| 1. |
- Hedegaard, Jakob, et al.
(författare)
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Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
- 2016
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 30:1, s. 27-42
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Tidskriftsartikel (refereegranskat)abstract
- Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
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| 2. |
- Nielsen, Jakob Toudahl, et al.
(författare)
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In situ high-resolution structure of the baseplate antenna complex in Chlorobaculum tepidum.
- 2016
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Ingår i: Nature Communications. - : Springer Science+Business Media B.V.. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Photosynthetic antenna systems enable organisms harvesting light and transfer the energy to the photosynthetic reaction centre, where the conversion to chemical energy takes place. One of the most complex antenna systems, the chlorosome, found in the photosynthetic green sulfur bacterium Chlorobaculum (Cba.) tepidum contains a baseplate, which is a scaffolding super-structure, formed by the protein CsmA and bacteriochlorophyll a. Here we present the first high-resolution structure of the CsmA baseplate using intact fully functional, light-harvesting organelles from Cba. tepidum, following a hybrid approach combining five complementary methods: solid-state NMR spectroscopy, cryo-electron microscopy, isotropic and anisotropic circular dichroism and linear dichroism. The structure calculation was facilitated through development of new software, GASyCS for efficient geometry optimization of highly symmetric oligomeric structures. We show that the baseplate is composed of rods of repeated dimers of the strongly amphipathic CsmA with pigments sandwiched within the dimer at the hydrophobic side of the helix.
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| 3. |
- Ankardal, Maud, 1957, et al.
(författare)
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Comparison of health care costs for open burch colposuspension, laparoscopic colposuspension and tension-free vaginal tape in the treatment of female urinary incontinence
- 2007
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Ingår i: Neurourol Urodyn.
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To compare direct health care costs of treatment for stress urinary incontinence in Sweden with four different procedures: (i) open Burch colposuspension (OBC); (ii) laparoscopic colposuspension with sutures (LCS); (iii) laparoscopic colposuspension with mesh and staples (LCM), and (iv) Tension-free Vaginal Tape (TVT). MATERIAL AND METHODS: A model was constructed representing a hospital with standardized surgical equipment, staff and average unit costs in 2003 Euros. The time used for anesthesia and surgery was calculated. Clinical data was collected from three different sources, a multicenter, randomized, prospective study comparing OBC with LCM with 1 year follow-up, a three-armed, prospective study where women were randomized to either OBC, LCM, or LCS with 1 year follow-up and a descriptive study reporting results of TVT with 5 year follow-up. Data collected from the studies and hospital cost data were put into the model to create the different cost elements. RESULTS: The total cost per individual, showed a lower cost for TVT compared to the other alternatives. The direct costs for a TVT, euro1,366 were only 56% of the costs for an OBC, euro2,431 (P < 0.001) and 59% of the costs for a LCS, euro2,310 (P < 0.001). CONCLUSIONS: When using a model and comparing health care costs for surgical treatment of female stress urinary incontinence in Sweden, the TVT procedure generated a lower direct cost than both open and laparoscopic colposuspension. Neurourol. Urodynam. (c) 2007 Wiley-Liss, Inc.
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| 4. |
- Björkman, Anders, et al.
(författare)
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Distal Scaphoid Fractures
- 2017
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Ingår i: Scaphoid Fractures : Evidence-Based Management - Evidence-Based Management. - 9780323485647 - 9780323496056 ; , s. 123-128
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Bokkapitel (refereegranskat)
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| 5. |
- Buijze, Geert A., et al.
(författare)
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Diagnostic Performance of Radiographs and Computed Tomography for Displacement and Instability of Acute Scaphoid Waist Fractures
- 2012
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Ingår i: Journal of Bone and Joint Surgery. American Volume. - 1535-1386. ; 94A:21, s. 1967-1974
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fracture displacement is the most important factor associated with nonunion of a scaphoid waist fracture. We evaluated the performance characteristics of radiographs and computed tomography (CT) in the diagnosis of intraoperative displacement and instability of scaphoid waist fractures using wrist arthroscopy as the reference standard. Methods: During a six-year period (2004 to 2010) at two institutions, forty-four adult patients with a scaphoid waist fracture underwent arthroscopy-assisted operative fracture treatment at a mean of nine days (range, two to twenty-two days) after injury. Subjects included all of those with a displaced scaphoid fracture seen on radiographs and a selection of patients with a nondisplaced scaphoid fracture. All patients had preoperative radiographs and CT. Arthroscopy with up to 5 kg of traction was the reference standard for fracture displacement and instability. Results: The reference standard (arthroscopy) led to a diagnosis of twenty-two displaced fractures (all unstable) and twenty-two nondisplaced fractures (seven unstable). Displacement was diagnosed in eleven patients (25%) with the use of radiographs and in twenty (45%) with CT. The sensitivity, specificity, and accuracy for diagnosing intraoperative displacement were 45%, 95%, and 70%, respectively, with the use of radiographs and 77%, 86%, and 82%, respectively, with CT. The sensitivity, specificity, and accuracy for diagnosing intraoperative instability were 34%, 93%, and 55%, respectively, with the use of radiographs and 62%, 87%, and 70%, respectively, with CT. Assuming a 10% prevalence of fracture displacement and instability among all scaphoid waist fractures, the positive and negative predictive values for displacement were 53% and 94%, respectively, with the use of radiographs and 39% and 97% with CT whereas the positive and negative predictive values for instability were 36% and 93%, respectively, with radiographs and 34% and 95% with CT. Conclusions: Radiographs and CT scans cannot be relied on to accurately diagnose intraoperative scaphoid fracture displacement or instability compared with arthroscopic examination. The influence, with regard to the risk of nonunion, of intraoperative instability of a scaphoid fracture that is seen to be nondisplaced on radiographs or CT is currently unknown.
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| 6. |
- Buijze, Geert A, et al.
(författare)
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Factors Associated With Arthroscopically Determined Scaphoid Fracture Displacement and Instability.
- 2012
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Ingår i: The Journal of Hand Surgery. - : Elsevier BV. - 1531-6564 .- 0363-5023. ; 37A:7, s. 1405-1410
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To identify factors associated with arthroscopically diagnosed scaphoid fracture displacement and instability. METHODS: This was a secondary use of data from 2 prospective cohort studies. The studies included 58 consecutive adult patients with a scaphoid fracture who elected arthroscopy-assisted operative fracture treatment: some for displacement, some as part of a prospective protocol, and others to avoid a cast. All patients had preoperative computed tomography with reconstructions in planes defined by the long axis of the scaphoid. RESULTS: Arthroscopy revealed 38 unstable fractures (movement between fracture fragments; 66%), 27 of which were also displaced. All arthroscopically determined displaced fractures were unstable, and 11 of the 31 arthroscopically determined, nondisplaced fractures were unstable. There was a significant correlation between radiographic comminution (more than 2 fracture fragments) and arthroscopically determined displacement and instability. CONCLUSIONS: Radiographic comminution is associated with displacement and instability as determined by arthroscopy.
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| 7. |
- Cederlund, Ragnhild, et al.
(författare)
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Activity limitations before and after surgical carpal tunnel release among patients with and without diabetes.
- 2012
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Ingår i: Journal of rehabilitation medicine : official journal of the UEMS European Board of Physical and Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1651-2081. ; 44:3, s. 261-267
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate activity limitations before and after carpal tunnel release among patients with and without diabetes, to explore differences between genders and the influence of grip strength on activity limitations. DESIGN: Prospective case-control study. PATIENTS: Thirty-three patients with diabetes and carpal tunnel syndrome (CTS) were age and gender matched with 30 patients without diabetes having idiopathic CTS. METHODS: Activity limitations were assessed pre-operatively, 3 and 12 months after surgery, with the self-administered Evaluation of Daily Activities Questionnaire (EDAQ) containing 102 activity items in 11 dimensions and 3 additional male-activity-oriented dimensions including 22 items. RESULTS: For all dimensions the mean score was higher for patients with diabetes compared with patients without diabetes. This indicates a more pronounced activity limitation for patients with diabetes. However, no statistical differences between the two groups could be demonstrated. In general, females have significantly higher activity limitation scores than males. CONCLUSION: CTS creates a broad variety of activity limitations for affected patients. After carpal tunnel release a significant alleviation of these limitations occurs within the first 3 months. Activity limitations seem not to be related to diabetes, but were more pronounced in women than in men, probably due to reduced grip strength.
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| 8. |
- Cederlund, Ragnhild, et al.
(författare)
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Hand disorders, hand function, and activities of daily living in elderly men with type 2 diabetes.
- 2009
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Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 23, s. 32-39
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: This study aimed to examine hand disorders, symptoms, overall hand function, activities of daily living (ADLs), and life satisfaction in elderly men with type 2 diabetes mellitus (DM), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). METHODS: Subjects were interviewed and evaluated with a battery of clinical and laboratory tests, including hand assessment, and a questionnaire. RESULTS: HbA1c differed between groups (highest in DM, especially in long-term DM). Limited joint motion (LJM), for example, prayer sign and Dupuytren's contracture, was most common in individuals with DM, followed by individuals with IGT, as compared to those with NGT. Vibrotactile sense was impaired symmetrically in the index and little fingers in DM. However, there were no differences for sensibility, dexterity, grip strength, and cold intolerance between groups. Individuals with long-term (>15 years) DM were more affected regarding sensibility and ADL than individuals with short-term DM, who had more sleep disturbances. ADL difficulties were less among IGT subjects. Vibrotactile sense showed correlations with Semmes-Weinstein monofilament test and static two-point discrimination. CONCLUSIONS/INTERPRETATION: Dupuytren's contracture and impaired vibrotactile sense in finger pulps occurred in patients with DM but not in those with IGT, although LJM occurred in both IGT and DM patients. A longer duration of DM was associated with more severe neuropathy and ADL difficulties. Life satisfaction was high, and hand disorders did not have a significant impact on ADL.
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| 9. |
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| 10. |
- Chattopadhyay, Subhayan, et al.
(författare)
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Enrichment of B cell receptor signaling and epidermal growth factor receptor pathways in monoclonal gammopathy of undetermined significance : a genome-wide genetic interaction study
- 2018
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Ingår i: Molecular Medicine. - : Springer Science and Business Media LLC. - 1528-3658 .- 1076-1551. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent identification of 10 germline variants predisposing to monoclonal gammopathy of undetermined significance (MGUS) explicates genetic dependency of this asymptomatic precursor condition with multiple myeloma (MM). Yet much of genetic burden as well as functional links remain unexplained. We propose a workflow to expand the search for susceptibility loci with genome-wide interaction and for subsequent identification of genetic clusters and pathways.METHODS: Polygenic interaction analysis on 243 cases/1285 controls identified 14 paired risk loci belonging to unique chromosomal bands which were then replicated in two independent sets (case only study, 82 individuals; case/control study 236 cases/ 2484 controls). Further investigation on gene-set enrichment, regulatory pathway and genetic network was carried out with stand-alone in silico tools separately for both interaction and genome-wide association study-detected risk loci.RESULTS: Intronic-PREX1 (20q13.13), a reported locus predisposing to MM was confirmed to have contribution to excess MGUS risk in interaction with SETBP1, a well-established candidate predisposing to myeloid malignancies. Pathway enrichment showed B cell receptor signaling pathway (P < 5.3 × 10- 3) downstream to allograft rejection pathway (P < 5.6 × 10- 4) and autoimmune thyroid disease pathway (P < 9.3 × 10- 4) as well as epidermal growth factor receptor regulation pathway (P < 2.4 × 10- 2) to be differentially regulated. Oncogene ALK and CDH2 were also identified to be moderately interacting with rs10251201 and rs16966921, two previously reported risk loci for MGUS.CONCLUSIONS: We described novel pathways and variants potentially causal for MGUS. The methodology thus proposed to facilitate our search streamlines risk locus-based interaction, genetic network and pathway enrichment analyses.
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