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1.
  • Ahlberg, Alexander, et al. (creator_code:aut_t)
  • Early self-care rehabilitation of head and neck cancer patients
  • 2011
  • record:In_t: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 131:5, s. 552-61
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • CONCLUSIONS: No positive effects of early preventive rehabilitation could be identified. The results do not contradict the proposition that rehabilitation based on self-care can be effective but it is important to establish evidence-based training programs and identify proper instruments for selection of patients and evaluation of intervention. OBJECTIVES: Patients with head and neck cancer suffer from functional impairments due to intense treatment. In this study, we investigated the effectiveness of an experimental early preventive rehabilitation using hard, objective end points in a nonselective, longitudinal, prospective cohort study. METHODS: In all, 190 patients were included in the program and received instructions for training before the start of treatment with the aim of reducing swallowing problems and reducing mouth opening and stiffness in the neck. A control group of 184 patients was recruited. RESULTS: There was no difference in weight loss and 2-year survival between the two groups. No positive effects concerning functional impairments were found in patient-reported outcome measures.
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2.
  • Ahlborg, Liv, et al. (creator_code:aut_t)
  • Visuospatial ability correlates with performance in simulated gynecological laparoscopy
  • 2011
  • record:In_t: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - : Elsevier BV. - 0301-2115 .- 1872-7654. ; 157:1, s. 73-77
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Objective: To analyze the relationship between visuospatial ability and simulated laparoscopy performed by consultants in obstetrics and gynecology (OBGYN). Study design: This was a prospective cohort study carried out at two community hospitals in Sweden. Thirteen consultants in obstetrics and gynecology were included. They had previously independently performed 10-100 advanced laparoscopies. Participants were tested for visuospatial ability by the Mental Rotations Test version A (MRT-A). After a familiarization session and standardized instruction, all participants subsequently conducted three consecutive virtual tubal occlusions followed by three virtual salpingectomies. Performance in the simulator was measured by Total Time, Score and Ovarian Diathermy Damage. Linear regression was used to analyze the relationship between visuospatial ability and simulated laparoscopic performance. The learning curves in the simulator were assessed in order to interpret the relationship with the visuospatial ability. Results: Visuospatial ability correlated with Total Time (r = -0.62; p = 0.03) and Score (r = 0.57; p = 0.05) in the medium level of the virtual tubal occlusion. In the technically more advanced virtual salpingectomy the visuospatial ability correlated with Total Time (r = -0.64; p = 0.02), Ovarian Diathermy Damage (r = -0.65; p = 0.02) and with overall Score (r = 0.64; p = 0.02). Conclusions: Visuospatial ability appears to be related to the performance of gynecological laparoscopic procedures in a simulator. Testing visuospatial ability might be helpful when designing individual training programs.
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3.
  • Albrecht, Letusa, et al. (creator_code:aut_t)
  • var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.2
  • 2011
  • record:In_t: Malaria Journal. - : BioMed Central. - 1475-2875 .- 1475-2875. ; 10
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Background: The pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra- vascular host cell receptors and serum-proteins. Binding of the pRBC is mediated by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large multi-variant molecule encoded by a family of approximate to 60 var genes. Methods: The study of var gene transcription in the parasite clone FCR3S1.2 was performed by semi-quantitative PCR and quantitative PCR (qPCR). The expression of the major PfEMP1 in FCR3S1.2 pRBC was analysed with polyclonal sera in rosette disruption assays and immunofluorecence. Results: Transcripts from var1 (FCR3S1.2(var1); IT4var21) and other var genes were detected by semi-quantitative PCR but results from qPCR showed that one var gene transcript dominated over the others (FCR3S1.2var2; IT4var60). Antibodies raised in rats to the recombinant NTS-DBL1a of var2 produced in E. coli completely and dosedependently disrupted rosettes (approximate to 95% at a dilution of 1/5). The sera reacted with the Maurer's clefts in trophozoite stages (IFA) and to the infected erythrocyte surface (FACS) indicating that FCR3S1.2var2 encodes the dominant PfEMP1 expressed in this parasite. Conclusion: The major transcript in the rosetting model parasite FCR3S1.2 is FCR3S1.2var2 (IT4var60). The results suggest that this gene encodes the PfEMP1-species responsible for the rosetting phenotype of this parasite. The activity of previously raised antibodies to the NTS-DBL1a of FCR3S1.2var1 is likely due to cross-reactivity with NTS-DBL1 alpha of the var2 encoded PfEMP1.
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4.
  • Ali, Tazeen S, et al. (creator_code:aut_t)
  • Gender roles and their influence on life prospects for women in urban Karachi, Pakistan : a qualitative study
  • 2011
  • record:In_t: Global Health Action. - Häggeby : CoAction Publishing. - 1654-9716 .- 1654-9880. ; 4, s. 7448-
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Background: Pakistan is a patriarchal society where men are the primary authority figures and women are subordinate. This has serious implications on women’s and men’s life prospects. Objective: The aim was to explore current gender roles in urban Pakistan, how these are reproduced and maintained and influence men’s and women’s life circumstances. Design: Five focus group discussions were conducted, including 28 women representing employed, unemployed, educated and uneducated women from different socio-economic strata. Manifest and latent content analyses were applied. Findings: Two major themes emerged during analysis: ‘Reiteration of gender roles’ and ‘Agents of change’. The first theme included perceptions of traditional gender roles and how these preserve women’s subordination. The power gradient, with men holding a superior position in relation to women, distinctive features in the culture and the role of the extended family were considered to interact to suppress women. The second theme included agents of change, where the role of education was prominent as well as the role of mass media. It was further emphasised that the younger generation was more positive to modernisation of gender roles than the elder generation. Conclusions: This study reveals serious gender inequalities and human rights violations against women in the Pakistani society. The unequal gender roles were perceived as static and enforced by structures imbedded in society. Women routinely faced serious restrictions and limitations of autonomy. However, attainment of higher levels of education especially not only for women but also for men was viewed as an agent towards change. Furthermore, mass media was perceived as having a positive role to play in supporting women’s empowerment.
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5.
  • Andersson, Ida E, 1982-, et al. (creator_code:aut_t)
  • Design of glycopeptides used to investigate class II MHC binding and T-Cell responses associated with autoimmune arthritis
  • 2011
  • record:In_t: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 6:3, s. e17881-
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • The glycopeptide fragment CII259–273 from type II collagen (CII) binds to the murine Aq and human DR4 class II Major Histocompatibility Complex (MHC II) proteins, which are associated with development of murine collagen-induced arthritis (CIA) and rheumatoid arthritis (RA), respectively. It has been shown that CII259–273 can be used in therapeutic vaccination of CIA. This glycopeptide also elicits responses from T-cells obtained from RA patients, which indicates that it has an important role in RA as well. We now present a methodology for studies of (glyco)peptide-receptor interactions based on a combination of structure-based virtual screening, ligand-based statistical molecular design and biological evaluations. This methodology included the design of a CII259–273 glycopeptide library in which two anchor positions crucial for binding in pockets of Aq and DR4 were varied. Synthesis and biological evaluation of the designed glycopeptides provided novel structure-activity relationship (SAR) understanding of binding to Aq and DR4. Glycopeptides that retained high affinities for these MHC II proteins and induced strong responses in panels of T-cell hybridomas were also identified. An analysis of all the responses revealed groups of glycopeptides with different response patterns that are of high interest for vaccination studies in CIA. Moreover, the SAR understanding obtained in this study provides a platform for the design of second-generation glycopeptides with tuned MHC affinities and T-cell responses.
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6.
  • Andersson, Ida E., 1982-, et al. (creator_code:aut_t)
  • (E)-Alkene and Ethylene Isosteres Substantially Alter the Hydrogen-Bonding Network in Class II MHC Aq/Glycopeptide Complexes and Affect T-Cell Recognition
  • 2011
  • record:In_t: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126. ; 133:36, s. 14368-14378
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • The structural basis for antigen presentation by class II major histocompatibility complex (MHC) proteins to CD4(+) T-cells is important for understanding and possibly treating autoimmune diseases. In the work described in this paper, (E)-alkene and ethylene amide-bond isosteres were used to investigate the effect of removing hydrogen-bonding possibilities from the CII259-270 glycopeptide, which is bound by the arthritis-associated murine A(q) class II MHC protein. The isostere-modified glycopeptides showed varying and unexpectedly large losses of A(q) binding that could be linked to the dynamics of the system. Molecular dynamics (MD) simulations revealed that the backbone of CII259-270 and the A(q) protein are able to form up to 11 hydrogen bonds, but fewer than this number are present at any one time. Most of the strong hydrogen-bond interactions were formed by the N-terminal part of the glycopeptide, i.e., in the region where the isosteric replacements were made. The structural dynamics also revealed that hydrogen bonds were strongly coupled to each other; the loss of one hydrogen-bond interaction had a profound effect on the entire hydrogen-bonding network. The A(q) binding data revealed that an ethylene isostere glycopeptide unexpectedly bound more strongly to A(q) than the corresponding (E)-alkene, which is in contrast to the trend observed for the other isosteres. Analysis of the MD trajectories revealed that the complex conformation of this ethylene isostere was structurally different and had an altered molecular interaction pattern compared to the other A(q)/glycopeptide complexes. The introduced amide-bond isosteres also affected the interactions of the glycopeptide/A(q) complexes with T-cell receptors. The dynamic variation of the patterns and strengths of the hydrogen-bond interactions in the class II MHC system is of critical importance for the class II MHC/peptide/TCR signaling system.
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7.
  • Andersson, Ida E., 1982-, et al. (creator_code:aut_t)
  • Oxazole-modified glycopeptides that target arthritis-associated class II MHC Aq and DR4 proteins
  • 2010
  • record:In_t: Organic and biomolecular chemistry. - : RSC Publishing. - 1477-0520 .- 1477-0539. ; 8:13, s. 2931-2940
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • The glycopeptide CII259-273, a fragment from type II collagen (CII), can induce tolerance in mice susceptible to collagen-induced arthritis (CIA), which is a validated disease model for rheumatoid arthritis (RA). Here, we describe the design and synthesis of a small series of modified CII259-273 glycopeptides with oxazole heterocycles replacing three potentially labile peptide bonds. These glycopeptidomimetics were evaluated for binding to murine CIA-associated A(q) and human RA-associated DR4 class II major histocompatibility complex (MHC) proteins. The oxazole modifications drastically reduced or completely abolished binding to A(q). Two of the glycopeptidomimetics were, however, well tolerated in binding to DR4 and they also induced strong responses by one or two DR4-restricted T-cell hybridomas. This work contributes to the development of an altered glycopeptide for inducing immunological tolerance in CIA, with the long-term goal of developing a therapeutic vaccine for treatment of RA.
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8.
  • Andersson, Jonas, et al. (creator_code:aut_t)
  • Markers of fibrinolysis as predictors for maintenance of sinus rhythm after electrical cardioversion
  • 2011
  • record:In_t: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 127:3, s. 189-192
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • No fibrinolytic component alone was found to be a predictor of recurrence of atrial fibrillation. In multivariate models lower PAI-1 mass was associated with sinus rhythm even after adjusting for CRP, markers of the metabolic syndrome and treatment with atorvastatin. Our findings suggest a patophysiological link between AF and PAI-1 mass but the relation to inflammation remains unclear.
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9.
  • Andersson, Ulrika, et al. (creator_code:aut_t)
  • A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk
  • 2010
  • record:In_t: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 12, s. 17-17
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p< 0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p< 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.
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10.
  • Asellus, Peter, et al. (creator_code:aut_t)
  • Cholesterol and CSF 5-HIAA in attempted suicide
  • 2010
  • record:In_t: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 25
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • BACKGROUND: Low serum cholesterol has been linked to suicide and violent behaviour. The same kind of associations has been reported regarding low levels of 5-hydroxyindolacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and suicidal behaviour. The hypothesis of the link between serum cholesterol and suicide incorporate serotonin. It proposes that low cholesterol is related to altered serotonergic neurotransmission. A correlation between CSF 5-HIAA and serum cholesterol has been shown in animal studies, but has not been found in humans.AIM: To study the interrelationship between serum cholesterol and CSF 5-HIAA in suicide attempters. Since both cholesterol and CSF 5-HIAA are associated with suicide and violent suicide attempts, we also investigated the correlation with suicide, violent suicide attempt method, suicide intent, hopelessness and depression severity.METHODS: Serum total cholesterol and CSF 5-HIAA were measured in 42 medication free suicide attempters. Patients were assessed with Becks's Hopelessness scale (BHS), Suicide Intent Scale (SIS) and Montgomery-Asberg depression rating scale (MADRS) and followed-up for causes of death.RESULTS: Serum total cholesterol and CSF 5-HIAA showed a significant positive correlation adjusted for age, body mass index and substance abuse diagnosis. Cholesterol and CSF 5-HIAA levels did not differ between violent and non-violent suicide attempters or between suicide completers and survivors.CONCLUSIONS: These findings indicate that the serotonergic system may be connected to serum cholesterol in patients with a recent suicide attempt.
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