (iii) explore the associations between perceived determinants and adherence-promotion actions. One-hundred and forty-two CPAP practitioners in Sweden and Norway, representing 93% of all Swedish and 62% of all Norwegian CPAP centres, were surveyed via a questionnaire exploring potential determinants (18 items) and adherence-promotion actions (20 items). Confirmatory factor analysis and second-order structural equational modelling were used to identify patterns of beliefs, and potential associations with adherence-promotion actions. Patients knowledge, motivation and attitudes were perceived by practitioners to be the main determinants of CPAP adherence, and educating patients about effects, management and treatment adjustments were the most common practices. Knowledge was shown to predict educational and informational actions (e.g. education about obstructive sleep apnea and CPAP). Educational and informational actions were associated with medical actions (e.g. treatment adjustment), but knowledge, attitude and support had no association with medical actions. These findings indicate that a wide variety of determinants and actions are considered important, though the only relationship observed between beliefs and actions was found for knowledge and educational and informational actions.

  • 137.
    Broström, Anders
    et al.
    Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US. Department of Nursing, School of Healthand Welfare, Jönköping University, Sweden.
    Pakpour, Amir H.
    School of Healthand Welfare, Jönköping University, Sweden; Social Determinants of Health ResearchCenter, Qazvin University of MedicalSciences, Ira.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Hedberg, Berith
    Jönköping Academy for Health and Welfare, Jönköping University, Sweden; Region Jönköpings län, Futurum, Jönköping,Sweden.
    Ulander, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US.
    Validation of CollaboRATE and SURE - two short questionnaires to measure shared decision making during CPAP initiation.2019Inngår i: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 28, nr 5, artikkel-id UNSP e12808Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adherence to continuous positive airway pressure (CPAP) treatment tends to be low. Brief validated instruments focusing on shared decision making have not been used in a CPAP context. The aim was to investigate factorial structure, categorical functioning of the response scale and differential item functioning across sub-populations of the CollaboRATE and Sure questionnaires among patients with obstructive sleep apnea (OSA) before CPAP treatment is initiated. A prospective design, including 193 objectively diagnosed (polygraphy) OSA patients (68% men, 59.7 years, SD 11.5) from two CPAP clinics was used. Data were collected with the following questionnaires; Sure, CollaboRATE, Attitudes to CPAP Inventory, Epworth sleepiness scale, minimal insomnia symptoms scale, and hospital anxiety and depression scale. Objective CPAP use was collected after 6 months; 49% demonstrated decisional conflict on SURE and 51% scored low levels of shared decision making on CollaboRATE. Unidimensionality was found for both CollaboRATE (one factor explaining 57.4%) and SURE (one factor explaining 53.7%), as well as local independence. Differential item functioning showed both to be invariant across both male and female patients. Internal consistency (Cronbach's alpha 0.83) and composite reliability (0.89) were good. Latent class analyses showed that patients with low decisional conflict and high shared decision making were more adherent to CPAP treatment. CollaboRATE and SURE provided good validity and reliability scores to measure shared decision making and decisional conflict in relation to CPAP treatment. The questionnaires can be used by healthcare personnel as a tool to simplify the assessment of shared decision making.

  • 138.
    Broström, Anders
    et al.
    Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US. Jonkoping Univ, Sweden.
    Pakpour, Amir H.
    Jonkoping Univ, Sweden; Qazvin Univ Med Sci, Iran.
    Ulander, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Development and psychometric evaluation of the Swedish propensity to achieve healthy lifestyle scale in patients with hypertension2018Inngår i: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 27, nr 21-22, s. 4040-4049Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PurposeTo develop and validate a Swedish questionnaire to measure propensity for behaviour change regarding food habits, physical activity and weight reduction in patients with hypertension. DesignCross-sectional design. MethodsA total of 270 consecutive patients with hypertension diagnosed at four primary care centres in Sweden were included. The 6-item Swedish version of the Propensity to Achieve Healthy Lifestyle Scale (PAHLS) was developed to measure propensity for behaviour change regarding food habits, physical activity and weight reduction. The PAHLS (i.e., including three items for preparedness and three items for capacity) was developed by three multiprofessional researchers inspired by the transtheoretical model of behaviour change in collaboration with clinically active nurses. Data were collected by questionnaires on food habits (i.e., the Food Frequency Questionnaire), physical activity (the International Physical Activity Questionnaire), propensity for a healthy lifestyle (the PHLQ), as well as during a clinical examination. Exploratory (EFA) and confirmatory factor analyses (CFA), as well as Rasch analysis, were used. ResultsOf the 270 patients (50% women), 27% scored low levels of physical activity on the International Physical Activity Questionnaire, and 34% of the patients were obese (body mass index 30kg/m(2)). The EFA (explaining 54% of the variance) showed unidimensionality for the PAHLS that was supported by both CFA and Rasch analyses. No floor and 1.9% ceiling effects were found. Multiple group CFA (an extension of structural equationmodelling) showed that the PAHLS operated equivalently across both male and female patients. Internal consistency (Cronbachs alpha 0.83) and composite reliability (0.89) were good. ConclusionThe initial testing of PAHLS provided good validity and reliability scores to measure propensity for behaviour change in patients with hypertension. Relevance to Clinical PracticeThe PAHLS can be used by nurses as a tool to simplify shared decision-making in relation to behavioural changes.

  • 139.
    Broström, Anders
    et al.
    Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US. Department of Nursing, School of Health and Welfare, Jönköping University, Sweden.
    Wahlin, Ake
    Institute of Gerontology, School of Health and Welfare, Jönköping University, Sweden.
    Alehagen, Urban
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Ulander, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US.
    Johansson, Peter
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Sex-Specific Associations Between Self-reported Sleep Duration, Cardiovascular Disease, Hypertension, and Mortality in an Elderly Population.2018Inngår i: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 33, nr 5, s. 422-428Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Both short and long sleep durations have been associated to increased mortality. Knowledge about sex-specific differences among elderly regarding associations between sleep duration, cardiovascular health, and mortality is sparse.

    OBJECTIVE: The aims of this study are to examine the association between self-reported sleep duration and mortality and to investigate whether this association is sex specific and/or moderated by cardiovascular morbidity, and also to explore potential mediators of sleep duration effects on mortality.

    METHODS: A population-based, observational, cross-sectional design with 6-year follow-up with mortality as primary outcome was conducted. Self-rated sleep duration, clinical examinations, echocardiography, and blood samples (N-terminal fragment of proBNP) were collected. A total of 675 persons (50% women; mean age, 78 years) were divided into short sleepers (≤6 hours; n = 231), normal sleepers (7-8 hours; n = 338), and long sleepers (≥9 hours; n = 61). Data were subjected to principal component analyses. Cardiovascular disease (CVD) and hypertension factors were extracted and used as moderators and as mediators in the regression analyses.

    RESULTS: During follow-up, 55 short sleepers (24%), 68 normal sleepers (20%), and 21 long sleepers (34%) died. Mediator analyses showed that long sleep was associated with mortality in men (hazard ratio [HR], 1.8; P = .049), independently of CVD and hypertension. In men with short sleep, CVD acted as a moderator of the association with mortality (HR, 4.1; P = .025). However, when using N-terminal fragment of proBNP, this effect became nonsignificant (HR, 3.1; P = .06). In woman, a trend to moderation involving the hypertension factor and short sleep was found (HR, 4.6; P = .09).

    CONCLUSION: Short and long sleep duration may be seen as risk markers, particularly among older men with cardiovascular morbidity.

  • 140.
    Broström, Anders
    et al.
    Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US. Jonkoping Univ, Sweden.
    Wahlin, Ake
    Jonkoping Univ, Sweden.
    Alehagen, Urban
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Ulander, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurofysiologiska kliniken US.
    Johansson, Peter
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Sex-specific associations between self-reported sleep duration, depression, anxiety, fatigue and daytime sleepiness in an older community-dwelling population2018Inngår i: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 32, nr 1, s. 290-298Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PurposeThe purpose of this study was to explore whether associations between self-reported sleep duration, depressive symptoms, anxiety, fatigue and daytime sleepiness differed in older community-dwelling men and women. DesignCross-sectional. MethodsA community-dwelling sample of 675 older men and women (mean age 77.7years, SD 3.8years) was used. All participants underwent a clinical examination by a cardiologist. Validated questionnaires were used to investigate sleep duration, depressive symptoms, anxiety, fatigue and daytime sleepiness. Subjects were divided into short sleepers (6hours), n=231; normal sleepers (7-8hours), n=338; and long sleepers (9hours), n=61. ancovas were used to explore sex-specific effects. ResultsDepressive symptoms were associated with short sleep in men, but not in women. Fatigue was associated with both short and long sleep duration in men. No sex-specific associations of sleep duration with daytime sleepiness or anxiety were found. ConclusionNurses investigating sleep duration and its correlates, or effects, in clinical practice need to take sex into account, as some associations may be sex specific. Depressive symptoms and fatigue can be used as indicators to identify older men with sleep complaints.

  • 141.
    Bruhn, H.
    et al.
    Cty Hosp Ryhov, Sweden.
    Strandeus, M.
    Cty Hosp Ryhov, Sweden.
    Milos, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Lind, Jonas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Cty Hosp Ryhov, Sweden.
    Improved survival of Swedish glioblastoma patients treated according to Stupp2018Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, nr 4, s. 332-337Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    ObjectivesThe median survival in glioblastoma (GBM) patients used to be less than 1year. Surgical removal of the tumor with subsequent concomitant radiation/temozolomide (the Stupp regimen) has been shown to prolong survival. The Stupp protocol was implemented in the county of Jonkoping in 2006. The purpose of this study was to examine if the Stupp treatment has prolonged overall survival, in an unselected patient cohort with histologically verified GBM. Material and MethodThis study includes all patients from the county of Jonkoping, with a diagnosis of GBM from January 2001 to December 2012. Patients were divided into 2 cohorts, 2001-2005 and 2006-2012, that is before and after implementation of the Stupp regimen. By reviewing the medical case notes, the dates of the histological diagnosis and of death were identified. The median and mean overall survival and Kaplan-Meier survival analysis were calculated and compared between the 2 cohorts. ResultsThe mean survival was 110days longer in the cohort treated according to the Stupp regimen. Four patients in the 2006-2012 cohort and 1 patient in the 2001-2005 cohort are still alive. When comparing survival in patients with radical surgery vs biopsy, those that underwent radical surgery survived longer. The significance was slightly greater in the 2001-2005 cohort (mean 163 vs 344days, Pamp;lt;.001) than in the 2006-2012 cohort (mean 220 vs 397days, P=.02). ConclusionSurvival significantly improved after the implementation of the Stupp regimen in the study region of Sweden.

  • 142.
    Brundin, L.
    et al.
    Van Andel Research Institute, MI 49503 USA.
    Sellgren, C. M.
    Karolinska Institute, Sweden; Broad Institute MIT and Harvard, MA USA; Massachusetts Gen Hospital, MA USA.
    Lim, C. K.
    Macquarie University, Australia.
    Grit, J.
    Van Andel Research Institute, MI 49503 USA.
    Palsson, E.
    Gothenburg University, Sweden.
    Landen, M.
    Gothenburg University, Sweden.
    Samuelsson, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Närsjukvården i centrala Östergötland, Psykiatriska kliniken. Karolinska Institute, Sweden.
    Lundgren, Kristoffer
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Brundin, P.
    Van Andel Research Institute, MI 49503 USA.
    Fuchs, D.
    Medical University of Innsbruck, Austria.
    Postolache, T. T.
    University of Maryland, MD 21201 USA; Rocky Mt MIRECC, CO USA.
    Traskman-Bendz, L.
    Lund University, Sweden.
    Guillemin, G. J.
    Macquarie University, Australia; NHMRC Centre Research Excellence Suicide Prevent CRESP, Australia.
    Erhardt, S.
    Karolinska Institute, Sweden.
    An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation2016Inngår i: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 6, nr e865Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-D-aspartate receptor agonist, are increased. The enzyme amino-beta-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Asberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (Pamp;lt;0.001) and blood (P=0.001 and Pamp;lt;0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.

  • 143.
    Bruno, Valentina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Tor Vergata Univ Hosp, Italy.
    Svensson Arvelund, Judit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Rubér, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Berg, Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Piccione, Emilio
    Tor Vergata Univ Hosp, Italy.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Effects of low molecular weight heparin on the polarization and cytokine profile of macrophages and T helper cells in vitro2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 4166Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Low molecular weight heparin (LMWH) is widely used in recurrent miscarriage treatment. The anticoagulant effects are established, while immunological effects are not fully known. Our aim was to assess LMWH effects on activation and polarization of central regulatory immune cells from healthy women, and on placenta tissues from women undergoing elective abortions. Isolated blood monocytes and T helper (Th) cells under different activation and polarizing conditions were cultured with or without LMWH. Flow cytometry showed that LMWH exposure induced increased expression of HLA-DR and CD206 in macrophages. This phenotype was associated with increased secretion of Th17-associated CCL20, and decreased secretion of CCL2 (M2-associated) and CCL22 (Th2), as measured by multiplex bead array. In accordance, LMWH exposure to Th cells reduced the proportion of CD25highFoxp3+ regulatory T-cells, intensified IFN-gamma secretion and showed a tendency to increase the lymphoblast proportions. Collectively, a mainly pro-inflammatory effect was noted on two essential tolerance-promoting cells. Although the biological significancies of these in vitro findings are uncertain and need to be confirmed in vivo, they suggest the possibility that immunological effects of LMWH may be beneficial mainly at an earlier gestational age to provide an appropriate implantation process in women with recurrent miscarriage.

  • 144.
    Brännström, Jonas K
    et al.
    Linköpings universitet, Filosofiska fakulteten. Dept of clinical science, Section of Logopedics, Phoiatrics and audiology, Lund University, Sweden.
    Öberg, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Öron- näsa- och halskliniken US.
    Ingo, Elisabeth
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten.
    Månsson, Kristoffer N. T.
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Psykologi. Linköpings universitet, Filosofiska fakulteten.
    Andersson, Gerhard
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Psykologi. Linköpings universitet, Filosofiska fakulteten. Karolinska Institute, Sweden.
    Lunner, Thomas
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutet för handikappvetenskap (IHV). Eriksholm Research Centre, Oticon A/S, Denmark.
    Laplante-Lévesque, Ariane
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten. Eriksholm Research Centre, Oticon A/S, Denmark.
    The Process of Developing an Internet-Based Support System for Audiologists and First-Time Hearing Aid Clients2015Inngår i: American Journal of Audiology, ISSN 1059-0889, E-ISSN 1558-9137, Vol. 24, nr 3, s. 320-324Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In audiologic practice, complementary information sources and access to the clinician between appointments improve information retention and facilitate adjustment behaviors. An Internet-based support system is a novel way to support information sharing and clinician access. Purpose: This research forum article describes the process of developing an Internet-based support system for audiologists and their first-time hearing aid clients. Method: The iterative development process, including revisions by 4 research audiologists and 4 clinical audiologists, is described. The final system is exemplified. Conclusion: An Internet-based support system was successfully developed for audiologic practice.

  • 145.
    Brännström, Jonas
    et al.
    Clinical Sciences Lund, Sweden.
    Öberg, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Östergötlands Läns Landsting, Sinnescentrum, Öron- näsa- och halskliniken US. Linköpings universitet, Medicinska fakulteten.
    Ingo, Elisabeth
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten.
    Månsson, Kristoffer N T
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Psykologi. Linköpings universitet, Filosofiska fakulteten.
    Andersson, Gerhard
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Psykologi. Linköpings universitet, Filosofiska fakulteten. Karolinska Institutet, Department of Clinical Neuroscience, Sweden.
    Lunner, Thomas
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutet för handikappvetenskap (IHV). Snekkersten, Oticon A/S, Eriksholm Research Centre, Denmark.
    Laplante-Lévesque, Ariane
    Linköpings universitet, Institutionen för beteendevetenskap och lärande, Handikappvetenskap. Linköpings universitet, Filosofiska fakulteten. Snekkersten, Oticon A/S, Eriksholm Research Centre, Denmark.
    The initial evaluation of an internet-based support system for audiologists and first-time hearing aid clientsThe process of developing an internet-based support system for audiologists and first-time hearing aid clients2016Inngår i: Internet Interventions, ISSN 2214-7829, Vol. 4, nr 1, s. 82-91Artikkel i tidsskrift (Fagfellevurdert)
  • 146.
    Buznyk, Oleksiy
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. National Academic Medical Science Ukraine, Ukraine.
    Pasyechnikova, Nataliya
    National Academic Medical Science Ukraine, Ukraine.
    Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Iakymenko, Stanislav
    National Academic Medical Science Ukraine, Ukraine.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Bioengineered Corneas Grafted as Alternatives to Human Donor Corneas in Three High-Risk Patients2015Inngår i: Clinical and Translational Science, ISSN 1752-8054, E-ISSN 1752-8062, Vol. 8, nr 5, s. 558-562Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Corneas with severe pathologies have a high risk of rejection when conventionally grafted with human donor tissues. In this early observational study, we grafted bioengineered corneal implants made from recombinant human collagen and synthetic phosphorylcholine polymer into three patients for whom donor cornea transplantation carried a high risk of transplant failure. These patients suffered from corneal ulcers and recurrent erosions preoperatively. The implants provided relief from pain and discomfort, restored corneal integrity by promoting endogenous regeneration of corneal tissues, and improved vision in two of three patients. Such implants could in the future be alternatives to donor corneas for high-risk patients, and therefore, merits further testing in a clinical trial.

  • 147.
    Bäckryd, Emmanuel
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum.
    Ghafouri, Bijar
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum. Region Östergötland, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Carlsson, Anders K
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum.
    Olausson, Patrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum.
    Gerdle, Björn
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum.
    Multivariate proteomic analysis of the cerebrospinal fluid of patients with peripheral neuropathic pain and healthy controls: a hypothesis-generating pilot study2015Inngår i: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 8, s. 321-333Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pain medicine lacks objective biomarkers to guide diagnosis and treatment. Combining two-dimensional gel proteomics with multivariate data analysis by projection, we exploratively analyzed the cerebrospinal fluid of eleven patients with severe peripheral neuropathic pain due to trauma and/or surgery refractory to conventional treatment and eleven healthy controls. Using orthogonal partial least squares discriminant analysis, we identified a panel of 36 proteins highly discriminating between the two groups. Due to a possible confounding effect of age, a new model with age as outcome variable was computed for patients (n=11), and four out of 36 protein spots were excluded due to a probable influence of age. Of the 32 remaining proteins, the following seven had the highest discriminatory power between the two groups: an isoform of angiotensinogen (upregulated in patients), two isoforms of alpha-1-antitrypsin (downregulated in patients), three isoforms of haptoglobin (upregulated in patients), and one isoform of pigment epithelium-derived factor (downregulated in patients). It has recently been hypothesized that the renin–angiotensin system may play a role in the pathophysiology of neuropathic pain, and a clinical trial of an angiotensin II receptor antagonist was recently published. It is noteworthy that when searching for neuropathic pain biomarkers with a purely explorative methodology, it was indeed a renin–angiotensin system protein that had the highest discriminatory power between patients and controls in the present study. The results from this hypothesis-generating pilot study have to be confirmed in larger, hypothesis-driven studies with age-matched controls, but the present study illustrates the fruitfulness of combining proteomics with multivariate data analysis in hypothesis-generating pain biomarker studies in humans.

  • 148.
    Bäckström, Denise
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken VIN.
    Larsen, Robert
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken US.
    Steinvall, Ingrid
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Gedeborg, Rolf
    Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden..
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken US.
    Deaths caused by injury among people of working age (18-64) are decreasing, while those among older people (64+) are increasing2018Inngår i: European Journal of Trauma and Emergency Surgery, ISSN 1863-9933, E-ISSN 1863-9941, Vol. 44, nr 4, s. 589-596Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Injury is an important cause of death in all age groups worldwide, and contributes to many losses of human and economic resources. Currently, we know a few data about mortality from injury, particularly among the working population. The aim of the present study was to examine death from injury over a period of 14 years (1999-2012) using the Swedish Cause of Death Registry (CDR) and the National Patient Registry, which have complete national coverage.

    METHOD: CDR was used to identify injury-related deaths among adults (18 years or over) during the years 1999-2012. ICD-10 diagnoses from V01 to X39 were included. The significance of changes over time was analyzed by linear regression.

    RESULTS: The incidence of prehospital death decreased significantly (coefficient -0.22, r (2) = 0.30; p = 0.041) during the study period, while that of deaths in hospital increased significantly (coefficient 0.20, r (2) = 0.75; p < 0.001). Mortality/100,000 person-years in the working age group (18-64 years) decreased significantly (coefficient -0.40, r (2) = 0.37; p = 0.020), mainly as a result of decrease in traffic-related deaths (coefficient -0.34, r (2) = 0.85; p < 0.001). The incidence of deaths from injury among elderly (65 years and older) patients increased because of the increase in falls (coefficient 1.71, r (2) = 0.84; p < 0.001) and poisoning (coefficient 0.13, r (2) = 0.69; p < 0.001).

    CONCLUSION: The epidemiology of injury in Sweden has changed during recent years in that mortality from injury has declined in the working age group and increased among those people 64 years old and over.

  • 149.
    Caban, Janusz
    et al.
    Vastervik Hospital, Sweden.
    Fermergard, Robert
    Vastervik Hospital, Sweden.
    Abtahi, Jahan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Käkkliniken US.
    Long-term evaluation of osteotome sinus floor elevation and simultaneous placement of implants without bone grafts: 10-Year radiographic and clinical follow-up2017Inngår i: Clinical Implant Dentistry and Related Research, ISSN 1523-0899, E-ISSN 1708-8208, Vol. 19, nr 6, s. 1023-1033Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BackgroundInsertion of an implant in the edentulous posterior maxilla is a challenging procedure because of poor bone quality and increased pneumatization of the maxillary sinus after tooth extraction. To increase the amount of bone, several surgical bone grafting techniques have been used?with considerable morbidity for patients. Osteotome sinus floor elevation (OSFE) is a less invasive technique. The clinical and radiographic outcome of 53 implants placed with this technique without bone graft has been reported previously. PurposeHere we report the clinical and radiographic findings after 10 years of implant load bearing. Material and methodsIn a retrospective study, 34 Astra implants in 25 patients were subjected to 10-year follow-up radiologically and clinically. Each patient received 1 or 2 conical Astra implants. The level of the marginal bone and the height of the residual peri-implant alveolar bone (RPAB) for each implant were measured from digital intra-oral radiographs. ResultsTwo implants in edentulous patients were lost at the 1-year follow-up, and 1 more at the 3-year examination. There was no loss between 3-year and 10-year follow-up. At 10-year follow-up 36 implants were included. Implants used in single-tooth replacements and in partially edentulous cases had a 100% survival rate. The mean marginal bone loss was 0.60.8 mm. The bone height at the time of implant insertion ranged from 1.8 to 6.9 mm, with a mean value of 4.3 +/- 1.0 mm. At 10-year follow-up the mean gain in bone at the implant sites for all implants was 2.6 +/- 1.2 mm. ConclusionsThe OSFE technique is a reliable method for rehabilitation of patients with atrophied posterior maxilla. However, the success of this method is associated with the amount of the residual bone. In the present study, this surgical approach without bone graft showed reliable long-term results with Astra implants.

  • 150.
    Capitanio, Arrigo
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Dina, R. E.
    Imperial Coll NHS Trust, England.
    Treanor, Darren
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi. Leeds Teaching Hosp NHS Trust, England.
    Digital cytology: A short review of technical and methodological approaches and applications2018Inngår i: Cytopathology, ISSN 0956-5507, E-ISSN 1365-2303, Vol. 29, nr 4, s. 317-325Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The recent years have been characterised by a rapid development of whole slide imaging (WSI) especially in its applications to histology. The application of WSI technology to cytology is less common because of technological problems related to the three-dimensional nature of cytology preparations (which requires capturing of z-stack information, with an increase in file size and usability issues in viewing cytological preparations). The aim of this study is to provide a review of the literature on the use of digital cytology and provide an overview of cytological applications of WSI in current practice as well as identifying areas for future development.

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