| 1. |
- Gerogianni, Alexandra, et al.
(författare)
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Heme Interferes With Complement Factor I-Dependent Regulation by Enhancing Alternative Pathway Activation
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Hemolysis, as a result of disease or exposure to biomaterials, is characterized by excess amounts of cell-free heme intravascularly and consumption of the protective heme-scavenger proteins in plasma. The liberation of heme has been linked to the activation of inflammatory systems, including the complement system, through alternative pathway activation. Here, we investigated the impact of heme on the regulatory function of the complement system. Heme dose-dependently inhibited factor I-mediated degradation of soluble and surface-bound C3b, when incubated in plasma or buffer with complement regulatory proteins. Inhibition occurred with factor H and soluble complement receptor 1 as co-factors, and the mechanism was linked to the direct heme-interaction with factor I. The heme-scavenger protein hemopexin was the main contaminant in purified factor I preparations. This led us to identify that hemopexin formed a complex with factor I in normal human plasma. These complexes were significantly reduced during acute vasoocclusive pain crisis in patients with sickle cell disease, but the complexes were normalized at their baseline outpatient clinic visit. Hemopexin exposed a protective function of factor I activity in vitro, but only when it was present before the addition of heme. In conclusion, we present a mechanistic explanation of how heme promotes uncontrolled complement alternative pathway amplification by interfering with the regulatory capacity of factor I. Reduced levels of hemopexin and hemopexin-factor I complexes during an acute hemolytic crisis is a risk factor for heme-mediated factor I inhibition.
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| 2. |
- Nilsson, Sheida, et al.
(författare)
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A retrospective clinical study of fixed tooth- and implant-supported prostheses in titanium and cobalt-chromium-ceramic: 5-9-year follow-up
- 2022
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Ingår i: Clinical Oral Investigations. - : Springer Science and Business Media LLC. - 1432-6981 .- 1436-3771. ; 26:10, s. 6097-6103
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this retrospective study was to evaluate the clinical outcome of fixed tooth- and implant-supported protheses manufactured in porcelain veneered cobalt-chromium (CoCr) or titanium with a follow-up period of 5-9 years. Materials and methods This study included 63 patients with a total of 86 fixed dental protheses (FDPs) (53 implant-supported and 33 tooth-supported). In total, 67 were short-span FDPs (3-5 units) and 19 were long-span FDPs (6-12 units). The FDPs were evaluated using a modified version of the California Dental Association (CDA). Results The binary regression analysis indicated that neither CoCr nor titanium had a statistically significant effect on the odds of success or survival of either tooth- or implant-supported FDPs. However, the success of FDPs was negatively affected by greater FDP length and general tooth wear. The survival of FDPs was negatively affected by increased FDP longevity. Conclusions This study found no statistically significant effect on the odds of success and survival outcomes for any combination of tooth-supported, implant-supported, porcelain-veneered CoCr, or porcelain-veneered titanium FDPs. As the number of FDPs was limited, the results should be interpreted with caution.
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| 3. |
- Halaas, Nathalie Bodd, et al.
(författare)
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CSF sTREM2 and Tau Work Together in Predicting Increased Temporal Lobe Atrophy in Older Adults.
- 2020
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Ingår i: Cerebral cortex (New York, N.Y. : 1991). - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 30:4, s. 2295-2306
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Tidskriftsartikel (refereegranskat)abstract
- Neuroinflammation may be a key factor in brain atrophy in aging and age-related neurodegenerative disease. The objective of this study was to test the association between microglial expression of soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2), as a measure of neuroinflammation, and brain atrophy in cognitively unimpaired older adults. Brain magnetic resonance imagings (MRIs) and cerebrospinal fluid (CSF) sTREM2, total tau (t-tau), phosphorylated181 tau (p-tau), and Aβ42 were analyzed in 115 cognitively unimpaired older adults, classified according to the A/T/(N)-framework. MRIs were repeated after 2 (n=95) and 4 (n=62) years. High baseline sTREM2 was associated with accelerated cortical thinning in the temporal cortex of the left hemisphere, as well as bilateral hippocampal atrophy, independently of age, Aβ42, and tau. sTREM2-related atrophy only marginally increased with biomarker positivity across the AD continuum (A-T- #x2292; A+T- #x2292; A+T+) but was significantly stronger in participants with a high level of p-tau (T+). sTREM2-related cortical thinning correlated significantly with areas of high microglial-specific gene expression in the Allen Human Brain Atlas. In conclusion, increased CSF sTREM2 was associated with accelerated cortical and hippocampal atrophy in cognitively unimpaired older participants, particularly in individuals with tau pathology. This suggests a link between neuroinflammation, neurodegeneration, and amyloid-independent tauopathy.
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| 4. |
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| 5. |
- Jernryd, Victoria, et al.
(författare)
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Myocardial injury biomarkers at point of care for early identification of primary graft dysfunction after heart transplantation.
- 2022
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Ingår i: Clinical transplantation. - : Wiley. - 1399-0012 .- 0902-0063. ; 36:2
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Tidskriftsartikel (refereegranskat)abstract
- Primary graft dysfunction (PGD) is a leading cause of 30- day mortality following heart transplantation, and early intervention in PGD may correlate to improved survival. Our analysis aimed to determine the feasibility of measuring cardiac biomarkers from the donor heart in the early phase for use as a predictor of PGD.Blood samples from the coronary sinus were obtained at the time of transplantation in hearts preserved by cold static storage. The samples were analyzed for CK-MB and cTnI with a point-of-care method. The primary outcome was severe PGD or the need for veno-arterial extracorporeal membrane oxygenation within 7 days, referred to as severe graft dysfunction.Of the total cohort (n = 63), eight patients (13%) were diagnosed with severe graft dysfunction within 7 days. Patients with high CK-MB had an increased risk for severe graft dysfunction with unadjusted Odds Ratio (OR) of 4.5 (95%CI 0.96-21.11 p = 0.057) and adjusted OR of 7.4 (95%CI 1.13-48.46, p = 0.037. Similar but non Clinical Transplantation For Review Only significant trends were observed for cTnI.By measuring CK-MB from the coronary effluent in the donor heart, it may be possible to identify patients at increased risk for severe PGD after heart transplantation. This article is protected by copyright. All rights reserved.
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| 6. |
- Jernryd, Victoria, et al.
(författare)
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The influence of ischemia and reperfusion time on outcome in heart transplantation
- 2020
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 34:5
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Tidskriftsartikel (refereegranskat)abstract
- Ischemia/reperfusion may lead to graft dysfunction in heart transplantation (HT). The purpose of this study was to evaluate the influence of ischemic and reperfusion time on acute cellular rejection (ACR) within the first-year post-HT and on long-term outcomes. Data were collected from 331 patients (mean age 49 ± 12 y, 28% females) who underwent HT 1988-2016. Endomyocardial biopsies obtained within the first year after HT were graded according to the 2004-ISHLT-WF. We classified the patients by ischemic time 4 hours, and of these, 31 (55%) patients had reperfusion with CPB ≥90 minutes. Ischemia >4 hours had an increased risk of ACR ≥ 2R during the first year (adjusted OR = 3.1, P =.016); however, an extended reperfusion ≥90 minutes reduced the risk (adjusted OR = 0.25, P =.024). The conditional probability of surviving 10 years post-transplant, given that the patients already survived first year, was inferior for recipients with ischemia ≥ 4 hours and reperfusion <90 minutes, 59%, compared with the other groups 83%, P =.016. Prolonged reperfusion appears to reduce the risk for ACR ≥ 2R and improve long-term survival.
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| 7. |
- Jones, Geraint H., et al.
(författare)
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The Comet Interceptor Mission
- 2024
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Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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| 8. |
- Kowar, J., et al.
(författare)
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Mortality in Edentulous Patients: A Registry-Based Cohort Study in Sweden Comparing 8463 Patients Treated with Removable Dentures or Implant-Supported Dental Prostheses
- 2021
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Ingår i: International Journal of Dentistry. - : Hindawi Limited. - 1687-8728 .- 1687-8736. ; 2021
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The purpose of this study was to investigate if edentulism is associated with all-cause mortality. The aims were to analyze the association between age, socioeconomic factors, and mortality in edentulous patients treated with either removable dentures or implant-supported prostheses. Methods. All patients who became edentulous according to the Swedish Social Insurance Agency (SSIA) between 2009 and 2013 (N = 8463) were analyzed regarding prosthetic treatment, age, gender, and socioeconomic status. The patients were divided into two groups, depending on whether they were treated with dental implants (implant group; IG) or with conventional removable dentures (denture group; DG). Data on mortality for all included individuals were obtained from the Swedish National Cause of Death Register and compared to a reference population. Cumulative survival rates were calculated, and a multivariable regression analysis for the included variables was performed. Results. Between 2009 and 2018, 2192 of the patients (25.9%) were treated with implant-supported dental prostheses (IG) and 6271 patients (74.1%) were treated with removable dentures without support of dental implants (DG). Altogether 2526 patients (30%) died until December 31, 2019, and the overall mortality was significantly higher for the DG compared to the IG during follow-up (p<0.001). Younger edentulous patients (<= 59 years) presented a higher mortality than the reference population, while implant patients over 79 years of age demonstrated a lower mortality. The final results from the multivariable logistic analysis showed that lower equalized disposable income (EDI) and the choice of conventional removable dentures are the most important factors for increased patient mortality (p<0.001). Conclusions. Edentulous patients have an overall higher mortality compared to a reference population. Low socioeconomic status increases all-cause mortality. Individuals treated with dental implants show statistically significant lower 10-year mortality compared to patients treated with conventional removable dentures, regardless of socioeconomic status.
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| 9. |
- Larisch, Lisa-Marie, et al.
(författare)
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Improving movement behavior in office workers : effects of two multi-level cluster-RCT interventions on mental health
- 2024
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Ingår i: BMC Public Health. - : Springer. - 1471-2458. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously reported on the design and efficacy of two cluster-randomized multi-level workplace interventions, attempting to decrease sedentary behavior (SED) or increase moderate to vigorous physical activity (MVPA) among office workers to improve mental health outcomes. The aim of this study was to investigate intervention effects on mental health outcomes, i.e., mental wellbeing, depression or anxiety symptoms, and stress immediately after the 6-month intervention period.Methods: Teams of 263 office workers were cluster-randomized to one of two interventions or a waitlist control group. The PA intervention (iPA) focused on increasing MVPA and the SED intervention (iSED) on reducing SED. Both multi-level interventions targeted individual office workers and their social, physical, and organizational work environment, incorporating counseling based on cognitive behavioral therapy and motivational interviewing. Mental health outcomes were assessed using validated questionnaires before and immediately after the intervention. Intervention effects were analyzed using linear mixed effects models.Results: Participants were mostly female and highly educated, with a mean age of 42 years and had favorable levels of mental health at baseline. Mental wellbeing improved for the iSED group (β = 8, 95% CI 1 to 15, p = 0.030) but not for the iPA group (β = 6, 95% CI -1 to 12, p = 0.072) compared to the control group. No effects were found for depression or anxiety symptoms or stress.Conclusions: The multi-level interventions improved mental wellbeing among this population of office workers, reaching statistical significance in the iSED group. The size of the effect can be regarded meaningful, considering favorable mental health and high PA level at baseline. Thus, workplace interventions that provide support on multiple levels appear to have potential for improving mental wellbeing, but not reducing ill-health variables, among healthy office workers. More research is needed to understand the mechanisms through which such improvements can be achieved and to identify the most effective intervention components.
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| 10. |
- Macpherson, Alex, et al.
(författare)
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The allosteric modulation of complement C5 by knob domain peptides
- 2021
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Ingår i: eLIFE. - : ELife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Bovines have evolved a subset of antibodies with ultra-long heavy chain complementarity determining regions that harbour cysteine-rich knob domains. To produce high-affinity peptides, we previously isolated autonomous 3-6 kDa knob domains from bovine antibodies. Here, we show that binding of four knob domain peptides elicits a range of effects on the clinically validated drug target complement C5. Allosteric mechanisms predominated, with one peptide selectively inhibiting C5 cleavage by the alternative pathway C5 convertase, revealing a targetable mechanistic difference between the classical and alternative pathway C5 convertases. Taking a hybrid biophysical approach, we present C5-knob domain co-crystal structures and, by solution methods, observed allosteric effects propagating >50 angstrom from the binding sites. This study expands the therapeutic scope of C5, presents new inhibitors, and introduces knob domains as new, low molecular weight antibody fragments, with therapeutic potential.
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