| 1. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 2. |
- Hadrevi, Jenny, et al.
(författare)
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Myosin light chain and calcium regulating protein differences in chronic musculoskeletal neck and shoulder pain
- 2016
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Ingår i: Journal of Integrated Omnics. - : Proteomass Scientific Society. - 2182-0287. ; 6:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Böthun, Alicia, et al.
(författare)
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Jaw–neck motor strategy during jaw‐opening with resistance load
- 2022
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 49:5, s. 514-521
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Tidskriftsartikel (refereegranskat)abstract
- Background: The jaw and neck motor systems have a close functional integration but the effect of resistance load to the mandible during jaw opening on the jaw-neck integration is not known.Objectives: To evaluate the effect of resistance load compared to no load on integrated jaw and neck motor function in individuals free from pain and dysfunction in the jaw and neck regions.Methods: Jaw and head movements during continuous jaw opening were recorded with an optoelectronic system (MacReflex® ) in 26 pain-free individuals (14 women, 12 men, mean age 22 years). Jaw opening was performed with and without resistance load (1600 g) to the mandible. The relationship between jaw movement amplitude, head movement amplitude, head/jaw ratio (quotient of head and jaw movement amplitude) and resistance load were modelled using linear mixed-model analysis. A p-value <.05 was considered statistically significant.Results: The expected head/jaw ratio mean was increased by 0.05 (95% CI: 0.03, 0.08, p < .001) with resistance load as compared to no load. This corresponds to an increase in expected mean by 55.6%. With resistance load, expected mean head movement amplitude increased by 1.4 mm (95% CI: 0.2, 2.5, p = .018), and expected mean jaw movement amplitude decreased by 3.7 mm (95% CI: -7.0, -0.5, p = .025).Conclusion: There is a compensation and adaptation of integrated jaw-neck motor function with an altered jaw-neck motor strategy during jaw opening with resistance load compared to no load. The head/jaw ratio demonstrates increased proportional involvement of the neck during increased load on the jaw system.
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| 4. |
- Dahlgren, David, et al.
(författare)
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Evaluation and validation of chemotherapy‐specific diarrhoea and histopathology in rats
- 2022
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : John Wiley & Sons. - 1742-7835 .- 1742-7843. ; 131:6, s. 536-546
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy-induced mucositis is characterized by diarrhoea and villous atrophy. However, it is not well-understood why diarrhoea arises, why it only occurs with some chemotherapeutics and how it is related to villus atrophy. The objectives in this study were to determine (i) the relationship between chemotherapy-induced diarrhoea and villus atrophy and to (ii) establish and validate a rat diarrhoea model with clinically relevant endpoints. Male Wistar Han IGS rats were treated with saline, doxorubicin, idarubicin, methotrexate, 5-fluorouracil, irinotecan or 5-fluorouracil+irinotecan. After 72 h, jejunal tissue was taken for morphological, apoptotic and proliferative analyses, and faecal water content and change in body weight were determined. All treatments except methotrexate caused a similar reduction (≈42%) in villus height, but none of them altered mucosal crypt cell proliferation or apoptosis. Doxorubicin, idarubicin, irinotecan and 5-fluorouracil+irinotecan caused body weight reduction, but only irinotecan and idarubicin caused diarrhoea. No direct correlation between diarrhoea and villus height or body weight loss was observed. Therefore, studies of the mechanisms for chemotherapy-induced diarrhoea should focus on functional factors. Finally, the irinotecan and idarubicin diarrhoea models established in this study will be useful in developing supportive treatments of this common and serious adverse effect in patients undergoing chemotherapy.
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| 5. |
- Hadrévi, Jenny, 1977-, et al.
(författare)
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Comparative metabolomics of muscle interstitium fluid in human trapezius myalgia: an in vivo microdialysis study
- 2013
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Ingår i: European Journal of Applied Physiology. - : Springer Verlag (Germany). - 1439-6319 .- 1439-6327. ; 113:12, s. 2977-2989
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Tidskriftsartikel (refereegranskat)abstract
- 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. less thanbrgreater than less thanbrgreater thanMicrodialysate 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. less thanbrgreater than less thanbrgreater thanA 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. less thanbrgreater than less thanbrgreater thanThis study provides important information regarding the metabolite content, thereby presenting new clues regarding the pathophysiology of the myalgic muscle.
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| 6. |
- Hadrévi, Jenny, 1977-, et al.
(författare)
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Multivariate Modeling of Proteins Related to Trapezius Myalgia, a Comparative Study of Female Cleaners with or without Pain
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:9, s. e73285-
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Hadrevi, Jenny, 1977-, et al.
(författare)
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Protein differences between human trapezius and vastus lateralis muscles determined with a proteomic approach
- 2011
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 12:181
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Hallman, David, 1979-, et al.
(författare)
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Symposium: Arbete, individ och nacksmärta : Forskning vid Forte-centret “Kroppen i arbete – från problem till potential”
- 2018
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Ingår i: FALF KONFERENS 2018 Arbetet - problem eller potential för en hållbar livsmiljö? 10-12 juni 2018 i Gävle. - Gävle : Gävle University Press. - 9789188145284 ; , s. 102-
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Konferensbidrag (refereegranskat)abstract
- Besvär ifrån kroppens muskler och leder såsom nack- och ryggbesvär är fortfarande ett stort problem inom arbetslivet. Muskuloskeletal diagnos är den vanligaste orsaken till lång sjukfrånvaro inom privat sektor och näst vanligast inom kommuner och landsting. Orsakerna till dessa besvär kan vara relaterade till exponering både under arbete och på fritid, men även till individfaktorer. Vår forskargrupp har en bred ansats för att fylla kunskapsluckor inom detta område och kommer att presentera resultat från flera forskningsprojekt i symposiet Arbete, individ och nacksmärta.Långvarigt sittande har blivit alltmer vanligt förekommande i många yrkesgrupper. Långvarigt sittande och låg fysisk aktivitet har också uppmärksammats som ett betydande hälsoproblem i dagens arbetsliv och även som en möjlig riskfaktor för smärta i nacke-skuldra. Men forskningen om betydelsen av långvarigt sittande för smärta i nacke-skuldra är fortfarande begränsad. Likaså är det oklart om huvudets hållning vid sittandet och nackens funktion, exempelvis nackens rörelsefunktion och styrka, har betydelse för besvärsutveckling. Statiskt arbete med nacken i vridna och böjda positioner misstänks vara en riskfaktor för nack-skuldersmärta i yrken såsom tandläkare, men det är oklart varför vissa exponerade individer drabbas medan andra inte får ont. För de med långvarig smärta krävs ofta rehabiliterande åtgärder, och hur väl dessa åtgärder lyckas kan även det vara beroende av individens fysiska och psykosociala arbetsmiljö. Individens arbetsmiljö påverkar således inte bara risken för om man får besvär utan kan också ha betydelse för hur rehabiliteringen av besvären lyckas.Syftet med detta symposium är att presentera studier från Centrum för belastningsskadeforskning som handlar om nacksmärta i arbetslivet, sammanfatta kunskapsläget inom området och diskutera hur arbetet kan utformas för att bli hållbart och inkluderande. De forskningsexempel som presenteras berör stillasittande och hållning i arbetslivet och dess tänkbara konsekvenser för nacksmärta och hälsa, riskfaktorer för nacksmärta i tandläkaryrket och arbetsmiljöns betydelse för resultatet av rehabilitering vid nacksmärta. Symposiet avslutas med en frågestund och gemensam diskussion.
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| 9. |
- Hellsmark, Hans, 1974, et al.
(författare)
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Teknologiska innovationssystem inom energiområdet: En praktisk vägledning till identifiering av systemsvagheter som motiverar särskilda politiska åtaganden
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med denna rapport är att illustrera hur ett praktiskt inriktat ramverk, tekno- logiska innovationssystem (TIS), kan användas av analytiker och beslutsfattare vid departement och myndigheter för att analysera strategiskt viktiga teknikområden ?????????????????????????????????????????????????????????????????????????????I rapporten analyseras fem TIS centrerade kring havsbaserad vindkraft, marin energi, ????????????????????????????????????????????????????????????????????????????????????? systemsvagheter som bromsar områdets vidare utveckling, vilka som kan åtgärdas av systemets aktörer och vilka som motiverar särskilda politiska åtaganden. Rapporten utgör därmed ett underlag för att formulera åtgärder för att åstadkomma ökad innova- tion, teknikspridning och industrialisering inom ovan nämnda teknikområden.Studien har även möjliggjort en jämförande analys av likheter och skillnader ???????????????????????????????????????????????????????????????????????????????? ?????????????????????????????????????????????????????????????????????????????????????? mellan områdena – de är starka respektive svaga av olika orsaker. Detta visar att ???????????????????????????????????????????????????????????????????????Samtidigt har områdena gemensamma drag. Systemets aktörer, där även politiska ???????????????????????????????????????????????????????????????????????????????????? ?????????????????????????????????????????????????????????????????????????????- skapsnätverk. Men de har varit sämre på att skapa tidiga nischmarknader som ger utrymme för fortsatt lärande och kostnadsreduktion. Sådana nischer kan ibland skapas av marknadens aktörer, men ofta krävs politiska styrmedel. De behövs för att investeringar i kunskapsutveckling ska kunna nyttiggöras och för att en bred industriell utveckling inom nya områden skall göras möjlig i Sverige.Vidare presenteras lärdomar kring vad en aktiv teknikpolitik innebär. Två huvud- ??????????????????????????????????????????????????????????????????????????????- hällsbygget och därför bör vara ett politikområde bland många samt att den skarpa ??????????????????????????????????????????????????????????????????????????????- ?????????????????????????????????????????????????????????????????????????????????? ?????????????????????????????????????????????????????????????????????????????????? olika faser av innovationssystemets utveckling.För att lyckas med en aktiv teknikpolitik behövs en hög grad av koordinering ??????????????????????????????????????????????????????????????????????? teknikområden så att ”rätt” typ av åtgärder kan sättas in vid ”rätt” tidpunkt av ”rätt” aktör. TIS-ramverket lyfts här fram som en metod för att skapa ett sådant underlag. Slutligen presenteras en metod för projektbedömningar som syftar till att stötta handläggare i utvärderingar av projekt inom nya teknikområden.Rapporten i sin helhet riktar sig särskilt till beslutsfattare och handläggare vid myndigheter, departement och politiker, men även andra organisationer och indi- vider med intresse av att högt ställda klimatmål ska kunna nås samtidigt som en positiv näringslivsutveckling möjliggörs.
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| 10. |
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