Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans

Background: Despite the good prognosis of erythema migrans (EM), some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e. g. the early interaction between Borrelia (B.) burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome. Methods: A prospective follow-up study of 109 patients with EM was conducted at the A land Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL)-4, IL-10, IL-12p70 and interferon (IFN)-gamma, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines. Findings: None of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-gamma in the EM biopsies (p = 0.003). B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels. Conclusion: Patients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the importance of an early, local Th1-type response for optimal resolution of LB.Original Publication: Johanna Sjöwall, Linda Fryland, Marika Nordberg, Florence Sjögren, Ulf Garpmo, Christian Jansson, Sten-Anders Carlsson, Sven Bergstrom, Jan Ernerudh, Dag Nyman, Pia Forsberg and Christina Ekerfelt, Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans, 2011, PLOS ONE, (6), 3, 0018220. http://dx.doi.org/10.1371/journal.pone.0018220 Copyright: Public Library of Science (PLoS) http://www.plos.org

Development of Indicator System for the Evaluation of the Universities Performance

Maģistra darba „Indikatoru sistēmas izstrāde universitāšu darbības izvērtēšanai” mērķis - izstrādāt un izvērtēt plašu un visaptverošu Latvijas Universitātes darbības rādītāju (indikatoru) sistēmu, kas raksturo galvenos LU darbības virzienus (studijas, pētniecība, inovācijas, dalība aktuālu valsts un sabiedrības problēmu risināšanā). Lai to sasniegtu, izvirzīti sekojoši uzdevumi: 1) izpētīt pasaules universitāšu pieredzi indikatoru izvēlē un darbības izvērtēšanā un salīdzināšanā; 2) izvēlēties un pamatot LU darbību raksturojošus rādītājus, kas atspoguļo organizācijas līdzsvarotu attīstību 4 virzienos (procesi, klienti, finanses, izaugsme); 3) organizēt ekspertu aptauju izvēlēto LU darbības indikatoru piemērotības un nozīmes LU darbības raksturošanā izvērtēšanai; 4) pārbaudīt izvēlēto indikatoru praktisko pielietojamību, veicot pilotprojektu – LU dabas zinātņu fakultāšu attīstības izvērtēšanu un salīdzināšanu pēc definētajiem indikatoriem. Darba teorētiskajā daļā analizēta indikatoru loma organizāciju darbības izvērtēšanā, universitāšu ranžēšanā un stratēģijas ieviešanā ar līdzsvarotās vadības kartes metodi. Praktiskajā daļā pamatota LU izvērtēšanai izmantojamo indikatoru izvēle, analizēti ekspertu aptaujas dati, aprakstīts izvēlēto indikatoru praktiskās izmantošanas pilotprojekts. Darba apjoms ir 117 lpp. (neskaitot pielikumus). Darbā iekļauti 6 attēli un 34 tabulas, pievienoti 8 pielikumi. Darbā izmantoti 84 literatūras un informācijs avoti.The objective of master paper „Development of indicator system for the evaluation of the universities performance” – to develop and evaluate broad and overall system of performance indicators of the University of Latvia which describes main directions of University performance (study, research, innovation, participation in the solving of burning problems of state and society). To achieve the objective, there are proposed such tasks as follows: 1) research the experience of world universities in the selection of indicators and evaluation and comparing of performance; 2) to choose and fortify indicators characterizing the performance of the University of Latvia that reflect the balanced development of the organization in 4 perspectives (processes, customers, finance, growth); 3) to perform an expert inquiry for the evaluation of the suitability and significance of the selected indicators in the characterization of the University performance; 4) to test the practical usability of selected indicators conducting pilot project – to evaluate and compare the development of faculties of natural sciences following selected indicators. The role of indicators in the performance evaluation of organization, universities ranking and implementation of strategy with the Balanced scorecard method has analyzed in the theoretical part of the work. The practical part includes such questions: justification of the choice of indicators for the evaluation of the University, analysis of data from the expert inquiry, description of the pilot project for the practical use of selected indicators. Size of master paper is 117 pages (without annexes). There are 6 figures and 34 tables included, 8 annexes enclosed. There are 84 literature and information sources used in the paper

The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury

Old age is associated with a poor recovery from traumatic brain injury (TBI). In a retrospective study we investigated if the biochemical response following TBI is age dependent. Extracellular fluids were continuously sampled by microdialysis in 69 patients admitted to our NSICU following severe TBI. The concentrations of glycerol, glutamate, lactate, pyruvate, and eight different cytokines (IL-1b, IL-6, IL-10, IL-8, MIP-1b, RANTES, FGF2, and VEGF) were determined by fluorescence multiplex bead technology. Patients in the oldest age group ( ‡ 65 years) had significantly higher microdialysate concentrations of glycerol and glutamate compared to younger patients: the mean microdialysate concentration of glycerol increased from 55.9 lmol/L (25–44 year) to 252 lmol/L ( ‡ 65 years; p < 0.0001); similarly glutamate increased from 15.8 mmol/L to 92.2 mmol/L ( p < 0.0001). The lactate-pyruvate ratio was also significantly higher in the patients ‡ 65 years of age (63.9) compared with all the other age groups. The patterns of cytokine responses varied. For some cytokines (IL-1b, IL-10, and IL-8) there were no differences between age groups, while for others (MIP-1b, RANTES, VEGF, and IL-6) some differences were observed, but with no clear correlation with increasing age. For FGF2 the mean microdialysate concentration was 43 pg/mL in patients ‡ 65 years old, significantly higher compared to all othe

Gene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ions

Background: Gold salts has previously been used in the treatment of rheumatoid arthritis but have been replaced by biologicals such as TNF-alpha inhibitors. The mechanisms behind the anti-inflammatory effect of metallic gold ions are still unknown, however, recent data showed that charged gold atoms are released from pure metallic gold implants by macrophages via a dissolucytosis membrane, and that gold ions are taken up by local macrophages, mast cells and to some extent fibroblasts. These findings open the question of possible immunomodulatory effects of metallic gold and motivate efforts on a deeper understanding of the effect of metallic gold on key inflammatory cells as macrophages. less thanbrgreater than less thanbrgreater thanMethods: Human macrophage cells (cell line THP-1) were grown on gold foils and intracellular uptake was analysed by autometallography. The impact of phagocytised gold ions on viability of THP-1 cells was investigated by trypan blue staining and TUNEL assay. The global gene expression profile of THP-1 cells after incorporation of gold ions was studied using microarray analysis comprising approximately 20,000 genes. The gene expression data was confirmed by measurement of secreted proteins. less thanbrgreater than less thanbrgreater thanResults: Autometallography showed intracellular uptake of gold ions into THP-1 cells. No significant effect on viability of THP-1 cells was demonstrated. Our data revealed a unique gene expression signature of dissolucytotic THP-1 cells that had taken up gold ions. A large number of regulated genes were functionally related to immunomodulation. Gold ion uptake induced downregulation of genes involved in rheumatoid arthritis such as hepatocyte growth factor, tenascin-C, inhibitor of DNA binding 1 and 3 and matrix metalloproteinase 13. less thanbrgreater than less thanbrgreater thanConclusion: The data obtained in this study offer new insights into the mode of action of gold ions and suggest for the investigation of effects on other key cells and a possible future role of metallic gold as implants in rheumatoid arthritis or other inflammatory conditions

Gene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ions

Abstract Background Gold salts has previously been used in the treatment of rheumatoid arthritis but have been replaced by biologicals such as TNF-α inhibitors. The mechanisms behind the anti-inflammatory effect of metallic gold ions are still unknown, however, recent data showed that charged gold atoms are released from pure metallic gold implants by macrophages via a dissolucytosis membrane, and that gold ions are taken up by local macrophages, mast cells and to some extent fibroblasts. These findings open the question of possible immunomodulatory effects of metallic gold and motivate efforts on a deeper understanding of the effect of metallic gold on key inflammatory cells as macrophages. Methods Human macrophage cells (cell line THP-1) were grown on gold foils and intracellular uptake was analysed by autometallography. The impact of phagocytised gold ions on viability of THP-1 cells was investigated by trypan blue staining and TUNEL assay. The global gene expression profile of THP-1 cells after incorporation of gold ions was studied using microarray analysis comprising approximately 20,000 genes. The gene expression data was confirmed by measurement of secreted proteins. Results Autometallography showed intracellular uptake of gold ions into THP-1 cells. No significant effect on viability of THP-1 cells was demonstrated. Our data revealed a unique gene expression signature of dissolucytotic THP-1 cells that had taken up gold ions. A large number of regulated genes were functionally related to immunomodulation. Gold ion uptake induced downregulation of genes involved in rheumatoid arthritis such as hepatocyte growth factor, tenascin-C, inhibitor of DNA binding 1 and 3 and matrix metalloproteinase 13. Conclusion The data obtained in this study offer new insights into the mode of action of gold ions and suggest for the investigation of effects on other key cells and a possible future role of metallic gold as implants in rheumatoid arthritis or other inflammatory conditions

Identification of key factors in Accelerated Low Water Corrosion through experimental simulation of tidal conditions: influence of stimulated indigenous microbiota

<div><p>Biotic and abiotic factors favoring Accelerated Low Water Corrosion (ALWC) on harbor steel structures remain unclear warranting their study under controlled experimental tidal conditions. Initial stimulation of marine microbial consortia by a pulse of organic matter resulted in localized corrosion and the highest corrosion rates (up to 12-times higher than non-stimulated conditions) in the low water zone, persisting after nine months exposure to natural seawater. Correlations between corrosion severity and the abundance and composition of metabolically active sulfate-reducing bacteria (SRB) indicated the importance and persistence of specific bacterial populations in accelerated corrosion. One phylotype related to the electrogenic SRB <i>Desulfopila corrodens</i> appeared as the major causative agent of the accelerated corrosion. The similarity of bacterial populations related to sulfur and iron cycles, mineral and tuberculation with those identified in ALWC support the relevance of experimental simulation of tidal conditions in the management of steel corrosion exposed to harbor environments.</p></div

A meta-analysis of four European genome screens (GIFT Consortium) shows evidence for a novel region on chromosome 17p11.2-q22 linked to type 2 diabetes.

Positional cloning is expected to identify novel susceptibility genes underlying complex traits, but replication of genome-wide linkage scan findings has proven erratic. To improve our ability to detect and prioritize chromosomal regions containing type 2 diabetes susceptibility genes, the GIFT consortium has implemented a meta-analysis of four scans conducted in European samples. These included the Botnia I and Botnia II scans, with respectively 58 and 353 pedigrees from Finland and Sweden, the Warren 2 scan performed in 573 multiplex sibships from the UK, and a scan of 143 families from France. The meta-analysis was implemented using the genome-search analysis method (GSMA), an exploratory data analysis technique which is robust across study designs. The analysis provided evidence for linkage of type 2 diabetes to six regions, with the strongest evidence on chromosome 17p11.2-q22 (P=0.0016), followed by 2p22.1-p13.2 (P=0.027), 1p13.1-q22 (P=0.028), 12q21.1-q24.12 (P=0.029), 6q21-q24.1 (P=0.033) and 16p12.3-q11.2 (P=0.033). Linkage analysis of the pooled raw genotype data generated maximum LOD scores in the same regions as identified by GSMA. Altogether, our results have indicated that GSMA is a valuable tool to identify chromosomal regions of interest and that accumulating evidence for linkage from small peaks detected across several samples may be more important than getting a high peak in a single sample. This meta-analysis has led to identification of a novel region on chromosome 17 linked to type 2 diabetes; this region has not been highlighted in any published scan to date but on the basis of these data justifies further exploration