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- Lingam, Ingran, et al.
(författare)
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Serial blood cytokine and chemokine mRNA and microRNA over 48h are insult specific in a piglet model of inflammation-sensitized hypoxia-ischaemia.
- 2021
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Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 89:3, s. 464-475
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to inflammation exacerbates injury in neonatal encephalopathy (NE). We hypothesized that brain biomarker mRNA, cytokine mRNA and microRNA differentiate inflammation (E. coli LPS), hypoxia (Hypoxia), and inflammation-sensitized hypoxia (LPS+Hypoxia) in an NE piglet model.Sixteen piglets were randomized: (i) LPS 2μg/kg bolus; 1μg/kg infusion (LPS; n=5), (ii) Saline with hypoxia (Hypoxia; n=6), (iii) LPS commencing 4h pre-hypoxia (LPS+Hypoxia; n=5). Total RNA was acquired at baseline, 4h after LPS and 1, 3, 6, 12, 24, 48h post-insult (animals euthanized at 48h). Quantitative PCR was performed for cytokines (IL1A, IL6, CXCL8, IL10, TNFA) and brain biomarkers (ENO2, UCHL1, S100B, GFAP, CRP, BDNF, MAPT). MicroRNA was detected using GeneChip (Affymetrix) microarrays. Fold changes from baseline were compared between groups and correlated with cell death (TUNEL) at 48h.Within 6h post-insult, we observed increased IL1A, CXCL8, CCL2 and ENO2 mRNA in LPS+Hypoxia and LPS compared to Hypoxia. IL10 mRNA differentiated all groups. Four microRNAs differentiated LPS+Hypoxia and Hypoxia: hsa-miR-23a, 27a, 31-5p, 193-5p. Cell death correlated with TNFA (R=0.69; p<0.01) at 1-3h and ENO2 (R=-0.69; p=0.01) at 48h.mRNA and miRNA differentiated hypoxia from inflammation-sensitized hypoxia within 6h in a piglet model. This information may inform human studies to enable triage for tailored neuroprotection in NE.Early stratification of infants with neonatal encephalopathy is key to provide tailored neuroprotection.IL1A, CXCL8, IL10, CCL2 and NSE mRNA are promising biomarkers of inflammation-sensitized hypoxia.IL10 mRNA levels differentiated all three pathological states; fold changes from baseline was the highest in LPS+Hypoxia animals, followed by LPS and Hypoxia at 6h.miR-23, -27, -31-5p and -193-5p were significantly upregulated within 6h of a hypoxia insult.Functional analysis highlighted the diverse roles of miRNA in the cellular processes.
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| 2. |
- Midtgaard, Kaare S., et al.
(författare)
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Biomechanical significance of the collateral ligaments in transolecranon fracture-dislocations
- 2021
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Ingår i: Journal of shoulder and elbow surgery. - : MOSBY-ELSEVIER. - 1058-2746 .- 1532-6500. ; 30:6, s. 1245-1250
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is widely accepted that transolecranon fracture-dislocations are not associated with collateral ligament disruption. The aim of the present study was to investigate the significance of the collateral ligaments in transolecranon fractures. Methods: Twenty cadaveric elbows with a mean age of 46.3 years were used. All soft tissue was dissected to the level of the capsule, leaving the anterior band of the medial collateral ligament (MCL) and lateral collateral ligament (LCL) intact. A standardized, oblique osteotomy starting from the distal margin of the cartilage bare area of the ulna was made. The elbows were loaded with an inferiorly directed force of 5 and 10 N in the intact, MCL cut, LCL cut, and both ligaments cut states. All measurements were recorded on lateral calibrated radiographs. Results: The mean inferior translation with intact ligaments (n 20) when the humerus was loaded with 5 and 10 N was 1.52 mm (95% confidence interval [CI], 1.02-2.02) and 2.23 mm (95% CI, 1.61-2.85), respectively. When the LCL was cut first (n = 10), the inferior translation with 5 and 10 N load was 4.11 mm (95% CI, 0.95-7.26) and 4.82 mm (95% CI, 1.91-7.72), respectively. When the MCL was cut first (n - 10), the inferior translation when loaded with 5 and 10 N was 3.94 mm (95% CI, 0.796-7.08) and 5.68 mm (95% CI, 3.03-8.33), respectively. The inferior translation when loaded with 5 and 10 N and both ligaments cut was 15.65 mm (95% CI, 12.59-18.79) and 17.50 mm (95% CI, 14.86-20.13), respectively. There was a statistical difference between the intact and MCL cut first at 10 N and when both ligaments were cut at 5 and 10 N. Conclusions: The findings suggest that collateral ligament disruption is a prerequisite for a transolecranon fracture-dislocation. An inferior translation of more than 3 mm suggests that at least one of the collateral ligaments is disrupted, and more than 7.5 mm indicates that both collateral ligaments are disrupted. (C) 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.
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