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| 2. |
- Kuhle, J., et al.
(författare)
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Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study
- 2015
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 21:8, s. 1013-1024
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
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| 6. |
- Petzold, Axel, et al.
(författare)
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Neurofilament ELISA validation
- 2010
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Ingår i: JOURNAL OF IMMUNOLOGICAL METHODS. - 0022-1759. ; 352:1-2, s. 23-31
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Petzold, Axel, et al.
(författare)
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Neurofilament ELISA validation
- 2010
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Ingår i: JIM - Journal of Immunological Methods. - : Elsevier BV. - 0022-1759 .- 1872-7905. ; 352:1-2, s. 23-31
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. METHODS: The UmanDiagnostics NF-light (R)enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses. RESULTS: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R=0.60, p<0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R=0.98, p<0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics. CONCLUSION: This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.
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| 8. |
- Pillon, NJ, et al.
(författare)
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Palmitate impairs circadian transcriptomics in muscle cells through histone modification of enhancers
- 2022
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Ingår i: Life science alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Obesity and elevated circulating lipids may impair metabolism by disrupting the molecular circadian clock. We tested the hypothesis that lipid overload may interact with the circadian clock and alter the rhythmicity of gene expression through epigenomic mechanisms in skeletal muscle. Palmitate reprogrammed the circadian transcriptome in myotubes without altering the rhythmic mRNA expression of core clock genes. Genes with enhanced cycling in response to palmitate were associated with post-translational modification of histones. The cycling of histone 3 lysine 27 acetylation (H3K27ac), a marker of active gene enhancers, was modified by palmitate treatment. Chromatin immunoprecipitation and sequencing confirmed that palmitate exposure altered the cycling of DNA regions associated with H3K27ac. The overlap between mRNA and DNA regions associated with H3K27ac and the pharmacological inhibition of histone acetyltransferases revealed novel cycling genes associated with lipid exposure of primary human myotubes. Palmitate exposure disrupts transcriptomic rhythmicity and modifies enhancers through changes in histone H3K27 acetylation in a circadian manner. Thus, histone acetylation is responsive to lipid overload and may redirect the circadian chromatin landscape, leading to the reprogramming of circadian genes and pathways involved in lipid biosynthesis in skeletal muscle.
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| 9. |
- Teunissen, C, et al.
(författare)
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Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis
- 2013
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 19:13, s. 1802-1809
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Tidskriftsartikel (refereegranskat)abstract
- The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control groups and a rationalized application of different control groups. We here propose consensus definitions and nomenclature for the following groups: healthy controls (HCs), spinal anesthesia subjects (SASs), inflammatory neurological disease controls (INDCs), peripheral inflammatory neurological disease controls (PINDCs), non-inflammatory neurological controls (NINDCs), symptomatic controls (SCs). Furthermore, we discuss the application of these control groups in specific study designs, such as for diagnostic biomarker studies, prognostic biomarker studies and therapeutic response studies. Application of these uniform definitions will lead to better comparability of biomarker studies and optimal use of available resources. This will lead to improved quality of CSF biomarker research in MS and related disorders.
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| 10. |
- Gohritz, A., et al.
(författare)
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Rekonstruktion der aktiven Ellbogenbeugung durch bipolare Transposition des Musculus latissimus dorsi : [Restoration of active elbow flexion by muscle transfer of the latissimus dorsi]
- 2009
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Ingår i: Operative Orthopädie und Traumatologie. - 0934-6694. ; 21:2, s. 115-25
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Reconstruction of active elbow flexion against gravity (strength grade > or =M(3)) by transfer of the latissimus dorsi muscle in order to improve the functionality of the upper extremity. INDICATIONS: Irreparable lesions of the musculocutaneous nerve (C(5)/6). Failure of regeneration after peripheral nerve reconstruction for the musculocutaneous nerve (neurolysis, suture, nerve grafting). Brachial plexus injury (lesions to the upper part, C(5)/6). Loss of biceps function due to trauma, ischemia, poliomyelitis or tumor. CONTRAINDICATIONS: Possible recovery of biceps function by reinnervation, spontaneously or after nerve reconstruction. Weakness of the latissimus dorsi muscle (strength grade < M(4)). Insufficient passive range of motion of the elbow joint (osteoarthritis, contracture). Lack of motivation, reliability, and cooperation of the patient in postoperative rehabilitation program. SURGICAL TECHNIQUE: The intact latissimus dorsi muscle is transferred with its origin and insertion ventrally and sutured with its thoracic aponeurosis into the insertion of the biceps tendon in order to act as an elbow flexor. POSTOPERATIVE MANAGEMENT: Following postoperative immobilization in an upper-arm Gilchrist bandage at 100 degrees flexion and supination (or neutral position, but not pronation) of the forearm for 6 weeks, passive motion exercises of the elbow are started. Active flexion and extension exercises begin at 8-10 weeks postoperatively. To prevent the deleterious effect of muscle and tendon elongation, an orthosis is used during the night to keep the elbow flexed at 90 degrees for 6 months. RESULTS: According to the authors' experience and the results reported in the literature, bipolar latissimus dorsi muscle transfer is a reliable method to restore functional elbow flexion regarding range of motion (> 90 degrees elbow flexion) and strength (at least antigravity strength, > or =M(3)) with acceptable donor morbidity and complication rate.
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| 13. |
- Altintas, A, et al.
(författare)
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Transcriptomic and epigenomics atlas of myotubes reveals insight into the circadian control of metabolism and development
- 2020
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 12:8, s. 701-713
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Innate circadian rhythms are critical for optimal tissue-specific functions, including skeletal muscle, a major insulin-sensitive tissue responsible for glucose homeostasis. We determined whether transcriptional oscillations are associated with CpG methylation changes in skeletal muscle. Materials & methods: We performed rhythmicity analysis on the transcriptome and CpG methylome of circadian synchronized myotubes. Results: We identified several transcripts and CpG-sites displaying oscillatory behavior, which were enriched with Gene Ontology terms related to metabolism and development. Oscillating CpG methylation was associated with rhythmic expression of 31 transcripts. Conclusion: Although circadian oscillations may be regulated by rhythmic DNA methylation, strong rhythmic associations between transcriptome and CpG methylation were not identified. This resource constitutes a transcriptomic/epigenomic atlas of skeletal muscle and regulation of circadian rhythms.
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| 14. |
- Aşçı, H.F, et al.
(författare)
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Gender differences in the relation of personality traits and self-presentation with physical activity
- 2015
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Ingår i: Science & sports. - : Elsevier BV. - 0765-1597. ; 30:1, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The purpose of this study was to examine the relation of physical activity with personality traits and self-presentation and gender differences in this relation. Methods Two hundred thirteen female (Mage = 21.73 ± 1.63), 247 male (Mage = 22.37 ± 2.19) exercisers voluntarily participated in this study. The Five Factor Personality Inventory (short version), Self Presentation in Exercise Questionnaire and The short version of International Physical Activity Questionnaire was administered to participants. Results Regression analysis indicated that openness to experience was a significant predictor of moderate physical activity in females. On the other hand, agreeableness, emotional stability and conscientiousness were related to vigorous physical activity in males. Analysis also revealed significant relationship between vigorous physical activity and impression motivation in both males and females. Furthermore, impression construction was also associated with vigorous physical activity in females. Conclusion This study extended the previous studies on Western culture to non-western culture of Turkey and also provided some explanation for inconclusive results about the gender differences in the relationship of personality and physical activity. The study also examined the relationship between self-presentation and physical activity in terms of gender, which is less frequently studied. The findings of this study indicated that the pattern of relation of physical activity with personality traits differed with regard to gender. For males, personality characteristic were related with vigorous physical activity but for females personality is predictor of moderate physical activity. The patterns of relation of physical activity with self-presentation are similar for males and females and self-presentation is related with the vigorous physical activity for both gender.
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| 16. |
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| 17. |
- Lundell, LS, et al.
(författare)
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Time-restricted feeding alters lipid and amino acid metabolite rhythmicity without perturbing clock gene expression
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4643-
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Tidskriftsartikel (refereegranskat)abstract
- Time-restricted feeding (TRF) improves metabolism independent of dietary macronutrient composition or energy restriction. To elucidate mechanisms underpinning the effects of short-term TRF, we investigated skeletal muscle and serum metabolic and transcriptomic profiles from 11 men with overweight/obesity after TRF (8 h day−1) and extended feeding (EXF, 15 h day−1) in a randomised cross-over design (trial registration: ACTRN12617000165381). Here we show that muscle core clock gene expression was similar after both interventions. TRF increases the amplitude of oscillating muscle transcripts, but not muscle or serum metabolites. In muscle, TRF induces rhythmicity of several amino acid transporter genes and metabolites. In serum, lipids are the largest class of periodic metabolites, while the majority of phase-shifted metabolites are amino acid related. In conclusion, short-term TRF in overweight men affects the rhythmicity of serum and muscle metabolites and regulates the rhythmicity of genes controlling amino acid transport, without perturbing core clock gene expression.
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| 19. |
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| 20. |
- Topuz, G., et al.
(författare)
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Jurassic ophiolite formation and emplacement as backstop to a subduction-accretion complex in northeast Turkey, the Refahıye ophiolite, and relation to the Balkan ophiolites
- 2013
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Ingår i: American Journal of Science. - : American Journal of Science (AJS). - 0002-9599. ; 313:10, s. 1054-1087
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Tidskriftsartikel (refereegranskat)abstract
- The eastern Mediterranean region within the Tethyan realm shows a high concentration of ophiolites with contrasting times of formation and emplacement along the belt: In the Balkans, the ophiolites formed during the early to medial Jurassic, and were obducted during the late Jurassic, whereas in Turkey and farther east, structurally intact Jurassic ophiolites are rare and Jurassic ophiolite obduction is unknown. Here we report a structurally intact, large ophiolite body of early Jurassic age from NE Turkey, the Refahiye ophiolite, located close to the suture zone between the Eastern Pontides and the Menderes-Taurus block. The Refahiye ophiolite forms an outcrop belt, 175 km long and 20 km wide, and is tectonically bound by the late Cretaceous ophiolitic melange to the south, and by the North Anatolian Transform Fault against the Triassic low-grade metamorphic rocks to the north. Early to medial Jurassic very low- to low-grade metamorphic rocks, interpreted as intraoceanic subduction-accretion complexes, occur either beneath the ophiolite or as thrust slices within it. The ophiolite body within the studied section is made up of mantle peridotite (clinopyroxene-bearing harzburgite and minor dunite) crosscut by up to 20 cm thick veins of clinopyroxenite and later dikes/pods/stocks of gabbro ranging in size from 2 m to several hundreds of meters. The gabbro is represented by two distinct types: (i) cumulate gabbro, and (ii) non-cumulate gabbro with locally well-developed igneous foliation. Within the non-cumulate gabbro or enclosing peridotite, there are up to 5 m and 50 cm-thick veins of trondhjemite and pegmatitic gabbro, respectively. LA-ICP-MS dating on zircons from two irondhjemite samples yielded weighted mean ages of similar to 184 +/- 4 Ma and 178 +/- 4 Ma (2 sigma), respectively, suggesting formation during early Jurassic time. Formation in a suprasubduction-zone forearc setting is inferred from (i) wide-ranging pyroxene and spinel compositions in the peridotites as documented in most suprasubduction-zone ophiolites, (ii) arc tholeiitic signature of the non-cumulate gabbros, and (iii) association of the ophiolite with the coeval subduction-accretion complexes. Emplacement of a trapped forearc ophiolite above its own subduction-accretion complex as a backstop is proposed based on a series of field relationships such as (i) intimate association of the unsubducted suprasubduction-zone ophiolite with coeval accretionary complexes, (ii) absence of unambiguous relationship to the southern Atlantic-type continental margin, and (iii) absence of any stratigraphic indications for the ophiolite obduction in the southern Atlantic-type continental margin during Jurassic time. This is a clear difference from the Jurassic ophiolites in the Balkans that were obducted over the Atlantic-type continental margin. This difference in mode of emplacement is most probably related to the greater distance of the intra-oceanic subduction zone to the Atlantic-type continental margin than it was in the Balkans, which is commensurate with the greater width of the Tethys in the east during Jurassic time.
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