Lymph node removal enhances corneal graft survival in mice at high risk of rejection

Peer reviewedPublisher PD

cis-Urocanic Acid Attenuates Acute Dextran Sodium Sulphate-Induced Intestinal Inflammation

On exposure to sunlight, urocanic acid (UCA) in the skin is converted from trans to the cis form and distributed systemically where it confers systemic immunosuppression. The aim of this study was to determine if administration of cis-UCA would be effective in attenuating colitis and the possible role of IL-10. Colitis was induced in 129/SvEv mice by administering 5% dextran sodium sulfate (DSS) for 7 days in drinking water. During this period mice received daily subcutaneously injections of cis-UCA or vehicle. To examine a role for IL-10, 129/SvEv IL-10−/− mice were injected for 24 days with cis-UCA or vehicle. Clinical disease was assessed by measurement of body weight, stool consistency, and presence of blood. At sacrifice, colonic tissue was collected for histology and measurement of myeloperoxidase and cytokines. Splenocytes were analyzed for CD4+CD25+FoxP3+ T-regulatory cells via flow cytometry. Murine bone-marrow derived antigen-presenting cells were treated with lipopolysaccharide (LPS) ± UCA and cytokine secretion measured. Our results demonstrated that cis-UCA at a dose of 50 µg was effective in ameliorating DSS-induced colitis as evidenced by reduced weight loss and attenuated changes in colon weight/length. This protection was associated with reduced colonic expression of CXCL1, an increased expression of IL-17A and a significant preservation of splenic CD4+CD25+FoxP3+ T-regulatory cells. cis-UCA decreased LPS induced CXCL1, but not TNFα secretion, from antigen-presenting cells in vitro. UCA reduced colonic levels of IFNγ in IL-10−/− mice but did not attenuate colitis. In conclusion, this study demonstrates that cis-urocanic acid is effective in reducing the severity of colitis in a chemically-induced mouse model, indicating that pathways induced by ultraviolet radiation to the skin can influence distal sites of inflammation. This provides further evidence for a possible role for sunlight exposure in modulating inflammatory disorders

The Hall Technique; a randomized controlled clinical trial of a novel method of managing carious primary molars in general dental practice: acceptability of the technique and outcomes at 23 months

<p>Abstract</p> <p>Background</p> <p>Scotland has high levels of untreated dental caries in primary teeth. The Hall Technique is a simplified method of managing carious primary molars using preformed metal crowns (PMCs) cemented with no local anaesthesia, caries removal or tooth preparation. This study compared the acceptability of the Hall Technique for children, their carers, and dentists, and clinical outcomes for the technique, with conventional restorations.</p> <p>Methods</p> <p>General dental practice based, split mouth, randomized controlled trial (132 children, aged 3–10). General dental practitioners (GDPs, n = 17) in Tayside, Scotland (dmft 2.7) placed conventional (Control) restorations in carious primary molars, and Hall Technique PMCs on the contralateral molar (matched clinically and radiographically). Dentists ranked the degree of discomfort they felt the child experienced for each procedure; then children, their carers and dentists stated which technique they preferred. The teeth were followed up clinically and radiographically.</p> <p>Results</p> <p>128 conventional restorations were placed on 132 control teeth, and 128 PMCs on 132 intervention teeth. Using a 5 point scale, 118 Hall PMCs (89%) were rated as no apparent discomfort up to mild, not significant; for Control restorations the figure was 103 (78%). Significant, unacceptable discomfort was recorded for two Hall PMCs (1.5%) and six Control restorations (4.5%). 77% of children, 83% of carers and 81% of dentists who expressed a preference, preferred the Hall technique, and this was significant (Chi square, p < 0.0001). There were 124 children (94% of the initial sample) with a minimum follow-up of 23 months. The Hall PMCs outperformed the Control restorations:</p> <p>a) 'Major' failures (signs and symptoms of irreversible pulpal disease): 19 Control restorations (15%); three Hall PMCs (2%) (P < 0.000);</p> <p>b) 'Minor' failures (loss of restoration, caries progression): 57 Control restorations (46%); six Hall PMCs (5%) (P < 0.000)</p> <p>c) Pain: 13 Control restorations (11%); two Hall PMCs (2%) (P = 0.003).</p> <p>Conclusion</p> <p>The Hall Technique was preferred to conventional restorations by the majority of children, carers and GDPs. After two years, Hall PMCs showed more favourable outcomes for pulpal health and restoration longevity than conventional restorations. The Hall Technique appears to offer an effective treatment option for carious primary molar teeth.</p> <p>Trial registration number</p> <p>Current Controlled Trials ISRCTN47267892 – A randomized controlled trial in primary care of a novel method of using preformed metal crowns to manage decay in primary molar teeth: the Hall technique.</p

Once bitten, not necessarily shy? Determinants of foreign market re-entry commitment strategies

We investigate foreign market re-entry commitment strategies, namely the changes in the modes of operation (commitment) undertaken by multinational enterprises (MNEs) as they return to foreign markets from which they had previously exited. We combine organisational learning theory with the institutional change literature to examine the antecedents of re-entry commitment strategies. From an analysis of 1,020 re-entry events between 1980 and 2016, we find that operation mode prior to exit is a strong predictor of subsequent re-entry mode. Contrary to the predictions of learning theory, we did not find support for the effect of experience accumulated during the initial market endeavour on the re-entry commitment strategies of MNEs. In turn, exit motives significantly impact on the re-entrants' decision to re-enter via a different mode of operation, by either increasing or decreasing their commitment to the market. We show that re-entrants do not replicate unsuccessful operation mode strategies if they had previously underperformed in the market. When favourable host institutional changes occur during the time-out period re-entrants tend to increase commitment in the host market irrespective of the degree of prior experience accumulated in the market