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  • 1.
    Barbe, MF
    et al.
    Department of Anatomy and Cell biology, Temple University, Philadelphia, USA.
    Xin, DL
    Department of Surgery, University of Pennsylvania, USA.
    Hadrevi, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Elliott, ME
    Department of Neurosurgery, Thomas Jefferson University, USA.
    Barr-Gillespie, A
    College of Health Professions, Pacific University, USA.
    Sickness behaviors (reduced social interaction and pain behaviors) are linked to inflammatory mechanisms in a rat model of work-related musculoskeletal disorders2016In: Proceedings of the Human Factors and Ergonomics Society Annual Meeting, ISSN 1541-9312, Vol. 60, no 1, p. 975-979Article in journal (Refereed)
    Abstract [en]

    We sought to determine if sickness behaviors (decreased social interaction and pain) are induced in a rat model of work-related overuse and effectiveness of anti-inflammatory treatments. Rats first trained to learn a high force reaching task (15 min/week day for 6 wks), with subsets treated prophylactically with ibuprofen or anti-TNFalpha. Others performed a high repetition high force (HRHF) task for 6 or 12 weeks (2 hrs/day, 3 days/wk) untreated, or with ibuprofen, anti-TNFalpha or rest treatments beginning task week 5. Untreated HRHF rats had increased IL-1beta, IL-6 and TNFalpha in serum and brain, increased Substance P in spinal cord, decreased social interaction and increased forepaw allodynia. Secondary antiinflammatory treatments attenuated social interaction and brain changes, but not allodynia or spinal cord changes; rest provided partial attenuation. Prophylactic treatments prevented all changes. Thus, inflammatory mechanisms mediate the development of sickness behaviors induced by work-related overuse, but not maintenance of allodynia.

  • 2. Dahlman, Anna Sjors
    et al.
    Jonsdottir, Ingibjorg H.
    Hadrévi, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Burnout patients' metabolic responses to acute stress2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 107, p. 24-25Article in journal (Other academic)
  • 3.
    Hadrevi, Jenny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Ca 2+ regulatory proteins of muscle contraction: a possible marker of chronic muscle myalgia2014Conference paper (Refereed)
    Abstract [en]

    Aim of Investigation

    Work related illnesses are one of the main reasons for sick-leave in the western world. One of the most common is pain and discomfort in the neck-shoulder region affecting the trapezius muscle, trapezius myalgia (TM). Patients suffering from work related chronic trapezius myalgia experience muscle stiffness, weakness and tension. The biochemical mechanisms behind these sensations are not yet known. Recent proteomic screening results indicate an increased abundance of the calcium regulatory fast myosin light chains in myalgic muscle suggesting an altered contractibility in the myalgic trapezius. To characterize a general increase of Ca2+ in the myalgic muscle the expression level of sarco/endoplasmic reticulum Ca2+-ATPase, (SERCA-1) was analyzed. The aim of this study was to compare the level of Ca2+ regulated proteins in cleaners with trapezius myalgia (TM) and cleaners without trapezius myalgia (CON) and to verify a possible difference in phosphorylation of the contractile regulatory myosin light chains.

    Methods

    Two-dimensional gel electrophoresis was used to separate proteins of interest. The proteomic correlation pattern of the myosin light chain proteins and the differences between healthy and myalgic muscle were investigated using a multivariate Partial Least Square Discriminant Analysis (PLS-DA). Phosphorylations of the fast regulatory myosin light chains were analyzed using serine and tyrosin antibodies. The characterization of myosin isoforms was performed using advanced Orbitrap LC-MS/MS. The expression level of SERCA-1 was analyzed in muscle biopsies from 11 professional cleaners with TM and 11 CON using Simple western size assay (Peggy, Protein simple, CA, US)

    Results

    The detected systematic differences between myosin light chain proteins showed according to the PLS-DA analysis that the fast regulatory light chains were generally more abundant in the MYA group. Ten protein spots were identified as different myosin light chains isoforms according to the amino acid sequencing. Phosphorylated serine was detected in 6 of the isoforms, though there were no differences in amount of phosphorylation between spots. The expression level of Serca-1 was significantly (p = 0.017) higher in TM subjects compared to the CON.

    Conclusions

    There is a higher abundance of fast contracting calcium regulatory myosin light chains in muscle experiencing chronic myalgia. This increased abundance of the regulatory fast myosin light chains supports the previously presented results showing an altered contractibility of the myalgic trapezius muscle. Our results show no difference in phosphorylation between the different spots contradictory to previously published results; suggesting phosphorylation of the protein being the reason for the separation of spots on the two dimensional gels. Instead our results show the spots to have different amino acid sequences. The actual function of the detected myosin light chain proteins remains to be elucidated. The increased abundance of fast contracting regulatory light chains together with the significantly increased abundance of Serca-1 proteins in the MYA muscle supports a higher abundance of Ca2+ in the myalgic muscle. The increased abundance of Serca-1 might be an indication of an adaptation due to peripheral sensitization or increased neuronal signaling altering the contrability of the muscle.       

     

    Acknowledgments

    Supported by Postdoctoral Grant from Swedish Research Council for Health, Working Life and Welfare (Forte) 2013-1259 and Medical Research Council of Southeast Sweden (FORSS-159031,LIO-35923, SC-2013-00395-36).

     

     

     

  • 4.
    Hadrevi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Barbe, M. F.
    Ortenblad, N.
    Frandsen, U.
    Boyle, E.
    Lazar, S.
    Sjogaard, G.
    Sogaard, K.
    Calcium Fluxes in Work-Related Muscle Disorder: Implications from a Rat Model2019In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, Vol. 2019, article id 5040818Article in journal (Refereed)
    Abstract [en]

    Introduction: Ca2+ regulatory excitation-contraction coupling properties are key topics of interest in the development of work-related muscle myalgia and may constitute an underlying cause of muscle pain and loss of force generating capacity.

    Method: A well-established rat model of high repetition high force (HRHF) work was used to investigate if such exposure leads to an increase in cytosolic Ca2+ concentration ([Ca2+]i) and changes in sarcoplasmic reticulum (SR) vesicle Ca2+ uptake and release rates.

    Result: Six weeks exposure of rats to HRHF increased indicators of fatigue, pain behaviors, and [Ca2+]i, the latter implied by around 50–100% increases in pCam, as well as in the Ca2+ handling proteins RyR1 and Casq1 accompanied by an ∼10% increased SR Ca2+ uptake rate in extensor and flexor muscles compared to those of control rats. This demonstrated a work-related altered myocellular Ca2+ regulation, SR Ca2+ handling, and SR protein expression.

    Discussion: These disturbances may mirror intracellular changes in early stages of human work-related myalgic muscle. Increased uptake of Ca2+ into the SR may reflect an early adaptation to avoid a sustained detrimental increase in [Ca2+]i similar to the previous findings of deteriorated Ca2+ regulation and impaired function in fatigued human muscle.

  • 5.
    Hadrevi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    Bjorklund, Martin
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Kosek, E.
    Hallgren, Solveig
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Professionell Development.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fahlstrom, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Professionell Development.
    Hellstrom, F.
    Systemic differences in serum metabolome: a cross sectional comparison of women with localised and widespread pain and controls2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 15925Article in journal (Refereed)
    Abstract [en]

    Chronic musculoskeletal pain exists either as localised to a single region or as widespread to multiple sites in several quadrants of the body. Prospective studies indicate that widespread pain could act as a far end of a continuum of musculoskeletal pain that started with chronic localised pain. The mechanism by which the transition from localised pain to widespread occurs is not clear, although many studies suggest it to be an altered metabolism. In this study, systemic metabolic differences between women with chronic localised neck-shoulder pain (NP), women with chronic widespread pain (CWP) and women who were healthy (CON) were assessed. Blood samples were analysed taking a metabolomics approach using gas chromatography mass spectrometry (GC-MS) and orthogonal partial least square discriminant analysis (OPLS-DA). The metabolomics analysis showed a clear systematic difference in the metabolic profiles between the subjects with NP and the CON but only a weak systematic difference between the subjects with CWP and the CON. This most likely reflects a difference in the portion of the metabolome influenced by the two pain conditions. In the NP group, the overall metabolic profile suggests that processes related to energy utilisation and lipid metabolism could be central aspects of mechanisms maintaining disorder.

  • 6.
    Hadrevi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hellström, Fredrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Kieselbach, Thomas
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Malm, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Protein differences between human trapezius and vastus lateralis muscles determined with a proteomic approach2011In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 12, no 181, p. 11-Article in journal (Refereed)
    Abstract [en]

    Background: The trapezius muscle is a neck muscle that is susceptible to chronic pain conditions associated with repetitive tasks, commonly referred to as chronic work-related myalgia, hence making the trapezius a muscle of clinical interest. To provide a basis for further investigations of the proteomic traits of the trapezius muscle in disease, two-dimensional difference gel electrophoresis (2D-DIGE) was performed on the healthy trapezius using vastus lateralis as a reference. To obtain as much information as possible from the vast proteomic data set, both one-way ANOVA, with and without false discovery rate (FDR) correlation, and partial least square projection to latent structures with discriminant analysis (PLS-DA) were combined to compare the outcome of the analysis.

    Results: The trapezius and vastus lateralis showed significant differences in metabolic, contractile and regulatory proteins, with different results depending on choice of statistical approach and pre-processing technique. Using the standard method, FDR correlated one-way ANOVA, 42 protein spots differed significantly in abundance between the two muscles. Complementary analysis using immunohistochemistry and western blot confirmed the results from the 2D-DIGE analysis.

    Conclusions: The proteomic approach used in the present study combining 2D-DIGE and multivariate modelling provided a more comprehensive comparison of the protein profiles of the human trapezius and vastus lateralis muscle, than previously possible to obtain with immunohistochemistry or SDS-PAGE alone. Although 2D-DIGE has inherent limitations it is particularly useful to comprehensively screen for important structural and metabolic proteins, and appears to be a promising tool for future studies of patients suffering from chronic work related myalgia or other muscle diseases.

  • 7.
    Hadrevi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    Turkina, Maria V
    Department of Clinical and Experimental Medicine, Linköpings universitet.
    Carlsson, Anders
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Gerdle, Björn
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Larsson, Britt
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Hellström, Fredrik
    Department of Occupational and Public Health Sciences, Högskolan i Gävle.
    Ghafouri, Bijar
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Myosin light chain and calcium regulating protein differences in chronic musculoskeletal neck and shoulder pain2016In: Journal of Integrated Omnics, ISSN 2182-0287, Vol. 6, no 1, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Proteomic screening analysis has detected myosin light chain (MLC) as a protein implied to be involved in chronic musculoskeletal neck and shoulder pain. Several analyses of MLC proteins have stated a difference in phosphorylation being the determining factor for protein activation hence altered contrability of the muscle in i.e. senescence. In continuation of a previous publication, this study is an attempt to analyze the different MLC isoforms by mass spectrometry and immune-analyses in myalgic and healthy trapezius muscle. In the present study no differences in phosphorylation level between the corresponding individual proteins were detected using LC-MSMS and immunoblotting; instead we assigned different isoforms of regulatory MLCs. To further elucidate the contrability: calcium (Ca2+) regulatory proteins, sarco(endo)plasmic reticulum Ca2+ ATPase 1 (SERCA-1) and calsequestrine (CSQ) were analyzed by western blot. The analysis revealed a significantly increased abundance of SERCA-1 protein in the myalgic muscle and a significantly increased abundance of CSQ in healthy muscle. Myalgic muscle contraction patterns have in previous studies shown to differ from healthy muscle which may be connected to the Ca2+ availability in the muscle. Here we present the proteomic characterization of differences in Ca2+ regulating proteins and particularly regulatory MLCs in trapezius muscle of women with chronic musculoskeletal neck and shoulder pain.

  • 8.
    Hadrévi, Jenny
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Applying proteomics and metabolomics for studying human skeletal muscle with a focus on chronic trapezius myalgia2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Work related musculoskeletal disorders are the dominating causes of reported ill-health in industrialized countries. These chronic pain conditions are one of the most costly public health problems in Europe and North America. When work related musculoskeletal disorders are considered to be of muscular origin and the trapezius muscle is affected, the common appellation is trapezius myalgia. Since little is known about the genesis or how it is maintained, it is of great importance to better understand the pathophysiology of trapezius myalgia; doing so will better enable recommendations for prevention, treatment and rehabilitation. Several hypotheses have been presented based on biochemical alterations in the muscle, suggesting increased signaling of inflammatory substances and altered metabolism. Previous research has not been able to present the comprehensive picture of the muscle in pain. Thus there is a demand for more comprehensive research regarding the biochemical milleu of the chronic trapezius muscle.

    Proteomic and metabolomic methods allow non-targeted simultaneous analyses of a large number of proteins and metabolites. The main emphasis in this thesis is on a proteomic method, two-dimensional differential gel electrophoresis (2D-DIGE). The method is validated to human skeletal muscle biopsy research with laboratory specific settings. In the baseline study, there were 14 metabolic, contractile, structural and regulatory proteins that differed significantly in abundance when trapezius and vastus lateralis muscles were compared. Using the validated 2D-DIGE method and the baseline study, a comparison between healthy and myalgic muscles was made. Biopsies from female cleaners with and without myalgia were compared to obtain results from women with the same type of work exposure. In the multivariate model, 28 identified unique proteins separated healthy and myalgic muscle and were grouped according to function: metabolic (n=10), contractile (n=9), regulatory (n=3), structural (n=4), and other (n=2). Finally, a second screening method, metabolomics, was introduced to analyze differences in metabolite content as a complement to and verification of the proteomic results. Gas chromatography-mass spectrometry (GC-MS) was performed on muscle interstitial fluid samples obtained with microdialysis, and differences in the abundance of extracellular metabolites were revealed.

     The 2D-DIGE method is a reliable method to analyze human skeletal muscle. The outcomes of the proteomic analyses were dependant on the statistical approach. Systematic differences in protein and metabolite content were detected using a multivariate approach. Univariate analyses were used to analyze individual proteins for their significance. The significant proteins in the baseline study were predominately related to muscle fiber type which correlated with the differences in fiber type content between trapezius and vastus lateralis. The proteomic and metabolomics studies where myalgic and healthy muscles were compared provide us with new clues and new aspects regarding the pathophysiology of the myalgic muscle.

    Technically advanced methods employed in the thesis enabled an explorative screening of proteins of relevance for the pathophysiology of the myalgic muscle. The results of these analyses may contribute to the formulation of future hypothesis that need to be further evaluated.

  • 9.
    Hadrévi, Jenny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine. Högskolan i Gävle, Centrum för belastningsskadeforskning.
    New Aspects on Chronic Trapezius Myalgia: Contribution of Metabolomics and Proteomics2014In: Journal of Musculoskeletal Pain, ISSN 1058-2452, E-ISSN 1540-7012, Vol. 22, no 4, p. 382-388Article, review/survey (Refereed)
    Abstract [en]

    Several hypotheses regarding the underlying mechanisms and the maintenance behind chronic work-related musculoskeletal disorders have been presented. Chronic low load work and psychosocial stress is believed to be the underlying causes to these pain conditions. The recent application of comprehensive screening methods: omnics methods; to this field of research could contribute to current knowledge regarding the pathophysiology of these disorders. The pathophysiological mechanisms behind chronic trapezius myalgia are discussed in the context of new findings obtained with proteomic and metabolomic methods. Proteins and metabolites which differ in abundance between healthy muscle and muscle suffering from chronic trapezius myalgia are presented. Primarily, the pathways and effects of the proteins and metabolites found in three recently published papers are discussed. Proteomics and metabolomics are efficient screening methods enabling the presentation of potential biomarkers and pathophysiological mechanisms explaining the pathophysiology of chronic work-related trapezius myalgia. The previous findings detecting systematic differences of proteins and metabolites when comparing chronic myalgic muscle to healthy muscle, indicating a higher glycogen metabolism, increased muscle turnover and increased neuronal signalling in the myalgic muscle, are discussed in this review.

  • 10.
    Hadrévi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Ghafouri, Bijar
    Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University and Pain and Rehabilitation Centre, County Council of Östergötland, SE 581 85 Linköping, Sweden.
    Larsson, Britt
    Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University.
    Gerdle, Björn
    Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University.
    Hellström, Fredrik
    Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, Faculty of Health and Occupational Studies , University of Gävle, Umeå, Sweden.
    Multivariate Modeling of Proteins Related to Trapezius Myalgia, a Comparative Study of Female Cleaners with or without Pain2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, p. e73285-Article in journal (Refereed)
    Abstract [en]

    The prevalence of chronic trapezius myalgia is high in women with high exposure to awkward working positions, repetitive movements and movements with high precision demands. The mechanisms behind chronic trapezius myalgia are not fully understood. The purpose of this study was to explore the differences in protein content between healthy and myalgic trapezius muscle using proteomics. Muscle biopsies from 12 female cleaners with work-related trapezius myalgia and 12 pain free female cleaners were obtained from the descending part of the trapezius. Proteins were separated with two-dimensional differential gel electrophoresis (2D-DIGE) and selected proteins were identified with mass spectrometry. In order to discriminate the two groups, quantified proteins were fitted to a multivariate analysis: partial least square discriminate analysis. The model separated 28 unique proteins which were related to glycolysis, the tricaboxylic acid cycle, to the contractile apparatus, the cytoskeleton and to acute response proteins. The results suggest altered metabolism, a higher abundance of proteins related to inflammation in myalgic cleaners compared to healthy, and a possible alteration of the contractile apparatus. This explorative proteomic screening of proteins related to chronic pain in the trapezius muscle provides new important aspects of the pathophysiology behind chronic trapezius myalgia.

  • 11.
    Hadrévi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Ghafouri, Bijar
    Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University and Pain and Rehabilitation Centre, County Council of Östergötland, SE 581 85 Linköping, Sweden.
    Sjörs, Anna
    Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University and Pain and Rehabilitation Centre, County Council of Östergötland, SE 581 85 Linköping, Sweden; Institute of Stress Medicine, Carl Skottsbergs gata 22B, SE 41319 Gothenburg, Sweden.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Larsson, Britt
    Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University and Pain and Rehabilitation Centre, County Council of Östergötland, SE 581 85 Linköping, Sweden.
    Crenshaw, A. G.
    Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, Faculty of Health and Occupational Studies , University of Gävle, Umeå, Sweden.
    Gerdle, Björn
    Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University and Pain and Rehabilitation Centre, County Council of Östergötland, SE 581 85 Linköping, Sweden.
    Hellström, Fredrik
    Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, Faculty of Health and Occupational Studies , University of Gävle, Umeå, Sweden.
    Comparative metabolomics of muscle interstitium fluid in human trapezius myalgia: an in vivo microdialysis study2013In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 113, no 12, p. 2977-2989Article in journal (Other academic)
    Abstract [en]

    The mechanisms behind trapezius myalgia are unclear. Many hypotheses have been presented suggesting an altered metabolism in the muscle. Here, muscle microdialysate from healthy and myalgic muscle is analysed using metabolomics. Metabolomics analyse a vast number of metabolites, enabling a comprehensive explorative screening of the cellular processes in the muscle.

    Microdialysate samples were obtained from the shoulder muscle of healthy and myalgic subjects that performed a work and stress test. Samples from the baseline period and from the recovery period were analysed using gas chromatography-mass spectrometry (GC-MS) together with multivariate analysis to detect differences in extracellular content of metabolites between groups. Systematic differences in metabolites between groups were identified using multivariate analysis and orthogonal partial least square discriminate analysis (OPLS-DA). A complementary Mann-Whitney U test of group difference in individual metabolites was also performed.

    A large number of metabolites were detected and identified in this screening study. At baseline, no systematic differences between groups were observed according to the OPLS-DA. However, two metabolites, l-leucine and pyroglutamic acid, were significantly more abundant in the myalgic muscle compared to the healthy muscle. In the recovery period, systematic difference in metabolites between the groups was observed according to the OPLS-DA. The groups differed in amino acids, fatty acids and carbohydrates. Myristic acid and putrescine were significantly more abundant and beta-d-glucopyranose was significantly less abundant in the myalgic muscle.

    This study provides important information regarding the metabolite content, thereby presenting new clues regarding the pathophysiology of the myalgic muscle.

  • 12.
    Hadrévi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jonsdottir, Ingibjörg H.
    Institutet för Stressmedicin, Göteborg.
    Jansson, Per-Anders
    Sahlgrenska, Göteborgs Universitet.
    Eriksson, Jan W.
    Uppsala Universitet.
    Sjörs, Anna
    Institutet för Stressmedicin, Göteborg.
    Plasma metabolomic patterns in patients with exhaustion disorder2019In: Stress, ISSN 1025-3890, E-ISSN 1607-8888, Vol. 22, no 1, p. 17-26Article in journal (Refereed)
    Abstract [en]

    Exhaustion disorder (ED) is a stress-related disorder that often implies a great burden on the individual patient as well as on society. Previous studies have shown that ED is associated with metabolic deviations, such as lowered fasting glucose. Several mechanisms have been discussed as a plausible explanation of the lack of energy described by these patients. Metabolic processes and reduced ability to mobilize energy have been suggested as important factors. This study investigated metabolomics in 20 patients diagnosed with ED and compared them with 21 healthy controls. Plasma metabolic profiles were examined in both fasting and nonfasting (postprandial) conditions. Blood plasma samples were analyzed for metabolite content using gas chromatography mass spectrometry. A total of 62 different metabolites were simultaneously detected in each of the samples. Multivariate models indicated systematic differences between patients with ED and healthy controls in both their fasting and nonfasting plasma metabolite levels. Lysine and octadecenoic acid were more abundant and glutamine, glycine, serine and gluconic acid were less abundant in the patients across both conditions. In the present study, we comprehensively and simultaneously screen for changes in a large number of metabolites. Our results show a difference in systemic metabolites between patients with exhaustion disorder and healthy controls both in the fasting and in the postprandial states. Here, we present new potential biomarkers mirroring exhaustion disorder metabolism.

  • 13.
    Hadrévi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Søgaard, Karen
    Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark & Department of Clinical Research, University of Southern Denmark, Kløvervænget 3, Indgang, 5000 Odense, Denmark.
    Reffstrup Christensen, Jeanette
    Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark & Department of Public Health, University of Southern Denmark, JB Winsløwsvej 9A, 5000 Odense, Denmark.
    Dietary Fiber Intake among Normal-Weight and Overweight Female Health Care Workers: An Exploratory Nested Case-Control Study within FINALE-Health2017In: Journal of Nutrition and Metabolism, ISSN 2090-0724, E-ISSN 2090-0732, article id 1096015Article in journal (Refereed)
    Abstract [en]

    Socioeconomic factors affect choice of diet, that is, dietary fiber intake. Underreporting of food consumption in diet surveys has been reported higher in low-income, low-education groups compared to high-income, high-education groups. This paper examines in a socioeconomic homogenous low-income low-education group of females the relation between dietary fiber intake and overweight and scrutinizes if the level of underreporting is equally large in normal-weight and overweight groups. Thirty-four female health care workers classified as either normal-weight () or obese () based on BMI, fat percentage, and waist circumference participated. A detailed food-diary was used to record their dietary intake in 9 days. Average dietary fiber intake in the normal-weight group was 2.73 +/− 0.65 g/MJ, while it was 2.15 +/− 0.64 g/MJ for the women in the obese group. In both groups, the overall food intake was underreported. In spite of a significantly lower dietary fiber intake in the obese group, the present population of women working within health care all showed an overall low dietary fiber intake and a general underreporting of food intake. These results indicate a clear need for dietary advice especially on fiber intake to increase general health and decrease weight.

  • 14.
    Malm, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Hadrevi, Jenny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Bergström, Sven-Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pedrosa-Domellof, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Svensson, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Frängsmyr, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Evaluation of 2-D DIGE for skeletal muscle: Protocol and repeatability2008In: The Scandinavian Journal of Clinical & Laboratory Investigation, Vol. 68, no 8, p. 793-800Article in journal (Refereed)
    Abstract [en]

    Proteomic analysis has the potential to yield vast amounts of data. The available proteomic methods have been hampered by methodological errors in quantification due to large gel-to-gel variations. The inclusion of an internal standard greatly reduces this variation, and therefore the purpose of this investigation was: 1) to develop a sample preparation protocol for human skeletal muscle for two-dimensional differentiated gel electrophoresis (DIGE) and 2) to investigate the repeatability of one particular system, the Ettan™ DIGE. To test repeatability, nine aliquots from the same homogenate were labelled with three different CyDye™ dyes (Cy2, Cy3, Cy5). Samples were run on 1824 cm gels, scanned with a Typhoon™ 9410 laser scanner and analysed in the DeCyder™ software. When selecting spots appearing only in triplicate (n = 1314), the mean error was 1.7 % (SD: 10.5 %; 95 % CI: 1.1-2.4 %). When setting the significance level to 99 %, no false-positive changes in protein volume ratios were detected. In the protocol presented here, only 0.5 mg tissue was used and separation of >2500 distinct protein spots in the pH range 3-11 and MW 10-200 kDa. Changes in protein abundance of <20 % could be detected. The method is especially useful when comparing muscle proteins between different conditions; for example, healthy and diseased tissue, before and after treatment or different exercise protocols.

  • 15.
    Nordström, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hadrévi, Jenny
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Lunds Universitet.
    The Higher Prevalence of Type 2 Diabetes in Men Than in Women is Associated with Differences in Visceral Fat Mass2016In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 101, no 10, p. 3740-3746Article in journal (Refereed)
    Abstract [en]

    Context: We have previously found that visceral fat is a stronger predictor for cardiovascular risk factors than body mass index (BMI). Objective: To investigate the prevalence of diabetes in elderly men and women in relation to objectively assessed visceral fat volume. Design and settings: The cohort consisted of a population-based sample of 705 men and 688 women, all aged 70 years at the time of examination. Main outcome measures: Associations between body fat estimates, plasma glucose level and diabetes prevalence were investigated using multivariable-adjusted statistical models.Results:Theprevalence of type2 diabetes was 14.6% in men and 9.1% inwomen (p0.001). Mean BMI was slightly higher in men than in women (27. 3 vs. 26.6 kg/m2, p 0.01), with a greater difference in mean visceral fat mass (1987 vs. 1087 g, p 0.001). After adjustment for physical activity and smoking, men had about twice the odds of having type 2 diabetes compared with women (OR, 1.95; 95% CI, 1.38–2.76). The inclusion of BMI in this model did not change the risk associated with male sex (OR, 1.93; 95% CI, 1.34–2.77). However, when visceral fat was included as a covariate, male sex was not associated with increased risk of type 2 diabetes (OR, 0.77; 95% CI, 0.51–1.18).Conclusions: The higher prevalence of type 2 diabetes in older men than in older women was associated with larger amount of visceral fat in men. In contrast, differences in BMI was not associated with this difference.

  • 16.
    Reffstrup Christensen, Jeanette
    et al.
    Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
    Viskum Gjelstrup Bredahl, Thomas
    Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
    Hadrévi, Jenny
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    Sjøgaard, Gisela
    Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
    Søgaard, Karen
    Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
    Background, design and conceptual model of the cluster randomized multiple-component workplace study: FRamed Intervention to Decrease Occupational Muscle pain - "FRIDOM"2016In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 16, article id 1116Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Several RCT studies have aimed to reduce either musculoskeletal disorders, sickness presenteeism, sickness absenteeism or a combination of these among females with high physical work demands. These studies have provided evidence that workplace health promotion (WHP) interventions are effective, but long-term effects are still uncertain. These studies either lack to succeed in maintaining intervention effects or lack to document if effects are maintained past a one-year period. This paper describes the background, design and conceptual model of the FRIDOM (FRamed Intervention to Decrease Occupational Muscle pain) WHP program among health care workers. A job group characterized by having high physical work demands, musculoskeletal disorders, high sickness presenteeism - and absenteeism.

    METHODS:

    FRIDOM aimed to reduce neck and shoulder pain. Secondary aims were to decrease sickness presenteeism, sickness absenteeism and lifestyle-diseases such as other musculoskeletal disorders as well as metabolic-, and cardiovascular disorders - and to maintain participation to regular physical exercise training, after a one year intervention period. The entire concept was tailored to a population of female health care workers. This was done through a multi-component intervention including 1) intelligent physical exercise training (IPET), dietary advice and weight loss (DAW) and cognitive behavioural training (CBT).

    DISCUSSION:

    The FRIDOM program has the potential to provide evidence-based knowledge of the pain reducing effect of a multi component WHP among a female group of employees with a high prevalence of musculoskeletal disorders and in a long term perspective evaluate the effects on sickness presenteeism and absenteeism as well as risk of life-style diseases.

    TRIAL REGISTRATION:

    NCT02843269 , 06.27.2016 - retrospectively registered.

  • 17.
    Signoret, Carine
    et al.
    Linnaeus Centre HEAD, Swedish Institute for Disability Research, Department of Behavioural Sciences and Learning, Linköping University, Linköping, Sweden.
    Ng, Elaine
    Linnaeus Centre HEAD, Swedish Institute for Disability Research, Department of Behavioural Sciences and Learning, Linköping University, Linköping, Sweden.
    Da Silva, Stéphanie
    Department of Clinical and Experimental Medicine, Division of Surgery, Faculty of Health Sciences, Linköping University, County Council of Östergötland, Linköping, Sweden.
    Tack, Ayco
    Department of Ecology, Environment and Plant Sciences, Stockholm University, Stockholm, Sweden.
    Voss, Ulrikke
    Department of Experimental Medical Sciences, Future Faculty, Lund University, Lund, Sweden.
    Lidö, Helga H.
    Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Patthey, Cedric
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Ericsson, Madelene
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hadrevi, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Balachandran, Chanchal
    Department of Management and Engineering (IEI), The Institute for Analytical Sociology, Linköping University, Linköping, Sweden.
    Well-being of early-career researchers: insights from a Swedish survey2019In: Higher Education Policy, ISSN 0952-8733, E-ISSN 1740-3863, Vol. 32, no 2, p. 273-296Article in journal (Refereed)
    Abstract [en]

    Several studies have documented the importance of optimal work situation and the general well-being of early-career researchers (ECRs) for enhancing the academic performance of universities. Yet, most studies focused on specific categories of ECRs, or on specific academic disciplines as well as on specific outcomes. With this study, we recognize the need for a broader sample encompassing different categories of ECRs across academic disciplines. In a national survey of Swedish universities, the National Junior Faculty of Sweden (NJF) collected data from ECRs in order to study the influence of work situation and well-being on perceived scientific environment. We observed that work situation and well-being are interdependent and jointly influence each other in shaping the conditions for ideal scientific environment. Importantly, we employ structural equation model (SEM) analysis to account for the endogenous relationship between work situation and personal well-being in predicting perceived scientific environment. Results from SEM indicate that support from the university, work time management, job clarity, contract length and quality of life satisfaction were related to the perceived possibility of conducting the best science. Our research also highlighted individual differences across demographic factors and contract length in the perceived work situation and the possibility of conducting the best science.

  • 18. Vihlborg, Per
    et al.
    Graff, Pål
    Hagenbjörk, Annika
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Hadrévi, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Bryngelsson, Ing-Liss
    Eriksson, Kåre
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Serum Metabolites in Hand-Arm Vibration Exposed Workers2020In: Journal of Occupational and Environmental Medicine, ISSN 1076-2752, E-ISSN 1536-5948Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate whether low molecular organic biomarkers could be identified in blood samples from vibration exposed workers using a metabolomics.

    Methods: The study population consisted of 38 metalworkers. All participants underwent a standardized medical examination. Blood samples were collected before and after work shift and analyzed with GC-TOFMS. Multivariate modeling (orthogonal partial least-squares analysis with discriminant analysis [OPLS-DA]) were used to verify differences in metabolic profiles.

    Results: Twenty-two study participants reported vascular symptoms judged as vibration-related. The metabolic profile from participants with vibration-induced white fingers (VWF) was distinctly separated from participants without VWF, both before and after vibration exposure.

    Conclusion: Metabolites that differed between the groups were identified both before and after exposure. Some of these metabolites might be indicators of health effects from exposure to vibrations. This is the first time that a metabolomic approach has been used in workers exposed to vibrations.

  • 19.
    Xin, D. L.
    et al.
    Department of Surgery, University of Pennsylvania, USA.
    Hadrevi, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Elliott, M. E.
    Department of Neurosurgery, Thomas Jefferson University, USA.
    Amin, M
    Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadephia, USA.
    Harris, M. Y.
    Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, USA.
    Barr-Gillespie, A
    College of Health Professions, Pacific University, USA.
    Barbe, M. F.
    Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, USA.
    Effectiveness of conservative interventions for sickness and pain behaviors induced by a high repetition high force upper extremity task2017In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 18, article id 36Article in journal (Refereed)
    Abstract [en]

    Background: Systemic inflammation is known to induce sickness behaviors, including decreased social interaction and pain. We have reported increased serum inflammatory cytokines in a rat model of repetitive strain injury (rats perform an upper extremity reaching task for prolonged periods). Here, we sought to determine if sickness behaviors are induced in this model and the effectiveness of conservative treatments.

    Methods: Experimental rats underwent initial training to learn a high force reaching task (10 min/day, 5 days/week for 6 weeks), with or without ibuprofen treatment (TRHF vs. TRHF + IBU rats). Subsets of trained animals went on to perform a high repetition high force (HRHF) task for 6 or 12 weeks (2 h/day, 3 days/week) without treatment, or received two secondary interventions: ibuprofen (HRHF + IBU) or a move to a lower demand low repetition low force task (HRHF-to-LRLF), beginning in task week 5. Mixed-effects models with repeated measures assays were used to assay duration of social interaction, aggression, forepaw withdrawal thresholds and reach performance abilities. One-way and two-way ANOVAs were used to assay tissue responses. Corrections for multiple comparisons were made.

    Results: TRHF + IBU rats did not develop behavioral declines or systemic increases in IL-1beta and IL-6, observed in untreated TRHF rats. Untreated HRHF rats showed social interaction declines, difficulties performing the operant task and forepaw mechanical allodynia. Untreated HRHF rats also had increased serum levels of several inflammatory cytokines and chemokines, neuroinflammatory responses (e.g., increased TNFalpha) in the brain, median nerve and spinal cord, and Substance P and neurokinin 1 immunoexpression in the spinal cord. HRHF + IBU and HRHF-to-LRLF rats showed improved social interaction and reduced inflammatory serum, nerve and brain changes. However, neither secondary treatment rescued HRHF-task induced forepaw allodynia, or completely attenuated task performance declines or spinal cord responses.

    Conclusions: These results suggest that inflammatory mechanisms induced by prolonged performance of high physical demand tasks mediate the development of social interaction declines and aggression. However, persistent spinal cord sensitization was associated with persistent behavioral indices of discomfort, despite use of conservative secondary interventions indicating the need for prevention or more effective interventions.

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