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- Johansson, Bente Berg, et al.
(författare)
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Nuclear import of glucokinase in pancreatic beta-cells is mediated by a nuclear localization signal and modulated by SUMOylation
- 2017
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207. ; 454, s. 146-157
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Tidskriftsartikel (refereegranskat)abstract
- The localization of glucokinase in pancreatic beta-cell nuclei is a controversial issue. Although previous reports suggest such a localization, the mechanism for its import has so far not been identified. Using immunofluorescence, subcellular fractionation and mass spectrometry, we present evidence in support of glucokinase localization in beta-cell nuclei of human and mouse pancreatic sections, as well as in human and mouse isolated islets, and murine MIN6 cells. We have identified a conserved, seven-residue nuclear localization signal (30LKKVMRR36) in the human enzyme. Substituting the residues KK31,32 and RR35,36 with AA led to a loss of its nuclear localization in transfected cells. Furthermore, our data indicates that SUMOylation of glucokinase modulates its nuclear import, while high glucose concentrations do not significantly alter the enzyme nuclear/cytosolic ratio. Thus, for the first time, we provide data in support of a nuclear import of glucokinase mediated by a redundant mechanism, involving a nuclear localization signal, and which is modulated by its SUMOylation. These findings add new knowledge to the functional role of glucokinase in the pancreatic beta-cell.
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| 4. |
- Mansoor, Nadia, et al.
(författare)
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Accuracy and complication rates of external ventricular drain placement with twist drill and bolt system versus standard trephine and tunnelation: a retrospective population-based study.
- 2020
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Ingår i: Acta neurochirurgica. - : Springer Science and Business Media LLC. - 0942-0940 .- 0001-6268. ; 162, s. 755-761
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Tidskriftsartikel (refereegranskat)abstract
- An external ventricular drain (EVD) is typically indicated in the presence of hydrocephalus and increased intracranial pressure (ICP). Procedural challenges have prompted the development of different methods to improve accuracy, safety, and logistics.EVD placement and complications rates were compared using two surgical techniques; the standard method (using a 14-mm trephine burrhole with the EVD tunnelated through the skin) was compared to a less invasive method (EVD placed through a 2.7-3.3-mm twist drill burrhole and fixed to the bone with a bolt system).Retrospective observational study in a single-centre setting between 2008 and 2018. EVD placement was assessed using the Kakarla scoring system. We registered postoperative complications, surgery duration and number of attempts to place the EVD.Two hundred seventy-two patients received an EVD (61 bolt EVDs, 211 standard EVDs) in the study period. Significant differences between the bolt system and the standard method were observed in terms of revision surgeries (8.2% vs. 21.5%, p=0.020), surgery duration (mean 16.5 vs. 28.8min, 95% CI 7.64, 16.8, p<0.001) and number of attempts to successfully place the first EVD (mean 1.72±1.2 vs. 1.32±0.8, p=0.017). There were no differences in accuracy of placement or complication rates.The two methods show similar accuracy and postoperative complication rates. Observed differences in both need for revisions and surgery duration favoured the bolt group. Slightly, more attempts were needed to place the initial EVD in the bolt group, perhaps reflecting lower flexibility for angle correction with a twist drill approach.
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| 5. |
- McLinden, C. A., et al.
(författare)
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OSIRIS: A Decade of Scattered Light
- 2012
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Ingår i: Bulletin of the American Meteorological Society. - 0003-0007 .- 1520-0477. ; 93:12, s. 1845-1863
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Tidskriftsartikel (refereegranskat)abstract
- Into year 11 of a 2-yr mission, OSIRIS is redefining how limb-scattered sunlight can be used to probe the atmosphere, even into the upper troposphere.
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| 7. |
- Solheim, Nils, et al.
(författare)
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Modified Guide Walls for Incremental Increase of Spillway Capacity
- 2023
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Ingår i: Proceedings of the 40th IAHR World Congress. - : International Association for Hydro-Environment Engineering and Research. ; , s. 1978-1983
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Konferensbidrag (refereegranskat)abstract
- This paper presents the results from a physical model study of a fixed crest ogee spillway with lateral inflow creating a contraction loss at the inlet reducing the effective spillway width. The model represents a scenario faced by some spillway structures in low head run-of-river hydropower schemes. The contraction caused at the corner of the spillway inlet is quantified for varying discharges and its influence on the spillway capacity is evaluated. To improve the capacity of the spillway, firstly the approach angle is altered. The spillway capacity is measured for multiple headwall angles, finding a relative increase of 6.2 % in discharge capacity for a 55° approach. Secondly, guide walls of varying designs in the direction of the lateral flow are introduced. The design of the modified guide wall seeks to smoothen the approach and reduces the ensuing flow separation, thus increasing the capacity of the spillway. The greatest improvement is found for an elliptic guide wall which increased the discharge capacity by 6.7 %. Ultimately, small structural changes can make significant improvements to spillway capacity.
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| 8. |
- Solheim, N., et al.
(författare)
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Randomized controlled trial of intra-articular ketorolac on pain and inflammation after minor arthroscopic knee surgery
- 2018
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 62:6, s. 829-838
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ketorolac is an effective non-steroidal anti-inflammatory drug, commonly used with local anaesthetics as part of local infiltration analgesia protocols following orthopaedic surgery. However, systemic uptake and drug action may be the major mechanism after local infiltration. The aims of this project were to study the effects of a small, systemically ineffective dose of ketorolac given intra-articularly for post-operative pain and also to study synovial inflammatory biomarkers. We investigated whether ketorolac affects pro-inflammatory biomarkers in an invitro model, as well.Methods: In this placebo-controlled, blind, randomized study, we analysed intra-articular ketorolac (5mg) in ambulatory minor knee surgery patients with moderate or severe pain (n=44). We assessed post-operative pain intensity (n=44) and analysed microdialysis samples taken from knee synovial tissue every 20min (n=34). We also tested cyclooxygenase-independent effects of ketorolac in synovial cells stimulated by prostaglandin E-2 and chondroitin sulphate invitro.Results: Intra-articular ketorolac (5mg) administration did not reduce pain or synovial pro-inflammatory cytokines CXCL1, IL-8, and MCP-1, 0-120min after knee arthroscopy. Female gender was a risk factor for moderate or severe pain (relative risk 1.45, 95% confidence interval 1.04-2.01). Paradoxically, ketorolac increased the release of CXCL1 and IL-8 in prostaglandin E-2 and chondroitin sulphate-stimulated synovial cells invitro.Conclusion: Ketorolac prescribed at a low dose intra-articularly does not produce any detectable analgesic effect after minor knee surgery.
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| 9. |
- Staartjes, Victor E, et al.
(författare)
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Development and external validation of a clinical prediction model for functional impairment after intracranial tumor surgery.
- 2021
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Ingår i: Journal of neurosurgery. - 1933-0693. ; 134, s. 1743-1750
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Tidskriftsartikel (refereegranskat)abstract
- Decision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on subjective experience and generalized numbers from the literature, but even experienced surgeons overestimate functional outcome after surgery. Today, there is no reliable and objective way to preoperatively predict an individual patient's risk of experiencing any functional impairment.The authors developed a prediction model for functional impairment at 3 to 6 months after microsurgical resection, defined as a decrease in Karnofsky Performance Status of ≥ 10 points. Two prospective registries in Switzerland and Italy were used for development. External validation was performed in 7 cohorts from Sweden, Norway, Germany, Austria, and the Netherlands. Age, sex, prior surgery, tumor histology and maximum diameter, expected major brain vessel or cranial nerve manipulation, resection in eloquent areas and the posterior fossa, and surgical approach were recorded. Discrimination and calibration metrics were evaluated.In the development (2437 patients, 48.2% male; mean age ± SD: 55 ± 15 years) and external validation (2427 patients, 42.4% male; mean age ± SD: 58 ± 13 years) cohorts, functional impairment rates were 21.5% and 28.5%, respectively. In the development cohort, area under the curve (AUC) values of 0.72 (95% CI 0.69-0.74) were observed. In the pooled external validation cohort, the AUC was 0.72 (95% CI 0.69-0.74), confirming generalizability. Calibration plots indicated fair calibration in both cohorts. The tool has been incorporated into a web-based application available at https://neurosurgery.shinyapps.io/impairment/.Functional impairment after intracranial tumor surgery remains extraordinarily difficult to predict, although machine learning can help quantify risk. This externally validated prediction tool can serve as the basis for case-by-case discussions and risk-to-benefit estimation of surgical treatment in the individual patient.
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| 10. |
- Yang, Yang, et al.
(författare)
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The association of patient age with postoperative morbidity and mortality following resection of intracranial tumors.
- 2021
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Ingår i: Brain & spine. - : Elsevier BV. - 2772-5294. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- The postoperative functional status of patients with intracranial tumors is influenced by patient-specific factors, including age.This study aimed to elucidate the association between age and postoperative morbidity or mortality following the resection of brain tumors.A multicenter database was retrospectively reviewed. Functional status was assessed before and 3-6 months after tumor resection by the Karnofsky Performance Scale (KPS). Uni- and multivariable linear regression were used to estimate the association of age with postoperative change in KPS. Logistic regression models for a ≥10-point decline in KPS or mortality were built for patients ≥75 years.The total sample of 4864 patients had a mean age of 56.4±14.4 years. The mean change in pre-to postoperative KPS was -1.43. For each 1-year increase in patient age, the adjusted change in postoperative KPS was -0.11 (95% CI -0.14 - - 0.07). In multivariable analysis, patients ≥75 years had an odds ratio of 1.51 to experience postoperative functional decline (95%CI 1.21-1.88) and an odds ratio of 2.04 to die (95%CI 1.33-3.13), compared to younger patients.Patients with intracranial tumors treated surgically showed a minor decline in their postoperative functional status. Age was associated with this decline in function, but only to a small extent.Patients ≥75 years were more likely to experience a clinically meaningful decline in function and about two times as likely to die within the first 6 months after surgery, compared to younger patients.
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