In vitro Evaluation der lateralen Guttapercha-Kondensationstechnik mit Fingerspreadern verschiedener Spitzengeometrie.

Ziel: Ziel der Studie war es, den Einfluss von Spreaderform und Aufbereitungstaper bei der lateralen Kondensation auf die Dichtigkeit der Wurzelfüllungen zu untersuchen. Für diese Studie wurde ein handelsüblicher Spreader so modifiziert, dass seine Arbeitsspitze durch Abflachung Pluggerfunktionalität erhält. Material&Methode: Insgesamt n=75 frisch extrahierte menschliche Zähne mit geraden Wurzeln wurden so vorbereitet, dass 75 gerade Zahnwurzeln. Diese Zahnwurzeln wurden randomisiert so auf 5 Gruppen aufgeteilt, mit rotierenden Ni/Ti Instrumenten vom Typ Profile 02/50 und 04/50 aufbereitet und unter Verwendung der lateraler Kondensation mit den konventionellen Spreadern „pointed“ sowie modifizierten Spreadern "flat tip“ gefüllt. Eine negative Kontrollgruppe wurde unter Anwendung der Zentralstifttechnik ohne Sealer abgefüllt. Die Wurzeln wurden bis auf 1 mm oberhalb des Apex mit Nagellack überzogen und anschließend verblindet. Nach Lagerung in 2%-Methylenblau für 4 Tage wurden die Proben in Kaltpolymerisat eingebettet und es wurden sechs serielle Querschnitte im Abstand von 0,8 mm ab dem Apex angefertigt. Die Querschnitte wurden digitalisiert. Bewertet wurden die Penetrationstiefe in mm ab dem Apex und der Penetrationsgrad. Ergebnisse: Alle Proben zeigten eine ausgeprägte Penetration. Lediglich der Parameter Penetrationsgrad konnte für eine Differenzierung zwischen den Prüfgruppen verwendet werden. Es zeigte sich ein signifikanter Unterschied zwischen der Kontrollgruppe und allen Prüfgruppen. Innerhalb der Prüfgruppen, welche als normalverteilt und varianzhomogen befunden wurden, wurde eine zweifaktorielle Varianzanalyse für die Faktoren "Spreader" und "Taper" durchgeführt. Es ergab sich für den Faktor "Spreader" ein signifikanter Unterschied (p=0,030) ebenso wie für den Faktor "Taper" (p=0,006). Wurzelfüllungen welche mit dem modifizierten Spreader angefertigt wurden zeigen demnach eine statistisch signifikant schlechtere Dichtigkeit (gemessen mittels Penetrationsgrad) als solche die mit konventionellem Spreader kondensiert wurden. Eine Aufbereitung auf einen Taper von 0,04 führt zu einer statistisch signifikant besseren Dichtigkeit (gemessen mittels Penetrationsgrad) als eine Aufbereitung auf einen ISO-normkonformen Taper von 0,02. Schlussfolgerung: Es konnte gezeigt werden, dass mit dem gewählten Spreaderdesign kein zusätzlicher Nutzen verbunden ist, ja sogar die Dichtigkeit der resultierenden Wurzelfüllungen abnahm. Es ist also nicht angezeigt, Spreader in der beschriebenen Form klinisch zu verwenden. Weiterhin konnte gezeigt werden, dass die Verwendung eines größeren Aufbereitungstapers auch bei lateraler Kondensation zu dichteren Füllungen führt. Klinisch sollte daher ein entsprechend großer Aufbereitungskonus angestrebt werden

Full length talin stimulates integrin activation and axon regeneration.

Integrin function is regulated by activation involving conformational changes that modulate ligand-binding affinity and downstream signaling. Activation is regulated through inside-out signaling which is controlled by many signaling pathways via a final common pathway through kindlin and talin, which bind to the intracellular tail of beta integrins. Previous studies have shown that the axon growth inhibitory molecules NogoA and chondroitin sulfate proteoglycans (CSPGs) inactivate integrins. Overexpressing kindlin-1 in dorsal root ganglion (DRG) neurons activates integrins, enabling their axons to overcome inhibitory molecules in the environment, and promoting regeneration in vivo following dorsal root crush. Other studies have indicated that expression of the talin head alone or with kindlin can enhance integrin activation. Here, using adult rat DRG neurons, we investigate the effects of overexpressing various forms of talin on axon growth and integrin signaling. We found that overexpression of the talin head activated axonal integrins but inhibited downstream signaling via FAK, and did not promote axon growth. Similarly, co-expression of the talin head and kindlin-1 prevented the growth-promoting effect of kindlin-1, suggesting that the talin head acts as a form of dominant negative for integrin function. Using full-length talin constructs in PC12 cells we observed that neurite growth was enhanced by the expression of wild-type talin and more so by two 'activated' forms of talin produced by point mutation (on laminin and aggrecan-laminin substrates). Nevertheless, co-expression of full-length talin with kindlin did not promote neurite growth more than either molecule alone. In vivo, we find that talin is present in PNS axons (sciatic nerve), and also in CNS axons of the corticospinal tract.This work was funded by grants from the Medical Research Council (G1000864), the Henry Smith Charity, the Christopher and Dana Reeve Foundation, the John and Lucille van Geest Foundation, the European Union Framework 7 Programmes Spinal Cord Repair (201144) and Plasticise (223524), and the NIHR Cambridge Biomedical Research Centre. CLT was supported by the Merck, Sharpe and Dohme Fund. We thank Rienhardt Fassler for kindlin constructs and advice, David Critchley for talin antibodies and constructs and Mark Ginsberg for talin constructs.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.mcn.2015.03.01

Double In Situ Approach for the Preparation of Polymer Nanocomposite with Multi-functionality

A novel one-step synthetic route, the double in situ approach, is used to produce both TiO2nanoparticles and polymer (PET), and simultaneously forming a nanocomposite with multi-functionality. The method uses the release of water during esterification to hydrolyze titanium (IV) butoxide (Ti(OBu)4) forming nano-TiO2in the polymerization vessel. This new approach is of general significance in the preparation of polymer nanocomposites, and will lead to a new route in the synthesis of multi-functional polymer nanocomposites

Mycobacterium ulcerans DNA Not Detected in Faecal Samples from Buruli Ulcer Patients: Results of a Pilot Study

It has recently been shown that in a Buruli ulcer (BU) endemic region of southeastern Australia, significant numbers of possums (native tree-dwelling marsupials) have clinical BU disease. Furthermore, based on quantitative PCR (qPCR) analysis, animals with BU lesions (and some without) shed M. ulcerans DNA in their faeces, indicative of bacterial loads of up to 108 organisms/gram. These findings led us to propose that humans might also harbour M. ulcerans in their gastrointestinal tract and shed the bacterium in their faeces. We conducted a pilot study and collected faecal swabs from 26 patients with confirmed BU and 31 healthy household controls. Faecal samples were also collected from 10 healthy controls from non-endemic regions in Ghana. All 67 specimens were negative when tested by IS2404 PCR. The detection sensitivity of this method was ≥104 bacteria per gram (wet-weight) of human faecal material. We conclude that the human gastrointestinal tract is unlikely to be a significant reservoir of M. ulcerans

“That little doorway where I could suddenly start shouting out”: barriers and enablers to the disclosure of distressing voices

Hearing distressing voices is a key feature of psychosis. The time between voice onset and disclosure may be crucial as voices can grow in complexity. This study investigated barriers and enablers to early voice disclosure. Interviews with 20 voice hearers underwent Thematic Analysis. Beliefs about the effect of disclosure on self and others acted as a barrier and enabler to voices being discussed. Voice hearing awareness should be increased amongst young people, the public and care services. To support earlier disclosure measures need to increase skill amongst those likely to be disclosed to

Normal levels of p27Xic1 are necessary for somite segmentation and determining pronephric organ size

The Xenopus laevis cyclin dependent kinase inhibitor p27Xic1 has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27Xic1 is expressed in the developing kidney in the nephrostomal regions. Using over-expression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27Xic1 regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27Xic1 expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27Xic1 are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27Xic1, and reveal its differentiation function is not universally utilised in all developing tissues

Clinical research:Developing an appropriate career structure

The veterinary profession needs to become more successful in producing the next generation of clinician scientists, say Richard Mellanby and others, who set out a roadmap for future academic postgraduate clinical training

Publishing and sharing multi-dimensional image data with OMERO

Imaging data are used in the life and biomedical sciences to measure the molecular and structural composition and dynamics of cells, tissues, and organisms. Datasets range in size from megabytes to terabytes and usually contain a combination of binary pixel data and metadata that describe the acquisition process and any derived results. The OMERO image data management platform allows users to securely share image datasets according to specific permissions levels: data can be held privately, shared with a set of colleagues, or made available via a public URL. Users control access by assigning data to specific Groups with defined membership and access rights. OMERO’s Permission system supports simple data sharing in a lab, collaborative data analysis, and even teaching environments. OMERO software is open source and released by the OME Consortium at www.openmicroscopy.org

Gas-cushioned droplet impacts with a thin layer of porous media

The authors are grateful to Dr. Manish Tiwari for introducing them to experiments involving droplet impacts with textured substrates. PDH is grateful for the use of the Maxwell High-Performance Computing Cluster of the University of Aberdeen IT Service. RP is grateful for the use of the High-Performance Computing Cluster supported by the Research and Specialist Computing Support service at the University of East Anglia.Peer reviewedPostprin

Mycolactone Diffuses into the Peripheral Blood of Buruli Ulcer Patients - Implications for Diagnosis and Disease Monitoring.

BACKGROUND: Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU), is unique among human pathogens in its capacity to produce a polyketide-derived macrolide called mycolactone, making this molecule an attractive candidate target for diagnosis and disease monitoring. Whether mycolactone diffuses from ulcerated lesions in clinically accessible samples and is modulated by antibiotic therapy remained to be established. METHODOLOGY/PRINCIPAL FINDING: Peripheral blood and ulcer exudates were sampled from patients at various stages of antibiotic therapy in Ghana and Ivory Coast. Total lipids were extracted from serum, white cell pellets and ulcer exudates with organic solvents. The presence of mycolactone in these extracts was then analyzed by a recently published, field-friendly method using thin layer chromatography and fluorescence detection. This approach did not allow us to detect mycolactone accurately, because of a high background due to co-extracted human lipids. We thus used a previously established approach based on high performance liquid chromatography coupled to mass spectrometry. By this means, we could identify structurally intact mycolactone in ulcer exudates and serum of patients, and evaluate the impact of antibiotic treatment on the concentration of mycolactone. CONCLUSIONS/SIGNIFICANCE: Our study provides the proof of concept that assays based on mycolactone detection in serum and ulcer exudates can form the basis of BU diagnostic tests. However, the identification of mycolactone required a technology that is not compatible with field conditions and point-of-care assays for mycolactone detection remain to be worked out. Notably, we found mycolactone in ulcer exudates harvested at the end of antibiotic therapy, suggesting that the toxin is eliminated by BU patients at a slow rate. Our results also indicated that mycolactone titres in the serum may reflect a positive response to antibiotics, a possibility that it will be interesting to examine further through longitudinal studies