| 1. |
- Sylwander, Charlotte, 1992-, et al.
(författare)
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The impact of chronic widespread pain on health status and long-term health predictors: a general population cohort study
- 2020
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Ingår i: BMC Musculoskeletal Disorders. - London : Springer Science and Business Media LLC. - 1471-2474. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Chronic widespread pain (CWP) has a negative impact on health status, but results have varied regarding gender-related differences and reported health status. The aim was to study the impact of CWP on health status in women and men aged 35-54 years in a sample of the general population. The aim was further to investigate lifestyle-related predictors of better health status in those with CWP in a 12- and 21-year perspective. Method A general population cohort study including 975 participants aged 35-54 years, with a 12- and 21-year follow-up. CWP was measured with a pain mannequin, and the questionnaire included questions on lifestyles factors with SF-36 for measurement of health status. Differences in health status were analysed with independent samples t-test and health predictors with logistic regression analysis. Results The prevalence of CWP was higher in women at all time points, but health status was reduced in both women and men with CWP (p < 0.001) with no gender differences of clinical relevance. At the 12-year follow-up, a higher proportion of women than men had developed CWP (OR 2.04; CI 1.27-3.26), and at the 21-year follow-up, a higher proportion of men had recovered from CWP (OR 3.79; CI 1.00-14.33). In those reporting CWP at baseline, a better SF-36 health status (Physical Functioning, Vitality or Mental Health) at the 12-year follow-up was predicted by male gender, having personal support, being a former smoker, and having no sleeping problems. In the 21-year follow-up, predictors of better health were male gender, a weekly intake of alcohol, and having no sleeping problems. Conclusion Women and men with CWP have the same worsening of health status, but men recover from CWP to a greater extent in the long-term. Being male, having social support, being a former smoker, and having no sleeping problems were associated with better health status in those with CWP.
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| 2. |
- Andersson, Ingemar, 1950-
(författare)
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Rehabilitering vid långvarig smärta
- 2010. - 2
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Ingår i: Smärta och smärtbehandling. - Stockholm : Liber. - 9789147084135 ; , s. 401-409
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Fan, Yue, et al.
(författare)
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Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Single-cell and spatial transcriptomics analysis of human knee articular cartilage tissue to present a comprehensive transcriptome landscape and osteoarthritis (OA)-critical cell populations.METHODS: Single-cell RNA sequencing and spatially resolved transcriptomic technology have been applied to characterise the cellular heterogeneity of human knee articular cartilage which were collected from 8 OA donors, and 3 non-OA control donors, and a total of 19 samples. The novel chondrocyte population and marker genes of interest were validated by immunohistochemistry staining, quantitative real-time PCR, etc. The OA-critical cell populations were validated through integrative analyses of publicly available bulk RNA sequencing data and large-scale genome-wide association studies.RESULTS: We identified 33 cell population-specific marker genes that define 11 chondrocyte populations, including 9 known populations and 2 new populations, that is, pre-inflammatory chondrocyte population (preInfC) and inflammatory chondrocyte population (InfC). The novel findings that make this an important addition to the literature include: (1) the novel InfC activates the mediator MIF-CD74; (2) the prehypertrophic chondrocyte (preHTC) and hypertrophic chondrocyte (HTC) are potentially OA-critical cell populations; (3) most OA-associated differentially expressed genes reside in the articular surface and superficial zone; (4) the prefibrocartilage chondrocyte (preFC) population is a major contributor to the stratification of patients with OA, resulting in both an inflammatory-related subtype and a non-inflammatory-related subtype.CONCLUSIONS: Our results highlight InfC, preHTC, preFC and HTC as potential cell populations to target for therapy. Also, we conclude that profiling of those cell populations in patients might be used to stratify patient populations for defining cohorts for clinical trials and precision medicine.
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| 4. |
- Wang, Xi, et al.
(författare)
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Comparison of the major cell populations among osteoarthritis, Kashin-Beck disease and healthy chondrocytes by single-cell RNA-seq analysis
- 2021
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Ingår i: Cell Death and Disease. - : Springer Nature. - 2041-4889 .- 2041-4889. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Chondrocytes are the key target cells of the cartilage degeneration that occurs in Kashin-Beck disease (KBD) and osteoarthritis (OA). However, the heterogeneity of articular cartilage cell types present in KBD and OA patients and healthy controls is still unknown, which has prevented the study of the pathophysiology of the mechanisms underlying the roles of different populations of chondrocytes in the processes leading to KBD and OA. Here, we aimed to identify the transcriptional programmes and all major cell populations in patients with KBD, patients with OA and healthy controls to identify the markers that discriminate among chondrocytes in these three groups. Single-cell RNA sequencing was performed to identify chondrocyte populations and their gene signatures in KBD, OA and healthy cells to investigate their differences as related to the pathogenetic mechanisms of these two osteochondral diseases. We performed immunohistochemistry and quantitative reverse-transcription PCR (qRT-PCR) assays to validate the markers for chondrocyte population. Ten clusters were labelled by cell type according to the expression of previously described markers, and one novel population was identified according to the expression of a new set of markers. The homeostatic and mitochondrial chondrocyte populations, which were identified by the expression of the unknown markers MT1X and MT2A and MT-ND1 and MT-ATP6, were markedly expanded in KBD. The regulatory chondrocyte population, identified by the expression of CHI3L1, was markedly expanded in OA. Our study allows us to better understand the heterogeneity of chondrocytes in KBD and OA and provides new evidence of differences in the pathogenetic mechanisms between these two diseases.
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| 5. |
- Eriksson, Catharina, 1955-
(författare)
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Immunological mechanisms in systemic autoimmunity : autoantibodies and chemokines in systemic lupus erythematosus and during treatment with TNF inhibitors in rheumatoid arthritis
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background. Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease that, without powerful treatment, may lead to irreversible joint damage. During the past decade, anti-cytokine therapy has become available, e.g., infliximab, a chimeric antibody targeting the pro-inflammatory cytokine TNF that has a central role in the inflammatory process in RA patients. Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that may affect all organs and is characterized by a massive antibody production. Chemokines, chemokine receptors and lipoprotein receptor-related protein 1(CD91) are regulators of inflammation in autoimmune diseases and T-cell migration. Objectives. The aim of this study was to get a deeper understanding how TNF blocking treatment influences inflammatory mechanisms and autoantibody formation in RA with special reference to similarities and differences with SLE. Methods. In patients with RA treated with anti-TNF, and in SLE patients (ACR criteria) clinical evaluation was performed and blood samples analyzed. Autoantibodies were analyzed using indirect immunofluorescence, ELISA and multiplex flow cytometry in samples from anti-TNF treated RA patients (n=59) followed longitudinally for 54 weeks, in pre-diseased samples from SLE patients (n=38) and matched population-based controls (n=152). T-cell expression of chemokine receptors and CD91 was analyzed by flow cytometry, whilst serum levels of chemokines were determined using ELISA in anti-TNF treated RA-patients (n=24) followed longitudinally (30 weeks), and cross-sectionally in SLE-patients (n=23). Expression of mRNA for chemokines was analyzed in T-cells from SLE-patients (n=10) using PCR. Results. After treatment with infliximab, RA patients produced ANA, anti-dsDNA and anti-nucleosome antibodies, but not anti-ENA antibodies. Although these antibodies are considered typical for SLE only one patient developed a transient lupus-syndrome. Antibodies against cell nuclear antigens, including ENA, were detected several years before the first clinical symptom of SLE; anti-SSA was the earliest detectable antibody. In RA-patients before infliximab treatment, the T-cell expression of several chemokine receptors was elevated compared with healthy controls. In contrast, only one soluble chemokine, IP-10 was elevated. After treatment the levels of soluble MIP-1β, MCP-1 and IP-10, and the T-cell expression of CCR2 were decreased. In SLE-patients MIP-1β, MCP-1, SDF-1, IP-10 and RANTES in blood were elevated, whilst expression of CXCR5 and CCR6 on T-cells was lower than in healthy controls. T-cell expression of CXCR2 and CCR1 was elevated in active disease (measured as SLEDAI index), whereas the CXCR5 and CCR2 expression was lower in inactive SLE. In SLE patients with nephritis IP-10 was lower and T-cell expression of CXCR3 and CCR3 elevated compared with patients without nephritis. The expression of CD91 was higher on T-cells from patients not responsive to infliximab treatment compared with responders. Conclusion. These findings indicate that anti-TNF (infliximab) treatment in RA-patients has a major impact on the production of autoantibodies and chemokines. The autoantibody profile in infliximab-treated patients was similar to that predating disease onset in SLE patients with the exception of anti-ENA being detectable in SLE, but the development of lupus-syndromes was rare. The expression of CD91 on T-cells may predict responsiveness to infliximab. The expression of chemokine receptors in SLE- patients seemed to be related to disease activity. Anti-nuclear antibodies were detectable years before clinical disease onset in patients who developed SLE suggesting a gradual pathogenic process.
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| 6. |
- Kahn, Robin, et al.
(författare)
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Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms
- 2022
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:2, s. 354-62
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Our aim was to describe the outcomes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Methods: This national, population-based, longitudinal, multicentre study used Swedish data that were prospectively collected between 1 December 2020 and 31 May 2021. All patients met the World Health Organization criteria for MIS-C. The outcomes 2 and 8weeks after diagnosis are presented, and follow-up protocols are suggested. Results: We identified 152 cases, and 133 (87%) participated. When followed up 2weeks after MIS-C was diagnosed, 43% of the 119 patients had abnormal results, including complete blood cell counts, platelet counts, albumin levels, electrocardiograms and echocardiograms. After 8weeks, 36% of 89 had an abnormal patient history, but clinical findings were uncommon. Echocardiogram results were abnormal in 5% of 67, and the most common complaint was fatigue. Older children and those who received intensive care were more likely to report symptoms and have abnormal cardiac results. Conclusion: More than a third (36%) of the patients had persistent symptoms 8weeks after MIS-C, and 5% had abnormal echocardiograms. Older age and higher levels of initial care appeared to be risk factors. Structured follow-up visits are important after MIS-C.
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| 7. |
- Andersson, Maria L.E., et al.
(författare)
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Cohort profile: the Halland osteoarthritis (HALLOA) cohort-from knee pain to osteoarthritis: a longitudinal observational study in Sweden
- 2022
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Ingår i: Bmj Open. - London : BMJ. - 2044-6055. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The overall objective in this study is to investigate the early development of radiographic knee osteoarthritis (OA) and its association with hand or/and knee OA, metabolic diseases, biomarkers, chronic pain, physical function and daily physical activity types. Participants The Halland osteoarthritis (HALLOA) cohort is a longitudinal cohort study that includes individuals with knee pain in the southwest of Sweden. Enrolment took place from 2017 to 2019. The inclusion criteria were current knee pain, with no former known radiographic knee OA and no cruciate ligament rupture or rheumatological disorder. The participants were recruited: (1) when seeking care for knee pain in primary healthcare or (2) by advertisements in local newspapers. There are 306 individuals included in the study, mean age (SD) 51.7 (8.7) years and 69% are women. The baseline and follow-ups include clinical tests, radiographical examinations, blood samples, metabolic measures, pain pressure thresholds, tests of physical functions, daily physical activity types and patient-reported outcomes. Findings to date There were associations between metabolic factors and radiographic knee OA, even in those with normal body mass index at baseline. In addition, clinical hand OA was positively associated with fasting plasma glucose. We also found that modifiable factors as increased visceral fat and total body fat were associated with increased pain sensitivity among individuals with knee pain. Future plans By studying possible pathophysiological mechanisms of OA over time, we aim to provide new insights on OA progression, identify usable preventive measures helping the clinicians in the management of the disease and improve health for the patients. It is also important to study the development of chronic pain in OA, to get tools to identify individuals at risk and to be able to offer them treatment.
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| 8. |
- Westman, Gabriel, 1977-, et al.
(författare)
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Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis.
- 2021
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Ingår i: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 27:8, s. 1131-1136
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim was to investigate the correlation between biomarkers of brain injury and long-term neurocognitive outcome, and the interplay with intrathecal inflammation and neuronal autoimmunity, in patients with herpes simplex encephalitis (HSE).METHODS: A total of 53 adult/adolescent HSE patients were included from a prospective cohort in a randomized placebo-controlled trial investigating the effect of a 3-month follow-up treatment with valaciclovir. Study subjects underwent repeated serum/cerebrospinal fluid (CSF) sampling and brain magnetic resonance imaging in the first 3 months along with cognitive assessment using the Mattis Dementia Rating Scale (MDRS) at 24 months. CSF samples were analysed for biomarkers of brain injury, inflammation and synaptic autoimmunity. The predefined primary analysis was the correlation between peak CSF neurofilament protein (NFL), a biomarker of neuronal damage, and MDRS at 24 months.RESULTS: Impaired cognitive performance significantly correlated with NFL levels (rho = -0.36, p = 0.020). Development of IgG anti-N-methyl-D-aspartate receptor (NDMAR) antibodies was associated with a broad and prolonged proinflammatory CSF response. In a linear regression model, lower MDRS at 24 months was associated with previous development of IgG anti-N-methyl-D-aspartate receptor (NMDAR) (beta = -0.6249, p = 0.024) and age (z-score beta = -0.2784, p = 0.024), but not CSF NFL, which however significantly correlated with subsequent NMDAR autoimmunization (p = 0.006).DISCUSSION: Our findings show that NFL levels are predictive of long-term neurocognitive outcome in HSE, and suggest a causative chain of events where brain tissue damage increases the risk of NMDAR autoimmunisation and subsequent prolongation of CSF inflammation. The data provides guidance for a future intervention study of immunosuppressive therapy administered in the recovery phase of HSE.
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| 9. |
- Åkerman, Linda, 1983-
(författare)
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Aspects of the Pre-Diabetic Period in Type 1 Diabetes
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency, due to immune-mediated destruction of beta cells. Current knowledge regarding the period preceding disease onset comes, to a large extent, from studying risk cohorts based on relatives of T1D-patients, as they have an increased disease risk. Among T1D patients in general, however, few have the disease in their immediate family. It is therefore important to study risk cohorts from the general population as well. An ongoing autoimmune reaction can often be seen in the blood long before disease onset, by detection of autoantibodies directed towards beta cell antigens. By autoantibody screening among participants in the ABIS (All Babies in the South-east of Sweden) cohort, we could identify a group of children from the general population with increased risk for T1D, positive for multiple autoantibodies. They were enrolled in a 2-year prospective follow-up aiming to characterize the prediabetic period and to identify factors indicative of progression/non-progression to T1D. We assessed glucose homeostasis and autoantibody titers over time, and searched for risk-biomarkers by analyzing the expression of immune-related genes (Th1-Th2-Th3) in peripheral blood mononuclear cells (PBMC) from these children, in comparison to healthy children and newly diagnosed T1D patients. In the same groups we also compared serum micro RNA (miRNA) profiles, knowing that miRNA molecules have desirable biomarker properties. We found that two specific autoantibodies, IA2A and ZnT8A, were detected at higher concentrations in risk-individuals who progressed to overt T1D during or after the follow-up period, compared to those who still have not. We also observed disturbed glucose homeostasis long before onset in the progressors, but it was seen among those who remain symptom free as well. Further, we found support for the possible role of insulin resistance as an accelerator of the disease process. For gene expression and serum miRNA, few differences were observed between risk-individuals and healthy children overall. However, for PBMC gene expression and serum miRNA both, there were associations to beta cell function and glucose homeostasis, and for miRNA also to islet autoantibodies. Although specific profiles for prediction of disease onset or identification of risk-individuals could not be found, these results are interesting and deserve to be evaluated further. As part of another sub-study within ABIS, the effects of physical activity on glucose homeostasis were assessed in healthy schoolchildren. The level of physical activity, measured by pedometers, was related to insulin resistance and beta cell-stress, and decreased physical activity was associated with increased insulin resistance and load on the insulin-producing beta cells, already at school-age.
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| 10. |
- Sylwander, Charlotte, 1992-
(författare)
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Multiple perspectives on health promotion in individuals with knee pain
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic musculoskeletal pain impacts the individual in multiple aspects of life (biological, psychological, and social). Individuals with knee pain have a higher risk of developingchronic widespread pain and knee osteoarthritis, compared to the general population, and the prevalence of chronic pain is estimated to rise. As a result, there is a global call for more health-promotive research in chronic pain. Hence, this thesis aimed to investigate multiple perspectives on health promotion by studying early factors associated with chronic pain and pain development as well as experiences of health-promoting activities and health literacy in individuals with knee pain. The studies are part of the Halland osteoarthritis (HALLOA) cohort, where 306 individuals with knee pain aged 30-65 years were included. Study I was a cross-sectional descriptive study (n=280), which aimed to investigate pain sensitivity and associations with radiographic knee osteoarthritis, chronic widespread pain, and overweight/obesity. Pain sensitivity was measured with pressure pain thresholds, and overweight was assessed using body mass index, visceral fat area and body fat percentage. Study II was a longitudinal study (n=251), aiming to examine whether or not health status and lifestyle habits have an impact on reporting chronic pain after two years. Lifestyle-related habits were overweight, physical activity, diet, alcohol intake, and tobacco use. Study III was an explorative qualitative study including 22 semi-structured interviews. The study aimed to explore health-promotive activities and was analysed with qualitative content analysis. Study IV had a convergent parallel mixed-methods design (n=221), including 19 interviews, and aimed to understand health literacy among individuals with knee pain. Quantitative variables were health literacy, health status, lifestyle habits, and pain distribution. The findings showed that higher pain sensitivity was associated with being female, having more pain sites, chronic widespread pain, higher body fat and visceral fat area (study I). Additionally, overweight/obesity and lower health status were associated with reporting chronic widespread pain after two years. Conversely, being normal-weighted and reporting better health status was associated with no chronic pain (study II). Striving for balance in everyday life was important to experiencing health among individuals with knee pain, and it was achieved by taking care of the body and managing life stressors (study III). Many reported sufficient health literacy, which was also associated with reporting better general health and less pain. How individuals found or received information, processed it, and took a stand based on trust and motivation, affected their decision-making processes (study IV). This thesis concludes that overweight/obesity and lower health status play an essential role in chronic pain. Health literacy and the everyday life of an individual are important when it comes to health promotion; and it is vital to consider what individuals with knee pain need in a given situation in order to prevent chronic pain.
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