| 1. |
- Björklund, Catarina, 1981-, et al.
(författare)
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Design and synthesis of potent and selective BACE-1 inhibitors
- 2010
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society. - 0022-2623 .- 1520-4804. ; 53:4, s. 1458-1464
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Tidskriftsartikel (refereegranskat)abstract
- Several highly potent BACE-1 protease inhibitors have been developed from an inhibitor series containing a novel hydroxyethylene (HE) core structure displaying aryloxymethyl or benzyloxymethyl P1 side chains and a methoxy P1’ side chain. The target molecules were readily synthesized from chiral carbohydrate starting materials, furnishing the inhibitor compounds in good overall yields. The inhibitors show both high BACE-1 potency and good selectivity against cathepsin D, where the most potent inhibitor furnish a BACE-1 IC50 value of 0.32 nM and displays > 3000 fold selectivity over cathepsin D.
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| 2. |
- Hamrin Senorski, Eric, 1989, et al.
(författare)
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“I never made it to the pros…” Return to sport and becoming an elite athlete after pediatric and adolescent anterior cruciate ligament injury - Current evidence and future directions
- 2018
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:4, s. 1011-1018
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Tidskriftsartikel (refereegranskat)abstract
- The management of anterior cruciate ligament (ACL) injuries in the skeletally immature and adolescent patient remains an area of controversy in sports medicine. This study, therefore, summarizes and discusses the current evidence related to treating pediatric and adolescent patients who sustain an ACL injury. The current literature identifies a trend towards ACL reconstruction as the preferred treatment option for ACL injuries in the young, largely justified by the risk of further structural damage to the knee joint. Worryingly, a second ACL injury is all too common in the younger population, where almost one in every three to four young patients who sustain an ACL injury and return to high-risk pivoting sport will go on to sustain another ACL injury. The clinical experience of these patients emphasizes the rarity of an athlete who makes it to elite level after a pediatric or adolescent ACL injury, with or without reconstruction. If these patients are unable to make it to an elite level of sport, treatment should possibly be modified to take account of the risks associated with returning to pivoting and strenuous sport. The surveillance of young athletes may be beneficial when it comes to reducing injuries. Further research is crucial to better understand specific risk factors in the young and to establish independent structures to allow for unbiased decision-making for a safe return to sport after ACL injury. Level of evidence V.
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| 3. |
- Johansson, Johas, et al.
(författare)
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Tekniska Infrastruktures sårbarhet
- 2010
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Ingår i: FRIVA - risk, sårbarhet och förmåga. - 9789163376917 ; , s. 111-128
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Nilsson, Magnus, et al.
(författare)
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Discovery of 4 '-azido-2 '-deoxy-2 '-C-methyl cytidine and prodrugs thereof : A potent inhibitor of Hepatitis C virus replication
- 2012
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 22:9, s. 3265-3268
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Tidskriftsartikel (refereegranskat)abstract
- 4'-Azido-2'-deoxy-2'-methylcytidine (14) is a potent nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase, displaying an EC50 value of 1.2 mu M and showing moderate in vivo bioavailability in rat (F = 14%). Here we describe the synthesis and biological evaluation of 4'-azido-2'-deoxy-2'-methylcytidine and prodrug derivatives thereof. (C) 2012 Elsevier Ltd. All rights reserved.
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| 5. |
- Nilsson, Magnus, et al.
(författare)
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Synthesis and SAR of potent inhibitors of the Hepatitis C virus NS3/4A protease : Exploration of P2 quinazoline substituents
- 2010
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 20:14, s. 4004-4011
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Tidskriftsartikel (refereegranskat)abstract
- Novel NS3/4A protease inhibitors comprising quinazoline derivatives as P2 substituent were synthesized. High potency inhibitors displaying advantageous PK properties have been obtained through the optimization of quinazoline P2 substituents in three series exhibiting macrocyclic P2 cyclopentane dicarboxylic acid and P2 proline urea motifs. For the quinazoline moiety it was found that 8-methyl substitution in the P2 cyclopentane dicarboxylic acid series improved on the metabolic stability in human liver microsomes. By comparison, the proline urea series displayed advantageous Caco-2 permeability over the cyclopentane series. Pharmacokinetic properties in vivo were assessed in rat on selected compounds, where excellent exposure and liver-to-plasma ratios were demonstrated for a member of the 14-membered quinazoline substituted P2 proline urea series. (C) 2010 Elsevier Ltd. All rights reserved.
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| 6. |
- Samuelsson, Kristian, 1977, et al.
(författare)
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Equivalent Knee Injury and Osteoarthritis Outcome Scores 12 and 24 Months After Anterior Cruciate Ligament Reconstruction: Results From the Swedish National Knee Ligament Register.
- 2017
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Ingår i: The American Journal of Sports Medicine. - : SAGE Publications. - 1552-3365 .- 0363-5465. ; 45:9, s. 2085-2091
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Tidskriftsartikel (refereegranskat)abstract
- It is not clear whether Knee injury and Osteoarthritis Outcome Score (KOOS) results will be different 1 or 2 years after anterior cruciate ligament (ACL) reconstruction.To investigate within individual patients enrolled in the Swedish National Knee Ligament Register whether there is equivalence between KOOS at 1 and 2 years after primary ACL reconstruction.Cohort study; Level of evidence, 2.This cohort study was based on data from the Swedish National Knee Ligament Register during the period January 1, 2005, through December 31, 2013. The longitudinal KOOS values for each individual at the 1- and 2-year follow-up evaluations were assessed through the two one-sided test (TOST) procedure with an acceptance criterion of 4. Subset analysis was performed with patients classified by sex, age, graft type, and type of injury (meniscal and/or cartilage injury).A total of 23,952 patients were eligible for analysis after exclusion criteria were applied (10,116 women, 42.2%; 13,836 men, 57.8%). The largest age group was between 16 and 20 years of age (n = 6599; 27.6%). The most common ACL graft was hamstring tendon (n = 22,504; 94.0%), of which the combination of semitendinosus and gracilis was the most common. A total of 7119 patients reported on the KOOS Pain domain at both 1- and 2-year follow-ups, with a mean difference of 0.21 (13.1 SD, 0.16 SE [90% CI, -0.05 to 0.46], P < .001). The same results were found for the other KOOS subscales: symptoms (mean difference -0.54, 14.1 SD, 0.17 SE [90% CI, -0.81 to -0.26], P < .001), activities of daily living (mean difference 0.45, 10.8 SD, 0.13 SE [90% CI, 0.24 to 0.66], P < .001), sports and recreation (mean difference -0.35, 22.7 SD, 0.27 SE [90% CI, -0.79 to 0.09], P < .001), quality of life (mean difference -0.92, 20.0 SD, 0.24 SE [90% CI, -1.31 to -0.53], P < .001), and the combined KOOS-4 score (mean difference -0.41, 14.5 SD, 0.17 SE [90% CI, -0.70 to -0.13], P < .001). Analyses within specific subsets of patients showed equivalent results between the 2 follow-up evaluations.Equivalent results within patients were found in KOOS values at 1- and 2-year follow-ups after ACL reconstruction. The finding was consistent across all KOOS subscales and for all evaluated subsets of patients. This result implies that there is no additional value in capturing both 1- and 2-year KOOS outcomes after ACL reconstruction. However, these findings of equivalence at 1- and 2-year endpoints do not alleviate the need for longer follow-up periods.
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| 7. |
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