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- Alim, Abdul, 1983-
(författare)
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Mechanisms in Tendon Healing : Pain, Biomarkers and the Role of Mast Cells
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tendon injuries and tendinopathy are common disorders, but the underlying mechanisms are not well understood. The overall aim of this thesis was to better understand the mechanisms underlying tendon healing, pain, and inflammation.The aim of the first study was to assess biomarkers of tendon healing, including procollagen type I (PINP) and type III (PIIINP) in relation to patient outcome in 65 patients with Achilles tendon rupture (ATR). At two weeks post-ATR, PINP and PIIINP-levels were quantified using microdialysis followed by ELISA. At one-year post-ATR patient outcome was assessed using the validated Achilles tendon Total Rupture Score. We found that higher ratio of PINP and PIIINP to total protein were significantly associated with less pain but more fatigue in the affected limb.In the second study, we applied Intermittent Pneumatic Compression (IPC) therapy for two weeks to stimulate tendon healing. The patients received either adjuvant IPC treatment or treatment-as-usual in a plaster cast without IPC. We observed that IPC therapy significantly increased PINP levels in the injured tendon, suggesting enhanced healing response.In our third study, we investigated healing response and the role of mast cells (MCs) in-vivo using an ATR rat model. Three weeks postoperatively, we demonstrated an increased number of MCs and a higher proportion of degranulated MCs in the injured tendon compared to the control. We further established that MCs in the injured tendon were positive for the glutamate receptor NMDAR1.In our final study, we assessed the effect of glutamate stimulation on in-vitro-derived mouse bone marrow MCs. Mast cell degranulation was quantified through β-hexosaminidase release, immunofluorescence was used to quantify NMDARs at the protein level, and RT-qPCR/microarray was used to study the expression of NMDARs and associated genes. Glutamate induced a robust upregulation of glutamate receptors of both ionotropic and metabotropic type, both at the mRNA and at protein level. NMDAR1 co-localized with glutamate in the membrane of MCs, thereby confirming an interaction between glutamate and its receptor. Glutamate also induced expression of pro-inflammatory compounds such as IL-6 and CCL2 and transcription factors such as Egr2, Egr3 and FosB. Moreover, the NMDA-channel blocker MK-801 completely abrogated the response of MCs to glutamate, supporting a functional glutamate–glutamate receptor axis in MCs.Together, findings presented in this dissertation reveal possible mechanisms of tendon healing in relation to pain and function, and establish a novel principle for how immune cells can communicate with nerve cells after ATR.
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| 2. |
- Andersén, Åsa, 1975-
(författare)
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Self-efficacy, Vocational Rehabilitation and Transition to Work
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to examine the relationship between self-efficacy, individually tailored vocational rehabilitation and transition to work or studies.Study I was a cross-sectional study based on questionnaire- and registry data, investigating whether factors related to sick leave predict self-efficacy in women on long-term sick leave (n= 337) due to pain and/or mental illness. General self-efficacy was low. Anxiety and depression were the strongest predictors for low self-efficacy.Study II used longitudinal data from a randomised controlled trial, comprising partly the same women (n=401) as in Study I. Participants were allocated to either 1) assessment of multidisciplinary team and multimodal intervention (TEAM), 2) acceptance and commitment therapy (ACT), or 3) control group. Self-efficacy increased in the TEAM group in comparison with the control group.Study III had a descriptive qualitative design with individual interviews, studying participants’ (n=14) experiences with an individually tailored vocational rehabilitation project, and encounters with professionals working in it. The participants, who were on long-term sick leave due to mental illness or pain reported overall positive experiences with the project. The project was based on collaboration between authorities and motivational interviewing. The positive experiences were based on four categories: Opportunities for receiving various dimensions of support, Good overall treatment by the professionals, Satisfaction with the working methods of the project, and Opportunities for personal development.Study IV was a prospective cohort study investigating perceived self-efficacy in unemployed young adults (n= 249) aged 19-29 year with disabilities, and the association between self-efficacy and transition to work or studies. The study used questionnaire- and registry data from a vocational rehabilitation project. Higher levels of self-efficacy were associated with increased odds for ‘transition to work’. General self-efficacy was low, and young adults with lower self-efficacy reported worse self-rated health compared with those with higher self-efficacy.This thesis showed that multidisciplinary assessment with a multimodal intervention had positive effects on self-efficacy. Individually tailored vocational rehabilitation, based on cooperation and motivational interviewing, may be beneficial for individuals on long-term sick leave and the interactions between participants and the professionals may affect participants’ self-efficacy positively. Mental health needs to be considered when targeting self-efficacy in vocational rehabilitation. Furthermore, research is needed to a) clarify which components in the multidisciplinary team intervention can increase self-efficacy, b) study the effects of vocational rehabilitation based on an individual design, cooperation and motivational interviewing on self-efficacy, health and transition to work, and c) develop interventions that can increase self-efficacy and support transition to work/ studies in young adults with disabilities.
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