| 1. |
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| 2. |
- Anthon, Carl Thomas, et al.
(författare)
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Thrombocytopenia and platelet transfusions in ICU patients : an international inception cohort study (PLOT-ICU)
- 2023
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Ingår i: Intensive Care Medicine. - 0342-4642. ; 49:11, s. 1327-1338
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Thrombocytopenia (platelet count < 150 × 10 9/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses.RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42).CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.
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| 3. |
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| 4. |
- Axelsson, Eva, et al.
(författare)
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Recessiveness and Dominance in Barley Mutants Deficient in Mg-Chelatase Subunit D, an AAA Protein Involved in Chlorophyll Biosynthesis.
- 2006
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Ingår i: Plant Cell. - : Oxford University Press (OUP). - 1040-4651 .- 1532-298X. ; 18:12, s. 3606-3616
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Tidskriftsartikel (refereegranskat)abstract
- Mg-chelatase catalyzes the insertion of Mg2+ into protoporphyrin IX at the first committed step of the chlorophyll biosynthetic pathway. It consists of three subunits: I, D, and H. The I subunit belongs to the AAA protein superfamily ( ATPases associated with various cellular activities) that is known to form hexameric ring structures in an ATP-dependant fashion. Dominant mutations in the I subunit revealed that it functions in a cooperative manner. We demonstrated that the D subunit forms ATP-independent oligomeric structures and should also be classified as an AAA protein. Furthermore, we addressed the question of cooperativity of the D subunit with barley (Hordeum vulgare) mutant analyses. The recessive behavior in vivo was explained by the absence of mutant proteins in the barley cell. Analogous mutations in Rhodobacter capsulatus and the resulting D proteins were studied in vitro. Mixtures of wild-type and mutant R. capsulatus D subunits showed a lower activity compared with wild-type subunits alone. Thus, the mutant D subunits displayed dominant behavior in vitro, revealing cooperativity between the D subunits in the oligomeric state. We propose a model where the D oligomer forms a platform for the stepwise assembly of the I subunits. The cooperative behavior suggests that the D oligomer takes an active part in the conformational dynamics between the subunits of the enzyme.
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| 5. |
- Blechinger, Tobias, et al.
(författare)
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6 av 10 ST-läkare på BUP funderar på att hoppa av - Upplevelse av brist på effektiv psykologisk behandling och låg autonomi på arbetsplatsen främsta orsaker
- 2019
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Ingår i: Läkartidningen. - 0023-7205. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Association for Child and Adolescent Psychiatry conducted a survey among their specialty trainees in 2018. Of the 48% response rate, around 48% admitted hesitancy to continue in their chosen specialty. A further 12% planned to depart from their field after completion of training. Factors associated with discontinuation in training were the perception of ineffective psychotherapeutic treatments and a lack of autonomy at work; which was strongly correlated to the doctor's role and team collaboration. Workload was generally perceived as excessive, with not enough time for after work recovery and the subsequent negative impact on private life. However, these factors were not found to significantly affect trainees' decision to leave. The doctor's role requires better clarification and medical leadership needs to be improved, so that evidence based treatments can be offered.
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| 6. |
- Blomström Lundqvist, Carina, et al.
(författare)
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Impact of non-adherence to direct oral anticoagulants amongst Swedish patients with non-valvular atrial fibrillation: results from a real-world cost-utility analysis
- 2022
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Ingår i: Journal of Medical Economics. - : Taylor & Francis. - 1369-6998 .- 1941-837X. ; 25:1, s. 1085-1091
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Tidskriftsartikel (refereegranskat)abstract
- Aims: A third of non-valvular atrial fibrillation (NVAF) patients are non-adherent to direct oral anticoagulants (DOACs). Estimates of the economic value of full adherence and the cost of two types of adherence improving interventions are important to healthcare planners and decision-makers.Methods: A cost-utility analysis estimated the impact of non-adherence over a 20-year horizon, for a patient cohort with a mean age of 77 years, based on data from the Stockholm Healthcare database of NVAF patients with incident stroke between 2011 and 2018. Adherence was defined using a medication possession ratio (MPR) cut-off of 90%; primary outcomes were the number of ischemic strokes and associated incremental cost–utility ratio.Results: Hypothetical comparisons between cohorts of 1,000 patients with varying non-adherence levels and full adherence (MPR >90%) predicted an additional number of strokes ranging from 117 (MPR = 81–90%) to 866 (MPR <60%), and years of life lost ranging from 177 (MPR = 81– 90%) to 1,318 (MPR < 60%; discounted at 3%). Chronic disease co-management intervention occurring during each DOAC prescription renewal and patient education intervention at DOAC initiation will be cost-saving to the health system if its cost is below SEK 143 and SEK 4,655, and cost-effective if below SEK 858 and SEK 28,665, respectively.Conclusion: Adherence improving interventions for NVAF patients on DOACs such as chronic disease co-management and patient education can be cost-saving and cost-effective, within a range of costs that appear reasonable to the Swedish healthcare system.
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| 7. |
- Chen, Xinsong, et al.
(författare)
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Breast cancer patient-derived whole-tumor cell culture model for efficient drug profiling and treatment response prediction
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 120:1
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer (BC) is a complex disease comprising multiple distinct subtypes with different genetic features and pathological characteristics. Although a large number of antineoplastic compounds have been approved for clinical use, patient-to-patient variability in drug response is frequently observed, highlighting the need for efficient treatment prediction for individualized therapy. Several patient-derived models have been established lately for the prediction of drug response. However, each of these models has its limitations that impede their clinical application. Here, we report that the whole-tumor cell culture (WTC) ex vivo model could be stably established from all breast tumors with a high success rate (98 out of 116), and it could reassemble the parental tumors with the endogenous microenvironment. We observed strong clinical associations and predictive values from the investigation of a broad range of BC therapies with WTCs derived from a patient cohort. The accuracy was further supported by the correlation between WTC-based test results and patients' clinical responses in a separate validation study, where the neoadjuvant treatment regimens of 15 BC patients were mimicked. Collectively, the WTC model allows us to accomplish personalized drug testing within 10 d, even for small-sized tumors, highlighting its potential for individualized BC therapy. Furthermore, coupled with genomic and transcriptomic analyses, WTC-based testing can also help to stratify specific patient groups for assignment into appropriate clinical trials, as well as validate potential biomarkers during drug development.
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| 8. |
- Chen, Zhiqiang, et al.
(författare)
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Method for accurate fiber length determination from increment cores for large-scale population analyses in Norway spruce
- 2016
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Ingår i: Holzforschung. - : Walter de Gruyter GmbH. - 0018-3830 .- 1437-434X. ; 70:9, s. 829-838
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Tidskriftsartikel (refereegranskat)abstract
- Fiber (tracheid) length is an important trait targeted for genetic and silvicultural improvement. Such studies require large-scale non-destructive sampling, and accurate length determination. The standard procedure for non-destructive sampling is to collect increment cores, singularize their cells by maceration, measure them with optical analyzer and apply various corrections to suppress influence of non-fiber particles and cut fibers, as fibers are cut by the corer. The recently developed expectation-maximization method (EM) not only addresses the problem of non-fibers and cut fibers, but also corrects for the sampling bias. Here, the performance of the EM method has been evaluated by comparing it with length-weighing and squared length-weighing, both implemented in fiber analyzers, and with microscopy data for intact fibers, corrected for sampling bias, as the reference. This was done for 12-mm increment cores from 16 Norway spruce (Picea abies (L.) Karst) trees on fibers from rings 8-11 (counted from pith), representing juvenile wood of interest in breeding programs. The EM-estimates provided mean-fiber-lengths with bias of only +2.7% and low scatter. Length-weighing and length2-weighing gave biases of-7.3% and +9.3%, respectively, and larger scatter. The suggested EM approach constitutes a more accurate non-destructive method for fiber length (FL) determination, expected to be applicable also to other conifers.
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| 9. |
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| 10. |
- Clausen, Fredrik, et al.
(författare)
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Oxygen free radical-dependent activation of extracellular signal-regulated kinase mediates apoptosis-like cell death after traumatic brain injury
- 2004
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Ingår i: Journal of Neurotrauma. ; 21:9, s. 1168-1182
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Tidskriftsartikel (refereegranskat)abstract
- Mitogen-activated protein kinase (MAPK) cascades are membrane-to-nucleus signaling modules that recently have been implicated as mediators of cellular injury. In this study, we investigated the involvement of the MAP kinase p44/p42 (extracellular signal-regulated kinase [ERK1/2]) in traumatic brain injury (TBI) in rats. There was a strong increase in activated, phosphorylated ERK 1/2 (p-ERK 1/2) protein at 10 min up to 24 h after the injury. Expression of p-ERK occurred in cells identified as neurons, astrocytes, and microglia. Most of the cells expressing p-ERK were TUNEL positive at later time points. Treatment with the MEK inhibitor U0126 or the free radical scavenger S-PBN, both with neuroprotective properties in TBI, attenuated the early activation of ERK and resulted in less activation of caspase-3 and subsequent DNA fragmentation. Post-treatment with U0126 resulted in a significant decrease (-60%) in cortical cavity size and cortical atrophy at 2 weeks after trauma. Overall, the results suggest that ERK activation is initiated by increased oxygen radical activity and that overactivation of ERK sets off secondary cell death mechanisms in TBI. Clinical studies are warranted to evaluate the concept of MEK inhibition in head-injured patients.
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| 11. |
- Corvigno, Sara, et al.
(författare)
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High density of stroma-localized CD11c-positive macrophages is associated with longer overall survival in high-grade serous ovarian cancer.
- 2020
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 159:3, s. 860-868
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Pre-clinical studies have identified marker- and tumor compartment-defined functionally distinct macrophage subsets. Our study analyzes marker-defined macrophage subsets in different tumor compartments of high-grade serous ovarian cancer (HGSC).METHODS: A discovery cohort (N = 113) was subjected to immunohistochemistry (IHC) analyses. CD68-positivity was confirmed for CD11c-, CD80- and CD163-positive cells. Subset-marker-positive cells were scored in the total tumor and in four tumor compartments. Correlation analyses investigated co-expression of subsets, relationship to CD8+ cells and survival associations. A validation cohort (N = 121) was used to confirm selected findings from the discovery cohort.RESULTS: CD163-positve cells was the most abundant subtype in all compartments. CD11c and CD163 subsets were strongly correlated with each other in stroma and epithelial areas, whereas CD80 and CD163 were correlated in epithelial areas. CD80 and CD11c in perivascular areas showed low correlations. Strong associations were detected between CD8 and CD80 in the tumor epithelium-dominated areas, and between CD8 and CD11c in stroma areas. High stromal CD11c density was associated with a longer median overall survival in the discovery cohort (HR 0.39; CI 95%, 0.23-0.68; p = 0.001) and in the validation cohort (HR 0.46; CI 95%, 0.22-0.93; p = 0.03).CONCLUSIONS: Our study supports the existence of clinically relevant marker- and localization defined macrophage subsets in HGSC, which are independently regulated. Moreover, it suggests stromal CD11c as a novel prognostic marker in HGSC.
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| 12. |
- Corvigno, Sara, et al.
(författare)
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Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival
- 2016
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Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 7:14, s. 18573-18584
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Tidskriftsartikel (refereegranskat)abstract
- Inter- and intra-patient variations in tumor microenvironment of serous ovarian cancer are largely unexplored. We aimed to explore potential co-regulation of tumor stroma characteristics, analyze their concordance in primary and metastatic lesions, and study their impact on survival. A tissue microarray (TMA) with 186 tumors and 91 matched metastases was subjected to immunohistochemistry double staining with endothelial cell marker CD34 and fibroblast and pericyte markers alpha-SMA, PDGF beta R and desmin. Images were digitally analyzed to yield "metrics" related to vasculature and stroma features. Intra-case analyses showed that PDGF beta R in perivascular cells and fibroblasts were strongly correlated. Similar findings were observed concerning `-SMA. Most stroma characteristics showed large variations in intra-case comparisons of primary tumors and metastasis. Large PDGF beta R-positive stroma fraction and high PDGF beta FR positive perivascular intensity were both significantly associated with shorter survival in uni- and multi-variate analyses (HR 1.7, 95% CI 1.1-2.5; HR 1.7, 95% CI 1.1-2.8). In conclusion, we found PDGF beta R- and alpha-SMA-expression to be largely independent of each other but concordantly activated in perivascular cells and in fibroblasts within the primary tumor. Stromal characteristics differed between primary tumors and metastases. PDGF beta R in perivascular cells and in fibroblasts may be novel prognostic markers in serous ovarian cancer.
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| 13. |
- Cukalevski, Risto, et al.
(författare)
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Structural Changes in Apolipoproteins Bound to Nanoparticles
- 2011
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 27:23, s. 14360-14369
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles are widely used in the pharmaceutical and food industries, but the consequences of exposure to the human body have not been thoroughly investigated. Apolipoprotein A-I (apoAI), the major protein in high-density lipoprotein (HDL), and other lipoproteins are found in the corona around many nanopartides, but data on protein structural and functional effects are lacking. Here we investigate the structural consequences of the adsorption of apoAI, apolipoprotein B100 (apoB100), and HDL on polystyrene nanoparticles with different surface charges. The results of circular dichroism, fluorescence spectroscopy, and limited proteolysis experiments indicate effects on both secondary and tertiary structures. Plain and negatively charged nanoparticles induce helical structure in apoAI (negative net charge) whereas positively charged nanoparticles reduce the amount of helical structure. Plain and negatively charged partides induce a small blue shift in the tryptophan fluorescence spectrum, which is not noticed with the positively charged particles. Similar results are observed with reconstituted HDL. In apoB100, both secondary and tertiary structures are perturbed by all particles. To investigate the generality of the role of surface charge, parallel experiments were performed using human Serum albumin (HSA, negative net charge) and lysozyme (positive net charge). Again, the secondary structure is most affected by nanoparticles carrying an opposite surface charge relative to the protein. Nanoparticles carrying the same net charge as the protein induce only minor structural changes in lysozyme whereas a moderate change is observed for HSA. Thus, surface charge is a critical parameter for predicting structural changes in adsorbed proteins, yet the effect is specific for each protein.
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| 14. |
- Dell'Orco, Daniele, et al.
(författare)
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Delivery success rate of engineered nanoparticles in the presence of the protein corona: a systems-level screening
- 2012
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Ingår i: Nanomedicine: Nanotechnology, Biology and Medicine. - : Elsevier BV. - 1549-9642 .- 1549-9634. ; 8:8, s. 1271-1281
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles (NPs) for medical applications are often introduced into the body via intravenous injections, leading to the formation of a protein corona on their surface due to the interaction with blood plasma proteins. Depending on its composition and time evolution, the corona will modify the biological behavior of the particle. For successful delivery and targeting, it is therefore important to assess on a quantitative basis how and to what extent the presence of the corona perturbs the specific interaction of a designed NP with its cellular target. We present a theoretical systems-level analysis, in which peptides have been covalently coupled to the surface of nanoparticles, describing the delivery success rate in varying conditions, with regard to protein composition of the surrounding fluid. Dynamic modeling and parameter sensitivity analysis proved to be useful and computationally affordable tools to aid in the design of NPs with increased success rate probability in a biological context. FROM THE CLINICAL EDITOR: The formation of a protein corona consisting of blood plasma proteins on the surface of intravenously delivered nanoparticles may modify the biological behavior of the particles. This team of investigators present a theoretical systems-level analysis of this important and often neglected phenomenon.
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| 15. |
- Dell'Orco, Daniele, et al.
(författare)
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Mathematical modeling of the protein corona: implications for nanoparticulate delivery systems
- 2014
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Ingår i: Nanomedicine. - 1743-5889. ; 9:6, s. 851-858
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Tidskriftsartikel (refereegranskat)abstract
- This article discusses the role of the protein corona in delivery systems with tagged nanoparticles and how knowledge of the protein corona can help in optimizing delivery. The basic question is whether and how the binding of proteins and other biomolecules at the nanoparticle surface interfere with the interaction between a tag and its receptor. This is an interesting problem in many respects, but most intriguing are the observed differences in delivery efficiency in vivo compared with protein-free in vitro conditions. In order to understand possible situations that the nanoparticle will face in a protein-rich biological environment, we will first describe the formation of a protein corona and thereafter discuss potential perturbations of the delivery systems when moving from in vitro testing to in vivo applications. We emphasize the role of mathematical modeling in optimizing the design of functionalized nanoparticles to achieve high success of delivery.
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| 16. |
- Dell'Orco, Daniele, et al.
(författare)
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Mathematical modeling of the protein corona : Implications for nanoparticulate delivery systems
- 2016. - 2
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Ingår i: Handbook of Immunological Properties of Engineered Nanomaterials: : Haematocompatibility of Engineered Nanomaterials - Haematocompatibility of Engineered Nanomaterials. - : WORLD SCIENTIFIC. - 9789814699167 - 9789814699174 ; 2, s. 53-65
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Bokkapitel (refereegranskat)abstract
- This article discusses the role of the protein corona in delivery systems with tagged nanoparticles and how knowledge of the protein corona can help in optimizing delivery. The basic question is whether and how the binding of proteins and other biomolecules at the nanoparticle surface interfere with the interaction between a tag and its receptor. This is an interesting problem in many respects, but most intriguing are the observed differences in delivery effi ciency in vivo compared with protein-free in vitro conditions. In order to understand possible situations that the nanoparticle will face in a protein-rich biological environment, we will fi rst describe the formation of a protein corona and thereafter discuss potential perturbations of the delivery systems when moving from in vitro testing to in vivo applications. We emphasize the role of mathematical modeling in optimizing the design of functionalized nanoparticles to achieve high success of delivery.
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| 17. |
- Dell'Orco, Daniele, et al.
(författare)
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Modeling the Time Evolution of the Nanoparticle-Protein Corona in a Body Fluid
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nanoparticles in contact with biological fluids interact with proteins and other biomolecules, thus forming a dynamic corona whose composition varies over time due to continuous protein association and dissociation events. Eventually equilibrium is reached, at which point the continued exchange will not affect the composition of the corona. Results: We developed a simple and effective dynamic model of the nanoparticle protein corona in a body fluid, namely human plasma. The model predicts the time evolution and equilibrium composition of the corona based on affinities, stoichiometries and rate constants. An application to the interaction of human serum albumin, high density lipoprotein (HDL) and fibrinogen with 70 nm N-iso-propylacrylamide/N-tert-butylacrylamide copolymer nanoparticles is presented, including novel experimental data for HDL. Conclusions: The simple model presented here can easily be modified to mimic the interaction of the nanoparticle protein corona with a novel biological fluid or compartment once new data will be available, thus opening novel applications in nanotoxicity and nanomedicine.
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| 18. |
- Domínguez Del Campo, Marta, et al.
(författare)
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Cross-cultural adaptation and psychometric properties of the Spanish Quality in Psychiatric Care Forensic Inpatient Staff (QPC-FIPS) instrument
- 2022
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Ingår i: Scientific Reports. - : Nature portfolio. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Quality in Psychiatric Care-Forensic Inpatient Staff (QPC-FIPS) is an instrument of Swedish origin validated to measure the perception of the quality of mental health care provided by forensic psychiatry professionals. The aim of this study was to cross-culturally adapt the QPC-FIPS instrument and to evaluate the psychometric properties of the Spanish version of the instrument. A psychometric study was carried out. For validity, content validity, convergent validity and construct validity were included. For reliability, the analysis of internal consistency and temporal stability was included. The sample consisted of 153 mental health professionals from four Forensic Psychiatry units. The adapted Spanish version of the QPC-FIPS scale was configured with the same number of items and dimensions as the original. The psychometric properties, in terms of temporal stability and internal consistency, were adequate and the factor structure, such as the homogeneity of the dimensions of the Spanish version of the QPC-FIPS, was equivalent to the original Swedish version. We found that the QPC_FIPS-Spanish is a valid, reliable and easy-to-apply instrument for assessing the self-perception of professionals regarding the care they provide.
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| 19. |
- Drevinge, Christina, 1983, et al.
(författare)
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Perilipin 5 is protective in the ischemic heart
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 219, s. 446-454
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Tidskriftsartikel (refereegranskat)abstract
- Background: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. Methods and results: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5(-/-) mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction. Conclusion: Our findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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| 20. |
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| 21. |
- Ermert, David, et al.
(författare)
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The molecular basis of human igg-mediated enhancement of C4b-binding protein recruitment to group a streptococcus
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10:JUN
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes infects over 700 million people worldwide annually. Immune evasion strategies employed by the bacteria include binding of the complement inhibitors, C4b-binding protein (C4BP) and Factor H in a human-specific manner. We recently showed that human IgG increased C4BP binding to the bacterial surface, which promoted streptococcal immune evasion and increased mortality in mice. We sought to identify how IgG promotes C4BP binding to Protein H, a member of the M protein family. Dimerization of Protein H is pivotal for enhanced binding to human C4BP. First, we illustrated that Protein H, IgG, and C4BP formed a tripartite complex. Second, surface plasmon resonance revealed that Protein H binds IgG solely through Fc, but not Fab domains, and with high affinity (IgG-Protein H: KD = 0.4 nM; IgG-Fc-Protein H: KD ≤1.6 nM). Each IgG binds two Protein H molecules, while up to six molecules of Protein H bind one C4BP molecule. Third, interrupting Protein H dimerization either by raising temperature to 41°C or with a synthetic peptide prevented IgG-Protein H interactions. IgG-Fc fragments or monoclonal human IgG permitted maximal C4BP binding when used at concentrations from 0.1 to 10 mg/ml. In contrast, pooled human IgG enhanced C4BP binding at concentrations up to 1 mg/ml; decreased C4BP binding at 10 mg/ml occurred probably because of Fab-streptococcal interactions at these high IgG concentrations. Taken together, our data show how S. pyogenes exploits human IgG to evade complement and enhance its virulence. Elucidation of this mechanism could aid design of new therapeutics against S. pyogenes.
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| 22. |
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| 23. |
- Haemig, Paul D, et al.
(författare)
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Ecology and phylogeny of birds foraging at outdoor restaurants in Sweden
- 2015
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Ingår i: Biodiversity Data Journal. - : Pensoft Publishers. - 1314-2836 .- 1314-2828. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Birds frequently visit the outdoor serving areas of restaurants to feed on scraps of food and leftovers. Although this feeding association between humans and birds is widespread and could have significant effects, both positive and negative, for all taxa involved, the authors know of no published studies that have investigated restaurant bird communities. To lay the foundation for future research, the authors conducted a basic study of birds at 80 outdoor restaurants in Sweden, identifying which species and taxonomic clades of birds visited the restaurants and comparing restaurant birds in urban and rural environments. New information: Thirteen species of birds visited the outdoor restaurants. Eight of these species were predominant, i.e. accounting for 51% or more of bird presence (sum of minutes of all individual birds) at one or more restaurants. Every restaurant studied had a predominant species, but species often differed from each other in frequency of predominance in different landscapes. No endangered species were seen visiting restaurants. However, three farmland bird species (House Sparrow Passer domesticus, White Wagtail Motacilla alba, Eurasian Tree Sparrow Passer montanus), whose numbers are reported to be declining in the countryside, were predominant at the majority of restaurants in rural areas, suggesting that rural restaurants might be able to contribute to the conservation of these species. The thirteen species of restaurant-visiting birds belonged to five monophyletic clades. Ninety percent of all restaurants had, as their predominant species, birds from either Clade A (Passeridae, Motacillidae, Fringillidae) or Clade C (Corvidae). Statistical testing revealed that Clade A and Clade C were distributed differently in environments along the urban-rural gradient. At all spatial scales measured, birds of Clade C were predominant at the majority of restaurants in urban areas, while birds of Clade A were the predominant clade at the majority of restaurants in rural areas. The authors use this evidence, and observations of birds foraging in association with other primates, to hypothesize that the outdoor serving areas of modern restaurants may be helping to preserve and nurture ancient human-bird symbioses that have been part of human ecology since antiquity.
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| 24. |
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| 25. |
- Jönsson, Lisbeth, et al.
(författare)
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Mothers of children with down syndrome : A qualitative study of experiences of breastfeeding and breastfeeding support
- 2022
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Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 36:4, s. 1156-1164
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children with down syndrome (DS) are breastfed to a lesser extent than infants in general, despite research showing that it is possible for these children to breastfeed successfully. Aim: The aim was to describe how mothers of children with DS experienced breastfeeding and breastfeeding support from healthcare professionals. Method: A qualitative study with an inductive approach. Individual interviews were performed with seven mothers from southern Sweden. The interviews were analysed using qualitative content analysis. Result: The mothers felt that the support varied, as some healthcare professionals were supportive, while others had preconceptions regarding breastfeeding and DS. They also experienced that the guidelines could be an obstacle in the encounter with healthcare professionals thereby affecting the possibility to establish breastfeeding. Information and support were important to the mothers, and when insufficient, they turned to the internet for help. Conclusions: Mothers felt that healthcare professionals were bound to ward routines and guidelines, which could be contrary to their own and the family's wishes. They were also sensitive to the attitudes of healthcare professionals, which can affect their own state of mind. Healthcare professionals' preconceptions regarding breastfeeding and DS have not changed, despite research showing that infants with DS can breastfeed successfully. Increased awareness of the possibility to breastfeed an infant with DS is needed to provide better support to mothers.
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| 26. |
- Jönsson, Malin, et al.
(författare)
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CaRA – A multi-purpose phage display library for selection of calcium-regulated affinity proteins
- 2022
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Ingår i: New Biotechnology. - : Elsevier B.V.. - 1871-6784 .- 1876-4347. ; 72, s. 159-167
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Tidskriftsartikel (refereegranskat)abstract
- Protein activity regulated by interactions with metal ions can be utilized for many different purposes, including biological therapies and bioprocessing, among others. Calcium ions are known to interact with the frequently occurring EF-hand motif, which can alter protein activity upon binding through an induced conformational change. The calcium-binding loop of the EF-hand motif has previously been introduced into a small protein domain derived from staphylococcal Protein A in a successful effort to render antibody binding dependent on calcium. Presented here, is a combinatorial library for calcium-regulated affinity, CaRA, based on this domain. CaRA is the first alternative scaffold library designed to achieve novel target specificities with metal-dependent binding. From this library, several calcium-dependent binders could be isolated through phage display campaigns towards a set of unrelated target proteins (IgE Cε3-Cε4, TNFα, IL23, scFv, tPA, PCSK9 and HER3) useful for distinct applications. Overall, these monomeric CaRA variants showed high stability and target affinities within the nanomolar range. They displayed considerably higher melting temperatures in the presence of 1 mM calcium compared to without calcium. Further, all discovered binders proved to be calcium-dependent, with the great majority showing complete lack of target binding in the absence of calcium. As demonstrated, the CaRA library is highly capable of providing protein-binding domains with calcium-dependent behavior, independent of the type of target protein. These binding domains could subsequently be of great use in gentle protein purification or as novel therapeutic modalities.
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| 27. |
- Kerekes, Nora, 1969-, et al.
(författare)
-
The associations between ADHD, pain, inflammation, and quality of life in children and adolescents-a clinical study protocol
- 2022
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 17:9 September
-
Tidskriftsartikel (refereegranskat)abstract
- New research shows that the prevalence of neurodevelopmental disorders, such as attention- deficit/hyperactivity disorder (ADHD), is increased in children and adolescents as well as in adults with chronic pain, compared to those without chronic pain. Children and adolescents with ADHD also have an increased incidence of various physical conditions associated with pain, and they more frequently suffer from inflammatory diseases. Moreover, parents of children with ADHD can often suffer from pain conditions. These epidemiological and clinical observations form the scientific basis of our study, which aims to map the relationships between ADHD, altered pain experiences/central sensitization, and inflammation in children and adolescents. We will investigate the presence of central sensitization in children and adolescents with newly diagnosed ADHD and compare it with those who have not been diagnosed with ADHD. Participants (and their biological parents) will complete surveys about their somatic health, pain experience, and quality of life. Biological samples (saliva and stool) will be collected, aiming to utilize proteome and metabolome data to discover disease mechanisms and to predict, prevent and treat them. The results from our investigation should enable an expanded understanding of the pathophysiology behind both ADHD and pain/central sensitization. Presently, there are no established protocols for addressing psychiatric symptoms when examining patients with pain conditions in a somatic care setting, nor is there any knowledge of offering patients with ADHD or other neurodevelopmental disorders adapted treatments for pain conditions. Our results, therefore, can contribute to the development of new treatment strategies for pathological pain conditions in children and adolescents with ADHD. They may also increase awareness about and provide opportunities for the treatment of attention and impulse control problems in children and adolescents with pain syndromes. © 2022 Kerekes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 28. |
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| 29. |
- Linse, Sara, et al.
(författare)
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Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies
- 2020
-
Ingår i: Nature Structural and Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 27:12, s. 1125-1133
-
Tidskriftsartikel (refereegranskat)abstract
- The amyloid cascade hypothesis, according to which the self-assembly of amyloid-β peptide (Aβ) is a causative process in Alzheimer’s disease, has driven many therapeutic efforts for the past 20 years. Failures of clinical trials investigating Aβ-targeted therapies have been interpreted as evidence against this hypothesis, irrespective of the characteristics and mechanisms of action of the therapeutic agents, which are highly challenging to assess. Here, we combine kinetic analyses with quantitative binding measurements to address the mechanism of action of four clinical stage anti-Aβ antibodies, aducanumab, gantenerumab, bapineuzumab and solanezumab. We quantify the influence of these antibodies on the aggregation kinetics and on the production of oligomeric aggregates and link these effects to the affinity and stoichiometry of each antibody for monomeric and fibrillar forms of Aβ. Our results reveal that, uniquely among these four antibodies, aducanumab dramatically reduces the flux of Aβ oligomers.
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| 30. |
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| 31. |
- Lundqvist-Gustafsson, Helen, 1966-, et al.
(författare)
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Involvement of p38-mitogen-activated protein kinase in staphylococcus aureus-induced neutrophil apoptosis
- 2001
-
Ingår i: Journal of Leukocyte Biology. - 0741-5400 .- 1938-3673. ; 70:4, s. 642-648
-
Tidskriftsartikel (refereegranskat)abstract
- Apoptosis occurred in human neutrophils within an hour of exposure to viable serumopsonized Staphylococcus aureus, as indicated by appearance of cells with condensed nuclei, fragmented DNA, and increased phosphatidylserine exposure. In contrast, serum-opsomized, heat-killed S. aureus did not induce apoptosis. This discrepancy could not be explained by differences in bacterial uptake or total NADPH-oxidase activity. Suppressing phagocytosis by pretreating the neutrophils with cytochalasin b or by using nonopsonized bacteria did not prevent apoptosis. A supernatant from bacteria grown for 2 h in nutrient broth had a strong proapoptotic influence that was abrogated by heat treatment. Exposure to viable S. aureus or supernatant also led to activation of p38-mitogen-activated protein kinase in the neutrophils. Inhibition of this kinase with SB203580 reduced the apoptosis-inducing capacity of both bacteria and supernatant. We conclude that S. aureus activates p38-mitogen-activated protein kinase in neutrophils and induces apoptosis, probably mediated by a bacteria-derived soluble factor(s).
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| 32. |
- Lundqvist, Martin, et al.
(författare)
-
Expression, purification and characterisation of large quantities of recombinant human IAPP for mechanistic studies
- 2021
-
Ingår i: Biophysical Chemistry. - : Elsevier BV. - 0301-4622. ; 269
-
Tidskriftsartikel (refereegranskat)abstract
- Malfunction and amyloid formation of the Islet Amyloid Polypeptide (IAPP) are factors contributing to Type 2 diabetes. Unravelling the mechanism of IAPP aggregate formation may forward our understanding of this process and its effect on pancreatic β-islet cell. Such mechanistic studies require access to sequence homogeneous and highly pure IAPP. Here we present a new facile protocol for the production of pure recombinant human IAPP at relatively high yield. The protocol uses a His-tagged version of the Npro mutant EDDIE, which drives expression to inclusion bodies, from which the peptide is purified using sonication, refolding and auto-cleavage, removal of EDDIE using Ni-NTA chromatography and reverse-phase HPLC. The purified material is used at multiple concentrations in aggregation kinetics measurements monitored by thioflavin-T fluorescence. Global analysis of the data implies a double nucleation aggregation mechanism including both primary and secondary nucleation.
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| 33. |
- Lundqvist, Martin, et al.
(författare)
-
Rapid and facile purification of apolipoprotein A-I from human plasma using thermoresponsive nanoparticles
- 2011
-
Ingår i: Journal of Biomaterials and Nanobiotechnology. - : Scientific Research Publishing, Inc.. - 2158-7027 .- 2158-7043. ; 2:3, s. 258-266
-
Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles can be used to purify proteins from plasma. We report here the purification of apolipoprotein A-I (apoA-I) with high specificity from human plasma using copolymeric nanoparticles. We present an optimized protocol using 50:50 NiPAM:BAM copolymer nanoparticles with thermo-responsive properties as an affinity resin. Repeated pelleting and washing of nanoparticle-captured apoA-I is achieved through temperature cycling. The protein is then eluted using urea followed by an ion exchange step for protein concentration and depletion of nanoparticles
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| 34. |
- Lundqvist, Martin, et al.
(författare)
-
The nanoparticle protein corona formed in human blood or human blood fractions
- 2017
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
-
Tidskriftsartikel (refereegranskat)abstract
- The protein corona formed around nanoparticles in protein-rich fluids plays an important role for nanoparticle biocompatibility, as found in several studies during the last decade. Biological fluids have complex compositions and the molecular components interact and function together in intricate networks. Therefore, the process to isolate blood or the preparation of blood derivatives may lead to differences in the composition of the identified protein corona around nanoparticles. Here, we show distinct differences in the protein corona formed in whole blood, whole blood with EDTA, plasma, or serum. Furthermore, the ratio between particle surface area to protein concentration influences the detected corona. We also show that the nanoparticle size per se influences the formed protein corona due to curvature effects. These results emphasize the need of investigating the formation and biological importance of the protein corona in the same environment as the nanoparticles are intended for or released into.
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| 35. |
- Lundqvist, Sara
(författare)
-
Abandoning Silos for Integration: Implementing Enterprise Risk Management and Risk Governance
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Firms began to abandon the “silo” approach to risk management for more integration in the risk management system. Enterprise risk management (ERM) emerged as a framework for the management of integrated risks in a strategy setting supported by risk governance. Practically and empirically there has been no real consensus about what an ERM firm looks like. ERM frameworks provide a variety of conceptualizations of ERM, and empirically there are numerous ways of measuring and identifying ERM. There has been a stagnant and inconsistent development of the theoretical foundations of ERM, and empirically there has been inconsistent evidence on the determinants and value of ERM. Though there has been momentum in exploring enterprise risk management, there is a continuing lack of consensus which this dissertation approaches by answering the following questions: What does an ERM firm look like? Why do firms implement ERM? What effect does ERM have on the firm? The first article explores what an ERM firm looks like and identifies four underlying pillars of ERM based on how firms actually implement ERM dimensions. The identifying component of ERM implementation is the holistic organization of risk management - the implementation of risk governance. The second article uses this new conceptualization of ERM to investigate why firms take the step beyond traditional risk management and implement risk governance. Determinants of risk governance implementation are found to be the size of the firm, leverage and dividend payments, and the chief executive officer’s influence on the board. The final article proposes that the reduction of credit risk may be a new way to measure the success of ERM in firms; the findings suggest that credit default swap spreads are significantly and negatively related to ERM implementation in banks while credit ratings are not significantly related to ERM when overall corporate governance is controlled for.
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| 36. |
- Lundqvist, Sara
(författare)
-
An Exploratory Study of Enterprise Risk Management Pillars of ERM
- 2014
-
Ingår i: Journal of Accounting, Auditing & Finance. - 2160-4061. ; 29:3, s. 393-429
-
Tidskriftsartikel (refereegranskat)abstract
- There is a general consensus that enterprise risk management’s (ERM) popularity has resulted from a response to pressure on organizations to holistically manage risk. Multiple frameworks for implementation of ERM contribute to an overall uncertainty regarding the essential components of ERM. This uncertainty carries forward to empirical studies of ERM where results regarding value creation are inconclusive. There exists no real consensus about what the principal components of ERM are; this has led to identification and measurement methods that are inconsistent. By using inconsistent indicators and measures of ERM implementation, it is impossible to compare “apples to apples” and arrive at conclusive and convincing results regarding ERM’s ability to create value. This is an exploratory study of ERM aimed at determining the integral components of ERM based on how firms actually implement ERM dimensions. The result is the identification of four discrete components, or pillars, of ERM implementation; two prerequisite components related to the general internal environment and control activities of the firm, one component identifying risk management activities of the firm and one component with the defining attributes of ERM implementation. All four components must be implemented to have well-implemented ERM, but only one separates ERM firms from non-ERM firms. The resulting four components challenge existing frameworks to adapt to better reflect how firms implement ERM and can have a valuable impact on identifying and measuring ERM, leading to more informative empirical studies on the value creating abilities of ERM.
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| 37. |
- Lundqvist, Sara, 1985, et al.
(författare)
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Enterprise Risk Management and Default Risk: Evidence from the Banking Industry
- 2018
-
Ingår i: Journal of Risk and Insurance. - : Wiley. - 0022-4367. ; 85:1, s. 127-157
-
Tidskriftsartikel (refereegranskat)abstract
- Enterprise risk management (ERM) has emerged as a framework for more holistic and integrated risk management with an emphasis on enhanced governance of the risk management system. ERM should theoretically reduce the volatility of cash flows, agency risk, and information riskultimately reducing a firm's default risk. We empirically investigate the relationship between the degree of ERM implementation and default risk in a panel data set covering 78 of the world's largest banks. We create a novel measure of the degree of ERM implementation. We find that a higher degree of ERM implementation is negatively related to the credit default swap (CDS) spread of a bank. When a rich set of control variables and fixed effects are included, a one-standard-deviation increase in the degree of ERM implementation decreases CDS spreads by 21 basis points. The degree of ERM implementation is, however, not a significant determinant of credit ratings when controls for corporate governance are included.
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| 38. |
- Lundqvist, Sara, et al.
(författare)
-
Prevalence of chronic pain in children and adolescents with psychiatric conditions.
- 2023
-
Ingår i: Paediatric & neonatal pain. - : John Wiley & Sons. - 2637-3807. ; 5:2, s. 50-56
-
Tidskriftsartikel (refereegranskat)abstract
- The prevalence of pain in children and adolescents with psychiatric conditions is rarely investigated. The aims of the current study were to (a) describe the prevalence of headaches and abdominal pain in children and adolescents with psychiatric conditions, (b) compare the prevalence of pain in children and adolescents with psychiatric conditions with that in the general population, and (c) investigate the associations between pain experience and different types of psychiatric diagnoses. Families with a child aged 6-15 years who had been referred to a child and adolescent psychiatry (CAP) clinic completed the Chronic Pain in Psychiatric Conditions questionnaire. Information about the child/adolescent's psychiatric diagnosis(es) was extracted from the CAP clinic's medical records. The children and adolescents included in the study were divided into diagnostic groups and compared. Their data were also compared with data of control subjects collected during a previous study of the general population. Abdominal pain was more common among girls with a psychiatric diagnosis (85%) than in the matched control population (62%, p = 0.031). Children and adolescents with neurodevelopmental diagnoses had a higher prevalence of abdominal pain than children and adolescents with other psychiatric diagnoses. Pain conditions in children and adolescents with a psychiatric diagnosis are common and must be addressed.
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| 39. |
- Lundqvist, Sara
(författare)
-
Why firms implement risk governance - Stepping beyond traditional risk management to enterprise risk management
- 2015
-
Ingår i: Journal of Accounting and Public Policy. - : Elsevier BV. - 1873-2070 .- 0278-4254. ; 34:5, s. 441-466
-
Tidskriftsartikel (refereegranskat)abstract
- Stakeholders of firms have pushed for enterprise risk management (ERM) as a response to flawed risk management and corporate governance systems (Kirkpatrick, 2009). Previous studies explaining why ERM is implemented have been informative but overly simplified. The basic argument presented in this study is that ERM should be seen as a composition of traditional risk management and risk governance, each with their own determining factors. Implementation of risk governance is the active step beyond traditional risk management to ERM. This study addresses the complexity of ERM by dividing it into its traditional risk management and risk governance components and investigating the determinants of these components separately but simultaneously. Based on a survey of 145 firms, empirical evidence suggests that the level of risk governance in a firm is related to the size of the firm, leverage and dividend payments and the chief executive officer's influence on the board; this may suggest that corporate governance motives, like the need for governance, existing governance and the control a CEO has over governance decisions, determine the decision to take the step toward implementing ERM. This study is a step toward clarifying the existing ad hoc theoretical foundations of ERM and implies that firms are implementing ERM in accordance with stakeholder desires for better governance of the risk management system. (C) 2015 Elsevier Inc. All rights reserved.
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| 40. |
- Lynch, Iseult, et al.
(författare)
-
The nanoparticle - protein complex as a biological entity; a complex fluids and surface science challenge for the 21st century
- 2007
-
Ingår i: Advances in Colloid and Interface Science. - : Elsevier BV. - 1873-3727 .- 0001-8686. ; 134-135, s. 167-174
-
Tidskriftsartikel (refereegranskat)abstract
- The major aim of our current work is to develop a deep understanding of biological effects of nanoparticles and how these effects are mediated by proteins that are adsorbed on the nanoparticles under different biological circumstances. Due to their small size, nanoparticles have distinct properties compared to the bulk form of the same materials, and these properties are rapidly revolutionizing many areas of medicine and technology. However, relatively little is known about the interaction of nanoscale objects with biological systems, as this requires quite different concepts from more established nanoscience. Thus, we have argued that in a biological fluid, proteins associate with nanoparticles, and it is the amount and presentation of the proteins on the surface rather than the particles themselves that are the cause of numerous biological responses. It is this outer layer of proteins that is seen by the biological cells, and leads to their responses. We are developing novel techniques to identify and quantify the proteins that are consistently associated with nanoparticles, as a function of the nanoparticle size, shape, and surface properties, and to correlate the adsorbed protein identities with their association and dissociation rates to and from the nanoparticles. We also seek to understand the degree of conformational change that they undergo upon adsorption to the nanoparticles. In essence, we wish to create "epitope maps" of the protein corona that surrounds nanoparticles in biological solutions, as it is the particle-protein complex that is the biologically active entity. (c) 2007 Elsevier B.V. All rights reserved.
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| 41. |
- Lynch, Iseult, et al.
(författare)
-
The nanoparticle - protein complex as a biological entity; a complex fluids and surface science challenge for the 21st century
- 2007
-
Ingår i: Advances in Colloid and Interface Science. - Univ Coll Dublin, Sch Chem & Chem Biol, Dublin, Ireland. Conway Inst Biomed & Biomol Res, Dublin, Ireland. Lund Univ, SE-22100 Lund, Sweden. : ELSEVIER. - 0001-8686 .- 1873-3727. ; 134-35, s. 167-174
-
Tidskriftsartikel (refereegranskat)abstract
- The major aim of our current work is to develop a deep understanding of biological effects of nanoparticles and how these effects are mediated by proteins that are adsorbed on the nanoparticles under different biological circumstances. Due to their small size, nanoparticles have distinct properties compared to the bulk form of the same materials, and these properties are rapidly revolutionizing many areas of medicine and technology. However, relatively little is known about the interaction of nanoscale objects with biological systems, as this requires quite different concepts from more established nanoscience. Thus, we have argued that in a biological fluid, proteins associate with nanoparticles, and it is the amount and presentation of the proteins on the surface rather than the particles themselves that are the cause of numerous biological responses. It is this outer layer of proteins that is seen by the biological cells, and leads to their responses. We are developing novel techniques to identify and quantify the proteins that are consistently associated with nanoparticles, as a function of the nanoparticle size, shape, and surface properties, and to correlate the adsorbed protein identities with their association and dissociation rates to and from the nanoparticles. We also seek to understand the degree of conformational change that they undergo upon adsorption to the nanoparticles. In essence, we wish to create "epitope maps" of the protein corona that surrounds nanoparticles in biological solutions, as it is the particle-protein complex that is the biologically active entity. (c) 2007 Elsevier B.V. All rights reserved.
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| 42. |
- Majano, Sara Benitez, et al.
(författare)
-
Surgical treatment and survival from colorectal cancer in Denmark, England, Norway, and Sweden : a population-based study
- 2019
-
Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 20:1, s. 74-87
-
Tidskriftsartikel (refereegranskat)abstract
- Background Survival from colorectal cancer has been shown to be lower in Denmark and England than in comparable high-income countries. We used data from national colorectal cancer registries to assess whether differences in the proportion of patients receiving resectional surgery could contribute to international differences in colorectal cancer survival.Methods In this population-based study, we collected data from all patients aged 18-99 years diagnosed with primary, invasive, colorectal adenocarcinoma from Jan 1, 2010, to Dec 31, 2012, in Denmark, England, Norway, and Sweden, from national colorectal cancer registries. We estimated age-standardised net survival using multivariable modelling, and we compared the proportion of patients receiving resectional surgery by stage and age. We used logistic regression to predict the resectional surgery status patients would have had if they had been treated as in the best performing country, given their individual characteristics.Findings We extracted registry data for 139457 adult patients with invasive colorectal adenocarcinoma: 12958 patients in Denmark, 97466 in England, 11450 in Norway, and 17583 in Sweden. 3-year colon cancer survival was lower in England (63.9%, 95% CI 63.5-64.3) and Denmark (65.7%, 64.7-66.8) than in Norway (69.5%, 68.4-70.5) and Sweden (72.1%, 71.2-73.0). Rectal cancer survival was lower in England (69.7%, 69.1-70.3) than in the other three countries (Denmark 72.5%, 71.1-74.0; Sweden 74.1%, 72.7-75.4; and Norway 75.0%, 73.1-76.8). We found no significant differences in survival for patients with stage I disease in any of the four countries. 3-year survival after stage II or III rectal cancer and stage IV colon cancer was consistently lower in England (stage II rectal cancer 86.4%, 95% CI 85.0-87.6; stage III rectal cancer 75.5%, 74.2-76.7; and stage IV colon cancer 20.5%, 19.9-21.1) than in Norway (94.1%, 91.5-96.0; 83.4%, 80.1-86.1; and 33.0%, 31.0-35.1) and Sweden (92.9%, 90.8-94.6; 80.6%, 78.2-82.7; and 23.7%, 22.0-25.3). 3-year survival after stage II rectal cancer and stage IV colon cancer was also lower in England than in Denmark (stage II rectal cancer 91.2%, 88.8-93.1; and stage IV colon cancer 23.5%, 21.9-25.1). The total proportion of patients treated with resectional surgery ranged from 47803 (68.4%) of 69867 patients in England to 9582 (81.3%) of 11786 in Sweden for colon cancer, and from 16544 (59.9%) of 27599 in England to 4106 (70.8%) of 5797 in Sweden for rectal cancer. This range was widest for patients older than 75 years (colon cancer 19078 [59.7%] of 31946 patients in England to 4429 [80.9%] of 5474 in Sweden; rectal cancer 4663 [45.7%] of 10195 in England to 1342 [61.9%] of 2169 in Sweden), and the proportion of patients treated with resectional surgery was consistently lowest in England. The age gradient of the decline in the proportion of patients treated with resectional surgery was steeper in England than in the other three countries in all stage categories. In the hypothetical scenario where all patients were treated as in Sweden, given their age, sex, and disease stage, the largest increase in resectional surgery would be for patients with stage III rectal cancer in England (increasing from 70.3% to 88.2%).Interpretation Survival from colon cancer and rectal cancer in England and colon cancer in Denmark was lower than in Norway and Sweden. Survival paralleled the relative provision of resectional surgery in these countries. Differences in patient selection for surgery, especially in patients older than 75 years or individuals with advanced disease, might partly explain these differences in international colorectal cancer survival.
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| 43. |
- Nasir, Irem, et al.
(författare)
-
High Throughput Screening Method to Explore Protein Interactions with Nanoparticles.
- 2015
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
-
Tidskriftsartikel (refereegranskat)abstract
- The interactions of biological macromolecules with nanoparticles underlie a wide variety of current and future applications in the fields of biotechnology, medicine and bioremediation. The same interactions are also responsible for mediating potential biohazards of nanomaterials. Some applications require that proteins adsorb to the nanomaterial and that the protein resists or undergoes structural rearrangements. This article presents a screening method for detecting nanoparticle-protein partners and conformational changes on time scales ranging from milliseconds to days. Mobile fluorophores are used as reporters to study the interaction between proteins and nanoparticles in a high-throughput manner in multi-well format. Furthermore, the screening method may reveal changes in colloidal stability of nanomaterials depending on the physicochemical conditions.
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| 44. |
- Nordin, Steven, et al.
(författare)
-
Impact of Health-Risk Perception on Odor Perception and Cognitive Performance
- 2013
-
Ingår i: Chemosensory Perception. - : Springer Science and Business Media LLC. - 1936-5802 .- 1936-5810. ; 6:4, s. 190-197
-
Tidskriftsartikel (refereegranskat)abstract
- Indications of adverse effects of nontoxic malodorous chemical exposure on work performance and safety and the role of health-risk perception on odor perception motivated the present study of the impact of health-risk perception on odor perception and cognitive performance. Healthy young adults were informed that they were to be exposed to an odorous substance that is either potentially health-enhancing (positive information bias, n = 24) or hazardous (negative information bias, n = 25). The two groups, screened for loss in odor-detection sensitivity, were matched for age, sex, chemical intolerance, and negative affectivity. During each of 14 trials of exposure to 433 mg/m(3) of n-butanol, the participants rated the intensity and valence of odor perception and performed a cognitive task that taxed working memory and attention. The results showed that the negative-bias group rated the odor perception as more unpleasant than did the positive-bias group during the entire session, but significantly more unpleasant only during the first half of the session. The negative-bias group was also found to perform significantly poorer on the cognitive task during both halves of the session. No effect of information bias was found on perceived odor intensity. The results provide experimental support for the hypotheses that belief that exposure to an odorous chemical is hazardous contributes to the odor perception being more unpleasant and to poorer cognitive performance.
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| 45. |
- Pettersson, Agneta, et al.
(författare)
-
Förebygga självskadebeteende och suicidförsök hos barn och ungdomar – effekter av riktade interventioner. : En systematisk översikt och utvärdering av medicinska, hälsoekonomiska och etiska aspekter
- 2024. - 378
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Ingår i: SBU Utvärderar. ; :378
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- HuvudbudskapDialektisk beteendeterapi för ungdomar (DBT-A) förebygger återfall i självskadebeteende. Internetförmedlad känsloregleringsterapi (IERITA) kan förebygga nya episoder av icke-suicidalt självskadebeteende.SlutsatserEfter att ha granskat den vetenskapliga litteraturen har SBU dragit följande slutsatser:DBT-A minskar antalet ungdomar med självskadebeteende som får ett återfall. Behandlingen uppskattas av ungdomarna och deras föräldrar. DBT-A under fyra månader kan vara kostnadseffektivt jämfört med sedvanlig vård, men svenska hälsoekonomiska studier behövs.IERITA som bygger på DBT-A kan möjligen minska antalet ungdomar med icke-suicidalt självskadebeteende som får ett återfall men här behövs fler randomiserade studier som bekräftar resultaten. I svenska studier är IERITA uppskattat av ungdomar, föräldrar och vården.Ungdomar som identifierar sig som att tillhöra en sexuell minoritet eller har ett riskfyllt substansbruk, eller är omhändertagna i rättssystemet, har en förhöjd risk för självskadebeteende. Studier på förebyggande interventioner saknas eller är få och små.Det behövs forskning om specifika behandlingar som ökar säkerheten kring en ungdom akut efter ett suicidförsök. En säkerhetsplan, färdighetsträning och komponenter riktade till familjen verkar vara centralt, exempelvis familjeinterventionen SAFETY.Det behövs effektiv heldygnsvård med mindre risk för långa vårdförlopp och försämring av hälsotillståndet. Forskning med före-eftermätningar och kvalitativa studier pekar på värdet av brukarstyrda inläggningar men det behövs svenska randomiserade studier.Vad skulle resultaten kunna innebära?Resultaten tyder på att det finns en potential för att fler ungdomar med självskadebeteende kan få tillgång till effektiva behandlingar. DBT-A är idag den enda metod som har vetenskapligt stöd för att minska risken för upprepade självskadeförsök men erbjuds i huvudsak i storstadsregionerna. Behandlingen kan pågå i upp till ett år. Studierna visar dock att redan fyra månaders DBT-A är effektivt, något som skulle kunna frigöra resurser för att behandla fler. För att införa DBT-A på fler kliniker kommer det att krävas omfattande utbildnings- och rekryteringsinsatser, sannolikt med förhöjda kostnader på kort sikt.Vidare skulle IERITA kunna komplettera vårdutbudet för ungdomar med icke-suicidalt självskadebeteende utan omedelbar suicidrisk. IERITA är inte lika etablerad som DBT-A och det kommer krävas utbildningsinsatser.Vad handlar rapporten om?Självskadebeteende, oavsett om avsikten är att avsluta sitt liv eller inte, hos barn och ungdomar är ett globalt hälsoproblem och suicid är den vanligaste dödsorsaken för ungdomar. Självskadebeteende ökar också risken för framtida suicidhandlingar, annan psykisk ohälsa, riskfyllt substansbruk och kriminalitet.Syftet med rapporten var att utvärdera om det finns några interventioner som kan förebygga självskadebeteende. Interventionerna skulle ges till barn och ungdomar som redan har ett självskadebeteende eller till sådana som tillhör några specifika riskgrupper.Utvärderingen gjordes som en systematisk översikt med metaanalyser, kompletterad med systematiska översikter till grund för hälsoekonomiska och etiska aspekter. Vilka studier ligger till grund för resultaten?Resultaten baseras på 28 randomiserade studier och en systematisk översikt. Två hälsoekonomiska studier och elva studier med kvalitativ metodik ingår också i rapporten. Studierna har publicerats från år 1990 och framåt och de flesta har genomförts i USA och Storbritannien.Samtliga studier utvärderade någon form av psykologisk behandling förutom en studie om brukarstyrda inläggningar. Studier på läkemedel och andra tänkbara behandlingar saknades för ungdomar med självskador eller suicidalt beteende.
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| 46. |
- Richardson, Sara, et al.
(författare)
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Initial Characterization of Ethyl(hydroxyethyl) Cellulose Using Enzymic Degradation and Chromatographic Methods
- 2002
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1526-4602 .- 1525-7797. ; 3:6, s. 1359-1363
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Tidskriftsartikel (refereegranskat)abstract
- Two different ethyl(hydroxyethyl) cellulose (EHEC) samples were characterized by size-exclusion chromatography (SEC) with multiangle light scattering (MALS) detection and high-performance anion-exchange chromatography (HPAEC) with pulsed amperometric detection (PAD). The aim of the study was to investigate the molar mass distribution and the heterogeneity of the substituent distribution, factors that are thought to affect the functional properties of EHEC. The presence of blocks of unsubstituted glucose units was studied by enzymic degradation of EHEC by two different endoglucanases from Trichoderma reesei. The SEC-MALS analysis of the hydrolysis products showed that both enzymes were strongly inhibited by the large number of substituents along the cellulose chain. However, as the weight-average molar mass was reduced from approximately 360 000 to 80 000 g/mol in one of the polymers and from 770 000 to 60 000 g/mol in the other polymer, it was suggested that both samples were composed of some unsubstituted regions where the enzymes got access to the glucosidic bonds. The amount of glucose released upon endoglucanase hydrolysis was determined by HPAEC-PAD, which gave information on the homogeneity of the substituent distribution. The production of unsubstituted glucose units indicated that one of the polymers had a more uneven distribution compared with the other. It was demonstrated that chemical characterization of EHEC is a complex task, which requires an analytical approach involving numerous different methods and techniques.
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| 47. |
- Ringström, Gisela, 1964, et al.
(författare)
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Development of an educational intervention for patients with Irritable Bowel Syndrome (IBS): a pilot study.
- 2009
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Ingår i: BMC gastroenterology. - 1471-230X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many IBS patients experience that they receive limited information and that the health care system does not take their complaints seriously. We aimed to develop a structured patient education, an 'IBS school', and investigate if the efficacy could be evaluated in terms of improved knowledge, symptom severity and health related quality of life (HRQOL). METHODS: The IBS school consisted of six weekly two hour sessions in a group setting. Five different health care professionals were responsible for one session each. Questionnaires covering patients' experience of the education, perceived knowledge about IBS, gastrointestinal symptoms, and HRQOL, were used for evaluation at baseline and at three, six, and twelve months after education. RESULTS: Twelve IBS patients were included. The patients were overall satisfied with the IBS school. In line with this, the gastrointestinal symptoms, HRQOL, and perceived knowledge about IBS improved significantly after the education. CONCLUSION: An IBS school seems to be a proper method to meet the patients' need of information about IBS and also to improve the patients' gastrointestinal symptoms, HRQOL, and knowledge about IBS. Further controlled studies are now needed in larger numbers of patients to confirm these preliminary results in order to implement this intervention in clinical practice.
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| 48. |
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| 49. |
- Rodriguez Camargo, Diana C., et al.
(författare)
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Surface-Catalyzed Secondary Nucleation Dominates the Generation of Toxic IAPP Aggregates
- 2021
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Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media SA. - 2296-889X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The aggregation of the human islet amyloid polypeptide (IAPP) is associated with diabetes type II. A quantitative understanding of this connection at the molecular level requires that the aggregation mechanism of IAPP is resolved in terms of the underlying microscopic steps. Here we have systematically studied recombinant IAPP, with amidated C-terminus in oxidised form with a disulphide bond between residues 3 and 7, using thioflavin T fluorescence to monitor the formation of amyloid fibrils as a function of time and IAPP concentration. We used global kinetic analyses to connect the macroscopic measurements of aggregation to the microscopic mechanisms, and show that the generation of new aggregates is dominated by the secondary nucleation of monomers on the fibril surface. We then exposed insulinoma cells to aliquots extracted from different time points of the aggregation process, finding the highest toxicity at the midpoint of the reaction, when the secondary nucleation rate reaches its maximum. These results identify IAPP oligomers as the most cytotoxic species generated during IAPP aggregation, and suggest that compounds that target secondary nucleation of IAPP could be most effective as therapeutic candidates for diabetes type II.
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| 50. |
- Roldán-Merino, Juan Francisco, et al.
(författare)
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Quality in Psychiatric Care in the Community Mental Health Setting from the Perspective of Patients and Staff
- 2023
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 20:5
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Tidskriftsartikel (refereegranskat)abstract
- The current paradigm of mental health care focuses on care provided in the community, increasingly moving away from hospital care models that involve considerable economic burden. Patient and staff perspectives on the quality of psychiatric care can highlight strengths and areas for improvement to ensure better care provision. The aim of this study was to describe and compare perceptions of quality of care among patients and staff in community mental health services and to determine possible relationships between these perceptions and other study variables. A comparative cross-sectional descriptive study was conducted in a sample of 200 patients and 260 staff from community psychiatric care services in the area of Barcelona (Spain). The results showed high overall levels of quality of care from patient (m = 104.35 ± 13.57) and staff (m =102.06 ± 8.80) perspectives. Patients and staff both gave high scores to Encounter and Support factors, while factors concerning patient Participation and Environment received the lowest scores. Continuous assessment of the quality of psychiatric care in the community setting is essential to ensure the highest quality of care, taking the perspectives of those involved into account.
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