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  • 1.
    Aaseth, Jan
    et al.
    Innlandet Hosp Trust, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Alehagen, Urban
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Coenzyme Q(10) supplementation - In ageing and disease2021In: Mechanisms of Ageing and Development, ISSN 0047-6374, E-ISSN 1872-6216, Vol. 197, article id 111521Article in journal (Refereed)
    Abstract [en]

    Coenzyme Q(10) (CoQ(10)) is an essential component of the mitochondrial electron transport chain. It is also an antioxidant in cellular membranes and lipoproteins. All cells produce CoQ(10) by a specialized cytoplasmatic-mitochondrial pathway. CoQ(10) deficiency can result from genetic failure or ageing. Some drugs including statins, widely used by inter alia elderly, may inhibit endogenous CoQ(10) synthesis. There are also chronic diseases with lower levels of CoQ(10) in tissues and organs. High doses of CoQ(10) may increase both circulating and intracellular levels, but there are conflicting results regarding bioavailability. Here, we review the current knowledge of CoQ(10) biosynthesis and primary and acquired CoQ(10) deficiency, and results from clinical trials based on CoQ(10) supplementation. There are indications that supplementation positively affects mitochondrial deficiency syndrome and some of the symptoms of ageing. Cardiovascular disease and inflammation appear to be alleviated by the antioxidant effect of CoQ(10). There is a need for further studies and well-designed clinical trials, with CoQ(10) in a formulation of proven bioavailability, involving a greater number of participants undergoing longer treatments in order to assess the benefits of CoQ(10) treatment in neurodegenerative disorders, as well as in metabolic syndrome and its complications.

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  • 2.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Bélteky, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Brain size is reduced by selectionfor tameness in Red Junglefowl–correlated effects in vital organs2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 3306Article in journal (Refereed)
    Abstract [en]

    During domestication animals have undergone changes in size of brain and other vital organs. We hypothesize that this could be a correlated effect to increased tameness. Red Junglefowl (ancestors of domestic chickens) were selected for divergent levels of fear of humans for five generations. The parental (P0) and the fifth selected generation (S5) were culled when 48–54 weeks old and the brains were weighed before being divided into telencephalon, cerebellum, mid brain and optic lobes. Each single brain part as well as the liver, spleen, heart and testicles were also weighed. Brains of S5 birds with high fear scores (S5 high) were heavier both in absolute terms and when corrected for body weight. The relative weight of telencephalon (% of brain weight) was significantly higher in S5 high and relative weight of cerebellum was lower. Heart, liver, testes and spleen were all relatively heavier (% of body weight) in S5 high. Hence, selection for tameness has changed the size of the brain and other vital organs in this population and may have driven the domesticated phenotype as a correlated response.

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  • 3.
    Ahlström, Christer
    et al.
    Swedish National Rd and Transport Research Institute VTI, S-58195 Linkoping, Sweden.
    Jansson, Sabina
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Anund, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine. Swedish National Rd and Transport Research Institute VTI, S-58195 Linkoping, Sweden.
    Local changes in the wake electroencephalogram precedes lane departures2017In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 26, no 6, p. 816-819Article in journal (Refereed)
    Abstract [en]

    The objective of this exploratory study is to investigate if lane departures are associated with local sleep, measured via source-localized electroencephalography (EEG) theta power in the 5-9 Hz frequency range. Thirty participants drove in an advanced driving simulator, resulting in 135 lane departures at high levels of self-reported sleepiness. These lane departures were compared to matching non-departures at the same sleepiness level within the same individual. There was no correspondence between lane departures and global theta activity. However, at the local level an increased risk for lane departures was associated with increased theta content in brain regions related to motor function.

  • 4.
    Alehagen, Urban
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Shamoun, Levar
    Jonkoping Cty, Sweden; Uppsala Univ, Sweden.
    Wagsater, Dick
    Uppsala Univ, Sweden.
    Genetic variance and plasma concentration of CD93 is associated with cardiovascular mortality: Results from a 6.7-year follow-up of a healthy community-living elderly population2020In: Molecular Medicine Reports, ISSN 1791-2997, E-ISSN 1791-3004, Vol. 22, no 6, p. 4629-4636Article in journal (Refereed)
    Abstract [en]

    Inflammation is one of the fundamental processes in numerous diseases. Cluster of differentiation (CD) 93, a glycoprotein, has been reported to be associated with a number of these diseases. There are reports indicating that a high plasma level of CD93 is associated with adverse events in ischaemic heart disease. Additionally, there are reports indicating different cardiovascular risks between different single nucleotide polymorphisms (SNPs) of CD93. Therefore, the present study aimed to determine whether the plasma concentration of CD93 and polymorphism of rs2749812 in CD93 were associated with clinical conditions and mortality in an elderly population. In 470 healthy elderly community-living individuals a novel clinical examination involving echocardiography and blood sampling was performed. The population was followed for 6.7 years. Plasma levels of CD93 and SNP analyses of rs2749812 of CD93 using PCR methodology were used. During the follow-up period, 106 (22.6%) all-cause and 61 (13.0%) cardiovascular deaths were registered. Those with the highest plasma concentration had markedly higher all-cause mortality. Evaluating the A/A, A/G and G/G genotypes, the G/G group exhibited significantly higher cardiovascular mortality (P=0.026), and an almost two-fold increased risk in a multivariate Cox regression model compared with the A/G genotype. Evaluation of subgroups with respect to sex, diabetes and hypertension revealed markedly increased cardiovascular risk in the G/G genotype in all subgroups. All results persisted in the multiple models used. In the present study, the glycoprotein CD93 was demonstrated to have prognostic cardiovascular information, with increased risk for those with a high plasma concentration. Furthermore, the G/G genotype of rs2749812 of CD93 has a significantly higher cardiovascular risk, as demonstrated here, and could therefore be regarded as a possible cardiovascular risk biomarker that might in the future be used to offer optimised cardiovascular patient handling. However, this was a small study, and more research is required.

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  • 5.
    Alexanderson, Mikaela
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences.
    Borg, Hanna
    Linköping University, Department of Health, Medicine and Caring Sciences.
    Adolphson, Vilma
    Linköping University, Department of Health, Medicine and Caring Sciences.
    Patienters perspektiv på behov av information i samband med behandling inom neurologisk rehabilitering: -        En kvalitativ intervjustudie2022Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Sammanfattning 

    Bakgrund: Neurologisk rehabilitering innefattar ofta livslånga kontinuerliga insatser. För att få ett önskvärt resultat av rehabilitering krävs en god följsamhet från patienten. Forskning har visat att god följsamhet kräver att patienten får information om sin behandling samt känner sig delaktig. Det saknas dock forskning om vilken information och vilken typ av informationsform patienten efterfrågar inom neurologisk rehabilitering. 

    Syfte: Syftet med studien var att beskriva patientens perspektiv på behovet av information vid rehabilitering av neurologiska funktionsnedsättningar, och vad de upplever betydelsefullt för att uppnå följsamhet och delaktighet.

    Metod: En kvalitativ intervjustudie med semistrukturerade frågor (Januari 2022). Data analyserades genom kvalitativ innehållsanalys med induktiv ansats. Inklusive pilotintervju genomfördes 10 intervjuer med patienter som deltagit i neurologisk rehabilitering.

    Resultat: Analys av materialet resulterade i 4 kategorier, Erhållen information, Önskad information, Delaktighet, Fysioterapeuten bemötande och Kommunikation. Varje kategori kompletterades även med underrubriker. 

    Konklusion:  I resultatet framkom det att patienter har behov av en mångsidig information både avseende informationens innehåll och förmedling. Det framkom även att fysioterapeutens bemötande och en god kommunikation var viktiga faktorer för informationsförmedlingen och därmed betydelsefullt för att uppnå delaktighet och följsamhet. 

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  • 6.
    Ali, Tahir
    et al.
    Univ Calgary, Canada.
    Klein, Antonia N.
    Univ Calgary, Canada.
    McDonald, Keegan
    Univ Calgary, Canada.
    Johansson, Lovisa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Mukherjee, Priyanka Ganguli
    Univ Calgary, Canada.
    Hallbeck, Martin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Doh-ura, Katsumi
    Tohoku Univ, Japan.
    Schatzl, Hermann M.
    Univ Calgary, Canada.
    Gilch, Sabine
    Univ Calgary, Canada.
    Cellulose ether treatment inhibits amyloid beta aggregation, neuroinflammation and cognitive deficits in transgenic mouse model of Alzheimers disease2023In: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 20, no 1, article id 177Article in journal (Refereed)
    Abstract [en]

    Alzheimers disease (AD) is an incurable, progressive and devastating neurodegenerative disease. Pathogenesis of AD is associated with the aggregation and accumulation of amyloid beta (A & beta;), a major neurotoxic mediator that triggers neuroinflammation and memory impairment. Recently, we found that cellulose ether compounds (CEs) have beneficial effects against prion diseases by inhibiting protein misfolding and replication of prions, which share their replication mechanism with A & beta;. CEs are FDA-approved safe additives in foods and pharmaceuticals. Herein, for the first time we determined the therapeutic effects of the representative CE (TC-5RW) in AD using in vitro and in vivo models. Our in vitro studies showed that TC-5RW inhibits A & beta; aggregation, as well as neurotoxicity and immunoreactivity in A & beta;-exposed human and murine neuroblastoma cells. In in vivo studies, for the first time we observed that single and weekly TC-5RW administration, respectively, improved memory functions of transgenic 5XFAD mouse model of AD. We further demonstrate that TC-5RW treatment of 5XFAD mice significantly inhibited A & beta; oligomer and plaque burden and its associated neuroinflammation via regulating astrogliosis, microgliosis and proinflammatory mediator glial maturation factor beta (GMF & beta;). Additionally, we determined that TC-5RW reduced lipopolysaccharide-induced activated gliosis and GMF & beta; in vitro. In conclusion, our results demonstrate that CEs have therapeutic effects against A & beta; pathologies and cognitive impairments, and direct, potent anti-inflammatory activity to rescue neuroinflammation. Therefore, these FDA-approved compounds are effective candidates for developing therapeutics for AD and related neurodegenerative diseases associated with protein misfolding.

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  • 7.
    Alimoradi, Zainab
    et al.
    Qazvin Univ Med Sci, Iran.
    Jafari, Elahe
    Qazvin Univ Med Sci, Iran.
    Broström, Anders
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Jonkoping Univ, Sweden.
    Ohayon, Maurice M.
    Stanford Univ, CA 94305 USA.
    Lin, Chung-Ying
    Natl Cheng Kung Univ, Taiwan; Natl Cheng Kung Univ, Taiwan; Natl Cheng Kung Univ, Taiwan; Natl Cheng Kung Univ, Taiwan.
    Griffiths, Mark D.
    Nottingham Trent Univ, England.
    Blom, Kerstin
    Karolinska Inst, Sweden; Huddinge Hosp, Sweden.
    Jernelöv, Susanna
    Karolinska Inst, Sweden; Huddinge Hosp, Sweden; Karolinska Inst, Sweden.
    Kaldo, Viktor
    Karolinska Inst, Sweden; Huddinge Hosp, Sweden; Linnaeus Univ, Sweden.
    Pakpour, Amir H.
    Jonkoping Univ, Sweden.
    Effects of cognitive behavioral therapy for insomnia (CBT-I) on quality of life: A systematic review and meta-analysis2022In: Sleep Medicine Reviews, ISSN 1087-0792, E-ISSN 1532-2955, Vol. 64, article id 101646Article, review/survey (Refereed)
    Abstract [en]

    The effects of cognitive behavioral therapy for insomnia (CBT-I) have consistently been shown to improve insomnia symptoms and other health-related outcomes, but the effects on QoL have been inconsistent. Many factors including the type CBT-I delivery and type of instrument used to assess QoL make the topic complex. The present systematic review and meta-analysis synthesized the evidence of CBT-I efficacy on QoL outcomes across different populations, delivery modes, and methodological aspects. Following the guidelines on preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a literature search was conducted through PubMed, Web of Science, Scopus, and PsycINFO using keywords from relevant MeSH terms based on PICOS (Participants, Intervention, Comparison, Outcome and Study) criteria. Clinical trials investigating the effect of CBT-I as an intervention on QoL with any kind of control group were eligible if they reported mean scores and variation of QoL. Meta-analysis using a random-effect model was conducted to calculate the standardized mean differences (SMDs) in a set including all identified studies, as well as in three sub-sets: face-to-face CBT-I using randomized controlled trials (RCTs), online CBT-I using RCTs, and one-group pre- and post-treatment design. A total of 24 studies comprising 1977 participants (808 in an intervention group) from 12 countries were eligible for meta-analysis. The overall pooled estimate of SMD of QoL when all 24 studies were included was 0.47 (95% CI: 0.22; 0.72; I-2 = 84.5%; tau(2) = 0.31; p < 0.001). The overall pooled estimate of SMD of QoL was 0.46 (95% CI: 0.01-0.90; I-2 = 87.5%; tau(2) = 0.48, p < 0.001) for intervention groups with face-to-face CBT-I compared to controls; 0.47 (95% CI: 0.02-0.92; I-2 = 88.3%; tau(2) = 0.36; p = 0.04) for intervention groups with digital CBT-I compared to controls, and 0.46 (95% CI: 0.12-0.80; I-2 = 52.9%; tau(2) = 0.07; p = 0.08) for one-group pre- and post-comparison using CBT-I intervention compared to baseline. Moreover, effects of CBT-I on QoL were different across populations (pooled SMD = 0.59 for patients with insomnia; 0.29 for patients with insomnia comorbid with another major disorder; and 0.48 for other conditions) and types of QoL instruments (pooled SMD = 0.36 for disease-specific QoL instrument not on insomnia, 0.43 for generic QoL instrument, and 0.67 for a single-QoL-item instrument). The probability of publication bias was ruled out in overall and design specific sub-group analysis based on funnel plot and Eggers test. In conclusion, this meta-analysis confirmed a moderate, overall effect of CBT-I in improving QoL. However, due to small power and heterogeneity, future studies are needed to better explore the impact of moderating factors such as mode of delivery and type of QoL measure for assessment used.

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  • 8.
    Alimoradi, Zainab
    et al.
    Qazvin Univ Med Sci, Iran.
    Lin, Chung-Ying
    Hong Kong Polytech Univ, Peoples R China.
    Broström, Anders
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Jonkoping Univ, Sweden.
    Bulow, Pia H.
    Jonkoping Univ, Sweden.
    Bajalan, Zahra
    Qazvin Univ Med Sci, Iran.
    Griffiths, Mark D.
    Nottingham Trent Univ, England.
    Ohayon, Maurice M.
    Stanford Univ, CA 94305 USA.
    Pakpour, Amir H.
    Qazvin Univ Med Sci, Iran; Jonkoping Univ, Sweden.
    Internet addiction and sleep problems: A systematic review and meta-analysis2019In: Sleep Medicine Reviews, ISSN 1087-0792, E-ISSN 1532-2955, Vol. 47, p. 51-61Article, review/survey (Refereed)
    Abstract [en]

    The pathological use of the internet - conceptualized as internet addiction - might be crucial in initiating and increasing sleep disturbances in the community. While inconsistent evidence is reported regarding the association of internet addiction and sleep disturbances, the severity of this association remains unclear. This systematic review and meta-analysis were conducted to increase our understanding of the relationship between internet addiction and sleep disturbances. A systematic review was conducted through Scopus, PubMed Central, ProQuest, ISI Web of Knowledge, and EMBASE using keywords related to internet addiction and sleep problems. Observational studies (cohort, case-control or cross-sectional studies) focusing on association between internet addiction and sleep disturbances including sleep problems and sleep duration were selected. A meta-analysis using random-effect model was conducted to calculate the odds ratio (OR) for experiencing sleep problems and standardized mean differences (SMDs) for sleep duration. Eligible studies (N = 23) included 35,684 participants. The overall pooled OR of having sleep problems if addicted to the internet was 2.20 (95% CI: 1.77-2.74). Additionally, the overall pooled SMDs for sleep duration for the IA group compared to normal internet users was -0.24 (95% CI: -0.38, -0.10). Results of the meta-analysis revealed a significant OR for sleep problems and a significant reduced sleep duration among individuals addicted to the internet. (C) 2019 Elsevier Ltd. All rights reserved.

  • 9.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Zsigmond, Peter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Influence of Virchow-Robin spaces on the electric field distribution in subthalamic nucleus deep brain stimulation2021In: Clinical neurology and neurosurgery, ISSN 0303-8467, E-ISSN 1872-6968, Vol. 204, article id 106596Article in journal (Refereed)
    Abstract [en]

    Patient MRI from DBS implantations in the subthalamic nucleus (STN) were reviewed and it was found that around 10% had Virchow-Robin spaces (VRS). Patient-specific models were developed to evaluate changes in the electric field (EF) around DBS leads. The patients (n = 7) were implanted bilaterally either with the standard voltage-controlled lead 3389 or with the directional current-controlled lead 6180. The EF distribution was evaluated by comparing simulations using patient-specific models with homogeneous models without VRS. The EF, depicted with an isocontour of 0.2 V/mm, showed a deformation in the presence of the VRS around the DBS lead. For patient-specific models, the radial extension of the EF isocontours was enlarged regardless of the operating mode or the DBS lead used. The location of the VRS in relation to the active contact and the stimulation amplitude, determined the changes in the shape and extension of the EF. It is concluded that it is important to take the patients? brain anatomy into account as the high conductivity in VRS will alter the electric field if close to the DBS lead. This can be a cause of unexpected side effects.

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  • 10.
    Alonso, Fabiola
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Virchow-Robin spaces in subthalamic nucleus Deep Brain Stimulation - Influence in the electric field2019Conference paper (Other academic)
  • 11.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology. Karolinska Inst, Sweden.
    The latest developments with internet-based psychological treatments for depression2024In: Expert Review of Neurotherapeutics, ISSN 1473-7175, E-ISSN 1744-8360, Vol. 24, no 2, p. 171-176Article, review/survey (Refereed)
    Abstract [en]

    IntroductionInternet-based psychological treatments for depression have been around for more than 20 years. There has been a continuous line of research with new research questions being asked and studies conducted.Areas coveredIn this paper, the author reviews studies with a focus on papers published from 2020 and onwards based on a Medline and Scopus search. Internet-based cognitive behavior therapy (ICBT) programs have been developed and tested for adolescents, older adults, immigrant groups and to handle a societal crisis (e.g. COVID-19). ICBT works in regular clinical settings and long-term effects can be obtained. Studies on different treatment orientations and approaches such as acceptance commitment therapy, unified protocol, and tailored treatments have been conducted. Effects on quality-of-life measures, knowledge acquisition and ecological momentary assessment as a research tool have been reported. Factorial design trials and individual patient data meta-analysis are increasingly used in association with internet intervention research. Finally, prediction studies and recent advances in artificial intelligence are mentioned.Expert opinionInternet-delivered treatments are effective, in particular if therapist guidance is provided. More target groups have been covered but there are many remaining challenges including how new tools like artificial intelligence will be used when treating depression.

  • 12.
    Andersson, Gerhard
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Rozental, Alexander
    Stockholm University, Sweden; UCL, England.
    Shafran, Roz
    UCL, England.
    Carlbring, Per
    Stockholm University, Sweden; UCL, England.
    Long-term effects of internet-supported cognitive behaviour therapy2018In: Expert Review of Neurotherapeutics, ISSN 1473-7175, E-ISSN 1744-8360, Vol. 18, no 1, p. 21-28Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Internet-supported and therapist-guided cognitive behaviour therapy (ICBT) is effective for a range of problems in the short run, but less is known about the long-term effects with follow-ups of two years or longer.Areas covered: This paper reviews studies in which the long-term effects of guided ICBT were investigated. Following literature searches in PubMed and other sources meta-analytic statistics were calculated for 14 studies involving a total of 902 participants, and an average follow-up period of three years. Studies were from Sweden (n=11) or the Netherlands (n=3). Long-term outcome studies were found for panic disorder, social anxiety disorder, generalized anxiety disorder, depression, mixed anxiety and depression, obsessive-compulsive disorder, pathological gambling, stress and chronic fatigue. The duration of the treatments was usually short (8-15weeks). The pre-to follow-up effect size was Hedges g=1.52, but with a significant heterogeneity. The average symptom improvement across studies was 50%. Treatment seeking in the follow-up period was not documented and few studies mentioned negative effects.Expert commentary: While effects may be overestimated, it is likely that therapist-supported ICBT can have enduring effects. Long-term follow-up data should be collected for more conditions and new technologies like smartphone-delivered treatments.

  • 13.
    Andreasson, Mattias
    et al.
    Acad Specialist Ctr, Sweden; Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Lagali, Neil
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Sensory Organs and Communication. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Badian, Reza A.
    Oslo Univ Hosp, Norway.
    Utheim, Tor Paaske
    Oslo Univ Hosp, Norway.
    Scarpa, Fabio
    Univ Padua, Italy.
    Colonna, Alessia
    Univ Padua, Italy.
    Allgeier, Stephan
    Karlsruhe Inst Technol KIT, Germany.
    Bartschat, Andreas
    Karlsruhe Inst Technol KIT, Germany.
    Koehler, Bernd
    Karlsruhe Inst Technol KIT, Germany.
    Mikut, Ralf
    Karlsruhe Inst Technol KIT, Germany.
    Reichert, Klaus-Martin
    Karlsruhe Inst Technol KIT, Germany.
    Solders, Goran
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Samuelsson, Kristin
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Zetterberg, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; UCL Inst Neurol, England; UK Dementia Res Inst, England.
    Blennow, Kaj
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Svenningsson, Per
    Acad Specialist Ctr, Sweden; Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Parkinson's disease with restless legs syndrome - an in vivo corneal confocal microscopy study2021In: NPJ Parkinson's disease, ISSN 2373-8057, Vol. 7, no 1, article id 4Article in journal (Refereed)
    Abstract [en]

    Small fiber neuropathy (SFN) has been suggested as a trigger of restless legs syndrome (RLS). An increased prevalence of peripheral neuropathy has been demonstrated in Parkinsons disease (PD). We aimed to investigate, in a cross-sectional manner, whether SFN is overrepresented in PD patients with concurrent RLS relative to PD patients without RLS, using in vivo corneal confocal microscopy (IVCCM) and quantitative sensory testing (QST) as part of small fiber assessment. Study participants comprised of age- and sex-matched PD patients with (n = 21) and without RLS (n = 21), and controls (n = 13). Diagnosis of RLS was consolidated with the sensory suggested immobilization test. Assessments included nerve conduction studies (NCS), Utah Early Neuropathy Scale (UENS), QST, and IVCCM, with automated determination of corneal nerve fiber length (CNFL) and branch density (CNBD) from wide-area mosaics of the subbasal nerve plexus. Plasma neurofilament light (p-NfL) was determined as a measure of axonal degeneration. No significant differences were found between groups when comparing CNFL (p = 0.81), CNBD (p = 0.92), NCS (p = 0.82), and QST (minimum p = 0.54). UENS scores, however, differed significantly (p = 0.001), with post-hoc pairwise testing revealing higher scores in both PD groups relative to controls (p = 0.018 and p = 0.001). Analysis of all PD patients (n = 42) revealed a correlation between the duration of l-dopa therapy and CNBD (rho = -0.36, p = 0.022), and p-NfL correlated with UENS (rho = 0.35, p = 0.026) and NCS (rho = -0.51, p = 0.001). Small and large fiber neuropathy do not appear to be associated with RLS in PD. Whether peripheral small and/or large fiber pathology associates with central neurodegeneration in PD merits further longitudinal studies.

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  • 14.
    Andrén, Kerstin
    et al.
    Umeå universitet, Klinisk neurovetenskap, Sweden.
    Wikkelsö, Carsten
    Hydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden.
    Sundström, Nina
    Umeå universitet, Radiofysik, Sweden.
    Agerskov, Simon
    Hydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Th.
    Israelsson, Hanna
    Umeå universitet, Klinisk neurovetenskap, Sweden.
    Laurell, Katarina
    Umeå universitet, Klinisk neurovetenskap, Sweden.
    Hellström, Per
    nical Neuroscience, Institute of Neuroscience and Physiology, Th.
    Tullberg, Mats
    nical Neuroscience, Institute of Neuroscience and Physiology, Th.
    Long-term effects of complications and vascular comorbidity in idiopathic normal pressure hydrocephalus: a quality registry study2018In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 265, no 1, p. 178-186Article in journal (Refereed)
    Abstract [en]

    Background: There is little knowledge about the factors influencing the long-term outcome after surgery for idiopathic normal pressure hydrocephalus (iNPH).

    Objective: To evaluate the effects of reoperation due to complications and of vascular comorbidity (hypertension, diabetes, stroke and heart disease) on the outcome in iNPH patients, 2–6 years after shunt surgery.

    Methods: We included 979 patients from the Swedish Hydrocephalus Quality Registry (SHQR), operated on for iNPH during 2004–2011. The patients were followed yearly by mailed questionnaires, including a self-assessed modified Rankin Scale (smRS) and a subjective comparison between their present and their preoperative health condition. The replies were grouped according to the length of follow-up after surgery. Data on clinical evaluations, vascular comorbidity, and reoperations were extracted from the SHQR.

    Results: On the smRS, 40% (38–41) of the patients were improved 2–6 years after surgery and around 60% reported their general health condition to be better than preoperatively. Reoperation did not influence the outcome after 2–6 years. The presence of vascular comorbidity had no negative impact on the outcome after 2–6 years, assessed as improvement on the smRS or subjective improvement of the health condition, except after 6 years when patients with hypertension and a history of stroke showed a less favorable development on the smRS.

    Conclusion: This registry-based study shows no negative impact of complications and only minor effects of vascular comorbidity on the long-term outcome in iNPH.

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  • 15.
    Andrén, Kerstin
    et al.
    University of Gothenburg, Sweden.
    Wikkelsø, Carsten
    University of Gothenburg, Sweden.
    Sundström, Nina
    Umeå universitet, Radiofysik, Sweden.
    Israelsson, Hanna
    Umeå universitet, Klinisk neurovetenskap, Sweden.
    Agerskov, Simon
    University of Gothenburg, Sweden.
    Laurell, Katarina
    Umeå universitet, Klinisk neurovetenskap, Sweden.
    Hellström, Per
    University of Gothenburg, Sweden.
    Tullberg, Mats
    University of Gothenburg, Sweden.
    Survival in treated idiopathic normal pressure hydrocephalus2020In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 267, no 3, p. 640-648Article in journal (Refereed)
    Abstract [en]

    Objective: To describe survival and causes of death in 979 treated iNPH patients from the Swedish Hydrocephalus Quality Registry (SHQR), and to examine the influence of comorbidities, symptom severity and postoperative outcome.

    Methods: All 979 patients operated for iNPH 2004–2011 and registered in the SHQR were included. A matched control group of 4890 persons from the general population was selected by Statistics Sweden. Data from the Swedish Cause of Death Registry was obtained for patients and controls.

    Results: At a median 5.9 (IQR 4.2–8.1) year follow-up, 37% of the iNPH patients and 23% of the controls had died. Mortality was increased in iNPH patients by a hazard ratio of 1.81, 95% CI 1.61–2.04, p < 0.001. More pronounced symptoms in the preoperative ordinal gait scale and the Mini-mental State Examination were the most important independent predictors of mortality along with the prevalence of heart disease. Patients who improved in both the gait scale and in the modified Rankin Scale postoperatively (n = 144) had a similar survival as the general population (p = 0.391). Deaths due to cerebrovascular disease or dementia were more common in iNPH patients, while more controls died because of neoplasms or disorders of the circulatory system.

    Conclusions: Mortality in operated iNPH patients is 1.8 times increased compared to the general population, a lower figure than previously reported. The survival of iNPH patients who improve in gait and functional independence is similar to that of the general population, indicating that shunt surgery for iNPH, besides improving symptoms and signs, can normalize survival.

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  • 16.
    Arfvidsson, John
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Wilhelminen Hospital, Austria.
    Ahlin, Fredrik
    Linköping University, Faculty of Medicine and Health Sciences. Wilhelminen Hospital, Austria.
    Vargas, Kris G.
    Wilhelminen Hospital, Austria.
    Thaler, Barbara
    Medical University of Vienna, Austria.
    Wojta, Johann
    Medical University of Vienna, Austria.
    Huber, Kurt
    Wilhelminen Hospital, Austria; Ludwig Boltzmann Cluster Cardiovasc Research, Austria; Sigmund Freud Private University, Austria.
    Monocyte subsets in myocardial infarction: A review2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 231, p. 47-53Article, review/survey (Refereed)
    Abstract [en]

    Background: Monocytes form an important part of the human innate immune system by taking part in inflammatory reactions. With time, monocytes have gained interest in the role they may play during the event of myocardial infarction (MI). The current paradigm suggests that monocytes consist of three subdivisions which differ in phenotypic and dynamic patterns after an MI. In the inflammation that ensues, the different subsets have been shown to have an impact on reparative processes and patient recovery. Methods results: We searched Medline and Embase until April 5, 2016, for observational studies or clinical trials regarding monocyte functions and dynamics in MI. Apart from studies in humans, extensive work has been done in mice in an effort to understand the complex nature of monocyte dynamics. Animal models might add useful information on mapping these processes. Conclusion: The question still remains whether animal data can, to a certain degree, be extrapolated to monocyte functions during human MI. This review aims to summarize current available evidence on both mice and men with particular focus on the understanding of monocyte subsets dynamics and effects in human MI. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 17.
    Attia, Zachi I.
    et al.
    Mayo Clin, MN USA.
    Kapa, Suraj
    Mayo Clin, MN USA.
    Dugan, Jennifer
    Mayo Clin, MN USA.
    Pereira, Naveen
    Mayo Clin, MN USA.
    Noseworthy, Peter A.
    Mayo Clin, MN USA.
    Jimenez, Francisco Lopez
    Mayo Clin, MN USA.
    Cruz, Jessica
    Mayo Clin, MN USA.
    Carter, Rickey E.
    Mayo Clin, FL 32224 USA.
    DeSimone, Daniel C.
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Signorino, John
    Mayo Clin, MN USA.
    Halamka, John
    Mayo Clin, MN USA.
    Gari, Nikhita R. Chennaiah
    Mayo Clin, MN USA.
    Madathala, Raja Sekhar
    Mayo Clin, MN USA.
    Platonov, Pyotr G.
    Lund Univ, Sweden.
    Gul, Fahad
    Einstein Healthcare Network, PA USA.
    Janssens, Stefan P.
    Katholieke Univ Leuven, Belgium.
    Narayan, Sanjiv
    Stanford Univ, CA 94305 USA; Stanford Univ, CA 94305 USA.
    Upadhyay, Gaurav A.
    Univ Chicago, IL 60637 USA.
    Alenghat, Francis J.
    Univ Chicago, IL 60637 USA.
    Lahiri, Marc K.
    Henry Ford Hosp, MI 48202 USA.
    Dujardin, Karl
    AZ Delta Hosp, Belgium.
    Hermel, Melody
    Scripps Hlth, CA USA; Scripps Clin, CA 92037 USA.
    Dominic, Paari
    Louisiana State Univ, LA 71105 USA.
    Turk-Adawi, Karam
    Qatar Univ, Qatar.
    Asaad, Nidal
    Hamad Med Corp, Qatar.
    Svensson, Anneli
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Cardiology in Linköping.
    Fernandez-Aviles, Francisco
    Univ Complutense, Spain.
    Esakof, Darryl D.
    Lahey Hosp & Med Ctr, MA USA.
    Bartunek, Jozef
    Onze Lieve Vrouw Hosp, Belgium.
    Noheria, Amit
    Univ Kansas Hlth Syst, KS USA.
    Sridhar, Arun R.
    Univ Washington, WA 98195 USA.
    Lanza, Gaetano A.
    Univ Cattolica Sacro Cuore, Italy.
    Cohoon, Kevin
    Froedtert & Med Coll Wisconsin, WI USA.
    Padmanabhan, Deepak
    Sri Jayadeva Inst Cardiovasc Sci & Res, India.
    Gutierrez, Jose Alberto Pardo
    Clin Santa Maria, Chile.
    Sinagra, Gianfranco
    Cardiovasc Dept Ospedali Riuniti, Italy; Univ Trieste, Italy.
    Merlo, Marco
    Cardiovasc Dept Ospedali Riuniti, Italy; Univ Trieste, Italy.
    Zagari, Domenico
    Humanitas Mater Domini Clin Inst, Italy.
    Escenaro, Brenda D. Rodriguez
    Medica Sur, Mexico.
    Pahlajani, Dev B.
    Breach Candy Hosp Trust, India.
    Loncar, Goran
    Inst Cardiovasc Dis Dedinje ICVDD, Serbia.
    Vukomanovic, Vladan
    Univ Hosp Ctr Dr Dragisa Misov Dedinje, Serbia.
    Jensen, Henrik K.
    Aarhus Univ Hosp, Denmark.
    Farkouh, Michael E.
    Univ Toronto, Canada.
    Luescher, Thomas F.
    Royal Brompton & Harefield Hosp, England.
    Ping, Carolyn Lam Su
    Natl Heart Ctr, Singapore; Duke Natl Univ Singapore, Singapore.
    Peters, Nicholas S.
    Imperial Coll London, England.
    Friedman, Paul A.
    Mayo Clin, MN USA.
    Rapid Exclusion of COVID Infection With the Artificial Intelligence Electrocardiogram2021In: Mayo Clinic proceedings, ISSN 0025-6196, E-ISSN 1942-5546, Vol. 96, no 8, p. 2081-2094Article in journal (Refereed)
    Abstract [en]

    Objective: To rapidly exclude severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using artificial intelligence applied to the electrocardiogram (ECG). Methods: A global, volunteer consortium from 4 continents identified patients with ECGs obtained around the time of polymerase chain reaction-confirmed COVID-19 diagnosis and age- and sex-matched controls from the same sites. Clinical characteristics, polymerase chain reaction results, and raw electrocardiographic data were collected. A convolutional neural network was trained using 26,153 ECGs (33.2% COVID positive), validated with 3826 ECGs (33.3% positive), and tested on 7870 ECGs not included in other sets (32.7% positive). Performance under different prevalence values was tested by adding control ECGs from a single high-volume site. Results: The area under the curve for detection of acute COVID-19 infection in the test group was 0.767 (95% CI, 0.756 to 0.778; sensitivity, 98%; specificity, 10%; positive predictive value, 37%; negative predictive value, 91%). To more accurately reflect a real-world population, 50,905 normal controls were added to adjust the COVID prevalence to approximately 5% (2657/58,555), resulting in an area under the curve of 0.780 (95% CI, 0.771 to 0.790) with a specificity of 12.1% and a negative predictive value of 99.2%. Conclusion: Infection with SARS-CoV-2 results in electrocardiographic changes that permit the artificial intelligence-enhanced ECG to be used as a rapid screening test with a high negative predictive value (99.2%). This may permit the development of electrocardiography-based tools to rapidly screen individuals for pandemic control. (C) 2021 Mayo Foundation Medical Education and Research

  • 18.
    Augutis, M
    et al.
    FoU, Sundsvall Hospital, Sundsvall, Sweden.
    Malker, H
    Mid Sweden Research and Development Center, Vasternorrland County Council, Sundsvall, Sweden.
    Levi, Richard
    Karolinska Institute and Frosunda Center, Stockholm, Sweden.
    Pediatric spinal cord injury in Sweden; how to identify a cohort of rare events.2003In: Spinal Cord, ISSN 1362-4393, E-ISSN 1476-5624, Vol. 41, no 6, p. 337-346Article in journal (Refereed)
    Abstract [en]

    STUDY DESIGN:: Register study enhanced and verified by medical records and personal interviews and examinations. SETTINGS:: Sweden. OBJECTIVES:: To define a method of identifying a study population of rare events. To point out the relative importance of every step, an example is given of identifying persons who sustained traumatic spinal cord injury (SCI) in childhood. METHODS:: Cases were identified in seven steps that all needed to be fulfilled, from definition of selection criteria through combination of several data sources, to the use of several verification methods. RESULTS:: Initial screening by registers identified 384 possible cases, which however were found by subsequent analysis to include a large number of incorrect cases. At completion of all analytic steps, 35 living cases could be fully verified and 14 deceased cases could be partially verified. CONCLUSIONS:: Registers offer a practical initial source for study population identification. The screening of International Classification of Diseases codes defining SCI only included less than 30% of true SCIs. Subsequently, further refinement and quality control is necessary in order to ensure validity. Such further verification is time-consuming, but nevertheless necessary in order to verify a true cohort.Spinal Cord (2003) 41, 337-346. doi:andlt;highlightandgt;10.1038andlt;/highlightandgt;/andlt;highlightandgt;sj.scandlt;/highlightandgt;.andlt;highlightandgt;3101456andlt;/highlightandgt; [ABSTRACT FROM AUTHOR]

  • 19.
    Augutis, Marika
    et al.
    Landstinget Västernorrland, Sweden.
    Ertzgaard, Per
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine.
    Levi, Richard
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Rehabilitation Medicine.
    Sverige bör centralisera den pediatriska ryggmärgsskadevården2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 35-36Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 20.
    Augutis, Marika
    et al.
    Karolinska Institute, Sweden.
    Levi, Richard
    Karolinska Institute, Sweden.
    Asplund, Kenneth
    Mid-Sweden University, Sundsvall, Sweden.
    Berg-Kelly, Kristina
    Karolinska Institute, Sweden.
    Psychosocial aspects of traumatic spinal cord injury with onset during adolescence: a qualitative study.2007In: Journal of Spinal Cord Medicine (JSCM), ISSN 1079-0268, E-ISSN 2045-7723, Vol. 30 Suppl 1, p. S55-S64Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVE: Spinal cord injury (SCI) occurring during adolescence poses additional challenges because of the concurrent age

  • 21.
    Awad, A
    et al.
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Levi, Richard
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Lindgren, L
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Hultling, C
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Westling, G
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Nyberg, L
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Eriksson, J
    Umeå Center for Functional Brain Imaging (UFBI), Umeå, Sweden..
    Preserved somatosensory conduction in a patient with complete cervical spinal cord injury.2015In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 47, no 5, p. 426-431Article in journal (Refereed)
    Abstract [en]

    Objective: Neurophysiological investigation has shown that patients with clinically complete spinal cord injury can have residual motor sparing ("motor discomplete"). In the current study somatosensory conduction was assessed in a patient with clinically complete spinal cord injury and a novel methodology for assessing such preservation is described, in this case indicating "sensory discomplete" spinal cord injury.andlt;br /andgt;Methods: Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) was used to examine the somatosensory system in a healthy subject and in a subject with a clinically complete cervical spinal cord injury, by applying tactile stimulation above and below the level of spinal cord injury, with and without visual feedback.andlt;br /andgt;Results: In the participant with spinal cord injury, somatosensory stimulation below the neurological level of the lesion gave rise to BOLD signal changes in the corresponding areas of the somatosensory cortex. Visual feedback of the stimulation strongly modulated the somatosensory BOLD signal, implying that cortico-cortical rather than spino-cortical connections can drive activity in the somatosensory cortex. Critically, BOLD signal change was also evident when the visual feedback of the stimulation was removed, thus demonstrating sensory discomplete spinal cord injury.andlt;br /andgt;Conclusion: Given the existence of sensory discomplete spinal cord injury, preserved but hitherto undetected somatosensory conduction might contribute to the unexplained variability related to, for example, the propensity to develop decubitus ulcers and neuropathic pain among patients with clinically complete spinal cord injury.

  • 22.
    Bajramaj, Ermira
    et al.
    Malmo Univ, Sweden.
    Haggman-Henrikson, Birgitta
    Malmo Univ, Sweden; Umea Univ, Sweden.
    Dawson, Andreas
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Public Dental Health Care, Center for Oral Rehabilitation Norrköping. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    The Effect of Microdialysis Catheter Insertion on Glutamate and Serotonin Levels in Masseter Muscle in Patients with Myofascial Temporomandibular Disorders and Healthy Controls2019In: Diagnostics (Basel), ISSN 2075-4418, Vol. 9, no 1, article id 14Article in journal (Refereed)
    Abstract [en]

    Myofascial temporomandibular disorders (TMD) are the most common cause of chronic pain in the orofacial region. Microdialysis has been used to study metabolic changes in the human masseter muscle. The insertion of the microdialysis probe causes acute tissue trauma that could affect the metabolic milieu and thereby influence the results when comparing healthy subjects to those with TMD. This study aimed to investigate the levels of serotonin and glutamate during the acute tissue trauma period in healthy subjects and in patients with TMD. Microdialysis was carried out in 15 patients with TMD and 15 controls, and samples were collected every 20 min during a period of 140 min. No significant alterations of serotonin or glutamate were observed over the 2 h period for the healthy subjects. For the TMD group, a significant decrease in serotonin was observed over time (p amp;lt; 0.001), followed by a significant increase between 120 and 140 min (p amp;lt; 0.001). For glutamate, a significant reduction was observed at 40 min compared to baseline. The results showed that there was a spontaneous increase of serotonin 2 h after the insertion of the catheter in patients with TMD. In conclusion, the results showed that there are differences in the masseter muscle levels of serotonin and glutamate during acute nociception in patients with myofascial TMD compared to healthy subjects.

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  • 23.
    Banefelt, J.
    et al.
    Quantify Research, Sweden.
    Hallberg, S.
    Quantify Research, Sweden.
    Fox, K. M.
    Strateg Healthcare Solut LLC, MD USA.
    Mesterton, J.
    Quantify Research, Sweden; Karolinska Institute, Sweden.
    Paoli, C. J.
    Amgen Inc, CA 91320 USA.
    Johansson, G.
    Uppsala University, Sweden.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Sobocki, P.
    Karolinska Institute, Sweden; IMS Heatlh, Sweden.
    Gandra, S. R.
    Amgen Inc, CA 91320 USA.
    Work productivity loss and indirect costs associated with new cardiovascular events in high-risk patients with hyperlipidemia: estimates from population-based register data in Sweden2016In: European Journal of Health Economics, ISSN 1618-7598, E-ISSN 1618-7601, Vol. 17, no 9, p. 1117-1124Article in journal (Refereed)
    Abstract [en]

    Objectives To estimate productivity loss and associated indirect costs in high-risk patients treated for hyperlipidemia who experience cardiovascular (CV) events. Methods Retrospective population-based cohort study conducted using Swedish medical records linked to national registers. Patients were included based on prescriptions of lipid-lowering therapy between 1 January 2006 and 31 December 2011 and followed until 31 December 2012 for identification of CV events and estimation of work productivity loss (sick leave and disability pension) and indirect costs. Patients were stratified into two cohorts based on CV risk level: history of major cardiovascular disease (CVD) and coronary heart disease (CHD) risk equivalent. Propensity score matching was applied to compare patients with new events (cases) to patients without new events (controls). The incremental effect of CV events was estimated using a difference-in-differences design, comparing productivity loss among cases and controls during the year before and the year after the cases event. Results The incremental effect on indirect costs was largest in the CHD risk equivalent cohort (n = 2946) at (sic)3119 (P value amp;lt;0.01). The corresponding figure in the major CVD history cohort (n = 4508) was (sic)2210 (P value amp;lt;0.01). There was substantial variation in productivity loss depending on the type of event. Transient ischemic attack and revascularization had no significant effect on indirect costs. Myocardial infarction ((sic)), unstable angina ((sic)) and, most notably, ischemic stroke ((sic)) yielded substantial incremental cost estimates (P values amp;lt;0.01). Conclusions Indirect costs related to work productivity losses of CV events are substantial in Swedish high-risk patients treated for hyperlipidemia and vary considerably by type of event.

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  • 24.
    Bartfai, Aniko
    et al.
    Karolinska Inst, Sweden; Danderyd Hosp, Sweden.
    Elg, Mattias
    Linköping University, Department of Management and Engineering, Logistics & Quality Management. Linköping University, Faculty of Science & Engineering.
    Schult, Marie-Louise
    Karolinska Inst, Sweden; Danderyd Hosp, Sweden.
    Markovic, Gabriela
    Karolinska Inst, Sweden; Danderyd Hosp, Sweden.
    Predicting Outcome for Early Attention Training After Acquired Brain Injury2022In: Frontiers in Human Neuroscience, E-ISSN 1662-5161, Vol. 16, article id 767276Article in journal (Refereed)
    Abstract [en]

    BackgroundThe training of impaired attention after acquired brain injury is central for successful reintegration in daily living, social, and working life. Using statistical process control, we found different improvement trajectories following attention training in a group of relatively homogeneous patients early after acquired brain injury (ABI). ObjectiveTo examine the contribution of pre-injury factors and clinical characteristics to differences in outcome after early attention training. Materials and MethodsData collected in a clinical trial comparing systematic attention training (APT) with activity-based attention training (ABAT) early after brain injury were reanalyzed. ResultsStroke patients (p = 0.004) with unifocal (p = 0.002) and right hemisphere lesions (p = 0.045), and those with higher mental flexibility (TMT 4) (p = 0.048) benefitted most from APT training. Cognitive reserve (p = 0.030) was associated with CHANGE and APT as the sole pre-injury factor. For TBI patients, there was no statistical difference between the two treatments. ConclusionOur study identifies indiscernible factors predicting improvement after early attention training. APT is beneficial for patients with right-hemispheric stroke in an early recovery phase. Knowledge of prognostic factors, including the level of attention deficit, diagnosis, and injury characteristics, is vital to maximizing the efficiency of resource allocation and the effectiveness of rehabilitative interventions to enhance outcomes following stroke and TBI.

  • 25.
    Bednarska, Olga
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Peripheral and Central Mechanisms in Irritable Bowel Syndrome: in search of links2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a chronic visceral pain disorder with female predominance, characterized by recurrent abdominal pain and disturbed bowel habits in the absence of an identifiable organic cause. This prevalent and debilitating disease, which accounts for a substantial economic and individual burden, lacks exact diagnostic tools and effective treatment, since its pathophysiology remains uncertain. The bidirectional and multilayered brain-gut axis is a well-established disease model, however, the interactions between central and peripheral mechanisms along the brain-gut axis remain incompletely understood. One of the welldescribed triggering factors, yet accounting for only a fraction of IBS prevalence, is bacterial gastroenteritis that affects mucosal barrier function. Altered gut microbiota composition as well as disturbed intestinal mucosal barrier function and its neuroimmune regulation have been reported in IBS, however, the impact of live bacteria, neither commensal nor pathogenic, on intestinal barrier has not been studied yet. Furthermore, abnormal central processing of visceral sensations and psychological factors such as maladaptive coping have previously been suggested as centrally-mediated pathophysiological mechanisms of importance in IBS. Brain imaging studies have demonstrated an imbalance in descending pain modulatory networks and alterations in brain regions associated with interoceptive awareness and pain processing and modulation, particularly in anterior insula (aINS), although biochemical changes putatively underlying these central alterations remain poorly understood. Most importantly, however, possible associations between these documented changes on central and peripheral levels, which may as complex interactions contribute to disease onset and chronification of symptoms, are widely unknown.

    This thesis aimed to investigate the peripheral and central mechanisms in women with IBS compared to female healthy controls (HC) and to explore possible mutual associations between these mechanisms.

    In Paper I, we studied paracellular permeability and passage of live bacteria, both commensal and pathogenic through colonic biopsies mounted in Ussing chambers. We explored the regulation of the mucosal barrier function by mast cells and the neuropeptide vasoactive intestinal polypeptide (VIP) as well as a correlation between mucosal permeability and gastrointestinal and psychological symptoms. We observed increased paracellular permeability and the passage of commensal and pathogenic live bacteria in patients with IBS compared with HC, which was diminished by blocking the VIP receptors as well as after stabilizing mast cells in both groups. Moreover, higher paracellular permeability was associated with less somatic and psychological symptoms in patients.

    In Paper II, we aimed to determine the association between colonic mucosa paracellular permeability and structural and resting state functional brain connectivity. We demonstrated different patterns of associations between mucosa permeability and functional and structural brain connectivity in IBS patients compared to HC. Specifically, lower paracellular permeability in IBS, similar to the levels detected in HC, was associated with more severe IBS symptoms and increased functional and structural connectivity between intrinsic brain resting state network and descending pain modulation brain regions. Our findings further suggested that this association between mucosa permeability and functional brain connectivity was mainly mediated by coping strategies.

    In Paper III, we investigated putative alterations in excitatory and inhibitory neurotransmission of aINS, as the brain’s key node of the salience network crucially involved in cognitive control, in IBS patients relative to HC and addressed possible connections with both symptoms and psychological factors. We found decreased concentrations of the excitatory neurotransmitter Glx in bilateral aINS in IBS patients compared to HC, while inhibitory neurotransmitter GABA+ levels were comparable. Further, we demonstrated hemisphere-specific associations between abdominal pain, coping and aINS excitatory neurotransmitter concentration.

    In conclusion, this thesis broadens the knowledge on peripheral and central mechanisms in IBS and presents novel findings that bring together the ends of brain-gut axis. Our results depict association between mucosal permeability, IBS symptoms and functional and structural connectivity engaging brain regions involved in emotion and pain modulation as well as underlying neurotransmitter alterations.

    List of papers
    1. Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome
    Open this publication in new window or tab >>Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome
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    2017 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 153, no 4, p. 948-+Article in journal (Refereed) Published
    Abstract [en]

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

    Place, publisher, year, edition, pages
    W B SAUNDERS CO-ELSEVIER INC, 2017
    Keywords
    Intestinal Permeability; Bacteria; Ketotifen; Inflammation
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:liu:diva-142158 (URN)10.1053/j.gastro.2017.06.051 (DOI)000411835200024 ()28711627 (PubMedID)
    Note

    Funding Agencies|Stiftelsen Halsofonden, County Council of Ostergotland; Diarrheal Disease Research Centre, Linkoping University; AFA research foundation; Bengt-Ihre fonden, County Council of Ostergotland; Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Subdireccion General de Investigacion Sanitaria, Ministerio de Economia y Competitividad [FI12/00254]; NIH [R01 DK048351]; [CP10/00502]; [PI13/00935]; [MV16/00028]; [CIBEREHD CB06/04/0021]

    Available from: 2017-10-24 Created: 2017-10-24 Last updated: 2024-01-10
    2. Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome
    Open this publication in new window or tab >>Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome
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    2019 (English)In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 21, article id 101602Article in journal (Refereed) Published
    Abstract [en]

    Changes in brain-gut interactions have been implicated in the pathophysiology of chronic visceral pain in irritable bowel syndrome (IBS). Different mechanisms of sensitization of visceral afferent pathways may contribute to the chronic visceral pain reports and associated brain changes that characterize IBS. They include increased gut permeability and gut associated immune system activation, and an imbalance in descending pain inhibitory and facilitatory mechanisms. In order to study the involvement of these mechanisms, correlations between gut epithelial permeability and live bacterial passage, and structural and functional brain connectivity were measured in women with moderate-to-severe IBS and healthy women. The relationships between gut permeability and functional and anatomical connectivity were significantly altered in IBS compared with the healthy women. IBS participants with lower epithelial permeability reported increased IBS symptoms, which was associated with increased functional and structural connectivity in endogenous pain facilitation regions. The findings suggest that relationships between gut permeability and the brain are significantly altered in IBS and suggest the existence of IBS subtypes based on these interactions.

    Place, publisher, year, edition, pages
    Elsevier, 2019
    Keywords
    Irritable bowel syndrome; Gut epithelial permeability; Resting state fMRI; Brain-gut interactions; Default mode network; Coping skills
    National Category
    Neurosciences
    Identifiers
    urn:nbn:se:liu:diva-155612 (URN)10.1016/j.nicl.2018.11.012 (DOI)000460337700015 ()30472166 (PubMedID)2-s2.0-85056893948 (Scopus ID)
    Note

    Funding Agencies|AFA FOrskning [AFA140417]; County Council of Ostergotland [SLS-693541, SLS-503411]; Region Ostergotland [LIO-700871, LIO-606201, LIO-536281, LIO-514271]; Deutsche Forschungsgemeinschaft [DFG IC 81/1-1]; Bengt-Ihre Fonden

    Available from: 2019-03-20 Created: 2019-03-20 Last updated: 2024-01-17Bibliographically approved
    3. Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome
    Open this publication in new window or tab >>Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome
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    2019 (English)In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 160, no 9, p. 2004-2012Article in journal (Refereed) Published
    Abstract [en]

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

    Place, publisher, year, edition, pages
    Lippincott Williams & Wilkins, 2019
    Keywords
    Irritable bowel syndrome, Functional magnetic resonance imaging, Quantitative magnetic resonance spectroscopy, Insula, Visceral pain, Coping
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:liu:diva-160012 (URN)10.1097/j.pain.0000000000001589 (DOI)000512903900011 ()31045748 (PubMedID)
    Note

    Funding agencies: NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P41-RR14075, R01 RR16594-01A1, R01 NS052585-01, K08 MH01573, K01 MH01798]; County Council of Ostergotland; AFA research foundation [DNR. 140407]; Bengt-Ihre f

    Available from: 2019-09-02 Created: 2019-09-02 Last updated: 2024-01-10Bibliographically approved
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  • 26.
    Bednarska, Olga
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Nyhlin, Nils
    Örebro Univ, Sweden.
    Schmidt, Peter Thelin
    Ersta Hosp, Sweden; Karolinska Inst, Sweden.
    Johansson, Gabriele Wurm
    Lund Univ, Sweden.
    Toth, Ervin
    Lund Univ, Sweden.
    Lindfors, Perjohan
    Karolinska Inst, Sweden; Aleris Gastromottagningen City, Sweden.
    The Effectiveness and Tolerability of a Very Low-Volume Bowel Preparation for Colonoscopy Compared to Low and High-Volume Polyethylene Glycol-Solutions in the Real-Life Setting2022In: Diagnostics, ISSN 2075-4418, Vol. 12, no 5, article id 1155Article in journal (Refereed)
    Abstract [en]

    Adequate bowel cleansing is essential for high-quality colonoscopy. Recently, a new very low-volume 1 litre (1L) polyethylene glycol (PEG) plus ascorbate solution (ASC) has been introduced. Our aims were to assess the effectiveness and tolerability of this product compared to low-volume 2L PEG-ASC and high-volume 4L PEG solutions, in a real-life setting. In six endoscopy units in Sweden, outpatients undergoing colonoscopy were either prescribed solutions according to local routines, or the very low-volume solution in split dose regimen. Bowel cleansing effectiveness and patient experience was assessed using the Boston Bowel preparation scale (BBPS) and a patient questionnaire. A total of 1098 patients (mean age 58 years, 52% women) were included. All subsegment and the total BBPS scores were significantly greater for 1L PEG-ASC in comparison to other solutions (p < 0.05 for 1L PEG-ASC and 4L PEG for transverse and left colon, otherwise p < 0.001). Nausea was more frequent with 1L PEG-ASC compared to 2L PEG-ASC (p < 0.001) and vomiting were more often reported compared to both other solutions (p < 0.01 and p < 0.05 for 2L PEG-ASC and 4L PEG, respectively). Smell, taste, and total experience was better for 1L PEG-ASC compared to 4L PEG (p < 0.001), and similar compared to the 2L PEG-ASC. In conclusion, 1L PEG-ASC leads to better bowel cleansing compared to 2L PEG-ASC or 4L PEG products, with similar or greater patient satisfaction.

  • 27.
    Behrens, Anders
    et al.
    Blekinge Hosp, Sweden; Umea Univ, Sweden.
    Elgh, Eva
    Umea Univ, Sweden.
    Leijon, Göran
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping.
    Kristensen, Bo
    Aalborg Univ Hosp, Denmark.
    Eklund, Anders
    Umea Univ, Sweden.
    Malm, Jan
    Umea Univ, Sweden.
    The Computerized General Neuropsychological INPH Test revealed improvement in idiopathic normal pressure hydrocephalus after shunt surgery2020In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 132, no 3, p. 733-740Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE The Computerized General Neuropsychological INPH Test (CoGNIT) provides the clinician and the researcher with standardized and accessible cognitive assessments in patients with idiopathic normal pressure hydrocephalus (INPH). CoGNIT includes tests of memory, executive functions, attention, manual dexterity, and psychomotor speed. Investigations of the validity and reliability of CoGNIT have been published previously. The aim of this study was to evaluate CoGNITs sensitivity to cognitive change after shunt surgery in patients with INPH. METHODS Forty-one patients with INPH (median Mini-Mental State Examination score 26) were given CoGNIT preoperatively and at a postoperative follow-up 4 months after shunt surgery. Scores were compared to those of 44 healthy elderly control volunteers. CoGNIT was administered by either a nurse or an occupational therapist. RESULTS Improvement after shunt surgery was seen in all cognitive domains: memory (10-word list test, p amp;lt; 0.01); executive functions (Stroop incongruent color and word test, p amp;lt; 0.01); attention (2-choice reaction test, p amp;lt; 0.01); psychomotor speed (Stroop congruent color and word test, p amp;lt; 0.01); and manual dexterity (4-finger tapping, p amp;lt; 0.01). No improvement was seen in the Mini-Mental State Examination score. Preoperative INPH test scores were significantly impaired compared to healthy control subjects (p amp;lt; 0.001 for all tests). CONCLUSIONS In this study the feasibility for CoGNIT to detect a preoperative impairment and postoperative improvement in INPH was demonstrated. CoGNIT has the potential to become a valuable tool in clinical and research work.

  • 28.
    Bellon-Harn, Monica L.
    et al.
    Lamar University, TX 77710 USA.
    Hartwell Azios, Jamie
    Lamar University, TX 77710 USA.
    Dockens, Ashley L.
    Lamar University, TX 77710 USA.
    Manchaiah, Vinaya
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. Lamar University, TX 77710 USA; Audiol India, India.
    Speech-language pathologists preferences for patient-centeredness2017In: Journal of Communication Disorders, ISSN 0021-9924, E-ISSN 1873-7994, Vol. 68, p. 81-88Article in journal (Refereed)
    Abstract [en]

    Purpose: Preferences for patient-centeredness is an important indicator in healthcare service delivery. However, it remains largely unexplored in the field of communication science and disorders. This study investigated speech-language pathologists (SLPs) preferences for patient-centeredness Method: The study involved a cross-sectional survey design. SLPs (n = 102) fully completed the modified Patient-Practitioner Orientation Scale (PPOS; Krupat et al, 2000) and also provided demographic details. Data were analyzed using descriptive statistics, correlation, and linear regression methods. Results: Mean PPOS scores indicated that SLPs value patient-centeredness. There was a strong positive correlation among sharing and caring subscales with the full-scale. Results from the linear regression modeling suggested no relationship between demographic factors and preferences for patient-centeredness. Conclusions: SLPs value patient-centeredness, although there may be regional and cultural variations. Qualitative investigations may help uncover dimensions of patient-centeredness that were not captured in the PPOS scale. In addition, further research should explore congruence in preferences for patient-centeredness among SLPs and patients.

  • 29.
    Bergquist, Filip
    et al.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Ehrnebo, Mats
    Uppsala Univ, Sweden; Pharm Assist Sweden AB, Sweden.
    Nyholm, Dag
    Uppsala Univ, Sweden.
    Johansson, Anders
    Karolinska Inst, Sweden.
    Lundin, Fredrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Odin, Per
    Lund Univ, Sweden.
    Svenningsson, Per
    Karolinska Inst, Sweden.
    Hansson, Fredrik
    CTC Clin Trial Consultants AB, Sweden.
    Bring, Leif
    Dizlin Pharmaceut, Sweden.
    Eriksson, Elias
    Univ Gothenburg, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in Advanced Parkinson Disease2022In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 99, no 10, p. E965-E976Article in journal (Refereed)
    Abstract [en]

    Background and Objectives Intestinal levodopa/carbidopa gel infusion (LCIG) is superior to oral treatment in advanced Parkinson disease. The primary objective of this trial was to investigate whether continuous subcutaneous or intravenous infusion with a continuously buffered acidic levodopa/carbidopa solution yields steady-state plasma concentrations of levodopa that are equivalent in magnitude, and noninferior in variability, to those obtained with LCIG in patients with advanced Parkinson disease. Methods A concentrated acidic levodopa/carbidopa (8:1) solution buffered continuously and administered intravenously (DIZ101) or subcutaneously (DIZ102) was compared with an approved LCIG in a randomized, 3-period crossover, open-label, multicenter trial. Formulations were infused for 16 hours to patients with Parkinson disease who were using LCIG as their regular treatment. Patients were recruited from several university neurology clinics but came to the same phase I unit for treatment. Pharmacokinetic variables and safety including dermal tolerance are reported. The primary outcomes were bioequivalence and noninferior variability of DIZ101 and DIZ102 vs LCIG with respect to levodopa plasma concentrations. Results With dosing adjusted to estimated bioavailability, DIZ101 and DIZ102 produced levodopa plasma levels within standard bioequivalence limits compared with LCIG in the 18 participants who received all treatments. Although the levodopa bioavailability for DIZ102 was complete, it was 80% for LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of DIZ102 as with LCIG and remained stable throughout the infusions. Owing to poor uptake of LCIG, carbidopa levels in plasma were higher with DIZ101 and DIZ102 than with the former. All individuals receiving any of the treatments (n = 20) were included in the evaluation of safety and tolerability. Reactions at the infusion sites were mild and transient. Discussion It is feasible to rapidly achieve high and stable levodopa concentrations by means of continuous buffering of a subcutaneously administered acidic levodopa/carbidopa-containing solution.

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  • 30.
    Bergquist, Filip
    et al.
    Sahlgrenska Academy, Göteborg, Sweden .
    Johansson, Anders
    Karolinska Universitetssjukhuset, Stockholm, Sweden.
    Dizdar Segrell, Nil
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Widner, Håkan
    Lunds universitet Medicinska fakulteten, Lund, Sweden .
    Nyholm, Dag
    Akademiska sjukhuset, Uppsala, Sweden .
    Odin, Per
    Lunds universitet Medicinska fakulteten, Lund, Sweden.
    Svenningsson, Per
    Karolinska Universitetssjukhuset, Tema Neuro Stockholm, Sweden .
    Parkinsons sjukdom [Parkinsons disease]: heterogen och komplex i sitt kliniska uttryck [heterogeneous and complex in its clinical presentation]2020In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 117Article in journal (Refereed)
    Abstract [en]

    Parkinsons disease is the second most common neurodegenerative disease. Lewy bodies with alpha-synuclein as the major component and loss of dopaminergic nerve cells in substantia nigra are neuropathological features. The diagnosis of Parkinsons disease is based on the occurrence of bradykinesia, rigidity and resting tremor. The disease is also associated with several non-motor symptoms. The therapy is mainly based on pharmacological treatment to increase dopamine signaling and neurosurgical deep brain stimulation. The symptoms and signs of the progressive disease change over time, requiring treatment adjustments. Patients should be followed by a physician, nurse and a multidisciplinary team with expertise in Parkinsons disease.

  • 31.
    Berntsson, S. G.
    et al.
    Uppsala Univ, Sweden.
    Kristoffersson, A.
    Uppsala Univ, Sweden; Motala Gen Hosp, Sweden.
    Boström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Feresiadou, A.
    Uppsala Univ, Sweden.
    Burman, J.
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala Univ, Sweden; Motala Gen Hosp, Sweden.
    Rapidly increasing off-label use of rituximab in multiple sclerosis in Sweden Outlier or predecessor?2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 4, p. 327-331Article in journal (Refereed)
    Abstract [en]

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

  • 32.
    Berntsson, Shala G.
    et al.
    Uppsala Univ, Sweden.
    Gauffin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Melberg, Atle
    Uppsala Univ, Sweden.
    Holtz, Anders
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala Univ, Sweden.
    Inherited Ataxia and Intrathecal Baclofen for the Treatment of Spasticity and Painful Spasms2019In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 97, no 1, p. 18-23Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 33.
    Berntsson, Shala Ghaderi
    et al.
    Uppsala Univ, Sweden.
    Kristoffersson, Anna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Daniilidou, Makrina
    Uppsala Univ, Sweden.
    Dahl, Niklas
    Uppsala Univ, Sweden.
    Ekstrom, Curt
    Uppsala Univ, Sweden.
    Semnic, Robert
    Uppsala Univ, Sweden.
    Markstrom, Agneta
    Uppsala Univ, Sweden.
    Niemela, Valter
    Uppsala Univ, Sweden.
    Partinen, Markku
    Helsinki Sleep Clin, Finland; Univ Helsinki, Finland.
    Hallbook, Finn
    Uppsala Univ, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping. Uppsala Univ, Sweden.
    Aniridia with PAX6 mutations and narcolepsy2020In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 29, no 6, article id e12982Article in journal (Refereed)
    Abstract [en]

    PAX6 gene mutations cause a variety of eye and central nervous system (CNS) abnormalities. Aniridia is often accompanied by CNS abnormalities such as pineal gland atrophy or hypoplasia, leading to disturbed circadian rhythm and sleep disorders. Less is known on the coincidence of narcolepsy in this patient group. We aimed to find out whether the circadian rhythm or sleep-wake structure was affected in patients with aniridia. Four members of a family segregating with congenital aniridia in two generations were included in the study. The patients were subjected to genetic testing for a PAX6 mutation, multiple sleep latency test, whole-brain magnetic resonance imaging (MRI), hypocretin-1 in cerebrospinal fluid, and Human Leukocyte Antigen DQ beta1*06:02. All four members were heterozygous for the pathogenic c.959-1Gamp;gt;A mutation in the PAX6 gene. Sleep disturbance was observed in all family members. The index patient was diagnosed with narcolepsy. MRI showed a hypoplastic pineal gland in all members. We describe the first case of a patient with PAX6 haploinsufficiency, aniridia and pineal gland hypoplasia diagnosed with narcolepsy type-1, suggesting a complex sleep disorder pathogenesis.

  • 34.
    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
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala. Uppsala University, Sweden.
    Patterns of antiepileptic drug prescription in Sweden: A register-based approach2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 136, no 5, p. 521-527Article in journal (Refereed)
    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.

  • 35.
    Bolin, K.
    et al.
    University of Gothenburg, Sweden; University of Gothenburg, Sweden.
    Berggren, F.
    UCB Pharma, Denmark.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Prevalence and cost of epilepsy in Sweden - a register-based approach2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 131, no 1, p. 37-44Article in journal (Refereed)
    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.

  • 36. Order onlineBuy this publication >>
    Boman, Andrea
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Lysosomal network proteins as biomarkers and therapeutic targets in neurodegenerative disease2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The pre-symptomatic stage of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) occurs several decades before the clinical onset. Changes in the lysosomal network, i.e. the autophagosomal, endosomal and lysosomal vesicular system, are among the first alterations observed. There are currently no treatments to slow or cure neurodegenerative diseases, and there is a great need for discovery of treatment targets in cellular pathways where pathology pre-dates the neuronal death. It is also crucial to be able to diagnose neurodegenerative diseases earlier, both to enable early intervention treatment and aid in selecting clinical trial populations before the patient has widespread pathology.

    This thesis aims at investigating the potential of lysosomal network proteins as biomarkers and therapeutic targets in neurodegenerative disease.

    A targeted search for lysosomal network proteins was performed in cerebrospinal fluid (CSF) from AD patients, and seven proteins: early endosomal antigen 1 (EEA1), lysosomal-associated membrane proteins 1 and 2 (LAMP-1, LAMP-2), lysozyme, microtubule-associated protein 1 light chain 3 (LC3), Rab3 and Rab7, were elevated. The levels of EEA1, LAMP-1, LAMP-2, LC3, lysozyme and Rab3 were also measured in CSF from parkinsonian syndrome patients: PD, clinically diagnosed 4-repeat tauopathy, pathologically confirmed corticobasal degeneration (CBD) and pathologically confirmed progressive supranuclear palsy (PSP) patients. LAMP-1 and LAMP-2 were decreased in PD. LC3 and lysozyme levels were increased in 4-repeat tauopathy patients. EEA1 was decreased and lysozyme increased in PSP, and LAMP-1, LAMP-2, LC3 and lysozyme were increased in CBD. The lysosomal network proteins had different CSF protein profiles in all the parkinsonian syndromes, as well as in AD. It should be emphasized that only a select few of the lysosomal network proteins were observed to be changed, rather than a general change in lysosomal network proteins, which implicates the involvement of these seven proteins in specific pathological processes. The most interesting candidates, LAMP-2 and lysozyme, were selected for further study for their involvement in the pathology of AD.

    Lysozyme was found to co-localise with Aβ plaques in AD patients and overexpression prolonged survival and improved the activity in a Drosophila model of AD. Lysozyme was found to alter the aggregation pathway of Aβ1-42, to counteract the formation of toxic Aβ species and to protect from Aβ1-42 induced cell toxicity. Aβ1-42 in turn was found to increase the expression of lysozyme in both neuronal and glial cells. These data suggest that lysozyme levels rise in AD as a compensatory response which is protective against Aβ associated toxicity.

    LAMP-2 mRNA and protein were found increased in brain areas relevant for AD pathology and various cellular models showed complex involvement of LAMP-2 in Aβ related pathology, with extensive crosstalk between LAMP-2 and Aβ. Exposure to oligomeric Aβ1-42 caused an upregulation of LAMP-2 and in turn, overexpression of LAMP-2 caused a reduction in secreted levels of Aβ1-42, as well as changing the generation pattern of Aβ and affecting clearance and secretion of Aβ1-42. These data indicate that the increased levels of LAMP-2 in AD could be an attempt to regulate Aβ generation and secretion.

    In summary, this thesis reports that utilising lysosomal network proteins as biomarkers and novel therapeutic targets for neurodegenerative diseases holds great promise.

    List of papers
    1. Lysosomal Network Proteins as Potential Novel CSF Biomarkers for Alzheimers Disease
    Open this publication in new window or tab >>Lysosomal Network Proteins as Potential Novel CSF Biomarkers for Alzheimers Disease
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    2014 (English)In: Neuromolecular medicine, ISSN 1535-1084, E-ISSN 1559-1174, Vol. 16, no 1, p. 150-160Article in journal (Refereed) Published
    Abstract [en]

    The success of future intervention strategies for Alzheimers disease (AD) will likely rely on the development of treatments starting early in the disease course, before irreversible brain damage occurs. The pre-symptomatic stage of AD occurs at least one decade before the clinical onset, highlighting the need for validated biomarkers that reflect this early period. Reliable biomarkers for AD are also needed in research and clinics for diagnosis, patient stratification, clinical trials, monitoring of disease progression and the development of new treatments. Changes in the lysosomal network, i.e., the endosomal, lysosomal and autophagy systems, are among the first alterations observed in an AD brain. In this study, we performed a targeted search for lysosomal network proteins in human cerebrospinal fluid (CSF). Thirty-four proteins were investigated, and six of them, early endosomal antigen 1 (EEA1), lysosomal-associated membrane proteins 1 and 2 (LAMP-1, LAMP-2), microtubule-associated protein 1 light chain 3 (LC3), Rab3 and Rab7, were significantly increased in the CSF from AD patients compared with neurological controls. These results were confirmed in a validation cohort of CSF samples, and patients with no neurochemical evidence of AD, apart from increased total-tau, were found to have EEA1 levels corresponding to the increased total-tau levels. These findings indicate that increased levels of LAMP-1, LAMP-2, LC3, Rab3 and Rab7 in the CSF might be specific for AD, and increased EEA1 levels may be a sign of general neurodegeneration. These six lysosomal network proteins are potential AD biomarkers and may be used to investigate lysosomal involvement in AD pathogenesis.

    Place, publisher, year, edition, pages
    Humana Press, 2014
    Keywords
    PICALM; DRAM; TFEB; Cathepsins; Proteasome; hsc70
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-105235 (URN)10.1007/s12017-013-8269-3 (DOI)000331101900015 ()
    Available from: 2014-03-14 Created: 2014-03-14 Last updated: 2018-01-11
    2. Protective properties of lysozyme on β-amyloid pathology: implications for Alzheimer disease
    Open this publication in new window or tab >>Protective properties of lysozyme on β-amyloid pathology: implications for Alzheimer disease
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    2015 (English)In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 83, p. 122-133Article in journal (Refereed) Published
    Abstract [en]

    The hallmarks of Alzheimer disease are amyloid-β plaques and neurofibrillary tangles accompanied by signs of neuroinflammation. Lysozyme is a major player in the innate immune system and has recently been shown to prevent the aggregation of amyloid-β1-40 in vitro. In this study we found that patients with Alzheimer disease have increased lysozyme levels in the cerebrospinal fluid and lysozyme co-localized with amyloid-β in plaques. In Drosophila neuronal co-expression of lysozyme and amyloid-β1-42 reduced the formation of soluble and insoluble amyloid-β species, prolonged survival and improved the activity of amyloid-β1-42 transgenic flies. This suggests that lysozyme levels rise in Alzheimer disease as a compensatory response to amyloid-β increases and aggregation. In support of this, in vitro aggregation assays revealed that lysozyme associates with amyloid-β1-42 and alters its aggregation pathway to counteract the formation of toxic amyloid-β species. Overall, these studies establish a protective role for lysozyme against amyloid-β associated toxicities and identify increased lysozyme in patients with Alzheimer disease. Therefore, lysozyme has potential as a new biomarker as well as a therapeutic target for Alzheimer disease.

    Place, publisher, year, edition, pages
    Elsevier, 2015
    Keywords
    Lysozyme, Biomarker, Alzheimer disease, Drosophila, Aβ aggregation
    National Category
    Cell and Molecular Biology Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-122341 (URN)10.1016/j.nbd.2015.08.024 (DOI)000366230000012 ()26334479 (PubMedID)
    Available from: 2015-10-29 Created: 2015-10-29 Last updated: 2021-12-28Bibliographically approved
    3. Distinct lysosomal network protein profiles in parkinsonian syndrome cerebrospinal fluid
    Open this publication in new window or tab >>Distinct lysosomal network protein profiles in parkinsonian syndrome cerebrospinal fluid
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    2016 (English)In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 6, no 2, p. 307-315Article in journal (Refereed) Published
    Abstract [en]

    Introduction: Clinical diagnosis of parkinsonian syndromes like Parkinson’s disease, corticobasal degeneration and progressive supranuclear palsy is hampered by overlapping symptomatology and lack of biomarkers for diagnosis, and definitive diagnosis is only possible post-mortem. Since impaired protein degradation plays an important role in many neurodegenerative disorders, we hypothesized that levels and profiles of lysosomal network proteins in cerebrospinal fluid could be changed in these parkinsonian syndromes.

    Methods: Cerebrospinal fluid samples were collected from Parkinson’s disease patients (n=18), clinically diagnosed 4-repeat tauopathy patients, corticobasal syndrome (n=6) and progressive supranuclear palsy (n=5), pathologically diagnosed progressive supranuclear palsy (n=8) and corticobasal degeneration patients (n=7). Each patient set was compared to its appropriate control group consisting of the same number of age and gender matched individuals. Lysosomal network protein levels were detected via Western blotting.

    Results: Lysosomal network proteins have markedly different cerebrospinal fluid protein levels and profiles in Parkinson’s disease, corticobasal degeneration and progressive supranuclear palsy. Lysosomal-associated membrane proteins 1 and 2 were significantly decreased in Parkinson´s disease; early endosomal antigen 1 was decreased and lysozyme increased in progressive supranuclear palsy; and lysosomal-associated membrane proteins 1 and 2, microtubule-associated protein 1 light chain 3 and lysozyme were increased in corticobasal degeneration.

    Conclusions: Lysosomal network proteins hold promise of being interesting novel candidates for biomarker studies and for elucidating disease mechanisms of Parkinson’s disease, corticobasal degeneration and progressive supranuclear palsy, but further validation studies will be needed to assess the specificity and the predictive value of these proteins in CSF.

    Place, publisher, year, edition, pages
    IOS Press, 2016
    National Category
    Cell and Molecular Biology Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-122342 (URN)10.3233/JPD-150759 (DOI)000378352200004 ()
    Note

    Funding agencies:This work was supported by the Swedish Alzheimer foundation, the Swedish Dementia foundation, Linkoping University Neurobiology Center, Karin & Sten CBD Solutions AB, AZ-KI TSC, ALF, US National Institutes of Health R01AG038791 and U54NS092089, the Tau Consortium, the Hellman Family Foundation.

    Vid tiden för disputationen förelåg publikationen endast som manuskript

    Available from: 2015-10-29 Created: 2015-10-29 Last updated: 2018-01-10Bibliographically approved
    4. The role of LAMP-2 in AβPP processing and Aβ degradation; implications for Alzheimer’s Disease
    Open this publication in new window or tab >>The role of LAMP-2 in AβPP processing and Aβ degradation; implications for Alzheimer’s Disease
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    2015 (English)Manuscript (preprint) (Other academic)
    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.

    Keywords
    AβPP processing, Alzheimer’s disease, β-amyloid, autophagy, LAMP-2, lysosome
    National Category
    Cell and Molecular Biology Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-122345 (URN)
    Available from: 2015-10-29 Created: 2015-10-29 Last updated: 2018-01-10Bibliographically approved
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  • 37.
    Boman, John
    Linköping University, Department of Behavioural Sciences and Learning, Education and Sociology. Linköping University, Faculty of Arts and Sciences.
    Efter stroken2005In: Sjukdomsvärldar: om människors erfarenhet av kroppslig ohälsa / [ed] Bengt Richt, Gunilla Tegern, Lund: Studentlitteratur AB, 2005, Vol. Sidorna 259-275, p. 259-275Chapter in book (Other academic)
    Abstract [sv]

    Stroke och slaganfall är två alternativa namn på en akut inträdande funktionsnedsättning i hjärnan. Stroke uppkommer genom störningar i blodflödet till hjärnan, vilka i sin tur ger upphov till mer eller mindre omfattande vävnadsskador. Det finns två stora undergrupper av stroke: hjärninfarkter och hjärnblödningar. Infarkter är sådana vävnadsskador som uppstår till följd av att blodflödet i ett kärl stoppas. Vid hjärnblödningar uppstår vävnadsskadan till följd av att ett blodkärl brister.

  • 38.
    Borgström, Max
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Tisell, Anders
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Link, Hans
    Karolinska Inst, Sweden.
    Wilhelm, Elisabeth
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Lundberg, Peter
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Huang-Link, YuMin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Neurologiska kliniken i Linköping.
    Retinal thinning and brain atrophy in early MS and CIS2020In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 142, no 5, p. 418-427Article in journal (Refereed)
    Abstract [en]

    Background Optical coherence tomography (OCT) could be complementary to magnetic resonance imaging (MRI) of the brain in monitoring course of multiple sclerosis (MS) and clinically isolated syndrome (CIS). Thinning of neurons in ganglion cell-inner plexiform layer (GCIPL) measured by OCT is assumed to be associated with brain atrophy. Objectives To evaluate association of GCIPL with brain parameters detected by quantitative MRI (qMRI) and MR-spectroscopy (MRS) in early MS and CIS. Methods Seventeen newly diagnosed MS and 18 CIS patients were prospectively included. The patients were assessed at baseline as well as at 1 year follow-up by OCT, qMRI and MRS. Brain parenchymal and myelin volumes (BPV, MYV respectively) and the corresponding fractions (BPF, MYF) were measured with qMRI. Metabolites including myo-inositol (myo-Ins) were measured in the normal-appearing white matter (NAWM) using MRS. T-tests and ANOVA were used to analyze group differences, and linear regression models to evaluate association of GCIPL with BPV, MYV and myo-Ins after correlation analysis. Results Disease activity reflected by lesions on MRI and presence of CSF oligoclonal IgG bands were more prominent in MS compared to CIS. GCIPL, BPV, MYV, BPF and MYF were reduced, while concentration of myo-Ins was increased in MS compared to CIS. Follow-up showed consistency of thinner GCIPL in MS compared to CIS. GCIPL thinning correlated with reduced BPV and MYV (P &lt; .05 for both), but with increased myo-Ins (P &lt; .01). Conclusions Significant GCIPL thinning occurs in early MS and is associated with enhanced brain inflammation and atrophy.

  • 39.
    Borland, Emma
    et al.
    Lund University, Malmö, Sweden; Skåne University Hospital, Sweden.
    Nägga, Katarina
    Lund University, Malmö, Sweden.
    Nilsson, Peter M
    Lund University, Malmö, Sweden.
    Minthon, Lennart
    Lund University, Malmö, Sweden.
    Nilsson, Erik D
    Lund University, Malmö, Sweden.
    Palmqvist, Sebastian
    Lund University, Malmö, Sweden; Skåne University Hospital, Sweden.
    The Montreal Cognitive Assessment: Normative Data from a Large Swedish Population-Based Cohort.2017In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 59, no 3, p. 893-901Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Montreal Cognitive Assessment (MoCA) has a high sensitivity for detecting cognitive dysfunction. Swedish normative data does not exist and international norms are often derived from populations where cognitive impairment has not been screened for and not been thoroughly assessed to exclude subjects with dementia or mild cognitive impairment.

    OBJECTIVE: To establish norms for MoCA and develop a regression-based norm calculator based on a large, well-examined cohort.

    METHODS: MoCA was administered on 860 randomly selected elderly people from a population-based cohort from the EPIC study. Cognitive dysfunction was screened for and further assessed at a memory clinic. After excluding cognitively impaired participants, normative data was derived from 758 people, aged 65-85.

    RESULTS: MoCA cut-offs (-1 to -2 standard deviations) for cognitive impairment ranged from <25 to <21 for the lowest educated and <26 to <24 for the highest educated, depending on age group. Significant predictors for MoCA score were age, sex and level of education.

    CONCLUSION: We present detailed normative MoCA data and cut-offs according to the DSM-5 criteria for cognitive impairment based on a large population-based cohort of elderly individuals, screened and thoroughly investigated to rule out cognitive impairment. Level of education, sex, and age should be taken in account when evaluating MoCA score, which is facilitated by our online regression-based calculator that provide percentile and z-score for a subject's MoCA score.

  • 40.
    Boström, Inger
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala University, Sweden.
    Does the changing sex ratio of multiple sclerosis give opportunities for intervention?2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 132, p. 42-45Article, review/survey (Refereed)
    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.

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  • 41.
    Broström, Anders
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Nilsen, Per
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Gardner, Benjamin
    University College London, UK.
    Johansson, Peter
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Neurophysiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Fridlund, Bengt
    Jönköping University, Sweden.
    Arestedt, Kristofer
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences. Linnaeus University & Palliative Research Centre, Ersta Sköndal University College and Ersta Hospital, Stockholm.
    Validation of the CPAP Habit Index-5: A Tool to Understand Adherence to CPAP Treatment in Patients with Obstructive Sleep Apnea.2014In: Sleep Disorders, ISSN 2090-3545, E-ISSN 2090-3553, Vol. 2014, p. 1-9, article id 929057Article in journal (Refereed)
    Abstract [en]

    Long-term adherence to continuous positive airway pressure (CPAP) is low among patients with obstructive sleep apnea (OSA). The potential role of "habit" in sustaining adherence to CPAP use has not been studied. This study aimed to establish the relevance of habit to CPAP adherence, via validation of an adaptation of the Self-Report Habit Index (the CPAP Habit Index-5; CHI-5). Analyses focused on the homogeneity, reliability, and factor structure of the CHI-5 and, in line with theoretical predictions, its utility as a predictor of long-term CPAP adherence in middle-aged patients with OSA. A prospective longitudinal design was used. 117 patients with objectively verified OSA intended for CPAP treatment were recruited. Data was collected via clinical examinations, respiratory recordings, questionnaires, and CPAP devices at baseline, 2 weeks, 6 months, and 12 months. The CHI-5 showed satisfactory homogeneity interitem correlations (0.42-0.93), item-total correlations (0.58-0.91), and reliability ( α = 0.92). CHI-5 data at 6 months showed a one-factor solution and predicted 63% of variance in total CPAP use hours after 12 months. Based on the satisfactory measurement properties and the high amount of CPAP use variance it explained, the CHI-5 can be seen as a useful tool in clinical practice.

  • 42.
    Broström, Anders
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. 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
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Fridlund, B.
    CICE Linneus University, Sweden.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    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.2019In: Sleep and Breathing, ISSN 1520-9512, E-ISSN 1522-1709, Vol. 23, no 3, p. 761-768Article in journal (Refereed)
    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.

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  • 43.
    Broström, Anders
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. 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
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hedberg, Berith
    Jönköping Academy for Health and Welfare, Jönköping University, Sweden; Region Jönköpings län, Futurum, Jönköping,Sweden.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Validation of CollaboRATE and SURE - two short questionnaires to measure shared decision making during CPAP initiation.2019In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 28, no 5, article id UNSP e12808Article in journal (Refereed)
    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.

  • 44.
    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
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry. Karolinska Institute, Sweden.
    Lundgren, Kristoffer
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    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 neuroinflammation2016In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 6, no e865Article in journal (Refereed)
    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.

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  • 45.
    Bunketorp Kall, Lina
    et al.
    Sahlgrenska Univ Hosp Molndal, Sweden; Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Friden, Jan
    Sahlgrenska Univ Hosp Molndal, Sweden; Swiss Parapleg Ctr, Switzerland.
    Björnsdotter Åberg, Malin
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Gothenburg, Sweden.
    Regional estimates of cortical thickness in brain areas involved in control of surgically restored limb movement in patients with tetraplegia2020In: Journal of Spinal Cord Medicine (JSCM), ISSN 1079-0268, E-ISSN 2045-7723, Vol. 43, no 4, p. 462-469Article in journal (Refereed)
    Abstract [en]

    Context/Objective:Spinal cord injury (SCI) causes atrophy of brain regions linked to motor function. We aimed to estimate cortical thickness in brain regions that control surgically restored limb movement in individuals with tetraplegia. Design:Cross-sectional study. Setting:Sahlgrenska University hospital, Gothenburg, Sweden. Participants:Six individuals with tetraplegia who had undergone surgical restoration of grip function by surgical transfer of one elbow flexor (brachioradialis), to the paralyzed thumb flexor (flexor pollicis longus). All subjects were males, with a SCI at the C6 or C7 level, and a mean age of 40 years (range = 31-48). The average number of years elapsed since the SCI was 13 (range = 6-26). Outcome measures:We used structural magnetic resonance imaging (MRI) to estimate the thickness of selected motor cortices and compared these measurements to those of six matched control subjects. The pinch grip control area was defined in a previous functional MRI study. Results:Compared to controls, the cortical thickness in the functionally defined pinch grip control area was not significantly reduced (P = 0.591), and thickness showed a non-significant but positive correlation with years since surgery in the individuals with tetraplegia. In contrast, the anatomically defined primary motor cortex as a whole exhibited substantial atrophy (P = 0.013), with a weak negative correlation with years since surgery. Conclusion:Individuals with tetraplegia do not seem to have reduced cortical thickness in brain regions involved in control of surgically restored limb movement. However, the studied sample is very small and further studies with larger samples are required to establish these findings.

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  • 46.
    Bäcklund, Tomas
    et al.
    Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden.
    Frankel, Jennifer
    Department of Radiation Sciences, Radiation Physics, Umeå University, Umeå, Sweden.
    Israelsson, Hanna
    Region Östergötland. Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Malm, Jan
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Sundström, Nina
    Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden.
    Trunk sway in idiopathic normal pressure hydrocephalus-Quantitative assessment in clinical practice2017In: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 54, p. 62-70Article in journal (Refereed)
    Abstract [en]

    In diagnosis and treatment of patients with idiopathic normal pressure hydrocephalus (iNPH), there is need for clinically applicable, quantitative assessment of balance and gait. Using a body-worn gyroscopic system, the aim of this study was to assess postural stability of iNPH patients in standing, walking and during sensory deprivation before and after cerebrospinal fluid (CSF) drainage and surgery. A comparison was performed between healthy elderly (HE) and patients with various types of hydrocephalus (ventriculomegaly (VM)).

  • 47.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Edström, Sofia
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Do fragments and glycosylated isoforms of alpha-1-antitrypsin in CSF mirror spinal pathophysiological mechanisms in chronic peripheral neuropathic pain? An exploratory, discovery phase study2018In: BMC Neurology, E-ISSN 1471-2377, Vol. 18, article id 116Article in journal (Refereed)
    Abstract [en]

    Background: Post-translational modifications (PTMs) generate a tremendous protein diversity from the similar to 20,000 protein-coding genes of the human genome. In chronic pain conditions, exposure to pathological processes in the central nervous system could lead to disease-specific PTMs detectable in the cerebrospinal fluid (CSF). In a previous hypothesis-generating study, we reported that seven out of 260 CSF proteins highly discriminated between neuropathic pain patients and healthy controls: one isoform of angiotensinogen (AG), two isoforms of alpha-1-antitrypsin (AT), three isoforms of haptoglobin (HG), and one isoform of pigment epithelium-derived factor (PEDF). The present study had three aims: (1) To examine the multivariate inter-correlations between all identified isoforms of these seven proteins; (2) Based on the results of the first aim, to characterize PTMs in a subset of interesting proteins; (3) To regress clinical pain data using the 260 proteins as predictors, thereby testing the hypothesis that the above-mentioned seven discriminating proteins and/or the characterized isoforms/fragments of aim (2) would be among the proteins having the highest predictive power for clinical pain data. Methods: CSF samples from 11 neuropathic pain patients and 11 healthy controls were used for biochemical analysis of protein isoforms. PTM characterization was performed using enzymatic reaction assay and mass spectrometry. Multivariate data analysis (principal component analysis and orthogonal partial least square regression) was applied on the quantified protein isoforms. Results: We identified 5 isoforms of AG, 18 isoforms of AT, 5 isoforms of HG, and 5 isoforms of PEDF. Fragments and glycosylated isoforms of AT were studied in depth. When regressing the pain intensity data of patients, three isoforms of AT, two isoforms of PEDF, and one isoform of angiotensinogen "reappeared" as major results, i.e., they were major findings both when comparing patients with healthy controls and when regressing pain intensity in patients. Conclusions: Altered levels of fragments and/or glycosylated isoforms of alpha-1-antitrypsin might mirror pathophysiological processes in the spinal cord of neuropathic pain patients. In particular, we suggest that a putative disease-specific combination of the levels of two different N-truncated fragments of alpha-1-antitrypsin might be interesting for future CSF and/or plasma biomarker investigations in chronic neuropathic pain.

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  • 48.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Lind, Anne-Li
    Uppsala University, Sweden.
    Thulin, Mans
    Uppsala University, Sweden.
    Larsson, Anders
    Uppsala University, Sweden.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gordh, Torsten
    Uppsala University, Sweden.
    High levels of cerebrospinal fluid chemokines point to the presence of neuroinflammation in peripheral neuropathic pain: a cross-sectional study of 2 cohorts of patients compared with healthy controls2017In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 158, no 12, p. 2487-2495Article in journal (Refereed)
    Abstract [en]

    Animal models suggest that chemokines are important mediators in the pathophysiology of neuropathic pain. Indeed, these substances have been called "gliotransmitters," a term that illustrates the close interplay between glial cells and neurons in the context of neuroinflammation and pain. However, evidence in humans is scarce. The aim of the study was to determine a comprehensive cerebrospinal fluid (CSF) inflammatory profile of patients with neuropathic pain. Our hypothesis was that we would thereby find indications of a postulated on-going process of central neuroinflammation. Samples of CSF were collected from 2 cohorts of patients with neuropathic pain (n = 11 and n = 16, respectively) and healthy control subjects (n 5 11). The samples were analyzed with a multiplex proximity extension assay in which 92 inflammation-related proteins were measured simultaneously (Proseek Multiplex Inflammation I; Olink Bioscience, Uppsala, Sweden). Univariate testing with control of false discovery rate, as well as orthogonal partial least squares discriminant analysis, were used for statistical analyses. Levels of chemokines CXCL6, CXCL10, CCL8, CCL11, CCL23 in CSF, as well as protein LAPTGF-beta-1, were significantly higher in both neuropathic pain cohorts compared with healthy controls, pointing to neuroinflammation in patients. These 6 proteins were also major results in a recent similar study in patients with fibromyalgia. The findings need to be confirmed in larger cohorts, and the question of causality remains to be settled. Because it has been suggested that prevalent comorbidities to chronic pain (eg, depression, anxiety, poor sleep, and tiredness) also are associated with neuroinflammation, it will be important to determine whether neuroinflammation is a common mediator.

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  • 49.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Tanum, Lars
    Akershus University Hospital, Norway.
    Lind, Anne-Li
    Uppsala University, Sweden.
    Larsson, Anders
    Uppsala University, Sweden.
    Gordh, Torsten
    Uppsala University, Sweden.
    Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma2017In: Journal of Pain Research, E-ISSN 1178-7090, Vol. 10Article in journal (Refereed)
    Abstract [en]

    In addition to central hyperexcitability and impaired top-down modulation, chronic inflammation probably plays a role in the pathophysiology of fibromyalgia (FM). Indeed, on the basis of both animal experiments and human studies involving the analysis of cytokines and other inflammation-related proteins in different body fluids, neuroinflammatory mechanisms are considered to be central to the pathophysiology of many chronic pain conditions. However, concerning FM, previous human plasma/serum and/or cerebrospinal fluid (CSF) cytokine studies have looked only at a few predetermined cytokine candidates. Instead of analyzing only a few substances at a time, we used a new multiplex protein panel enabling simultaneous analysis of 92 inflammation-related proteins. Hence, we investigated the CSF and plasma inflammatory profiles of 40 FM patients compared with CSF from healthy controls (n= 10) and plasma from blood donor controls (n= 46). Using multivariate data analysis by projection, we found evidence of both neuroinflammation (as assessed in CSF) and chronic systemic inflammation (as assessed in plasma). Two groups of proteins (one for CSF and one for plasma) highly discriminating between patients and controls are presented. Notably, we found high levels of CSF chemokine CX3CL1 (also known as fractalkine). In addition, previous findings concerning IL-8 in FM were replicated, in both CSF and plasma. This is the first time that such an extensive inflammatory profile has been described for FM patients. Hence, FM seems to be characterized by objective biochemical alterations, and the lingering characterization of its mechanisms as essentially idiopathic or even psychogenic should be seen as definitively outdated.

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  • 50.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Thordeman, Katarina
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Cerebrospinal Fluid Metabolomics Identified Ongoing Analgesic Medication in Neuropathic Pain Patients2023In: Biomedicines, E-ISSN 2227-9059, Vol. 11, no 9, article id 2525Article in journal (Refereed)
    Abstract [en]

    Background: Cerebrospinal fluid (CSF) can reasonably be hypothesized to mirror central nervous system pathophysiology in chronic pain conditions. Metabolites are small organic molecules with a low molecular weight. They are the downstream products of genes, transcripts and enzyme functions, and their levels can mirror diseased metabolic pathways. The aim of this metabolomic study was to compare the CSF of patients with chronic neuropathic pain (n = 16) to healthy controls (n = 12). Methods: Nuclear magnetic resonance spectroscopy was used for analysis of the CSF metabolome. Multivariate data analysis by projection discriminant analysis (OPLS-DA) was used to separate information from noise and minimize the multiple testing problem. Results: The significant OPLS-DA model identified 26 features out of 215 as important for group separation (R2 = 0.70, Q2 = 0.42, p = 0.017 by CV-ANOVA; 2 components). Twenty-one out of twenty-six features were statistically significant when comparing the two groups by univariate statistics and remained significant at a false discovery rate of 10%. For six out of the top ten metabolite features, the features were absent in all healthy controls. However, these features were related to medication, mainly acetaminophen (=paracetamol), and not to pathophysiological processes. Conclusion: CSF metabolomics was a sensitive method to detect ongoing analgesic medication, especially acetaminophen.

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