| 1. |
- Aschim, Elin L, et al.
(författare)
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The RsaI polymorphism in the ER{beta} gene is associated with male infertility.
- 2005
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 90:Jul 5, s. 5343-5348
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Tidskriftsartikel (refereegranskat)abstract
- Context: Hypospadias, cryptorchidism, testicular cancer, and low semen quality have been proposed as being parts of the testicular dysgenesis syndrome (TDS) hypothetically due to changes in the androgen- estrogen balance in utero. Estrogens and estrogen receptors (ERs) play a role in regulating testicular function. ER beta contains two silent polymorphisms, RsaI (G1082A) and AluI (G1730A). Objective: We investigated the significance of these polymorphisms in the etiology of disorders being part of TDS. Setting: The patients were recruited consecutively through university hospital clinics. Participants: Four groups of Caucasian patients were included: 106 men from infertile couples with a sperm concentration less than 5 x 106 spermatozoa/ ml, 86 testicular cancer patients, 51 boys with hypospadias, and 23 cases with cryptorchidism. Military conscripts (n = 186) with sperm concentration higher than 5 x 10(6) spermatozoa/ ml served as controls. Main Outcome Measures: ER beta polymorphisms RsaI and AluI were determined by allele-specific PCR. In addition, reproductive hormone analyses were performed in controls and infertile men. Results: Compared with the controls, the frequency of the heterozygous RsaI AG-genotype was three times higher in infertile men (13.2 vs. 4.3%; P = 0.01). The heterozygous RsaI AG-genotype was associated with an approximately 20% reduction in LH concentration, compared with the wild-type RsaI GG genotype in both controls and infertile men. Subjects with testicular cancer, hypospadias, or cryptorchidism did not differ from controls regarding the frequency of any of the polymorphisms. Conclusions: Polymorphisms in ER beta may have modulating effects on human spermatogenesis. The phenotype of TDS seems to be, at least partly, determined by the genotype.
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| 2. |
- Bobjer, Johannes, et al.
(författare)
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Location of retroperitoneal lymph node metastases in upper tract urothelial carcinoma : results from a prospective lymph node mapping study
- 2023
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 57, s. 37-44
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is limited information on the distribution of retroperitoneal lymph node metastases (LNMs) in upper tract urothelial carcinoma (UTUC).Objective: To investigate the location of LNMs in UTUC of the renal pelvis or proximal ureter and short-term complications after radical nephroureterectomy (RNU) with lymph node dissection (LND).Design, setting, and participants: This was a prospective Nordic multicenter study (four university hospitals, two county hospitals). Patients with clinically suspected locally advanced UTUC (stage >T1) and/or clinical lymph node–positive (cN+) disease were invited to participate. Participants underwent RNU and fractionated retroperitoneal LND using predefined side-specific templates.Outcome measurements and statistical analysis: The location of LNMs in the LND specimen and retroperitoneal lymph node recurrences during follow-up was recorded. Postoperative complications within 90 d of surgery were ascertained from patient charts. Descriptive statistics were used.Results and limitations: LNMs were present in the LND specimen in 23/100 patients, and nine of 100 patients experienced a retroperitoneal recurrence. Distribution per side revealed LNMs in the LND specimen in 11/38 (29%) patients with right-sided tumors, for whom the anatomically larger, right-sided template was used, in comparison to 12/62 (19%) patients with left-sided tumors, for whom a more limited template was used. High-grade complications (Clavien grade ≥3) within 90 d of surgery were registered for 13/100 patients. The study is limited in size and not powered to assess survival estimates.Conclusions: The suggested templates that we prospectively applied for right-sided and left-sided LND in patients with advanced UTUC included the majority of LNMs. High-grade complications directly related to the LND part of the surgery were limited.Patient summary: This study describes the location of lymph node metastases in patients with cancer in the upper urinary tract who underwent surgery to remove the affected kidney and ureter. The results show that most metastases occur within the template maps for lymph node surgery that we investigated, and that this surgery can be performed with few severe complications.
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| 3. |
- Boonstra, M. D., et al.
(författare)
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Social Insurance Literacy of Dutch Workers Receiving Disability Benefits and its Associations with Socio-Economic Characteristics
- 2022
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Ingår i: Journal of occupational rehabilitation. - : Springer / Plenum. - 1053-0487 .- 1573-3688. ; 32, s. 494-504
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Tidskriftsartikel (refereegranskat)abstract
- Purpose This study explores the concept social insurance literacy (SIL) and corresponding questionnaire (SILQ) among workers receiving disability benefits and the comprehensibility of the social security institute (SSI), and examines associations with socio-economic characteristics. Methods 1753 panel members of the Dutch SSI were approached to complete the SILQ-NL37. This measure was based on the original SILQ. The SILQ-NL37 contains domains for obtaining, understanding and acting upon information for both individual SIL and system comprehensibility. A higher score means better SIL or comprehensibility. Data on age, gender, education, living situation, Dutch skills and time receiving disability benefits were also collected. With k-means clustering, groups with adequate and limited SIL were created. Associations with socio-economic characteristics were examined with independent t-tests and linear regression analyses for both the total scores and within domain scores. Cronbach alpha and Spearman rhos indicated measurement properties were good to acceptable for the SILQ-NL37. Results Thirty-five percent of the 567 participants were in the group with limited SIL. Higher individual SILQ-NL37 scores were associated with having a partner (p = 0.018) and northeastern living region (p = 0.031). Higher scores for obtaining (p = 0.041) and understanding (p = 0.049) information were associated with female sex, and for acting on information with younger age (p = 0.020). People with limited Dutch skills (p = 0.063) and a partner (p = 0.085) rated system comprehensibility higher. Conclusions According to the SILQ-NL37 scores, about 35% of the panel members have limited ability to obtain, understand and act upon social insurance systems information. Limited SIL is associated with several socio-economic factors. Future researches should study the concept in a more representative sample, and in different countries and social insurance contexts.
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| 4. |
- Boutajangout, Allal, et al.
(författare)
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Affibody-Mediated Sequestration of Amyloid beta Demonstrates Preventive Efficacy in a Transgenic Alzheimer's Disease Mouse Model
- 2019
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Different strategies for treatment and prevention of Alzheimer's disease (AD) are currently under investigation, including passive immunization with anti-amyloid beta (anti-A beta) monoclonal antibodies (mAbs). Here, we investigate the therapeutic potential of a novel type of A beta-targeting agent based on an affibody molecule with fundamentally different properties to mAbs. We generated a therapeutic candidate, denoted Z(SYM73)-albumin-binding domain (ABD; 16.8 kDa), by genetic linkage of the dimeric Z(SYM73) affibody for sequestering of monomeric A beta-peptides and an ABD for extension of its in vivo half-life. Amyloid precursor protein (APP)/PS1 transgenic AD mice were administered with Z(SYM73)-ABD, followed by behavioral examination and immunohistochemistry. Results demonstrated rescued cognitive functions and significantly lower amyloid burden in the treated animals compared to controls. No toxicological symptoms or immunology-related side-effects were observed. To our knowledge, this is the first reported in vivo investigation of a systemically delivered scaffold protein against monomeric A beta, demonstrating a therapeutic potential for prevention of AD.
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| 5. |
- Carlsson, Jörgen, et al.
(författare)
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Polypeptides having binding affinity for HER2
- 2003
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Patent (populärvet., debatt m.m.)abstract
- A polypeptide is provided, which has a binding affinity for HER2 and which is related to a domain of staphylococcal protein A (SPA) in that the sequence of the polypeptide corresponds to the sequence of the SPA domain having from 1 to about 20 substitution mutations. Nucleic acid encoding the polypeptide, as well as expression vector and host cell for expressing the nucleic acid, are also provided. Also provided is the use of such a polypeptide as a medicament, and as a targeting agent for directing substances conjugated thereto to cells overexpressing HER2. Methods, and kits for performing the methods, are also provided, which methods and kits rely on the binding of the polypeptide to HER2.
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| 6. |
- Fleetwood, Filippa, et al.
(författare)
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Simultaneous targeting of two ligand-binding sites on VEGFR2 using biparatopic Affibody molecules results in dramatically improved affinity
- 2014
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4, s. 7518-
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis plays an important role in cancer and ophthalmic disorders such as age-related macular degeneration and diabetic retinopathy. The vascular endothelial growth factor (VEGF) family and corresponding receptors are regulators of angiogenesis and have been much investigated as therapeutic targets. The aim of this work was to generate antagonistic VEGFR2-specific affinity proteins having adjustable pharmacokinetic properties allowing for either therapy or molecular imaging. Two antagonistic Affibody molecules that were cross-reactive for human and murine VEGFR2 were selected by phage and bacterial display. Surprisingly, although both binders independently blocked VEGF-A binding, competition assays revealed interaction with non-overlapping epitopes on the receptor. Biparatopic molecules, comprising the two Affibody domains, were hence engineered to potentially increase affinity even further through avidity. Moreover, an albumin-binding domain was included for half-life extension in future in vivo experiments. The best-performing of the biparatopic constructs demonstrated up to 180-fold slower dissociation than the monomers. The new Affibody constructs were also able to specifically target VEGFR2 on human cells, while simultaneously binding to albumin, as well as inhibit VEGF-induced signaling. In summary, we have generated small antagonistic biparatopic Affibody molecules with high affinity for VEGFR2, which have potential for both future therapeutic and diagnostic purposes in angiogenesis-related diseases.
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| 7. |
- Grönwall, Caroline, et al.
(författare)
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Selection and characterization of Affibody ligands binding to Alzheimer amyloid beta peptides
- 2007
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Ingår i: Journal of Biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 128:1, s. 162-183
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Tidskriftsartikel (refereegranskat)abstract
- Affibody (Affibody) ligands specific for human amyloid beta (Abeta) peptides (40 or 42 amino acid residues in size), involved in the progress of Alzheimer's disease, were selected by phage display technology from a combinatorial protein library based on the 58-amino acid residue staphylococcal protein A-derived Z domain. Post-selection screening of 384 randomly picked clones, out of which 192 clones were subjected to DNA sequencing and clustering, resulted in the identification of 16 Affibody variants that were produced and affinity purified for ranking of their binding properties. The two most promising Affibody variants were shown to selectively and efficiently bind to Abeta peptides, but not to the control proteins. These two Affibody ligands were in dimeric form (to gain avidity effects) coupled to affinity resins for evaluation as affinity devices for capture of Abeta peptides from human plasma and serum. It was found that both ligands could efficiently capture Abeta that were spiked (100 microgml(-1)) to plasma and serum samples. A ligand multimerization problem that would yield suboptimal affinity resins, caused by a cysteine residue present at the binding surface of the Affibody ligands, could be circumvented by the generation of second-generation Affibody ligands (having cysteine to serine substitutions). In an epitope mapping effort, the preferred binding site of selected Affibody ligands was mapped to amino acids 30-36 of Abeta, which fortunately would indicate that the Affibody molecules should not bind the amyloid precursor protein (APP). In addition, a significant effort was made to analyze which form of Abeta (monomer, dimer or higher aggregates) that was most efficiently captured by the selected Affibody ligand. By using Western blotting and a dot blot assay in combination with size exclusion chromatography, it could be concluded that selected Affibody ligands predominantly bound a non-aggregated form of analyzed Abeta peptide, which we speculate to be dimeric Abeta. In conclusion, we have successfully selected Affibody ligands that efficiently capture Abeta peptides from human plasma and serum. The potential therapeutic use of these optimized ligands for extracorporeal capture of Abeta peptides in order to slow down or reduce amyloid plaque formation, is discussed.
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| 8. |
- Karlsson, Elin, 1985-, et al.
(författare)
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Communication characteristics between clients and stakeholders within the Swedish sickness insurance system : a document analysis of granted and withdrawn sickness benefit claims
- 2020
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Ingår i: Disability and Rehabilitation. - : Taylor & Francis. - 0963-8288 .- 1464-5165. ; 42:23, s. 3316-3326
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to investigate how communication within the Swedish sickness insurance system differs between cases of sick leave and how this may affect clients’ cases.Materials and methods: This was a document study using 30 client files from the Swedish Social Insurance Agency (SIA). The clients included had been on a work ability evaluation during their sick leave spell and were aged 32–64 years. The material was analyzed using qualitative document analysis.Results: The results show different approaches to communication, characterized by emotional argumentation, matter-of-fact driven argumentation and information exchange, which have diverse success in affecting official decisions. Arguments characterized by emotions such as frustration or desperation are to a larger extent neglected by the authorities compared to those characterized by a matter-of-fact driven approach and referring to regulations and medical certificates.Conclusion: There are differences regarding how clients and stakeholders communicate the clients’ needs and pre-requisites, and how this affects official decisions. Further research must be carried out in order to establish social insurance literacy, initially for individuals on sick leave within the sickness insurance system, and whether there are differences between diverse groups that could lead to injustices.Implications for rehabilitationWithin a social insurance context, professionals need to provide clients with adequate and individually adapted information in order for procedures to be perceived as comprehensible and manageable by the clients.The support from stakeholders such as the treating physician and/or employer can affect clients’ sick-leave process.Clients’ treating medical professionals can contribute to ensuring that clients rights are met by communicating the clients’ needs to other stakeholders in a formal way.
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| 9. |
- Karlsson, Elin, 1985-, et al.
(författare)
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Communication Characteristics Between Clients And Stakeholders Within The Swedish Sickness Insurance System – A Document Analysis Of Granted And Withdrawn Sickness Benefit Claims
- 2019
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Konferensbidrag (refereegranskat)abstract
- INTRODUCTION: Previous studies show differences regarding which clients receive sickness benefits as well as which clients are questioned or not within the sickness insurance system. There are indications that the characteristics of communication can have an impact on the sick leave process, which motivates this study with the following purpose.PURPOSE: The purpose of this study was to investigate how communication within the Swedish sickness insurance system differs between cases of sick leave and how this may affect the clients’ case.MATERIALS AND METHODS: This was a document study using thirty client files including the correspondence between clients, their case-manager at the Swedish Social Insurance Agency (SIA) as well as other stakeholders. The clients included had been on a work capacity evaluation during their sick leave spell and were aged 32-64 years. There were twenty women and ten men in this study, with a variety of the degree of sickness absence, disability pension and part time work. The material was analyzed using qualitative document analysis.RESULTS: The results show different approaches in communication, characterized by emotional communication, matter-of-fact driven communication and information exchange, which have diverse success in affecting authority decisions. Arguments characterized by emotions such as frustration or desperation are to a larger extent neglected compared to those characterized by a matter-of-fact driven approach and referring to regulations and medical certificates. There are also differences in how information about the client is interpreted by different professionals.CONCLUSION: There are differences regarding how clients and stakeholders communicate the clients’ needs and prerequisites, and how this affect the SIA. Further research must be carried out in order to establish social insurance literacy, initially for individuals on sick leave within the sickness insurance, and whether there are differences between diverse groups that could lead to injustice in the system.
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| 10. |
- Karlsson, Elin, et al.
(författare)
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Exploring Interactions in the Sickness Insurance System in Terms of Power and Trust
- 2022
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Ingår i: Journal of occupational rehabilitation. - : Springer / Plenum. - 1053-0487 .- 1573-3688. ; 32:3, s. 483-493
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Activation policies and efforts to reduce sick leave rates has influenced sickness insurance systems in Western countries, which has led to social security being more connected with work and attempts to expose malingering among the sickness absent. The aim of this study was to explore how power and trust are expressed by clients and stakeholders within the Swedish sickness insurance system. Methods This was a longitudinal qualitative study based on semi structured interviews and case files from 31 clients on sick leave in Sweden. Data was analyzed using a thematic analysis. Results The main theme Acts of power and distrust illustrates how stakeholders express suspicions towards each other, and how clients need to demonstrate desire and efforts to return to work which other stakeholders verified. Conclusions The clients desire to prove themselves able to contribute to society was prominent in this study and power relations need to be acknowledged, in particular between client and the SIA. Further, to preserve citizens trust in the system, the system needs to demonstrate trust also in the clients.
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