Activated matrix metalloproteinase 8 in serum predicts severity of acute pancreatitis

Objectives: Severe acute pancreatitis (SAP) has high morbidity and mortality but there are no widely accepted predictive biomarkers in clinical use. Matrix metalloproteinases (MMPs) are active in tissue destruction and inflammatory responses. We studied whether serum levels of activated MMP-8 (aMMP8), MMP-9 and their regulators tissue inhibitor of matrix metalloproteinases (TIMP)-1, myeloperoxidase (MPO) and human neutrophil elastase (HNE) could predict the development of SAP. Methods: The study comprised 214 AP patients (revised Atlanta classification: 142 mild, MAP; 54 moderately severe, MSAP; 18 SAP) referred to Helsinki University Hospital. A venous blood sample was taken within 72 h from the onset of symptoms. Serum levels of aMMP-8 were determined using immunofluorometric assay, and those of MMP-9, TIMP-1, MPO and HNE using enzyme-linked immunosorbent assay. AP groups were compared using Jonckheere-Terpstra test and predictive value for SAP was analyzed using receiver operating characteristics (ROC) analysis. Results: Serum aMMP-8 levels were higher in SAP (median 657 ng/ml, interquartile range 542-738 ng/ ml) compared to MSAP (358 ng/ml, 175-564 ng/ml; p < 0.001) and MAP (231 ng/ml, 128-507 ng/ml; p < 0.001). Similar trend was seen with TIMP-1 and MPO. In ROC analysis aMMP-8, MPO and TIMP-1 emerged as potential markers for the development of SAP (areas under ROC curves 0.83, 0.71 and 0.69, respectively). Conclusions: Serum aMMP-8 measured early in the course of AP (within 72 h of symptom onset) predicted the development of SAP. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of IAP and EPC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer reviewe

Estimating Operability of Ships in Ridged Ice Fields

A method for estimating ship's resistance caused by sea ice ridge keels is revised and used as a part of a method for predicting performance of ships in ridged ice conditions. The resistance method is based on a continuum plasticity model of ridge rubble and is simple to compute. The performance prediction method combines deterministic simulations of ship motion with probabilistic modelling of ridged ice fields. Performance estimates given by the model are distribution of attainable mean speeds for given ice conditions and probability of the ship being able to operate independently. A comprehensive sensitivity analysis was performed to gain insight into the model and identify possible problematic parameters. The sensitivity analysis covered both the ice conditions and modelling assumptions. Two data-sets were used to test the simulation method. One set included the depth profile of sea ice, machinery data and the speed of a ship operating in ridged ice. The resistance method was able to predict the meanspeed over 3km well. The second data-set consisted of a history of ship's speeds and positions from AIS data and ice conditions estimated by a numerical ice model HELMI, developed in the Finnish Meteorological Institute. Observed mean speeds were mostly well within the distributions of mean speeds simulated by the transit simulation model. Predictions of independent operation were also promising.Peer reviewe

Multiparameter Phospho-Flow Analysis of Lymphocytes in Early Rheumatoid Arthritis: Implications for Diagnosis and Monitoring Drug Therapy

The precise mechanisms involved in the initiation and progression of rheumatoid arthritis (RA) are not known. Early stages of RA often have non-specific symptoms, delaying diagnosis and therapy. Additionally, there are currently no established means to predict clinical responsiveness to therapy. Immune cell activation is a critical component therefore we examined the cellular activation of peripheral blood mononuclear cells (PBMCs) in the early stages of RA, in order to develop a novel diagnostic modality.PBMCs were isolated from individuals diagnosed with early RA (ERA) (n = 38), longstanding RA (n = 10), osteoarthritis (OA) (n = 19) and from healthy individuals (n = 10). PBMCs were examined for activation of 15 signaling effectors, using phosphorylation status as a measure of activation in immunophenotyped cells, by flow cytometry (phospho-flow). CD3+CD4+, CD3+CD8+ and CD20+ cells isolated from patients with ERA, RA and OA exhibited activation of multiple phospho-epitopes. ERA patient PBMCs showed a bias towards phosphorylation-activation in the CD4+ and CD20+ compartments compared to OA PBMCs, where phospho-activation was primarily observed in CD8+ cells. The ratio of phospho (p)-AKT/p-p38 was significantly elevated in patients with ERA and may have diagnostic potential. The mean fluorescent intensity (MFI) levels for p-AKT and p-H3 in CD4+, CD8+ and CD20+ T cells correlated directly with physician global assessment scores (MDGA) and DAS (disease activity score). Stratification by medications revealed that patients receiving leflunomide, systemic steroids or anti-TNF therapy had significant reductions in phospho-specific activation compared with patients not receiving these therapies. Correlative trends between medication-associated reductions in the levels of phosphorylation of specific signaling effectors and lower disease activity were observed.Phospho-flow analysis identified phosphorylation-activation of specific signaling effectors in the PB from patients with ERA. Notably, phosphorylation of these signaling effectors did not distinguish ERA from late RA, suggesting that the activation status of discrete cell populations is already established early in disease. However, when the ratio of MFI values for p-AKT and p-p38 is >1.5, there is a high likelihood of having a diagnosis of RA. Our results suggest that longitudinal sampling of patients undergoing therapy may result in phospho-signatures that are predictive of drug responsiveness

The exploration of dominant spoilage bacteria in blue mussels (Mytilus edulis) stored under different modified atmospheres by MALDI-TOF MS in combination with 16S rRNA sequencing

Few studies have addressed species-level identification of spoilage bacteria in blue mussels packed under modified atmospheres (MAs). We investigated the effect of MAs and seasons on the tentative species-level of dominant spoilage bacteria in blue mussels. Summer (s) and winter (w) blue mussels were stored at 4 °C in the atmospheres (CO2/O2/N2): A40s (30/40/30), B60s (40/60/0), C60s (0/60/40), A40w (30/40/30), and D75w (25/75/0). In total, 122 culturable isolates were obtained at the final stage of shelf life, when mortality was high (56–100) and total psychrotrophic bacteria counted >7 log CFU g−1. Biochemical properties were analyzed using gram reactions, catalase and oxidase activities, and salt tolerance tests. Culturable isolates were identified through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16 S rRNA gene sequence analysis. Spoilage potential tests were investigated by evaluating protease, lipase, and fermentation activities as well as gas and H2S production. The culturable isolates showed tolerance to varied salt concentrations. Psychromonas arctica, Pseudoalteromonas elyakovii, and Shewanella frigidimarina were dominating in specific MAs. Winter blue mussels resulted in a higher variation of spoilage bacteria, including S. frigidimarina, S. vesiculosa, S. polaris, Micrococcus luteus, Paeniglutamicibacter terrestris sp. nov., and Alteromonas sp. © 2023 Elsevier Lt

Genetic variants in toll-like receptors are not associated with rheumatoid arthritis susceptibility or anti-tumour necrosis factor treatment outcome

Contains fulltext : 88531.pdf (publisher's version ) (Open Access)BACKGROUND: Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication. METHODOLOGY AND PRINCIPAL FINDINGS: 22 single nucleotide polymorphisms (SNPs) in seven TLR genes were genotyped in a Dutch cohort consisting of 378 RA patients and 294 controls. Significantly associated variants were investigated in replication cohorts from The Netherlands, United Kingdom and Sweden (2877 RA patients and 2025 controls). 182 of the Dutch patients were treated with anti-TNF medication. Using these patients and a replication cohort (269 Swedish patients) we analysed if genetic variants in TLR genes were associated with anti-TNF outcome. In the discovery phase of the study we found a significant association of SNPs rs2072493 in TLR5 and rs3853839 in TLR7 with RA disease susceptibility. Meta-analysis of discovery and replication cohorts did not confirm these findings. SNP rs2072493 in TLR5 was associated with anti-TNF outcome in the Dutch but not in the Swedish population. CONCLUSION: We conclude that genetic variants in TLRs do not play a major role in susceptibility for developing RA nor in anti-TNF treatment outcome in a Caucasian population

Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study.

Contains fulltext : 97228.pdf (publisher's version ) (Open Access)BACKGROUND: Various cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA). We hypothesized that polymorphisms in selected inflammatory response and tissue repair genes contribute to the susceptibility to and severity of RA. METHODS: Polymorphisms in TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH, PARP, TLR2 and TLR4 were genotyped in 376 Caucasian RA patients and 463 healthy Caucasian controls using single base extension. Genotype distributions in patients were compared with those in controls. In addition, the association of polymorphisms with the need for anti-TNF-alpha treatment as a marker of RA severity was assessed. RESULTS: The IL8 781 CC genotype was associated with early onset of disease. The TNFA -238 G/A polymorphism was differentially distributed between RA patients and controls, but only when not corrected for age and gender. None of the polymorphisms was associated with disease severity. CONCLUSIONS: We here report an association between IL8 781 C/T polymorphism and age of onset of RA. Our findings indicate that there might be a role for variations in genes involved in the immune response and in tissue repair in RA pathogenesis. Nevertheless, additional larger genomic and functional studies are required to further define their role in RA