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- Gustafsson, Susanne, et al.
(author)
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Tailored implementation of evidence-based practice in the community care for the aged - initial experiences in a collaborative project in the city of Gothenburg, Sweden
- 2015
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In: Nordic Conference on implementation of Evidence-Based Practice 20150203-20150204 Bergen, Norge.
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Conference paper (peer-reviewed)abstract
- Background: Evidence-based practice (EBP) appears promising in order to strengthen both interprofessional team work and the client´s involvement in his/her care processes. It is therefore of interest to implement EBP in the community care for the aged. But implementation is not always a simple and straightforward process; it may face resistance or difficulties. Factors such as usability, adaptations, barriers, fidelity, and anticipated impact need to be studied when implementing EBP in a new context. Aim: To evaluate the implementation of EBP in community health and social care for the aged in a Swedish setting. This includes the study of the implementation process as well as the impact of EBP on interprofessional teamwork and the care receivers' experiences of care quality. Methods: An explanatory case study in two urban districts in the city of Gothenburg, Sweden, where the implementation of EBP is delivered as a collaborative project with a tailored multifaceted implementation strategy. Data will be collected through documentary information, observations, focus groups, interviews, and a survey, and analyzed using both qualitative and quantitative methods. Results: The collaborative project is on-going with three facilitators using a multifaceted implementation strategy including cooperation between researchers and users, education/learning, and facilitation. Data collection has commenced. Initial experiences reveal that the introductory phase, containing time for persons involved in the collaborative project to get to know each other, each other's areas of expertise and respective organizations, took longer than expected. Also, different care-professions have experienced thus far conducted educational activities in different ways, and some express limited ability to prioritize project activities. Conclusion: The future results of this explanatory case study may be useful for gaining knowledge of and understanding the implementation of EBP in community care for the aged, and to improve the quality of care, support and rehabilitation of older persons.
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| 2. |
- Gustafsson Sfetcovici, Manuela O
(author)
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Characterization of ankyrin repeat domain 54 (ANKRD54) and its role on the regulation and subcellular localization of Bruton’s tyrosine kinase (BTK)
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Bruton's tyrosine kinase (BTK) is an important cytoplasmic signaling protein, where the kinase activity plays a pivotal role in the development, proliferation and differentiation of B-cell lineages. Ankyrin repeat domain 54 (ANKRD54) is a nuclear-resident adaptor protein, where the ankyrin domain repeats are critical for specific protein-protein interaction, while the NLS and NES motifs control the nucleo-cytoplasmic shuttling ability. We have identified and characterized ANKRD54 as a novel functional (paper I), interaction-partner for BTK using proteomics analysis. ANKRD54 is the first protein identified that specially influences the nuclear export of both BTK and TXK/RLK, in a Crm-1 dependent manner. Further, we mapped the interaction site to the C -terminus of BTK-SH3 domain, by using a synthetic peptide of BTK, covering the following region: C- ARDKNGQEEGYIPSNYVTEAEDS. In addition, tyrosine phosphorylation of BTK was investigated in the presence of increased amount of ANKRD54 and selectively the phosphorylation of BTK was down regulated. We have presented a second novel interaction-partner and regulator of BTK (paper II), the 14-3-3 ζ protein, which is also identified by proteomics strategy. In this work, we have mapped the interaction sites on BTK to phospho-serine pS51 in the (RGRRGpS)-motif in the PH-domain and phospho-threonine pT495 in the (RHRFQpT)-motif in the kinase domain. Additionally, a newly characterized 14-3-3 inhibitor (BV02) interfered binding with BTK and siRNA knockdown of 14-3-3ζ increased the nuclear translocation of BTK, while overexpression of 14-3-3ζ resulted in accumulation of BTK in the perinuclear region. We have generated single ankryin domain deletions of ANKRD54 and subsequently characterized their binding capacity and also their influence on the sub-cellular localization of BTK (paper III). In this work, we report that three out of four ankyrin repeats are required for the interaction and nucleo-cytoplasmic shuttling of BTK. Inhibition of Crm-1 nuclear export pathway influences differently the nuclear shuttling; rapid-ANKRD54 versus slow-BTK nuclear accumulation. Furthermore, we have determined that the interaction between BTK and ANKRD54 establishes in the nuclear compartment. We have classified ANKRD54 as a prime interactor to the SH3-domain of BTK (paper IV). In this study, we utilized a screening strategy based on phage display libraries of the complete human “SH3-domainome” as a possible binding-target for ANKRD54. The aim is to identify the target spectrum and specificity of ANKRD54 for SH3 domain library, containing all the 296 human SH3 domains. The novel finding is that BTK is not only binding to ANKRD54, but also stands out as the preferred interactor, being highly dominant over all other human SH3 domains. However, other lower colony-score candidates for SH3-domain interactions were found, but without any further in vivo/in vitro validation.
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| 4. |
- Lebens, Michael, 1956, et al.
(author)
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Construction and preclinical evaluation of mmCT, a novel mutant cholera toxin adjuvant that can be efficiently produced in genetically manipulated Vibrio cholerae
- 2016
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In: Vaccine. - : Elsevier Ltd. - 0264-410X .- 1873-2518. ; 34:18, s. 2121-2128
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Journal article (peer-reviewed)abstract
- There is an urgent need for new adjuvants that are effective with mucosally administered vaccines. Cholera toxin (CT) is the most powerful known mucosal adjuvant but is much too toxic for human use. In an effort to develop a useful mucosal adjuvant we have generated a novel non-toxic mutant CT molecule that retains much of the adjuvant activity of native CT. This was achieved by making the enzymatically active A subunit (CTA) recalcitrant to the site-specific proteolytic cleavage ("nicking") required for toxicity, which was found to require mutations not only in the two residues rendering the molecule resistant to trypsin but also in neighboring sites protecting against cleavage by Vibrio cholerae proteases. This multiple-mutated CT (mmCT) adjuvant protein could be efficiently produced in and purified from the extracellular medium of CT-deleted V. cholerae. The mmCT completely lacked detectable enterotoxicity in an infant mouse model and had >1000-fold reduced cAMP inducing activity compared to native CT in a sensitive mammalian target cell system. It nonetheless proved to have potent adjuvant activity on mucosal and systemic antibody as well as cellular immune responses to mucosally co-administered antigens including oral cholera and intranasal influenza vaccines. We conclude that mmCT is an attractive novel non-toxic mucosal adjuvant for enhancing immune responses to co-administered mucosal vaccines
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