| 1. |
- Högström, Sofie, et al.
(author)
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Dance and Yoga Reduced Functional Abdominal Pain in Young Girls : A Randomized Controlled Trial
- 2022
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In: European Journal of Pain. - : John Wiley & Sons. - 1090-3801 .- 1532-2149. ; 26:2, s. 336-348
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Journal article (peer-reviewed)abstract
- Background: Functional abdominal pain disorders (FAPDs) affect children, especially girls, all over the world. The evidence for existing treatments is mixed, and effective accessible treatments are needed. Dance, a rhythmic cardio-respiratory activity, combined with yoga, which enhances relaxation and focus, may provide physiological and psychological benefits that could help to ease pain.Objectives: The aim with this study was to evaluate the effects of a dance and yoga intervention on maximum abdominal pain in 9- to 13-year- old girls with FAPDs.Methods: This study was a prospective randomised controlled trial with 121 participants recruited from outpatient clinics as well as the general public. The intervention group participated in dance and yoga twice weekly for 8 months; controls received standard care. Abdominal pain, as scored on the Faces Pain Scale–Revised, was recorded in a pain diary. A linear mixed model was used to estimate the outcomes and effect sizes.Results: Dance and yoga were superior to standard healthcare alone, with a medium to high between-group effect size and significantly greater pain reduction (b = −1.29, p = 0.002) at the end of the intervention.Conclusions: An intervention using dance and yoga is likely a feasible and beneficial complementary treatment to standard health care for 9- to 13-year-old girls with FAPDs.Significance: FAPDs affect children, especially girls, all over the world. The negative consequences such as absence from school, high consumption of medical care and depression pose a considerable burden on children and their families and effective treatments are needed. This is the first study examining a combined dance/yoga intervention for young girls with FAPDs and the result showed a reduction of abdominal pain. These findings contribute with new evidence in the field of managing FAPDs in a vulnerable target group.
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| 5. |
- Areskoug Sandberg, Elin, et al.
(author)
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Saliva Cortisol in Girls With Functional Abdominal Pain Disorders : A Randomized Controlled Dance and Yoga Intervention.
- 2022
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In: Frontiers in Pediatrics. - : Frontiers Media S.A.. - 2296-2360. ; 10
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Functional abdominal pain disorders (FAPDs) are common among girls and has been associated with stress. Cortisol is one of the major stress hormones. Dance and yoga have been shown to reduce abdominal pain among girls with FAPDs.AIM: To investigate the effect of an 8-month intervention with dance and yoga on cortisol levels in saliva among girls with FAPDs.METHODS: A total of 121 girls aged 9-13 years with irritable bowel syndrome (IBS) or functional abdominal pain were included in the study. Participants were randomized into an intervention group and a control group. The intervention group attended a combined dance and yoga session twice a week for 8 months. Saliva samples were collected during 1 day, in the morning and evening, at baseline, and at 4 and 8 months. Subjective pain and stress were assessed as well.RESULTS: No significant effects on saliva cortisol levels between groups were observed after completion of the intervention at 8 months. However, evening cortisol and evening/morning quotient were significantly reduced at 4 months in the intervention group compared to the control group (p = 0.01, p = 0.004). There was no association between cortisol quota and pain or stress.CONCLUSION: Improvements in cortisol levels were seen in the intervention group at 4 months but did not persist until the end of the study. This indicates that dance and yoga could have a stress-reducing effect during the ongoing intervention.
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| 6. |
- Asplund, Maria, 1978-, et al.
(author)
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Biocompatibility of PEDOT/biomolecular composites intended for neural communication electrodes
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Other publication (pop. science, debate, etc.)abstract
- Electrodes of the conjugated polymer poly(3,4-ethylene dioxythiophene) (PEDOT) have been shown to possess very attractive electrochemical properties for functional electrical stimulation (FES) or recording in the nervous system. Biomolecules already present in nervous tissue, added as counter ions in PEDOT electropolymerisation, could be a route to further improve the biomaterial properties of PEDOT, eliminating the need of surfactant counter ions like docedyl benzene sulphonate (DBS) or polystyrene sulphonate (PSS) in the polymerisation process. Such PEDOT/biomolecular composites using heparin, or hyaluronic acid, have been electrochemically investigated in a previous study and have been shown to retain the attractive electrochemical properties already proven for PEDOT:PSS. The aim of the present study is to evaluate biocompatibility of these PEDOT/biomolecular composites in vitro and also evaluate PEDOT:heparin biocompatibility in cortical tissue in vivo. Hereby, we also aim to identify a suitable test protocol, that can be used in future evaluations when further material developments are made. Material toxicity was first tested on cell lines, both through a standardised agarose overlay assay on L929 fibroblasts, and through elution tests on human neuroblastoma SH-SY5Y cells. Subsequently, a biocompatibility in vivo test was performed using PEDOT:heparin coated platinum probes implanted in the cerebral cortex of Sprague-Dawley rats. Tissue was collected at three weeks and six weeks of implantation and evaluated by immunohistochemistry. No cytotoxic response was seen to any of the PEDOT:biomolecular composites tested here. Furthermore, elution tests were found to be a practical and effective way of screening materials for toxicity and had a clear advantage over the agarose overlay assay, which was difficult to apply on other cell types than fibroblasts. Elution tests would therefore be recommendable as a screening method, at all stages of material development. In the in vivo tests, the stiffness of the platinum substrate was a significant problem, and extensive glial scarring was seen in most cases irrespective of implant material. However, quantification of immunological response through distance measurements from implant site to closest neuron, and counting of macrophage densities in proximity to polymer surface, was comparable to those of platinum controls. These results indicate that PEDOT:heparin surfaces were as compatible with cortical tissue as pure platinum controls.
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| 7. |
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| 8. |
- Berg, Lotta, et al.
(author)
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Yttrande från SLUs vetenskapliga råd för djurskydd om hållande av hund och katt
- 2018
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Other publication (other academic/artistic)abstract
- Detta yttrande är skrivet på uppdrag av Jordbruksverket i samband med verkets översyn av föreskrifterna för hund och katt. För att Jordbruksverkets föreskrifter ska vara väl förankrade i den senaste forskningen önskar verket inhämta underlag från det vetenskapliga rådet för djurskydd vid Sveriges lantbruksuniversitet, specifikt gällande områdena rörelsebehov, social kontakt och avvänjning.
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| 11. |
- Chorell, Elin, 1981-, et al.
(author)
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Plasma metabolomic response to postmenopausal weight loss induced by different diets
- 2016
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In: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 12:5
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Journal article (peer-reviewed)abstract
- Background Menopause is associated with increased abdominal fat and increased risk of developing diabetes and cardiovascular disease. Objectives The present study evaluated the plasma metabolic response in relation to insulin sensitivity after weight loss via diet intervention. Methods This work includes two studies; i) Ten women on a 5 weeks Paleolithic-type diet (PD, 30 energy percent (E%) protein, 40 E% fat, 30 E% carbohydrates), ii) 55 women on 6 months of either PD or Nordic Nutrition Recommendations diet (NNR, 15 E% protein, 30 E% fat, and 55 E% carbohydrates). Plasma metabolic profiles were acquired at baseline and post diet using gas chromatography time-of-flight/mass spectrometry and investigated in relation to insulin sensitivity using multivariate bioinformatics. Results Both the PD and NNR diet resulted in significant weight loss, reduced waist circumference, improved serum lipid profiles, and improved insulin sensitivity. We detected a baseline metabolic profile that correlated significantly with insulin sensitivity, and of which components increased significantly in the PD group compared to NNR. Specifically, a significant increase in myo-inositol (MI), a second messenger of insulin action, and beta-hydroxybutyric acid (beta-HB)increased while dihomogamma-linoleic acid (DGLA) decreased in PD compared to NNR, which correlated with improved insulin sensitivity. We also detected a significant decrease in tyrosine and tryptophan, potential markers of insulin resistance when elevated in the circulation, with the PD but not the NNR. Conclusions Using metabolomics, we detected changes in the plasma metabolite profiles associated with weight loss in postmenopausal women by different diets. The metabolic profiles following 6 months of PD were linked to beneficial effects on insulin sensitivity compared to NNR.
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| 12. |
- Correa, Fernando, et al.
(author)
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The Nrf2-inducible antioxidant defense in astrocytes can be both up- and down-regulated by activated microglia:Involvement of p38 MAPK.
- 2011
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In: Glia. - : Wiley. - 1098-1136 .- 0894-1491. ; 59:5, s. 785-99
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Journal article (peer-reviewed)abstract
- The effects of microglia-conditioned medium (MCM) on the inducible Nrf2 system in astrocyte-rich cultures were investigated by determination of glutathione (GSH) levels, γglutamylcysteine ligase (γGCL) activity, the protein levels of Nrf2, Keap1, the modulatory subunit of γGCL (γGCL-M) and activated MAP kinases (ERK1/2, JNK and p38). Microglia were either cultured for 24 h in serum-free culture medium to achieve microglia-conditioned medium from non-activated cells (MCM(0) ), used as control condition, or activated with different concentrations (0.1-1,000 ng mL(-1) ) of lipopolysaccharide (LPS) to produce MCM(0.1-1,000) . Acute exposure (24 h) to MCM(100) increased GSH, γGCL activity, the protein levels of γGCL-M, Nrf2, and activated JNK and ERK1/2 in astrocyte-rich cultures. In contrast, treatment with MCM(10) for 24 h decreased components of the Nrf2 system in parallel with activation of p38 MAPK. Stimulation of the Nrf2 system by tBHQ was partly intact after 24 h but blocked after 72 h treatment with MCM(10) and MCM(100) . This down-regulation after 72 h correlated with activation of p38 MAPK and lack of ERK1/2 and JNK activation. The negative effects were partly reversed by an inhibitor of p38 which restored tBHQ mediated protection against oxidative stress. In conclusion, the study showed a negative effect of MCM(10) on the inducible anti-oxidant defense in astrocyte-rich cultures at both 24 and 72 h that correlated with activation of p38 and was partly reversed by a p38 inhibitor. A transient protective effect of MCM(100) on astrocyte-rich cultures against H(2)O(2) toxicity was observed at 24 h which coincided with activation of JNK and ERK1/2.
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| 13. |
- Correa, Fernando, et al.
(author)
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Time-Dependent Effects of Systemic Lipopolysaccharide Injection on Regulators of Antioxidant Defence Nrf2 and PGC-1α in the Neonatal Rat Brain.
- 2013
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In: Neuroimmunomodulation. - : S. Karger AG. - 1423-0216 .- 1021-7401. ; 20:4, s. 185-193
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Journal article (peer-reviewed)abstract
- Background/Aims: Both excitotoxicity and neuroinflammation are associated with oxidative stress. One transcription factor, nuclear factor E2-related factor 2 (Nrf2), and one transcription cofactor, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), increase the endogenous antioxidant defence and can thus modulate neuronal cell death. Here, we investigated the temporal effects (after 24 and 72 h) of systemic (i.p.) administration of lipopolysaccharide (LPS) on the cerebral Nrf2 and PGC-1α systems. Methods and Results: Seven-day-old rat pups were injected with LPS (0.3 mg/kg). After 24 h, the protein levels of γ-glutamylcysteine ligase modulatory subunit, γ-glutamylcysteine ligase catalytic subunit, Nrf2, PGC-1α and manganese superoxide dismutase (MnSOD) were increased in parallel with decreased levels of Keap1. These effects were correlated with an increased level of phosphorylated Akt and elevated acetylation of histone 4. In contrast, 72 h following LPS, a decrease in the components of the Nrf2 system in parallel with an increase in Keap1 was observed. The down-regulation after 72 h correlated with phosphorylation of p38 mitogen-activated protein kinase, while there were no changes in PGC-1α and MnSOD protein levels or the acetylation/methylation pattern of histones. Conclusion: Systemic LPS in neonatal rats induced time-dependent changes in brain Nrf2 and PGC-1α that correlated well with the protective effect observed after 24 h (pre-conditioning) and the deleterious effects observed after 72 h (sensitizing) of systemic LPS reported earlier. Collectively, the results point towards Nrf2 and PGC-1α as a possible mechanism behind these effects.
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| 16. |
- Ekblom Bak, Elin, 1981-, et al.
(author)
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Accelerometer derived physical activity and subclinical coronary and carotid atherosclerosis : cross-sectional analyses in 22 703 middle-aged men and women in the SCAPIS study
- 2023
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:11
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The aim included investigation of the associations between sedentary (SED), low-intensity physical activity (LIPA), moderate-to-vigorous intensity PA (MVPA) and the prevalence of subclinical atherosclerosis in both coronaries and carotids and the estimated difference in prevalence by theoretical reallocation of time in different PA behaviours.DESIGN: Cross-sectional.SETTING: Multisite study at university hospitals.PARTICIPANTS: A total of 22 670 participants without cardiovascular disease (51% women, 57.4 years, SD 4.3) from the population-based Swedish CArdioPulmonary bioImage study were included. SED, LIPA and MVPA were assessed by hip-worn accelerometer.PRIMARY AND SECONDARY OUTCOMES: Any and significant subclinical coronary atherosclerosis (CA), Coronary Artery Calcium Score (CACS) and carotid atherosclerosis (CarA) were derived from imaging data from coronary CT angiography and carotid ultrasound.RESULTS: High daily SED (>70% ≈10.5 hours/day) associated with a higher OR 1.44 (95% CI 1.09 to 1.91), for significant CA, and with lower OR 0.77 (95% CI 0.63 to 0.95), for significant CarA. High LIPA (>55% ≈8 hours/day) associated with lower OR for significant CA 0.70 (95% CI 0.51 to 0.96), and CACS, 0.71 (95% CI 0.51 to 0.97), but with higher OR for CarA 1.41 (95% CI 1.12 to 1.76). MVPA above reference level, >2% ≈20 min/day, associated with lower OR for significant CA (OR range 0.61-0.67), CACS (OR range 0.71-0.75) and CarA (OR range 0.72-0.79). Theoretical replacement of 30 min of SED into an equal amount of MVPA associated with lower OR for significant CA, especially in participants with high SED 0.84 (95% CI 0.76 to 0.96) or low MVPA 0.51 (0.36 to 0.73).CONCLUSIONS: MVPA was associated with a lower risk for significant atherosclerosis in both coronaries and carotids, while the association varied in strength and direction for SED and LIPA, respectively. If causal, clinical implications include avoiding high levels of daily SED and low levels of MVPA to reduce the risk of developing significant subclinical atherosclerosis.
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| 17. |
- Grooten, Wilhelmus Johannes Andreas, et al.
(author)
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Reliability and validity of a novel Kinect-based software program for measuring posture, balance and side-bending
- 2018
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In: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 19:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Clinical examinations are subjective and often show a low validity and reliability. Objective and highly reliable quantitative assessments are available in laboratory settings using 3D motion analysis, but these systems are too expensive to use for simple clinical examinations. Qinematic™ is an interactive movement analyses system based on the Kinect camera and is an easy-to-use clinical measurement system for assessing posture, balance and side-bending. The aim of the study was to test the test-retest the reliability and construct validity of Qinematic™ in a healthy population, and to calculate the minimal clinical differences for the variables of interest. A further aim was to identify the discriminative validity of Qinematic™ in people with low-back pain (LBP).METHODS: We performed a test-retest reliability study (n = 37) with around 1 week between the occasions, a construct validity study (n = 30) in which Qinematic™ was tested against a 3D motion capture system, and a discriminative validity study, in which a group of people with LBP (n = 20) was compared to healthy controls (n = 17). We tested a large range of psychometric properties of 18 variables in three sections: posture (head and pelvic position, weight distribution), balance (sway area and velocity in single- and double-leg stance), and side-bending.RESULTS: The majority of the variables in the posture and balance sections, showed poor/fair reliability (ICC < 0.4) and poor/fair validity (Spearman <0.4), with significant differences between occasions, between Qinematic™ and the 3D-motion capture system. In the clinical study, Qinematic™ did not differ between people with LPB and healthy for these variables. For one variable, side-bending to the left, there was excellent reliability (ICC =0.898), excellent validity (r = 0.943), and Qinematic™ could differentiate between LPB and healthy individuals (p = 0.012).CONCLUSION: This paper shows that a novel software program (Qinematic™) based on the Kinect camera for measuring balance, posture and side-bending has poor psychometric properties, indicating that the variables on balance and posture should not be used for monitoring individual changes over time or in research. Future research on the dynamic tasks of Qinematic™ is warranted.
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| 20. |
- Lindberg, David, 1986, et al.
(author)
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Steady-state and time-resolved Thioflavin-T fluorescence can report on morphological differences in amyloid fibrils formed by A beta(1-40) and A beta(1-42)
- 2015
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 458:2, s. 418-423
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Journal article (peer-reviewed)abstract
- Thioflavin-T (ThT) is one of the most commonly used dyes for amyloid detection, but the origin of its fluorescence enhancement is not fully understood. Herein we have characterised the ThT fluorescence response upon binding to the A beta(1-40) and A beta(1-42) variants of the Alzheimer's-related peptide amyloid-beta, in order to explore how the photophysical properties of this dye relates to structural and morphological properties of two amyloid fibril types formed by peptides with a high degree of sequence homology. We show that the steady-state ThT fluorescence is 1.7 times more intense with A beta(1-40) compared to A beta(1-42) fibrils in concentration matched samples prepared under quiescent conditions. By measuring the excited state lifetime of bound ThT, we also demonstrate a distinct difference between the two fibril isoforms, with A beta(1-42) fibrils producing a longer ThT fluorescence lifetime compared to A beta(140). The substantial steady-state intensity difference is therefore not explained by differences in fluorescence quantum yield. Further, we find that the ThT fluorescence intensity, but not the fluorescence lifetime, is dependent on the fibril preparation method (quiescent versus agitated conditions). We therefore propose that the fluorescence lifetime is inherent to each isoform and sensitively reports on fibril microstructure in the protofilament whereas the total fluorescence intensity relates to the amount of exposed beta-sheet in the mature A beta fibrils and hence to differences in their morphology. Our results highlight the complexity of ThT fluorescence, and demonstrate its extended use in amyloid fibril characterisation.
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| 21. |
- Lundin, Elin, 1983-
(author)
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RNA-based spatial characterization of cell and tissue heterogeneity
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Technical advances in cell biology have revolutionized the field of cell biology. With new technology it is now possible to address scientific questions in cell biology at the molecular level. Single-cell RNA-sequencing can reveal transcriptomic information for single cells and spatially resolved transcriptomic technology can visualize thousands or millions of cells and transcripts for spatial molecular profiling. The work in this thesis describes the technological development from traditional in situ hybridization to the current state-of-the-art technology for spatial multiplexed gene expression analysis. This development has enabled RNA-based molecular characterization of cells and tissues with the spatial dimension maintained. The work included in the thesis highlights the potential and the advantages of padlock-probe-based technology for spatial RNA-based profiling of cells and tissues. Furthermore, it demonstrates the possibilities arising from the inherent ability of padlock probes to distinguish between transcripts based on differences in single nucleotides.The study in paper I investigates the prevalence of Enterovirus species B in patients with Crohn’s disease by a chromogenic in situ hybridization assay combined with immunohistochemistry to detect viral RNA and proteins directly in tissue samples.In paper II, padlock probes were used to study the spatial gene expression of gene homologs from the X and Y chromosome in human embryonic nervous tissue. Furthermore, a strategy was devised to visualize and evaluate spatial expression patterns.The padlock probe-based approach for multiplexed spatial transcriptional profiling, in situ sequencing, was applied in paper III to study the regional and cell-type-specific dynamics of A-to-I RNA editing in the developing mouse brain.In paper IV, a technical characterization of padlock probes was performed with the aim of determining how to design a padlock probe to obtain optimal detection efficiency.The work in this thesis demonstrates the dramatic shift in how biological questions in cell and tissue biology can be addressed, enabled by the technological evolution of traditional in situ hybridization assays into high-throughput, multiplexed spatial transcription profiling.
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| 22. |
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| 23. |
- Nilsson, Anne, et al.
(author)
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Gut microbiota mediated benefits of barley kernel products on metabolism, gut hormones, and inflammatory markers as affected by co-ingestion of commercially available probiotics : a randomized controlled study in healthy subjects
- 2016
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In: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 15, s. 49-56
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Journal article (peer-reviewed)abstract
- Background and aims Barley kernel based products have been shown to induce benefits on blood glucose regulation, cardio-metabolic risk markers and appetite regulating hormones in a time perspective of 11–16 h after intake. The mechanisms have been assigned to gut fermentation of indigestible carbohydrates. The purpose of the present study was to evaluate if the modulatory effects of barley on markers of metabolic- and appetite regulation are affected by a dietary background including a mixture of commercially available probiotics. Methods Barley kernel bread was included in the normal diet of 21 healthy subjects in two 4-day intervention periods; with (BB-pro) or without (BB) dietary supplement with a combination of probiotics (Bifidobacterium animalis DN-173 010, Lactobacillus reuteri DSM 17938, and Lactobacillus plantarum 299v). A white wheat flour based bread was included as a reference product (WWB-ref) in a separate 4-day bread intervention period. A cross-over design was applied concerning BB- and WWB-ref; the BB-pro intervention was last in the test sequence. The BB-pro intervention was preceded by 10 days priming with probiotics. The 4 day BB- and WWB-ref intervention periods included dietary supplementation with placebo, and the interventions were preceded with 10 days priming with the placebo. The day after each intervention period, blood samples were collected at fasting and postprandially after a standardized breakfast (0–210 min) for determination of markers of glucose metabolism (blood glucose, serum (s-) insulin), inflammation (s-IL-6, s-IL-18, s-CRP, PAI-1), and concentrations of gut derived hormones involved in satiety and glucose homeostasis (plasma (p-) PYY, p-GLP-1) and intestinal barrier integrity (p-GLP-2). Breath hydrogen was determined as a marker of colonic fermentation. Results Four days intervention with BB, in comparison to WWB-ref, lowered blood glucose response after a subsequent standardized breakfast (0–210 min, P < 0.05). BB and BB-pro interventions increased p-GLP-1 (0–120 min, P < 0.05) and breath H2 (0–210 min, P < 0.05). BB-pro intervention, in comparison to BB and WWB-ref, increased levels of s-PAI-1 (P < 0.05), and p-GLP-2 (0–210 min, P < 0.05) after the standardized breakfast. Conclusions With the exception of increased p-GLP-2 and an unexpected increase in s-PAI-1 concentrations, co-ingestion of a mixture of probiotics did not affect the metabolic outcome of BB; neither positively nor importantly negatively. The study was registered at: ClinicalTrials.gov, register number NCT01718418 (www.clinicaltrials.gov/ct2/show/NCT01718418).
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| 24. |
- Philipsson, Anna, 1978-, et al.
(author)
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”Just in TIME” - Intervention med dans och yoga för flickor med funktionell magsmärta och IBS
- 2019
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Conference paper (peer-reviewed)abstract
- Bakgrund och syfteFunktionell magsmärta drabbar många barn i skolåldern, mestadels flickor. Det kan leda till minskad livskvalitet, skolfrånvaro, sämre sömn, försämrade kamratkontakter och ökad vårdkonsumtion. Det vetenskapliga underlaget för interventioner vid långvarig smärta hos barn är begränsat. Dans kan öka rörelseglädje och förbättra kroppskännedom, vilket i sin tur påverkar självtillit och kan öka psykiskt välbefinnande. Yoga kan ge mental avslappning och reducera stressreaktioner. Syftet med studien är att utvärdera effekten av en intervention med dans och yoga på återkommande magsmärta, stress och depressiva symtom samt på funktion i vardagen hos flickor 9-13 år som har funktionell buksmärta och IBS.MetodEn randomiserad kontrollerad studie genomförs med forskningspersoner som identifieras via diagnosregister samt barnmottagningarna i Västerås och Örebro, samt från primärvården. Interventionen består av dans och yoga med fokus på rörelseglädje, gemenskap och kravlöshet, och utförs som gruppaktivitet två ggr/veckan under 8 månader. Primärt utfall är förändring av magsmärta efter 8 mån. Flickorna följs upp under fem år avseende magsmärta, självskattad hälsa, stress och psykiskt välmående, fysisk aktivitet och skolfunktioner. Vidare studeras kostnad i relation till nytta.Resultat/(Planerade studier)Projektet pågår och de första resultaten beräknas publiceras hösten 2019. Projektet utvärderas både kvalitativt, genom intervjuer med flickor och vårdnadshavare, och kvantitativt, genom bland annat analys av smärtdagböcker, upplevd hälsa, stress samt med en hälsoekonomisk analys. Därutöver utvärderas salivkortisol och faeces som objektiva mått. KonklusionStudien förväntas leda till ökad kunskap om icke-farmakologiska insatser för barn samt hur behandlingsinsatser för målgruppen kan breddas med ett kostnadseffektivt alternativ till ”standard care”.
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| 25. |
- Rydgren, Tobias, et al.
(author)
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Administration of IL-1 Trap prolongs survival of transplanted pancreatic islets to type 1 diabetic NOD mice
- 2013
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In: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 63:2, s. 123-129
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Journal article (peer-reviewed)abstract
- We previously reported that IL-1 Trap (a hybrid molecule consisting of the extracellular domain of IL-1 receptor accessory protein and IL-1 receptor type 1 arranged inline and fused to the Fc-portion of IgG1) can protect rat pancreatic islets in vitro against noxious effects induced by IL-1 beta. In this study we tested the effect of administration of a murine IL-1 Trap on the recurrence of disease (ROD) model in non-obese diabetic (NOD) mice. Spontaneously diabetic female NOD mice received implantation of a curative number (600) of syngeneic pancreatic islets beneath their left kidney capsule from young healthy NOD mouse donors. Once a day, the mice were injected subcutaneously with IL-1 Trap (30 mg/kg bodyweight), or an equimolar dose Fc-control protein (8.4 mg/kg bodyweight) or saline. The treatments were maintained until ROD (i.e. a blood glucose value >= 11.1 mM for 2 consecutive days) or until 5 days after transplantation. 3 out of 11 mice treated with IL-1 Trap showed a significantly increased graft survival compared to all other mice, and analysis of relative cytokine mRNA levels in isolated spleen cells showed elevated IL-4 mRNA levels, but no differences in FoxP3 or iNOS staining of grafts, from mice treated with IL-1 Trap, at both endpoints, compared to both control groups. Administration of IL-1 Trap counteracts islet cell destruction in the NOD mouse model of type 1 diabetes. In part this could be due to a shift towards Th2 cytokine production seen in IL-1 Trap treated animals.
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| 26. |
- Sanaee, Maryam, et al.
(author)
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Antibody-loading of biological nanocarrier vesicles derived from red-blood-cell membranes
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Other publication (other academic/artistic)abstract
- Antibodies, disruptive potent therapeutic agents against pharmacological targets, face a barrier crossing immune-system and cellular-membranes. To overcome these, various strategies have been explored including shuttling via liposomes or bio-camouflaged nanoparticles.Here, we demonstrate the feasibility to load antibodies into exosome-mimetic nanovesicles derived from human red-blood-cell-membranes. The goat-anti-chicken antibodies are loaded into erythrocyte-membrane derived nanovesicles and their loading yields are characterized and compared with smaller dUTP-cargo. Applying dual-color coincident fluorescence burst methodology, the loading yield of nanocarriers is profiled at single-vesicle level overcoming their size-heterogeneity and achieving a maximum of 38-41% antibody-loading yield at peak radius of 52 nm. The average of 14 % yield and more than two antibodies per vesicle is estimated, comparable to those of dUTP-loaded nanovesicles after additional purification through exosomespin-column. These results suggest a promising route for enhancing biodistribution andintracellular accessibility for therapeutic antibodies using novel, biocompatible, and lowimmunogenicity nanocarriers, suitable for large-scale pharmacological applications.
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| 27. |
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| 28. |
- Sanaee, Maryam, et al.
(author)
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Dual-Color Confocal Fluorescence Characterizations of Antibody Loading in Bioengineered Nanovesicles
- 2023
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In: 2023 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference, CLEO/Europe-EQEC 2023. - : Institute of Electrical and Electronics Engineers (IEEE).
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Conference paper (peer-reviewed)abstract
- Confocal fluorescence microscopy is powerful for microscopic and nanoscopic analyses with a broad range of applications in biology and medicine, affording high specificity and sensitivites down to single-molecule level [1]. Here we apply a novel dual-color confocal fluorescence microscopy methodology based on coincident burst analysis [2] to quantitative study of the loading yields of bioengineered nanovesicles derived from human red blood cell (RBC) membranes loaded with fluorescently-tagged Antibody (Ab) or dUTP cargo molecules. We prove the successful loading of the RBC nanovesicles with both types of cargo molecules, assess their size statistics and provide quantifications of the loading at single-vesicle level. Fig. 1a shows the tagging scheme adopted for the experiment where Cellvue claret and Alexa488 dyes are respectively used to fluorescently label the outer membrane of the nanovesicles and the cargo molecules. The experimental setup is shown in Fig. 1b, consisting of an inverted microscope with dual excitations at λ1= 640 nm and λ2 = 485 nm. The fluorescence signals centered at λred= 720 nm and λgreen= 535 nm are single-photon-detected and post-selected in separate time gating windows with a delay of 25ns (Fig. 1c). After looking for coincident red-green bursts in the measured time traces (Fig. 1d), size histograms of the loaded vesicles are retrieved (Fig. 1e-f), obtaining average loading yields of 5% and 20% for Ab and dUTP cargos, respectively. Average values of 1.5 and 1.4 loaded Ab (dUTP) cargo molecules per nanovesicle are retrieved from the histograms of Fig. 1g (Fig. 1h). The average size of Ab-loaded nanovesicles is found to be slightly (≈10 nm in radius) larger than the one of dUTP-loaded ones.
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| 29. |
- Sandberg, Elin
(author)
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Advanced fluorescence-based fluctuation methods for biosensing
- 2022
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Doctoral thesis (other academic/artistic)abstract
- In addition to use traditional fluorescence parameters for biological studies,the main focus of this thesis is on the monitoring of photoinduced fluorophoretransient states. These dark states, such as the triplet state, redox states andphotoisomers that are formed upon excitation, are long-lived in comparisonto the fluorescent singlet state and therefor more sensitive to the surroundingenvironment and their sensitivity are to biological relevant conditions. Themain method used to study these states is called transient state monitoring(TRAST) and based on laser-modulation over the sample. Different modalities using this approach, are explored to characterize blinking kinetics offluorophores in varying contexts. A multiparameter confocal laser-scanningsetup with TCSPC and correlation capabilities is used as a complement to thementioned method and used solely in one of the works. It is motivated howthe transient states adds dimensions of information. They can with advantagebe used as an additional fluorescence read-out in imaging and spectroscopicstudies of fluorophore tagged biological samples.In paper I, the autofluorescent co-enzyme NAD(P)H was studied byTRAST, showing a redox sensitivity. A two-photon excitation (2PE) scanning TRAST approach was established. With this label-free approach, cellular images reflecting local redox environments could be obtained and visualizechanges in the environment after disturbing the cellular metabolism.In paper II, single-molecule confocal TCSPC with pulsed interleavedexcitation and burst-analysis was used to study loading yields of exosomemimetic nanovesicles.In paper III, the photodynamics of two dyes used in photodynamic therapy (PDT) were characterized. It was motivated how TRAST can be used asa method for live-monitoring in PDT and be used as feed-back to optimizetreatment. A fiber-based TRAST approach was demonstrated and used tomeasure the fluorophores in tissue.Paper IV and paper V focuses on the photodynamics of the cyaninedyes Cy7 and Cy5. A second emissive photoisomerized state in addition tothe ground state (trans) is found and confirmed by various methods, amongthem an approach where TRAST-curves can be selectively be produced fromdifferent bands of the full emission spectrum. This method was establishedduring this work. Differences between fluorescence correlation spectroscopy(FCS) and TRAST are discussed and included in the analysis of data. Varioussensing parameters of Cy7 are explored.In paper VI it is shown how the blinking dynamics from the photoinduced transient states can be used for fluorescence barcoding and muliplexing.FCS, laser-modulated TRAST and flow-based TRAST, where the sample isflowing through the excitation light, are used to demonstrate this encodingdimension of free dyes and tagged vesicles. Labelled cells are imaged, wheremultiple colors can be produced by the fluorophore specific blinking characteristics.
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| 30. |
- Sandberg, Elin, et al.
(author)
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Combined Fluorescence Fluctuation and Spectrofluorometric Measurements Reveal a Red-Shifted, Near-IR Emissive Photo-Isomerized Form of Cyanine 5
- 2023
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 24:3
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Journal article (peer-reviewed)abstract
- Cyanine fluorophores are extensively used in fluorescence spectroscopy and imaging. Upon continuous excitation, especially at excitation conditions used in single-molecule and super-resolution experiments, photo-isomerized states of cyanines easily reach population probabilities of around 50%. Still, effects of photo-isomerization are largely ignored in such experiments. Here, we studied the photo-isomerization of the pentamethine cyanine 5 (Cy5) by two similar, yet complementary means to follow fluorophore blinking dynamics: fluorescence correlation spectroscopy (FCS) and transient-state (TRAST) excitation-modulation spectroscopy. Additionally, we combined TRAST and spectrofluorimetry (spectral-TRAST), whereby the emission spectra of Cy5 were recorded upon different rectangular pulse-train excitations. We also developed a framework for analyzing transitions between multiple emissive states in FCS and TRAST experiments, how the brightness of the different states is weighted, and what initial conditions that apply. Our FCS, TRAST, and spectral-TRAST experiments showed significant differences in dark-state relaxation amplitudes for different spectral detection ranges, which we attribute to an additional red-shifted, emissive photo-isomerized state of Cy5, not previously considered in FCS and single-molecule experiments. The photo-isomerization kinetics of this state indicate that it is formed under moderate excitation conditions, and its population and emission may thus deserve also more general consideration in fluorescence imaging and spectroscopy experiments.
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| 31. |
- Sandberg, Elin, 1989-, et al.
(author)
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Dance intervention for adolescent girls : Effects on daytime tiredness, alertness and school satisfaction. A randomized controlled trial
- 2021
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In: Journal of Bodywork & Movement Therapies. - : Elsevier. - 1360-8592 .- 1532-9283. ; 26, s. 505-514
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Journal article (peer-reviewed)abstract
- Introduction: Daytime tiredness is a risk factor for poor health and well-being in the short and long term and is often associated with sleep problems, stress-related mental health complaints and decreased school functioning. This study investigates the effect of an 8 month dance intervention study on daytime tiredness, alertness, sleep duration, sleep quality and school satisfaction.Methods: Randomized controlled intervention study that included a total of 112 girls aged 13-18 years old with stress-related mental health problems. Dance intervention with focus on enjoyment were performed semiweekly for 8 months. Questionnaire-based measurements regarding self-reported daytime tiredness, alertness, school satisfaction, sleep duration and quality were evaluated at baseline and at 8-, 12- and 20- month follow-ups.Results: Daytime tiredness decreased significantly in the dance group compared to control group at all follow-ups. Alertness increased significant within the dance group, but there were no significant difference compared to the controls. Significant improvements were found in all sleep quality items within the dance group, between groups only one significant result was found. No conclusive changes in sleep duration were observed. School satisfaction increased significantly in the dance intervention group; however, its significance compared to that of the control group faded after adjustment for differences between groups at baseline.Conclusions: This study suggests that a dance intervention focusing on enjoyment can be effective in decreasing daytime tiredness. This study also adds to the growing body of evidence for the benefits of using nonpharmacological interventions to decrease stress-related problems among adolescents.
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| 32. |
- Sandberg, Elin, et al.
(author)
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Fluorescence Bar-Coding and Flowmetry Based on Dark State Transitions in Fluorescence Emitters
- 2024
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 128:1, s. 125-136
-
Journal article (peer-reviewed)abstract
- Reversible dark state transitions in fluorophores represent a limiting factor in fluorescence-based ultrasensitive spectroscopy, are a necessary basis for fluorescence-based super-resolution imaging, but may also offer additional, largely orthogonal fluorescence-based readout parameters. In this work, we analyzed the blinking kinetics of Cyanine5 (Cy5) as a bar-coding feature distinguishing Cy5 from rhodamine fluorophores having largely overlapping emission spectra. First, fluorescence correlation spectroscopy (FCS) solution measurements on mixtures of free fluorophores and fluorophore-labeled small unilamellar vesicles (SUVs) showed that Cy5 could be readily distinguished from the rhodamines by its reversible, largely excitation-driven trans-cis isomerization. This was next confirmed by transient state (TRAST) spectroscopy measurements, determining the fluorophore dark state kinetics in a more robust manner, from how the time-averaged fluorescence intensity varies upon modulation of the applied excitation light. TRAST was then combined with wide-field imaging of live cells, whereby Cy5 and rhodamine fluorophores could be distinguished on a whole cell level as well as in spatially resolved, multiplexed images of the cells. Finally, we established a microfluidic TRAST concept and showed how different mixtures of free Cy5 and rhodamine fluorophores and corresponding fluorophore-labeled SUVs could be distinguished on-the-fly when passing through a microfluidic channel. In contrast to FCS, TRAST does not rely on single-molecule detection conditions or a high time resolution and is thus broadly applicable to different biological samples. Therefore, we expect that the bar-coding concept presented in this work can offer an additional useful strategy for fluorescence-based multiplexing that can be implemented on a broad range of both stationary and moving samples.
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| 33. |
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| 34. |
- Sandberg, Elin, et al.
(author)
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Local monitoring of photosensitizer transient states provides feedback for enhanced efficiency and targeting selectivity in photodynamic therapy
- 2023
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1, s. 16829-
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Journal article (peer-reviewed)abstract
- Photodynamic therapy (PDT) fundamentally relies on local generation of PDT precursor states in added photosensitizers (PS), particularly triplet and photo-radical states. Monitoring these states in situ can provide important feedback but is difficult in practice. The states are strongly influenced by local oxygenation, pH and redox conditions, often varying significantly at PDT treatment sites. To overcome this problem, we followed local PDT precursor state populations of PS compounds, via their fluorescence intensity response to systematically varied excitation light modulation. Thereby, we could demonstrate local monitoring of PDT precursor states of methylene blue (MB) and IRdye700DX (IR700), and determined their transitions rates under different oxygenation, pH and redox conditions. By fiber-optics, using one fiber for both excitation and fluorescence detection, the triplet and photo-radical state kinetics of locally applied MB and IR700 could then be monitored in a tissue sample. Finally, potassium iodide and ascorbate were added as possible PDT adjuvants, enhancing intersystem crossing and photoreduction, respectively, and their effects on the PDT precursor states of MB and IR700 could be locally monitored. Taken together, the presented procedure overcomes current methodological limitations and can offer feedback, guiding both excitation and PDT adjuvant application, and thereby more efficient and targeted PDT treatments.
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| 35. |
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| 36. |
- Sandberg, Elin, et al.
(author)
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Photoisomerization of Heptamethine Cyanine Dyes Results in Red-Emissive Species : Implications for Near-IR, Single-Molecule, and Super-Resolution Fluorescence Spectroscopy and Imaging
- 2023
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 127:14, s. 3208-3222
-
Journal article (peer-reviewed)abstract
- Photoisomerization kinetics of the near-infrared (NIR) fluorophore Sulfo-Cyanine7 (SCy7) was studied by a combination of fluorescence correlation spectroscopy (FCS) and transient state (TRAST) excitation modulation spectroscopy. A photoisomerized state with redshifted emission was identified, with kinetics consistent with a three-state photoisomerization model. Combining TRAST excitation modulation with spectrofluorimetry (spectral-TRAST) further confirmed an excitation-induced redshift in the emission spectrum of SCy7. We show how this red-emissive photoisomerized state contributes to the blinking kinetics in different emission bands of NIR cyanine dyes, and how it can influence single-molecule, super-resolution, as well as Förster resonance energy transfer (FRET) and multicolor readouts. Since this state can also be populated at moderate excitation intensities, it can also more broadly influence fluorescence readouts, also readouts not relying on high excitation conditions. However, this additional red-emissive state and its photodynamics, as identified and characterized in this work, can also be used as a strategy to push the emission of NIR cyanine dyes further into the NIR and to enhance photosensitization of nanoparticles with absorption spectra further into the NIR. Finally, we show that the photoisomerization kinetics of SCy7 and the formation of its redshifted photoisomer depend strongly on local environmental conditions, such as viscosity, polarity, and steric constraints, which suggests the use of SCy7 and other NIR cyanine dyes as environmental sensors. Such environmental information can be monitored by TRAST, in the NIR, with low autofluorescence and scattering conditions and on a broad range of samples and experimental conditions.
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| 37. |
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| 38. |
- Taube, Elin, et al.
(author)
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Loneliness and health care consumption among older people
- 2014
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In: Scandinavian Journal of Caring Sciences. - : John Wiley & Sons. - 0283-9318 .- 1471-6712. ; 29:3, s. 435-443
-
Journal article (peer-reviewed)abstract
- Few studies have investigated loneliness in relation to health care consumption among frail older people. The aim of this study was to examine loneliness, health-related quality of life (HRQoL), and health complaints in relation to health care consumption of in- and outpatient care among frail older people living at home. The study, with a cross-sectional design, comprised a sample of 153 respondents aged from 65 years (mean age 81.5 years) or older, who lived at home and were frail. Data was collected utilising structured interviews in the respondent's home assessing demographic data, loneliness, HRQoL and health complaints. Patient administrative registers were used to collect data on health care consumption. Loneliness was the dependent variable in the majority of the analyses and dichotomised. For group comparisons Student′s t-test, Mann–Whitney U-test and Chi-square test were used. The results showed that 60% of the respondents had experienced loneliness during the previous year, at least occasionally. The study identified that lonely respondents had a lower HRQoL (p = 0.022), with a higher total number of reported health complaints (p = 0.001), and used more outpatient services including more acute visits at the emergency department, compared to not lonely respondents (p = 0.026). Multiple linear regression analysis showed that a depressed mood was independently associated to total use of outpatient care (B = 7.4, p < 0.001). Therefore, it might not be loneliness, per se, that is the reason for seeking health care. However, reasons for using health care services are difficult to determine due to the complex situation for the frail older person. To avoid emergency department visits and to benefit the well-being of the frail older person, interventions targeting the complex health situation, including loneliness, are suggested.
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| 39. |
- Tornmalm, Johan, et al.
(author)
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Local redox conditions in cells imaged via non-fluorescent transient states of NAD(P)H
-
Other publication (other academic/artistic)abstract
- The autofluorescent coenzyme nicotinamide adenine dinucleotide (NADH) and its phosphorylated form (NADPH) are major determinants of cellular redox balance. Both their fluorescence intensities and lifetimes are extensively used as label-free readouts in cellular metabolic imaging studies. Here, we introduce fluorescence blinking of NAD(P)H as an additional, orthogonal readout in such studies. Blinking of fluorophores and their underlying dark state transitions are specifically sensitive to redox conditions and oxygenation, parameters of particular relevance in cellular metabolic studies. We show that such dark state transitions in NAD(P)H can be quantified via the average fluorescence intensity recorded upon modulated one-photon excitation, so-called transient state (TRAST) monitoring. Thereby, transitions in NAD(P)H, previously only accessible from elaborate spectroscopic cuvette measurements, can be imaged at subcellular resolution in live cells. We then demonstrate that these transitions can be imaged with a standard laser-scanning confocal microscope and two-photon excitation, in parallel with regular fluorescence lifetime imaging (FLIM). In contrast to FLIM, TRAST imaging of NAD(P)H clearly reveals an altered oxidative environment in the cytosols of cells treated with a mitochondrial un-coupler. We propose TRAST imaging as a straightforward and widely applicable modality, extending the range of information obtainable from cellular metabolic imaging of NAD(P)H fluorescence.
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| 40. |
- Tornmalm, Johan, et al.
(author)
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Local redox conditions in cells imaged via non-fluorescent transient states of NAD(P)H
- 2019
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In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
-
Journal article (peer-reviewed)abstract
- The autofluorescent coenzyme nicotinamide adenine dinucleotide (NADH) and its phosphorylated form (NADPH) are major determinants of cellular redox balance. Both their fluorescence intensities and lifetimes are extensively used as label-free readouts in cellular metabolic imaging studies. Here, we introduce fluorescence blinking of NAD(P)H, as an additional, orthogonal readout in such studies. Blinking of fluorophores and their underlying dark state transitions are specifically sensitive to redox conditions and oxygenation, parameters of particular relevance in cellular metabolic studies. We show that such dark state transitions in NAD(P)H can be quantified via the average fluorescence intensity recorded upon modulated one-photon excitation, so-called transient state (TRAST) monitoring. Thereby, transitions in NAD(P)H, previously only accessible from elaborate spectroscopic cuvette measurements, can be imaged at subcellular resolution in live cells. We then demonstrate that these transitions can be imaged with a standard laser-scanning confocal microscope and two-photon excitation, in parallel with regular fluorescence lifetime imaging (FLIM). TRAST imaging of NAD(P)H was found to provide additional, orthogonal information to FLIM and allows altered oxidative environments in cells treated with a mitochondrial un-coupler or cyanide to be clearly distinguished. We propose TRAST imaging as a straightforward and widely applicable modality, extending the range of information obtainable from cellular metabolic imaging of NAD(P)H fluorescence.
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| 41. |
- Wikner, Anna, et al.
(author)
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Lower bone strength in young patients with Fontan circulation compared to controls
- 2024
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In: Cardiology in the Young. - : Cambridge University Press. - 1047-9511 .- 1467-1107.
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Journal article (peer-reviewed)abstract
- Objectives: Previous reports indicate bone deficits in patients with Fontan circulation. However, the consequences of these deficits on bone strength and when these changes occur are unclear.Aim: To compare the tibial bone strength-strain index between young patients (6-19 years) with Fontan circulation and age- and sex-matched controls, and to determine strength-strain-index in subgroups of children (6-12 years) and adolescents (13-19 years) versus controls.Method: The tibia was examined with peripheral quantitative CT. Based on the assessed data, bone strength-strain index was calculated in the lateral and anterior-posterior directions.Results: Twenty patients with Fontan and twenty controls (mean age 13.0 ± 4.4 years; 50% females) were examined. Patients had a lower strength-strain index in the lateral direction compared to controls (808.4 ± 416.8mm3 versus 1162.5 ± 552.1mm3, p = 0.043). Subgroup analyses showed no differences regarding strength-strain index in children (6-12 years) with Fontan circulation compared to controls. However, the adolescents (13-19 years) with Fontan circulation had lower strength-strain indexes in both the lateral and anterior-posterior directions compared to controls (1041.4 ± 299.8mm3 versus 1596.4 ± 239.6mm3, p < 0.001, and 771.7 ± 192.4mm3 versus 1084.9 ± 215.0mm3, p = 0.004). When adjusted for height, there were differences between patients (6-19 years) and controls in strength-strain indexes in both the lateral and anterior-posterior directions. In subgroup analyses, the results remained robust.Conclusion: Young patients (6-19 years) with Fontan circulation have a lower strength-strain index in the tibia compared to controls. Subgroup analyses show that this deficit is mainly driven by the differences in adolescents (13-19 years), which might suggest that bone strength decreases with age.
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| 42. |
- Yang, Qigui, et al.
(author)
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Cu precipitation in electron-irradiated iron alloys for spent-fuel canisters
- 2022
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In: Journal of Nuclear Materials. - : Elsevier B.V.. - 0022-3115 .- 1873-4820. ; 572
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Journal article (peer-reviewed)abstract
- In this work, the Cu clustering in Fe under irradiation is investigated using experiments, cluster dynamics and atomistic kinetic Monte Carlo (AKMC) simulations. In experiments, cast iron and model FeCu alloy samples were irradiated with 2 MeV electrons for 143 h at 140 °C. The post-irradiation microstructure was characterized using atom probe tomography. Cluster dynamics and AKMC methods were used to simulate the Cu clustering under the same irradiation conditions. Both simulation methods show satisfactory agreement with experiments, lending strength to the validity of the models. Finally, the Cu clustering in spent-fuel repository conditions for 105 years at 100 °C was simulated using both methods. The results indicate that potential hardening by Cu clustering is insignificant over 105 years.
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