| 1. |
- Agarwal, Prasoon, et al.
(författare)
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Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target.
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:6, s. 6809-6923
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a malignancy of the antibody-producing plasma cells. MM is a highly heterogeneous disease, which has hampered the identification of a common underlying mechanism for disease establishment as well as the development of targeted therapy. Here we present the first genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in MM patient samples, defining a common set of active H3K4me3-enriched genes and silent genes marked by H3K27me3 (H3K27me3 alone or bivalent) unique to primary MM cells, when compared to normal bone marrow plasma cells. Using this epigenome profile, we found increased silencing of H3K27me3 targets in MM patients at advanced stages of the disease, and the expression pattern of H3K27me3-marked genes correlated with poor patient survival. We also demonstrated that pharmacological inhibition of EZH2 had anti-myeloma effects in both MM cell lines and CD138+ MM patient cells. In addition, EZH2 inhibition decreased the global H3K27 methylation and induced apoptosis. Taken together, these data suggest an important role for the Polycomb repressive complex 2 (PRC2) in MM, and highlights the PRC2 component EZH2 as a potential therapeutic target in MM.
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| 2. |
- Enthoven, Paul, et al.
(författare)
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Validity, internal consistency and self-rated change of the patient enablement instrument in patients with chronic musculoskeletal pain
- 2019
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 51:8, s. 587-597
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Patient enablement reflects patient's understanding of and coping with illness. The aim of this study was to investigate the content validity, construct validity, internal consistency and selfrated change (SRC) of the Patient Enablement Instrument (PEI) in patients with whiplash-associated disorders, cervical radiculopathy and mixed chronic pain treated in different settings.Design: Psychometric analyses. Participants: Patients with disabling non-malignant chronic musculoskeletal pain.Methods: Participants answered questionnaires on disability (Neck Disability Index (NDI) or Functional Rating Index (FRI)), anxiety/depression (Hospital Anxiety and Depression Scale; HADS) and general health (EuroQol; EQ-5D). Content validity, construct validity (confirmatory factor analysis), internal consistency and cut-off for SRC were investigated for the PEI after treatment. The SRC value was the receiver operating characteristic (ROC) curve optimal cut-off point.Results: After treatment all items were completed by 516 patients (mean standard deviation (SD) age 45.1 years (SD 10.1), women 75% (n=385)). The 1-factor PEI model had approximate fit to the data. The internal consistency Cronbach's alpha was between 0.878 and 0.929 for the 3 groups. Correlations between the PEI and the NDI/FRI, HADS and EQ-5D were fair to good. The SRCROC for whiplash-associated disorders, cervical radiculopathy and mixed chronic pain groups was 5, 6 and 4 points in the PEI, respectively.Conclusion: The PEI showed fair content validity, construct validity and internal consistency. However, the scale needs further development to improve measurement of change.
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| 3. |
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| 4. |
- Ng, Eunice, et al.
(författare)
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Factors Associated With Work Ability in Patients Undergoing Surgery for Cervical Radiculopathy
- 2015
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Ingår i: Spine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0362-2436 .- 1528-1159. ; 40:16, s. 1270-1276
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Tidskriftsartikel (refereegranskat)abstract
- Study Design. Cross-sectional study. Objective. To investigate the factors associated with work ability in patients undergoing surgery for cervical radiculopathy. Summary of Background Data. Surgery is a common treatment of cervical radiculopathy in people of working age. However, few studies have investigated the impact on the work ability of these patients. Methods. Patients undergoing surgery for cervical radiculopathy (n = 201) were recruited from spine centers in Sweden to complete a battery of questionnaires and physical measures the day before surgery. The associations between various individual, psychological, and work-related factors and self-reported work ability were investigated by Spearman rank correlation coefficient, multivariate linear regression, and forward stepwise regression analyses. Factors that were significant (P < 0.05) in each statistical analysis were entered into the successive analysis to reveal the factors most related to work ability. Work ability was assessed using the Work Ability Index. Results. The mean Work Ability Index score was 28 (SD, 9.0). The forward stepwise regression analysis revealed 6 factors significantly associated with work ability, which explained 62% of the variance in the Work Ability Index. Factors highly correlated with greater work ability included greater self-efficacy in performing self-cares, lower physical load on the neck at work, greater self-reported chance of being able to work in 6 months time, greater use of active coping strategies, lower frequency of hand weakness, and higher health-related quality of life. Conclusion. Psychological, work-related and individual factors were significantly associated with work ability in patients undergoing surgery for cervical radiculopathy. High self-efficacy was most associated with greater work ability. Consideration of these factors by surgeons preoperatively may provide optimal return to work outcomes after surgery.
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| 5. |
- Odqvist, Lina, et al.
(författare)
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Genetic variations in A20 DUB domain provide a genetic link to citrullination and neutrophil extracellular traps in systemic lupus erythematosus
- 2019
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 78:10, s. 1363-1370
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Genetic variations in TNFAIP3 (A20) de-ubiquitinase (DUB) domain increase the risk of systemic lupus erythematosus (SLE) and rheumatoid arthritis. A20 is a negative regulator of NF-κB but the role of its DUB domain and related genetic variants remain unclear. We aimed to study the functional effects of A20 DUB-domain alterations in immune cells and understand its link to SLE pathogenesis. Methods: CRISPR/Cas9 was used to generate human U937 monocytes with A20 DUB-inactivating C103A knock-in (KI) mutation. Whole genome RNA-sequencing was used to identify differentially expressed genes between WT and C103A KI cells. Functional studies were performed in A20 C103A U937 cells and in immune cells from A20 C103A mice and genotyped healthy individuals with A20 DUB polymorphism rs2230926. Neutrophil extracellular trap (NET) formation was addressed ex vivo in neutrophils from A20 C103A mice and SLE-patients with rs2230926. Results: Genetic disruption of A20 DUB domain in human and murine myeloid cells did not give rise to enhanced NF-κB signalling. Instead, cells with C103A mutation or rs2230926 polymorphism presented an upregulated expression of PADI4, an enzyme regulating protein citrullination and NET formation, two key mechanisms in autoimmune pathology. A20 C103A cells exhibited enhanced protein citrullination and extracellular trap formation, which could be suppressed by selective PAD4 inhibition. Moreover, SLE-patients with rs2230926 showed increased NETs and increased frequency of autoantibodies to citrullinated epitopes. Conclusions: We propose that genetic alterations disrupting the A20 DUB domain mediate increased susceptibility to SLE through the upregulation of PADI4 with resultant protein citrullination and extracellular trap formation.
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| 6. |
- Peolsson, Anneli, et al.
(författare)
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Postoperative structured rehabilitation in patients undergoing surgery for cervical radiculopathy: a 2-year follow-up of a randomized controlled trial
- 2019
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Ingår i: Journal of Neurosurgery. - : AMER ASSOC NEUROLOGICAL SURGEONS. - 1547-5654 .- 1547-5646. ; 31:1, s. 60-69
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Information about postoperative rehabilitation for cervical radiculopathy (CR) is scarce. The aim of this study was to investigate the additional benefits of structured postoperative rehabilitation (SPT), which was performed in all patients, compared with a pragmatic standard postoperative approach (SA), in which rehabilitation was used as needed and patients sought physiotherapy on their own without a referral, in patients with MRI evidence of disc herniation and concomitant clinical signs who underwent surgery for CR. METHODS Patients (n = 202) were randomized to receive SPT or SA. Included key variables in the present study were primary and selected secondary outcomes of a prospective randomized controlled multicenter study. The main outcome was the Neck Disability Index (NDI) score. The NDI score, pain variables, self-efficacy, and health-related quality of life were investigated at baseline and 3, 6, 12, and 24 months postoperatively. RESULTS SPT provided no additional benefits over SA (p = 0.08 to p = 0.99) at the postoperative 2-year follow-up. Both groups improved over time (p amp;lt; 0.0001), with no reported adverse effects. CONCLUSIONS One can conclude that SPT offered no additional benefits over SA; however, patients tolerated postoperative neck exercises without any negative side effects. These findings are important for the development of future active and neck-specific post-operative rehabilitation interventions for patients with CR.
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| 7. |
- Törngren, Martin, 1963-, et al.
(författare)
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Competence Networks in the Era of CPS : Lessons Learnt in the ICES Cross-Disciplinary and Multi-domain Center
- 2019
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Ingår i: Proceedings of the International Workshop on Design, Modeling, and Evaluation of Cyber Physical Systems, CyPhy 2019. - Cham : Springer International Publishing. - 9783030411305 - 9783030411312 ; , s. 264-283
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Konferensbidrag (refereegranskat)abstract
- Cyber-Physical Systems (CPS) are evolving to become more intelligent, autonomous and collaborating, playing an important role in societal infrastructure. The amount of knowledge required in developing and managing future CPS will be unprecedented, leading to stronger needs for collaboration, competence provisioning, continuous learning and renewal of education. This is where “competence” (or learning) “networks” involving academia and industry play an important role. We elaborate and discuss needs, lessons learnt and challenges for such competence networks in the context of CPS. We draw upon our experiences gained from ICES - the KTH-industry cross-disciplinary and multi-domain competence network which in 2019 has been operational for 11 years, growing from 6 to more than 30 participating organizations. The ICES network focuses on activities to support students, industrial engineers and managers, and academic faculty, acting as a network, catalyst and competence provider directed towards these stakeholders. We elaborate challenges faced during the operation of ICES including the lack of prioritization of competence networks and education, the paradox with strong needs for competence networks but perceived lack of time, the challenges of reaching out to stakeholders, and fragmented efforts addressing competence provisioning. We finally discuss ways forward. In conclusion, we believe that the ICES type of network could be relevant in many other areas characterized by complex systems.
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| 8. |
- Wibault, Johanna, 1978-
(författare)
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Neck disability in patients with cervical radiculopathy and evaluation of structured postoperative physiotherapy
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Non-surgical and surgical approaches to treatment are used in patients with cervical radiculopathy (CR) due to disc disease. Overall, good effects of surgery have been reported on arm pain and neurological symptoms. However, the effects on neck functioning are more uncertain. Studies have shown persistent activity limitations; participation restrictions; and impairments in neck-related body functions after surgery. Structured physiotherapy combining neck-specific exercises with a behavioural approach has been suggested as treatment before as well as after surgery to improve clinical outcomes in patients with CR. Randomized clinical trials of postoperative physiotherapy to inform evidence-based clinical guidelines for the treatment of patients with CR are lacking.The overall aim of the thesis was to investigate the additional benefit of structured postoperative physiotherapy combining neck-specific exercises with a behavioural approach compared to standard postoperative approach in patients with CR. A further aim was to evaluate the contribution of different aspects of neck-related body functions and mental functions on preoperative neck disability in these patients.A total of 202 patients with CR who were scheduled for surgery were recruited, and randomized preoperatively to either structured postoperative physiotherapy, or standard postoperative approach. Standard postoperative approach was in accordance with Swedish postoperative care, and may have included pragmatic physiotherapy after surgery when needed. Patients were evaluated with a set of questionnaires and clinical examinations before surgery and at 3 and 6 months after surgery. Outcomes included patient-reported measures of pain, neck functioning, global outcome, clinical evaluation of neckrelated body functions, self-efficacy and coping strategies, as well as expectation fulfilment and enablement. Differences between treatment groups were investigated in complete case and per-protocol approaches (Paper III & IV). A sub-sample of patients with CR who were scheduled for surgery were also compared with neck-healthy individuals for assessment of head repositioning accuracy with a cervical range of motion device (Paper I). In patients with CR who were scheduled for surgery, associations between preoperative measures of neck-related body functions, mental functions, and other contextual factors with patientreported neck disability were studied (Paper II).With the exception of greater expectation fulfilment in patients who received structured postoperative physiotherapy (p = 0.01), there were no differences between the treatment groups in outcomes at 6 months after surgery. There were no differences reported for changes in outcomes from before surgery to 6 months after surgery between the groups, but all outcomes significantly improved from baseline in both groups (p<0.001) (Paper III & IV). However, global outcome and frequency of neck pain improved during the postoperative period only in patients who received structured postoperative physiotherapy (p< 0.01) (Paper III). Six months after surgery, patients with at least 50% attendance to treatment sessions in the structured postoperative physiotherapy group reported less neck pain frequency (p = 0.05), and greater expectation fulfilment (p = 0.001), and enablement (p = 0.04) than those who received standard postoperative approach. These patients also had larger improvements in neck functioning, arm pain and catastrophizing during the rehabilitation period from 3 to 6 months after surgery (p< 0.03). Sixty-one percent of the patients who received standard postoperative approach reported additional use ofpostoperative physiotherapy. These patients had a worse surgical outcome compared with patients who reported no additional use of postoperative physiotherapy. In patients with CR who were scheduled for surgery, larger errors in head repositioning accuracy were found compared to neck-healthy individuals (Paper I). Preoperative measures of neck-related body functions, mental functions and other contextual factors explained 73% of the variance in Neck Disability Index scores in patients with CR who were scheduled for surgery (Paper II).The results may suggest a benefit from combining surgery with structured postoperative physiotherapy in patients with CR. Moreover, the results confirm that neck-specific exercises are tolerated by patients with CR after surgery. However, CR is a heterogeneous condition and specific subgroups of patients are likely to benefit from different interventions. More studies are needed to inform evidence-based clinical guidelines for the treatment of patients with CR. A broader preoperative assessment in patients with CR improved the description of patient-reported neck disability.
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| 9. |
- Wibault, Johanna, et al.
(författare)
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Neck-related physical function, self-efficacy and coping strategies in patients with cervical radiculopathy : a randomized clinical trial of postoperative physiotherapy
- 2017
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Ingår i: Journal of Manipulative and Physiological Therapeutics. - : Elsevier BV. - 0161-4754 .- 1532-6586. ; 40:5, s. 330-339
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare postoperative rehabilitation with structured physiotherapy to standard approach in patients with cervical radiculopathy (CR) based on measures of neck-related physical function, self-efficacy and coping strategies at 6 months follow-up.Design: A randomized clinical trial of postoperative physiotherapy in patients with CR.Subjects: Patients (n= 202) with persistent CR who were scheduled for surgery.Methods: Patients were preoperatively randomized to receive structured postoperative physiotherapy (SPT, n=101) or standard postoperative approach (SA, n=101). SPT combined neck-specific exercises with a behavioral approach. Baseline, 3-month, and 6-month evaluations included questionnaires and clinical examinations. Neck muscle endurance, active cervical range of motion, self-efficacy, pain catastrophizing (CSQ_CAT), perceived control over pain, and ability to decrease pain were analyzed for between-group differences using complete case and per-protocol approaches.Results: No between-group difference was reported at the 6-month follow-up (p = 0.05 to 0.99), but all outcomes had improved from baseline (p<0.001). Patients in the SPT group with ≥50% attendance to treatment sessions showed larger improvements in CSQ_CAT (p= 0.04) during the rehabilitation period from 3 to 6 months after surgery compared to the patients who received SA.Conclusion: No between-group difference in outcomes was found at 6 months after surgery based on measures of neck-related physical function, self-efficacy and coping strategies. However, the results confirm that neck-specific exercises are tolerated by patients with CR after surgery, and that there may be a benefit from combining surgery with structured postoperative physiotherapy in patients with CR.
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| 10. |
- Wibault, Johanna, et al.
(författare)
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Structured postoperative physiotherapy in patients with cervical radiculopathy : 6-month outcomes of a randomized clinical trial
- 2018
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Ingår i: Journal of Neurosurgery: Spine. - : American Association of Neurological Surgeons. - 1547-5654 .- 1547-5646. ; 28:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the additional benefit of structured postoperative physiotherapy combining neck-specific exercises with a behavioral approach to standard postoperative approach in patients with cervical radiculopathy (CR) at 6 months after surgery.Design: A prospective multi-center randomized clinical trial.Subjects: Patients with CR (n=202, mean age 50.0, SD 8.4) who were scheduled for surgery.Methods: Patients were randomized pre-operatively to structured postoperative physiotherapy (n=101) or standard approach (n=101) which in accordance with Swedish usual care may have included pragmatic physiotherapy after surgery when needed. Outcome measures at baseline and at 3 and 6 months follow-up included the Neck Disability Index (NDI), pain intensity in the neck and arm measured with a visual analogue scale (VAS) and global outcome of treatment. Between-group differences were investigated using complete case and per-protocol approaches.Results: No between-group difference was found in NDI, VAS, or global outcome at 6 months after surgery (p> 0.18). The NDI and VAS neck and arm pain were improved in both groups from before surgery to 6 months after surgery (p< 0.001). Sixty-one percent of the patients who received SA reported additional use of postoperative physiotherapy. Global outcome improved during the postoperative period in patients who received structured postoperative physiotherapy only (p< 0.01).Conclusions: No additional benefit of structured postoperative physiotherapy compared to standard postoperative approach was found at 6 months of follow-up based on patientreported measures of pain, neck disability and global outcome. However, many patients with CR perceived a need for additional treatments after surgery; and the results may suggest a benefit from combining surgery with structured postoperative physiotherapy in patients with CR. Moreover, the results confirm that neck-specific exercises are tolerated by patients with CR after surgery.
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