| 43601. |
- Kawamura, Takuya, et al.
(författare)
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Therapeutic Effect of Nicotinamide Mononucleotide for Hypoxic-Ischemic Brain Injury in Neonatal Mice
- 2023
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Ingår i: Asn Neuro. - 1759-0914. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- A clinical challenge remains in the treatment of hypoxic-ischemic brain injury in newborns. Nicotinamide adenine dinucleotide (NAD+) has beneficial effects in animal models of adult stroke. Here, we aimed to understand the short- and long-term neuroprotective effects of NAD+-promoting substance nicotinamide mononucleotide (NMN) in a well-established brain injury model in neonatal mice. Postnatal day (PND) 9 male and female mice were subjected to cerebral hypoxia-ischemia and treated with saline or NMN (50 mg/kg) immediately after hypoxia-ischemia. At different time points after hypoxia-ischemia, hippocampal NAD+, caspase-3 activity, protein expression of SIRT1, SIRT6, release of high mobility group box-1 (HMGB1), long-term neuropathological outcome, short-term developmental behavior, and long-term motor and memory function were evaluated. Neonatal hypoxia-ischemia reduced NAD+ and SIRT6 levels, but not SIRT1, in the injured hippocampus, while HMGB1 release was significantly increased. NMN treatment normalized hippocampal NAD+ and SIRT6 levels, while caspase-3 activity and HMGB1 release were significantly reduced. NMN alleviated tissue loss in the long-term and improved early developmental behavior, as well as motor and memory function. This study shows that NMN treatment provides neuroprotection in a clinically relevant neonatal animal model of hypoxia-ischemia in mice suggesting as a possible novel treatment for neonatal brain injury.Summary StatementNeonatal hypoxia-ischemia reduces nicotinamide adenine dinucleotide (NAD+) and SIRT6 levels in the injured hippocampus.Hippocampal high mobility group box-1 (HMGB1) release is significantly increased after neonatal hypoxia-ischemia.Nicotinamide mononucleotide (NMN) treatment normalizes hippocampal NAD+ and SIRT6 levels, with significant decrease in caspase-3 activity and HMGB1 release.NMN improves early developmental behavior, as well as motor and memory function. Graphical AbstractThis is a visual representation of the abstract.
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| 43602. |
- Kawashima, T., et al.
(författare)
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Examination of fragment ions of polystyrene in TOF-SIMS spectra using MS/MS
- 2014
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Ingår i: Surface and Interface Analysis. - : Wiley. - 0142-2421 .- 1096-9918. ; 46, s. 92-95
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Tidskriftsartikel (refereegranskat)abstract
- In this study, tendencies of ionization and cleavage processes of time-of-flight (TOF)-SIMS were examined using MS/MS, which enables an easy qualitative analysis of organic matters, to clarify the fragment ions showing structures of the organic materials. In this paper, a result of reviewing fragment ions in TOF-SIMS spectra for polystyrene (PS) as the representative material is shown. Samples were measured with collision induced dissociation (CID)-MS/MS of 1200L (Varian Inc., USA) and TOF-SIMS J105 (Ionoptika Ltd, UK) for the examination of fragment ions of the PS in TOF-SIMS spectra. The use of CID MS/MS with a wide range of energy distribution is effective for the study of the ionization and cleavage process of TOF-SIMS. As a result, the fragment ions representing the PS structure were clarified, which is useful for the material definition. The qualitative analysis was also applied to the fragment ions particularly obtained in this examination. It is suggested that the examination of the fragmentation process using MS/MS is useful for the mass spectra analysis of organic materials in TOF-SIMS. Copyright (c) 2014 John Wiley & Sons, Ltd.
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| 43603. |
- Kawchuk, G. N., et al.
(författare)
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Bulging of the inner and outer annulus during in vivo axial loading of normal and degenerated discs
- 2009
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Ingår i: Journal of Spinal Disorders & Techniques. - 1539-2465. ; 22:3, s. 214-8
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: Comparison of in vivo biomechanical outcomes between experimental and control group animals. OBJECTIVE: To quantify the in vivo bulging response of the inner and outer annulus in animals with and without disc degeneration. SUMMARY OF BACKGROUND DATA: Prior attempts to quantify the load-deformation response of the inner annulus have most often relied on in vitro preparations. Unfortunately, to visualize the inner annulus, these in vitro approaches rely on disc modifications that may result in nonphysiologic behaviors. In response to this problem, in vivo techniques were developed to quantify regional bulging of the inner and outer annulus during applied axial loading. METHODS: Two groups of pigs were tested: a normal group and a group having disc degeneration that was induced surgically 3 months earlier. Eight adolescent pigs were evaluated and for each animal, a miniature servohydraulic actuator was attached to the third and fourth lumbar vertebrae to deliver a cyclic axial loading protocol (300 N, 1 Hz, 10 cycles) whereas regional deformations of the annulus were visualized ultrasonically via retroperitoneal access. RESULTS: For the normal animals, image analysis demonstrated a significantly greater bulging of the inner annular region when compared with the outer annular region. In animals with disc degeneration, the inner and outer annular regions were equal in their bulging response, which ranged from 0 bulging to 37% greater than the average response of the normal animals. CONCLUSIONS: This work supports prior in vitro studies that observed maximal disc bulging in the inner annulus and minimal bulging in the external annulus. Results for this in vivo study suggest that this normal bulging gradient is lost with degenerative disc disease. Compared with in vitro approaches, this new in vivo technique has the potential to demonstrate disc behavior in a variety of loading conditions and/or with a variety of induced disc pathologies.
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| 43604. |
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| 43605. |
- Kay, E., et al.
(författare)
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NanoSIMS Imaging Reveals the Impact of Ligand-ASO Conjugate Stability on ASO Subcellular Distribution
- 2022
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- The delivery of antisense oligonucleotides (ASOs) to specific cell types via targeted en-docytosis is challenging due to the low cell surface expression of target receptors and inefficient escape of ASOs from the endosomal pathway. Conjugating ASOs to glucagon-like peptide 1 (GLP1) leads to efficient target knockdown, specifically in pancreatic β-cells. It is presumed that ASOs dissociate from GLP1 intracellularly to enable an ASO interaction with its target RNA. It is unknown where or when this happens following GLP1-ASO binding to GLP1R and endocytosis. Here, we use correlative nanoscale secondary ion mass spectroscopy (NanoSIMS) and transmission electron microscopy to explore GLP1-ASO subcellular trafficking in GLP1R overexpressing HEK293 cells. We isotopically label both eGLP1 and ASO, which do not affect the eGLP1-ASO conjugate function. We found that the eGLP1 peptide and ASO are not detected at the same level in the same endosomes, within 30 min of GLP1R-HEK293 cell exposure to eGLP1-ASO. When we utilized different linker chemistry to stabilize the GLP1-ASO conjugate, we observed more ASO located with GLP1 compared to cell incubation with the less stable conjugate. Overall, our work suggests that the ASO separates from GLP1 relatively early in the endocytic pathway, and that linker chemistry might impact the GLP1-ASO function. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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| 43606. |
- Kay, J., et al.
(författare)
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A guide to appropriately planning and conducting meta-analyses-Part 1: indications, assumptions and understanding risk of bias
- 2023
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347.
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Tidskriftsartikel (refereegranskat)abstract
- A meta-analysis is the quantitative synthesis of data from two or more individual studies and are as a rule an important method of obtaining a more accurate estimate of the direction and magnitude of a treatment effect. However, it is imperative that the meta-analysis be performed with proper, rigorous methodology to ensure validity of the results and their interpretation. In this article the authors will review the most important questions researchers should consider when planning a meta-analysis to ensure proper indications and methodologies, minimize the risk of bias, and avoid misleading conclusions.
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| 43607. |
- Kay, J., et al.
(författare)
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A Historical Analysis of Randomized Controlled Trials in Anterior Cruciate Ligament Surgery
- 2017
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Ingår i: Journal of Bone and Joint Surgery - American Volume. - : Ovid Technologies (Wolters Kluwer Health). - 0021-9355 .- 1535-1386. ; 99:24, s. 2062-2068
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of this systematic review was to comprehensively assess the quality of reporting of randomized controlled trials (RCTs) relating to anterior cruciate ligament (ACL) reconstruction. Specifically, this review explored factors related to the quality of the RCTs and trends in the quality of reporting over time. Methods: The online databases PubMed, Ovid (MEDLINE), and Embase were used to search for all RCTs on the topic of ACL reconstruction from database inception until April 14, 2016. The quality of reporting was evaluated using the Detsky quality index and the Consolidated Standards of Reporting Trials (CONSORT) checklist for reporting trials of non-pharmacologic treatments. A multivariate regression analysis was used to assess predictors of quality reporting. Results: The online search yielded 2,933 articles, 412 of which met the inclusion criteria and were assessed for quality of reporting. There was a significant (p < 0.0001) increase in the number of RCTs published over time. The mean Detsky score (and standard deviation) across all included RCTs was 68.9% +/- 13.2%. The strongest predictors of quality reporting were the inclusion of a CONSORT flow diagram (b-coefficient, 10.0; 95% confidence interval [CI]: 8.45 to 11.61; p < 0.0001) and being published in the year 2009 or later (b-coefficient, 5.2; 95% CI: 3.87 to 6.45; p < 0.0001). The factors demonstrating the greatest improvement over time were the inclusion of a full description of the randomization procedure (p = 0.001) and prospective calculation of the sample size (p = 0.002). Conclusions: There has been a significant increase in both the quantity and quality of RCTs relating to ACL reconstruction over time. Specifically, the reporting of a methodologically sound randomization process and prospective calculation of sample size have significantly improved in recent years. However, since the year 2009, the number of trials and reporting in these trials has remained relatively consistent. The use of a CONSORT flow diagram is a strong predictor of high-quality reporting.
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| 43608. |
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| 43609. |
- Kay, J., et al.
(författare)
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Earlier anterior cruciate ligament reconstruction is associated with a decreased risk of medial meniscal and articular cartilage damage in children and adolescents: a systematic review and meta-analysis
- 2018
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:12, s. 3738-3753
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To evaluate the association between surgical timing and the incidence of secondary meniscal or chondral damage in children and adolescents with anterior cruciate ligament (ACL) ruptures. Methods Three electronic databases, PubMed, MEDLINE, and EMBASE, were systematically searched from database inception until October 16, 2017 by two reviewers independently and in duplicate. The inclusion criteria were English language studies that reported the incidence of meniscal and articular cartilage damage in children or adolescent athletes with ACL injuries as well as the timing of their ACL reconstruction (ACLR). Risk ratios were combined in a meta-analysis using a random effects model. Results A total of nine studies including 1353 children and adolescents met the inclusion criteria. The mean age of patients included was 14.2 years (range 6-19), and 45% were female. There was a significantly decreased risk of concomitant medial meniscal injury in those reconstructed early (26%) compared to those with delayed reconstruction (47%) [pooled risk ratio (RR) = 0.49, 95% CI 0.36-0.65, p < 0.00001]. There was also a significantly reduced risk of medial femoral chondral (RR = 0.48, 95% CI 0.31-0.75, p = 0.001), lateral femoral chondral (RR = 0.38, 95% CI 0.20-0.75, p = 0.005), tibial chondral (RR = 0.45, 95% CI 0.27-0.75, p = 0.002), and patellofemoral chondral (RR = 0.41, 95% CI 0.20-0.82, p = 0.01) damage in the early reconstruction group in comparison to the delayed group. Conclusion Pooled results from observational studies suggest that early ACLR results in a significantly decreased risk of secondary medial meniscal injury, as well as secondary medial, lateral, and patellofemoral compartment chondral damage in children and adolescents. This study provides clinicians with valuable information regarding the benefits of early ACL reconstruction in children and adolescents, and can be used in the decision making for athletes in this population.
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| 43610. |
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