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Sökning: WFRF:(Forsgren Mikael)

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51.
  • Lind, Mikael, et al. (författare)
  • Co-design as social constructive pragmatism
  • 2008
  • Ingår i: In proceeding of The Inaugural meeting of The AIS Special Interest Group on Pragmatist IS Research (SIGPrag 2008) at International Conference on Information Systems (ICIS2008), France. - : The AIS Special Interest Group on Pragmatist IS Research (SIGPrag 2008) – www.sigprag.org.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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52.
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53.
  • Lind, Mikael, et al. (författare)
  • The e-Co Model : Citizens´Driving E-service Quality
  • 2007
  • Ingår i: Proceedings of the 51st Annual Conference (The International Society for the Systems Sciences) – Integrated Systems Scieces: Systems thinking, Modeling and Practice.. - : Tokyo Institute of Technology, Tokyo, Japan.
  • Konferensbidrag (refereegranskat)
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54.
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55.
  • Lundberg, Peter, 1958-, et al. (författare)
  • Breast density is strongly associated with multiparametric magnetic resonance imaging biomarkers and pro-tumorigenic proteins in situ
  • 2022
  • Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 127, s. 2025-2033
  • Tidskriftsartikel (refereegranskat)abstract
    • Background High mammographic density is an independent risk factor for breast cancer by poorly understood molecular mechanisms. Women with dense breasts often undergo conventional magnetic resonance imaging (MRI) despite its limited specificity, which may be increased by diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) and contrast. How these modalities are affected by breast density per se and their association with the local microenvironment are undetermined. Methods Healthy postmenopausal women attending mammography screen with extremely dense or entirely fatty breasts underwent multiparametric MRI for analyses of lean tissue fraction (LTF), ADC and perfusion dynamics. Microdialysis was used for extracellular proteomics in situ. Results Significantly increased LTF and ADC and delayed perfusion were detected in dense breasts. In total, 270 proteins were quantified, whereof 124 related to inflammation, angiogenesis, and cellular growth were significantly upregulated in dense breasts. Most of these correlated significantly with LTF, ADC and the perfusion data. Conclusions ADC and perfusion characteristics depend on breast density, which should be considered during the implementation of thresholds for malignant lesions. Dense and nondense breasts are two essentially different biological entities, with a pro-tumorigenic microenvironment in dense breasts. Our data reveal several novel pathways that may be explored for breast cancer prevention strategies.
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56.
  • Lundberg, Peter, et al. (författare)
  • Kvantifiering av leversteatos: diagnostisk utvärdering av protonmagnetresonansspektroskopi jämfört med histologiska metoder
  • 2016
  • Konferensbidrag (refereegranskat)abstract
    • BakgrundLeversteatos är den vanligaste manifestationen av leversjukdom i västvärlden. Leverbiopsi med semikvantitativ histologisk gradering är referensmetod vid gradering av leversteatos. Med protonmagnetsresonansspektroskopi (1H-MRS), en metod som föreslagits ersätta leverbiopsi för värdering av steatos, kan leverns innehåll av triglycerider mätas icke-invasivt. Triglyceridinnehåll >5,00 % används ofta som ett diagnostiskt kriterium för leversteatos vid undersökning med 1H-MRS. Syftet med studien var att jämföra 1H-MRS med semikvantitativ histologisk steatosgradering och kvantitativ histologisk steatosmätning.MetodPatienter remitterade för utredning av förhöjda leverenzymer in-kluderades i studien. Samtliga patienter genomgick klinisk undersökning, laboratorieprovtagning samt 1H-MRS direkt följd av leverbiopsi. För konventionell histologisk semikvantitativ gradering av steatos användes kriterierna utarbetade av Brunt och medarbetare. Kvantitativ mätning av fett i biopsierna utfördes genom att med hjälp av stereologisk punkträkning (SPC) mäta andelen av ytan som innehöll fettvakuoler.ResultatI studien inkluderades 94 patienter, varav 37 hade icke-alkoholor-sakad fettleversjukdom (NAFLD), 49 hade andra leversjukdomar och 8 hade normal leverbiopsi. En stark korrelation noterades mel-lan 1H-MRS och SPC (r=0,92, p<0,0001; к=0.82). Korrelationen mellan 1H-MRS och Brunts kriterier (к=0.26) samt mellan SPC och Brunts kriterier (к=0.38) var betydligt sämre. När patologens gradering (Brunts kriterier) användes som referensmetod för diag-nos av leversteatos så hade alla patienter med triglyceridinnehåll >5,00 % mätt med 1H-MRS steatos (specificitet 100 %). Emellertid hade 22 av 69 patienter med triglyceridinnehåll ≤5,00 % också le-versteatos enligt Brunts kriterier (sensitivitet 53 %). Motsvarande siffror när man använde gränsvärdet 3,02 % var sensitivitet 79 % och specificitet 100 %. Vid ytterligare reduktion av gränsvärdet för triglyceridinnehåll till 2,00 % ökade sensitiviteten till 87 % med upprätthållande av hög specificitet (94 %).Slutsats1H-MRS och SPC uppvisade en mycket hög korrelation vid kvantifiering av leversteatos. SPC borde därför föredras framför Brunts kriterier när noggrann histologisk kvantifiering av leversteatos är önskvärd. Många patienter kan ha histologisk leversteatos trots triglyceridinnehåll ≤5,00 % mätt med 1H-MRS. Gränsvärdet för diagnostisering av leversteatos med 1H-MRS bör därför reduceras.
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57.
  • Mandic, Mirko, et al. (författare)
  • Interval-induced metabolic perturbation determines tissue fluid shifts into skeletal muscle
  • 2021
  • Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 9:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Intense interval exercise has proven to be as effective as traditional endurance exercise in improving maximal oxygen uptake. Shared by these two exercise regimes is an acute reduction in plasma volume, which is a suggested stimulus behind exercise-induced increases in blood volume and maximal oxygen uptake. This study aimed to link exercise-induced metabolic perturbation with volume shifts into skeletal muscle tissue. Ten healthy subjects (mean age 33 +/- 8 years, 5 males and 5 females) performed three 30 s all-out sprints on a cycle ergometer. Upon cessation of exercise magnetic resonance imaging, (31)Phosphorus magnetic resonance spectroscopy and blood samples were used to measure changes in muscle volume, intramuscular energy metabolites and plasma volume. Compared to pre-exercise, muscle volume increased from 1147.1 +/- 35.6 ml to 1283.3 +/- 11.0 ml 8 min post-exercise. At 30 min post-exercise, muscle volume was still higher than pre-exercise (1147.1 +/- 35.6 vs. 1222.2 +/- 6.8 ml). Plasma volume decreased by 16 +/- 3% immediately post-exercise and recovered back to - 5 +/- 6% after 30 min. Principal component analysis of exercise performance, muscle and plasma volume changes as well as changes in intramuscular energy metabolites showed generally strong correlations between metabolic and physiological variables. The strongest predictor for the volume shifts of muscle and plasma was the magnitude of glucose-6-phosphate accumulation post-exercise. Interval training leads to large metabolic and hemodynamic perturbations with accumulation of glucose-6-phosphate as a possible key event in the fluid flux between the vascular compartment and muscle tissue.
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58.
  • Mikael, Fallgren, et al. (författare)
  • Optimization approach to joint cell, channel and power allocation in wireless communication networks
  • 2012
  • Ingår i: 2012 Proceedings of the 20th European Signal Processing Conference (EUSIPCO). - New York : IEEE conference proceedings. ; , s. 829-833
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • In multicell wireless networks the resource allocation task includes the selection of the serving cell and the allocation of channels and transmission powers. While all of these tasks have been studied in the past, all three jointly are seldom addressed. In this paper we formulate the joint cell, channel and power allocation problem as an optimization task, whose purpose is to maximize the total user throughput. The joint problem is decomposed into separate subproblems of cell, channel and power allocation. We propose heuristic and optimization based algorithms to solve each of these tasks and present numerical results that give new and valuable insights into a sum throughput optimal joint resource allocation strategy.
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59.
  • Nasr, Patrik, et al. (författare)
  • A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease : the ACCESS-ESLD study protocol
  • 2023
  • Ingår i: BMC Gastroenterology. - : BioMed Central (BMC). - 1471-230X. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Liver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures. This study aims to formulate novel blood- and imaging-centric methodologies for monitoring liver cirrhosis patients.METHODS: In this prospective study, 150 liver cirrhosis patients will be enrolled from three Swedish liver clinics. Their conditions will be assessed through extensive blood-based markers and magnetic resonance imaging (MRI). The MRI protocol encompasses body composition profile with Muscle Assement Score, portal flow assessment, magnet resonance elastography, and a abbreviated MRI for HCC screening. Evaluation of lifestyle, muscular strength, physical performance, body composition, and quality of life will be conducted. Additionally, DNA, serum, and plasma biobanking will facilitate future investigations.DISCUSSION: The anticipated outcomes involve the identification and validation of non-invasive blood- and imaging-oriented biomarkers, enhancing the care paradigm for liver cirrhosis patients. Notably, the temporal evolution of these biomarkers will be crucial for understanding dynamic changes.TRIAL REGISTRATION: Clinicaltrials.gov, registration identifier NCT05502198. Registered on 16 August 2022. Link: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05502198 .
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60.
  • Nasr, Patrik, 1987-, et al. (författare)
  • Using a 3% Proton Density Fat Fraction as a Cut-off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results from Histopathology Analysis
  • 2017
  • Ingår i: Gastroenterology. - : Elsevier. - 0016-5085 .- 1528-0012. ; 153:1, s. 53-
  • Tidskriftsartikel (refereegranskat)abstract
    • It is possible to estimate hepatic triglyceride content by calculating the proton density fat fraction (PDFF), using proton magnetic resonance spectroscopy (less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS), instead of collecting and analyzing liver biopsies to detect steatosis. However, the current PDFF cut-off value (5%) used to define steatosis by magnetic resonance was derived from studies that did not use histopathology as the reference standard. We performed a prospective study to determine the accuracy of less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF in measurement of steatosis using histopathology analysis as the standard. We collected clinical, serologic, less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF, and liver biopsy data from 94 adult patients with increased levels of liver enzymes (6 months or more) referred to the Department of Gastroenterology and Hepatology at Linköping University Hospital in Sweden from 2007 through 2014. Steatosis was graded using the conventional histopathology method and fat content was quantified in biopsy samples using stereological point counts (SPCs). We correlated less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF findings with SPCs (r = 0.92; P less than.001). less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF results correlated with histopathology results (ρ = 0.87; P less than.001), and SPCs correlated with histopathology results (ρ = 0.88; P less than.001). All 25 subjects with PDFF values of 5.0% or more had steatosis based on histopathology findings (100% specificity for PDFF). However, of 69 subjects with PDFF values below 5.0% (negative result), 22 were determined to have steatosis based on histopathology findings (53% sensitivity for PDFF). Reducing the PDFF cut-off value to 3.0% identified patients with steatosis with 100% specificity and 79% sensitivity; a PDFF cut-off value of 2.0% identified patients with steatosis with 94% specificity and 87% sensitivity. These findings might be used to improve non-invasive detection of steatosis.
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61.
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62.
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63.
  • Norén, Bengt, et al. (författare)
  • Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA
  • 2013
  • Ingår i: European Radiology. - : Springer. - 0938-7994 .- 1432-1084. ; 23:1, s. 174-181
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesTo apply dynamic contrast-enhanced (DCE) MRI on patients presenting with elevated liver enzymes without clinical signs of hepatic decompensation in order to quantitatively compare the hepatocyte-specific uptake of Gd-EOB-DTPA with histopathological fibrosis stage.MethodsA total of 38 patients were prospectively examined using 1.5-T MRI. Data were acquired from regions of interest in the liver and spleen by using time series of single-breath-hold symmetrically sampled two-point Dixon 3D images (non-enhanced, arterial and venous portal phase; 3, 10, 20 and 30 min) following a bolus injection of Gd-EOB-DTPA (0.025 mmol/kg). The signal intensity (SI) values were reconstructed using a phase-sensitive technique and normalised using multiscale adaptive normalising averaging (MANA). Liver-to-spleen contrast ratios (LSC_N) and the contrast uptake rate (KHep) were calculated. Liver biopsy was performed and classified according to the Batts and Ludwig system.ResultsArea under the receiver-operating characteristic curve (AUROC) values of 0.71, 0.80 and 0.78, respectively, were found for KHep, LSC_N10 and LSC_N20 with regard to severe versus mild fibrosis. Significant group differences were found for KHep (borderline), LSC_N10 and LSC_N20.ConclusionsLiver fibrosis stage strongly influences the hepatocyte-specific uptake of Gd-EOB-DTPA. Potentially the normalisation technique and KHep will reduce patient and system bias, yielding a robust approach to non-invasive liver function determination.
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64.
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65.
  • Norén, Bengt, et al. (författare)
  • Visual assessment of biliary excretion of Gd-EOB-DTPA in patients with suspected diffuse liver disease–A biopsy-verified prospective study
  • 2015
  • Ingår i: European Journal of Radiology Open. - : Elsevier BV. - 2352-0477. ; 2, s. 19-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To qualitatively evaluate late dynamic contrast phases, 10, 20 and 30. min, after administration of Gd-EOB-DTPA with regard to biliary excretion in patients presenting with elevated liver enzymes without clinical signs of cirrhosis or hepatic decompensation and to compare the visual assessment of contrast agent excretion with histo-pathological fibrosis stage, contrast uptake parameters and blood tests. Methods: 29 patients were prospectively examined using 1.5T MRI. The visually assessed presence or absence of contrast agent for each of five anatomical regions in randomly reviewed time-series was summarized on a four grade scale for each patient. The scores, including a total visual score, were related to the histo-pathological findings, the quantitative contrast agent uptake parameters, expressed as KHep or LSC_N, and blood tests. Results: No relationship between the fibrosis grade or contrast uptake parameters could be established. A negative correlation between the visual assessment and alkaline phosphatase (ALP) was found. Comparing a sub-group of cholestatic patients with fibrosis score and Gd-EOB-DTPA dynamic parameters did not add any additional significant correlation. Conclusions: No correlation between visually assessed biliary excretion of Gd-EOB-DTPA and histo-pathological or contrast uptake parameters was found. A negative correlation between the visual assessment and alkaline phosphatase (ALP) was found.
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66.
  • Persson, Lennart, et al. (författare)
  • Skeletal Myosteatosis is Associated with Systemic Inflammation and a Loss of Muscle Bioenergetics in Stable COPD
  • 2022
  • Ingår i: Journal of Inflammation Research. - : DOVE MEDICAL PRESS LTD. - 1178-7031. ; 15, s. 4367-4384
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Common features among patients with more advanced chronic obstructive pulmonary disease (COPD) are systemic inflammation and a loss of both muscle mass and normal muscle composition. In the present study, we investigated COPD subjects to better understand how thigh muscle fat infiltration (MFI) and energy metabolism relate to each other and to clinical features of COPD with emphasis on systemic inflammation. Methods: Thirty-two Caucasians with stable COPD were investigated using questionnaires, lung function tests, blood analysis and magnetic resonance imaging (MRI) for analysis of body-and thigh muscle composition. Bioenergetics in the resting thigh muscle, expressed as the PCr/Pi ratio, were analysed using (31)phosphorus magnetic resonance spectroscopy (P-31-MRS). Results: Based on the combination of the MFI adjusted for sex (MFIa) and the thigh fat-tissue free muscle volume, expressed as the deviation from the expected muscle volume of a matched virtual control group (FFMVvcg), all COPD subjects displayed abnormally composed thigh muscles. Clinical features of increased COPD severity, including a decrease of blood oxygenation (r = -0.44, p < 0.05) and FEV1/FVC ratio, reflecting airway obstruction (r = -0.53, p < 0.01) and an increase of COPD symptoms (r = 0.37, p < 0.05) and breathing frequency at rest (r = 0.41, p < 0.05), were all associated with a raise of the PCr/Pi ratio in the thigh muscle. Increased MFIa of the thigh muscle correlated positively with markers of systemic inflammation (white blood cell count, r = 0.41, p < 0.05; fibrinogen, r = 0.44, p < 0.05), and negatively with weekly physical activity (r = -0.40, p < 0.05) and the PCr/Pi ratio in the resting thigh muscle (r = -0.41, p < 0.05). Conclusion: The present study implies a link between systemic inflammation, excessive MFI and a loss of bioenergetics in subjects with stable COPD.
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67.
  • Resman, Fredrik, et al. (författare)
  • Increase of beta-Lactam-Resistant Invasive Haemophilus influenzae in Sweden, 1997 to 2010
  • 2012
  • Ingår i: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 56:8, s. 4408-4415
  • Tidskriftsartikel (refereegranskat)abstract
    • The proportions of Haemophilus influenzae resistant to ampicillin and other beta-lactam antibiotics have been low in Sweden compared to other countries in the Western world. However, a near-doubled proportion of nasopharyngeal Swedish H. influenzae isolates with resistance to beta-lactams has been observed in the last decade. In the present study, the epidemiology and mechanisms of antimicrobial resistance of H. influenzae isolates from blood and cerebrospinal fluid in southern Sweden from 1997 to 2010 (n = 465) were studied. Antimicrobial susceptibility testing was performed using disk diffusion, and isolates with resistance to any tested beta-lactam were further analyzed in detail. We identified a significantly increased (P = 0.03) proportion of beta-lactam-resistant invasive H. influenzae during the study period, which was mainly attributed to a significant recent increase of beta-lactamase-negative beta-lactam-resistant isolates (P = 0.04). Furthermore, invasive beta-lactamase-negative beta-lactam-resistant H. influenzae isolates from 2007 and onwards were found in higher proportions than the corresponding proportions of nasopharyngeal isolates in a national survey. Multiple-locus sequence typing (MIST) of this group of isolates did not completely separate isolates with different resistance phenotypes. However, one cluster of beta-lactamase-negative ampicillin-resistant (BLNAR) isolates was identified, and it included isolates from all geographical areas. A truncated variant of a beta-lactamase gene with a promoter deletion, bla(TEM-1)-P Delta dominated among the beta-lactamase-positive H. influenzae isolates. Our results show that the proportions of beta-lactam-resistant invasive H. influenzae have increased in Sweden in the last decade.
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68.
  • Resman, Fredrik, et al. (författare)
  • Invasive disease caused by Haemophilus influenzae in Sweden 1997-2009; evidence of increasing incidence and clinical burden of non-type b strains
  • 2011
  • Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1469-0691 .- 1198-743X. ; 17:11, s. 1638-1645
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction of a conjugated vaccine against encapsulated Haemophilus influenzae type b (Hib) has led to a dramatic reduction of invasive Hib disease. However, an increasing incidence of invasive disease by H. influenzae non-type b has recently been reported. Non-type b strains have been suggested to be opportunists in an invasive context, but information on clinical consequences and related medical conditions is scarce. In this retrospective study, all H. influenzae isolates (n = 410) from blood and cerebrospinal fluid in three metropolitan Swedish regions between 1997 and 2009 from a population of approximately 3 million individuals were identified. All available isolates were serotyped by PCR (n = 250). We observed a statistically significant increase in the incidence of invasive H. influenzae disease, ascribed to non-typeable H. influenzae (NTHi) and encapsulated strains type f (Hif) in mainly individuals >60 years of age. The medical reports from a subset of 136 cases of invasive Haemophilus disease revealed that 48% of invasive NTHi cases and 59% of invasive Hif cases, respectively, met the criteria of severe sepsis or septic shock according to the ACCP/SCCM classification of sepsis grading. One-fifth of invasive NTHi cases and more than one-third of invasive Hif cases were admitted to intensive care units. Only 37% of patients with invasive non-type b disease had evidence of immunocompromise, of which conditions related to impaired humoral immunity was the most common. The clinical burden of invasive non-type b H. influenzae disease, measured as days of hospitalization/100 000 individuals at risk and year, increased significantly throughout the study period.
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69.
  • Riesbeck, Kristian, et al. (författare)
  • Superinduction of cytokine gene transcription by ciprofloxacin
  • 1994
  • Ingår i: Journal of Immunology. - 0022-1767. ; 153:1, s. 343-352
  • Tidskriftsartikel (refereegranskat)abstract
    • In addition to their antibacterial properties, certain antibiotics are also biologic response modifiers. The fluorinated 4-quinolone, ciprofloxacin, for example, up-regulates IL-2 and IFN-γ production in PBLs stimulated in vitro. In the present study, ciprofloxacin was shown to increase the levels of mRNA for IL-1α, IL-2 and its receptor, IFN-γ, IL-3, IL-4, granulocyte- macrophage/CSF, TNF-α, and lymphotoxin. As investigated with different T cell mitogens and alloantigens, the up-regulation of IL-2 production by ciprofloxacin was found to be independent of the mode of stimulation. Analysis of transcription activity showed that ciprofloxacin enhances IL-2 gene induction. The concentrations of nuclear factor of activated T cells (NF-AT-1) and AP-1 were also found to be increased by ciprofloxacin. Thus, ciprofloxacin interferes with a regulative pathway common to several cytokines.
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70.
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71.
  • Sahlin, Karin, 1991, et al. (författare)
  • Nanocellulose in biocomposites
  • 2016
  • Ingår i: Proc Materials for Tomorrow 2016. ; , s. Nr 41-
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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72.
  • Sahlin, Karin, 1991, et al. (författare)
  • Surface treatment of cellulose nanocrystals (CNC): effects on dispersion rheology
  • 2018
  • Ingår i: Cellulose. - : Springer Science and Business Media LLC. - 0969-0239 .- 1572-882X. ; 25:1, s. 331-345
  • Tidskriftsartikel (refereegranskat)abstract
    • Cellulose nanocrystals (CNC) were surface modified by grafting azetidinium salts onto the sulphate ester groups on the cellulosic surfaces. The modified CNC were characterized using NMR, FTIR spectroscopy, conductometric titration and measurement of the zeta-potential. Thermal gravimetrical analysis revealed that the onset temperature for the thermal degradation was shifted upwards by almost 100 degrees C as a result of the surface grafting. The rheological properties of dispersions based on unmodified and modified CNC were evaluated in detail. Two solids contents were studied; 0.65 and 1.3 wt%. In general, the grafting of the salts significantly increased the shear viscosity at a given shear rate as well as the storage and loss moduli of the dispersions. The CNC concentration at the gel point (network formation) decreased in a corresponding manner when the nanocellulosic particles were surface modified. This may be associated with pronounced hydrophobic attractive interactions between the grafted substituents.
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73.
  • Siddiqui, Mohammad S., et al. (författare)
  • Differential fuel utilization in liver transplant recipients and its relationship with non-alcoholic fatty liver disease
  • 2022
  • Ingår i: Liver international (Print). - : Wiley. - 1478-3223 .- 1478-3231. ; 42:6, s. 1401-1409
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT). Methods Patients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation). Results The two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p < .001), indicative of impaired FA utilization. In subgroup analysis of the NASH cohort, body mass index but not liver fat content (MRI-PDFF) was an independent predictor of fasting RQ. In NASH, fasting RQ inversely correlated with fat-free muscle volume and directly with visceral adipose tissue. Conclusion Reduced metabolic flexibility in patients transplanted for NASH cirrhosis may precede the development of non-alcoholic fatty liver disease after LT.
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74.
  • Siddiqui, Mohammad Shadab, et al. (författare)
  • Saroglitazar improves nonalcoholic fatty liver disease and metabolic health in liver transplant recipients
  • 2023
  • Ingår i: Liver transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1527-6465 .- 1527-6473. ; 29:9, s. 979-986
  • Tidskriftsartikel (refereegranskat)abstract
    • NAFLD is common after liver transplantation (LT) and is associated with an increased metabolic burden. Currently, there is a paucity of investigations into the treatment of post-LT NAFLD. In the present study, we evaluated the safety and efficacy of saroglitazar, a novel dual peroxisome proliferator-associated receptor & alpha;/& gamma; agonist, on the treatment of post-LT NAFLD and metabolic burden. This is a phase 2A, single-center, open-label, single-arm study in which patients with post-LT NAFLD received saroglitazar magnesium 4 mg daily for 24 weeks. NAFLD was defined by a controlled attenuation parameter & GE;264 dB/m. The primary endpoint was the reduction in liver fat as measured by MRI proton density fat fraction (MRI-PDFF). Secondary MRI-based metabolic endpoints included visceral adipose tissue, abdominal subcutaneous adipose tissue volumes, muscle fat infiltration, and fat-free muscle volume. Saroglitazar treatment led to a reduction in MRI-PDFF from 10.3 & PLUSMN;10.5% at baseline to 8.1 & PLUSMN;7.6%. A relative 30% reduction from baseline MRI-PDFF value was noted in 47% of all patients and 63% of patients with baseline MRI-PDFF >5%. Reduction in serum alkaline phosphatase was an independent predictor of MRI-PDFF response. Saroglitazar did not decrease fat-free muscle volume nor increase muscle fat infiltration, but did lead to a mild increase in visceral adipose tissue and abdominal subcutaneous adipose tissue. The study drug was well tolerated and a mild nonsignificant increase in serum creatinine was noted. Saroglitazar did not affect the weight. The study provides preliminary data demonstrating the safety and metabolic benefits of saroglitazar in LT recipients and underscores the importance of future studies to establish its efficacy after LT.
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75.
  • Söderberg, Lina, et al. (författare)
  • Transformation. En del av en skulpturstig i Österbybruk : Modell av en pendel
  • 2019
  • Ingår i: Som en utställning I galleri Sadelmakarlängan I Österbybruk, Uppland. Detta drivs av Katarina Persson som också är projektledare..
  • Konstnärligt arbete (övrigt vetenskapligt/konstnärligt)abstract
    • Katarina Persson har initierat projektet med konstnärsgruppen Transformation som hon tidigare har samarbetat och gjort utställningar med. Jag, Lina Söderberg är medlem i Transformation, och deltagare i detta projekt. Projektet startade i somras med att gruppen träffades i Österbybruk och hade studiebesök och föreläsningar på orten i en vecka. Detta utmynnade i en skissutställning under hösten.
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76.
  • Walter, Susanna A, et al. (författare)
  • Positive Allosteric Modulator of GABA Lowers BOLD Responses in the Cingulate Cortex
  • 2016
  • Ingår i: PLOS ONE. - San Francisco, CA, United States : Public Library of Science. - 1932-6203. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms.
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