| 1. |
- Kanatsuna, N, et al.
(författare)
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Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes
- 2015
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Ingår i: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 0300-9475 .- 1365-3083. ; 82:4, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P < 0.001). Irrespective of age at diagnosis, 19% (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (P < 0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.
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| 2. |
- Andersson, Claes, et al.
(författare)
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Mebendazole is unique among tubulin-active drugs in activating the MEK-ERK pathway
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity in monocyte/macrophage models and induces ERK signalling. In the present study we investigated whether MBZ induced ERK activation is shared by other tubulin binding agents (TBAs) and if it is observable also in other human cell types. Curated gene signatures for a panel of TBAs in the LINCS Connectivity Map (CMap) database showed a unique strong negative correlation of MBZ with MEK/ERK inhibitors indicating ERK activation also in non-haematological cell lines. L1000 gene expression signatures for MBZ treated THP-1 monocytes also connected negatively to MEK inhibitors. MEK/ERK phosphoprotein activity testing of a number of TBAs showed that only MBZ increased the activity in both THP-1 monocytes and PMA differentiated macrophages. Distal effects on ERK phosphorylation of the substrate P90RSK and release of IL1B followed the same pattern. The effect of MBZ on MEK/ERK phosphorylation was inhibited by RAF/MEK/ERK inhibitors in THP-1 models, CD3/IL2 stimulated PBMCs and a MAPK reporter HEK-293 cell line. MBZ was also shown to increase ERK activity in CD4+ T-cells from lupus patients with known defective ERK signalling. Given these mechanistic features MBZ is suggested suitable for treatment of diseases characterized by defective ERK signalling, notably difficult to treat autoimmune diseases.
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| 3. |
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| 4. |
- Blom, Kristin, et al.
(författare)
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Mebendazole-induced M1 polarisation of THP-1 macrophages may involve DYRK1B inhibition
- 2019
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Ingår i: BMC Research Notes. - : Springer Nature. - 1756-0500. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity by inducing a M2 to M1 phenotype switch in monocyte/macrophage models. In the present study we investigated the potential role of protein kinases in mediating this effect.Results: MBZ potently binds and inhibits Dual specificity tyrosine-phosphorylation-regulated kinase 1B (DYRK1B) with a Kd and an IC50 of 7 and 360 nM, respectively. The specific DYRK1B inhibitor AZ191 did not mimic the cytokine release profile of MBZ in untreated THP-1 monocytes. However, in THP-1 cells differentiated into macrophages, AZ191 strongly induced a pro-inflammatory cytokine release pattern similar to MBZ and LPS/IFNγ. Furthermore, like MBZ, AZ191 increased the expression of the M1 marker CD80 and decreased the M2 marker CD163 in THP-1 macrophages. In this model, AZ191 also increased phospho-ERK activity although to a lesser extent compared to MBZ. Taken together, the results demonstrate that DYRK1B inhibition could, at least partly, recapitulate immune responses induced by MBZ. Hence, DYRK1B inhibition induced by MBZ may be part of the mechanism of action to switch M2 to M1 macrophages.
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| 5. |
- Blom, Kristin, et al.
(författare)
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The anticancer effect of mebendazole may be due to M1 monocyte/macrophage activation via ERK1/2 and TLR8-dependent inflammasome activation
- 2017
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Ingår i: Immunopharmacology and immunotoxicology. - : Informa UK Limited. - 0892-3973 .- 1532-2513. ; 39:4, s. 199-210
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Tidskriftsartikel (refereegranskat)abstract
- Mebendazole (MBZ), a drug commonly used for helminitic infections, has recently gained substantial attention as a repositioning candidate for cancer treatment. However, the mechanism of action behind its anticancer activity remains unclear. To address this problem, we took advantage of the curated MBZ-induced gene expression signatures in the LINCS Connectivity Map (CMap) database. The analysis revealed strong negative correlation with MEK/ERK1/2 inhibitors. Moreover, several of the most upregulated genes in response to MBZ exposure were related to monocyte/macrophage activation. The MBZ-induced gene expression signature in the promyeloblastic HL-60 cell line was strongly enriched in genes involved in monocyte/macrophage pro-inflammatory (M1) activation. This was subsequently validated using MBZ-treated THP-1 monocytoid cells that demonstrated gene expression, surface markers and cytokine release characteristic of the M1 phenotype. At high concentrations MBZ substantially induced the release of IL-1 beta and this was further potentiated by lipopolysaccharide (LPS). At low MBZ concentrations, cotreatment with LPS was required for MBZ-stimulated IL-1 beta secretion to occur. Furthermore, we show that the activation of protein kinase C, ERK1/2 and NF-kappaB were required for MBZ-induced IL-1 release. MBZ-induced IL-1 release was found to be dependent on NLRP3 inflammasome activation and to involve TLR8 stimulation. Finally, MBZ induced tumor-suppressive effects in a coculture model with differentiated THP-1 macrophages and HT29 colon cancer cells. In summary, we report that MBZ induced a pro-inflammatory (M1) phenotype of monocytoid cells, which may, at least partly, explain MBZ's anticancer activity observed in animal tumor models and in the clinic.
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| 6. |
- Bülow Anderberg, Sara, et al.
(författare)
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Increased levels of plasma cytokines and correlations to organ failure and 30-day mortality in critically ill Covid-19 patients
- 2021
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Ingår i: Cytokine. - : Springer Nature. - 1043-4666 .- 1096-0023. ; 138
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The infection caused by SARS CoV-2 has been postulated to induce a cytokine storm syndrome that results in organ failure and even death in a considerable number of patients. However, the inflammatory response in Corona virus disease-19 (Covid-19) and its potential to cause collateral organ damage has not been fully elucidated to date. This study aims to characterize the acute cytokine response in a cohort of critically ill Covid-19 patients.METHOD: 24 adults with PCR-confirmed Covid-19 were included at time of admission to intensive care a median of eleven days after initial symptoms. Eleven adult patients admitted for elective abdominal surgery with preoperative plasma samples served as controls. All patients were included after informed consent was obtained. 27 cytokines were quantified in plasma. The expression of inflammatory mediators was then related to routine inflammatory markers, SAPS3, SOFA score, organ failure and 30-day mortality.RESULTS: A general increase in cytokine expression was observed in all Covid-19 patients. A strong correlation between respiratory failure and IL-1ra, IL-4, IL-6, IL-8 and IP-10 expression was observed. Acute kidney injury development correlated well with increased levels of IL-1ra, IL-6, IL-8, IL-17a, IP-10 and MCP-1. Generally, the cohort demonstrated weaker correlations between cytokine expression and 30-day mortality out of which IL-8 showed the strongest signal in terms of mortality.CONCLUSION: The present study found that respiratory failure, acute kidney injury and 30-day mortality in critically ill Covid-19 patients are associated with moderate increases of a broad range of inflammatory mediators at time of admission.
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| 7. |
- Dwibedi, Chinmay Kumar, et al.
(författare)
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Biological amplification of low frequency mutations unravels laboratory culture history of the bio-threat agent Francisella tularensis
- 2020
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 45
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Tidskriftsartikel (refereegranskat)abstract
- Challenges of investigating a suspected bio attack include establishing if microorganisms have been cultured to produce attack material and to identify their source. Addressing both issues, we have investigated genetic variations that emerge during laboratory culturing of the bacterial pathogen Francisella tularensis. Key aims were to identify genetic variations that are characteristic of laboratory culturing and explore the possibility of using biological amplification to identify genetic variation present at exceedingly low frequencies in a source sample. We used parallel serial passage experiments and high-throughput sequencing of F. tularensis to explore the genetic variation. We found that during early laboratory culture passages of F. tularensis, gene duplications emerged in the pathogen genome followed by single-nucleotide polymorphisms in genes for bacterial capsule synthesis. Based on a biological enrichment scheme and the use of high-throughput sequencing, we identified genetic variation that likely pre-existed in a source sample. The results support that capsule synthesis gene mutations are common during laboratory culture, and that a biological amplification strategy is useful for linking a F. tularensis sample to a specific laboratory variant among many highly similar variants.
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| 8. |
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| 9. |
- Fryknäs, Mårten, et al.
(författare)
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Screening for phenotype selective activity in multidrug resistant cells identifies a novel tubulin active agent insensitive to common forms of cancer drug resistance
- 2013
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13, s. 374-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Drug resistance is a common cause of treatment failure in cancer patients and encompasses a multitude of different mechanisms. The aim of the present study was to identify drugs effective on multidrug resistant cells. Methods: The RPMI 8226 myeloma cell line and its multidrug resistant subline 8226/Dox40 was screened for cytotoxicity in response to 3,000 chemically diverse compounds using a fluorometric cytotoxicity assay (FMCA). Follow-up profiling was subsequently performed using various cellular and biochemical assays. Results: One compound, designated VLX40, demonstrated a higher activity against 8226/Dox40 cells compared to its parental counterpart. VLX40 induced delayed cell death with apoptotic features. Mechanistic exploration was performed using gene expression analysis of drug exposed tumor cells to generate a drug-specific signature. Strong connections to tubulin inhibitors and microtubule cytoskeleton were retrieved. The mechanistic hypothesis of VLX40 acting as a tubulin inhibitor was confirmed by direct measurements of interaction with tubulin polymerization using a biochemical assay and supported by demonstration of G2/M cell cycle arrest. When tested against a broad panel of primary cultures of patient tumor cells (PCPTC) representing different forms of leukemia and solid tumors, VLX40 displayed high activity against both myeloid and lymphoid leukemias in contrast to the reference compound vincristine to which myeloid blast cells are often insensitive. Significant in vivo activity was confirmed in myeloid U-937 cells implanted subcutaneously in mice using the hollow fiber model. Conclusions: The results indicate that VLX40 may be a useful prototype for development of novel tubulin active agents that are insensitive to common mechanisms of cancer drug resistance.
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| 10. |
- Johansson, Malin E V, 1971, et al.
(författare)
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Composition and functional role of the mucus layers in the intestine.
- 2011
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Ingår i: Cellular and Molecular Life Sciences. - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 68, s. 3635-3641
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Forskningsöversikt (refereegranskat)abstract
- In discussions on intestinal protection, the protective capacity of mucus has not been very much considered. The progress in the last years in understanding the molecular nature of mucins, the main building blocks of mucus, has, however, changed this. The intestinal enterocytes have their apical surfaces covered by transmembrane mucins and the whole intestinal surface is further covered by mucus, built around the gel-forming mucin MUC2. The mucus of the small intestine has only one layer, whereas the large intestine has a two-layered mucus where the inner, attached layer has a protective function for the intestine, as it is impermeable to the luminal bacteria.
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| 11. |
- Kanatsuna, Norio, et al.
(författare)
-
Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes.
- 2015
-
Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 82:4, s. 361-369
-
Tidskriftsartikel (refereegranskat)abstract
- The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ, or both, in newly diagnosed type 1 diabetes patients and controls. Patients (n=676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n=363) were analyzed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA, and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than controls (p<0.001). Irrespective of age at diagnosis, 19 % (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (p<0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR=1.509; 95th CI 1.011, 2.252; p=0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans, rather than cis heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes. This article is protected by copyright. All rights reserved.
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| 12. |
- Khodaverdi, Azin, et al.
(författare)
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The feasibility of using center frequency spectra in photoacoustic imaging for tissue characterization
- 2023
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Ingår i: IUS 2023 - IEEE International Ultrasonics Symposium, Proceedings. - 1948-5727 .- 1948-5719. - 9798350346459
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Konferensbidrag (refereegranskat)abstract
- In photoacoustic imaging, the amplitude of the photoacoustic signal is used for mapping the spatial distribution of a chromophore in the body and few studies have focused on the potential of using frequency content of the photoacoustic data. This study investigates the feasibility of using the photoacoustic center frequency spectrum in differentiating microspheres of various sizes and colors in phantoms. The microspheres with colors of green and blue, and the same size showed different center frequency spectrum shapes while keeping the offset (mean frequency) approximately the same. In addition, smaller microspheres showed higher center frequency offset, while larger microspheres showed smaller offset, suggesting the potential to use the center frequency spectrum for differentiating chromophores of various optical properties in the body.
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| 13. |
- Larsson, Ingrid, et al.
(författare)
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Viktminskning utan kirurgi kräver energirestriktion och följsamhet - Ger minskat nyinsjuknande i diabetes och förbättrade kardiovaskulära riskfaktorer, visar litteraturgenomgång.
- 2017
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Ingår i: Läkartidningen. - 1652-7518. ; 114
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Forskningsöversikt (refereegranskat)abstract
- Energy restriction and adherence required for weight loss without surgery Non-surgical weight loss treatment has not been shown to reduce mortality or cardiovascular morbidity, but can prevent diabetes mellitus and improves cardiovascular risk factors. For weight loss, energy restriction is fundamental and can lead to an average 2 to 20 kg loss over 6 to 12 months. Pharmacological treatment, behaviour therapy, physical activity and weight loss advice through web sites and smartphone applications and combinations in addition to energy restriction can contribute to further, but relatively limited weight loss up to 30 months. Adherence to the treatment is necessary for both weight loss and long-term weight loss maintenance.
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| 14. |
- Larsson, Malin, 1983-, et al.
(författare)
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A new ultrasound-based approach to visualize target specific polymeric contrast agent
- 2011
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Ingår i: 2011 IEEE International Ultrasonics Symposium (IUS). - : IEEE. - 9781457712524 ; , s. 1626-1629
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Konferensbidrag (refereegranskat)abstract
- There are advantages of using a polymeric shelled contrast agent (CA) during ultrasound imaging instead of lipid shelled CA, e.g. particles can be attached to the surface, which enables an introduction of antibodies to the surface making the CA target specific. For this application it is essential to have a sensitive imaging technique suitable for polymeric CA. However, previously presented results have indicated difficulties in visualizing polymeric CA with commercially available contrast algorithms. Therefore a new subtraction algorithm (SA), was developed that define the difference between contrast and reference images. The aim of this study was to evaluate the response from a polymeric CA, when using the SA and compare it with existing contrast algorithms. Moreover, the possibility to detect a thin layer of CA was tested using the SA.Ultrasound short-axis images of a tissue-mimicking vessel phantom with a pulsating flow were obtained using a GE Vivid7 system (M12L) and a Philips iE33 system (S5-1). Repeated (n=91) contrast to tissue ratios (CTR) calculated at various mechanical index (MI) using the contrast algorithms pulse inversion (PI), power modulation (PM) and SA at a concentration of 105microbubbles/ml.The developed SA showed improvements in CTR compared to existing contrast algorithms. The CTRs were -0.99 dB ± 0.67 (MI 0.2), 9.46 dB ± 0.77 (MI 0.4) and 2.98 dB ± 0.60 (MI 0.8) with PI, 8.17 dB ± 1.15 (MI 0.2), 15.60 dB ± 1.29 (MI0.4) and 11.60 dB ± 0.73 (MI 0.8) with PM and 14.97 dB ± 3.97 (MI 0.2), 20.89 dB ± 3.54 (MI 0.4) and 21.93 dB ± 4.37 (MI 0.8) with the SA. In addition to this, the layer detection, when using the SA was successful.
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| 15. |
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| 16. |
- Larsson, Malin K., et al.
(författare)
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Endocardial border delineation capability of a multimodal polymer-shelled contrast agent
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundA novel polymer-shelled contrast agent (CA) with high mechanical and chemical stability was recently developed [1]. In excess to its ultrasound properties, it also supports targeted and multimodal imaging [2-4]. Even though these new possibilities have the potential to lead to new methodologies and approaches for non-invasive diagnosis, it is important that the fundamental diagnostic features in contrast-enhanced ultrasound are preserved. The aim of this study was therefore to examine the clinical use of the polymer-shelled CA by analyzing the left ventricular endocardial border delineation capability in a porcine model. In addition, physiological effects due to CA injections were studied.MethodsThe endocardial border delineation capability was assessed in a comparative study, which included three doses (1.5 ml, 3 ml and 5 ml, [5x108 MBs/ml]) of the polymer-shelled CA and the commercially available CA SonoVue® (1.5 ml, [2-5x108 MBs/ml]). Ultrasound images of the left ventricle were evaluated manually by blinded observers (n=3) according to a 6-segment model, in which each segment was graded as 0=not visible, 1=barely visible or 2=well visible, as well as semi-automatically by a segmentation software. Furthermore, duration of clinically useful contrast enhancement and changes in physiological parameters were evaluated.ResultsFor the highest dose of the polymer-shelled CA, the obtained segment scores, time for clinically sufficient contrast enhancement and semi-automatic delineation capability were comparable to SonoVue®. Moreover, neither dose of the polymer-shelled CA did affect the physiological parameters.ConclusionThis study demonstrated that the polymer-shelled CA can be used in contrast-enhanced diagnostic imaging without influence on major physiological parameters.
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| 17. |
- Larsson, Malin K., et al.
(författare)
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Endocardial border delineation capability of a novel multimodal polymer-shelled contrast agent
- 2014
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Ingår i: Cardiovascular Ultrasound. - : Springer Science and Business Media LLC. - 1476-7120. ; 12, s. 24-
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Tidskriftsartikel (refereegranskat)abstract
- Background: A novel polymer-shelled contrast agent (CA) with multimodal and target-specific potential was developed recently. To determine its ultrasonic diagnostic features, we evaluated the endocardial border delineation as visualized in a porcine model and the concomitant effect on physiological variables. Methods: Three doses of the novel polymer-shelled CA (1.5 ml, 3 ml, and 5 ml [5 x 10(8) microbubbles (MBs)/ml]) and the commercially available CA SonoVue (1.5 ml [2-5 x 10(8) MBs/ml]) were used. Visual evaluations of ultrasound images of the left ventricle were independently performed by three observers who graded each segment in a 6-segment model as either 0 = not visible, 1 = weakly visible, or 2 = visible. Moreover, the duration of clinically useful contrast enhancement and the left ventricular opacification were determined. During anesthesia, oxygen saturation, heart rate, and arterial pressure were sampled every minute and the effect of injection of CA on these physiological variables was evaluated. Results: The highest dose of the polymer-shelled CA gave results comparable to SonoVue. Thus, no significant difference in the overall segment score distribution (2-47-95 vs. 1-39-104), time for clinically sufficient contrast enhancement (20-40 s for both) and left ventricular overall opacification was found. In contrast, when comparing the endocardial border delineation capacity for different regions SonoVue showed significantly higher segment scores for base and mid, except for the mid region when injecting 1.5 ml of the polymer-shelled CA. Neither high nor low doses of the polymer-shelled CA significantly affected the investigated physiological variables. Conclusions: This study demonstrated that the novel polymer-shelled CA can be used in contrast-enhanced diagnostic imaging without influence on major physiological variables.
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| 18. |
- Larsson, Malin, et al.
(författare)
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Visualization of multimodal polymer-shelled contrast agents using ultrasound contrast sequences : an experimental study in a tissue mimicking flow phantom
- 2013
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Ingår i: Cardiovascular Ultrasound. - : Springer Science and Business Media LLC. - 1476-7120. ; 11, s. 33-
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Tidskriftsartikel (refereegranskat)abstract
- Background: A multimodal polymer-shelled contrast agent (CA) with target specific potential was recently developed and tested for its acoustic properties in a single element transducer setup. Since the developed polymeric CA has different chemical composition than the commercially available CAs, there is an interest to study its acoustic response when using clinical ultrasound systems. The aim of this study was therefore to investigate the acoustic response by studying the visualization capability and shadowing effect of three polymer-shelled CAs when using optimized sequences for contrast imaging. Methods: The acoustic response of three types of the multimodal CA was evaluated in a tissue mimicking flow phantom setup by measuring contrast to tissue ratio (CTR) and acoustic shadowing using five image sequences optimized for contrast imaging. The measurements were performed over a mechanical index (MI) range of 0.2-1.2 at three CA concentrations (10(6), 10(5), 10(4) microbubbles/ml). Results: The CTR-values were found to vary with the applied contrast sequence, MI and CA. The highest CTR-values were obtained when a contrast sequence optimized for higher MI imaging was used. At a CA concentration of 106 microbubbles/ml, acoustic shadowing was observed for all contrast sequences and CAs. Conclusions: The CAs showed the potential to enhance ultrasound images generated by available contrast sequences. A CA concentration of 106 MBs/ml implies a non-linear relation between MB concentration and image intensity.
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| 19. |
- Leuchowius, Karl-Johan, et al.
(författare)
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High content screening for inhibitors of protein interactions and post-translational modifications in primary cells by proximity ligation
- 2010
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 9:1, s. 178-183
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Tidskriftsartikel (refereegranskat)abstract
- The cost of developing new drugs is a major obstacle for pharmaceutical companies and academia with many drugs identified in the drug discovery process failing approval for clinical use due to lack of intended effect or because of severe side effects. Since the early 1990 s, high throughput screening of drug compounds has increased enormously in capacity but has not resulted in a higher success rate of the identified drugs. Thus, there is a need for methods that can identify biologically relevant compounds and more accurately predict in vivo effects early in the drug discovery process. To address this, we developed a proximity ligation-based assay for high content screening of drug effects on signaling pathways. As a proof of concept, we used the assay to screen through a library of previously identified kinase inhibitors, including six clinically used tyrosine kinase inhibitors, to identify compounds that inhibited the platelet-derived growth factor (PDGF) receptor beta signaling pathway in stimulated primary human fibroblasts. Thirteen of the 80 compounds were identified as hits, and the dose responses of these compounds were measured. The assay exhibited a very high Z' factor (0.71) and signal to noise ratio (11.7), demonstrating excellent ability to identify compounds interfering with the specific signaling event. A comparison with regular immunofluorescence detection of phosphorylated PDGF receptor demonstrated a far superior ability by the in situ proximity ligation assay to reveal inhibition of receptor phosphorylation. In addition, inhibitor-induced perturbation of protein-protein interactions of the PDGF signaling pathway could be quantified, further demonstrating the usefulness of the assay in drug discovery.
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| 20. |
- Liin, Sara, et al.
(författare)
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Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac I-Ks channel
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:18, s. 5714-5719
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Tidskriftsartikel (refereegranskat)abstract
- Polyunsaturated fatty acids (PUFAs) affect cardiac excitability. Kv7.1 and the beta-subunit KCNE1 form the cardiac I-Ks channel that is central for cardiac repolarization. In this study, we explore the prospects of PUFAs as I-Ks channel modulators. We report that PUFAs open Kv7.1 via an electrostatic mechanism. Both the polyunsaturated acyl tail and the negatively charged carboxyl head group are required for PUFAs to open Kv7.1. We further show that KCNE1 coexpression abolishes the PUFA effect on Kv7.1 by promoting PUFA protonation. PUFA analogs with a decreased pK(a) value, to preserve their negative charge at neutral pH, restore the sensitivity to open I-Ks channels. PUFA analogs with a positively charged head group inhibit I-Ks channels. These different PUFA analogs could be developed into drugs to treat cardiac arrhythmias. In support of this possibility, we show that PUFA analogs act antiarrhythmically in embryonic rat cardiomyocytes and in isolated perfused hearts from guinea pig.
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| 21. |
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| 22. |
- Nilsson, Malin, et al.
(författare)
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Bomullssvälten
- 2023
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Ingår i: Bildningsboxen 2. - 9789113128597 ; 2
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 23. |
- Olsson, Pål Axel, et al.
(författare)
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Värdväxten Johannesört Hypericum spp.
- 2022
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Ingår i: Yrfän. - Sverige : Sveriges entomologiska förening. ; 3, s. 18-20
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Johannesörter Hypericum spp. är ett släkte med sju arter i Sverige. De känns igen på de gula femtaliga blommorna med många ståndare. Fem av arterna är antingen sällsynta eller väldigt lokalt förekommande. Man syftar därför främst på de två vanliga arterna äkta johannesört H. perforatum och fyrkantig johannesört H.maculatum när man pratar om demsom värdväxter för insekter. Dessatvå arter förekommer i liknande biotoper, främst på torra till medelfuktiga gräsmarker och ruderatmarker. De kan förekomma i stor mängd på igenväxningsmarker. Fyrkantig johannesört finns generellt på lite fuktigare marker och längre norrut än äkta johannesört. Johannesörthar också kallats mannablod eftersom krossade blomknoppar ger enblodröd färg.
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| 24. |
- Palstam, Annie, 1981, et al.
(författare)
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Perceived exertion at work in women with fibromyalgia: Explanatory factors and comparison with healthy women
- 2014
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 46, s. 773-780
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate perceived exertion at work in women with fibromyalgia. Design: A controlled cross-sectional multi-centre study. Subjects and methods: Seventy-three women with fibromyalgia and 73 healthy women matched by occupation and physical workload were compared in terms of perceived exertion at work (0–14), muscle strength, 6-min walk test, symptoms rated by Fibromyalgia Impact Questionnaire (FIQ), work status (25–100%), fear avoidance work beliefs (0–42), physical activity at work (7–21) and physical workload (1–5). Spearman’s correlation coefficient and linear regression analysis were conducted. Results: Perceived exertion at work was significantly higher in the fibromyalgia group than in the reference group (p = 0.002), while physical activity at work did not differ between the groups. Physical capacity was lower and symptom severity higher in fibromyalgia compared with references (p < 0.05). In fibromyalgia, perceived exertion at work showed moderate correlation with physical activity at work, physical workload and fear avoidance work beliefs (rs = 0.53– 0.65, p < 0.001) and a fair correlation with anxiety (rs = 0.26, p = 0.027). Regression analysis indicated that the physical activity at work and fear avoidance work beliefs explained 50% of the perceived exertion at work. Conclusion: Women with fibromyalgia perceive an elevated exertion at work, which is associated with physical workrelated factors and factors related to fear and anxiety.
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| 25. |
- Segerman, Anna, et al.
(författare)
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Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition
- 2016
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 17:11, s. 2994-3009
-
Tidskriftsartikel (refereegranskat)abstract
- Intratumoral heterogeneity is a hallmark of glioblastoma multiforme and thought to negatively affect treatment efficacy. Here, we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability among clones, including a range of responses to radiation and drugs. This widespread variability was observed as a continuumof multitherapy resistance phenotypes linked to a proneural-mesenchymal shift in the transcriptome. Multitherapy resistance was associated with a semi-stable cell state that was characterized by an altered DNA methylation pattern at promoter regions of mesenchymal master regulators and enhancers. The gradient of cell states within the GIC compartment constitutes a distinct form of heterogeneity. Our findings may open an avenue toward the development of new therapeutic rationales designed to reverse resistant cell states.
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| 26. |
- Selvin, Tove, et al.
(författare)
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Immuno-oncological effects of standard anticancer agents and commonly used concomitant drugs : an in vitro assessment
- 2024
-
Ingår i: BMC Pharmacology & Toxicology. - : BioMed Central (BMC). - 2050-6511. ; 25:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundIt has become evident in the field of oncology that the outcome of medical treatment is influenced by the combined effect exerted on both cancer- and immune cells. Therefore, we evaluated potential immunological effects of 46 standard anticancer agents and 22 commonly administered concomitant non-cancer drugs.MethodsWe utilized a miniaturized in vitro model system comprised of fluorescently labeled human colon and lung cancer cell lines grown as monocultures and co-cultured with activated peripheral blood mononuclear cells (PBMCs). The Bliss Independence Model was then applied to detect antagonism and synergy between the drugs and activated immune cells.ResultsAmong the standard anticancer agents, tyrosine kinase inhibitors (TKIs) stood out as the top inducers of both antagonism and synergy. Ruxolitinib and dasatinib emerged as the most notably antagonistic substances, exhibiting the lowest Bliss scores, whereas sorafenib was shown to synergize with activated PBMCs. Most concomitant drugs did not induce neither antagonism nor synergy. However, the statins mevastatin and simvastatin were uniquely shown to synergize with activated PBMC at all tested drug concentrations in the colon cancer model.ConclusionWe utilized a miniaturized tumor-immune model to enable time and cost-effective evaluation of a broad panel of drugs in an immuno-oncology setting in vitro. Using this approach, immunomodulatory effects exerted by TKIs and statins were identified.
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| 27. |
- Selvin, Tove, et al.
(författare)
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Phenotypic screening platform identifies statins as enhancers of immune cell-induced cancer cell death.
- 2023
-
Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- High-throughput screening (HTS) of small molecule drug libraries has greatly facilitated the discovery of new cancer drugs. However, most phenotypic screening platforms used in the field of oncology are based solely on cancer cell populations and do not allow for the identification of immunomodulatory agents.We developed a phenotypic screening platform based on a miniaturized co-culture system with human colorectal cancer- and immune cells, providing a model that recapitulates part of the tumor immune microenvironment (TIME) complexity while simultaneously being compatible with a simple image-based readout. Using this platform, we screened 1,280 small molecule drugs, all approved by the Food and Drug Administration (FDA), and identified statins as enhancers of immune cell-induced cancer cell death.The lipophilic statin pitavastatin had the most potent anti-cancer effect. Further analysis demonstrated that pitavastatin treatment induced a pro-inflammatory cytokine profile as well as an overall pro-inflammatory gene expression profile in our tumor-immune model.Our study provides an in vitro phenotypic screening approach for the identification of immunomodulatory agents and thus addresses a critical gap in the field of immuno-oncology. Our pilot screen identified statins, a drug family gaining increasing interest as repurposing candidates for cancer treatment, as enhancers of immune cell-induced cancer cell death. We speculate that the clinical benefits described for cancer patients receiving statins are not simply caused by a direct effect on the cancer cells but rather are dependent on the combined effect exerted on both cancer and immune cells.
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| 28. |
- Selvin, Tove, et al.
(författare)
-
The Immuno-Oncology Hollow Fiber Assay
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In order to facilitate the translation of novel immunotherapies from bench to bedside, continued development of predictive preclinical models is essential. Herein, we developed the immuno-oncology hollow fiber assay (HFA) to bridge the gap between cell based in vitro assays and more complex mouse models for evaluation of immuno-oncological agents. The colorectal cancer (CRC) cell line HCT116-GFP and human peripheral blood mononuclear cells (PBMCs) were co-cultured inside semipermeable hollow fibers. As a proof of concept, aCD3 and IL-2 was used to induce immune cell-mediated cancer cell death. During in vitro characterization of the model system, an enhanced effect of aCD3 and IL-2 was observed in the HFA compared to conventional monolayers. Further investigation demonstrated that increased cell proximity alone is sufficient to augment immune cell activation and effector function. To assess the functionality of the assay in vivo, a pilot study was performed using nude mice. Hollow fibers were surgically implanted intraperitoneally (i.p.) and the mice received local injections of aCD3 at the time of implantation and/ or systemic IL-2 via i.p. injection once daily for 3 consecutive days. Compared to untreated mice and mice receiving IL-2 alone, the combination of aCD3 and IL-2 resulted in a significant decrease in cancer cell viability. Traditional in vivo models often necessitate lengthy observation periods to monitor tumor growth and treatment response. We have developed a simplified model system that enables initial in vivo evaluation of immunological agents on cancer and immune cells of human origin within a matter of days.
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| 29. |
- Wester, Axel, et al.
(författare)
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An Increased Diagnostic Sensitivity of Truncated GAD65 Autoantibodies in Type 1 Diabetes May Be Related to HLA-DQ8
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 66:3, s. 735-740
-
Tidskriftsartikel (refereegranskat)abstract
- N-terminally truncated (96-585) GAD65 (tGAD65) autoantibodies may better delineate type 1 diabetes than full-length GAD65 (fGAD65) autoantibodies. We aimed to compare the diagnostic sensitivity and specificity between fGAD65 and tGAD65 autoantibodies for type 1 diabetes in relation to HLA-DQ. Sera from children and adolescents with newly diagnosed type 1 diabetes (n = 654) and healthy control subjects (n = 605) were analyzed in radiobinding assays for fGAD65 (fGADA), tGAD65 (tGADA), and commercial (125)I-GAD65 (RSRGADA) autoantibodies. The diagnostic sensitivity and specificity in the receiver operating characteristic curve did not differ between fGADA and tGADA. At the optimal cutoff, the diagnostic sensitivity for fGADA was lower than tGADA at similar diagnostic specificities. In 619 patients, 64% were positive for RSRGADA compared with 68% for fGADA and 74% for tGADA. Using non-DQ2/non-DQ8 patients as reference, the risk of being diagnosed with fGADA and tGADA was increased in patients with DQ2/2 and DQ2/8. Notably, logistic regression analysis suggested that DQ8/8 patients had an increased risk to be diagnosed with tGADA (P = 0.003) compared with fGADA (P = 0.09). tGADA had a higher diagnostic sensitivity for type 1 diabetes than both fGADA and RSRGADA. As DQ8/8 patients represent 10-11% of patients with newly diagnosed type 1 diabetes <18 years of age, tGADA analysis should prove useful for disease classification.
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| 30. |
- Abrahamsson, Malin, et al.
(författare)
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Degeneration pattern in somatic embryos of Pinus sylvestris L.
- 2017
-
Ingår i: In Vitro Cellular and Developmental Biology - Plant. - : Springer Science and Business Media LLC. - 1054-5476 .- 1475-2689. ; 53, s. 86-96
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Tidskriftsartikel (refereegranskat)abstract
- Somatic embryos can be used for propagating forest trees vegetatively, which is of great importance for capturing the genetic gain in breeding programs. However, many economically important Pinus species are difficult or impossible to propagate via somatic embryogenesis. In order to get a better understanding of the difficulties to propagate Pinus species via somatic embryogenesis, we are studying the developmental pathway of somatic embryos in different cell lines. In a previous study, we showed that the morphology of early somatic embryos in Scots pine (Pinus sylvestris) differs between cell lines giving rise to normal or abnormal cotyledonary embryos. In this study, we have compared the proliferation and degeneration pattern of early and late embryos in a normal and abnormal cell line. In both cell lines, a high frequency of the embryos degenerated. Among the degenerating embryos, two main degeneration patterns could be distinguished. In the normal cell line, the embryos degenerated similar to how the subordinate embryos are degraded in the seed. In the abnormal cell line, the degeneration of the embryos resulted in a continuous loop of embryo degeneration and differentiation of new embryos. We observed a similar degeneration pattern when embryogenic tissue was initiated from megagametophytes containing zygotic embryos at the stage of cleavage polyembryony. Based on our results, we suggest that the degeneration pattern in abnormal cell lines starts during initiation of embryogenic cultures.
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| 31. |
- Abrahamsson, Malin, et al.
(författare)
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Patterning during somatic embryogenesis in Scots pine in relation to polar auxin transport and programmed cell death
- 2012
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Ingår i: Plant Cell, Tissue and Organ Culture. - : Springer Science and Business Media LLC. - 0167-6857 .- 1573-5044. ; 109, s. 391-400
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Tidskriftsartikel (refereegranskat)abstract
- Somatic embryogenesis is a useful tool to propagate conifers vegetatively. However, a major limitation in many pine species is the low quality of cotyledonary somatic embryos. The aim of this study has been to elucidate the developmental pathway of somatic embryos in Scots pine (Pinus sylvestris), to identify deviations from the normal pathway and to identify processes that might disturb normal development. Initially we compared the developmental pathway of somatic embryogenesis in representative cell lines yielding cotyledonary embryos with normal and abnormal morphology. Early embryos carrying suspensor cells in excess of the normal number (supernumerary) were more frequent in cell lines giving rise to abnormal cotyledonary embryos. In this study we show that the frequency of early somatic embryos with supernumerary suspensor cells increased after treatment with the auxin transport inhibitor 1-N-naphtylphthalamic acid (NPA). Furthermore, the yield of developing embryos increased significantly after treatment with the antiauxin 2-(4-chlorophenoxy)-2-methylpropionic acid (PCIB), but the morphology of the embryos was not affected. The number of cells undergoing PCD was analyzed using a TUNEL-assay. The frequency of TUNEL-positive cells was high both in proliferating cultures and during differentiation of early somatic embryos. However, the pattern of TUNEL-positive cells was similar in normal somatic embryos and in embryos with supernumerary suspensor cells. Together our results suggest that the presence of supernumerary suspensor cells in early somatic embryos of Scots pine is caused by disturbed polar auxin transport and results in aberrant embryo development.
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| 32. |
- Al-Mudhaffar, Azhar, et al.
(författare)
-
Ny ekvation för beräkning av uppställningsbehov i bussterminaler
- 2024
-
Ingår i: Sammanställning av referat från Transportforum 2024. - Linköping : Statens väg- och transportforskningsinstitut. ; , s. 106-107
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Behov för uppställningsplatser (UP) kan delas in i tre olika kategorier; reglering, paus och rast. Reglering avser buss som står parkerad med förare ombord för att vänta in nästa körtid. Tidsregleringen pågår normalt upp till 15 minuter. Paus och rast avser parkerad buss utan förare, i nära anslutning till paus-/rastlokal. En kortare paus är normalt ≥ 10 minuter och en planerad rast ≥30 minuter. Flera bussterminaler i Stockholmsregion har brist på påstigningshållplatser och uppställningsplatser, vilket är ett resultat av intresset för att minimera ytan eftersom bussterminaler vanligtvis upptar attraktiv mark nära stadskärnor. Metoder för beräkning av framtidsbehov är inte bristfria och behöver utvecklas för att säkerställa kapaciteten med optimal markanvändning. En befintlig metod som används av Trafikförvaltningen uppskattar att den erforderliga UP är lika med antalet busslinjer med turtäthet upp till 8 avgångar/tim. Linjer med högre turtäthet behöver mer än en plats. Denna metod är mer lämplig med linjer som har 6-8 avg./tim, men för lägre turtäthet resulterar den i behovsöverskattning. En ekvation i “Transit Capacity and Quality of Service Manual TCQSM, Report 165.” antar att UP (Nberths) för en linje beror på uppehållstiden (tlayover) och tidsavståndet mellan på följande bussar (theadway): Nberths = 1.2*(tlayover/theadway) Denna metod kräver data om tidsavstånd som är svårt att uppskatta vid framtids bussterminal i Stockholmsregion eftersom bussarna, efter uppehållstiden, inte alltid återvänder som samma linje. Därför finns det ett behov av att utveckla en användbar metod för att uppskatta antalet UP med tillgängliga data.Metoden har innefattat:LitteraturstudierFältobservationer av beläggning i uppställningsplatserWorkshops och intervjuer med trafikutövareFramtagande av ny linjär ekvation UP=a+(avg./tim)/bTillämpning och utvärderingJämförelse av resultat med andra metoderDiskussion och beslut om metoden i intern terminalgrupp.Den utvecklade metoden är inte applicerbar i alla regioner utan kalibrering eftersom den är anpassade till förhållande i Stockholmsregion. Arbetet med att utforma den mest optimala och effektiva bussterminalen kommer att fortsätta i takt med att metoderna blir bättre på att identifiera och fastställa de uppställningsplatser som behövs. Detta är ett arbete där teoretiska studier kommer att kombineras med erfarenhet och kunskapsöverföring.
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| 33. |
- Alam, Mehboob, et al.
(författare)
-
Prevalence of Escherichia coli O157:H7 on spinach and rocket as affected by inoculum and time to harvest
- 2014
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Ingår i: Scientia Horticulturæ. - : Elsevier BV. - 0304-4238 .- 1879-1018. ; 165, s. 235-241
-
Tidskriftsartikel (refereegranskat)abstract
- Irrigation water is an important vehicle for dissemination of human pathogens to plants. As contamination in an early stage of the production chain cannot necessarily be counteracted later, cultural measures to reduce the contamination risk need to be adopted during primary production. In a two-factorial greenhouse experiment, we studied the impact of inoculum density and the interval between irrigation and haivest on the prevalence of an inoculated gfp-tagged non-pathogenic strain of Escherichia coli O157:H7. The strain was inoculated with the irrigation water at a density of log 5.6, log 6.6 and log 7.6 CFU ml(-1) into the phyllosphere of fully grown crops of rocket and spinach (BBCH 49). The crops were then harvested after 3, 24,48 and 72 h. The introduced strain decreased exponentially in numbers within 72 h, to 49.6%, 52.6% and 50.6%, respectively, in the spinach and to 58.5%, 67.4% and 73.4% in the rocket. No differences were found in the number of the total viable count of aerobic bacteria and of Enterobacteriaceae as assessed on tryptic soy agar (TSA) and violet red bile dextrose agar (VRBD), respectively. Sequencing of the 16S rRNA genes of randomly selected isolates from VRBD were identified as Enterobacter cloaceae, Enterobacter ludwigii, Pantoea sp. and Raoultella planticola as the dominant Enterobacteriaceae species in the rocket and spinach phyllosphere. We found that cessation of irrigation for three days seems not to be an adequate sanitisation treatment to exclude the possibility of viable E. coil 0157:H7 cells on spinach or rocket. (C) 2013 Elsevier B.V. All rights reserved.
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| 34. |
- Alrutz, Marie, et al.
(författare)
-
Projektledning
- 2013
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Bok (populärvet., debatt m.m.)abstract
- Projektledning är ett yrke med egen certifiering. Det pågår en spännande utveckling inom området och det blir allt viktigare att hålla sig ajour med utvecklingen.Det övergripande målet med den här handboken är att vara en ständigt aktuell heltäckande bok om projektarbete. Innehållsmässigt täcker den både frågor som har med struktur och styrning att göra och frågor om ledning av människor och mänskliga processer i grupp. Kompetens inom projekt byggs av både kunskap och erfarenhet. Vi följer kontinuerligt aktuell forskning inom dessa områden och bjuder in intressanta forskare att medverka som författare. Vi skildrar verkliga projekt och låter erfarenheterna få plats, både de bästa erfarenheterna och de utmaningar som man tagit sig igenom.Handboken är levande och det innebär att artiklar tas bort för att ge plats för nya, i takt med att den uppdateras fortlöpande.
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| 35. |
- Alsanius, Beatrix, et al.
(författare)
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EHEC's öde på frilandsodlade grönsaker
- 2010
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Ingår i: LTJ-fakultetens faktablad.
-
Annan publikation (populärvet., debatt m.m.)abstract
- Sjukdomsutbrott orsakade av tarmsmittor (t.ex. Salmonella, Campylobacter, E. coli, Shigella, Norovirus) har tidigare främst förknippats med animaliska produkter. Under de senaste åren har dock utbrott relaterade till frukt och grönt ökat; 49 frukt- och grönt relaterade utbrott med ca 2500 sjukdomsfall registrerades under tiden 1997-2009. Mörkertalet är dock stort och kan beroende på sjukdomsalstraren vara 4-10 gånger högre. Fram till 2004 klassades hotet från frukt och grönt som ringa. Det svenska utbrottet av EHEC, en aggressiv form av E. coli, i samband med produktion av isbergssallad under hösten 2005, satte problemet med fekal förorening i frukt och grönt på den svenska agendan. Smittorna kan överföras i hela kedjan från jord till bord och problemet är mest påtagligt för frukt och grönt som konsumeras rå eller med minimal tillredning. Organisk gödsel och bevattningsvatten har identifierats som huvudsakliga smittkällor vid odling av frilandskulturer, men det finns även andra smittkällor, t.ex. vilda djur, husdjur och människor. För att förhindra dessa utbrott är det viktigt att bryta smittcykeln. Vi har studerat om E. coli, i synnerhet EHEC, överlever på grönt, när smittan överförts med bevattningsvatten. Vi använde oss av en EHEC-stam som inte kan framkalla sjukdom, men som i övrigt har de för EHEC unika miljömässiga egenskaperna (biokemisk EHEC). Enligt våra resultat minskar förekomsten av biokemisk EHEC med ökande tidsintervall mellan bevattnings- och skördetillfälle. Minskningen beror på halten av biokemisk EHEC i bevattningsvattnet. Val av E. coli-stam för provokation och analyssätt är väsentliga. För att undvika sjukdomsutbrott i samband med odling av persilja, ska ett intervall av 72 timmar mellan bevattning med smittat bevattningsvatten och skörd inte underskridas
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| 36. |
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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Alsved, Malin, et al.
(författare)
-
Airborne bacteria in hospital operating rooms during ongoing surgery
- 2018
-
Konferensbidrag (refereegranskat)abstract
- IntroductionPost-operative infections obtained from open-wound surgeries constitute an unnecessary load on both healthcare and affected patients. It is well established that increased air cleanliness reduces the number of post-operative infections. Therefore, the ventilation system is important in order to reduce the number of infectious particles in the air during surgery. Ventilation with high airflow, as in operating rooms, consumes a high amount of energy and it is thus desirable to find energy efficient solutions. ObjectivesThe purpose of this work was to evaluate air quality, energy efficiency and working environment comfort for three different ventilation techniques in operating rooms. MethodThe newly developed ventilation system temperature controlled airflow (TcAF) was compared with the conventionally used turbulent mixed airflow (TMA) and laminar airflow (LAF). In total, 750 air sample measurements were performed during 45 orthopaedic operations: 15 for each type of ventilation system [1]. The concentration of colony forming units (CFU)/m3 was measured at three locations in the rooms: close to the wound (<0.5 m), at the instrument table and peripherally in the room. The working environment comfort was evaluated in a questionnaire.ResultsOur study shows that both LAF and TcAF maintains CFU concentrations in the air during ongoing surgery significantly below 10 CFU/m3 at the wound and at the instrument table, and for TcAF also in the periphery of the room, see Figure 1. The median CFU concentration in TMA was at or above 10 CFU/m3 at all locations. TcAF used less than half the airflow to that of LAF, resulting in a 28% reduction in energy consumption. The working environment comfort was perceived less noisy and having less draft in the TcAF than the LAF ventilation.SummaryBoth the LAF and TcAF ventilation maintain high air cleanliness with low CFU concentrations throughout the operation. TMA is less efficient in removing bacteria from the air close to the patient.
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Alvinius, Aida, 1979-, et al.
(författare)
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Leaders as emotional managers : Emotion management in response organisations during a hostage taking in a Swedish prison
- 2015
-
Ingår i: Leadership & Organization Development Journal. - 0143-7739 .- 1472-5347. ; 36:6, s. 697-711
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose - The purpose of this paper is to develop a deeper understanding of how leaders manage their own and others' emotions in professional crisis management organizations during severely demanding episodes. The empirical case is a hostage drama that occurred in a small Swedish town. Although staff at the local prison were situationally prepared and trained in incident exercises, two inmates with knives fled the prison after taking a warden hostage.Design/methodology/approach - A grounded theory approach was used. In all, 14 informants from four Swedish authorities were interviewed on the basis of their involvement in the hostage drama.Findings - According to the analysis, an emergency response leader's emotion management is framed by an organizationally embedded emotional regime which is summed up in two core themes: focus on the task and do not let emotions interfere; and provide the task force with maximum physical and psychological security. The leader's emotion management within this framework consists of two interdependent processes, one more organization oriented and one more individual oriented.Research limitations/implications - Small sample, lack of representativeness, and lack of illumination of possible gender-related aspects.Practical implications - The suggested model may be valuable in educational settings.Originality/value - A new integrative, theoretical process model of leadership and emotion management in complex, stressful operations.
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| 46. |
- Andersson, Mats X., 1977, et al.
(författare)
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Phosphate-deficient oat replaces a major portion of the plasma membrane phospholipids with the galactolipid digalactosyldiacylglycerol.
- 2003
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Ingår i: FEBS letters. - 0014-5793. ; 537:1-3, s. 128-32
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Tidskriftsartikel (refereegranskat)abstract
- The plasma membranes of oat normally resemble those of other eukaryotes in containing mainly phospholipids and sterols. We here report the novel finding that the galactolipid digalactosyldiacylglycerol (DGDG) can constitute a substantial proportion of oat plasma membrane lipids, in both shoots and roots. When oat was cultivated under severe phosphate limitation, up to 70% of the plasma membrane phosphoglycerolipids were replaced by DGDG. Our finding not only reflects a far more developed potential for plasticity in plasma membrane lipid composition than often assumed, but also merits interest in the context of the limited phosphate availability in many soils.
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| 47. |
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| 48. |
- Antonsson, Malin, 1986, et al.
(författare)
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High-level language ability in healthy individuals and its relationship with verbal working memory
- 2016
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Ingår i: Clinical Linguistics & Phonetics. - : Informa UK Limited. - 0269-9206 .- 1464-5076. ; 30:12, s. 944-958
-
Tidskriftsartikel (refereegranskat)abstract
- The aims of the study were to investigate healthy subjects' performance on a clinical test of high-level language (HLL) and how it is related to demographic characteristics and verbal working memory (VWM). One hundred healthy subjects (20-79 years old) were assessed with the Swedish BeSS test (Laakso, Brunnegard, Hartelius, & Ahlsen, 2000) and two digit span tasks. Relationships between the demographic variables, VWM and BeSS were investigated both with bivariate correlations and multiple regression analysis. The results present the norms for BeSS. The correlations and multiple regression analysis show that demographic variables had limited influence on test performance. Measures of VWM were moderately related to total BeSS score and weakly to moderately correlated with five of the seven subtests. To conclude, education has an influence on the test as a whole but measures of VWM stood out as the most robust predictor of HLL.
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| 49. |
- Antusheva, E., et al.
(författare)
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Outbreak of tuberculosis in a closed setting: views on transmission based on results from molecular and conventional methods
- 2016
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Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701. ; 93:2, s. 187-190
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study describes an outbreak of tuberculosis (TB) in a nursing home for men with mental disorders where residency is lengthy or permanent. This type of setting can provide a model of transmission as contact with the rest of society is extremely limited. Aim: To determine if cases of TB, diagnosed around the same time and in the same place, are linked based on results using molecular and conventional methods. Methods: The strains of Mycobacterium tuberculosis were analysed by drug resistance testing and mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTRV). Microbiological results were related to clinical history and time of diagnosis. Findings: Nine patients were diagnosed with TB, and strains were recovered from seven of these patients. Unexpectedly, the strains with the same genotype showed different patterns of resistance, and only two strains demonstrated identical patterns. MIRU-VNTR analysis demonstrated that one patient was infected with two different strains. Conclusion: Variation between the strains indicates that the outbreak may have arisen from several sources of infection. The variation in resistance indicates that rapid emergence of antimicrobial resistance is possible. As such, several questions are raised concerning source of infection, development of disease, resistance and mixed infections. (C) 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
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| 50. |
- Asad, Samina, et al.
(författare)
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HTR1A a Novel Type 1 Diabetes Susceptibility Gene on Chromosome 5p13-q13
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD less than= 2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D susceptibility genes. Methodology/Principal Findings: Microsatellites were genotyped in the Scandinavian families to fine-map the previously linked region. Further, SNPs were genotyped in Swedish and Danish families as well as Swedish sporadic cases. In the Swedish families we detected genome-wide significant linkage to the 5-hydroxytryptamine receptor 1A (HTR1A) gene (LOD 3.98, pless than9.8x10(-6)). Markers tagging two separate genes; the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families (pless than0.002, pless than0.001 respectively). The association was not confirmed in sporadic cases. Conditional analysis indicates that the primary association was to HTR1A. Quantitative PCR show that transcripts of both HTR1A and RNF180 are present in human islets of Langerhans. Moreover, immunohistochemical analysis confirmed the presence of the 5-HTR1A protein in isolated human islets of Langerhans as well as in sections of human pancreas. Conclusions: We have identified and confirmed the association of both HTR1A and RFN180, two genes in high linkage disequilibrium (LD) to T1D in two separate family materials. As both HTR1A and RFN180 were expressed at the mRNA level and HTR1A as protein in human islets of Langerhans, we suggest that HTR1A may affect T1D susceptibility by modulating the initial autoimmune attack or either islet regeneration, insulin release, or both.
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