Rough titanium alloys regulate osteoblast production of angiogenic factors

Multiple biomaterials are clinically available to spine surgeons for performing interbody fusion. Poly-ether-ether-ketone (PEEK) is used frequently for lumbar spine interbody fusion, but alternative materials are also used, including titanium (Ti) alloys. Previously, we showed that osteoblasts exhibit a more differentiated phenotype when grown on machined or grit-blasted titanium aluminum vanadium (Ti6Al4V) alloys with micron-scale roughened surfaces than when grown on smoother Ti6Al4V surfaces or on tissue culture polystyrene (TCPS). We hypothesized that osteoblasts cultured on rough Ti alloy substrates would present a more mature osteoblast phenotype than cells cultured on PEEK, suggesting that textured Ti6Al4V implants may provide a more osteogenic surface for interbody fusion devices. PURPOSE: The aim of the present study was to compare osteoblast response to smooth Ti6Al4V (sTiAlV) and roughened Ti6Al4V (rTiAlV) with their response to PEEK with respect to differentiation and production of factors associated with osteogenesis. STUDY DESIGN: This in vitro study compared the phenotype of human MG63 osteoblast-like cells cultured on PEEK, sTiAlV, or rTiAlV surfaces and their production of bone morphogenetic proteins (BMPs). METHODS: Surface properties of PEEK, sTiAlV, and rTiAlV discs were determined. Human MG63 cells were grown on TCPS and the discs. Confluent cultures were harvested, and cell number, alkaline phosphatase–specific activity, and osteocalcin were measured as indicators of osteoblast maturation. Expression of messenger RNA (mRNA) for BMP2 and BMP4 was measuredMultiple biomaterials are clinically available to spine surgeons for performing interbody fusion. Poly-ether-ether-ketone (PEEK) is used frequently for lumbar spine interbody fusion, but alternative materials are also used, including titanium (Ti) alloys. Previously, we showed that osteoblasts exhibit a more differentiated phenotype when grown on machined or grit-blasted titanium aluminum vanadium (Ti6Al4V) alloys with micron-scale roughened surfaces than when grown on smoother Ti6Al4V surfaces or on tissue culture polystyrene (TCPS). We hypothesized that osteoblasts cultured on rough Ti alloy substrates would present a more mature osteoblast phenotype than cells cultured on PEEK, suggesting that textured Ti6Al4V implants may provide a more osteogenic surface for interbody fusion devices. PURPOSE: The aim of the present study was to compare osteoblast response to smooth Ti6Al4V (sTiAlV) and roughened Ti6Al4V (rTiAlV) with their response to PEEK with respect to differentiation and production of factors associated with osteogenesis. STUDY DESIGN: This in vitro study compared the phenotype of human MG63 osteoblast-like cells cultured on PEEK, sTiAlV, or rTiAlV surfaces and their production of bone morphogenetic proteins (BMPs). METHODS: Surface properties of PEEK, sTiAlV, and rTiAlV discs were determined. Human MG63 cells were grown on TCPS and the discs. Confluent cultures were harvested, and cell number, alkaline phosphatase–specific activity, and osteocalcin were measured as indicators of osteoblast maturation. Expression of messenger RNA (mRNA) for BMP2 and BMP4 was measure

Evaluating major curriculum change:the effect on student confidence

Aim: The aim of this study was to evaluate the effect of major curriculum change within a UK dental school on final-year student self-rated confidence levels. Methods: Final-year dental students graduating in each year between 2007 and 2012 completed the same course evaluation questionnaire, which assessed their confidence in relation to a range of clinical procedures using a Likert-type scale. This period spanned the introduction of a new curriculum and allowed analysis of differences in self-rated confidence between students graduating from the old (2007 and 2008) and new (2009–2012) curricula, across thirty key procedures. Results: New curriculum students showed significantly higher self-confidence ratings in nineteen of the thirty procedures, compared with those on the old curriculum. For the remaining eleven procedures there was no significant difference between the two curricula. The proportion of students on the outcomes-based curriculum rating themselves as 'confident” was statistically significantly higher in seven out of the thirty procedures, when compared with the traditional curriculum, and unchanged or nonsignificantly increased in the remainder. Discussion and conclusions: The relationship between specific curricular innovations and student confidence is considered, as is the usefulness of self-rated confidence in curriculum evaluation. Curriculum change appeared to have a positive effect on student confidence across a range of procedures

OPN/CD44v6 overexpression in laryngeal dysplasia and correlation with clinical outcome

Laryngeal dysplasia is a common clinical concern. Despite major advancements, a significant number of patients with this condition progress to invasive squamous cell carcinoma. Osteopontin (OPN) is a secreted glycoprotein, whose expression is markedly elevated in several types of cancers. We explored OPN as a candidate biomarker for laryngeal dysplasia. To this aim, we examined OPN expression in 82 cases of dysplasia and in hyperplastic and normal tissue samples. OPN expression was elevated in all severe dysplasia samples, but not hyperplastic samples, with respect to matched normal mucosa. OPN expression levels correlated positively with degree of dysplasia (P=0.0094) and negatively with disease-free survival (P<0.0001). OPN expression was paralleled by cell surface reactivity for CD44v6, an OPN functional receptor. CD44v6 expression correlated negatively with disease-free survival, as well (P=0.0007). Taken as a whole, our finding identify OPN and CD44v6 as predictive markers of recurrence or aggressiveness in laryngeal intraepithelial neoplasia, and overall, point out an important signalling complex in the evolution of laryngeal dysplasia

Oral Ondansetron Administration in Emergency Departments to Children with Gastroenteritis: An Economic Analysis

Stephen Freedman and colleagues performed a cost analysis of the routine administration of ondansetron in both the United States and Canada and show that its routine administration to eligible children in such settings could provide substantial benefit

Bone Tissue Response to Porous and Functionalized Titanium and Silica Based Coatings

Background: Topography and presence of bio-mimetic coatings are known to improve osseointegration. The objective of this study was to evaluate the bone regeneration potential of porous and osteogenic coatings. Methodology: Six-implants [Control (CTR); porous titanium coatings (T1, T2); thickened titanium (Ti) dioxide layer (TiO2); Amorphous Microporous Silica (AMS) and Bio-active Glass (BAG)] were implanted randomly in tibiae of 20-New Zealand white rabbits. The animals were sacrificed after 2 or 4 weeks. The samples were analyzed histologically and histomorphometrically. In the initial bone-free areas (bone regeneration areas (BRAs)), the bone area fraction (BAF) was evaluated in the whole cavity (500 mm, BAF-500), in the implant vicinity (100 mm, BAF-100) and further away (100–500 mm, BAF-400) from the implant. Bone-to-implant contact (BIC-BAA) was measured in the areas where the implants were installed in contact to the host bone (bone adaptation areas (BAAs)) to understand and compare the bone adaptation. Mixed models were used for statistical analysis. Principal Findings: After 2 weeks, the differences in BAF-500 for different surfaces were not significant (p.0.05). After 4 weeks, a higher BAF-500 was observed for BAG than CTR. BAF-100 for AMS was higher than BAG and BAF-400 for BAG was higher than CTR and AMS. For T1 and AMS, the bone regeneration was faster in the 100-mm compared to the 400-mm zone. BIC-BAA for AMS and BAG was lower after 4 than 2 weeks. After 4 weeks, BIC-BAA for BAG was lower than AMS and CTR. Conclusions: BAG is highly osteogenic at a distance from the implant. The porous titanium coatings didn’t stimulate bone regeneration but allowed bone growth into the pores. Although AMS didn’t stimulate higher bone response, it has a potential of faster bone growth in the vicinity compared to further away from the surface. BIC-BAA data were inconclusive to understand the bone adaptation.status: publishe

Long-term natural history data in Duchenne muscular dystrophy ambulant patients with mutations amenable to skip exons 44, 45, 51 and 53

INTRODUCTION: The aim of this international collaborative effort was to report 36-month longitudinal changes using the 6MWT in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons 44, 45, 51 or 53. MATERIALS AND METHODS: Of the 92 patients included in the study, 24 had deletions amenable to skip exon 44, 27 exon 45, 18 exon 51, and 28 exon 53. Five patients with a single deletion of exon 52 were counted in both subgroups skipping exon 51 and 53. RESULTS: The difference between subgroups amenable to skip different exons was not significant at 12 months but became significant at both 24 (p≤0.05) and 36 months (p≤0.01). DISCUSSION: Mutations amenable to skip exon 53 had lower baseline values and more negative changes than the other subgroups while those amenable to skip exon 44 had better results both at baseline and at follow up. Deletions amenable to skip exon 45 were associated with a more variable pattern of progression. Single exon deletions were more often associated with less drastic changes but this was not always true in individual cases. CONCLUSION: Our results confirm that the progression of disease can differ between patients with different deletions, although the changes only become significant from 24 months onwards. This information is relevant because there are current clinical trials specifically targeting patients with these subgroups of mutations