| 1. |
- Carlsson, Susanne, et al.
(författare)
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Affinity of galectin-8 and its carbohydrate recognition domains for ligands in solution and at the cell surface.
- 2007
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 17:6, s. 663-76
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-8 has two different carbohydrate recognition domains (CRDs), the N-terminal Gal-8N and the C-terminal Gal-8C linked by a peptide, and has various effects on cell adhesion and signaling. To understand the mechanism for these effects further, we compared the binding activities of galectin-8 in solution with its binding and activation of cells. We used glycan array analysis to broaden the specificity profile of the two galectin-8 CRDs, as well as intact galectin-8s (short and long linker), confirming the unique preference for sulfated and sialylated glycans of Gal-8N. Using a fluorescence anisotropy assay, we examined the solution affinities for a subset of these glycans, the highest being 50 nM for NeuAcalpha2,3Lac by Gal-8N. Thus, carbohydrate-protein interactions can be of high affinity without requiring multivalency. More importantly, using fluorescence polarization, we also gained information on how the affinity is built by multiple weak interactions between different fragments of the glycan and its carrier molecule and the galectin CRD subsites (A-E). In intact galectin-8 proteins, the two domains act independently of each other in solution, whereas at a surface they act together. Ligands with moderate or weak affinity for the isolated CRDs on the array are bound strongly by intact galectin-8s. Also galectin-8 binding and signaling at cell surfaces can be explained by combined binding of the two CRDs to low or medium affinity ligands, and their highest affinity ligands, such as sialylated galactosides, are not required.
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| 2. |
- Nicholls, Ian A., et al.
(författare)
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Theoretical and Computational Strategies for Rational Molecularly Imprinted Polymer Design
- 2009
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Ingår i: Biosensors & bioelectronics. - : Elsevier BV. - 0956-5663 .- 1873-4235. ; 25:3, s. 543-552
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Tidskriftsartikel (refereegranskat)abstract
- The further evolution of molecularly imprinted polymer science and technology necessitates the development of robust predictive tools capable of handling the complexity of molecular imprinting systems. A combination of the rapid growth in computer power over the past decade and significant software developments have opened new possibilities for simulating aspects of the complex molecular imprinting process. We present here a survey of the current status of the use of in silico-based approaches to aspects of molecular imprinting. Finally, we highlight areas where ongoing and future efforts should yield information critical to our understanding of the underlying mechanisms sufficient to permit the rational design of molecularly imprinted polymers.
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| 3. |
- Nordanstig, Annika, 1974, et al.
(författare)
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EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
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| 4. |
- Teneberg, Susanne, et al.
(författare)
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Lactotetraosylceramide, a novel glycosphingolipid receptor for Helicobacter pylori, present in human gastric epithelium
- 2002
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Ingår i: Journal of Biological Chemistry. - Bethesda : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 277:22, s. 19709-19719
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Tidskriftsartikel (refereegranskat)abstract
- The binding of Helicobacter pylori to glycosphingolipids was examined by binding of 35S-labeled bacteria to glycosphingolipids on thin-layer chromatograms. In addition to previously reported binding specificities, a selective binding to a non-acid tetraglycosylceramide of human meconium was found. This H. pylori binding glycosphingolipid was isolated and, on the basis of mass spectrometry, proton NMR spectroscopy, and degradation studies, were identified as Galβ3GlcNAcβ3-Galβ4Glcβ1Cer (lactotetraosylceramide). When using non-acid glycosphingolipid preparations from human gastric epithelial cells, an identical binding of H. pylori to the tetraglycosylceramide interval was obtained in one of seven samples. Evidence for the presence of lactotetraosylceramide in the binding-active interval was obtained by proton NMR spectroscopy of intact glycosphingolipids and by gas chromatography-electron ionization mass spectrometry of permethylated tetrasaccharides obtained by ceramide glycanase hydrolysis. The lactotetraosylceramide binding property was detected in 65 of 74 H. pylori isolates (88%) Binding of H. pylori to lactotetraosylceramide on thin-layer chromatograms was inhibited by preincubation with lactotetraose but not with lactose. Removal of the terminal galactose of lactotetraosylceramide by galactosidase hydrolysis abolished the binding as did hydrazinolysis of the acetamido group of the N-acetylglucosamine. Therefore, Galβ3GlcNAc is an essential part of the binding epitope.
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| 5. |
- Åsberg, Dennis, 1988-, et al.
(författare)
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A quality control method enhancement concept : Continual improvement of regulatory approved QC methods
- 2016
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Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier. - 0731-7085 .- 1873-264X. ; 129, s. 273-281
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Tidskriftsartikel (refereegranskat)abstract
- Quality Control methods (QC-methods) play an important role in the overall control strategy for drug manufacturing. However, efficient life-cycle management and continual improvement are hindered due to a variety of post-approval variation legislations across territories and a lack of harmonization of the requirements. As a result, many QC-methods fall behind the technical development. Developing the QC-method in accordance with the Quality by Design guidelines gives the possibility to do continual improvements inside the original Method Operable Design Region (MODR). However, often it is necessary to do changes outside the MODR, e.g. to incorporate new technology that was not available at the time the original method was development. Here, we present a method enhancement concept which allows minor adjustments, within the same measuring principle, outside the original MODR without interaction with regulatory agencies. The feasibility of the concept is illustrated by a case study of a QC-method based on HPLC, assumed to be developed before the introduction of UHPLC, where the switch from HPLC to UHPLC is necessary as a continual improvement strategy. The concept relies on the assumption that the System Suitability Test (SST) and failure modes are relevant for other conditions outside the MODR as well when the same measuring principle is used. It follows that it should be possible to move outside the MODR as long as the SST has passed. All minor modifications of the original, approved QC-method must be re-validated according to a template given in the original submission and a statistical equivalence should be shown between the original and modified QC-methods. To summarize, revalidation is handled within the pharmaceutical quality control system according to internal change control procedures, but without interaction with regulating agencies.
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| 6. |
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| 7. |
- Ahlgren, Serina, et al.
(författare)
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Description of the Agrosfär model – a tool for climate impact assessment of crop and animal production systems in Sweden : Version 1: Crops, milk and beef
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The agricultural sector in Sweden needs to cut GHG emissions and contribute to the climate goal of net-zero emissions by 2045. The GHG reduction goal for agricultural emissions is not quantified, but the Swedish climate policy framework states that ‘the Swedish food production shall increase as much as possible with as little climate impact as possible’ and multiple key actors within the sector of food and agriculture have developed roadmaps or industry specific goals for reducing GHG emissions from the sector. Consequently, requirements of transparent GHG accounting and reporting are increasing within the agricultural sector, both at national and international level. The purpose of the Agrosfär tool is to establish an automatic data driven climate calculator used to calculate GHG emissions from agricultural products and on farm enterprise level. The automation and automatic data collection will save time, increase accuracy of the calculations, and simplify updates of the tool to keep it aligned with the most recent climate data and climate reporting methodology. It will make it possible to continuously carry out follow-ups on climate performance indicators and measure improvements from climate measures taken. A working group consisting of Swedish agricultural life cycle assessment experts have developed the framework of the tool, e.g. setting system boundaries, selecting methodologies and input data. A technical team has developed algorithms, a digital interface and coupled the tool to other existing agricultural databases providing farm specific information on crop and animal production data, soil characteristics, carbon footprints and amounts of purchased inputs etc. The tool and user interface have been developed based on input from farmers through prototyping and in-depth interviews. For general guidelines on methodology the calculation model follows the Product Environmental Footprint Category Rules (PEFCR), the International Dairy Federation (IDF)’s approach for carbon footprint for the dairy sector and FAO Livestock Environmental Assessment and Performance guidelines (FAO LEAP). Where standards have diverged or where assumptions have been required the working group has made expert judgements on which method/guideline to follow or what assumptions to make. A first version of the tool, a so called minimal viable product (MVP) has been developed which will be the basis for further development. The MVP contains an animal and crop module and can calculate the carbon footprint of crops, milk and beef. Future development possibilities of the tool and calculation model is described in chapter 7, such as enabling climate calculations on enterprise level, develop modules for more animal production types, deepen the integration between the crop and animal modules, expand sources for automatic data collection, develop a carbon sequestration module and other technical and methodological improvements to ensure alignment with important climate reporting standards. The report will be repeatedly updated as the tool develops, and new versions of the tool are released.
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| 8. |
- Ahlstedt Karlsson, Susanne, et al.
(författare)
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An intervention mapping-based support program that empowers patients with endocrine therapy management
- 2022
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Ingår i: Evaluation and Program Planning. - : Elsevier BV. - 0149-7189. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: For women diagnosed with hormone-receptor-positive breast cancer, endocrine therapy (ET) is recommended. Patients experience diverse side effects, and difficulties in managing these side effects have been identified as obstacles for treatment continuation. The aim of this study was to describe the development of a support program for patients prescribed ET. Methods: Intervention mapping (IM) a comprehensive theory-based approach was used in the support program development. A participatory design was used and four advisory groups was formed including both patients and healthcare professionals. Results: This study employed the systematic stages of IM to develop a theory-based support program with the goal to empower patients prescribed ET to manage ETrelated symptoms and problems, and to illuminate the healthcare structure. The needs assessment identified three performance objectives: (1) Patients have knowledge of and understand their symptoms and their management strategies. (2) Patients have the knowledge and confidence to express their care needs and to ask for guidance from healthcare professionals. (3) Patients are active in and lead their healthcare process. Conclusion: This is a systematic developed model, built upon aspects of ET both from a patient´ perspective as well as from healthcare professionals’ perspectives.
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| 9. |
- Ahlstedt Karlsson, Susanne
(författare)
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Designing, developing, and evaluating a person-centered support model for women with breast cancer treated with endocrine therapy
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is the most common cancer among women worldwide. Approximately 70% of all breast cancers are estrogen positive and are recommended for treatment with adjuvant endocrine therapy (ET) for five to ten years, which significantly reduces mortality rates. However, problems related to ET can be experienced by patients. The overall aim of this thesis is to design, develop and evaluate a person-centered support model (PSM) to empower patients with breast cancer treated with ET. This PSM will be delivered by a nurse navigator at a surgical outpatient clinic. The methods used included focus group interviews (Study I) with 25 patients approximately three years after they started ET. A mixed method study (Study II) was performed that included 39 patients who described their first three months of experience with their ET in a diary. Intervention mapping was used in Study III to design and develop a PSM using an action research design. Study IV tested the feasibility of the PSM with 20 patients in a control group and 21 patients in an intervention group using a quasi-experimental design. Three questionnaires regarding patient self-efficacy, perceived symptoms and quality of care were administered at baseline and after three months. The findings showed that ET needed to be managed due to side effects but also that prior knowledge caused hesitation. The analysis resulted in three categories that described patients’ experiences: ET created discomfort, patients experienced feelings of abandonment, and the most frequently reported problem was sleeping difficulties. Patients used both emotion- and problem-focused coping mechanisms. In the development of the PSM, patients’ diverse views of ET and needs were highlighted, and a support model built upon a person-centered approach seemed appropriate. The PSM was evaluated for its feasibility. Ninety-five percent of patients completed the PSM. The preferred follow-up was by telephone, and up to four follow-up sessions were held during the 12-week intervention. There were no significant differences in patient self-efficacy, perceived symptoms, or quality of care between the control and intervention groups. The conclusion is that the PSM was perceived to be feasible in terms of its process, resources, scientific challenges and acceptability among patients
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| 10. |
- Ahlstedt Karlsson, Susanne, et al.
(författare)
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Experiences of endocrine therapy after breast cancer surgery
- 2019
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Ingår i: Annals of Oncology. Abstract Book of the 44th ESMO Congress (ESMO 2019) 27 September – 1 October 2019, Barcelona, Spain. Vol. 30, Suppl. 5, s. v840. - : Elsevier BV. - 0923-7534.
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Konferensbidrag (refereegranskat)abstract
- Background For patients diagnosed with hormone-receptor-positive breast cancer, endocrine therapy (ET) is prescribed, which reduces recurrence and mortality rates (Early Breast Cancer Trialists’ Collaborative Group, 2011). Despite the prognostic benefits of ET, the adherence to treatment varies, and 30%–70% of the patients discontinue their treatment within five years (Daly et al., 2017; Tinari et al., 2015; Ursem et al., 2015), often during their first year of treatment (He et al., 2015), due to the fact that ET is associated with adverse side-effects (Regan et al., 2011). Methods The study was conducted in a surgical out-patient care unit at a hospital in Sweden. Inclusion criteria were women diagnosed with breast cancer and treated with ET after surgery. Forty-eight patients were invited to participate, of which 23 declined, thus 25 women were included. Seven focus group interviews, with two to five participants in each group, were conducted using an interview guide according to Krueger’s (2014) strategy. The interview guide contained six open-ended questions aiming to explore the women’s experiences of ET after breast cancer surgery. Inductive qualitative content analysis was used (Graneheim & Lundman, 2004). Results The analysis resulted in three categories that described the women’s experiences: the treatment “creates discomfort”; “promotes levels of management”; and “causes feelings of abandonment”. Women’s experiences of treatment could at first glance be seen as positive, as perceived protection, but after further analysis, a deeper meaning was identified: protection with reservation. When experiencing discomfort, the women were urged to manage the situation, although the mode of management sometimes varied. The women reported that they needed support, but when the support did not appear, they felt as though they had been abandoned. Moreover, knowledge about side-effects became an obstacle. The participants described feeling abandoned, but they also described their disease as “cancer light”. Conclusions Professionals need to explore the pre-knowledge and preconceptions that patients might have. This could be achieved by listening to the patient before providing them with information. The information needs to be customized specifically to each person. Funding Assar Gabrielsson’s Foundation, Herbert and Karin Jacobsson’s Foundation, and the Swedish Society of Nursing. Disclosure All authors have declared no conflicts of interest.
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