| 1. |
- Bruun, Jesper, et al.
(författare)
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Network analysis and qualitative discourse analysis of a classroom group discussion
- 2019
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Ingår i: International Journal of Research and Method in Education. - Abingdon-on-Thames : Routledge. - 1743-727X .- 1743-7288. ; 42:3, s. 317-339
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Tidskriftsartikel (refereegranskat)abstract
- A new methodology is proposed for qualitative discourse analysis (QDA) aimed at gaining enhanced insights into learning possibilities and indicators that arise during classroom group discussions. The constitution of this new methodology has two principle components: a discourse analysis approach that aims to identify the relationships between content and group dynamics; and a network analysis (NA) approach that uses the same data to identify meaning-related structural dynamics found in the data. The proposed methodology pairs these two components to create a supplementary iterative interchange that facilitates the attainment of greater analytic insights than are achievable by either of the two components individually. The critical aspects of the methodology are illustrated and discussed using real classroom data in ways that provide a procedural exemplar. The strengths and limitations of the proposed methodology are also discussed.
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| 2. |
- Jornvall, Hans, et al.
(författare)
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Oligomerization and insulin interactions of proinsulin C-peptide : Threefold relationships to properties of insulin
- 2010
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 391:3, s. 1561-1566
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Tidskriftsartikel (refereegranskat)abstract
- Three principally different sites of action have been reported for proinsulin C-peptide, at surface-mediated, intracellular, and extracellular locations. Following up on the latter, we now find that (i) mass spectrometric analyses reveal the presence of the C-peptide monomer in apparent equilibrium with a low-yield set of oligomers in weakly acidic or basic aqueous solutions, even at low peptide concentrations (sub-mu M). It further shows not only C-peptide to interact with insulin oligomers (known before), but also the other way around. (ii) Polyacrylamide gel electrophoresis of C-peptide shows detectable oligomers upon Western blotting. Formation of thioflavin T positive material was also detected. (iii) Cleavage patterns of analogues are compatible with C-peptide as a substrate of insulin degrading enzyme. Combined, the results demonstrate three links with insulin properties, in a manner reminiscent of amyloidogenic peptides and their chaperons in other systems. If so, peripheral C-peptide/insulin interactions, absolute amounts of both peptides and their ratios may be relevant to consider in diabetic and associated diseases.
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| 3. |
- Lind, Jesper, et al.
(författare)
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Structural features of proinsulin C-peptide oligomeric and amyloid states
- 2010
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 277:18, s. 3759-68
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Tidskriftsartikel (refereegranskat)abstract
- The formation and structure of proinsulin C-peptide oligomers has been investigated by PAGE, NMR spectroscopy and dynamic light scattering. The results obtained show that C-peptide forms oligomers of different sizes, and that their formation and size distribution is altered by salt and divalent metal ions, which indicates that the aggregation process is mediated by electrostatic interactions. It is further demonstrated that the size distribution of the C-peptide oligomers, in agreement with previous studies, is altered by insulin, which supports a physiologically relevant interaction between these two peptides. A small fraction of oligomers has previously been suggested to be in equilibrium with a dominant fraction of soluble monomers, and this pattern also is observed in the present study. The addition of modest amounts of sodium dodecyl sulphate at low pH increases the relative amount of oligomers, and this effect was used to investigate the details of both oligomer formation and structure by a combination of biophysical techniques. The structural properties of the SDS-induced oligomers, as obtained by thioflavin T fluorescence, CD spectroscopy and IR spectroscopy, demonstrate that soluble aggregates are predominantly in β-sheet conformation, and that the oligomerization process shows characteristic features of amyloid formation. The formation of large, insoluble, β-sheet amyloid-like structures will alter the equilibrium between monomeric C-peptide and oligomers. This leads to the conclusion that the oligomerization of C-peptide may be relevant also at low concentrations.
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| 4. |
- Lindahl, Jesper, et al.
(författare)
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Add-on pramipexole for anhedonic depression : study protocol for a randomised controlled trial and open-label follow-up in Lund, Sweden
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 13:11, s. 9
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Many depressed patients do not achieve remission with available treatments. Anhedonia is a common residual symptom associated with treatment resistance as well as low function and quality of life. There are currently no specific and effective treatments for anhedonia. Some trials have shown that dopamine agonist pramipexole is efficacious for treating depression, but more data is needed before it could become ready for clinical prime time. Given its mechanism of action, pramipexole might be a useful treatment for a depression subtype characterised by significant anhedonia and lack of motivation-symptoms associated with dopaminergic hypofunction. We recently showed, in an open-label pilot study, that add-on pramipexole is a feasible treatment for depression with significant anhedonia, and that pramipexole increases reward-related activity in the ventral striatum. We will now confirm or refute these preliminary results in a randomised controlled trial (RCT) and an open-label follow-up study. METHODS AND ANALYSIS: Eighty patients with major depression (bipolar or unipolar) or dysthymia and significant anhedonia according to the Snaith Hamilton Pleasure Scale (SHAPS) are randomised to either add-on pramipexole or placebo for 9 weeks. Change in anhedonia symptoms per the SHAPS is the primary outcome, and secondary outcomes include change in core depressive symptoms, apathy, sleep problems, life quality, anxiety and side effects. Accelerometers are used to assess treatment-associated changes in physical activity and sleep patterns. Blood and brain biomarkers are investigated as treatment predictors and to establish target engagement. After the RCT phase, patients continue with open-label treatment in a 6-month follow-up study aiming to assess long-term efficacy and tolerability of pramipexole. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. The study is externally monitored according to Good Clinical Practice guidelines. Results will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05355337 and NCT05825235.
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| 5. |
- Lindahl, Mats, 1957-, et al.
(författare)
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Demonstration of different forms of the anti-inflammatory proteins lipocortin-1 and Clara cell protein-16 in human nasal and bronchoalveolar lavage fluids
- 1999
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Ingår i: Electrophoresis. - 0173-0835 .- 1522-2683. ; 20:4-5, s. 881-890
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Tidskriftsartikel (refereegranskat)abstract
- The anti-inflammatory proteins lipocortin-1 and Clara cell protein-16 (CC-16) were studied in two-dimensional gel electrophoresis (2-DE) protein patterns of human nasal lavage fluids (NLFs) and bronchoalveolar lavage fluids (BALFs). Seven forms of lipocortin-1 were detected with Western immunoblots: three isoforms with an apparently normal Mr of 38 kDa and pI of 5.9, 6.0 and 6.1, and four truncated variants with pI/kDa 6.0/36, 6.4/36, 7.0/33, and 7.4/34. Four 6 kDa isoforms of CC-16 were found with pI 4.6, 4.8, 4.9, and 5.2. Lipocortin-1 and CC-16 were expressed in all individuals tested although not all variants were found in each individual. The overall levels of lipocortin-1 were higher in BALF than NLF and there were significant differences in the distribution of the different lipocortin-1 forms between BALFs and NLFs. One patient with occupational asthma and four children with rhinitis had increased levels of one of the truncated lipocortin-1 forms in NLF (pI/kDa: 7.4/34) and decreased levels of the major CC-16 form (pI/kDa: 4.8/6). The levels of CC-16 but not of lipocortin-1 were higher in BALF from smokers than from nonsmokers. These results indicate that the levels of lipocortin-1 and CC-16 in NLF and BALF may be altered in inflammatory airway disorders. Furthermore, the identification of different forms of the two proteins makes possible more detailed studies on the role of these proteins in inflammatory disease processes and anti-inflammatory therapies.
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| 6. |
- Lindahl, Mats, 1955-, et al.
(författare)
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Integrating text-mining, network analysis and thematic discourse analysis to produce maps of student discussions about sustainability
- 2016
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Ingår i: A methodological approach to PER.
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Konferensbidrag (refereegranskat)abstract
- We use a combination of network analysis (NA), text-mining (TM) techniques, and thematic discourse analysis (TDA) to characterise and compare student discussions about sustainable development. Three student groups at three different times were analysed. The analysis entails an iterative design where NA, TM, and TDA continuously inform each other to produce a rich and coherent picture of the discussions. The output of such an analysis is a set of maps of these discussions, which have both qualitative and quantitative uses. Qualitatively, the maps show how thematic patterns in the discussions are related for each group, and we can see how discourses differ between groups as well as over time. Quantitatively, we use network motif analysis, entropy based measures, and degree distributions to distinguish between discussions.
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| 7. |
- Lindahl, Mats, et al.
(författare)
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Medicin, hälsa och ohälsa i undervisningen
- 2019
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Annan publikation (populärvet., debatt m.m.)abstract
- Texten syftar till att ge några tillbakablickar och kommentarer baserade på modulens övriga delar. Vissa ämnesområden, som behandlats tidigare i modulen, skulle kunna användas som alternativ till kontroverserna kring vacciner och antibiotika.
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| 8. |
- Loberg, John, 1980-, et al.
(författare)
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Homogenization of Cross Sections and Computation of Discontinuity Factors for a Real 3D BWR Bottom Reflector for Comparison with Lattice and Nodal Codes
- 2012
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Ingår i: Nuclear Technology. - 0029-5450 .- 1943-7471. ; 177:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Boiling water reactor (BWR) bottom reflector calculations in lattice codes such as CASMO are presently used only to produce accurate boundary conditions for core interfaces in nodal diffusion codes. Homogenized cross-section constants and discontinuity factors are calculated in one dimension (1-D) without the explicit presence of the control rod absorber. If the spatial flux in a BWR bottom reflector is required, for example, for depletion calculations of withdrawn control rods, the homogenization of the reflector must be based on a representation of the three-dimensional (3-D) geometry and material composition that is as true as possible. This paper investigates differences in cross-section and discontinuity factors from 1-D calculations in CASMO with 3-D Monte Carlo calculations of a realistic bottom reflector model in MCNP5. The cross-section and discontinuity factors from CASMO and MCNP5 are furthermore implemented in the nodal diffusion code SIMULATES to investigate the effect on the neutron fluxes in the bottom reflector. The results show that for the case investigated, the 1-D homogenization in CASMO5 produces a 26% overestimation of the homogenized thermal absorption cross section in the reflector and a 62% underestimation of the homogenized fast absorption cross section. These cross-section differences have essentially no impact on the neutron flux in the core but cause a 4.5% and 12.3% underestimation of the thermal and fast neutron flux, respectively, in the reflector region.
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| 9. |
- Loberg, John, 1980-, et al.
(författare)
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Simulations and Models of Neutron Fluxes in BWRs Intended for Depletion Calculations of Withdrawn Control Rods
- 2011
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Ingår i: Nuclear science and engineering. - 0029-5639 .- 1943-748X. ; 177:3, s. 221-229
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Tidskriftsartikel (refereegranskat)abstract
- Models of the neutron flux shape in a withdrawn control rod in a boiling water reactor (BWR) bottom reflector have been constructed from simulations with the Monte Carlo code MCNP. These neutron flux models are intended for determining absorber depletion and fast fluence accumulation for withdrawn control rods with nodal codes. So-called G-factors are created for coupling the neutron flux models to a conventional nodal code via the core bottom neutron flux. The neutron flux models and G-factors are created for three different neutron energies, and their dependence on various parameters such as blanket enrichments, Hf and B(4)C control rod absorber, and depletion and reflector geometry is investigated. The neutron flux models and G-factors are found to be very insensitive; the neutron flux models predict the simulated neutron flux in the withdrawn control rod from MCNP over a variety of reflector configurations with an error < 3.0%. This implies that the neutron flux models constructed in this paper are generally applicable for BWR reflectors and control rods not fundamentally deviating from the designs investigated in this paper.
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| 10. |
- Sandin, Charlotta, et al.
(författare)
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Isolation and detection of human IgA using a streptococcal IgA-binding peptide.
- 2002
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Ingår i: Journal of Immunology. - 1550-6606. ; 169:3, s. 1357-1364
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial proteins that bind to the Fc part of IgG have found widespread use in immunology. A similar protein suitable for the isolation and detection of human IgA has not been described. Here, we show that a 50-residue synthetic peptide, designated streptococcal IgA-binding peptide (Sap) and derived from a streptococcal M protein, can be used for single-step affinity purification of human IgA. High affinity binding of IgA required the presence in Sap of a C-terminal cysteine residue, not present in the intact M protein. Passage of human serum through a Sap column caused depletion of >99% of the IgA, and elution of the column allowed quantitative recovery of highly purified IgA, for which the proportions of the IgA1 and IgA2 subclasses were the same as in whole serum. Moreover, immobilized Sap could be used for single-step purification of secretory IgA of both subclasses from human saliva, with a recovery of approximately 45%. The Sap peptide could also be used to specifically detect IgA bound to Ag. Together, these data indicate that Sap is a versatile Fc-binding reagent that may open new possibilities for the characterization of human IgA.
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| 11. |
- Suneson, Klara, et al.
(författare)
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Efficacy of eicosapentaenoic acid in inflammatory depression : study protocol for a match-mismatch trial
- 2022
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Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most antidepressant treatment studies have included patients strictly based on the Diagnostic and Statistical Manual of Mental Disorders definition of Major Depressive Disorder (MDD). Given the heterogeneity of MDD, this approach may have obscured inter-patient differences and hampered the development of novel and targeted treatment strategies. An alternative strategy is to use biomarkers to delineate endophenotypes of depression and test if these can be targeted via mechanism-based interventions. Several lines of evidence suggest that “inflammatory depression” is a clinically meaningful subtype of depression. Preliminary data indicate that omega-3 fatty acids, with their anti-inflammatory and neuroprotective properties, may be efficacious in this subtype of depression, and this study aims to test this hypothesis. Method: We conduct a match-mismatch-trial to test if add-on omega-3 fatty acid eicosapentaenoic acid (EPA) reduces depressive symptoms in patients with MDD and systemic low-grade inflammation. MDD patients on a stable antidepressant treatment are stratified at baseline on high sensitivity-C-reactive protein (hs-CRP) levels to a high-inflammation group (hs-CRP ≥ 3 mg/L) or a low-inflammation group (hs-CRP < 3 mg/L). Both groups receive add-on EPA (2 g per day) for 8 weeks with three study visits, all including blood draws. Patients and raters are blind to inflammation status. Primary outcome measure is change in Hamilton Depression Rating Scale score between baseline and week 8. We hypothesize that the inflammation group has a superior antidepressant response to EPA compared to the non-inflammation group. Secondary outcomes include a composite score of “inflammatory depressive symptoms”, quality of life, anxiety, anhedonia, sleep disturbances, fatigue, cognitive performance and change in biomarkers relating to inflammation, oxidative stress, metabolomics and cellular aging. Discussion: In this study we will, for the first time using a match-mismatch trial design, test if omega-3 is an efficacious treatment for inflammatory depression. If our study is successful, it could add to the field of precision psychiatry. Trial registration: This trial was registered May 8, 2017 on clinicaltrials.gov under the reference number NCT03143075.
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| 12. |
- Suneson, Klara, et al.
(författare)
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Inflammatory depression—mechanisms and non-pharmacological interventions
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:4
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Forskningsöversikt (refereegranskat)abstract
- Treatment of depression is hampered by the failure to identify distinct symptom profiles with distinct pathophysiologies that differentially respond to distinct treatments. We posit that inflammatory depression is a meaningful depression subtype associated with specific symptoms and biological abnormalities. We review several upstream, potentially causative, mechanisms driving low-grade inflammation in this subtype of depression. We also discuss downstream mechanisms mediating the link between inflammation and symptoms of depression, including alterations in dopaminergic neurotransmission and tryptophan metabolism. Finally, we review evidence for several non-pharmacological interventions for inflammatory depression, including probiotics, omega-3 fatty acids, and physical exercise interventions. While some evidence suggests that these interventions may be efficacious in inflammatory depression, future clinical trials should consider enriching patient populations for inflammatory markers, or stratify patients by inflammatory status, to confirm or refute this hypothesis.
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| 13. |
- Suneson, Klara, et al.
(författare)
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Omega-3 fatty acids for inflamed depression - A match/mismatch study
- 2024
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Ingår i: Brain, Behavior, and Immunity. - 1090-2139. ; 118, s. 192-201
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Tidskriftsartikel (refereegranskat)abstract
- Despite decades of research on the pathophysiology of depression, the development of new therapeutic interventions has been slow, and no biomarkers of treatment response have been clinically implemented. Several lines of evidence suggest that the clinical and biological heterogeneity among patients with major depressive disorder (MDD) has hampered progress in this field. MDD with low-grade inflammation - "inflamed depression" - is a subtype of depression that may be associated with a superior antidepressant treatment response to anti-inflammatory compounds. Omega-3 fatty acid eicosapentaenoic acid (EPA) has anti-inflammatory properties, and preliminary data suggest that it may be particularly efficacious in inflamed depression. In this study we tested the hypothesis that add-on EPA has greater antidepressant efficacy in MDD patients with high baseline high-sensitivity C-reactive protein (hs-CRP) compared to MDD patients with low hs-CRP. All subjects received 2.2 g EPA, 400 mg docosahexaenoic acid and 800 mg of other fatty acids daily for 8 weeks, added to stable ongoing antidepressant treatment. The primary outcome was change in the 17-item Hamilton Depression Rating Scale (HAMD-17). Patients and raters were blind to baseline hs-CRP status. In an intention-to-treat analysis including all subjects with at least one post baseline visit (n = 101), ahs-CRPcut-off of ≥1 mg/L, but not ≥3 mg/L, was associated with a greater improvement in HAMD-17 total score. In addition to a general antidepressant effect among patients with hs-CRP ≥ 1 mg/L, adjuvant EPA treatment improved symptoms putatively related to inflamed depression such as fatigue and sleep difficulties. This adds to the mounting evidence that delineation of MDD subgroups based on inflammation may be clinically relevant to predict treatment response to anti-inflammatory interventions.
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| 14. |
- Ventorp, Filip, et al.
(författare)
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Preliminary Evidence of Efficacy and Target Engagement of Pramipexole in Anhedonic Depression
- 2022
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Ingår i: Psychiatric Research and Clinical Practice. - : John Wiley and Sons Inc.. - 2575-5609. ; 4:2, s. 42-47
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Tidskriftsartikel (refereegranskat)abstract
- Objective : To investigate feasibility and target engagement of high-dose, add-on pramipexole treatment in anhedonic depression. Method : In this open-label pilot study, we included 12 patients with unipolar or bipolar, moderate-to-severe depression and with significant anhedonia symptoms. All patients were on a stable dose of one or a combination of antidepressants and/or mood stabilizers and received 10 weeks of adjunctive pramipexole titrated to a maximum dose of 4.5 mg salt/day. All patients were rated with the Dimensional Anhedonia Rating Scale (DARS), the Montgomery Åsberg Depression Rating (MADRS) and the Snaith Hamilton Pleasure Scale (SHAPS). Serum high-sensitivity C-reactive protein (hs-CRP) was analyzed pre- and post-treatment. Eight patients underwent fMRI pre- and post-treatment and a simplified version of the monetary incentive delay task was used to investigate the effect of treatment on striatal activity during reward anticipation. Results : DARS, MADRS and SHAPS scores all improved significantly over 10 weeks of pramipexole treatment (p<0.01). Mean levels of hs-CRP decreased significantly over the course of treatment from mean 3.8 mg/L at baseline to 2.6 mg/L at endpoint (p<0.01). There were significant treatment-associated increases in reward related activity in several brain areas including the right lateral putamen, anterior left caudate, left posterior putamen, right dorsal caudate, left anterior putamen, and the right nucleus accumbens. Conclusions : This is the first study to suggest efficacy and target engagement of pramipexole in anhedonic depression. Larger randomized controlled trials are needed to confirm or refute these preliminary findings.
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| 15. |
- Waldenström, Jesper, 1985, et al.
(författare)
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Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naive patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-alpha (pegIFN-alpha), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-alpha, or (iii) standard-of-care (SOC) ribavirin dosing concurrent with pegIFN-alpha. Four weeks of ribavirin mono-therapy resulted in a mean 0.46 log(10) IU/mL HCV RNA reduction differentially regulated across IL28B genotypes (0.89 vs. 0.21 log(10) IU/mL for CC and CT/TT respectively; P = 0.006), increased likelihood of undetectable HCV RNA week 4 after initiating pegIFN-alpha and thus shortened treatment duration (P < 0.05), and decreased median IP-10 concentration from 550 to 345 pg/mL (P < 0.001). Both experimental strategies impacted on ribavirin concentrations, and high levels were achieved after one week of double dosing. However, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an antiviral effect differently regulated across IL28B genotypes.
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