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  • 201.
    Tsartsalis, D.
    et al.
    Department of Cardiology, "Hippokration" Hospital, Athens; 1st Department of Cardiology, University of Athens, Medical School, "Hippokration" Hospital, Athens, Greece.
    Dragioti, Elena
    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.
    Kontoangelos, K.
    1st Department of Psychiatry, University of Athens, Medical School, Eginition University Hospital, Athens, Greece; University Mental Health Research Institute, Athens, Greece.
    Pitsavos, C.
    1st Department of Cardiology, University of Athens, Medical School, "Hippokration" Hospital, Athens, Greece.
    Sakkas, P.
    1st Department of Psychiatry, University of Athens, Medical School, Eginition University Hospital, Athens, Greece.
    Papadimitriou, G. N.
    1st Department of Psychiatry, University of Athens, Medical School, Eginition University Hospital, Athens, Greece.
    Stefanadis, C.
    1st Department of Cardiology, University of Athens, Medical School, "Hippokration" Hospital, Athens, Greece.
    Kallikazaros, I.
    Department of Cardiology, "Hippokration" Hospital, Athens, Greece.
    The impact of depression and cardiophobia on quality of life in patients with essential hypertension.2016In: Psychiatrike = Psychiatriki, ISSN 1105-2333, Vol. 27, no 3, p. 192-203Article in journal (Refereed)
    Abstract [en]

    Patients with chronic conditions like hypertension may experience many negative emotions which endorse the development of anxiety and depression symptomatology, thus they increase their risk for poor quality of life. Several studies have shown an association between symptoms of psychological distress and hypertension. In this study we aimed to quantify the link between depression, cardiophobia and quality of life in hypertensive patients. A cross-sectional design was employed. A sample of 197 hypertensive patients (89 men-108 women, mean age 53 years, SD=12 ranged 25-78) from a university outpatient hypertension clinic in Greece participated. Ninety-four (47.7%) of the participants suffered from essential grade I hypertension; 68 (34.5%) were grade II; 16 (8.1%) were categorized as grade III, while only 11 (5.6%) patients were recorded as normotensives with high normal values. The questionnaires included: (a) question for the recording of social-demographic characteristics and clinical features, (b) The Short Form (SF-36) Health Survey, (c) The Beck Depression Inventory -I, and (d) The Cardiac Anxiety Questionnaire. There were no significant differences between the two genders with exception of marital status (p=0.010), dyslipidemia (p=0.050), grade of hypertension (p=0.014), cardiac left ventricular hypertrophy (p=0.004), renal failure (p=0.043) and stroke (p=0.024). Lower levels of quality of life and higher levels of depression and cardiophobia were observed compared to the general population. There were no significant differences on psychological measures between the two sexes (p>0.05). Cardiophobia was positively related to depressive symptomatology (r=0.533, p=0.000) while negatively to both physical and mental health summary measures of SF-36 health survey (r=-0.467, p=0.000 r=-0.537, p=0.000 respectively). Multiple linear regression models found that for psychical health depression and cardiac anxiety, avoidance activities had an influence on levels of quality of life in hypertensive patients, after controlling for age and other socio-demographic variables and clinical characteristics (Beta=-0.133, p=0.007, Beta=-0.364 p=0.000 and Beta=-0.167 p=0.006, respectively). For mental component summary depression and cardiophobia, heart focused attention had also impact on mental health in hypertensives (Beta=-0.438, p=0.016, Beta=-0.564, p=0.000 and Beta=-0.223, p=0.037, respectively) after adjustments. Heart focused anxiety symptoms-as avoidance activities and/or attention and monitoring cardiac activity, are related to hypertensive patients' present deteriorated depressive symptoms and levels of quality of life. Both depressive symptomatology and heart focused anxiety may be a mechanism partly responsible for hypertensive patients' present impaired levels of quality of life.

  • 202.
    Tseli, Elena
    et al.
    Karolinska Inst, Sweden.
    Boersma, Katja
    Orebro Univ, Sweden.
    Stalnacke, Britt-Marie
    Karolinska Inst, Sweden; Danderyd Hospital, Sweden; Umea Univ, Sweden.
    Enthoven, Paul
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    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.
    Ang, Bjorn O.
    Karolinska Inst, Sweden; Dalarna Univ, Sweden; Uppsala Univ, Sweden.
    Grooten, Wilhelmus J. A.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Prognostic Factors for Physical Functioning After Multidisciplinary Rehabilitation in Patients With Chronic Musculoskeletal Pain A Systematic Review and Meta-Analysis2019In: The Clinical Journal of Pain, ISSN 0749-8047, E-ISSN 1536-5409, Vol. 35, no 2, p. 148-173Article, review/survey (Refereed)
    Abstract [en]

    Objectives: This systematic review aimed to identify and evaluate prognostic factors for long-term (amp;gt;= 6 mo) physical functioning in patients with chronic musculoskeletal pain following multidisciplinary rehabilitation (MDR). Materials and Methods: Electronic searches conducted in MEDLINE, PsycINFO, EMBASE, CINAHL, Web of Science, and Cochrane CENTRAL revealed 25 original research reports, published 1983-2016, (n=9436). Potential prognostic factors relating to initial pain and physical and psychological functioning were synthesized qualitatively and quantitatively in random effects meta-analyses. The level of evidence (LoE) was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Pain-related factors (intensity and chronicity) were not associated with function/disability at long-term follow-up, odds ratio (OR)=0.84; 95% confidence interval (CI), 0.65-1.07 and OR=0.97; 95% CI, 0.93-1.00, respectively (moderate LoE). A better function at follow-up was predicted by Physical factors; higher levels of initial self-reported functioning, OR= 1.07; 95% CI, 1.02-1.13 (low LoE), and Psychological factors; low initial levels of emotional distress, OR= 0.77; 95% CI, 0.65-0.92, low levels of cognitive and behavioral risk factors, OR=0.85; 95% CI, 0.77-0.93 and high levels of protective cognitive and behavioral factors, OR=1.49; 95% CI, 1.17-1.90 (moderate LoE). Discussion: While pain intensity and long-term chronicity did not predict physical functioning in chronic pain patients after MDR, poor pretreatment physical and psychological functioning influenced the prognosis negatively. Thus, treatment should further target and optimize these modifiable factors and an increased focus on positive, psychological protective factors may perhaps provide an opening for yet untapped clinical gains.

  • 203.
    Tseli, Elena
    et al.
    Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Sweden.
    Grooten, Wilhelmus Johannes Andreas
    Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Sweden; Functional Area Occupational Therapy and Physiotherapy, Allied Health Professionals Function, Karolinska University Hospital, Stockholm, Sweden.
    Stålnacke, Britt-Marie
    Department of Community Medicine and Rehabilitation, Rehabilitation Medicine, Umeå University, Umeå, Sweden; Department of Clinical Sciences, Department of Rehabilitation Medicine, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Boersma, Katja
    School of Law, Psychology and Social Work, Örebro University, Örebro, Sweden.
    Enthoven, Paul
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    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.
    Äng, Björn Olov
    Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Sweden; Functional Area Occupational Therapy and Physiotherapy, Allied Health Professionals Function, Karolinska University Hospital, Stockholm, Sweden; School of Education, Health and Social Studies, Dalarna University, Falun, Sweden.
    Predictors of multidisciplinary rehabilitation outcomes in patients with chronic musculoskeletal pain: protocol for a systematic review and meta-analysis2017In: Systematic Reviews, E-ISSN 2046-4053, Vol. 6, no 1, article id 199Article in journal (Refereed)
    Abstract [en]

    Background

    Chronic musculoskeletal pain is a major public health problem. Early prediction for optimal treatment results has received growing attention, but there is presently a lack of evidence regarding what information such proactive management should be based on. This study protocol, therefore, presents our planned systematic review and meta-analysis on important predictive factors for health and work-related outcomes following multidisciplinary rehabilitation (MDR) in patients with chronic musculoskeletal pain.

    Methods

    We aim to perform a synthesis of the available evidence together with a meta-analysis of published peer-reviewed original research that includes predictive factors preceding MDR. Included are prospective studies of adults with benign, chronic (> 3 months) musculoskeletal pain diagnoses who have taken part in MDR. In the studies, associations between personal and rehabilitation-based factors and the outcomes of interest are reported. Outcome domains are pain, physical functioning including health-related quality of life, and work ability with follow-ups of 6 months or more. We will use a broad, explorative approach to any presented predictive factors (demographicsymptoms-relatedphysicalpsychosocialwork-related, and MDR-related) and these will be analyzed through (a) narrative synthesis for each outcome domain and (b) if sufficient studies are available, a quantitative synthesis in which variance-weighted pooled proportions will be computed using a random effects model for each outcome domain. The strength of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation.

    Discussion

    The strength of this systematic review is that it aims for a meta-analysis of prospective cohort or randomized controlled studies by performing an extensive search of multiple databases, using an explorative study approach to predictive factors, rather than building on single predictor impact on the outcome or on predefined hypotheses. In this way, an overview of factors central to MDR outcome can be made and will help strengthen the evidence base and inform a wide readership including health care practitioners and policymakers.

  • 204.
    Turkina, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Ghafouri, Nazdar
    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.
    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.
    Evaluation of dynamic changes in interstitial fluid proteome following microdialysis probe insertion trauma in trapezius muscle of healthy women2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 43512Article in journal (Refereed)
    Abstract [en]

    Microdialysis ( MD) has been shown to be a promising technique for sampling of biomarkers. Implantation of MD probe causes an acute tissue trauma and provokes innate response cascades. In order to normalize tissue a two hours equilibration period for analysis of small molecules has been reported previously. However, how the proteome profile changes due to this acute trauma has yet to be fully understood. To characterize the early proteome events induced by this trauma we compared proteome in muscle dialysate collected during the equilibration period with two hours later in "post-trauma". Samples were collected from healthy females using a 100 kDa MW cut off membrane and analyzed by high sensitive liquid chromatography tandem mass spectrometry. Proteins involved in stress response, immune system processes, inflammatory responses and nociception from extracellular and intracellular fluid spaces were identified. Sixteen proteins were found to be differentially abundant in samples collected during first two hours in comparison to "post-trauma". Our data suggests that microdialysis in combination with mass spectrometry may provide potentially new insights into the interstitial proteome of trapezius muscle, yet should be further adjusted for biomarker discovery and diagnostics. Moreover, MD proteome alterations in response to catheter injury may reflect individual innate reactivity.

  • 205.
    Vaz, Sharmila
    et al.
    Curtin University, Australia.
    Cordier, Reinie
    Curtin University, Australia.
    Boyes, Mark
    Curtin University, Australia.
    Parsons, Richard
    Curtin University, Australia.
    Joosten, Annette
    Curtin University, Australia.
    Ciccarelli, Marina
    Curtin University, Australia.
    Falkmer, Marita
    Curtin University, Australia; Jonköping University, Sweden.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin University, Australia.
    Is Using the Strengths and Difficulties Questionnaire in a Community Sample the Optimal Way to Assess Mental Health Functioning?2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 1, p. e0144039-Article in journal (Refereed)
    Abstract [en]

    An important characteristic of a screening tool is its discriminant ability or the measures accuracy to distinguish between those with and without mental health problems. The current study examined the inter-rater agreement and screening concordance of the parent and teacher versions of SDQ at scale, subscale and item-levels, with the view of identifying the items that have the most informant discrepancies; and determining whether the concordance between parent and teacher reports on some items has the potential to influence decision making. Cross-sectional data from parent and teacher reports of the mental health functioning of a community sample of 299 students with and without disabilities from 75 different primary schools in Perth, Western Australia were analysed. The study found that: a) Intraclass correlations between parent and teacher ratings of childrens mental health using the SDQ at person level was fair on individual child level; b) The SDQ only demonstrated clinical utility when there was agreement between teacher and parent reports using the possible or 90% dichotomisation system; and c) Three individual items had positive likelihood ratio scores indicating clinical utility. Of note was the finding that the negative likelihood ratio or likelihood of disregarding the absence of a condition when both parents and teachers rate the item as absent was not significant. Taken together, these findings suggest that the SDQ is not optimised for use in community samples and that further psychometric evaluation of the SDQ in this context is clearly warranted.

  • 206.
    Vaz, Sharmila
    et al.
    Curtin University, Australia.
    Cordier, Reinie
    Curtin University, Australia.
    Falkmer, Marita
    Curtin University, Australia; Jonköping University, Sweden.
    Ciccarelli, Marina
    Curtin University, Australia.
    Parsons, Richard
    Curtin University, Australia; Curtin University, Australia.
    McAuliffe, Tomomi
    James Cook University, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin University, Australia.
    Should Schools Expect Poor Physical and Mental Health, Social Adjustment, and Participation Outcomes in Students with Disability?2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, p. e0126630-Article in journal (Refereed)
    Abstract [en]

    The literature on whether students with disabilities have worse physical and mental health, social adjustment, and participation outcomes when compared to their peers without disabilities is largely inconclusive. While the majority of case control studies showed significantly worse outcomes for students with disabilities; the proportion of variance accounted for is rarely reported. The current study used a population cross-sectional approach to determine the classification ability of commonly used screening and outcome measures in determining the disability status. Furthermore, the study aimed to identify the variables, if any, that best predicted the presence of disability. Results of univariate discriminant function analyses suggest that across the board, the sensitivity of the outcome/screening tools to correctly identify students with a disability was 31.9% higher than the related Positive Predictive Value (PPV). The lower PPV and Positive Likelihood Ratio (LR+) scores suggest that the included measures had limited discriminant ability (17.6% to 40.3%) in accurately identifying students at-risk for further assessment. Results of multivariate analyses suggested that poor health and hyperactivity increased the odds of having a disability about two to three times, while poor close perceived friendship and academic competences predicted disability with roughly the same magnitude. Overall, the findings of the current study highlight the need for researchers and clinicians to familiarize themselves with the psychometric properties of measures, and be cautious in matching the function of the measures with their research and clinical needs.

  • 207.
    Vaz, Sharmila
    et al.
    Curtin University, Australia.
    Falkmer, Marita
    Curtin University, Australia; Jonköping University, Sweden.
    Ciccarelli, Marina
    Curtin University, Australia.
    Passmore, Anne
    Curtin University, Australia.
    Parsons, Richard
    Curtin University, Australia; Curtin University, Australia.
    Black, Melissa
    Curtin University, Australia.
    Cuomo, Belinda
    Curtin University, Australia.
    Tan, Tele
    Curtin University, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin University, Australia.
    Belongingness in Early Secondary School: Key Factors that Primary and Secondary Schools Need to Consider2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, p. e0136053-Article in journal (Refereed)
    Abstract [en]

    It is unknown if, and how, students redefine their sense of school belongingness after negotiating the transition to secondary school. The current study used longitudinal data from 266 students with, and without, disabilities who negotiated the transition from 52 primary schools to 152 secondary schools. The study presents the 13 most significant personal student and contextual factors associated with belongingness in the first year of secondary school. Student perception of school belongingness was found to be stable across the transition. No variability in school belongingness due to gender, disability or household-socio-economic status (SES) was noted. Primary school belongingness accounted for 22% of the variability in secondary school belongingness. Several personal student factors (competence, coping skills) and school factors (low-level classroom task-goal orientation), which influenced belongingness in primary school, continued to influence belongingness in secondary school. In secondary school, effort-goal orientation of the student and perception of their schools tolerance to disability were each associated with perception of school belongingness. Family factors did not influence belongingness in secondary school. Findings of the current study highlight the need for primary schools to foster belongingness among their students at an early age, and transfer students belongingness profiles as part of the handover documentation. Most of the factors that influenced school belongingness before and after the transition to secondary are amenable to change.

  • 208.
    Vaz, Sharmila
    et al.
    Curtin University, Australia.
    Falkmer, Marita
    Curtin University, Australia; Jonköping University, Sweden.
    Ciccarelli, Marina
    Curtin University, Australia.
    Passmore, Anne
    Curtin University, Australia.
    Parsons, Richard
    Curtin University, Australia; Curtin University, Australia.
    Tan, Tele
    Curtin University, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin University, Australia.
    The Personal and Contextual Contributors to School Belongingness among Primary School Students2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, p. e0123353-Article in journal (Refereed)
    Abstract [en]

    School belongingness has gained currency among educators and school health professionals as an important determinant of adolescent health. The current cross-sectional study presents the 15 most significant personal and contextual factors that collectively explain 66.4% (two-thirds) of the variability in 12-year old students perceptions of belongingness in primary school. The study is part of a larger longitudinal study investigating the factors associated with student adjustment in the transition from primary to secondary school. The study found that girls and students with disabilities had higher school belongingness scores than boys, and their typically developing counterparts respectively; and explained 2.5% of the variability in school belongingness. The majority (47.1% out of 66.4%) of the variability in school belongingness was explained by student personal factors, such as social acceptance, physical appearance competence, coping skills, and social affiliation motivation; followed by parental expectations (3% out of 66.4%), and school-based factors (13.9% out of 66.4%) such as, classroom involvement, task-goal structure, autonomy provision, cultural pluralism, and absence of bullying. Each of the identified contributors of primary school belongingness can be shaped through interventions, system changes, or policy reforms.

  • 209.
    Vaz, Sharmila
    et al.
    Curtin University, Australia.
    Wilson, Nathan
    University of Western Sydney, Australia.
    Falkmer, Marita
    Curtin University, Australia; Jonköping University, Sweden.
    Sim, Angela
    Curtin University, Australia.
    Scott, Melissa
    Curtin University, Australia.
    Cordier, Reinie
    Curtin University, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin University, Australia.
    Factors Associated with Primary School Teachers Attitudes Towards the Inclusion of Students with Disabilities2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 8, p. e0137002-Article in journal (Refereed)
    Abstract [en]

    Objective Teachers attitudes toward inclusion are often based on the practical implementation of inclusive education rather than a specific ideology and understanding of inclusiveness. This study aimed to identify the factors associated with primary school teachers attitudes towards inclusion of students with all disabilities in regular schools. Method Seventy four primary school teachers participated in a cross-sectional survey conducted in Western Australia. Teachers attitudes and efficacy toward integration of students with disabilities were measured using the Opinions Relative to Integration of Students with Disabilities scale and Banduras Teacher Efficacy scale respectively. Results Four teacher attributes-age, gender, teaching self-efficacy and training collectively explained 42% of the variability in teachers attitude toward including students with disabilities. Conclusion The current study further contributes to the accumulation of knowledge that can unpack the complex pattern of factors that should be considered to promote positive attitudes towards inclusive schools.

  • 210.
    Veenstra, Helene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Alföldi, Péter
    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.
    Södermark, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Graven-Nielsen, Thomas
    Aalborg Univ, Denmark.
    Sjors, Anna
    Univ Gothenburg, Sweden.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    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. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Chronic widespread pain patients show disrupted cortical connectivity in default mode and salience networks, modulated by pain sensitivity2019In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 12, p. 1743-1755Article in journal (Refereed)
    Abstract [en]

    Purpose: The remodeling of functional neuronal connectivity in chronic widespread pain (CWP) patients remains largely unexplored. This study aimed to investigate functional connectivity in CWP patients in brain networks related to chronic pain for changes related to pain sensitivity, psychological strain, and experienced pain.

    Patients and methods: Functional connectivity strength of the default mode network (DMN) and the salience network (SN) was assessed with functional magnetic resonance imaging. Between-group differences were investigated with an independent component analysis for altered connectivity within the whole DMN and SN. Then, changes in connectivity between nodes of the DMN and SN were investigated with the use of a seed-target analysis in relation to the covariates clinical pain intensity, pressure pain sensitivity, psychological strain, and as an effect of experienced experimental cuff-pressure pain.

    Results: CWP patients showed decreased connectivity in the inferior posterior cingulate cortex (PCC) in the DMN and increased connectivity in the left anterior insula/superior temporal gyrus in the SN when compared to controls. Moreover, higher pain sensitivity in CWP when compared to controls was related to increased connectivity within the SN (between left and right insula) and between SN and DMN (between right insula and left lateral parietal cortex).

    Conclusion: This study shows that connectivity within the DMN was decreased and connectivity within the SN was increased for CWP. Furthermore, we present a novel finding of interaction of pain sensitivity with SN and DMN-SN functional connectivity in CWP.

  • 211.
    Ward, Liam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Olausson, Patrik
    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.
    Li, Wei
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Yuan, Ximing
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Proteomics and multivariate modelling reveal sex-specific alterations in distinct regions of human carotid atheroma2018In: Biology of Sex Differences, ISSN 2042-6410, Vol. 9, article id 54Article in journal (Refereed)
    Abstract [en]

    BackgroundAtherosclerotic lesions are comprised of distinct regions with different proteomic profiles. Men and women develop differences in lesion phenotype, with lesions from women generally being more stable and less prone to rupture. We aimed to investigate the differences in proteomic profiles between sexes, including distinct lesion regions, to identify altered proteins that contribute to these differences observed clinically.MethodsCarotid endarterectomy samples (ten men/ten women) were obtained, and intraplaque biopsies from three distinct regions (internal control, fatty streak and plaque) were analysed by tandem-mass spectrometry. Multivariate statistical modelling, using orthogonal partial least square-discriminant analysis, was used to discriminate the proteomes between men and women.ResultsMultivariate discriminant modelling revealed proteins from 16 functional groups that displayed sex-specific associations. Additional statistics revealed ten proteins that display region-specific alterations when comparing sexes, including proteins related to inflammatory response, response to reactive oxygen species, complement activation, transport and blood coagulation. Transport protein afamin and blood coagulation proteins antithrombin-III and coagulation factor XII were significantly increased in plaque region from women. Inflammatory response proteins lysozyme C and phospholipase A2 membrane-associated were significantly increased in plaque region from men. Limitations with this study are the small sample size, limited patient information and lack of complementary histology to control for cell type differences between sexes.ConclusionsThis pilot study, for the first time, utilises a multivariate proteomic approach to investigate sexual dimorphism in human atherosclerotic tissue, and provides an essential proteomic platform for further investigations to help understand sexual dimorphism and plaque vulnerability in atherosclerosis.

  • 212.
    Wigston, Christine
    et al.
    Curtin University, Australia.
    Falkmer, Marita
    Curtin University, Australia; Jonköping University, Sweden.
    Vaz, Sharmila
    Curtin University, Australia.
    Parsons, Richard
    Curtin University, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin University, Australia; La Trobe University, Australia.
    Participation in extracurricular activities for children with and without siblings with autism spectrum disorder2017In: Developmental Neurorehabilitation, ISSN 1751-8423, E-ISSN 1751-8431, Vol. 20, no 1, p. 25-39Article in journal (Refereed)
    Abstract [en]

    Objective: To compare the number, frequency, enjoyment and performance in extracurricular activities of siblings of children with autism spectrum disorders (ASD) to their typically developing (TD) peers, and to identify differences between actual and desired participation. Methods: A case-control study with 30 siblings of children with ASD and 30 siblings of TD children was conducted using the Paediatric Interest Profiles and a questionnaire. Results: Siblings of children with ASD participated in fewer extracurricular activities than those with TD siblings. ASD symptoms were significantly associated with the sibling participating in fewer extracurricular activities. Children with TD siblings had higher enjoyment scores in relaxation activities than children with siblings with ASD. Conclusion: While results were mainly positive, some differences indicated that having a sibling with ASD may impact participation in extracurricular activities. Assessments of participation barriers, as well as support to minimise participation restrictions among siblings of children with ASD are required.

  • 213.
    Wiklund, Tobias
    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.
    Linton, Steven J.
    Örebro Univ, Sweden.
    Alföldi, Peter
    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.
    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.
    Is sleep disturbance in patients with chronic pain affected by physical exercise or ACT-based stress management? - A randomized controlled study2018In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 19, article id 111Article in journal (Refereed)
    Abstract [en]

    Background: Most people suffering chronic pain are plagued by sleeping difficulties. Cognitive behaviour therapy has produced promising results for insomnia comorbid with chronic pain, but the access to such treatment is often limited. Over the last ten years, interventions aiming to increase cognitive flexibility and physical activity have been assumed to be effective treatments for a variety of conditions, including insomnia and chronic pain. If proven effective, these treatments could constitute the first steps in a stepped care model for chronic pain and insomnia. Methods: Two hundred ninety-nine chronic pain subjects were randomized to Exercise, ACT-based stress management (ACT-bsm), or an active control group. Two hundred thirty-two participants (78%) received their allocated intervention at least to some extent. These participants were evaluated using mixed model analyses for changes in sleep (Insomnia Severity Index, ISI), pain intensity, depression, and anxiety immediately after treatment, six months and twelve months after treatment. Results: The mixed model analyses revealed that Exercise had a positive effect on insomnia compared with the control group and the effect remained after 12 months. No clear effect (i.e., both for completers and for completers together with treatment non-completers) upon ISI was found for the ACT-bsm. Pain intensity decreased significantly both in the exercise group and in the control group. For the two psychological variables (i.e., symptoms of anxiety and depression) were found significant improvements over time but no group differences. The treatment effects for ISI and pain intensity did not reach clinical significance per definitions presented in other relevant studies. Conclusions: Beneficial significant effects on insomnia was confirmed in the exercise condition. However, these changes were probably not clinically important. For pain intensity a general decrease was found in the Exercise condition and in the control condition, while no change occurred in ACT-bsm. No group differences were found for the two psychological variables.

  • 214.
    Wåhlén, Karin
    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.
    Fornander, Louise
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Olausson, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ydreborg, Kjell
    Clinic of Otorhinolaryngology, County Hospital Ryhov, Jönköping, Sweden.
    Flodin, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Graff, Pål
    Department of Occupational and Environmental Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. 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, Pain and Rehabilitation Center. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Protein profiles of nasal lavage fluid from individuals with work-related upper airway symptoms associated to moldy and damp buildings2016In: Indoor Air, ISSN 0905-6947, E-ISSN 1600-0668, Vol. 26, no 5, p. 743-754Article in journal (Refereed)
    Abstract [en]

    Upper airway irritation is common among individuals working in moldy and damp buildings. The aim was to investigate effects on the protein composition of the nasal lining fluid. The prevalence of symptoms in relation to work was examined in 37 individuals working in two damp buildings. Microbial growth was confirmed in one of the buildings. Nasal lavage fluid was collected from 29 exposed subjects and 13 controls. Protein profiles were investigated with a proteomic approach and evaluated by multivariate statistical models. Subjects from both workplaces reported upper airway and ocular symptoms. Based on protein profiles, symptomatic subjects in the two workplaces were discriminated from each other and separated from healthy controls. The groups differed in proteins involved in inflammation and host defense. Measurements of innate immunity proteins showed a significant increa e of protein S100-A8 and decrease of SPLUNC1 in subjects from one workplace while alpha-1-antitrypsin was elevated in subjects from the other workplace, compared to healthy controls. The results show that protein profiles in nasal lavage fluid can be used to monitor airway mucosal effects in personnel working in damp buildings and indicate that the profile may be separate when the dampness is associated with the presence of molds.

  • 215.
    Wåhlén, Karin
    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.
    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.
    Ghafouri, Nazdar
    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.
    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.
    Plasma Protein Pattern Correlates With Pain Intensity and Psychological Distress in Women With Chronic Widespread Pain2018In: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 9, article id 2400Article in journal (Refereed)
    Abstract [en]

    Objectives: Although generalized muscle pain, tiredness, anxiety, and depression are commonly present among chronic widespread pain (CWP) patients, the molecular mechanisms behind CWP are not fully elucidated. Moreover, the lack of biomarkers often makes diagnosis and treatment problematic. In this study, we investigated the correlation between pain intensity, psychological distress, and plasma proteins among CWP patients and controls (CON). Methods: The plasma proteome of CWP (n = 15) and CON (n = 23) was analyzed using two-dimensional gel electrophoresis. Orthogonal Partial Least Square analysis (OPLS) was used to determine proteins associated with pain intensity (numeric rating scale) in CWP and psychological distress (Hospital and Depression Scale, HADS) in CWP and CON. Significant proteins were identified by MALDI-TOF and tandem MS. Results: In CWP, pain intensity was associated with plasma proteins mostly involved in metabolic and immunity processes (e.g., kininogen-1, fibrinogen gamma chain, and ceruloplasmin), and psychological distress was associated with plasma proteins related to immunity response, iron ion, and lipid metabolism (e.g., complement factor B, complement C1r subcomponent, hemopexin, and clusterin). Discussion: This study suggests that different plasma protein patterns are associated with different pain intensity and psychological distress in CWP. Proteins belonging to the coagulation cascade and immunity processes showed strong associations to each clinical outcome. Using the plasma proteome profile of CWP to study potential biomarker candidates provides a snapshot of ongoing systemic mechanisms in CWP.

  • 216.
    Wåhlén, Karin
    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.
    Olausson, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Carlsson, Anders K
    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, Nazdar
    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.
    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.
    Systemic alterations in plasma proteins from women with chronic widespread pain compared to healthy controls: a proteomic study2017In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 10, p. 797-809Article in journal (Refereed)
    Abstract [en]

    Chronic widespread pain (CWP) is a complex pain condition that is difficult to treat. The prevalence of CWP approximates similar to 10% of the general population, with higher prevalence in women. Lack of understanding of molecular mechanisms has been a challenge for diagnosis and treatment of chronic pain. The aim of this study was to explore the systemic protein changes in CWP compared to those in healthy controls (CON). By applying 2-dimensional gel electrophoresis, we analyzed the protein pattern of plasma samples from women with CWP (n=16) and healthy women (n=23). The proteomic data were analyzed using multivariate statistical models, and altered proteins were identified using mass spectrometry. The proteome analysis was further validated by gel-free Western blot. Multivariate statistical data analysis of quantified proteins revealed 22 altered proteins in women with CWP, compared to CON group. Many of the identified proteins are previously known to be involved in different parts of the complement system and metabolic and inflammatory processes, e.g., complement factor B, vitamin D-binding protein, ceruloplasmin, transthyretin and alpha-2-HS-glycoprotein. These results indicate that important systemic protein differences exist between women with CWP and healthy women. Further, this study illustrates the potential use of proteomics to detect biomarkers that may provide new insights into the molecular mechanism(s) of chronic pain. However, further larger investigations are required in order to confirm these findings before it will be possible to identify proteins as potential pain biomarkers for clinical use.

  • 217.
    Yan-Ting Chee, Derserri
    et al.
    Curtin University, Australia.
    Chung-Yeung Lee, Hoe
    Curtin University, Australia.
    Falkmer, Marita
    Jonkoping Univ, Inst Disabil Res, CHILD Programme, Sch Educ and Commun, Linkoping, Sweden; Curtin University, Australia.
    Barnett, Tania
    Curtin University, Australia.
    Falkmer, Olov
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Siljehav, Jessica
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin University, Australia; La Trobe University, Australia.
    Viewpoints on driving of individuals with and without autism spectrum disorder2015In: Developmental Neurorehabilitation, ISSN 1751-8423, E-ISSN 1751-8431, Vol. 18, no 1, p. 26-36Article in journal (Refereed)
    Abstract [en]

    Objective: Understanding the viewpoints of drivers with autism spectrum disorder (ASD) is crucial in the development of mobility support and driver training that is responsive to their needs. Methods: Fifty young adults with ASD and fifty seven typically developed adults participated in the study to form a contrasting group. Q-methodology was used to understand viewpoints on driving as a main mode of transportation. Data were analysed using a PQ by-person varimax rotation factor analysis. Results: Although some ASD participants perceived themselves as confident and independent drivers, others preferred other modes of transportation such as public transport and walking. Anxiety was also found to be a barrier to driving. The contrast group revealed consistent viewpoints on their driving ability. They preferred driving as their main mode of transportation and believed that they were competent, safe and independent drivers. Conclusion: These results are important in the planning of transport policies and driver training for individuals with ASD. Driver training manuals can be developed to address anxiety issues, hazard perception and navigation problems in the ASD population. Their use of public transport could be further facilitated through more inclusive transport policies.

  • 218.
    Yi, Jewel
    et al.
    Curtin University, Australia.
    Chung-Yeung Lee, Hoe
    Curtin University, Australia.
    Parsons, Richard
    Curtin University, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin University, Australia; La Trobe University, Australia.
    The Effect of the Global Positioning System on the Driving Performance of People with Mild Alzheimers Disease2015In: Gerontology, ISSN 0304-324X, E-ISSN 1423-0003, Vol. 61, no 1, p. 79-88Article in journal (Refereed)
    Abstract [en]

    Introduction: The initial symptoms of Alzheimers disease (AD) include attention deficits, memory loss and deficiencies in topographic and spatial orientation. People with AD may have way-finding difficulties in driving due to the deterioration of their navigation ability. Although the use of the Global Positioning System (GPS) has been proven to be a useful aid for older people in driving, there is no evidence to suggest that the benefit could extend to drivers with AD. Aim: This study aims to investigate the effectiveness of the GPS in assisting drivers with mild AD in finding their destination safely. Method: Twenty-eight drivers with mild to very mild AD, diagnosed by a general practitioner or a psychogeriatrician, completed all clinical and psychometric assessments including the Mini Mental State Examination, Trail Making Test B and Doors and People Test. During the driving assessment, 3 driving trials with different settings (normal, visualonly and audio-only) of the GPS were administered to all participants. The participants were required to follow instructions from the GPS and perform a variety of driving tasks on a driving simulator. The driving performances of participants were assessed by criteria specific to AD drivers. The driving assessment criteria were first combined to form the overall driving performance score: a higher score indicated a better overall driving performance. The other outcome of this study was the success of participants to navigate to a predetermined destination. Results: The driving performance of participants was different among the 3 settings (F = 72.8, p less than 0.001) and the pairwise comparison between the 3 settings was significant (p less than 0.001). The driving performance score was highest in the audio-only setting (mean: 20.0, SD: 2.2), moderate in the normal setting (mean: 16.7, SD: 2.6) and lowest in the visual-only setting (mean: 14.3, SD: 3.3). When compared with the visual-only setting, drivers using the audioonly setting (OR: 37.2, 95% CI: 9.2-151.2) and normal setting (OR: 37.2, 95% CI: 4.8-286.9) were more likely to successfully find their destination (p less than 0.05). Conclusion: This study has found that using single, simple auditory instructions with the absence of the visual output of the GPS could potentially help people with mild AD to improve their driving ability and reach their destination.

  • 219.
    Yuan, Xi-Ming
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Sultana, Nargis
    Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Siraj, Nabeel
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ward, Liam J
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Li, Wei
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Autophagy Induction Protects Against 7-Oxysterol-induced Cell Death via Lysosomal Pathway and Oxidative Stress2016In: Journal of cell death, ISSN 1179-0660, no 9, p. 1-7Article in journal (Refereed)
    Abstract [en]

    7-Oxysterols are major toxic components in oxidized low-density lipoprotein and human atheroma lesions, which cause lysosomal mem-brane permeabilization (LMP) and cell death. Autophagy may function as a survival mechanism in this process. Here, we investigated whether 7-oxysterols mixed in an atheroma-relevant proportion induce autophagy, whether autophagy induction influences 7-oxysterol-mediated cell death, and the underlying mechanisms, by focusing on cellular lipid levels, oxidative stress, and LMP in 7-oxysterol-treated macrophages. We found that 7-oxysterols induced cellular lipid accumulation, autophagy dysfunction, and cell death in the form of both apoptosis and necrosis. Exposure to 7-oxysterols induced autophagic vacu-ole synthesis in the form of increased autophagy marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and LC3-phosphatidylethanolamine conjugate (LC3-II) and autophagic vacuole formation. This led to an accumulation of p62, indicating a reduction in autophagic vacuole degradation. Importantly, autophagy induction significantly reduced 7-oxysterol-mediated cell death by diminishing LMP and oxidative stress. Moreover, autophagy induction minimized cellular lipid accumulation induced by 7-oxysterols. These findings highlight the importance of autophagy in combating cellular stress, LMP, and cell death in atherosclerosis. Therefore, activation of the autophagy pathway may be a potential therapeutic strategy for prevention of necrotic core formation in atherosclerotic lesions.

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