| 1. |
- Svenningsson, A., et al.
(författare)
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Safety and efficacy of rituximab versus dimethyl fumarate in patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome in Sweden: a rater-blinded, phase 3, randomised controlled trial
- 2022
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Ingår i: Lancet Neurology. - : Elsevier BV. - 1474-4422. ; 21:8, s. 693-703
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Tidskriftsartikel (refereegranskat)abstract
- Background B-cell depleting therapies are highly efficacious in relapsing-remitting multiple sclerosis but one such therapy, rituximab, is not approved for multiple sclerosis and no phase 3 trial data are available. We therefore examined the safety and efficacy of rituximab compared with dimethyl fumarate in patients with relapsing-remitting multiple sclerosis to obtain data that might allow inclusion of rituximab in treatment guidelines. Methods RIFUND-MS was a multicentre, rater-blinded, active-comparator, phase 3, randomised controlled trial done at 17 Swedish university and community hospitals. Key inclusion criteria for participants were: age 18-50 years; relapsing-remitting multiple sclerosis or clinically isolated syndrome according to prevailing McDonald criteria; 10 years or less since diagnosis; untreated or only exposed to interferons or glatiramer acetate; and with clinical or neuroradiological disease activity in the past year. Patients were automatically randomly assigned (1:1) by the treating physician using a randomisation module in the Swedish multiple sclerosis registry, without stratification, to oral dimethyl fumarate 240 mg twice daily or to intravenous rituximab 1000 mg followed by 500 mg every 6 months. Relapse evaluation, Expanded Disability Status Scale rating, and assessment of MRI scans were done by examining physicians and radiologists masked to treatment allocation. The primary outcome was the proportion of patients with at least one relapse (defined as subacute onset of new or worsening neurological symptoms compatible with multiple sclerosis with a duration of more than 24 h and preceded by at least 30 days of clinical stability), assessed in an intention-to-treat analysis using log-binomial regression with robust standard errors. This trial is registered at ClinicalTrials.gov, NCT02746744. Findings Between July 1, 2016, and Dec 18, 2018, 322 patients were screened for eligibility, 200 of whom were randomly assigned to a treatment group (100 assigned to rituximab and 100 assigned to dimethyl fumarate). The last patient completed 24-month follow-up on April 21, 2021. 98 patients in the rituximab group and 97 patients in the dimethyl fumarate group were eligible for the primary outcome analysis. Three (3%) patients in the rituximab group and 16 (16%) patients in the dimethyl fumarate group had a protocol-defined relapse during the trial, corresponding to a risk ratio of 0.19 (95% CI 0.06-0.62; p=0.0060). Infusion reactions (105 events [40.9 per 100 patient-years]) in the rituximab group and gastrointestinal reactions (65 events [47.4 per 100 patient-years]) and flush (65 events [47.4 per 100 patient-years]) in the dimethyl fumarate group were the most prevalent adverse events. There were no safety concerns. Interpretation RIFUND-MS provides evidence that rituximab given as 1000 mg followed by 500 mg every 6 months is superior to dimethyl fumarate in preventing relapses over 24 months in patients with early relapsing-remitting multiple sclerosis. Health economic and long-term safety studies of rituximab in patients with multiple sclerosis are needed.
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| 4. |
- Roland, P, et al.
(författare)
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A database generator for human brain imaging
- 2001
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Ingår i: TINS - Trends in Neurosciences. - 0166-2236 .- 1878-108X. ; 24:10, s. 562-564
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Tidskriftsartikel (refereegranskat)abstract
- Sharing scientific data containing complex information requires new concepts and new technology. NEUROGENERATOR is a database generator for the neuroimaging community. A database generator is a database that generates new databases. The scientists submit raw PET and fMRI data to NEUROGENERATOR, which then processes the data in a uniform way to create databases of homogenous data suitable for data sharing, met-analysis and modelling the human brain at the systems level. These databases are then distributed to the scientists.
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| 7. |
- Cordain, L, et al.
(författare)
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Acne vulgaris - A disease of western civilization
- 2002
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Ingår i: Archives of Dermatology. - : American Medical Association (AMA). - 0003-987X. ; 138:12, s. 1584-1590
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Tidskriftsartikel (refereegranskat)abstract
- Background: In westernized societies, acne vulgaris is a nearly universal skin disease afflicting 79% to 95% of the adolescent population. In men and women older than 25 years, 40% to 54% have some degree of facial acne, and clinical facial acne persists into middle age in 12% of women and 3% of men. Epidemiological evidence suggests that acne incidence rates are considerably lower in nonwesternized societies. Herein we report the prevalence of acne in 2 nonwesternized populations: the Kitavan Islanders of Papua New Guinea and the Ache hunter-gatherers of Paraguay. Additionally, we analyze how elements in nonwesternized environments may influence the development of acne. Observations: Of 1200 Kitavan subjects examined (including 300 aged 15-25 years), no case of acne (grade I with multiple comedones or grades 2-4) was observed. Of 115 Ache subjects examined (including 15 aged 15-25 years) over 843 days, no case of active acne (grades 1-4) was observed. Conclusions: The astonishing difference in acne incidence rates between nonwesternized and fully modernized societies cannot be solely attributed to genetic differences among populations but likely results from differing environmental factors. identification of these factors may be useful in the treatment of acne in Western populations.
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| 8. |
- Cordain, L, et al.
(författare)
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Origins and evolution of the Western diet: health implications for the 21st century
- 2005
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Ingår i: American Journal of Clinical Nutrition. - 1938-3207. ; 81:2, s. 341-354
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- There is growing awareness that the profound changes in the environment (eg, in diet and other lifestyle conditions) that began with the introduction of agriculture and animal husbandry approximate to10 000 y ago occurred too recently on an evolutionary time scale for the human genome to adjust. In conjunction with this discordance between our ancient, genetically determined biology and the nutritional, cultural, and activity patterns of contemporary Western populations, many of the so-called diseases of civilization have emerged. In particular, food staples and food-processing procedures introduced during the Neolithic and Industrial Periods have fundamentally altered 7 crucial nutritional characteristics of ancestral hominin diets: 1) glycemic load, 2) fatty acid composition, 3) macronutrient composition, 4) micronutrient density, 5) acid-base balance, 6) sodium-potassium ratio, and 7) fiber content. The evolutionary collision of our ancient genome with the nutritional qualities of recently introduced foods may underlie many of the chronic diseases of Western civilization.
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| 11. |
- Ericsson, Daniel J., et al.
(författare)
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Identification of small peptides mimicking the R2 C-terminus of Mycobacterium tuberculosis ribonucleotide reductase
- 2010
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Ingår i: Journal of Peptide Science. - : Wiley. - 1075-2617 .- 1099-1387. ; 16:3, s. 159-164
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Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotide reductase (RNR) is a viable target for new drugs against the causative agent of tuberculosis, Mycobacterium tuberculosis. Previous work has shown that an N-acetylated heptapeptide based on the C-terminal sequence of the smaller RNR subunit can disrupt the formation of the holoenzyme sufficiently to inhibit its function. Here the synthesis and binding affinity, evaluated by competitive fluorescence polarization, of several truncated and N-protected peptides are described. The protected single-amino acid Fmoc-Trp shows binding affinity comparable to the N-acetylated heptapeptide, making it an attractive candidate for further development of non-peptidic RNR inhibitors.
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| 12. |
- Flykt, Anders, et al.
(författare)
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Fear of Wolves and Bears : Physiological Responses and Negative Associations in a Swedish Sample
- 2013
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Ingår i: Human Dimensions of Wildlife. - : Informa UK Limited. - 1087-1209 .- 1533-158X. ; 18:6, s. 416-434
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Tidskriftsartikel (refereegranskat)abstract
- Human fear is important in wildlife management, but self-reported fear provides only partial information about fear reactions. Thus, eye movements, skin conductance, and changes in heart rate were assessed during picture viewing, visual search, and implicit evaluation tasks. Pictures of bears, wolves, moose, and hares were presented to participants who self-reported as fearful of bears (n = 8), fearful of bears and wolves (n = 15), or not fearful of bears or wolves (n = 14). The feared animal was expected to elicit strong physiological responses, be dwelled upon, and be associated with negative words. Independent of fearfulness, bear pictures elicited the strongest physiological responses, and wolf pictures showed the strongest negative associations. The bear-fearful group showed stronger physiological responses to bears. The bear- and wolf-fearful group showed more difficulty in associating bears with good words. Presence of a feared animal in the search task, resulted in prolonged response time.
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| 14. |
- Gemzell-Danielsson, Kristina, et al.
(författare)
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Comprehensive counseling about combined hormonal contraceptives changes the choice of contraceptive methods : results of the CHOICE program in Sweden
- 2011
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 90:8, s. 869-877
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To study the influence of counseling on women's contraceptive decisions. Design. A cross-sectional multicenter study. Setting. Seventy Swedish family planning clinics. Population. Women aged 15-40 years attending for a contraceptive consultation who expressed interest in a combined hormonal contraceptive (CHC) method. Methods. Structured counseling about three CHCs and questionnaires completed after counseling from the healthcare professional. Main Outcome Measures. Method originally requested, perceptions of CHC attributes, method chosen and reasons for the choice. Results. In all, 173 healthcare professionals and 1 944 women participated. The mean standard deviation (SD) age of the women was 22.6(6.1) years. After structured counseling, a majority of women (56.0%; n=1 069; 95% confidence interval (CI) 53.1-58.9) chose the daily pill, 6.2% (n=118; 95% CI 4.9-7.8) chose the weekly patch, and 22.5% ( n=430; 95% CI 20.2-25.1) chose the monthly ring. The weekly patch was chosen more often after counseling (6.2 vs 2.4% before counseling; p<0.0001). The greatest change was in the proportion of women who chose the contraceptive ring after counseling (22.5% vs. 8.5% before counseling; p<0.0001). The proportion of undecided women after counseling was reduced considerably (3.9% vs. 27.8% before counseling). Among the 523 women who were undecided before counseling, 50.6% chose the pill, 10.2% the patch and 24.6% the ring, while 20.9% of women who initially requested the pill changed to another method. Conclusions. Structured counseling facilitated choice of contraceptive method for most women, leading to changes in women's selection of a CHC method.
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| 22. |
- Lindeberg, Staffan, et al.
(författare)
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A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease.
- 2007
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 50:9, s. 1795-1807
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Most studies of diet in glucose intolerance and type 2 diabetes have focused on intakes of fat, carbohydrate, fibre, fruits and vegetables. Instead, we aimed to compare diets that were available during human evolution with more recently introduced ones. Methods Twenty-nine patients with ischaemic heart disease plus either glucose intolerance or type 2 diabetes were randomised to receive (1) a Palaeolithic ('CyOld Stone Age') diet (n=14), based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; or (2) a Consensus (Mediterranean-like) diet (n=15), based on whole grains, low-fat dairy products, vegetables, fruits, fish, oils and margarines. Primary outcome variables were changes in weight, waist circumference and plasma glucose AUC (AUC Glucose(0-120)) and plasma insulin AUC (AUC Insulin(0-120)) in OGTTs. Results Over 12 weeks, there was a 26% decrease of AUC Glucose(0-120) (p=0.0001) in the Palaeolithic group and a 7% decrease (p=0.08) in the Consensus group. The larger (p=0.001) improvement in the Palaeolithic group was independent (p=0.0008) of change in waist circumference (-5.6 cm in the Palaeolithic group, -2.9 cm in the Consensus group; p=0.03). In the study population as a whole, there was no relationship between change in AUC Glucose(0-120) and changes in weight (r=-0.06, p=0.9) or waist circumference (r=0.01, p=1.0). There was a tendency for a larger decrease of AUC Insulin(0-120) in the Palaeolithic group, but because of the strong association between change in AUC Insulin(0-120) and change in waist circumference (r=0.64, p=0.0003), this did not remain after multivariate analysis. Conclusions/interpretationA Palaeolithic diet may improve glucose tolerance independently of decreased waist circumference.
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| 23. |
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| 24. |
- Lindeberg, Tony, 1964-
(författare)
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Discrete Scale-Space Theory and the Scale-Space Primal Sketch
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis, within the subfield of computer science known as computer vision, deals with the use of scale-space analysis in early low-level processing of visual information. The main contributions comprise the following five subjects:The formulation of a scale-space theory for discrete signals. Previously, the scale-space concept has been expressed for continuous signals only. We propose that the canonical way to construct a scale-space for discrete signals is by convolution with a kernel called the discrete analogue of the Gaussian kernel, or equivalently by solving a semi-discretized version of the diffusion equation. Both the one-dimensional and two-dimensional cases are covered. An extensive analysis of discrete smoothing kernels is carried out for one-dimensional signals and the discrete scale-space properties of the most common discretizations to the continuous theory are analysed.A representation, called the scale-space primal sketch, which gives a formal description of the hierarchical relations between structures at different levels of scale. It is aimed at making information in the scale-space representation explicit. We give a theory for its construction and an algorithm for computing it.A theory for extracting significant image structures and determining the scales of these structures from this representation in a solely bottom-up data-driven way.Examples demonstrating how such qualitative information extracted from the scale-space primal sketch can be used for guiding and simplifying other early visual processes. Applications are given to edge detection, histogram analysis and classification based on local features. Among other possible applications one can mention perceptual grouping, texture analysis, stereo matching, model matching and motion.A detailed theoretical analysis of the evolution properties of critical points and blobs in scale-space, comprising drift velocity estimates under scale-space smoothing, a classification of the possible types of generic events at bifurcation situations and estimates of how the number of local extrema in a signal can be expected to decrease as function of the scale parameter. For two-dimensional signals the generic bifurcation events are annihilations and creations of extremum-saddle point pairs. Interpreted in terms of blobs, these transitions correspond to annihilations, merges, splits and creations.Experiments on different types of real imagery demonstrate that the proposed theory gives perceptually intuitive results.
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| 29. |
- Nash, Peppi, et al.
(författare)
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Placental dysfunction in Suramin-treated rats : a new model for pre-eclampsia
- 2005
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Ingår i: Placenta. - : Elsevier BV. - 0143-4004 .- 1532-3102. ; 26:5, s. 410-418
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Tidskriftsartikel (refereegranskat)abstract
- Impaired placentation and oxidative stress are proposed to play major roles in the pathogenesis of placental dysfunction and pre-eclampsia. This study was carried out to evaluate if inhibited angiogenesis by Suramin injections in early pregnancy may cause a condition resembling pre-eclampsia in rats. Rats of two different Sprague-Dawley strains, U and H, were given intraperitoneal injections of Suramin or saline in early pregnancy. The outcome of pregnancy was evaluated on gestational day 20. Suramin injections caused increased blood pressure and decreased renal blood flow in the U rats. In both rat strains Suramin decreased the placental blood flow and caused fetal growth retardation. In both strains the placental concentration of the isoprostane 8-epi-PGF2alpha was increased, indicating oxidative stress. The serum concentration of Endothelin-1 was increased in the U rats. The U strain had a lower basal placental blood flow, and the effects of Suramin were more pronounced in this strain. We conclude, that Suramin injections to pregnant rats cause a state of placental insufficiency, which partly resembles human pre-eclampsia. The induction of this condition is at least partly mediated by oxidative stress, and is subject to varied genetic susceptibility.
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| 30. |
- Nurbo, Johanna, et al.
(författare)
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Novel pseudopeptides incorporating a benzodiazepine-based turn mimetic – targeting Mycobacterium tuberculosis ribonucleotide reductase
- 2013
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 21:7, s. 1992-2000
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Tidskriftsartikel (refereegranskat)abstract
- Peptides mimicking the C-terminus of the small subunit (R2) of Mycobacterium tuberculosis ribonucleotide reductase (RNR) can compete for binding to the large subunit (R1) and thus inhibit RNR activity. Moreover, it has been suggested that the binding of the R2 C-terminus is very similar in M. tuberculosis and Salmonella typhimurium. Based on modeling studies of a crystal structure of the holocomplex of the S. typhimurium enzyme, a benzodiazepine-based turn mimetic was identified and a set of novel compounds incorporating the benzodiazepine scaffold was synthesized. The compounds were evaluated in a competitive fluorescence polarization assay and in an RNR activity assay. These studies revealed that the compounds incorporating the benzodiazepine scaffold have the ability to compete for the M. tuberculosis R2 binding site with low-micromolar affinity.
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| 31. |
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| 32. |
- Persson, E, et al.
(författare)
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Changes in metal concentrations during dry- and wet-storage of Norway spruce pulpwood
- 2001
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Ingår i: Nordic Pulp & Paper Research Journal. - 0283-2631 .- 2000-0669. ; 16, s. 327-332
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Tidskriftsartikel (refereegranskat)abstract
- The changes in concentrations and radial distribution of Ca, Fe and Mn in Norway spruce (Picea abies) pulpwood after three months of storage were evaluated. Three different storage alternatives were tested: dry storage, sprinkling with an intensity corresponding to the rate of evaporation and sprinkling with an intensity corresponding to twice the rate of the evaporation. The analyses were performed using energy dispersive x-ray fluorescence (EDXRF) and atomic absorption spectroscopy (AAS). In the dry-stored logs, the AAS analyses revealed a tendency for decreased concentrations of Ca and Fe after three months storage. The tendency in the sprinkled logs was, according to the AAS analyses, a small increase in Ca and Mn contents after three months storage. The EDXRF analyses indicated that the radial distribution of Ca and Mn might have been affected during storage.
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| 33. |
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| 34. |
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| 35. |
- Schmidt, Boris, et al.
(författare)
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Design, synthesis, and biological activities of four angiotensin IIreceptor ligands with gamma-turn mimetics replacing amino acid residues 3-5
- 1997
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 40, s. 903-919
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Tidskriftsartikel (refereegranskat)abstract
- Disulfide cyclization is a powerful method for reducing the conformational space of a peptide. This in turn may enable the study of its bioactive conformation. Several analogues of angiotensin II (Ang II) containing a disulfide bridge between amino acids 3 and 5 have been reported. Among these the cyclic octapeptides c[Hcy3,5]-Ang II, c[Cys3,5]-Ang II, and c[Pen 3,5]-Ang II showed significant activity at Ang II receptors. We have performed conformational analysis studies using theoretical calculations and 1H-NMR spectroscopy on tripeptide model compounds of these cyclic octapeptides which show that the cyclic moieties of c[Cys3,5]-Ang II and c[Pen3,5]-Ang II preferentially assume an inverse gamma-turn conformation. On the basis of these results, we substituted amino acid residues 3-5 in Ang II with two different gamma-turn mimetics giving four diastereomeric Ang II analogues. Interestingly, two of these are equipotent to Ang II in binding to AT1 receptors. In the contractile test using rabbit aorta rings, one of the analogues is an agonist with full contractile activity approximately equipotent to c[Pen3,5]-Ang II but 300-fold less potent than Ang II. This low potency may suggest that Ang II does not adopt a gamma-turn in the 3-5 region when interacting with the receptor.
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| 36. |
- Shapira, Yinon, et al.
(författare)
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Geographical Differences in Autoantibodies and Anti-infectious Agents Antibodies Among Healthy Adults
- 2012
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Ingår i: Clinical Reviews in Allergy & Immunology. - : Springer Science and Business Media LLC. - 1080-0549 .- 1559-0267. ; 42:2, s. 154-163
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Forskningsöversikt (refereegranskat)abstract
- Much is known about the geoepidemiology of defined autoimmune diseases (AD); however, there is currently limited data regarding the prevalence of autoantibodies among healthy populations of different geographical areas. The aim of this study was to evaluate a large profile of autoantibodies in healthy adults from distinct global regions as well as the prevalence of anti-infectious agents antibodies in those regions. Sera samples from 557 healthy donors were obtained at six centers located in different countries (i.e., Italy, Netherlands, Israel, Mexico, Columbia, Papua New Guinea (Kitavans)). Sera were tested for the presence of antinuclear antibodies (ANA) and autoantibodies associated with thrombophilia, vasculitis, and gastrointestinal (GI) disease. Sera samples were also screened for antibodies against infectious agents (i.e., EBV, CMV, HBV, Helicobacter pylori, Treponema pallidum, and Toxoplasma gondii). Tests were performed using the BioPlex 2200 or ELISA kits (Bio-Rad Laboratories, USA). We found a significant gradient of ANA positivity among the groups: 45% of Columbians, 38% of Kitavans, 26% of Mexicans, 12% of Italians, 12% of Dutch, and 11% of Israelis were ANA positive. Geographical differences were also observed regarding the prevalence of specific autoantibodies, namely ANA: anti-dsDNA, chromatin, SmRNP, Ro/SSA, La/SSB, Scl70; GI associated: antigliadin; and thrombophilia-associated: anti-beta 2GP1 and prothrombin. Additionally, significant differences were observed regarding serological markers of all infectious agents screened. The observed variance between healthy ethno-geographical distinct populations in prevalence of autoantibodies may represent different genetic or environmental (e.g., prior exposure to infection) influences. Thus may illuminate possible causes of geoepidemiological differences in AD.
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