In Vitro Biofilm Formation on Titanium and Zirconia Implant Surfaces

Background: It has been hypothesized that zirconia might have a reduced bacterial adhesion compared with titanium; however, results from experimental studies are rather controversial. The aim of the present study is to compare biofilm formation on zirconia and titanium implant surfaces using an in vitro three‐species biofilm and human plaque samples. Methods: Experimental disks made of titanium (Ti) or zirconia (ZrO₂) with a machined (M) or a sandblasted (SLA) and acid‐etched (ZLA) surface topography were produced. An in vitro three‐species biofilm or human plaque samples were applied for bacterial adhesion to each type of disk, which after 72 hours of incubation was assessed using an anaerobic flow chamber model. Results: Zirconia showed a statistically significant reduction in three‐species biofilm thickness compared with titanium (ZrO₂‐M: 8.41 μm; ZrO₂‐ZLA: 17.47 μm; Ti‐M: 13.12 μm; Ti‐SLA: 21.97 μm); however, no differences were found regarding three‐species‐biofilm mass and metabolism. Human plaque analysis showed optical density values of 0.06 and 0.08 for ZrO₂‐M and ZrO₂‐ZLA, and values of 0.1 and 0.13 for Ti‐M and Ti‐SLA, respectively; indicating a statistically significant reduction in human biofilm mass on zirconia compared with titanium. Additionally, zirconia revealed a statistically significant reduction in human plaque thickness (ZrO₂‐M: 9.04 μm; ZrO₂‐ZLA: 13.83 μm; Ti‐M: 13.42 μm; Ti‐SLA: 21.3 μm) but a similar human plaque metabolism compared with titanium. Conclusion: Zirconia implant surfaces showed a statistically significant reduction in human plaque biofilm formation after 72 hours of incubation in an experimental anaerobic flow chamber model compared with titanium implant surfaces.     

Stabilization of the dystroglycan complex in Cajal bands of myelinating Schwann cells through plectin‐mediated anchorage to vimentin filaments

Previous studies have unmasked plectin, a uniquely versatile intermediate filament‐associated cytolinker protein, to be essential for skin and skeletal muscle integrity. Different sets of isoforms of the protein were found to stabilize cells mechanically, regulate cytoskeletal dynamics, and serve as a scaffolding platform for signaling molecules. Here, we investigated whether a similar scenario prevails in myelinating Schwann cells. Using isoform‐specific antibodies, the two plectin variants predominantly expressed in the cytoplasmic compartment (Cajal bands) of Schwann cells were identified as plectin (P)1 and P1c. Coimmunoprecipitation and immunolocalization experiments revealed complex formation of Cajal band plectin with β‐dystroglycan, the core component of the dystrophin glycoprotein complex that in Schwann cells is crucial for the compartmentalization and stabilization of the myelin sheath. To study the functional implications of Schwann cell‐specific plectin‐β‐dystroglycan interaction, we generated conditional (Schwann cell‐restricted) plectin knockout mice. Ablation of plectin in myelinating Schwann cells (SCs) was found not to affect myelin sheath formation but to abrogate the tight association of the dystroglycan complex with the intermediate filament cytoskeleton. We show that the disruption of this association leads to the destabilization of the dystroglycan complex combined with increased myelin sheath deformations observed in the peripheral nerve during ageing of the animal. GLIA 2013;61:1274–1287     

Warming-induced shift in European mushroom fruiting phenology

In terrestrial ecosystems, fungi are the major agents of decomposition processes and nutrient cycling and of plant nutrient uptake. Hence, they have a vital impact on ecosystem processes and the terrestrial carbon cycle. Changes in productivity and phenology of fungal fruit bodies can give clues to changes in fungal activity, but understanding these changes in relation to a changing climate is a pending challenge among ecologists. Here we report on phenological changes in fungal fruiting in Europe over the past four decades. Analyses of 746,297 dated and geo-referenced mushroom records of 486 autumnal fruiting species from Austria, Norway, Switzerland, and the United Kingdom revealed a widening of the annual fruiting season in all countries during the period 1970-2007. The mean annual day of fruiting has become later in all countries. However, the interspecific variation in phenological responses was high. Most species moved toward a later ending of their annual fruiting period, a trend that was particularly strong in the United Kingdom, which may reflect regional variation in climate change and its effects. Fruiting of both saprotrophic and mycorrhizal fungi now continues later in the year, but mycorrhizal fungi generally have a more compressed season than saprotrophs. This difference is probably due to the fruiting of mycorrhizal fungi partly depending on cues from the host plant. Extension of the European fungal fruiting season parallels an extended vegetation season in Europe. Changes in fruiting phenology imply changes in mycelia activity, with implications for ecosystem function.     

Lung transplantation in children and young adults: a 20-year single-centre experience

Lung transplantation in adults is an accepted therapeutic option, whereas there is ongoing debate on its positive impact on survival in children. We report our experience of the first 20 yrs of paediatric lung transplantation at a single centre in Austria. Patient survival, organ survival and freedom from bronchiolitis obliterans were estimated by Kaplan-Meier curves. Pre- and post-transplant parameters were assessed and their influence on patient and organ survival evaluated by univariate tests and stepwise multivariate analyses. A total of 55 transplantations were performed in 43 patients. 1- and 5-yr patient survival rates were 72.1% and 60.6%, respectively, and 52.6% of patients were found to be free from bronchiolitis obliterans syndrome at 5 yrs post-transplant. Analysing different eras of transplantation suggests an improvement over the years with a 5-yr survival rate of 70.6% in the second decade. A positive effect of pre-transplant diabetes mellitus and immunosuppression was found with the newer drug tacrolimus, and a negative effect of pre-transplant in-hospital admission was reported. A high rate of successful re-transplantation prolonged total patient survival.     

Phosphoinositide‐dependent protein kinase 1 (PDK1) mediates potent inhibitory effects on eosinophils

Prostaglandin E₂ (PGE₂) protects against allergic responses via binding to prostanoid receptor EP4, which inhibits eosinophil migration in a PI3K/PKC‐dependent fashion. The phosphoinositide‐dependent protein kinase 1 (PDK1) is known to act as a downstream effector in PI3K signaling and has been implicated in the regulation of neutrophil migration. Thus, here we elucidate whether PDK1 mediates inhibitory effects of E‐type prostanoid receptor 4 (EP4) receptors on eosinophil function. Therefore, eosinophils were isolated from human peripheral blood or differentiated from mouse BM. PDK1 signaling was investigated in shape change, chemotaxis, CD11b, respiratory burst, and Ca²⁺ mobilization assays. The specific PDK1 inhibitors BX‐912 and GSK2334470 prevented the inhibition by prostaglandin E₂ and the EP4 agonist ONO‐AE1‐329. Depending on the cellular function, PDK1 seemed to act through PI3K‐dependent or PI3K‐independent mechanisms. Stimulation of EP4 receptors caused PDK1 phosphorylation at Ser396 and induced PI3K‐dependent nuclear translocation of PDK1. EP4‐induced inhibition of shape change and chemotaxis was effectively reversed by the Akt inhibitor triciribine. In support of this finding, ONO‐AE1‐329 induced a PI3K/PDK1‐dependent increase in Akt phosphorylation. In conclusion, our data illustrate a critical role for PDK1 in transducing inhibitory signals on eosinophil effector function. Thus, our results suggest that PDK1 might serve as a novel therapeutic target in diseases involving eosinophilic inflammation.     

CFTR Cl- channel function in native human colon correlates with the genotype and phenotype in cystic fibrosis

BACKGROUND & AIMS: Cystic fibrosis (CF) is caused by over 1000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and presents with a widely variable phenotype. Genotype-phenotype studies identified CFTR mutations that were associated with pancreatic sufficiency (PS). Residual Cl- channel function was shown for selected PS mutations in heterologous cells. However, the functional consequences of most CFTR mutations in native epithelia are not well established. METHODS: To elucidate the relationships between epithelial CFTR function, CFTR genotype, and patient phenotype, we measured cyclic adenosine monophosphate (cAMP)-mediated Cl- secretion in rectal biopsy specimens from 45 CF patients who had at least 1 non-DeltaF508 mutation carrying a wide spectrum of CFTR mutations. We compared CFTR genotypes and clinical manifestations of CF patients who expressed residual CFTR-mediated Cl- secretion with patients in whom Cl- secretion was absent. RESULTS: Residual anion secretion was detected in 40% of CF patients, and was associated with later disease onset (P < 0.0001), higher frequency of PS (P < 0.0001), and less severe lung disease (P < 0.05). Clinical outcomes correlated with the magnitude of residual CFTR activity, which was in the range of approximately 12%-54% of controls. CONCLUSIONS: Specific CFTR mutations confer residual CFTR function to rectal epithelia, which is related closely to a mild disease phenotype. Quantification of rectal CFTR-mediated Cl- secretion may be a sensitive test to predict the prognosis of CF disease and identify CF patients who would benefit from therapeutic strategies that would increase residual CFTR activity.     

Cytokine‐dependent regulation of dendritic cell differentiation in the splenic microenvironment

The DC‐derived chemokine CCL17, a ligand of CCR4, has been shown to promote various inflammatory diseases such as atopic dermatitis, atherosclerosis, and inflammatory bowel disease. Under steady‐state conditions, and even after systemic stimulation with LPS, CCL17 is not expressed in resident splenic DCs as opposed to CD8α^?CD11b⁺ LN DCs, which produce large amounts of CCL17 in particular after maturation. Upon systemic NKT cell activation through α‐galactosylceramide stimulation however, CCL17 can be upregulated in both CD8α^? and CD8α⁺ splenic DC subsets and enhances cross‐presentation of exogenous antigens. Based on genome‐wide expression profiling, we now show that splenic CD11b⁺ DCs are susceptible to IFN‐γ‐mediated suppression of CCL17, whereas LN CD11b⁺CCL17⁺ DCs downregulate the IFN‐γR and are much less responsive to IFN‐γ. Under inflammatory conditions, particularly in the absence of IFN‐γ signaling in IFN‐γRKO mice, CCL17 expression is strongly induced in a major proportion of splenic DCs by the action of GM‐CSF in concert with IL‐4. Our findings demonstrate that the local cytokine milieu and differential cytokine responsiveness of DC subsets regulate lymphoid organ specific immune responses at the level of chemokine expression.     

The Long-Term Effectiveness and Cost Effectiveness of Organized versus Opportunistic Screening for Breast Cancer in Austria

Background

In 2014, Austrian health authorities implemented an organized breast cancer screening program. Until then, there has been a long-standing tradition of opportunistic screening.

Distinctive toxicity of TiO2 rutile/anatase mixed phase nanoparticles on Caco-2 cells

Titanium dioxide has a long-standing use as a food additive. Micrometric powders are, e.g., applied as whiteners in confectionary or dairy products. Possible hazards of ingested nanometric TiO(2) particles for humans and the potential influence of varying specific surface area (SSA) are currently under discussion. Five TiO(2)-samples were analyzed for purity, crystallinity, primary particle size, SSA, ζ potential, and aggregation/agglomeration. Their potential to induce cytotoxicity, oxidative stress, and DNA damage was evaluated in human intestinal Caco-2 cells. Only anatase-rutile containing samples, in contrast to the pure anatase samples, induced significant LDH leakage or mild DNA damage (Fpg-comet assay). Evaluation of the metabolic competence of the cells (WST-1 assay) revealed a highly significant correlation between the SSA of the anatase samples and cytotoxicity. The anatase/rutile samples showed higher toxicity per unit surface area than the pure anatase powders. However, none of the samples affected cellular markers of oxidative stress. Our findings suggest that both SSA and crystallinity are critical determinants of TiO(2)-toxicity toward intestinal cells.