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  • Evans, M, et al. (author)
  • Association Between Implementation Of Novel Therapies And Improved Survival In Patients Starting Hemodialysis: The Swedish Renal Registry 2006-2015
  • 2021
  • In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 36:7, s. 1298-1306
  • Journal article (peer-reviewed)abstract
    • BackgroundThe recent years have witnessed significant therapeutic advances for patients on haemodialysis (HD). We evaluated temporal changes in treatments practices and survival rates among incident HD patients.MethodsThis was an observational study of patients initiating HD in Sweden in 2006–15. Trends of HD-related practices, medications and routine laboratory biomarkers were evaluated. The incidence of death and major cardiovascular events (MACEs) across calendar years were compared against the age- and sex-matched general population. Via Cox regression, we explored whether adjustment for implementation of therapeutic advances modified observed survival and MACE risks.ResultsAmong 6612 patients, age and sex were similar, but the burden of comorbidities increased over time. The proportion of patients receiving treatment by haemodiafiltration, ≥3 sessions/week, lower ultrafiltration rate and working fistulas increased progressively, as did use of non-calcium phosphate binders, cinacalcet and vitamin D3. The standardized 1-year mortality decreased from 13.2% in 2006–07 to 11.1% in 2014–15. The risk of death decreased by 6% [hazard ratio (HR) = 0.94, 95% confidence interval (CI) 0.90–0.99] every 2 years, and the risk of MACE by 4% (HR = 0.96, 95% CI 0.92–1.00). Adjustment for changes in treatment characteristics abrogated these associations (HR = 1.00, 95% CI 0.92–1.09 for death and 1.00, 0.94–1.06 for MACE). Compared with the general population, the risk of death declined from 6 times higher in 2006–07 [standardized incidence rate ratio (sIRR) = 6.0, 95% CI 5.3–6.9] to 5.6 higher in 2014–15 (sIRR = 5.57, 95% CI 4.8–6.4).ConclusionsGradual implementation of therapeutic advances over the last decade was associated with a parallel reduction in short-term risk of death and MACE among HD patients.
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  • Pagels, AA, et al. (author)
  • Patient-reported outcome measures as a new application in the Swedish Renal Registry: health-related quality of life through RAND-36
  • 2020
  • In: Clinical kidney journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 13:3, s. 442-449
  • Journal article (peer-reviewed)abstract
    • BackgroundAlthough patient-reported outcome measures (PROMs) are gaining increased interest in developing health care quality and are a useful tool in person-centered care, their use in routine care is still limited. The aim of this study is to describe the implementation and initial results of PROMs via the Swedish Renal Registry (SRR) on a national level.MethodsAfter testing and piloting the electronic PROM application, nationwide measures were carried out in 2017 for completing the RAND-36 questionnaire online or by paper in a wide range of chronic kidney disease (CKD) patients (Stages 3–5, dialysis and transplantation) through the SRR. Cross-sectional results during the first year were analyzed by descriptive statistics and stratified by treatment modality.ResultsA total of 1378 patients from 26 of 68 renal units (39%) completed the questionnaire. The response rate for all participating hemodialysis units was 38.9%. The CKD patients had an impaired health profile compared with a Swedish general population, especially regarding physical functions and assessed general health (GH). Transplanted patients had the highest scores, whereas patients on dialysis treatment had the lowest scores. The youngest age group assessed their physical function higher and experienced fewer physical limitations and less bodily pain than the other age groups but assessed their GH and vitality (VT) relatively low. The oldest age group demonstrated the lowest health profile but rated their mental health higher than the other age groups. The older the patient, the smaller the difference compared with persons of the same age in the general population.ConclusionsNationwide, routine collection of PROMs is feasible in Sweden. However, greater emphasis is needed on motivating clinical staff to embrace the tool and its possibilities in executing person-centered care. CKD patients demonstrate impaired health-related quality of life, especially regarding limitations related to physical problems, GH and VT/energy/fatigue.
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  • Andersson, K, et al. (author)
  • YopH of Yersinia pseudotuberculosis interrupts early phosphotyrosine signalling associated with phagocytosis.
  • 1996
  • In: Molecular Microbiology. - 0950-382X .- 1365-2958. ; 20:5, s. 1057-69
  • Journal article (peer-reviewed)abstract
    • The PTPase YopH of Yersinia is essential to the ability of these bacteria to block phagocytosis. Wild-type Yersinia pseudotuberculosis, but not the yopH mutant strain, resisted phagocytosis by J774 cells. Ingestion of a yopH mutant was dependent on tyrosine kinase activity. Transcomplementation with wild-type yopH restored the anti-phagocytic effect, whereas introduction of the gene encoding the catalytically inactive yopHC403A was without effect. The PTPase inhibitor orthovanadate impaired the anti-phagocytic effect of the wild-type strain, further demonstrating the importance of bacteria-derived PTPase activity for this event. The ability to resist phagocytosis indicates that the effect of the bacterium is immediately exerted when it becomes associated with the phagocyte. Within 30 s after the onset of infection, wild-type Y. pseudotuberculosis caused a YopH-dependent dephosphorylation of phosphotyrosine proteins in J774 cells. Furthermore, interaction of the cells with phagocytosable strains led to a rapid and transient increase in tyrosine phosphorylation of paxillin and some other proteins, an event dependent on the presence of the bacterial surface-located protein invasin. Co-infection with the phagocytosable strain and the wild-type strain abolished the induction of tyrosine phosphorylation. Taken together, the present findings demonstrate an immediate YopH-mediated dephosphorylation of macrophage phosphotyrosine proteins, suggesting that this PTPase acts by preventing early phagocytosis-linked signalling in the phagocyte.
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  • Charoenrat, Theppanya, et al. (author)
  • Oxygen-limited fed-batch process : an alternative control for Pichia pastoris recombinant protein processes
  • 2005
  • In: Bioprocess and biosystems engineering (Print). - : Springer Science and Business Media LLC. - 1615-7591 .- 1615-7605. ; 27:6, s. 399-406
  • Journal article (peer-reviewed)abstract
    • An oxygen-limited fed-batch technique (OLFB) was compared to traditional methanol-limited fed-batch technique (MLFB) for the production of recombinant Thai Rosewood beta-glucosidase with Pichia pastoris. The degree of energy limitation, expressed as the relative rate of respiration (q(O)/q(O,max)), was kept similar in both the types of processes. Due to the higher driving force for oxygen transfer in the OLFB, the oxygen and methanol consumption rates were about 40% higher in the OLFB. The obligate aerobe P. pastoris responded to the severe oxygen limitation mainly by increased maintenance demand, measured as increased carbon dioxide production per methanol, but still somewhat higher cell density (5%) and higher product concentrations (16%) were obtained. The viability was similar, about 90-95%, in both process types, but the amount of total proteins released in the medium was much less in the OLFB processes resulting in substantially higher (64%) specific enzyme purity for input to the downstream processing.
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  • Ernfors, Maria, 1973, et al. (author)
  • Nitrous oxide emissions from drained organic forest soils - an up-scaling based on C : N ratios
  • 2007
  • In: Biogeochemistry. - : Springer Science and Business Media LLC. - 0168-2563 .- 1573-515X. ; 84:2, s. 219-231
  • Journal article (peer-reviewed)abstract
    • Total emissions of N2O from drained organic forest soils in Sweden were estimated using an equation linking the C:N ratio of the soil to N2O emissions. Information on soil C:N ratios was derived from a national database. It was estimated that the emissions from Histosols amount to 2,820 tonnes N2O a(-1). This is almost five times the value calculated for the same soils using the method suggested by the Intergovernmental Panel on Climate Change: 580 tonnes N2O a(-1). The higher value in the present study can mainly be explained by improved accuracy of estimates of N2O emissions from nutrient-rich soils, including former agricultural soils. In Sweden, in addition to 0.94 Mha of drained Histosols, there are 0.55 Mha of other types of drained organic soils. The annual emissions from these soils were estimated to amount to 1,890 tonnes of N2O. The total emission value calculated for drained organic forest soils was thus 4,700 tonnes N2O a(-1), which, if added, would increase the current estimate of the Swedish anthropogenic N2O source strength by 18%. Of these emissions, 88% occur from sites with C:N ratios lower than 25. The exponential relationship between C:N ratio and N2O emissions, in combination with a scarcity of data, resulted in large confidence intervals around the estimates. However, by using the C:N ratio-based method, N2O emission estimates can be calculated from a variable that is readily available in databases. Also, the recent findings that there are exceptionally large emissions of N2O from the most nitrogen-rich drained organic forest soils are taken into account.
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  • Forsberg, Maria, et al. (author)
  • Differential effects of invasion by and phagocytosis of Salmonella typhimurium on apoptosis in human macrophages : potential role of Rho–GTPases and Akt
  • 2003
  • In: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 74:4, s. 620-629
  • Journal article (peer-reviewed)abstract
    • In addition to direct activation of caspase-1 and induction of apoptosis by SipB, invasive Salmonella stimulates multiple signaling pathways that are key regulators of host cell survival. Nevertheless, little is known about the relative contributions of these pathways to Salmonella-mediated death of macrophages. We studied human monocytic U937 cells and found that apoptosis was induced by invading wild-type Salmonella typhimurium but not by phagocytosed, serum-opsonized, noninvasive Salmonella mutants. Pretreating U937 cells with inhibitors of tyrosine kinases or phosphatidylinositol-3 kinase (PI-3K) completely blocked phagocytosis of opsonized Salmonella mutants but did not affect invasion by wild-type Salmonella or the apoptosis caused by invasion. However, pretreatment with GGTI-298, a geranylgeranyltransferase-1 inhibitor that prevents prenylation of Cdc42 and Rac1, suppressed Salmonella-induced apoptosis by ∼70%. Transduction of Tat fusion constructs containing dominant-negative Cdc42 or Rac1 significantly inhibited Salmonella-induced cell death, indicating that the cytotoxicity of Salmonella requires activation of Cdc42 and Rac. In contrast to phagocytosis of opsonized bacteria, invasion by S. typhimurium stimulated Cdc42 and Rac1, regardless of the activities of tyrosine- or PI-3K. Moreover, Salmonella infection activated Akt protein in a tyrosine-kinase or PI-3K-dependent manner, and a reduced expression of Akt by antisense transfection rendered the cells more sensitive to apoptosis induced by opsonized Salmonella. These results indicate that direct activation of Cdc42 and Rac1 by invasive Salmonella is a prerequisite of Salmonella-mediated death of U937 cells, whereas the simultaneous activation of Akt by tyrosine kinase and PI-3K during receptor-mediated phagocytosis protects cells from apoptosis.
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  • Gamfeldt, Lars, 1975, et al. (author)
  • Higher levels of multiple ecosystem services are found in forests with more tree species
  • 2013
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4
  • Journal article (peer-reviewed)abstract
    • Forests are of major importance to human society, contributing several crucial ecosystem services. Biodiversity is suggested to positively influence multiple services but evidence from natural systems at scales relevant to management is scarce. Here, across a scale of 400,000km2, we report that tree species richness in production forests shows positive to positively hump-shaped relationships with multiple ecosystem services. These include production of tree biomass, soil carbon storage, berry production and game production potential. For example, biomass production was approximately 50% greater with five than with one tree species. In addition, we show positive relationships between tree species richness and proxies for other biodiversity components. Importantly, no single tree species was able to promote all services, and some services were negatively correlated to each other. Management of production forests will therefore benefit from considering multiple tree species to sustain the full range of benefits that the society obtains from forests.
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  • Idh, Jonna, et al. (author)
  • Resistance to First-Line Anti-TB Drugs is Associated with Reduced Nitric Oxide Susceptibility in Mycobacterium tuberculosis
  • 2012
  • In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:1, s. e39891-
  • Journal article (peer-reviewed)abstract
    • Background and objective: The relative contribution of nitric oxide (NO) to the killing of Mycobacterium tuberculosis in human tuberculosis (TB) is controversial, although this has been firmly established in rodents. Studies have demonstrated that clinical strains of M. tuberculosis differ in susceptibility to NO, but how this correlates to drug resistance and clinical outcome is not known.Methods: In this study, 50 sputum smear- and culture-positive patients with pulmonary TB in Gondar, Ethiopia were included. Clinical parameters were recorded and drug susceptibility profile and spoligotyping patterns were investigated. NO susceptibility was studied by exposing the strains to the NO donor DETA/NO.Results: Clinical isolates of M. tuberculosis showed a dose- and time-dependent response when exposed to NO. The most frequent spoligotypes found were CAS1-Delhi and T3_ETH in a total of nine known spoligotypes and four orphan patterns. There was a significant association between reduced susceptibility to NO (>10% survival after exposure to 1mM DETA/NO) and resistance against first-line anti-TB drugs, in particular isoniazid (INH). Patients infected with strains of M. tuberculosis with reduced susceptibility to NO showed no difference in cure rate or other clinical parameters, but a tendency towards lower rate of weight gain after two months of treatment.Conclusion: There is a correlation between resistance to first-line anti-TB drugs and reduced NO susceptibility in clinical strains of M. tuberculosis. Further studies including the mechanisms of reduced NO susceptibility are warranted and could identify targets for new therapeutic interventions.
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  • Rauvala, M, et al. (author)
  • Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression.
  • 2006
  • In: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. - : BMJ. - 1048-891X .- 1525-1438. ; 16:3, s. 1297-302
  • Journal article (peer-reviewed)abstract
    • The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Umeå University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors.
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  • Schulman, H., et al. (author)
  • Sedimentation rate and suPAR in relation to disease activity and mortality in patients with tuberculosis
  • 2019
  • In: The International Journal of Tuberculosis and Lung Disease. - : INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D). - 1027-3719 .- 1815-7920. ; 23:11, s. 1155-1161
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE : To investigate how levels of the soluble urokinase plasminogen activator receptor (suPAR) and erythrocyte sedimentation rate (ESR) correlate with disease activity and prognosis in pulmonary tuberculosis (PTB). DESIGN: This was a retrospective analysis of patients with active PTB (n = 500) in Gondar, Ethiopia, for whom the suPAR (n = 301) and ESR (n = 330) were analysed at the start of treatment. Both biomarkers were available for 176 patients. Human immunodeficiency virus (HIV) status, chest X-ray (CXR) findings, classification according to the clinical TBscore and treatment outcome were all recorded. RESULTS : In a multivariable logistic regression analysis adjusted for age, sex and HIV status, surrogate markers of disease activity such as advanced CXR patterns correlated with increased levels of suPAR (adjusted OR [aOR] 8.24, Pamp;lt; 0.001) and of ESR (aOR 1.63, P = 0.030), whereas ESR only correlated significantly with a TBscore amp;gt;6 points. Increased levels of both suPAR and ESR were associated with unsuccessful treatment outcomes (aOR 2.93, P = 0.013; aOR 2.52, P = 0.025). The highest quartile of suPAR (aOR 13.3, P = 0.029) but not ESR levels correlated independently with increased mortality. CONCLUSION: SuPAR and ESR levels correlate with disease activity in PTB; however, the clinical role of these potentially prognostic biomarkers needs to be verified in prospective studies.
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  • Schulte, M., et al. (author)
  • Nordic forest management towards climate change mitigation : time dynamic temperature change impacts of wood product systems including substitution effects
  • 2022
  • In: European Journal of Forest Research. - : Springer Science and Business Media Deutschland GmbH. - 1612-4669 .- 1612-4677. ; 141, s. 845-
  • Journal article (peer-reviewed)abstract
    • Climate change mitigation trade-offs between increasing harvests to exploit substitution effects versus accumulating forest carbon sequestration complicate recommendations for climate beneficial forest management. Here, a time dynamic assessment ascertains climate change mitigation potential from different rotation forest management alternatives across three Swedish regions integrating the forest decision support system Heureka RegWise with a wood product model using life cycle assessment data. The objective is to increase understanding on the climate effects of varying the forest management. Across all regions, prolonging rotations by 20% leads on average to the largest additional net climate benefit until 2050 in both, saved emissions and temperature cooling, while decreasing harvests by 20% leads to the cumulatively largest net climate benefits past 2050. In contrast, increasing harvests or decreasing the rotation period accordingly provokes temporally alternating net emissions, or slight net emission, respectively, regardless of a changing market displacement factor. However, future forest calamities might compromise potential additional temperature cooling from forests, while substitution effects, despite probable prospective decreases, require additional thorough and time explicit assessments, to provide more robust policy consultation. © 2022, The Author(s).
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