| 1. |
- Andersson Ersman, Peter, et al.
(author)
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Integration of Screen Printed Piezoelectric Sensors for Force Impact Sensing in Smart Multifunctional Glass Applications
- 2022
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In: Advanced Engineering Materials. - : John Wiley & Sons, Ltd. - 1438-1656 .- 1527-2648. ; 24:11
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Journal article (peer-reviewed)abstract
- Screen printed piezoelectric polyvinylidene fluoride?trifluoro ethylene (PVDF?TrFE)-based sensors laminated between glass panes in the temperature range 80?110?°C are presented. No degradation of the piezoelectric signals is observed for the sensors laminated at 110?°C, despite approaching the Curie temperature of the piezoelectric material. The piezoelectric sensors, here monitoring force impact in smart glass applications, are characterized by using a calibrated impact hammer system and standardized impact situations. Stand-alone piezoelectric sensors and piezoelectric sensors integrated on poly(methyl methacrylate) are also evaluated. The piezoelectric constants obtained from the measurements of the nonintegrated piezoelectric sensors are in good agreement with the literature. The piezoelectric sensor response is measured by using either physical electrical contacts between the piezoelectric sensors and the readout electronics, or wirelessly via both noncontact capacitive coupling and Bluetooth low-energy radio link. The developed sensor concept is finally demonstrated in smart window prototypes, in which integrated piezoelectric sensors are used to detect break-in attempts. Additionally, each prototype includes an electrochromic film to control the light transmittance of the window, a screen printed electrochromic display for status indications and wireless communication with an external server, and a holistic approach of hybrid printed electronic systems targeting smart multifunctional glass applications.
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| 2. |
- Andréasson, Per, 1963-
(author)
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Emotional Empathy, Facial Reactions, and Facial Feedback
- 2010
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Doctoral thesis (other academic/artistic)abstract
- The human face has a fascinating capability to express emotions. The facial feedback hypothesis suggests that the human face not only expresses emotions but is also able to send feedback to the brain and modulate the ongoing emotional experience. It has furthermore been suggested that this feedback from the facial muscles could be involved in empathic reactions. This thesis explores the concept of emotional empathy and relates it to two aspects concerning activity in the facial muscles. First, do people high versus low in emotional empathy differ in regard to in what degree they spontaneously mimic emotional facial expressions? Second, is there any difference between people with high as compared to low emotional empathy in respect to how sensitive they are to feedback from their own facial muscles? Regarding the first question, people with high emotional empathy were found to spontaneously mimic pictures of emotional facial expressions while people with low emotional empathy were lacking this mimicking reaction. The answer to the second question is a bit more complicated. People with low emotional empathy were found to rate humorous films as funnier in a manipulated sulky facial expression than in a manipulated happy facial expression, whereas people with high emotional empathy did not react significantly. On the other hand, when the facial manipulations were a smile and a frown, people with low as well as high emotional empathy reacted in line with the facial feedback hypothesis. In conclusion, the experiments in the present thesis indicate that mimicking and feedback from the facial muscles may be involved in emotional contagion and thereby influence emotional empathic reactions. Thus, differences in emotional empathy may in part be accounted for by different degree of mimicking reactions and different emotional effects of feedback from the facial muscles.
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| 3. |
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| 4. |
- Bergh, Anders, et al.
(author)
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Cobalt-mediated solid phase synthesis of 3-O-alkynylbenzyl galactosides and their evaluation as galectin inhibitors
- 2006
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In: Tetrahedron. - : Elsevier BV. - 0040-4020. ; 62:35, s. 8309-8317
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Journal article (peer-reviewed)abstract
- Methyl beta-D-galactoside was converted to the corresponding 3,4-O-stannylene acetal, which was selectively benzylated with 3-iodobenzyl bromide and coupled to a polymer-bound propargylic ether via a Sonogashira reaction. The polymer-bound carbohydrate substrate was cleaved from the resin with different carbon nucleophiles in a cobalt-mediated Nicholas reaction. The product 3-O-alkynylbenzyl galactosides were screened towards galectin-1, -3, -7, -8N and -9N in a competitive fluorescence polarisation assay. Particularly potent inhibitors were identified against galectin-7 with affinity enhancements up to one order of magnitude due to the 3-O-alkynylbenzyl moiety. (c) 2006 Elsevier Ltd. All rights reserved.
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| 5. |
- Berglin, Ewa, MD, PhD, 1955-, et al.
(author)
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A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis
- 2004
-
In: Arthritis Research & Therapy. - : BioMed Central. - 1478-6362 .- 1465-9905. ; 6:4, s. R303-R308
-
Journal article (peer-reviewed)abstract
- Antibodies against cyclic citrullinated peptide (CCP) and rheumatoid factors (RFs) have been demonstrated to predate the onset of rheumatoid arthritis (RA) by years. A nested case–control study was performed within the Northern Sweden Health and Disease study cohort to analyse the presence of shared epitope (SE) genes, defined as HLA-DRB1*0404 or DRB1*0401, and of anti-CCP antibodies and RFs in individuals who subsequently developed RA. Patients with RA were identified from among blood donors whose samples had been collected years before the onset of symptoms. Controls matched for age, sex, and date of sampling were selected randomly from the same cohort. The SE genes were identified by polymerase chain reaction sequence-specific primers. Anti-CCP2 antibodies and RFs were determined using enzyme immunoassays. Fifty-nine individuals with RA were identified as blood donors, with a median antedating time of 2.0 years (interquartile range 0.9–3.9 years) before presenting with symptoms of RA. The sensitivity for SE as a diagnostic indicator for RA was 60% and the specificity was 64%. The corresponding figures for anti-CCP antibodies were 37% and 98%, and for RFs, 17–42% and 94%, respectively. In a logistic regression analysis, SE (odds ratio [OR] = 2.35), anti-CCP antibodies (OR = 15.9), and IgA-RF (OR = 6.8) significantly predicted RA. In a combination model analysis, anti-CCP antibodies combined with SE had the highest OR (66.8, 95% confidence interval 8.3–539.4) in predicting RA, compared with anti-CCP antibodies without SE (OR = 25.01, 95% confidence interval 2.8–222.2) or SE without anti-CCP antibodies (OR = 1.9, 95% confidence interval 0.9–4.2). This study showed that the presence of anti-CCP antibodies together with SE gene carriage is associated with a very high relative risk for future development of RA.
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| 6. |
- Bhattacharyya, T, et al.
(author)
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Synthesis of chiral, amphiphilic, and water-soluble chiral macrocycles via urea formation.
- 2003
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In: Tetrahedron. - : Elsevier BV. - 0040-4020. ; 59:40, s. 7921-7928
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Journal article (peer-reviewed)abstract
- A simple, efficient, and flexible procedure for the synthesis of chiral, amphiphilic, and water-soluble macrocycles is reported. Acylation of p-xylylenediamine with N-Fmoc-protected glycine, -aspartic acid, -glutamic acid, and -arginine, followed by removal of Fmoc-groups, gave amino acid:p-xylylene conjugate diamines, which were converted to ten macrocycles via stepwise urea formation using p-nitrophenyl chloroformate. -Aspartic acid-containing macrocyles proved to be soluble in aqueous buffers and a macrocycle containing four aspartate residues was found to recognize arginine and arginine esters with moderate affinity.
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| 7. |
- Björk, Jonas, et al.
(author)
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Prospects for improved glomerular filtration rate estimation based on creatinine—results from a transnational multicentre study
- 2020
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In: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 13:4, s. 674-683
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Journal article (peer-reviewed)abstract
- Background The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved.MethodsIn a cross-sectional analysis covering the years 2003–17, CKD-EPI was validated against measured GFR (mGFR; using various tracer methods) in patients with high likelihood of chronic kidney disease (CKD; five CKD cohorts, n = 8365) and in patients with low likelihood of CKD (six community cohorts, n = 6759). Comparisons were made with the Lund–Malmö revised equation (LMR) and the Full Age Spectrum equation.Results7In patients aged 18–39 years old, CKD-EPI overestimated GFR with 5.0–16 mL/min/1.73 m2 in median in both cohort types at mGFR levels <120 mL/min/1.73 m2. LMR had greater accuracy than CKD-EPI in the CKD cohorts (P30, the percentage of estimated GFR within 30% of mGFR, 83.5% versus 76.6%). CKD-EPI was generally the most accurate equation in the community cohorts, but all three equations reached P30 above the Kidney Disease Outcomes Quality Initiative benchmark of 90%.ConclusionsNone of the evaluated equations made optimal use of available data. Prospects for improved GFR estimation procedures based on creatinine exist, particularly in young adults and in settings where patients with suspected or manifest CKD are investigated.
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| 8. |
- Carlsson, Susanne, et al.
(author)
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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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In: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 17:6, s. 663-76
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Journal article (peer-reviewed)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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| 9. |
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| 10. |
- Cumpstey, Ian, et al.
(author)
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Double Affinity Amplification of Galectin-Ligand Interactions through Arginine-Arene Interactions: Synthetic, Thermodynamic, and Computational Studies with Aromatic Diamido-Thiodigalactosides.
- 2008
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In: Chemistry: A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 14:14, s. 4233-4245
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Journal article (peer-reviewed)abstract
- A series of aromatic mono- or diamido-thiodigalactoside derivatives were synthesized and studied as ligands for galectin-1, -3, -7, -8N terminal domain, and -9N terminal domain. The affinity determination in vitro with competitive fluorescence-polarization experiments and thermodynamic analysis by isothermal microcalorimetry provided a coherent picture of structural requirements for arginine-arene interactions in galectin-ligand binding. Computational studies were employed to explain binding preferences for the different galectins. Galectin-3 formed two almost ideal arene-arginine stacking interactions according to computer modeling and also had the highest affinity for the diamido-thiodigalactosides (K(d) below 50 nM). Site-directed mutagenesis of galectin-3 arginines involved in binding corroborated the importance of their interaction with the aromatic diamido-thiodigalactosides. Furthermore, the arginine mutants revealed distinct differences between free, flexible, and solvent-exposed arginine side chains and tightly ion-paired arginine side chains in interactions with aromatic systems.
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| 11. |
- Cumpstey, Ian, et al.
(author)
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Studies of arginine-arene interactions through synthesis and evaluation of a series of galectin-binding aromatic lactose esters
- 2007
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In: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 8:12, s. 1389-1398
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Journal article (peer-reviewed)abstract
- Aromatic lactose 2-O-esters were synthesized and used to probe arene-arginine interactions with the galectin family of proteins. They were found to be low mu m inhibitors of galectin-1, -3, and -9N-terminal domain and moderate inhibitors of galectin-7, but not inhibitors of galectin-8N-terminal, which locks an arginine residue close to the critical, esterified lactose 2-O-position. Molecular modeling of galectins in complex with aromatic lactose 2-O-esters, as well as binding studies with a galectin-3 R186S mutant, confirmed that the inhibitory efficiency of the lactose 2-O-esters was due to the formation of strong interactions between the aromatic ester moieties and the arginine guanidinium groups of galectin-1 and -3. An important common feature shared by galectin-1 and -3 was that the arginines formed in-plane ion pairs with two side-chain carboxylates, which resulted in extended planar pi-electron surfaces that did not require solvation by water; these surfaces were ideal for stocking with aromatic moieties of the ligands. The results provide a basis for the design of lectin inhibitors and drugs that exploit interactions with arginine side-chains via aromatic moieties, which are involved in intramolecular protein salt bridges.
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| 12. |
- Delanaye, Pierre, et al.
(author)
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Performance of creatinine-based equations to estimate glomerular filtration rate in White and Black populations in Europe, Brazil, and Africa
- 2022
-
In: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 38:1, s. 106-118
-
Journal article (peer-reviewed)abstract
- BACKGROUND: A new Chronic Kidney Disease Epidemiology equation without race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared to the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts.METHODS: Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France, (n = 4429, including 964 Black Europeans), from Brazil (n = 100), and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed.RESULTS: In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of -0.6 and -3.2, respectively versus 5.0 mL/min/1.73m², and accuracy within 30% of 86.9 and 87.4, respectively versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value ( = concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans, and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males.CONCLUSION: In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated, population-specific Q-values presents the best performance in the whole age range in the European and African populations included in this study.
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| 13. |
- Delanaye, Pierre, et al.
(author)
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Performance of creatinine-based equations to estimate glomerular filtration rate with a methodology adapted to the context of drug dosage adjustment
- 2022
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In: British Journal of Clinical Pharmacology. - : Wiley-Blackwell Publishing Inc.. - 0306-5251 .- 1365-2125. ; 88:5, s. 2118-2127
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Journal article (peer-reviewed)abstract
- AIM: The Cockcroft-Gault (CG) creatinine-based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over- or underdosing METHODS: In a cross-sectional analysis, CG was validated against measured GFR (mGFR) in 14,804 participants and compared with the Modification-of-Diet-in-Renal-Diseases (MDRD), Chronic-Kidney-Disease-Epidemiology (CKD-EPI), Lund-Malmö-Revised (LMR), and European-Kidney-Function-Consortium (EKFC) equations. Validation focused on bias, imprecision, and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age, and body mass index at mGFR <60 mL/min, as well as classification in mGFR stages.RESULTS: The CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD-EPI, but worse than LMR and EKFC. In subjects with mGFR<60 mL/min and at BMI [18.5-25[kg/m2 , all equations performed similarly and for BMI<18.5kg/m2 CG and LMR had the best results though all equations had poor P30-accuracy. At BMI≥25kg/m2 the bias of the CG increased with increasing BMI (+17.2mL/min at BMI≥40kg/m2 ). The four more recent equations also classified mGFR stages better than CG.CONCLUSIONS: The CG equation showed poor ability to estimate GFR overall and in analyses stratified for GFR, age, and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.
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| 14. |
- Dorell, Åsa, et al.
(author)
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Family Health Conversations have positive outcomes on families : A mixed method study
- 2017
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In: Open Nursing Journal. - : Bentham Open. - 1874-4346. ; :11, s. 14-25
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Journal article (peer-reviewed)abstract
- Background: A Family Systems Nursing intervention, “Family Health Conversations” (FamHC) was conducted in order to strengthen the health of families having relatives at residential home for older people. Having a family member living in a residential home affects the entire family and can be hard to handle. Family members require encouraging and open communication support from nurse during and after relocation to a residential home.Objectives: The aims of this study were to evaluate the responses to and effects of the Family Health Conversations in families with a member living at a residential home for older people and to integrate the empirical results with a theoretical assumption upon which the intervention was based.Methods: A mixed method research design was used. The Swedish Health-Related Quality of Life Survey and the Family Hardiness Index were administered before and 6 months after the intervention. Qualitative data was collected by semi-structured interviews with each family 6 months post-intervention. The sample included families of residents, a total of 10 families comprising 22 family members.Result: Main finding was that FamHCs helped family members process their feelings about having a member living at a residential home and made it easier for them to deal with their own situations. FamHCs helped to ease their consciences, improve their emotional well-being, and change their beliefs about their own insufficiency and guilt. Seeing problems from a different perspective facilitated the families’ thinking in a new way.Conclusion: These findings showed that FamHC can be an important type of intervention to improve family functioning and enhance the emotional well-being.
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| 15. |
- Fritzson, Ingela, et al.
(author)
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N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors
- 2011
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In: MedChemComm. - : Royal Society of Chemistry (RSC). - 2040-2511 .- 2040-2503. ; 2:9, s. 895-898
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Journal article (peer-reviewed)abstract
- In our continuing program to develop Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors, a series of N-substituted salicylamides were synthesized and their ability to selectively inhibit PfDHODH was examined. The synthetic program was based on 2-hydroxy-N-(2-phenylethyl)benzamide (1) that weakly inhibits both PfDHODH and human DHODH (hDHODH). Structure activity relationships were examined for developing derivatives. Selective PfDHODH inhibitors with improved potency were obtained by introducing a 2,2-diphenylethyl substitution on the salicylamidic nitrogen. Biological activity of the most potent compounds was confirmed on parasite infected cells in vitro.
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| 16. |
- Grundberg, Hans, et al.
(author)
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Absence of reverse anomeric effect in furanosides
- 2006
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In: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 1520-6904 .- 0022-3263. ; 71:16, s. 5892-5896
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Journal article (peer-reviewed)abstract
- A series of conformationally restricted N-"furanosides" has been synthesized, where the carbons of the tetrahydrofuran ring are kept in one plane by a rigid norbornane skeleton, permitting only the ring oxygen to move above or below the tetrahydrofuran ring plane. This causes the substituents of the anomeric carbon to occupy a pseudoaxial or a pseudoequatorial position. On protonation of these "norbornane-furanosides" with trifluoromethanesulfonic acid, all three compounds exhibited decreasing coupling constants for the anomeric proton, indicating a shift toward the pseudoaxial conformation. The coupling constant measurements were supported by volume integration of NOESY cross-peaks, which also showed a change toward the pseudoaxial conformation upon protonation of the nitrogen. These results provide no evidence for the so-called reverse anomeric effect; on the contrary they are in full agreement with a small normal anomeric effect.
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| 17. |
- Hasan, Mahmudul, et al.
(author)
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The structure of human dermatan sulfate epimerase 1 emphasizes the importance of C5-epimerization of glucuronic acid in higher organisms
- 2021
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In: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 12:5, s. 1869-1885
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Journal article (peer-reviewed)abstract
- Dermatan sulfate epimerase 1 (DS-epi1, EC 5.1.3.19) catalyzes the conversion of d-glucuronic acid to l-iduronic acid on the polymer level, a key step in the biosynthesis of the glycosaminoglycan dermatan sulfate. Here, we present the first crystal structure of the catalytic domains of DS-epi1, solved at 2.4 Å resolution, as well as a model of the full-length luminal protein obtained by a combination of macromolecular crystallography and targeted cross-linking mass spectrometry. Based on docking studies and molecular dynamics simulations of the protein structure and a chondroitin substrate, we suggest a novel mechanism of DS-epi1, involving a His/double-Tyr motif. Our work uncovers detailed information about the domain architecture, active site, metal-coordinating center and pattern of N-glycosylation of the protein. Additionally, the structure of DS-epi1 reveals a high structural similarity to proteins from several families of bacterial polysaccharide lyases. DS-epi1 is of great importance in a range of diseases, and the structure provides a necessary starting point for design of active site inhibitors.
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| 18. |
- Hassan, Mujtaba, et al.
(author)
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Benzimidazole–galactosides bind selectively to the Galectin-8 N-Terminal domain : Structure-based design and optimisation
- 2021
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In: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234. ; 223
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Journal article (peer-reviewed)abstract
- We have obtained the X-ray crystal structure of the galectin-8 N-terminal domain (galectin-8N) with a previously reported quinoline–galactoside ligand at a resolution of 1.6 Å. Based on this X-ray structure, a collection of galactosides derivatised at O3 with triazole, benzimidazole, benzothiazole, and benzoxazole moieties were designed and synthesised. This led to the discovery of a 3-O-(N-methylbenzimidazolylmethyl)–galactoside with a Kd of 1.8 μM for galectin-8N, the most potent selective synthetic galectin-8N ligand to date. Molecular dynamics simulations showed that benzimidazole–galactoside derivatives bind the non-conserved amino acid Gln47, accounting for the higher selectivity for galectin-8N. Galectin-8 is a carbohydrate-binding protein that plays a key role in pathological lymphangiogenesis, modulation of the immune system, and autophagy. Thus, the benzimidazole-derivatised galactosides represent promising compounds for studies of the pathological implications of galectin-8, as well as a starting point for the development of anti-tumour and anti-inflammatory therapeutics targeting galectin-8.
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| 19. |
- Hassan, Mujtaba, et al.
(author)
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Structure-Guided Design of d -Galactal Derivatives with High Affinity and Selectivity for the Galectin-8 N-Terminal Domain
- 2021
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In: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 12:11, s. 1745-1752
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Journal article (peer-reviewed)abstract
- Galectin-8 is a carbohydrate-binding protein that plays a crucial role in tumor progression and metastasis, antibacterial autophagy, modulation of the immune system, and bone remodeling. The design, synthesis, and protein affinity evaluation of a set of C-3 substituted benzimidazole and quinoline d-galactal derivatives identified a d-galactal-benzimidazole hybrid as a selective ligand for the galectin-8 N-terminal domain (galectin-8N), with a Kd of 48 μM and 15-fold selectivity over galectin-3 and even better selectivity over the other mammalian galectins. X-ray structural analysis of galectin-8N in complex with one benzimidazole- and one quinoline-galactal derivative at 1.52 and 2.1 Å together with molecular dynamics simulations and quantum mechanical calculations of galectin-8N in complex with the benzimidazole derivative revealed orbital overlap between a NH LUMO of Arg45 with electron rich HOMOs of the olefin and O4 of the d-galactal. Such overlap is hypothesized to contribute to the high affinity of the d-galactal-derived ligands for galectin-8N. A (3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay evaluation of the d-galactal-benzimidazole hybrid and an analogous galactoside derivative on a panel of cell lines with MTS assay showed no effect on cell viability up to 100 μM concentration. A subsequent functional assay using the MDA-MB-231 cell line demonstrated that the d-galactal-benzimidazole hybrid and the analogous galactoside derivative reduced the secretion of the proinflammatory cytokines interleukin-6 (IL-6) and IL-8 in a dose-dependent manner. Therefore, these compounds represent potential probes for galectin-8N pharmacology investigations and possibly promising leads for the design and synthesis of potent and selective galectin-8 inhibitors as potential antitumor and anti-inflammatory agents.
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| 20. |
- Klasson Sundin, Maria, 1961-
(author)
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Barnets religionsfrihet – en villkorad rättighet? : En filosofisk undersökning utifrån FN:s barnkonvention
- 2016
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Doctoral thesis (other academic/artistic)abstract
- This dissertation uses philosophical tools to examine the child’s right to freedom of religion within the context of the United Nations Convention on the Rights of the Child (CRC) and other international human rights instruments.Article 14 of the CRC establishes the right of the child to freedom of thought, conscience and religion. It also establishes the right of the child's parents to guide and support the child in its exercise of the right to freedom of religion, while adjusting this support according to the child's evolving capacities. The emphasis of the study is on how to understand the child as, on the one hand, agent and subject in the exercise of this right and, on the other, dependent on parental support and guidance. For this purpose, the theoretical underpinnings of the child’s right to freedom of religion are examined with a particular focus on the conceptualization of this right in relation to children. With the text of the CRC as a starting point, different theories on rights, autonomy and religion are analyzed in order to find those compatible with both aspects of Article 14: the child as agent and the child as dependent. Theories that demand fully developed cognitive abilities in order to be a moral agent and a rights holder are rejected, as are theories in which the parents are the sole decision-makers on the basis of their own view of what is in the child's interests. In the same way, conceptions of religion in purely cognitive terms, or not taking into account dimensions of practice and observance accessible to children, are rejected.The conclusion drawn from the analysis is that relational conceptualizations of rights and autonomy and multi-dimensional conceptualizations of religion are best served to include both aspects of the child's right to freedom of religion. In viewing all humans, adults and children alike, as both active agents and vulnerably dependent on others, these conceptualizations challenge traditional views on rights and autonomy, and modern views of religion. In the final chapter, aspects of these relational conceptions are put together into a relational, mutuality-oriented model of the child's right to freedom of religion.
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| 21. |
- Lundström, Emeli, et al.
(author)
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HLA-DRB1*04/*13 alleles are associated with vascular disease and antiphospholipid antibodies in systemic lupus erythematosus
- 2013
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 72:6, s. 1018-1025
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVES:Vascular disease is common in systemic lupus erythematosus (SLE) and patients with antiphospholipid antibodies (aPL) are at high risk to develop arterial and venous thrombosis. Since HLA class II genotypes have been linked to the presence of pro-thrombotic aPL, we investigated the relationship between HLA-DRB1 alleles, aPL and vascular events in SLE patients.METHODS:665 SLE patients of Caucasian origin and 1403 controls were included. Previous manifestations of ischaemic heart disease, ischaemic cerebrovascular disease (ICVD) and venous thromboembolism (together referred to as any vascular events (AVE)) were tabulated. aPL were measured with ELISA. Two-digit HLA-DRB1 typing was performed by sequence-specific primer-PCR.RESULTS: HLA-DRB1*04 was more frequent among SLE patients with ICVD compared to unaffected patients. This association remained after adjustment for known traditional cardiovascular risk factors. HLA-DRB1*13 was associated with AVE. All measured specificities of aPL—cardiolipin IgG and IgM, β2-glycoprotein-1 IgG, prothrombin (PT) IgG and a positive lupus anticoagulant test were associated with HLA-DRB1*04—while HLA-DRB1*13 was associated with IgG antibodies (β2-glycoprotein-1, cardiolipin and PT). In patients with the combined risk alleles, HLA-DRB1*04/*13, there was a significant additive interaction for the outcomes AVE and ICVD.CONCLUSIONS:The HLA-DRB1*04 and HLA-DRB1*13 alleles are associated with vascular events and an aPL positive immune-phenotype in SLE. Results demonstrate that a subset of SLE patients is genetically disposed to vascular vulnerability.
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| 22. |
- Madar Johansson, Miralda, et al.
(author)
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The binding mechanism of the virulence factor Streptococcus suis adhesin P subtype to globotetraosylceramide is associated with systemic disease
- 2020
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 295:42, s. 14305-14324
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Journal article (peer-reviewed)abstract
- Streptococcus suis is part of the pig commensal microbiome but strains can also be pathogenic, causing pneumonia and meningitis in pigs as well as zoonotic meningitis. According to genomic analysis, S. suis is divided into asymptomatic carriage, respiratory and systemic strains with distinct genomic signatures. Because the strategies to target pathogenic S. suis are limited, new therapeutic approaches are needed. The virulence factor S. suis adhesin P (SadP) recognizes the galabiose Gal alpha 1-4Gal-oligosaccharide. Based on its oligosaccharide fine specificity, SadP can be divided into subtypes P-N and P-O. We show here that subtype P-N is distributed in the systemic strains causing meningitis, whereas type P-O is found in asymptomatic carriage and respiratory strains. Both types of SadP are shown to predominantly bind to pig lung globotriaosylceramide (Gb3). However, SadP adhesin from systemic subtype P-N strains also binds to globotetraosylceramide (Gb4). Mutagenesis studies of the galabiose-binding domain of type P-N SadP adhesin showed that the amino acid asparagine 285, which is replaced by an aspartate residue in type P-O SadP, was required for binding to Gb4 and, strikingly, was also required for interaction with the glycomimetic inhibitor phenylurea-galabiose. Molecular dynamics simulations provided insight into the role of Asn-285 for Gb4 and phenylurea-galabiose binding, suggesting additional hydrogen bonding to terminal GalNAc of Gb4 and the urea group. Thus, the Asn-285-mediated molecular mechanism of type P-N SadP binding to Gb4 could be used to selectively target S. suis in systemic disease without interfering with commensal strains, opening up new avenues for interventional strategies against this pathogen.
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| 23. |
- Mahanti, Mukul, et al.
(author)
-
Epimers Switch Galectin-9 Domain Selectivity : 3 N-Aryl Galactosides Bind the C-Terminal and Gulosides Bind the N-Terminal
- 2020
-
In: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 11:1, s. 34-39
-
Journal article (peer-reviewed)abstract
- A series of 3-deoxy-3-N-arylated-β-d-galactoside and -guloside derivatives have been synthesized by cesium fluoride/trimetylsilylaryl triflate-mediated benzyne generation and N-arylation of 3-deoxy-3-amino-β-d-galactosides and -gulosides, respectively. Evaluation as ligands to galectin-1, 2, 3, 4N (N-terminal domain), 4C (C-terminal domain), 7, 8N, 8C, 9C, and 9N revealed that the galactosides selectively bound galectin-9C, whereas the gulosides selectively bound galectin-9N. Hence, the N-aryl group induces galectin-9 selectivity and the ligand 3C-configuration acts as an epimeric selectivity switch between the two domains of galectin-9. Furthermore, MD simulations revealed that galacto derivatives in galectin-9C and gulo derivatives in galectin-9N find stable poses with specific interactions, which proposes a possible explanation to the gal/gulo 9C/9N selectivity.
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| 24. |
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| 25. |
- Muth, Andreas, 1974, et al.
(author)
-
Nationellt vårdprogram för adrenala incidentalom - Programmet har harmoniserats med europeiska riktlinjer – ger förenklad handläggning av patienter.
- 2017
-
In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 114
-
Journal article (peer-reviewed)abstract
- Swedish guidelines for the management of adrenal incidentalomas Adrenal incidentalomas are seen in about five percent of abdominal CT examinations, and in most cases represent non-hormone-producing adrenocortical adenomas, but hormone-producing or malignant lesions occur. Revised Swedish guidelines for the evaluation and management of adrenal incidentalomas based on recently published European guidelines are presented. The importance of a thorough radiological, clinical and biochemical initial evaluation is emphasized. Long-term biochemical follow-up is not recommended and use of CT contrast medium »washout« calculation is omitted. No radiological evaluation or follow-up indicated for adrenal incidentalomas <1 cm size. For patients with diagnosed lipid rich adenomas (≤ 10 HU) 1-4 cm in size no radiological follow-up is suggested after initial evaluation.
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| 26. |
- Nilsson, Johan, et al.
(author)
-
Paracetamol analogues conjugated by FAAH induce TRPV1-mediated antinociception without causing acute liver toxicity
- 2021
-
In: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 213
-
Journal article (peer-reviewed)abstract
- Paracetamol, one of the most widely used pain-relieving drugs, is deacetylated to 4-aminophenol (4-AP) that undergoes fatty acid amide hydrolase (FAAH)-dependent biotransformation into N-arachidonoylphenolamine (AM404), which mediates TRPV1-dependent antinociception in the brain of rodents. However, paracetamol is also converted to the liver-toxic metabolite N-acetyl-p-benzoquinone imine already at therapeutic doses, urging for safer paracetamol analogues. Primary amine analogues with chemical structures similar to paracetamol were evaluated for their propensity to undergo FAAH-dependent N-arachidonoyl conjugation into TRPV1 activators both in vitro and in vivo in rodents. The antinociceptive and antipyretic activity of paracetamol and primary amine analogues was examined with regard to FAAH and TRPV1 as well as if these analogues produced acute liver toxicity. 5-Amino-2-methoxyphenol (2) and 5-aminoindazole (3) displayed efficient target protein interactions with a dose-dependent antinociceptive effect in the mice formalin test, which in the second phase was dependent on FAAH and TRPV1. No hepatotoxicity of the FAAH substrates transformed into TRPV1 activators was observed. While paracetamol attenuates pyrexia via inhibition of brain cyclooxygenase, its antinociceptive FAAH substrate 4-AP was not antipyretic, suggesting separate mechanisms for the antipyretic and antinociceptive effect of paracetamol. Furthermore, compound 3 reduced fever without a brain cyclooxygenase inhibitory action. The data support our view that analgesics and antipyretics without liver toxicity can be derived from paracetamol. Thus, research into the molecular actions of paracetamol could pave the way for the discovery of analgesics and antipyretics with a better benefit-to-risk ratio.
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| 27. |
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| 28. |
- Pal, Kumar Bhaskar, et al.
(author)
-
Quinoline-galactose hybrids bind selectively with high affinity to a galectin-8 N-terminal domain
- 2018
-
In: Organic and Biomolecular Chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 16:34, s. 6295-6305
-
Journal article (peer-reviewed)abstract
- Quinolines, indolizines, and coumarins are well known structural elements in many biologically active molecules. In this report, we have developed straightforward methods to incorporate quinoline, indolizine, and coumarin structures into galactoside derivatives under robust reaction conditions for the discovery of glycomimetic inhibitors of the galectin family of proteins that are involved in immunological and tumor-promoting biological processes. Evaluation of the quinoline, indolizine and coumarin-derivatised galactosides as inhibitors of the human galectin-1, 2, 3, 4N (N-terminal domain), 4C (C-terminal domain), 7, 8N, 8C, 9N, and 9C revealed quinoline derivatives that selectively bound galectin-8N, a galectin with key roles in lymphangiogenesis, tumor progression, and autophagy, with up to nearly 60-fold affinity improvements relative to methyl β-d-galactopyranoside. Molecular dynamics simulations proposed an interaction mode in which Arg59 had moved 2.5 Å and in which an inhibitor carboxylate and quinoline nitrogen formed structure-stabilizing water-mediated hydrogen bonds. The compounds were demonstrated to be non-toxic in an MTT assay with several breast cancer cell lines and one normal cell line. The improved affinity, selectivity, and low cytotoxicity suggest that the quinoline-galactoside derivatives provide an attractive starting point for the development of galectin-8N inhibitors potentially interfering with pathological lymphangiogenesis, autophagy, and tumor progression.
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| 29. |
- Pottel, Hans, et al.
(author)
-
Cystatin C–Based Equation to Estimate GFR without the Inclusion of Race and Sex
- 2023
-
In: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 388:4, s. 333-343
-
Journal article (peer-reviewed)abstract
- BACKGROUNDThe accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C–based EKFC equation would increase the accuracy of estimated GFR is unknown.METHODSWe used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex.RESULTSOn the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83+0.005×(age–50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone.CONCLUSIONSThe EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations.
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| 30. |
- Pottel, Hans, et al.
(author)
-
Cystatin C–Based Equation to Estimate GFR without the Inclusion of Race and Sex
- 2023
-
In: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 388:4, s. 333-343
-
Journal article (peer-reviewed)abstract
- BackgroundThe accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C–based EKFC equation would increase the accuracy of estimated GFR is unknown.MethodsWe used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex.ResultsOn the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83+0.005×(age–50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone.ConclusionsThe EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations. (Funded by the Swedish Research Council.)
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| 31. |
- Pottel, Hans, et al.
(author)
-
Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate : A Cross-sectional Analysis of Pooled Data
- 2021
-
In: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 174:2, s. 183-191
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low.OBJECTIVE: To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations.DESIGN: Cross-sectional analysis with separate pooled data sets for development and validation.SETTING: = 13) with measured GFR available.PATIENTS: 11 251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set).MEASUREMENTS: Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR.RESULTS: ] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations.LIMITATION: No Black patients were included.CONCLUSION: The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels.PRIMARY FUNDING SOURCE: Swedish Research Council (Vetenskapsrådet).
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| 32. |
- Pottel, Hans, et al.
(author)
-
Standardization of serum creatinine is essential for accurate use of unbiased estimated GFR equations : evidence from three cohorts matched on renal function
- 2022
-
In: Clinical Kidney Journal. - : Oxford University Press. - 2048-8505 .- 2048-8513. ; 15:12, s. 2258-2265
-
Journal article (peer-reviewed)abstract
- Background: Differences in the performance of estimated glomerular filtration rate (eGFR) equations have been attributed to the mathematical form of the equations and to differences between patient demographics and measurement methods. We evaluated differences in serum creatinine (SCr) and eGFR in cohorts matched for age, sex, body mass index (BMI) and measured GFR (mGFR).Methods: White North Americans from Minnesota (n = 1093) and the Chronic Renal Insufficiency Cohort (CRIC) (n = 1548) and White subjects from the European Kidney Function Consortium (EKFC) cohort (n = 7727) were matched for demographic patient characteristics (sex, age +/- 3 years, BMI +/- 2.5 kg/m(2)) and renal function (mGFR +/- 3 ml/min/1.73 m(2)). SCr was measured with isotope dilution mass spectrometry (IDMS)-traceable assays in the Minnesota and EKFC cohorts and with non-standardized SCr assays recalculated to IDMS in the CRIC. The Minnesota cohort and CRIC shared a common method to measure GFR (renal clearance of iothalamate), while the EKFC cohort used a variety of exogenous markers and methods, all with recognized sufficient accuracy. We compared the SCr levels and eGFR predictions [for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and EKFC equations] of patients fulfilling these matching criteria.Results: For 305 matched individuals, mean SCr (mg/dL) was not different between the Minnesota and EKFC cohorts (females 0.83 +/- 0.20 versus 0.86 +/- 0.23, males 1.06 +/- 0.23 versus 1.12 +/- 0.37; P > .05) but significantly different from the CRIC [females 1.13 +/- 0.23 (P < .0001), males 1.42 +/- 0.31 (P < .0001)]. The CKD-EPI equations performed better than the EKFC equation in the CRIC, while the opposite was true in the Minnesota and EKFC cohorts.Conclusion: Significant differences in SCr concentrations between the Minnesota and EKFC cohorts versus CRIC were observed in subjects with the same level of mGFR and equal demographic characteristics and can be explained by the difference in SCr calibration.Lay Summary: Standardization of serum creatinine (SCr) measurement is fundamental for estimating glomerular filtration rate (GFR). We used data with GFR measured by a reference method from three cohorts: Chronic Renal Insufficiency Cohort (CRIC, n = 1548), Minnesota cohort (n = 1093) and European Kidney Function Consortium cohort (EKFC; n = 7727). In the EKFC and Minnesota cohorts, SCr was measured by standardized methods, although SCr 'calibration' was more debatable in the CRIC. GFR was measured by the same method in the CRIC and Minnesota cohort. Then we matched 305 White subjects for sex, measured GFR (+/- 3 ml/min/1.73 m(2)), age (+/- 3 years) and body mass index (+/- 2.5 kg/m(2)). From these matched subjects we showed that the association between SCr and measured GFR was quite similar between subjects from the Minnesota and EKFC cohorts, but different between the CRIC and EKFC cohort and between the Minnesota cohort and CRIC. These differences lead to discrepancies in the analysis of the performance of different creatinine-based equations.
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| 33. |
- Pusa, Susanna, 1982-, et al.
(author)
-
Evaluation of the Implementation Process of a Family Systems Nursing Approach in Home Health Care : A Mixed-Methods Study
- 2021
-
In: Journal of Family Nursing. - : Sage Publications. - 1074-8407 .- 1552-549X. ; 27:3, s. 235-249
-
Journal article (peer-reviewed)abstract
- To support the incorporation of Family Systems Nursing (FSN) in clinical practice, more understanding is needed about the implementation of FSN in home health practice settings. Thus, the aim of this study was to evaluate nurses' perspectives about the implementation process of Family Systems Nursing Conversations (FSNCs) in home health care. A mixed-methods research design was used, integrating qualitative and quantitative data, and using triangulation as a methodological metaphor. The Quality Implementation Framework (QIF) was applied to guide the implementation process, and Proctor et al.'s taxonomy of implementation outcomes was used to evaluate the process. The findings demonstrated that FSN implementation was in progress. Overall, acceptability and appropriateness of FSNCs were evaluated as positive by home health nurses; however, some obstacles were found relating to feasibility, adoption, and fidelity. These results contribute to an increased understanding of the process and challenges of implementing FSNCs in home health care.
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| 34. |
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| 35. |
- Pusa, Susanna, 1982-
(author)
-
Vägen mot implementering av familjecentrerad omvårdnad
- 2019
-
Doctoral thesis (other academic/artistic)abstract
- Bakgrund: När människor är inkluderade i varandras liv påverkar en förändring av livssituationen hos en person även de övriga personerna som står den nära. Det innebär att när en person drabbas av ohälsa eller sjukdom påverkas även personens familj. Familjens upplevelse av den situation som uppstår i samband med ohälsa kan dessutom negativt påverka familjemedlemmarnas medvetenhet om familjens tillgängliga styrkor och resurser, vilket i sin tur kan påverka familjers kamp för att återfå och bibehålla hälsa. Traditionellt sett har vården fokuserat på att erbjuda stöd på personnivå, och främst då till patienter. De senaste decennierna har dock en tendens uppmärksammats till ökad förståelse för att hela familjen behöver inkluderas i omvårdnaden. Att anamma ett familjecentrerat förhållningssätt – det vill säga, att se och möta familjen som en enhet och som ett system – har visat sig ha flera fördelar utifrån såväl patient- och familje- som sjuksköterskeperspektiv. Detta har medfört en efterfrågan på forskning om hur familjecentrerad omvårdnad kan läras ut och implementeras i den kliniska hälso- och sjukvården.Syfte: Det övergripande syftet med avhandlingen är att belysa erfarenheter av stöd från distriktssköterskor/sjuksköterskor till familjer i ordinärt boende, samt att utvärdera implementering av familjecentrerade samtal.Metod: Avhandlingen inkluderar tre studier med kvalitativ design och en studie med mixad-metod design. I delstudie I samlades data in genom tio fokusgruppintervjuer med 36 distriktssköterskor och analyserades sedan med en fenomenologisk hermeneutisk metod. Datainsamlingen för delstudie II bestod av ljudinspelade familjecentrerade samtal med sju familjer, samt sju avslutande brev riktade till familjerna som distriktssköterskorna/sjuksköterskorna skrev efter samtalen med familjerna. Familjesamtalen och breven analyserades med hjälp av kvalitativ innehållsanalys. I delstudie III analyserades individuella intervjuer med 21 distriktssköterskor/sjuksköterskor med kvalitativ innehållsanalys. Mixad metod användes i delstudie IV, där kvantitativa data från instrumentet Families’ Importance in Nursing Care – Nurses’ Attitudes (FINC-NA) integrerades med kvalitativa data från individuella intervjuer med 14 distriktssköterskor/sjuksköterskor.Resultat: Resultatet visar att distriktssköterskor/sjuksköterskor strävar efter att stödja familjer (I, IV) och att familjecentrerad omvårdnad i form av familjecentrerade samtal kan vara ett sätt att stöda familjer att dela med sig av sina upplevelser och känslor både inom familjen och med distriktssköterskan/ sjuksköterskan (II, IV). Det upplevda stödet från såväl familjen som distriktssköterskan/sjuksköterskan ansågs värdefullt för att bättre hantera situationen och framtiden (II). Distriktssköterskorna/sjuksköterskorna uppfattade den webbaserade utbildningen i familjecentrerad omvårdnad inklusive familjecentrerade samtal som överlag funktionell och välanpassad (III). Utbildningen med den påföljande implementeringen beskrevs bidra till ett förändrat förhållningssätt hos dem, där de tänkte och arbetade mer inkluderande och stödjande gentemot familjer, även när de inte utförde familjecentrerade samtal enligt den tänkta strukturen (III, IV). Utvärderingen av implementeringen av de familjecentrerade samtalen visade att införandet av familjecentrerade samtal fortgick även om de inte hade implementerats fullt ut som avsett. Acceptans och lämplighet utvärderades överlag positivt, dock framkom personliga, sociala och organisatoriska hinder, vilka påverkade genomförandet, användningen och metodtroheten (IV).Konklusion: Stöd från distriktssköterskor/sjuksköterskor till familjer är en omvårdnadshandling som förutsätter medveten omsorg i ett aktivt möte med familjen, där varje enskild person, men även familjen som enhet, behöver beaktas. Detta stöd för familjers hälsa kan ske genom familjecentrerad omvårdnad. En webbaserad utbildning för distriktssköterskor/sjuksköterskor i familjecentrerad omvårdnad och familjecentrerade samtal utgör ett adekvat steg i processen att implementera detta arbetssätt i den kliniska verksamheten. Sammanfattningsvis bidrar avhandlingen till kunskap om hur stödjande familjecentrerade samtal kan implementeras i klinisk verksamhet och vilka aspekter som kan påverka detta.
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| 36. |
- Rajput, Vishal Kumar, et al.
(author)
-
Galactose-amidine derivatives as selective antagonists of galectin-9
- 2016
-
In: Canadian Journal of Chemistry. - : Canadian Science Publishing. - 0008-4042 .- 1480-3291. ; 94:11, s. 936-939
-
Journal article (peer-reviewed)abstract
- The family of galectin proteins involved in adhesion, growth regulation, immunity, and inflammatory events are important targets for development of small molecule antagonists. Here, N-sulfonyl amidine galactopyranoside derivatives obtained via a multicomponent reaction between galactose alkyne derivatives, sulfonyl azides, and amines were evaluated as antagonists of galectin-1,-2,-3,-4N (N-terminal domain),-4C (C-terminal domain),-8N,-9N, and-9C in a competitive fluorescence polarization assay. Highly selective compounds against galectin-9N with up to 30-fold improved affinity compared to the reference methyl β-d-galactopyranoside were identified. Molecular dynamics simulation suggested that the selectivity and affinity for galectin-9N originate from the N-sulfonyl amidine moieties forming tridentate hydrogen bonds to two asparagine side chains and one phenyl stacking edge-to-face to an arginine side chain. These selective galectin-9N antagonists are of significant value as chemical tools for studying galectin-9 biology and chemistry as well as possible starting structures for the discovery of galectin-9-targeting drugs influencing, e.g., immune regulation.
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| 37. |
- Rantapää-Dahlqvist, Solbritt, et al.
(author)
-
Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis
- 2003
-
In: Arthritis and Rheumatism. - : Wiley-Blackwell. - 0004-3591 .- 1529-0131. ; 48:10, s. 2741-2749
-
Journal article (peer-reviewed)abstract
- Methods: A case–control study was nested within the Northern Sweden Health and Disease Study and the Maternity cohorts of Northern Sweden. Patients with RA were identified among blood donors whose samples had been taken years before the onset of symptoms. Control subjects matched for age, sex, date of sampling, and residential area were selected randomly from the same cohorts. Anti‐CCP antibody and RFs were determined using enzyme immunoassays.Results: Eighty‐three individuals with RA were identified as having donated blood before presenting with any symptoms of joint disease (median 2.5 years [interquartile range 1.1–4.7] before RA). In samples obtained before the onset of RA, the prevalence of autoantibodies was 33.7% for anti‐CCP, 16.9% for IgG‐RF, 19.3% for IgM‐RF, and 33.7% for IgA‐RF (all highly significant compared with controls). The sensitivities for detecting these autoantibodies >1.5 years and ≤1.5 years before the appearance of any RA symptoms were 25% and 52% for anti‐CCP, 15% and 30% for IgM‐RF, 12% and 27% for IgG‐RF, and 29% and 39% for IgA‐RF. In conditional logistic regression models, anti‐CCP antibody and IgA‐RF were found to be significant predictors of RA.Conclusion: Anti‐CCP antibody and RFs of all isotypes predated the onset of RA by several years. The presence of anti‐CCP and IgA‐RF predicted the development of RA, with anti‐CCP antibody having the highest predictive value. This indicates that citrullination and the production of anti‐CCP and RF autoantibodies are early processes in RA.
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| 38. |
- Salameh, Bader A., et al.
(author)
-
1H-1,2,3-Triazol-1-yl thiodigalactoside derivatives as high affinity galectin-3 inhibitors
- 2010
-
In: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 18:14, s. 5367-5378
-
Journal article (peer-reviewed)abstract
- Galactose C3-triazole derivatives were synthesized by Cu(I)-catalyzed cycloaddition between acetylenes and galactose C3-azido derivatives. Evaluation against galectin-3, 7, 8N (N-terminal) and 9N (N-terminal) revealed 1,4-disubstituted triazoles to be high-affinity inhibitors of galectin-3 with selectivity over galectin-7, 8N, and 9N. Conformational analysis of 1,4-di-and 1,4,5-tri-substituted galactose C3-triazoles suggested that a triazole C5-substituent interfered sterically with the galectin proteins, which explained their poor affinities compared to the corresponding 1,4-disubstituted triazoles. Introduction of two 1,4-disubstituted triazole moieties onto thiodigalactoside resulted in affinities down to 29 nM for galectin-3. (C) 2010 Elsevier Ltd. All rights reserved.
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| 39. |
- Salameh, Bader, et al.
(author)
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Thioureido N-acetyllactosamine derivatives as potent galectin-7 and 9N inhibitors
- 2006
-
In: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 14:4, s. 1215-1220
-
Journal article (peer-reviewed)abstract
- Derivatives of N-acetyllactosamine carrying structurally diverse thioureido groups at galactose C3 were prepared from a C3'-azido N-acetyllactosamine derivative in a three-step reaction sequence involving azide reduction and isothiocyanate formation by thiophosgene treatment of the C3-amine, followed by reaction of the isothiocyanate with a panel of amines. Evaluation of the N-acetyllactosamine thioureas as inhibitors against galectins-1, 3, 7, 8N (N-terminal domain), and 9N (N-terminal domain) revealed thiourea-mediated affinity enhancements for galectins-1, 3, 7, and 9N. In particular, good inhibitors were discovered against galectin-7 and 9N (K-d 23 and 47 mu M, respectively, for a 3-pyridylinethylthiourea derivative), which represents more than an order of magnitude affinity enhancement over the parent natural N-acetyllactosamine. (c) 2005 Elsevier Ltd. All rights reserved.
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| 40. |
- Salomonsson, Emma, et al.
(author)
-
Monovalent Interactions of Galectin-1
- 2010
-
In: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 49:44, s. 9518-9532
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Journal article (peer-reviewed)abstract
- Galectin-1, beta-galactoside binding lectin involved in immunoregulation and cancer, binds natural and many synthetic multivalent glycoconjugates with an apparent glycoside cluster effect, that is, affinity above and beyond what would be expected from the concentration of the determinant sugar. Here we have analyzed the mechanism of such cluster effects in solution at physiological concentration using a fluorescence anisotropy assay with a novel fluorescent high-affinity galectin-1 binding probe. The interaction of native dimeric and monomeric mutants of rat and human galectin-1 with mono- and divalent small molecules, fetuin, asialofetuin, and human serum glycoproteins was analyzed. Surprisingly, high-affinity binding did not depend much on the dimeric state of galectin-1 and thus is due mainly to monomeric interactions of a single carbohydrate recognition domain. The mechanism for this is unknown, but one possibility includes additional interactions that high-affinity ligands make with an extended binding site on the carbohydrate recognition domain, It follows that such weak additional interactions must be important for the biological function of galectin-1 and also for the design of galectin-1 inhibitors.
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| 41. |
- Salomonsson, Emma, et al.
(author)
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Mutational tuning of galectin-3 specificity and biological function.
- 2010
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In: The Journal of biological chemistry. - 1083-351X. ; 285, s. 35079-35091
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Journal article (peer-reviewed)abstract
- Galectins are defined by a conserved beta-galactoside binding site, which has been linked to many of their important functions in e.g. cell adhesion, signaling and intracellular trafficking. Weak adjacent sites may enhance or decrease affinity for natural beta-galactoside containing glycoconjugates, but little is known about the biological role of this modulation of affinity (fine specificity). We have now produced 10 mutants of human galectin-3, with changes in these adjacent sites, which have altered carbohydrate-binding fine specificity but which retain the basic beta-galactoside binding activity as show by glycan-array binding and a solution-based fluorescence anisotropy assay. Each mutant was also tested in two biological assays to provide a correlation between fine specificity and function. Galectin-3 R186S, which has selectively lost affinity for LacNAc, a disaccharide moiety commonly found on glycoprotein glycans, has lost the ability to activate neutrophil leukocytes and intracellular targeting into vesicles. K176L has increased affinity for beta-galactosides substituted with GlcNAcbeta1-3 as found in poly-N-acetyllactosaminoglycans, and increased potency to activate neutrophil leukocytes, even though it has lost other aspects of galectin-3 fine specificity. G182A has altered carbohydrate-binding fine specificity and altered intracellular targeting into vesicles, a possible link to the intracellular galectin-3-mediated anti-apoptotic effect known to be lost by this mutant. Finally, the mutants have helped to define the differences in fine specificity shown by Xenopus, mouse and human galectin-3 and as such, evidence for adaptive change during evolution.
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| 42. |
- Siegbahn, Anna, et al.
(author)
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Rules for priming and inhibition of glycosaminoglycan biosynthesis; probing the beta 4GalT7 active site
- 2014
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In: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 5:9, s. 3501-3508
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Journal article (peer-reviewed)abstract
- beta-1,4-Gatactosyltransferase 7 (beta 4GalT7) is an essential enzyme in the biosynthesis of glycosaminoglycan (GAG) chains of proteoglycans (PGs). Mammalian cells produce PGs, which are involved in biological processes such as cell growth and differentiation. The PGs consist of a core protein, with one or several GAG chains attached. Both the structure of the PGs and the GAG chains, and the expression of the enzymes involved in their biosynthesis and degradation, vary between normal cells and tumor cells. The biosynthesis of GAG chains is initiated by xylosylation of a serine residue of the core protein, followed by galactosylation by beta 4GalT7. The biosynthesis can also be initiated by exogenously added beta-D-xylopyranosides with hydrophobic aglycons, which thus can act as acceptor substrates for beta 4GalT7. To determine the structural requirements for beta 4GalT7 activity, we have cloned and expressed the enzyme and designed a focused library of 2-naphthyl beta-D-xylopyranosides with modifications of the xylose moiety. Based on enzymatic studies, that is galactosylation and its inhibition, conformational analysis and molecular modeling using the crystal structure, we propose that the binding pocket of beta 4GalT7 is very narrow, with a precise set of important hydrogen bonds. Xylose appears to be the optimal acceptor substrate for galactosylation by beta 4GalT7. However, we show that modifications of the xylose moiety of the beta-D-xylopyranosides can render inhibitors of galactosylation. Such compounds will be valuable tools for the exploration of GAG and PG biosynthesis and a starting point for development of anti-tumor agents.
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| 43. |
- Singh, Birendra, et al.
(author)
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Haemophilus influenzae surface fibril (Hsf) is a unique twisted hairpin-like trimeric autotransporter
- 2015
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In: International Journal of Medical Microbiology. - : Elsevier BV. - 1618-0607 .- 1438-4221. ; 305:1, s. 27-37
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Journal article (peer-reviewed)abstract
- The Haemophilus surface fibril (Hsf) is an extraordinary large (2413 amino acids) trimeric autotransporter, present in all encapsulated Haemophilus influenzae. It contributes to virulence by directly functioning as an adhesin. Furthermore, Hsf recruits the host factor vitronectin thereby inhibiting the host innate immune response resulting in enhanced survival in serum. Here we observed by electron microscopy that Hsf appears as an 100. nm long fibril at the bacterial surface albeit the length is approximately 200. nm according to a bioinformatics based model. To unveil this discrepancy, we denaturated Hsf at the surface of Hib by using guanidine hydrochloride (GuHCl). Partial denaturation induced in the presence of GuHCl unfolded the Hsf molecules, and resulted in an increased length of fibres in comparison to the native trimeric form. Importantly, our findings were also verified by E. coli expressing Hsf at its surface. In addition, a set of Hsf-specific peptide antibodies also indicated that the N-terminal of Hsf is located near the C-terminal at the base of the fibril. Taken together, our results demonstrated that Hsf is not a straight molecule but is folded and doubled over. This is the first report that provides the unique structural features of the trimeric autotransporter Hsf.
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| 44. |
- Sundin, Mats, 1956-
(author)
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Bra läge men dåligt rykte : En jämförande historisk studie av tre stadsdelar i Borås, Eskilstuna och Gävle
- 2007
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Doctoral thesis (other academic/artistic)abstract
- Centrally located problem areas of today, with suburban-like modernist architecture, are an anomaly in Sweden. The purpose of the present study is to investigate this Swedish anomaly by comparing three such city sections – Norrby in Borås, Nyfors in Eskilstuna and Öster in Gävle – and to try to answer the question: what type of case is this? To answer this question, a theoretical perspective distinguishing habitation, population and images is developed using concepts from Bourdieu, Elias and Scotson, Goffman, Lefebvre and Østerberg. Methodologically, this is a detailed comparative case study of the history of these three city sections in three or four phases, from before to after their thorough urban renewal in the 1960s. Once, these habitations developed in concert with their city into a working-class area, just beside the city centre, but beyond the railway station. After WWII, they became subjects of renewal, thus afflicted by a slum process that preceded demolition. The new habitation was planned for housing a working-class population. Suburban-like in shape, it was nevertheless part of an inner-city renewal. The new habitation became a target for critique already during the renewal process, a critique that was cast in the same terms as the critique of the suburbs of the time: Images of poor and troublesome outdoor milieus, social problems of different kinds, empty apartments, high turn over, immigrants and refugees were produced, in the media but also by the inhabitants and their organizations, giving the city section a bad reputation. This was to last until the present. Yet with new investment in attractive housing in adjacent brown field areas, these areas have once again become the subject of renewal. Consequently, these areas can be identified as a case of a good location with a bad reputation, emerging from the inner-city renewal of a former working-class habitation.
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| 45. |
- Sundin, Maria, 1965, et al.
(author)
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Exoplaneter
- 2018
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In: Svenska Matematiker Samfundets Bulletin. ; :Februari 2018, s. 20-24
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Journal article (other academic/artistic)
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| 46. |
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| 47. |
- Svenungsson, Elisabet, et al.
(author)
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A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus
- 2010
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 69:5, s. 834-840
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Journal article (peer-reviewed)abstract
- Objective To investigate whether the risk allele for systemic lupus erythematosus (SLE) in the signal transducer and activator of transcription factor 4 (STAT4) gene, defined by the single nucleotide polymorphism (SNP) rs10181656(G), is associated with vascular events and/or presence of prothrombotic anti-phospholipid antibodies (aPL) in patients with SLE. Methods Two independent groups of unrelated patients with SLE of Swedish ethnicity (n=424 and 154) were genotyped, and occurrence of previous manifestations of ischaemic heart disease (IHD), ischaemic cerebrovascular disease (ICVD) and venous thromboembolic events (VTE) was tabulated. aPL values were measured by ELISA. Matched controls (n=492 and 194) were genotyped. Results The STAT4 risk allele was more frequent in patients with SLE with previous arterial events (combined OR (ORc)=1.5, 95% CI 1.1 to 2.0) compared to patients without such events. The association was mainly attributable to an accumulation of the risk allele among patients with ICVD (ORc=2.3, CI 1.6 to 3.3). There was no association with IHD or VTE. The presence of two or more aPLs was associated with the risk allele (ORc=1.6, 95% CI 1.2 to 2.0). In multivariable-adjusted logistic regression analyses treatment for hypertension, at least one STAT4 risk allele, older age, IgG anti-cardiolipin antibodies and longer SLE duration remained independently associated with previous ICVD (p≤0.02 for all). Conclusion Patients with SLE with the STAT4 risk allele had a strikingly increased risk of ICVD, comparable in magnitude to that of hypertension. The results imply that a genetic predisposition is an important and previously unrecognised risk factor for ICVD in SLE, and that aPLs may be one underlying mechanism.
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| 48. |
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| 49. |
- van Klaveren, Sjors, et al.
(author)
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Selective Galectin-8N Ligands : The Design and Synthesis of Phthalazinone-d-Galactals
- 2021
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In: ChemMedChem. - : Wiley. - 1860-7179 .- 1860-7187. ; 17:6
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Journal article (peer-reviewed)abstract
- Ligand selectivity among the highly conserved galectins has been an ever-challenging objective. For galectin-8, a protein prevalent in both pathology and tissue distribution, we report phthalazinone-galactals that show excellent selectivity for the galectin-8N-terminal domain. A dissection of structure–activity relationships of the phthalazinone and an extensive molecular dynamics meta-analysis accompany the discovery of the selective galectin-8N ligands presented here. These selective compounds will facilitate the study of galectin-8 biology and may have pharmaceutical relevance in the wide range of galectin-8 associated pathologies.
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| 50. |
- Wassélius, Johan, et al.
(author)
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High 18F-FDG Uptake in synthetic aortic vascular grafts on PET/CT in symptomatic and asymptomatic patients
- 2008
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 49:10, s. 1601-5
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Journal article (peer-reviewed)abstract
- Graft infection is a serious complication to vascular surgery. The aim of this study was to assess (18)F-FDG uptake in vascular grafts in patients with or without symptoms of graft infection. METHODS: In all 2,045 patients examined by PET/CT at our clinic, 16 patients with synthetic aortic grafts were identified and reevaluated for (18)F-FDG accumulation. Clinical and biochemical data were obtained from patient records. RESULTS: High (18)F-FDG uptake was found in 10 of 12 grafts in the patients who underwent open surgery and in 1 of 4 grafts in patients who underwent endovascular aneurysm repair. On the basis of biochemical and clinical data, it was concluded that 1 of the 16 patients had a graft infection at the time of investigation. CONCLUSION: (18)F-FDG uptake in vascular grafts was found in the vast majority of patients without graft infection. The risk of a false-positive diagnosis of graft infection by (18)F-FDG PET/CT is evident.
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