| 1. |
- Ahlgren, Christina, et al.
(författare)
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The meanings given to gender in studies on multimodal rehabilitation for patients with chronic musculoskeletal pain : a literature review
- 2016
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Ingår i: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 38:23, s. 2255-2270
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Forskningsöversikt (refereegranskat)abstract
- Purpose: The purpose of this study is to assess and describe the meanings given to "gender" in scientific publications that evaluate multidisciplinary, interdisciplinary or multimodal rehabilitation for patients with chronic musculoskeletal pain.Method: A systematic literature search for papers evaluating multimodal rehabilitation was conducted. The PubMed and EBSCO databases were searched from 1995 to 2015. Two or three researchers independently read each paper, performed a quality assessment and coded meanings of gender using qualitative content analysis.Results: Twenty-seven papers were included in the review. Gender was used very differently in the MMR studies investigated but primarily it referred to factual differences between men and women. Only one paper provided a definition of the concept of gender and how it had been used in that study. In the content analysis, the meaning of gender formed three categories: "Gender as a factual difference", "The man is the ideal" and "Gender as a result of social role expectations".Conclusions: The meaning of the concept of gender in multimodal rehabilitation is undefined and needs to be developed further. The way the concept is used should be defined in the design and evaluation of multimodal rehabilitation in future studies.Implications for rehabilitationHealthcare professionals should reflect on gender relations in encounters with patients, selection of patients into rehabilitation programs and design of programs. In rehabilitation for chronic pain the patients' social circumstances and cultural context should be given the same consideration as biological sex and pain symptoms.
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| 2. |
- Ahlgren, Eva Christina, et al.
(författare)
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Iron-induced oligomerization of human FXN81-210 and bacterial CyaY frataxin and the effect of iron chelators
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Patients suffering from the progressive neurodegenerative disease Friedreich’s ataxia have reduced expression levels of the protein frataxin. Three major isoforms of human frataxin have been identified, FXN42-210, FXN56-210 and FXN81-210, of which FXN81-210 is considered to be the mature form. Both long forms, FXN42-210 and FXN56-210, have been shown to spontaneously form oligomeric particles stabilized by the extended N-terminal sequence. The short variant FXN81-210, on other hand, has only been observed in the monomeric state. However, a highly homologous E. coli frataxin CyaY, which also lacks an N-terminal extension, has been shown to oligomerize in the presence of iron. To explore the mechanisms of stabilization of short variant frataxin oligomers we compare here the effect of iron on the oligomerization of CyaY and FXN81-210. Using dynamic light scattering, small-angle X-ray scattering, electron microscopy (EM) and cross linking mass spectrometry (MS), we show that at aerobic conditions in the presence of iron both FXN81-210 and CyaY form oligomers. However, while CyaY oligomers are stable over time, FXN81-210 oligomers are unstable and dissociate into monomers after about 24 h. EM and MS studies suggest that within the oligomers FXN81-210 and CyaY monomers are packed in a head-to-tail fashion in ring-shaped structures with potential iron-binding sites located at the interface between monomers. The higher stability of CyaY oligomers can be explained by a higher number of acidic residues at the interface between monomers, which may result in a more stable iron binding. We also show that CyaY oligomers may be dissociated by ferric iron chelators deferiprone and DFO, as well as by the ferrous iron chelator BIPY. Surprisingly, deferiprone and DFO stimulate FXN81-210 oligomerization, while BIPY does not show any effect on oligomerization in this case. The results suggest that FXN81-210 oligomerization is primarily driven by ferric iron, while both ferric and ferrous iron participate in CyaY oligomer stabilization. Analysis of the amino acid sequences of bacterial and eukaryotic frataxins suggests that variations in the position of the acidic residues in helix 1, β-strand 1 and the loop between them may control the mode of frataxin oligomerization.
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| 3. |
- Atroshi, Isam, et al.
(författare)
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Collagenase treatment of Dupuytrens contracture using a modified injection method
- 2015
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Ingår i: Acta Orthopaedica. - : Informa Healthcare: Creative Commons Attribution Non-Commercial / Informa Healthcare. - 1745-3674 .- 1745-3682. ; 86:3, s. 310-315
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Treatment of Dupuytrens contracture (DC) with collagenase Clostridium histolyticum (CCH) consists of injection followed by finger manipulation. We used a modified method, injecting a higher dose than recommended on the label into several parts of the cord, which allows treatment of multiple joint contractures in 1 session and may increase efficacy. We studied the occurrence of skin tears and short-term outcome with this procedure. Patients and methods - We studied 164 consecutive hands with DC, palpable cord, and extension deficit of greater than= 20 degrees in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joint (mean patient age 70 years, 82% men). A hand surgeon injected all the content of 1 CCH vial (approximately 0.80 mg) into multiple spots in the cord and performed finger extension under local anesthesia after 1 or 2 days. A nurse recorded skin tears on a diagram and conducted a standard telephone follow-up within 4 weeks. A hand therapist measured joint contracture before injection and at a median of 23 (IQR: 7-34) days after finger extension. Results - A skin tear occurred in 66 hands (40%). The largest diameter of the tear was less than= 5 mm in 30 hands and greater than 10 mm in 14 hands. Hands with skin tear had greater mean pretreatment MCP extension deficit than those without tear: 59 degrees (SD 26) as opposed to 32 degrees (SD 23). Skin tear occurred in 21 of 24 hands with MCP contracture of greater than= 75 degrees. All tears healed with open-wound treatment. No infections occurred. Mean improvement in total (MCP + PIP) extension deficit was 55 degrees (SD 28). Interpretation - Skin tears occurred in 40% of hands treated with collagenase injections, but only a fifth of them were larger than 1 cm. Tears were more likely in hands with severe MCP joint contracture. All tears healed without complications. Short-term contracture reduction was good.
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| 4. |
- Cazzaniga, Walter, et al.
(författare)
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Population-based, nationwide registration of prostatectomies in Sweden
- 2019
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Ingår i: Journal of Surgical Oncology. - : Wiley. - 0022-4790 .- 1096-9098. ; 120:4, s. 803-812
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Radical prostatectomy (RP) is a common surgical procedure with a risk of postoperative erectile dysfunction and urinary incontinence. There is a need for data on RP as a basis for quality assurance and benchmarking. Methods In 2015, prostatectomies in Sweden (PiS) form was implemented in the National Prostate Cancer Register (NPCR) of Sweden with data on pre-, peri- and post-operative variables. Results Out of all radical prostatectomies performed in 2016 in Sweden, 3096/3881 (80%) were registered in PiS. A total of 2605 (84%) were robot-assisted radical prostatectomy (RARP) and 491 (16%) were RRP (retropubic radical prostatectomy). RARP was performed by 91 surgeons of whom 47% operated more than 25 RP/year; and RRP was performed by 69 surgeons of whom 10% performed more than 25 RP/year. RARP had a longer operative time (median operating time: RARP 155 minutes [IQR 124-190]; RRP 129 minutes [IQR 105-171]; P < .001) but was associated with smaller bleeding (median intraoperative blood loss: RARP 100 mL [IQR 50-200], RRP 700 mL [IQR 500-1100]; P < .001). Conclusions We report on a nationwide, population-based register with transparent reporting of data on the performance of radical prostatectomy. These data are needed as a basis for quality assurance with comparisons of results from individual surgeons and hospitals.
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| 5. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 6. |
- Fekry, Mostafa, et al.
(författare)
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SAXS and stability studies of iron-induced oligomers of bacterial frataxin CyaY
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:9, s. 0184961-0184961
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Tidskriftsartikel (refereegranskat)abstract
- Frataxin is a highly conserved protein found in both prokaryotes and eukaryotes. It is involved in several central functions in cells, which include iron delivery to biochemical processes, such as heme synthesis, assembly of iron-sulfur clusters (ISC), storage of surplus iron in conditions of iron overload, and repair of ISC in aconitase. Frataxin from different organisms has been shown to undergo iron-dependent oligomerization. At least two different classes of oligomers, with different modes of oligomer packing and stabilization, have been identified. Here, we continue our efforts to explore the factors that control the oligomerization of frataxin from different organisms, and focus on E. coli frataxin CyaY. Using small-angle X-ray scattering (SAXS), we show that higher iron-to-protein ratios lead to larger oligomeric species, and that oligomerization proceeds in a linear fashion as a results of iron oxidation. Native mass spectrometry and online size-exclusion chromatography combined with SAXS show that a dimer is the most common form of CyaY in the presence of iron at atmospheric conditions. Modeling of the dimer using the SAXS data confirms the earlier proposed head-to-tail packing arrangement of monomers. This packing mode brings several conserved acidic residues into close proximity to each other, creating an environment for metal ion binding and possibly even mineralization. Together with negative-stain electron microscopy, the experiments also show that trimers, tetramers, pentamers, and presumably higher-order oligomers may exist in solution. Nano-differential scanning fluorimetry shows that the oligomers have limited stability and may easily dissociate at elevated temperatures. The factors affecting the possible oligomerization mode are discussed.
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| 7. |
- Gakh, Oleksandr, et al.
(författare)
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Architecture of the human mitochondrial iron-sulfur cluster assembly machinery
- 2016
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Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 291:40, s. 21296-21321
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Tidskriftsartikel (refereegranskat)abstract
- Fe-S clusters, essential cofactors needed for the activity of many different enzymes, are assembled by conserved protein machineries inside bacteria and mitochondria. As the architecture of the human machinery remains undefined, we co-expressed in Escherichia coli the following four proteins involved in the initial step of Fe-S cluster synthesis: FXN42-210 (iron donor); [NFS1]·[ISD11] (sulfur donor); and ISCU (scaffold upon which new clusters are assembled). We purified a stable, active complex consisting of all four proteins with 1:1:1:1 stoichiometry. Using negative staining transmission EM and single particle analysis, we obtained a three-dimensional model of the complex with ∼14 Å resolution. Molecular dynamics flexible fitting of protein structures docked into the EM map of the model revealed a [FXN42-210]24·[NFS1]24·[ISD11]24·[ISCU]24 complex, consistent with the measured 1:1:1:1 stoichiometry of its four components. The complex structure fulfills distance constraints obtained from chemical cross-linking of the complex at multiple recurring interfaces, involving hydrogen bonds, salt bridges, or hydrophobic interactions between conserved residues. The complex consists of a central roughly cubic [FXN42-210]24·[ISCU]24 sub-complex with one symmetric ISCU trimer bound on top of one symmetric FXN42-210 trimer at each of its eight vertices. Binding of 12 [NFS1]2·[ISD11]2 sub-complexes to the surface results in a globular macromolecule with a diameter of ∼15 nm and creates 24 Fe-S cluster assembly centers. The organization of each center recapitulates a previously proposed conserved mechanism for sulfur donation from NFS1 to ISCU and reveals, for the first time, a path for iron donation from FXN42-210 to ISCU.
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| 8. |
- Kimby, Eva, et al.
(författare)
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Two courses of four weekly infusions of rituximab with or without interferon-α2a : final results from a randomized phase III study in symptomatic indolent B-cell lymphomas
- 2015
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 56:9, s. 2598-2607
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Tidskriftsartikel (refereegranskat)abstract
- Patients with advanced CD20 + indolent lymphoma, requiring therapy, were randomized to rituximab (four weekly infusions of 375 mg/m(2)) or to rituximab combined with 5 weeks of interferon-α2a (IFN-α2a) (3-4.5 MIU daily) as priming. Responding patients were eligible for a second cycle with the same allocated treatment. In total, 156 patients were randomized to rituximab and 157 to rituximab + IFN-α2a. In the intention-to treat (ITT) population, 244 patients (78%) responded to cycle 1. After a second cycle the complete remission/complete remission unconfirmed (CR/CRu) rate was 41% with the combination versus 24% with monotherapy (p = 0.005). The median time to treatment failure (primary endpoint) in ITT patients was 28 vs. 21.5 months, respectively (p = 0.302). After a long median follow-up (61 months), 33% (42% of patients responding to cycle 1) were still failure-free with an overall survival rate of 88% and with no difference between the treatment groups. The trial was registered at ClinicalTrials.gov Identifier: NCT01609010.
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