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Sökning: WFRF:(Andersson Maria 1976)

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1.
  • Thollander, Patrik, 1976-, et al. (författare)
  • Energinyckeltal och växthusgasutsläpp baserade på industrins energianvändande processer
  • 2021
  • Rapport (refereegranskat)abstract
    • Svensk industri bör strategiskt arbeta mot ökad energi- och resurseffektivitet på en global marknad med knappare resurser. I detta sammanhang spelar beslutsunderlag och nyckeltal en central roll för att nå ökad effektivitet. Även för tillsynsmyndigheter är rättvisande nyckeltal avseende slutenergianvändning av mycket stor vikt för att kunna bedriva ett rättvist förebyggande och proaktivt arbete med svenska företag. De nyckeltal som finns på internationell och nationell nivå är baserade på tillförd energi och ofta relaterade till en ekonomisk output, till exempel förädlingsvärde. Det saknas emellertid nyckeltal kring slutenergianvändningen inom svensk industri fördelat på energibärare såsom el och olja och fördelat på slutenergiprocesser såsom ugnar, tryckluftskompressorer, etc. De siffror som ibland anges är baserade på grova uppskattningar. Projektets mål har därför varit att generera ett processträd avseende flera av de största, till slutenergianvändning räknat, svenska industribranscherna avseende hur slutenergianvändningen är fördelad på processnivå och olika energibärare, samt att allokera växthusgasutsläpp på dessa olika processer. Resultaten indikerar att nyckeltal baserade på energianvändning och indirekta växthusgasutsläpp på processnivå kan bidra till bättre kunskap om i vilka industriella energianvändande processer den största potentialen för energieffektivisering och minskning av växthusgasutsläpp finns. För att upprätthålla kunskap om var den största potentialen för förbättring finns krävs att energidata regelbundet samlas in efter en standardiserad kategorisering av energianvändande processer. Även om projektet har avgränsats till svensk industri kan resultatet vara till nytta också för andra medlemsstater inom EU liksom globalt.
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2.
  • Andersson, Irene, 1978, et al. (författare)
  • Endothelial dysfunction in growth hormone transgenic mice
  • 2006
  • Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 110:2, s. 217-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice. We studied the ACh (acetylcholine)-induced relaxation response in aortic and carotid rings of young (9-11 weeks) and aged (22-24 weeks) female bGH transgenic mice and littermate control mice, without and with the addition of a free radical scavenger {MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride]}. We also measured mRNA levels of eNOS (endothelial nitric oxide synthase) and EC-SOD (extracellular superoxide dismutase). Intracellular superoxide anion production in the vascular wall was estimated using a dihydroethidium probe. Carotid arteries from bGH transgenic mice had an impaired ACh-induced relaxation response (young, 46 +/- 7% compared with 69 +/- 8%; aged, 52 +/- 5% compared with 80 +/- 3%; P < 0.05), whereas endothelial function in aorta was intact in young but impaired in aged bGH transgenic mice. Endothelial dysfunction was corrected by addition of MnTBAP in carotid arteries from young mice and in aortas from aged mice; however, MnTBAP did not correct endothelial dysfunction in carotid arteries from aged bGH transgenic mice. There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P < 0.05). We interpret these data to suggest that bGH overexpression is associated with a time- and vessel-specific deterioration in endothelial function, initially caused by increased oxidative stress and later by other alterations in vascular function.
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3.
  • Andersson, Mattias, 1982, et al. (författare)
  • Dielectric loss determination of fine residual waste electrical and electronic equipment for understanding of heat development during microwave pyrolysis
  • 2013
  • Ingår i: Journal of Analytical and Applied Pyrolysis. - : Elsevier BV. - 0165-2370. ; 103, s. 142-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Waste electrical and electronic equipment (WEEE) contains rare and valuable metals which are important to recycle, but it also has high organic content. The conventional methods used today for treatment of WEEE cannot recycle 100%; they generate valuable fine residual fractions. For further processing of these residues, microwave pyrolysis has shown to be promising since it reduces the organic content and liberate enclosed metal pieces. However, to fully control the process, the dielectric properties of the materials need to be known but are difficult to determine due to the complex composition and structure of WEEE. This paper aims to describe a suitable procedure for determination of dielectric loss in six WEEE residual fine fractions and to correlate the results to heating behaviour during microwave pyrolysis. Three fractions are "dusts" (light, medium and heavy dust) and three fractions are called "particulate materials" and contain smaller particles (0-7 mm, 0-20 mm and 7-12 mm). The method chosen was Vector Network Analyzer (VNA) using waveguide WR430 equipped with polymer foam to contain the samples which consisted of 1 dl of WEEE fine fraction. The scattering parameters were measured and dielectric loss in the materials was calculated. The measurements were performed in frequency region 1.3-2.7 GHz to include the industrial frequency 2.45 GHz. Differences between dielectric losses for the materials were determined by ANOVA. It was shown that the scattering parameter measurements were rather stable for the dust materials and the losses could be determined. For the larger sized particulate materials a lot of reflection was observed during the measurements, due to fine metal wires in the material. The losses could be determined after removing these wires. The previously observed higher heating rate and shorter time for mass reduction of dusts could not be explained by differences in dielectric loss. However, since VNA measurements indicate that metal wires in the material disturb the field; presence of wires in the particulate materials might be one cause for slower heating rate and observed temperature drops during pyrolysis.
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4.
  • Andersson, Maria L.E., et al. (författare)
  • Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis
  • 2023
  • Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:7, s. 1110-1119
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints.Methods. We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead-based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n = 2,110), Swedish age- and sex-matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE).Results. Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98-100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19-26%) of early RA patients seronegative for anti-cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE.Conclusion. A multiplex immunoassay with peptides from disease-related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA.
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5.
  • Kalaitzakis, Evangelos, 1976, et al. (författare)
  • Factors related to fatigue in patients with cirrhosis before and after liver transplantation.
  • 2012
  • Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed a prospective study to evaluate fatigue and identify potential determinants among patients with cirrhosis. We also studied the effects of liver transplantation on fatigue in these patients.
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6.
  • Kalaitzakis, Evangelos, 1976, et al. (författare)
  • Hepatic encephalopathy is related to anemia and fat-free mass depletion in liver transplant candidates with cirrhosis.
  • 2013
  • Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 48:5, s. 577-584
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Background. Although muscle wasting may lead to decreased ammonia detoxification in cirrhosis, the potential role of lean mass depletion in hepatic encephalopathy (HE) has not been explored. Anemia, hormonal abnormalities, and psychological distress may contribute to cognitive dysfunction, but data on their potential relation to HE are limited. Methods. Data on 108 cirrhotic liver transplant candidates enrolled in a prospective study on fatigue were retrospectively analyzed. HE was assessed clinically and with the number connection tests (NCT) A and B. Psychosocial distress was assessed with a validated questionnaire. Fasting serum glucose, insulin, ammonia, and the glomerular filtration rate (GFR) were measured. Fat and fat-free mass was evaluated with dual-energy X-ray absorptiometry. Serum cortisol, testosterone, dehydroepiandrosterone, thyroid function tests, interleukin-6, and tumor necrosis factor-α (TNF-α) were measured in a subgroup of 80 patients. Results. A total of 28% of patients had (overt or minimal) HE. Anemia was present in 59%, diabetes in 29%, renal impairment in 16%, and fat-free mass depletion in 14%. In multivariate analysis, fat-free mass depletion was an independent predictor of HE and NCT-A; renal impairment of NCT-A and -B; and anemia of NCT-B (p < 0.05 for all). HE was also independently related to international normalized ratio and TNF-α (p < 0.05 for both), but not to other hormonal abnormalities or psychological distress. Plasma ammonia was independently associated to anemia (beta = 15.24, p = 0.049), fasting insulin (beta = 0.26, p < 0.05), and GFR (beta = -0.43, p = 0.003). Conclusions. Anemia and fat-free mass depletion are predictors of HE in cirrhotic liver transplant candidates along with liver failure, renal impairment, and systemic inflammation.
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7.
  • Pirazzi, Carlo, et al. (författare)
  • Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) affects hepatic VLDL secretion in humans and in vitro
  • 2012
  • Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 57:6, s. 1276-1282
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: The robust association between non-alcoholic fatty liver disease (NAFLD) and the genetic variant I148M (rs738409) in PNPLA3 has been widely replicated. The aim of this study was to investigate the effect of the PNPLA3 I148M mutation on: (1) hepatic secretion of very low density lipoproteins (VLDL) in humans; and (2) secretion of apolipoprotein B (apoB) from McA-RH 7777 cells, which secrete VLDL-sized apoB-containing lipoproteins. Methods: VLDL kinetics was analyzed after a bolus infusion of stable isotopes in 55 overweight/obese men genotyped for the PNPLA3 I148M variant. Intracellular lipid content, apoB secretion and glycerolipid metabolism were studied in McA-RH 7777 cells overexpressing the human 1481 wild type or 148M mutant PNPLA3 protein. Results: In humans, carriers of the PNPLA3 148M allele had increased liver fat compared to 1481 homozygotes, and kinetic analysis showed a relatively lower secretion of the large, triglyceride-rich VLDL (VLDL1) in 148M carriers vs. 1481 homozygotes for the same amount of liver fat. McA-RH 7777 cells overexpressing the 148M mutant protein showed a higher intracellular triglyceride content with a lower apoB secretion and fatty acid efflux, compared to cells overexpressing the 1481 wild type protein. The responses with 148M matched those observed in cells expressing the empty vector, indicating that the mutation results in loss of function. Conclusions: We have shown that PNPLA3 affects the secretion of apoB-containing lipoproteins both in humans and in vitro and that the 148M protein is a loss-of-function mutation. We propose that PNPLA3 148M promotes intracellular lipid accumulation in the liver by reducing the lipidation of VLDL.
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8.
  • Pirazzi, Carlo, et al. (författare)
  • PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:15, s. 4077-4085
  • Tidskriftsartikel (refereegranskat)abstract
    • Retinoids are micronutrients that are stored as retinyl esters in the retina and hepatic stellate cells (HSCs). HSCs are key players in fibrogenesis in chronic liver diseases. The enzyme responsible for hydrolysis and release of retinyl esters from HSCs is unknown and the relationship between retinoid metabolism and liver disease remains unclear. We hypothesize that the patatin-like phospholipase domain-containing 3 (PNPLA3) protein is involved in retinol metabolism in HSCs. We tested our hypothesis both in primary human HSCs and in a human cohort of subjects with non-alcoholic fatty liver disease (N = 146). Here we show that PNPLA3 is highly expressed in human HSCs. Its expression is regulated by retinol availability and insulin, and increased PNPLA3 expression results in reduced lipid droplet content. PNPLA3 promotes extracellular release of retinol from HSCs in response to insulin. We also show that purified wild-type PNPLA3 hydrolyzes retinyl palmitate into retinol and palmitic acid. Conversely, this enzymatic activity is markedly reduced with purified PNPLA3 148M, a common mutation robustly associated with liver fibrosis and hepatocellular carcinoma development. We also find the PNPLA3 I148M genotype to be an independent (P = 0.009 in a multivariate analysis) determinant of circulating retinol-binding protein 4, a reliable proxy for retinol levels in humans. This study identifies PNPLA3 as a lipase responsible for retinyl-palmitate hydrolysis in HSCs in humans. Importantly, this indicates a potential novel link between HSCs, retinoid metabolism and PNPLA3 in determining the susceptibility to chronic liver disease.
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10.
  • Ringlander, Johan, et al. (författare)
  • Deep sequencing of liver explant transcriptomes reveals extensive expression from integrated hepatitis B virus DNA
  • 2020
  • Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 27:11, s. 1162-1170
  • Tidskriftsartikel (refereegranskat)abstract
    • Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). Integration of HBV DNA into the human genome may contribute to oncogenesis and to the production of the hepatitis B surface antigen (HBsAg). Whether integrations contribute to HBsAg levels in the blood is poorly known. Here, we characterize the HBV RNA profile of HBV integrations in liver tissue in patients with chronic HBV infection, with or without concurrent hepatitis D infection, by transcriptome deep sequencing. Transcriptomes were determined in liver tissue by deep sequencing providing 200 million reads per sample. Integration points were identified using a bioinformatic pipeline. Explanted liver tissue from five patients with end-stage liver disease caused by HBV or HBV/HDV was studied along with publicly available transcriptomes from 21 patients. Almost all HBV RNA profiles were devoid of reads in the core and the 3 ' redundancy (nt 1830-1927) regions, and contained a large number of chimeric viral/human reads. Hence, HBV transcripts from integrated HBV DNA rather than from covalently closed circular HBV DNA (cccDNA) predominated in late-stage HBV infection, in particular in cases with hepatitis D virus co-infection. The findings support the suggestion that integrated HBV DNA can be a significant source of HBsAg in humans.
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11.
  • Ringlander, Johan, et al. (författare)
  • Enrichment Reveals Extensive Integration of Hepatitis B Virus DNA in Hepatitis Delta Virus-Infected Patients
  • 2024
  • Ingår i: JOURNAL OF INFECTIOUS DISEASES. - 0022-1899 .- 1537-6613.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Hepatitis B virus (HBV) DNA may become integrated into the human genome of infected human hepatocytes. Expression of integrations can produce the surface antigen (HBsAg) that is required for synthesis of hepatitis D virus (HDV) particles and the abundant subviral particles in the blood of HBV- and HDV-infected subjects. Knowledge about the extent and variation of HBV integrations and impact on chronic HDV is still limited. Methods. We investigated 50 pieces of liver explant tissue from 5 patients with hepatitis D-induced cirrhosis, using a deep-sequencing strategy targeting HBV RNA. Results. We found that integrations were abundant and highly expressed, with large variation in the number of integration-derived (HBV/human chimeric) reads, both between and within patients. The median number of unique integrations for each patient correlated with serum levels of HBsAg. However, most of the HBV reads represented a few predominant integrations. Conclusions. The results suggest that HBV DNA integrates in a large proportion of hepatocytes, and that the HBsAg output from these integrations vary >100-fold depending on clone size and expression rate. A small proportion of the integrations seems to determine the serum levels of HBsAg and HDV RNA in HBV/HDV coinfected patients with liver cirrhosis.
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12.
  • Ringlander, Johan, et al. (författare)
  • Hepatitis B virus particles in serum contain minus strand DNA and degraded pregenomic RNA of variable and inverse lengths
  • 2024
  • Ingår i: LIVER INTERNATIONAL. - 1478-3223 .- 1478-3231.
  • Tidskriftsartikel (refereegranskat)abstract
    • This study utilized digital PCR to quantify HBV RNA and HBV DNA within three regions of the HBV genome. Analysis of 75 serum samples from patients with chronic infection showed that HBV RNA levels were higher in core than in S and X regions (median 7.20 vs. 6.80 and 6.58 log copies/mL; p < .0001), whereas HBV DNA levels showed an inverse gradient (7.71 vs. 7.73 and 7.77 log copies/mL, p < .001). On average 80% of the nucleic acid was DNA by quantification in core. The core DNA/RNA ratio was associated with viral load and genotype. In individual patients, the relations between RNA levels in core, S and X were stable over time (n = 29; p = .006). The results suggest that pregenomic RNA is completely reverse transcribed to minus DNA in approximate to 75% of the virus particles, whereas the remaining 25% contain both RNA and DNA of lengths that reflect variable progress of the polymerase.
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13.
  • Sansone, Martina, et al. (författare)
  • Extensive Hospital In-Ward Clustering Revealed By Molecular Characterization of Influenza A Virus Infection.
  • 2020
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 71:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Nosocomial transmission of influenza A virus (InfA) infection is not fully recognized. The aim of this study was to describe the characteristics of hospitalized patients with InfA infections during an entire season and to investigate in-ward transmission at a large, acute-care hospital.During the 2016-17 season, all hospitalized patients≥18 years old with laboratory-verified (real-time polymerase chain reaction) InfA were identified. Cases were characterized according to age; sex; comorbidity; antiviral therapy; viral load, expressed as cycle threshold values; length of hospital stay; 30-day mortality; and whether the InfA infection met criteria for a health care-associated influenza A infection (HCAI). Respiratory samples positive for InfA that were collected at the same wards within 7 days were chosen for whole-genome sequencing (WGS) and a phylogenetic analysis was performed to detect clustering. For reference, concurrent InfA strains from patients with community-acquired infection were included.We identified a total of 435 InfA cases, of which 114 (26%) met the HCAI criteria. The overall 30-day mortality rate was higher among patients with HCAI (9.6% vs 4.6% among non-HCAI patients), although the difference was not statistically significant in a multivariable analysis, where age was the only independent risk factor for death (P<.05). We identified 8 closely related clusters (involving≥3 cases) and another 10 pairs of strains, supporting in-ward transmission.We found that the in-ward transmission of InfA occurs frequently and that HCAI may have severe outcomes. WGS may be used for outbreak investigations, as well as for evaluations of the effects of preventive measures.
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14.
  • Sundberg, Jonas, et al. (författare)
  • High-risk human papillomavirus in patients with oral leukoplakia and oral squamous cell carcinoma-A multi-centre study in Sweden, Brazil and Romania.
  • 2021
  • Ingår i: Oral Diseases. - : Wiley. - 1354-523X .- 1601-0825. ; 27:2, s. 183-192
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Although causal associations between oral leukoplakia (OL), oral squamous cell carcinoma (OSCC) and high-risk human papillomavirus (HR-HPV) have been speculated upon in several reports, conclusive evidence has not been presented. This study investigates whether the number of cases of HR-HPV in OL has increased over time and whether the prevalence of HR-HPV-positive OL differs in various parts of the world.PATIENTS AND METHODS: A total of 432 patients with OL from Sweden, Brazil and Romania were analysed. Patients were divided into historical (1992-2002) and contemporary (2011-2017) cohorts from the respective countries. Seventeen patients with OL developed oral squamous cell carcinoma (OSCC). A real-time PCR assay, targeting HPV sub-types 6,11,16,18,31,33,35,39,45,52,56,58 and 59, was performed to detect HR-HPV in patients with OL.RESULTS: In the Swedish and Romanian cohorts, none of the investigated HPV sub-types were detected. In the Brazilian cohorts, five patients with OL (3%) were positive for HR-HPV, including four patients from the contemporary cohort (HPV 16, 31, 33) and one from the historical cohort (HPV 11). All the cases of OL that transformed into OSCC were HR-HPV-negative, as were the corresponding tumours.CONCLUSIONS: In summary, the prevalence of HR-HPV in OL is low in all the tested countries, and the incidence has not changed over time. HR-HPV in OL does not seem to be a driver of oncogenesis.
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16.
  • Andersson, Dennis, et al. (författare)
  • Västlänken – en fråga om förtroende
  • 2018
  • Ingår i: Hemma Väst. - Göteborg : SOM-institutet, Göteborgs universitet. - 0284-4788. ; , s. 129-144
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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17.
  • Andersson, Gerhard, et al. (författare)
  • Therapeutic alliance in guided internet-delivered cognitive behavioural treatment of depression, generalized anxiety disorder and social anxiety disorder
  • 2012
  • Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 50:9, s. 544-550
  • Tidskriftsartikel (refereegranskat)abstract
    • Guided internet-delivered cognitive behaviour therapy (ICBT) has been found to be effective in several controlled trials, but the mechanisms of change are largely unknown. Therapeutic alliance is a factor that has been studied in many psychotherapy trials, but the role of therapeutic alliance in ICBT is less well known. The present study investigated early alliance ratings in three separate samples. Participants from one sample of depressed individuals (N = 49), one sample of individuals with generalized anxiety disorder (N = 35), and one sample with social anxiety disorder (N = 90) completed the Working Alliance Inventory (WAI) modified for ICBT early in the treatment (weeks 3-4) when they took part in guided ICBT for their conditions. Results showed that alliance ratings were high in all three samples and that the WAI including the subscales of Task, Goal and Bond had high internal consistencies. Overall, correlations between the WAI and residualized change scores on the primary outcome measures were small and not statistically significant. We conclude that even if alliance ratings are in line with face-to-face studies, therapeutic alliance as measured by the WAI is probably less important in ICBT than in regular face-to-face psychotherapy.
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18.
  • Andersson, Maria, 1976- (författare)
  • Chemically Induced DNA Damage in Extended-term Cultures of Human Lymphocytes
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Generation of DNA damage is regarded to be an important initial event in the development cancer. Consequently, a battery of tests have been developed to detect different types of genotoxic effects in order to be able to predict the potential genotoxicity and mutagenicity of chemicals, including both pharmaceutical drugs and various types of environmental and occupational agents, as well as dietary factors. The aim of this thesis was to evaluate whether the combination of the comet assay and the extended-term cultures of human lymphocytes (ETC) can be used as an alternative in vitro system to more commonly used transformed mammalian cell lines, and primary cell cultures from humans, when testing the potential genotoxicity of chemicals. Using the comet assay, a panel of reference compounds showed that the ETC were found to detect the DNA-damaging effects with no remarkable difference to what has been reported in other cell types. Moreover, in comparison with a well-established rodent cell line, the mouse lymphoma L5178Y cells, the ETC showed similar sensitivity to the DNA damaging effects of the genotoxic agents hydrogen peroxide and catechol. Although there was an interindividual variation in induced DNA damage and the subsequent repair when using ETC from different blood donors, it did not seem to be of crucial importance for the identification of DNA-damaging agents. The demonstrated difference in sensitivity to catechol-induced DNA damage between freshly isolated peripheral lymphocytes and ETC may very well be due to their different proliferative status but despite this difference, both in vitro systems were able to identify catechol as a DNA-damaging agent at the same concentration.Based on these results, it is proposed that the ETC and the comet assay are a useful combination when testing for the potential DNA damaging effects of chemicals. Representing easily cultivated cells possessing the normal human karyotype, where one blood sample can be used for numerous experiments performed over a long time, extended-term cultures appear to be a useful alternative, both to transformed mammalian cell lines, and primary cell cultures from humans. In fact, the extended-term lymphocytes, with or without S9 and/or lesion specific DNA repair enzymes, should be used more frequently when screening for the potential genotoxicity of chemicals.
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19.
  • Andersson, Maria, 1976- (författare)
  • Digital images as part of an implementation process : patterns in digital representations of community mental health service providers
  • 2014
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Systems for freedom of choice have been implemented as an organizational structure in public welfare in several western countries. The aim of the market model is to increase citizens’ freedom of choice, conduce diversification in service and providers of service, while contribute higher quality of service and facilitate efficient use of public funds. In Sweden “Act of Free Choice Systems” (2008:962) was introduced in 2009, and optional for municipalities to use. Several municipalities have opened up for both public and non-public providers for citizens’ to choose from in different welfare sectors. Mental health care was one of them. The implemented competitive market logic meant providers needed to promote themselves to attract users to be able to stay on the market.Aim: The aim of this study is to describe and analyse how public and non-public providers’ of community mental health care use digital pictures during the time of an implementation of a competitive market system in Sweden.Methods: A case study was conducted. A municipality was strategically selected because a free choice system was implemented in their community mental health care in 2010. Day centres, a common community mental health care support was selected to constitute the focus of the study. All providers had a digital space of their own at the municipality’s website. Digital pictures from each homepage were collected in 2012, when the new system had been running for a while. All pictures were included in the study. Pictures were transcribed using the semiotic model. Transcribed data was analysed with content analyse and categorized into themes. A frequency analysis was conducted to show similarities and differences in content.Results: Homepages showed between 0 and 88 digital pictures. Public providers displayed less pictures than non-public providers. The content analyse identified three main categories: 1. Presenting pictures 2. Illustrative pictures 3. Emotional intermediating pictures. The frequency analyse showed three main recurring contents: pastries (10 providers), flowers and trees (10 providers) and the building’s exterior (9 providers). Distinguishing pictures were; mountain climber (one provider), dogs at the Coffey table (two providers). Analyse/Discussion: Digital pictures seemed to fulfil different purposes; to present activities such as buildings and persons, to illustrate text and to convey feelings of growth, inclusion, participation and friendship. The most recurring picture content was interpreted as follows: pastries, as appealing to the sense of sweetness, something tasting good, homely, attractive; flowers and trees as appealing to growth, literal and symbolic; building’s exterior as representing the place physically. Mountain climber pictures were interpreted as appealing to adventure and excitement, dogs at the Coffey table as appealing to a wish for non-demanding fellowship, a wish for pets.Conclusion: Most providers used digital pictures in their promotion of themselves. Pictures were used in different ways and with different intentions. Non-public providers displayed more pictures than public providers. This might implicate non-public providers were more adjusted to the new competitive system where promotion was part of the game.
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20.
  • Andersson, Maria, 1976-, et al. (författare)
  • Extended freedom attained? : A case study of a free-choice market system in community mental health care.
  • 2013
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Background/Objectives Systems for freedom of choice within mental health has been implemented in several western countries to increase citizens’ freedom of choice, conduce diversification in service and providers of service, reduce inequalities by providing equitable choice to all users while contribute higher quality of service and facilitate efficient use of public funds. In Sweden “Act of Free Choice Systems” (2008:962) was introduced in 2009, and optional for municipalities to use. Community mental health is organized within the municipalities. The aim of this study is to describe the process of designing and constructing a market of free choice within community mental health, and analyse what kind of freedom of choice the citizen in need of community mental health have, in the example of Daily occupation.Methods A case study was conducted in Stockholm, the capital of Sweden, where free choice was implemented in January 2010. The study consists of semi-structured interviews with twenty-eight actors’ involved in the process, complemented with political documents. Interviews were conducted 2009 and 2012. To analyse the material direct content analysis was used, and theories regarding quasi-markets, market design and regulation of markets were applied.Results The design and construction of the market of community mental health have determined the degree of clients’ freedom of choice. The volume of the market was regulated by national legislation, but sometimes influenced by the local political budget, and users sometimes appealed their decisions in court to have their rights assessed by law. Admission rules set by authorities concerning management and staff qualifications, financial stability and technical documentation equipment, determined which providers could enter the market. Many user-led organisations were not able to enter due to the admission rules. Quality regulation was developed by authorities to examine providers within the system. The client should be provided neutral and rich information, though full information was hard to access.Discussion/Conclusion Freedom of choice seems to have been both extended and reduced by the design and construction of the new system. All users theoretically had the same possibilities to choose providers in the system. However the construction limited the actual client choice significantly.
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21.
  • Andersson, Mathias H, 1976-, et al. (författare)
  • Importance of Using Multiple Sampling Methodologies for Estimating of Fish Community Composition in Offshore Wind Power Construction Areas of the Baltic Sea
  • 2007
  • Ingår i: Ambio. - 0044-7447 .- 1654-7209. ; 36:8, s. 634-636
  • Tidskriftsartikel (refereegranskat)abstract
    • It is standard procedure that an Environmental Impact Assessment (EIA) is conducted before larger constructions are built. To adequately describe the impact, methods used in an EIA should be carefully adapted considering both the character of the constructions under development and the environment that will be affected. Various sampling techniques are applied to estimate fish abundances and species composition. Methods used, including trawling, seine and gill netting, angling, echo-sound sampling, fishery data, video recordings, dredging, and visual counts using SCUBA, will all give different estimates of fish community composition.
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22.
  • Andersson, Maria, 1976, et al. (författare)
  • Mild renal ischemia-reperfusion reduces charge and size selectivity of the glomerular barrier
  • 2007
  • Ingår i: American Journal of Physiology Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1931-857X .- 1522-1466. ; 292:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite recent discoveries of molecules in podocytes, the mechanisms behind most conditions of proteinuria are still poorly understood. To understand more about this delicate barrier, we studied the functional and morphological effects of mild (15 min) renal ischemia-reperfusion injury (IRI). Renal function was studied in rats in vivo, followed by a more detailed analysis of the glomerular barrier in cooled (8 degrees C) isolated perfused kidneys (cIPK). Renal blood flow was quickly restored, whereas the glomerular filtration rate remained halved 30 min after IRI. Tubular cell activity was intact as judged from the unaffected Cr-EDTA U/P concentration ratio. In vivo, the fractional clearance (theta) for albumin increased 16 times. In rats subjected to cIPK starting 30 min after in vivo IRI, theta(albumin) was 15 times and theta(Ficoll_36angstroms) 1.8 times higher than in control cIPKs. According to the heterogeneous charged fiber model, IRI reduced the fiber charge density to 38% of control (P < 0.01, n = 7). Morphometric analysis with electron microscopy did not reveal any changes in the podocytes or the glomerular basement membrane (GBM) after IRI, suggesting more subtle changes of the GBM and/or the endothelial glycocalyx. We conclude that mild renal IRI induces formation of reactive oxygen species, massive proteinuria, and loss of charged fibers with no apparent change in morphology. These novel findings stress the importance of other components of the barrier, such as proteoglycans produced by the glomerular cells, and provide a tentative explanation for the mechanisms behind proteinuria in glomerulonephritis, for example.
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23.
  • Andersson, Maria, 1976, et al. (författare)
  • Rotavirus genotype shifts among Swedish children and adults—Application of a real-time PCR genotyping
  • 2017
  • Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 96, s. 1-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background It is well known that human rotavirus group A is the most important cause of severe diarrhoea in infants and young children. Less is known about rotavirus infections in other age groups, and about how rotavirus genotypes change over time in different age groups. Objectives Develop a real-time PCR to easily genotype rotavirus strains in order to monitor the pattern of circulating genotypes. Study design In this study, rotavirus strains in clinical samples from children and adults in Western Sweden during 2010–2014 were retrospectively genotyped by using specific amplification of VP 4 and VP 7 genes with a new developed real-rime PCR. Results A genotype was identified in 97% of 775 rotavirus strains. G1P[8] was the most common genotype representing 34.9%, followed by G2P[4] (28.3%), G9P[8] (11.5%), G3P[8] (8.1%), and G4P[8] (7.9%) The genotype distribution changed over time, from predominance of G1P[8] in 2010–2012 to predominance of G2P[4] in 2013–2014. There were also age-related differences, with G1P[8] being the most common genotype in children under 2 years (47.6%), and G2P[4] the most common in those over 70 years of age (46.1%.). The shift to G2P[4] in 2013–2014 was associated with a change in the age distribution, with a greater number of rotavirus positive cases in elderly than in children. Conclusions By using a new real-time PCR method for genotyping we found that genotype distribution was age related and changed over time with a decreasing proportion of G1P[8]. © 2017
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24.
  • Andersson, Maria, 1976-, et al. (författare)
  • The implementation of a Free-choice Market System in Swedish Community Mental Health Services by the Example of Day Centres
  • 2014
  • Ingår i: Jubilee Congress 50 years WASP World Association of Social Psychiatry, London, November 13-15, 2014..
  • Konferensbidrag (refereegranskat)abstract
    • Marketization in community mental health services is a new phenomenon and might be the most comprehensive reform in the field since the deinstitutionalisation that occurred during the second half of the twentieth century. Historically, mental health services have been characterized by discipline and paternalistic practices.There has been an absence ofwhat is now, due to the new organizational model based on individual freedom of choice, is to be introduced. The aim of this study was to investigate the implementation of a free-choice market system in community mental health services, using the example of day centres for people with psychiatric disabilities. The study was conducted in a major city that was about to implement a free-choice market system due to a new legislation. Eighteen semi-structured interviews were conducted. Agents situated in different parts of the organization were interviewed one year before and two years after the free-choice system was launched in 2010. Data showed a top-down political process. The policy intentions of the new Act were in focus when studying the relation between policy and practice during the implementation process. A majority of the policy intentions of the new Act advocated individual autonomy as the market system’s main purpose, only one intention concerned organizational efficiency. Interview data reflected, however, that financial efficiency dominated the agents’ experiences of the implemented system. The twofold market purpose was clearly reflected in the interviews. Front-line staff hoped for improvements mainly for the users, when managers mainly focused on the market as a resource allocator.
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25.
  • Andresen Bergström, Moa, 1978, et al. (författare)
  • Detection of drugs and hepatitis C virus in used syringes from a needle exchange in Gothenburg, Sweden
  • 2023
  • Ingår i: Drug Testing and Analysis. - 1942-7603 .- 1942-7611.
  • Tidskriftsartikel (refereegranskat)abstract
    • People who inject drugs (PWID) are exposed to serious health risks such as lethal overdoses, addiction and infections. The patterns of drug use and the prevalence of hepatitis C virus (HCV) infection vary greatly between and even within countries. Data on drugs used for injection are important to inform PWID of risks and adapt healthcare. This study aimed to determine which substances are injected in Gothenburg, Sweden, and estimate the risk of HCV transmission. A total of 150 syringes handed in at the needle and syringe exchange program (NEP) in Gothenburg over a week in November 2021 were analysed for drug content using liquid chromatography coupled with high-resolution mass spectrometry. Using a dose-adjusted comparison, the main drug(s) injected was distinguished from the impurities in the syringes containing several drugs. HCV RNA was quantified by real-time PCR in an additional set of 150 syringes. Drugs were detected in >99% of analysed syringes, and the most common drugs were amphetamine (81%), followed by buprenorphine (8.0%), heroin (6.7%) and alprazolam (4.6%). Less common findings were testosterone (2.7%), methylphenidate (2.0%), MDMA (0.7%), trenbolone (0.7%) and zopiclone (0.7%). Eleven syringes (7.3%) contained more than one drug. HCV RNA was detected in 13% of the syringes, and one in 10 contained enough to potentially transmit an infection. This study underlines the importance of access to NEPs for PWID to reduce the risks associated with drug injection.
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26.
  • Argyri, Smaragda Maria, 1994, et al. (författare)
  • Customized and high-performing acoustic levitators for contact-free experiments
  • 2024
  • Ingår i: Journal of Science: Advanced Materials and Devices. - 2468-2284 .- 2468-2179. ; 9:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Acoustic levitators are becoming an increasingly common research instrumentation for contact-free, lab-in-a-droplet studies. Recently, levitators that employ multiple, small, ultrasonic transducers have gained popularity, given their low price, temperature and spatial stability, low voltage, and accessibility. Yet, the current state-of-the-art device, TinyLev, presents limitations for certain applications in terms of stability, strength, and compactness. Herein, we developed three new levitators and evaluated the effect of the construction parameters (e.g., distance of opposing arrays, number and arrangement of transducers, etc.) on their performance. Compared to TinyLev, the best performing levitator from this work had half the number of transducers while presenting 1.7 and 3.5 times higher levitation capacity along the horizontal and vertical configurations, respectively, while the horizontal and vertical stability of a levitated object was improved 4.7 and 2.0 times, respectively. Additionally, we present a direct means to evaluate the acoustic radiation net force acting on a deformable object for uniaxial levitators, without the use of a microphone or a schlieren deflectometer for this type of levitators. The theoretical and experimental observations provide insights for adapting the acoustic levitator design for specific applications. Finally, we developed an open-source software which allows the evaluation of the acoustic pressure field generated by customized designs and provides the necessary files for 3D printing the scaffold of the levitator. This study aims to increase accessibility and promote further developments in contact-free experiments.
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27.
  • Billingsley, Sunnee, 1976-, et al. (författare)
  • COVID-19 mortality across occupations and secondary risks for elderly individuals in the household : A population register-based study
  • 2022
  • Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 48:1, s. 52-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives This is the first population-level study to examine inequalities in COVID-19 mortality according to working-age individuals' occupations and the indirect occupational effects on COVID-19 mortality of older individuals who live with them.Methods We used early-release data for the entire population of Sweden of all recorded COVID-19 deaths from 12 March 2020 to 23 February 2021, which we linked to administrative registers and occupational measures. Cox proportional hazard models assessed relative risks of COVID-19 mortality for the working-aged population registered in an occupation in December 2018 and the older population who lived with them.Results Among working aged-adults, taxi/bus drivers had the highest relative risk of COVID-19 mortality: over four times that of skilled workers in IT, economics, or administration when adjusted only for basic demographic characteristics. After adjusting for socioeconomic factors (education, income and country of birth), there are no occupational groups with clearly elevated (statistically significant) COVID-19 mortality. Neither a measure of exposure within occupations nor the share that generally can work from home were related to working-aged adults' risk of COVID-19 mortality. Instead of occupational factors, traditional socioeconomic risk factors best explained variation in COVID-19 mortality. Elderly individuals, however, faced higher COVID-19 mortality risk both when living with a delivery or postal worker or worker(s) in occupations that generally work from home less, even when their socioeconomic factors are taken into account.Conclusions Inequalities in COVID-19 mortality of working-aged adults were mostly based on traditional risk factors and not on occupational divisions or characteristics in Sweden. However, older individuals living with those who likely cannot work from home or work in delivery or postal services were a vulnerable group.
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28.
  • Claeson, Magdalena, 1976, et al. (författare)
  • Incidence of cutaneous melanoma in Western Sweden, 1970-2007.
  • 2012
  • Ingår i: Melanoma research. - 1473-5636. ; 22:5, s. 392-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to describe the increasing incidence of cutaneous malignant melanoma (CMM) in Western Sweden during the period 1970-2007. A secondary aim was to show a geographical variation in incidence between coastal and inland areas, considering the effects of the local average duration of sunshine, and the sun exposure-related behavior in the populations. The Swedish Cancer Registry provided data on invasive melanomas during 1970-2007. Meteorological maps showed the annual average duration of sunshine during 1961-1990. A survey from 2007 with 2871 participants, carried out by the National Board of Health and Welfare, provided data on self-reported sun exposure. During the period studied, the age-standardized incidence for men in Western Sweden more than quadrupled to 31.1/100 000 inhabitants, whereas it tripled for women to 27.1/100 000. Coastal areas, including Gothenburg city, had a high average duration of sunshine (1701-1900 h of sun/year), whereas inland areas had lower average duration of sunshine (≤1700 h). The incidence of CMM was higher in coastal areas and in Gothenburg city, compared with inland areas. This may be linked to ultraviolet radiation, a consequence of the higher average duration of sunshine. The sun exposure survey showed additional factors, which possibly led to the increased incidence, for example high sun exposure on holidays abroad. The alarming increase in the incidence of CMM in Western Sweden, during the period 1970-2007, shows the need for additional primary preventive measures, for example sun protection programs targeted at populations in this area.
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29.
  • Claesson, Maria, 1985, et al. (författare)
  • Improved QCM-D signal-to-noise ratio using mesoporous silica and titania
  • 2012
  • Ingår i: Sensors and Actuators, B: Chemical. - : Elsevier BV. - 0925-4005. ; 166, s. 526-534
  • Tidskriftsartikel (refereegranskat)abstract
    • In many biological and environmental applications it is crucial to detect low concentrations of low molecular weight analytes. To accomplish this a variety of surface sensing techniques, such as quartz crystal microbalance with dissipation monitoring (QCM-D) and surface plasmon resonance (SPR), have been developed. These techniques provide good sensitivity and selectivity, however, there is a need to improve these even further by enhancing the signal-to-noise ratio. One suggestion to improve the QCM-D signal is to use mesoporous coated QCM-D sensor crystals as sensing substrate. Mesoporous materials are promising to use, since they possess a high specific surface area and that their properties, such as pore size, pore geometry and surface chemistry, can be controlled. Here we demonstrate a method to increase the signal-to-noise ratio of the QCM-D signal illustrated by adsorbing dendrimers on mesoporous silica and titania coated QCM-D crystals. The experiments were performed on cubic mesoporous silica having varying pore sizes and hexagonal and cubic mesoporous titania having similar pore size. The results showed that the QCM-D signal-to-noise was improved when mesoporous material was used and that the pore size and pore geometry determined the selectivity of the adsorbing analyte. These findings are important in the detection of analytes at low concentrations using QCM-D.
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30.
  • Eilard, Anders, et al. (författare)
  • Occult hepatitis B infection in children born to HBeAg-positive women confers a low long-term risk for HBsAg-positive infection
  • 2024
  • Ingår i: INFECTION. - 0300-8126 .- 1439-0973.
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Mother-to-child transmission (MTCT) has been the main cause of chronic hepatitis B virus (HBV) infection, particularly in East Asia. Hepatitis B immunoglobulin (HBIG) and vaccination given directly after birth effectively prevents hepatitis B surface antigen (HBsAg)-positive (overt) HBV infection, but occult hepatitis B infection (OBI) may develop despite adequate prophylaxis. The aim of this study was to investigate the long-term outcome in children born to mothers with very high HBV DNA levels with special focus on children discovered in early childhood with OBI.Methods One-year and long-term outcome regarding overt and occult HBV infection were analysed in 66 children born to hepatitis B e antigen (HBeAg)-positive mothers, and were compared with one-year outcome in 69 children born to HBeAg-negative mothers. The children were born between 1998 and 2018.Results Six children born to HBeAg-positive mothers developed overt chronic HBV infection, in two cases after normal pregnancies and despite HBIG and vaccination, but never when nucleotide analogue treatment was given during pregnancy. OBI with HBV DNA detected in serum in the absence of surface antigen (HBsAg) was observed in four children at the age of 1 year. One of them was transiently HBsAg-positive at the age of 7 years. At long-term follow-up, six children had overt chronic infection, one had OBI and six had previous OBI or positive anti-HBc suggesting resolved unidentified infections.Conclusion The results indicate that children born to mothers with high HBV DNA levels have approximately 10% risk to develop OBI despite antiviral treatment, vaccination and HBIG, but that such OBI confers a minimal long-term risk for overt infection, at least in immunocompetent children.
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31.
  • Eklundh, A., et al. (författare)
  • Etiology of Clinical Community-Acquired Pneumonia in Swedish Children Aged 1-59 Months with High Pneumococcal Vaccine Coverage-The TREND Study
  • 2021
  • Ingår i: Vaccines. - : MDPI AG. - 2076-393X. ; 9:4
  • Tidskriftsartikel (refereegranskat)abstract
    • (1) Immunization with pneumococcal conjugate vaccines has decreased the burden of community-acquired pneumonia (CAP) in children and likely led to a shift in CAP etiology. (2) The Trial of Respiratory infections in children for ENhanced Diagnostics (TREND) enrolled children 1-59 months with clinical CAP according to the World Health Organization (WHO) criteria at Sachs' Children and Youth Hospital, Stockholm, Sweden. Children with rhonchi and indrawing underwent "bronchodilator challenge". C-reactive protein and nasopharyngeal PCR detecting 20 respiratory pathogens, were collected from all children. Etiology was defined according to an a priori defined algorithm based on microbiological, biochemical, and radiological findings. (3) Of 327 enrolled children, 107 (32%) required hospitalization; 91 (28%) received antibiotic treatment; 77 (24%) had a chest X-ray performed; and 60 (18%) responded to bronchodilator challenge. 243 (74%) episodes were classified as viral, 11 (3%) as mixed viral-bacterial, five (2%) as bacterial, two (0.6%) as atypical bacterial and 66 (20%) as undetermined etiology. After exclusion of children responding to bronchodilator challenge, the proportion of bacterial and mixed viral-bacterial etiology was 1% and 4%, respectively. (4) The novel TREND etiology algorithm classified the majority of clinical CAP episodes as of viral etiology, whereas bacterial etiology was uncommon. Defining CAP in children <5 years is challenging, and the WHO definition of clinical CAP is not suitable for use in children immunized with pneumococcal conjugate vaccines.
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32.
  • Elfving, Kristina, et al. (författare)
  • Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar : Aetiologies, Antibiotic Treatment and Outcome
  • 2016
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission.METHODS: We prospectively studied the aetiology of febrile illness in 677 children aged 2-59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated.FINDINGS: NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia.CONCLUSIONS: This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low.
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33.
  • Enefalk, Hanna, 1976-, et al. (författare)
  • Våra studenter kan inte svenska
  • 2013
  • Ingår i: Uppsala Nya Tidning. ; 2 jan.
  • Tidskriftsartikel (populärvet., debatt m.m.)
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34.
  • Geijer, Cecilia, 1980, et al. (författare)
  • Initiation of the transcriptional response to hyperosmotic shock correlates with the potential for volume recovery.
  • 2013
  • Ingår i: The FEBS journal. - : Wiley. - 1742-4658 .- 1742-464X. ; 280:16, s. 3854-67
  • Tidskriftsartikel (refereegranskat)abstract
    • The control of activity and localization of transcription factors is critical for appropriate transcriptional responses. In eukaryotes, signal transduction components such as mitogen-activated protein kinase (MAPK) shuttle into the nucleus to activate transcription. It is not known in detail how different amounts of nuclear MAPK over time affect the transcriptional response. In the present study, we aimed to address this issue by studying the high osmolarity glycerol (HOG) system in Saccharomyces cerevisiae. We employed a conditional osmotic system, which changes the period of the MAPK Hog1 signal independent of the initial stress level. We determined the dynamics of the Hog1 nuclear localization and cell volume by single-cell analysis in well-controlled microfluidics systems and compared the responses with the global transcriptional output of cell populations. We discovered that the onset of the initial transcriptional response correlates with the potential of cells for rapid adaptation; cells that are capable of recovering quickly initiate the transcriptional responses immediately, whereas cells that require longer time to adapt also respond later. This is reflected by Hog1 nuclear localization, Hog1 promoter association and the transcriptional response, but not Hog1 phosphorylation, suggesting that a presently uncharacterized rapid adaptive mechanism precedes the Hog1 nuclear response. Furthermore, we found that the period of Hog1 nuclear residence affects the amplitude of the transcriptional response rather than the spectrum of responsive genes.
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35.
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36.
  • Holmbom, Martin, 1984-, et al. (författare)
  • Prehospital delay is an important risk factor for mortality in community-acquired bloodstream infection (CA-BSI) : a matched case–control study
  • 2021
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The aim of this study was to identify prehospital and early hospital risk factors associated with 30-day mortality in patients with blood culture-confirmed community-acquired bloodstream infection (CA-BSI) in Sweden.Methods A retrospective case–control study of 1624 patients with CA-BSI (2015–2016), 195 non-survivors satisfying the inclusion criteria were matched 1:1 with 195 survivors for age, gender and microorganism. All forms of contact with a healthcare provider for symptoms of infection within 7 days prior CA-BSI episode were registered. Logistic regression was used to analyse risk factors for 30-day all-cause mortality.Results Of the 390 patients, 61% (115 non-survivors and 121 survivors) sought prehospital contact. The median time from first prehospital contact till hospital admission was 13 hours (6–52) for non-survivors and 7 hours (3–24) for survivors (p&lt;0.01). Several risk factors for 30-day all-cause mortality were identified: prehospital delay OR=1.26 (95% CI: 1.07 to 1.47), p&lt;0.01; severity of illness (Sequential Organ Failure Assessment score) OR=1.60 (95% CI: 1.40 to 1.83), p&lt;0.01; comorbidity score (updated Charlson Index) OR=1.13 (95% CI: 1.05 to 1.22), p&lt;0.01 and inadequate empirical antimicrobial therapy OR=3.92 (95% CI: 1.64 to 9.33), p&lt;0.01. In a multivariable model, prehospital delay &gt;24 hours from first contact remained an important risk factor for 30-day all-cause mortality due to CA-BSI OR=6.17 (95% CI: 2.19 to 17.38), p&lt;0.01.Conclusion Prehospital delay and inappropriate empirical antibiotic therapy were found to be important risk factors for 30-day all-cause mortality associated with CA-BSI. Increased awareness and earlier detection of BSI in prehospital and early hospital care is critical for rapid initiation of adequate management and antibiotic treatment.All data relevant to the study are included in the article or uploaded as supplemental information.
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37.
  • Holst, Anna, et al. (författare)
  • Cost-effectiveness analysis of internet-mediated cognitive behavioural therapy for depression in the primary care setting : results based on a controlled trial
  • 2018
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 8:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To perform a cost-effectiveness analysis of a randomised controlled trial of internet-mediated cognitive behavioural therapy (ICBT) compared with treatment as usual (Tall) for patients with mild to moderate depression in the Swedish primary care setting. In particular, the objective was to assess from a healthcare and societal perspective the incremental cost-effectiveness ratio (ICER) of ICBT versus TaU at 12 months follow-up. Design A cost-effectiveness analysis alongside a pragmatic effectiveness trial. Setting Sixteen primary care centres (PCCs) in south-west Sweden. Participants Ninety patients diagnosed with mild to moderate depression at the PCCs. Main outcome measure ICERs calculated as (Cost(ICBT)-Cost(TaU))/(Health outcome(ICBT)-Health outcome(TaU))=Delta Cost/Delta Health outcomes, the health outcomes being changes in the Beck Depression Inventory-II (BDI-II) score and quality-adjusted life-years (QALYs). Results The total cost per patient for ICBT was 4044 Swedish kronor (SEK) ((sic)426) (healthcare perspective) and SEK47679 ((sic)5028) (societal perspective). The total cost per patient for TaU was SEK4434 ((sic)468) and SEK50 343 ((sic)5308). In both groups, the largest cost was associated with productivity loss. The differences in cost per patient were not statistically significant. The mean reduction in BDI-ll score was 13.4 and 13.8 units in the ICBT and Tall groups, respectively. The mean QALYs per patient was 0.74 and 0.79 in the ICBT and TaU groups, respectively. The differences in BDI-11 score reduction and mean QALYs were not statistically significant. The uncertainty of the study estimates when assessed by bootstrapping indicated that no firm conclusion could be drawn as to whether ICBT treatment compared with Tall was the most cost-effective use of resources. Conclusions ICBT was regarded to be as cost-effective as TaU as costs, health outcomes and cost-effectiveness were similar for ICBT and TaU, both from a healthcare and societal perspective.
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38.
  • Isaksson, Caroline, 1976, et al. (författare)
  • Sex and age differences in reflectance and biochemistry of carotenoid-based colour variation in the great tit Parus major
  • 2008
  • Ingår i: Biological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4066 .- 1095-8312. ; 95:4, s. 758-765
  • Tidskriftsartikel (refereegranskat)abstract
    • The plumage coloration in great tits (Parus major) is the subject of much behavioural and ecophysiological research, yet there is a lack of analyses of the natural colour variation and its mechanisms. We used reflectance spectrometry and high-performance liquid chromatography to explore individual, sexual and age-related variation in carotenoid coloration and pigmentation, paramount to the often presumed, but rarely substantiated, costs and 'honesty' of carotenoid displays. In adults, we found that sex was the strongest predictor of 'brightness' (higher in males) and of 'hue' (longer wavelength in females). There was no sex difference in 'carotenoid chroma' or carotenoid content of feathers which also was unrelated to adult age (1 or 2+ years) and condition. Similar patterns were revealed for nestlings. Regarding the biochemical 'signal content', 'carotenoid chroma', but not 'hue', was significantly related to the carotenoid content (lutein and zeaxanthin) of feathers. These results refute the previously assumed exaggeration of carotenoid pigmentation in male great tits, and question the condition-dependence of carotenoid coloration in this species. However, the sexual dimorphism in total reflectance or 'brightness', most likely due to melanins rather than carotenoids, may have implications for signalling or other adaptive explanations that need to be explored.
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39.
  • Isaksson, Caroline, 1976, et al. (författare)
  • Sexual, seasonal, and environmental variation in plasma carotenoids in great tits, Parus major
  • 2007
  • Ingår i: Biological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4066 .- 1095-8312. ; 92:3, s. 521-527
  • Tidskriftsartikel (refereegranskat)abstract
    • In many birds, carotenoids have dual functions as irreversible plumage pigments and as physiologically essential vitamins and antioxidants. They must be obtained through the diet and may therefore be a limiting resource, a constraint that is likely to vary with factors such as sex, habitat, and time of year. In the present study, we investigated signs of carotenoid limitation in great tits, Parus major, in relation to sex, season, year, and within an urban versus a rural habitat. The two main carotenoids, lutein and zeaxanthin, were analysed by high-performance liquid chromatography in the plasma and in the yellow carotenoid-based breast feathers. We found that plasma carotenoid concentrations were significantly influenced by sex, season, and year, but not by urban versus rural habitat. At moult, plasma concentration was positively correlated with feather pigmentation, independent of body condition and sex. During the breeding season, however, circulating carotenoid concentrations were negatively related to the feather pigmentation (i.e. from previous autumn moult). We suggest that great tits are carotenoid deprived before leaf emergence, and that carotenoid utilization and limitations are sex-specific, but that there are neither any obvious honesty-maintaining costs of pigmentation, nor any fitness consequences of the colour variation.
  •  
40.
  • Kabayiza, Jean-Claude, et al. (författare)
  • Comparison of rectal swabs and faeces for real-time PCR detection of enteric agents in Rwandan children with gastroenteritis
  • 2013
  • Ingår i: BMC Infectious Diseases. - 1471-2334. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Background Molecular diagnostics have emerged as an efficient and feasible alternative for broad detection of pathogens in faeces. However, collection of stool samples is often impractical in both clinical work and in epidemiology studies. The aim of this study was to investigate the diagnostic performance of rectal swabs as compared with traditional faeces samples for detection of enteric agents by PCR. Method Three hundred twenty-six pairs of rectal swab and stool samples, obtained from Rwandan children aged 0.5-4.99 years, with or without diarrhoea, were analysed by multiple real-time PCR amplifying 3 viral, 6 bacterial and one protozoan target. Results For all agents there was a significant correlation (R2 0.31-0.85) between Ct values in faeces and rectal swabs. For most agents the Ct values, a marker for target concentration, were significantly lower (by 1–3 cycles) in faeces, indicating pathogen content up to ten times higher than in rectal swabs. Despite this, there was no significant difference in detection rate between faeces and rectal swabs for any agent, reflecting that pathogen concentration was far above the limit of detection in the majority of cases. Conclusion The similar detection rates and the Ct value correlations as compared with traditional faeces samples indicate that rectal swabs are accurate for real-time PCR-based identification of enteric agents and may be used also for quantitative estimation of pathogen load.
  •  
41.
  • Khan, Omar M., 1980, et al. (författare)
  • Geranylgeranyltransferase type I (GGTase-I) deficiency hyperactivates macrophages and induces erosive arthritis in mice.
  • 2011
  • Ingår i: The Journal of clinical investigation. - 1558-8238. ; 121:2, s. 628-39
  • Tidskriftsartikel (refereegranskat)abstract
    • RHO family proteins are important for the function of inflammatory cells. They are modified with a 20-carbon geranylgeranyl lipid in a process catalyzed by protein geranylgeranyltransferase type I (GGTase-I). Geranylgeranylation is viewed as essential for the membrane targeting and activity of RHO proteins. Consequently, inhibiting GGTase-I to interfere with RHO protein activity has been proposed as a strategy to treat inflammatory disorders. However, here we show that mice lacking GGTase-I in macrophages develop severe joint inflammation resembling erosive rheumatoid arthritis. The disease was initiated by the GGTase-I-deficient macrophages and was transplantable and reversible in bone marrow transplantation experiments. The cells accumulated high levels of active GTP-bound RAC1, CDC42, and RHOA, and RAC1 remained associated with the plasma membrane. Moreover, GGTase-I deficiency activated p38 and NF-κB and increased the production of proinflammatory cytokines. The results challenge the view that geranylgeranylation is essential for the activity and localization of RHO family proteins and suggest that reduced geranylgeranylation in macrophages can initiate erosive arthritis.
  •  
42.
  • Larsson, Simon B., et al. (författare)
  • Self-reported symptom severity, general health, and impairment in post-acute phases of COVID-19: retrospective cohort study of Swedish public employees
  • 2022
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed to examine current symptom severity and general health in a sample of primarily non-hospitalized persons with polymerase chain reaction (PCR) confirmed COVID-19 in comparison to PCR negative controls. During the first quarter of 2021, we conducted an online survey among public employees in West Sweden, with a valid COVID-19 test result. The survey assessed past-month severity of 28 symptoms and signs, self-rated health, the WHO Disability Assessment Schedule (WHODAS) 2.0 and illness severity at the time of test. We linked participants' responses to their SARS-CoV-2 PCR tests results. We compared COVID-19 positive and negative participants using univariable and multivariable regression analyses. Out of 56,221 invited, 14,222 (25.3%) responded, with a response rate of 50% among SARS-CoV-2 positive individuals. Analysis included 10,194 participants (86.4% women, mean age 45 years) who tested positive 4-12 weeks (N = 1425; subacute) and > 12 weeks (N = 1584; postcovid) prior to the survey, and 7185 PCR negative participants who did not believe that they had had COVID-19. Symptoms were highly prevalent in all groups, with worst symptoms in subacute phase participants, followed by postcovid phase and PCR negative participants. The most specific symptom for COVID-19 was loss of smell or taste. Both WHODAS 2.0 score and self-rated health were worst in subacute participants, and modestly worse in postcovid participants than in negative controls. Female gender, older age and acute illness severity had larger effects on self-rated health and WHODAS 2.0 score in PCR positive participants than in PCR negative. Studies with longer follow-up are needed to determine the long-term improvement after COVID-19.
  •  
43.
  • Maglio, Cristina, 1983, et al. (författare)
  • The IRS1 rs2943641 Variant and Risk of Future Cancer Among Morbidly Obese Individuals.
  • 2013
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Context:Obesity and insulin resistance are risk factors for cancer development. The IRS1 rs2943641 genetic variant has been widely associated with insulin resistance.Objective:The aim of the study was to examine whether the IRS1 rs2943641 associates with cancer incidence in obese individuals.Design, Setting and Patients:The IRS1 rs2943641 was genotyped in participants from the Swedish Obese Subjects (SOS) study, an intervention trial on the effect of bariatric surgery on mortality and morbidity compared with usual care and in the population-based Malmö Diet and Cancer (MDC) cohort. In both studies, the median follow-up for cancer incidence was about 15 years.Intervention and Main Outcome Measure:Cancer incidence was assessed in both the SOS and the MDC cohorts through national and local registers.Results:The IRS1 T allele was associated with lower insulin resistance in both the SOS and the MDC studies. A lower cancer incidence was found in T allele carriers from the SOS control group (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.62-0.96; P = .021) and was restricted to morbidly obese individuals (HR 0.67, 95% CI 0.50-0.91; P = .011). No evidence of such association was detected in the surgery group (interaction P = .005). In the MDC cohort, a nonsignificant tendency for lower cancer incidence in T allele carriers was observed only in morbidly obese individuals. A meta-analysis of morbidly obese individuals (body mass index > 40 kg/m(2)) from the two cohorts strengthened the evidence for the association (HR 0.66, 95% CI 0.50-0.87; P = .004).Conclusions:Our results suggest that the T allele of rs2943641 near IRS1 may associate with lower cancer incidence in morbidly obese individuals.
  •  
44.
  • Nilsson, R. Henrik, 1976, et al. (författare)
  • Introducing guidelines for publishing DNA-derived occurrence data through biodiversity data platforms
  • 2022
  • Ingår i: Metabarcoding and Metagenomics. - : Pensoft Publishers. - 2534-9708. ; 6, s. 239-244
  • Tidskriftsartikel (refereegranskat)abstract
    • DNA sequencing efforts of environmental and other biological samples disclose unprecedented and largely untapped opportunities for advances in the taxonomy, ecology, and geographical distributions of our living world. To realise this potential, DNA-derived occurrence data (notably sequences with dates and coordinates) – much like traditional specimens and observations – need to be discoverable and interpretable through biodiversity data platforms. The Global Biodiversity Information Facility (GBIF) recently headed a community effort to assemble a set of guidelines for publishing DNA-derived data. These guidelines target the principles and approaches of exposing DNA-derived occurrence data in the context of broader biodiversity data. They cover a choice of terms using a controlled vocabulary, common pitfalls, and good practices, without going into platform-specific details. Our hope is that they will benefit anyone interested in better exposure of DNA-derived occurrence data through general biodiversity data platforms, including national biodiversity portals. This paper provides a brief rationale and an overview of the guidelines, an up-to-date version of which is maintained at https://doi.org/10.35035/doc-vf1a-nr22. User feedback and interaction are encouraged as new techniques and best practices emerge.
  •  
45.
  • Norberg, Maria, 1976- (författare)
  • In Vitro Drug Sensitivity and Apoptosis in Chronic Lymphocytic Leukemia
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Chronic lymphocytic leukemia (CLL) is a heterogeneous malignancy displaying varying clinical outcome, where molecular markers today can divide patients into prognostic subgroups. Despite the introduction of new agents for treatment, remissions are usually not sustained in CLL and resistance towards treatment can partly be explained by aberrant apoptosis. The aim of this thesis was to find new drugs for CLL patients resistant to conventional therapy and to analyze genes involved in apoptosis within different prognostic subgroups. In paper I-II, the in vitro activity of substances was investigated using the fluorometric microculture cytotoxicity assay (FMCA). When evaluating rapamycin (paper I), an inhibitor of mTOR, in 97 tumor samples from different entities, CLL was found to be one of the most sensitive tumor types. Combination experiments on patient CLL cells indicated that rapamycin acted synergistically with the CLL drugs vincristine and chlorambucil. An investigation of 20 anti-cancer agents in cells from 40 CLL patients (paper II) revealed that prednisolone and rolipram displayed high activity in poor-prognostic patients, in particular IGHV unmutated CLL. Furthermore, when used in combination these agents were found to produce a synergistic effect. In paper III, the anti-apoptotic BCL2 family member BFL1 was evaluated in 37 CLL cases. Levels of BFL1 were higher in fludarabine-resistant patients compared to fludarabine-sensitive patients. In addition, the high expression of BFL1 inversely correlated to fludarabine-induced apoptosis in CLL cells. A single nucleotide polymorphism in the anti-apoptotic BCL2 gene (-938C>A) has been suggested as a novel poor-prognostic marker in CLL. In paper IV, we investigated this BCL2 polymorphism in 268 CLL patients and correlated genotypes to clinical data. However, no association could be confirmed between this polymorphism and clinical outcome or established prognostic markers. In conclusion, this thesis has shown that rapamycin is a potential drug for treatment in CLL. Furthermore, prednisolone and rolipram were identified as interesting candidates for treatment of poor-prognostic patients. Finally, the anti-apoptotic protein BFL1 may contribute to chemoresistance and hence represents a potential therapeutic target in CLL, whereas from our data, the BCL2 -938C>A polymorphism does not appear to have any prognostic significance.
  •  
46.
  • Palosuo, Laura, 1976- (författare)
  • Yellow Stars and Trouser Inspections : Jewish Testimonies from Hungary, 1920–1945
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This study analyzes narratives of individual Jewish experiences of discrimination and genocidal violence in Hungary during the period of 1920–1945. The aim is to increase our knowledge and understanding of the events through an investigation of survivor testimonies concerning anti-Jewish laws and the Holocaust. The main focus is on how survivors perceived the treatment to which they and their fellow Jews were exposed, and how they responded to the persecution they faced. Perceptions and responses are analyzed through multiple factors such as gender, age, social class, and geographical place.The period under investigation stretches from 1920, when the law of Numerus Clausus (a quota system influencing admission to universities) was introduced, until the end of the Second World War in early 1945. Focus is placed on the war years, especially on 1944, the year of German occupation and the fascist Arrow Cross rule. Experiences from the labour service system, the Jewish houses in Budapest, and the ghettos, as well as of hiding and resistance, are some of the recurring themes which are examined here. Extensive interviews, along with eyewitness reports and memoirs, form the empirical basis of the study.The results demonstrate the complexity of individual experiences during times of upheaval, and the importance of the above factors is evident within the testimonies. The survivors’ experiences greatly depended on gender, age, social class, geographical place, civil status, religious orientation, as well as “race”. However, the importance of the different factors changed over time. For instance, in the beginning of this period, discrimination had a direct impact on adult males, while children, women, and the elderly were indirectly affected. Furthermore, persons belonging to the upper classes could circumvent the anti-Jewish laws in various ways. Ultimately, differences in treatment decreased, according to the testimonies. Women, children, and the elderly also became victims, as did individuals from all social classes.
  •  
47.
  • Prakash, Kasthuri, et al. (författare)
  • Hepatitis B Virus RNA Profiles in Liver Biopsies by Digital Polymerase Chain Reaction
  • 2020
  • Ingår i: Hepatology Communications. - : Ovid Technologies (Wolters Kluwer Health). - 2471-254X. ; 4:7, s. 973-982
  • Tidskriftsartikel (refereegranskat)abstract
    • Replication of hepatitis B virus (HBV) originates from covalently closed circular DNA (cccDNA) and involves reverse transcription of pregenomic RNA (pgRNA), which is also called core RNA and encodes the capsid protein. The RNA coding for hepatitis B surface antigen (HBsAg) in the envelope of viral or subviral particles is produced from cccDNA or from HBV DNA integrated into the host genome. Because only cccDNA can generate the core and the 3 ' redundancy regions of HBV RNA, we aimed to clarify to what extent such HBV integrations are expressed by quantifying the different HBV RNA species in liver tissue. Digital droplet polymerase chain reaction (ddPCR) was employed to quantify six HBV RNA targets in 76 liver biopsies from patients with chronic infection, comprising 14 who were hepatitis B e antigen (HBeAg) positive and 62 who were HBeAg negative. In patients who were HBeAg negative, HBV RNA from the S RNA region was >1.6 log(10) units higher than in the core and 3 ' redundancy regions (P < 0.0001), indicating that >90% of S RNA was integration derived. HBeAg-negative samples showed 10 times lower levels of pgRNA (5 ' core) compared with core RNA (3 ' part of core; P < 0.0001), suggesting that a large proportion of core RNA might have a downstream shift of the transcription starting point. In multiple regression analysis, HBV DNA levels in serum were most strongly dependent on pgRNA. Conclusion: In patients who were HBeAg negative, integration-derived S RNA seemed to predominate and a large proportion of the core RNA lacked the 5 ' part. Because this part comprises the down-regulator of transcription 1 sequences, which are necessary for virus production (plus strand translocation), the finding might help to explain the low level of HBV DNA in serum that frequently is observed in patients with chronic HBV infection who are HBeAg negative.
  •  
48.
  • Prakash, Kasthuri, et al. (författare)
  • High serum levels of pregenomic RNA reflect frequently failing reverse transcription in hepatitis B virus particles
  • 2018
  • Ingår i: Virology Journal. - : Springer Science and Business Media LLC. - 1743-422X. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hepatocytes infected by hepatitis B virus (HBV) produce different HBV RNA species, including pregenomic RNA (pgRNA), which is reverse transcribed during replication. Particles containing HBV RNA are present in serum of infected individuals, and quantification of this HBV RNA could be clinically useful. Methods: In a retrospective study of 95 patients with chronic HBV infection, we characterised HBV RNA in serum in terms of concentration, particle association and sequence. HBV RNA was detected by real-time PCR at levels almost as high as HBV DNA. Results: The HBV RNA was protected from RNase and it was found in particles of similar density as particles containing HBV DNA after fractionation on a Nycodenz gradient. Sequencing the epsilon region of the RNA did not reveal mutations that would preclude its binding to the viral polymerase before encapsidation. Specific quantification of precore RNA and pgRNA by digital PCR showed almost seven times lower ratio of precore RNA/pgRNA in serum than in liver tissue, which corresponds to poorer encapsidation of this RNA as compared with pgRNA. The serum ratio between HBV DNA and HBV RNA was higher in genotype D as compared with other genotypes. Conclusions: The results suggest that HBV RNA in serum is present in viral particles with failing reverse transcription activity, which are produced at almost as high rates as viral particles containing DNA. The results encourage further studies of the mechanisms by which these particles are produced, the impact of genotype, and the potential clinical utility of quantifying HBV RNA in serum.
  •  
49.
  • Rydell, Gustaf E, et al. (författare)
  • Abundance of non-circular intrahepatic hepatitis B virus DNA may reflect frequent integration into human DNA in chronically infected patients.
  • 2022
  • Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 225:11, s. 1982-1990
  • Tidskriftsartikel (refereegranskat)abstract
    • Hepatitis B virus (HBV) integration has implications for cancer development and surface antigen (HBsAg) production, but methods to quantify integrations are lacking. The aim of this study was to develop a digital PCR (ddPCR) assay discriminating between circular and integrated HBV DNA, and to relate the distribution between the two forms to other HBV markers.ddPCR comprising primers spanning the typical linearization breakpoint in the HBV genome allowed for quantification of the absolute copy numbers of total and circular HBV DNA, and calculation of linear HBV DNA.Analysis of 70 liver biopsies from patients with chronic HBV infection revealed that the fraction of linear HBV DNA, which includes integrations, was higher in HBeAg-negative patients than HBeAg-positive. The ratio between HBsAg and HBV DNA levels in serum correlated with the intrahepatic proportion of linear HBV DNA. Furthermore, ddPCR experiments on serum samples and experiments with nuclease indicated the contribution of encapsidated double-stranded linear DNA and replication intermediates to be limited.The degree of integration of intrahepatic HBV DNA in the HBeAg-negative stage may be higher than previously anticipated, and integrated DNA may explain the persistence of high HBsAg serum levels in patients with low HBV DNA levels.
  •  
50.
  • Skovbjerg, Susann, 1973, et al. (författare)
  • Inflammatory Mediator Profiles in Secretory Otitis Media in Relationship to Viable Bacterial Pathogens and Bacterial and Viral Nucleic Acids
  • 2020
  • Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1557-7465 .- 1079-9907. ; 40:12, s. 555-569
  • Tidskriftsartikel (refereegranskat)abstract
    • Secretory otitis media (SOM) is characterized by persistence of fluid in the middle ear, often following an episode of acute otitis media. Our hypothesis is that failure to eliminate bacterial or viral pathogens may result in persistent low-grade inflammation. In this study, we analyzed inflammatory mediators in middle ear fluids from 67 children with SOM. This was combined with determinations of viable bacteria by culture along with detection of bacterial and viral genetic material by real-time polymerase chain reaction (PCR). The inflammatory mediators found at the highest concentrations (>30 ng/mL) were stem cell growth factor-β (median 110 ng/mL), CXCL1, IL-16, IL-8, migration inhibitory factor, CXCL10, and CXCL9. Among bacterial pathogens, Moraxella catarrhalis and Haemophilus influenzae dominated, regardless of detection methods, while rhinovirus dominated among viral pathogens. Middle ear fluid levels of interleukin (IL)-1α, IL-17, IL-1β, fibroblast growth factor basic, and tumor necrosis factor correlated strongly with presence of bacteria detected either by culture or PCR, while IL-1RA, IL-3, IL-6, IL-8, CCL3, CCL4, and granulocyte-colony stimulating factor correlated significantly with real-time PCR values. CXCL10, CXCL9, CCL2, and TRAIL correlated significantly with viral nucleic acid levels. To conclude, persistence of viral and bacterial pathogens may fuel persistent inflammation in SOM. Bacteria caused a broad inflammatory response, while viruses chiefly elicited the interferon-induced chemokines CXCL9 and CXCL10.
  •  
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