Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogs.
Implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce relevant bone formation but also resident bone remodelling.



To compare the effect of implants fully or partially coated with rhBMP-2 on new bone formation and resident bone remodelling.



Twelve, male, adult, Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load/six animals) or by immersion of the entire implant in an rhBMP-2 solution (soak-load/six animals) for a total of 30 mug rhBMP-2/implant. All implants were air-dried. The animals were euthanized at 8 weeks for histometric evaluation.



Clinical healing was uneventful. Supraalveolar bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (+/- SE) 3.4 +/- 0.2 versus 3.5 +/- 0.4 mm and 2.6 +/- 0.4 versus 2.5 +/- 0.7 mm(2) for coronal-load and soak-load implants, respectively (p>0.05). The corresponding bone density and bone-implant contact (BIC) recordings averaged 38.0 +/- 3.8%versus 34.4 +/- 5.6% and 25.0 +/- 3.8%versus 31.2 +/- 3.3% (p>0.05). In contrast, resident bone remodelling was significantly influenced by the rhBMP-2 application protocol. Bone density outside the implants threads averaged 74.7 +/- 3.8% and 50.8 +/- 4.1% for coronal-load and soak-load implants, respectively (p<0.05); bone density within the thread area averaged 51.8 +/- 1.2% and 37.8 +/- 2.9%, and BIC 70.1 +/- 6.7% and 43.3 +/- 3.9% (p<0.05).



Local application of rhBMP-2 appears to be a viable technology to support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodelling without compromising new bone formation.

title: Evaluation of nano-technology-modified zirconia oral implants: a study in rabbits.
abstract: The objective of this study was to screen candidate nano-technology-modified, micro-structured zirconia implant surfaces relative to local bone formation and osseointegration.



Proprietary nano-technology surface-modified (calcium phosphate: CaP) micro-structured zirconia implants (A and C), control micro-structured zirconia implants (ZiUnite), and titanium porous oxide implants (TiUnite) were implanted into the femoral condyle in 40 adult male New Zealand White rabbits. Each animal received one implant in each hind leg; thus, 20 animals received A and C implants and 20 animals received ZiUnite and TiUnite implants in contralateral hind legs. Ten animals/group were euthanized at weeks 3 and 6 when biopsies of the implant sites were processed for histometric analysis using digital photomicrographs produced using backscatter scanning electron microscopy.



The TiUnite surface demonstrated significantly greater bone-implant contact (BIC) (77.6+/-2.6%) compared with the A (64.6+/-3.6%) and C (62.2+/-3.1%) surfaces at 3 weeks (p<0.05). Numerical differences between ZiUnite (70.5+/-3.1%) and A and C surfaces did not reach statistical significance (p>0.05). Similarly, there were non-significant differences between the TiUnite and the ZiUnite surfaces (p>0.05). At 6 weeks, there were no significant differences in BIC between the TiUnite (67.1+/-4.2%), ZiUnite (69.7+/-5.7%), A (68.6+/-1.9%), and C (64.5+/-4.1%) surfaces (p>0.05).



TiUnite and ZiUnite implant surfaces exhibit high levels of osseointegration that, in this model, confirm their advanced osteoconductive properties. Addition of CaP nano-technology to the ZiUnite surface does not enhance the already advanced osteoconductivity displayed by the TiUnite and ZiUnite implant surfaces.

title: The critical-size supraalveolar peri-implant defect model: reproducibility in histometric data acquisition of alveolar bone formation and osseointegration.
abstract: The objective of this report is to present the reproducibility of outcomes assessments in the Critical-Size Supraalveolar Peri-Implant Defect Model.



Two examiners without specific experience in histological analysis and one experienced examiner performed the histometric evaluation. A comprehensive training program in data acquisition and histological analysis was established, the inexperienced examiners underwent approximately 12 h of training over multiple sessions. A custom-designed image analysis software macro and a computer-based image system were used to analyse digital images generated by a microscope camera system. Nine parameters for newly formed and resident bone were evaluated. Examiners performed histometric analysis using 36 histologic sections selected from critical-size supraalveolar peri-implant defects in 12 male Hound Labrador Mongrel dogs. Buccal and lingual measurements were performed in 72 sites. Intra- and inter-examiner reproducibility were evaluated using the concordance correlation coefficient (CCC) and means +/- SD of the differences. Systematic errors were evaluated using an F-test for equality of means and variances.



Intra-examiner reproducibility was high for all parameters evaluated, the lowest CCC observed being 0.87. Inter-examiner reproducibility was also high, most CCCs exceeding 0.90. Minor systematic errors for intra- and inter-examiner comparisons were occasionally observed. The results imply a high temporal stability because recordings were performed 3 months apart. Measurement errors were stable throughout the range of observations for all parameters.



High examiner reproducibility and temporal stability can be achieved for histometric data acquisition using the Critical-Size Supraalveolar Peri-Implant Defect Model. Examiner reproducibility should be routinely assessed, reported, and accounted for to assure the quality of evidence generated by preclinical studies.

title: Periodontal regeneration: focus on growth and differentiation factors.
abstract: Several growth and differentiation factors have shown potential as therapeutic agents to support periodontal wound healing/regeneration, although optimal dosage, release kinetics, and suitable delivery systems are still unknown. Experimental variables, including delivery systems, dose, and the common use of poorly characterized preclinical models, make it difficult to discern the genuine efficacy of each of these factors. Only a few growth and differentiation factors have reached clinical evaluation. It appears that well-defined discriminating preclinical models followed by well-designed clinical trials are needed to further investigate the true potential of these and other candidate factors. Thus, current research is focused on finding relevant growth and differentiation factors, optimal dosages, and the best approaches for delivery to develop clinically meaningful therapies in patient-centered settings.

title: Bioconjugated superstructures of CdTe nanowires and nanoparticles: multistep cascade Förster resonance energy transfer and energy channeling.
abstract: Nanoparticle/nanowire assemblies with a degree of radial organization were prepared around luminescent semiconducting CdTe nanowires using bioconjugation with streptavidin and D-biotin linkers. Red-emitting nanowires (6.62 +/- 1.55 nm diameter, 512 +/- 119 nm length) and green-emitting nanoparticles (3.2 +/- 0.7 nm diameter) were surface-modified with biotin, while orange-emitting nanoparticles (4.1 +/- 1.2 nm diameter) were decorated with streptavidin. CdTe nanocrystals produced two fuzzy layers around the nanowires in which the diameter of CdTe nanoparticles decreased with the distance from the nanowire axis. Förster resonance energy transfer (FRET) from the outside layer of nanoparticles to the central nanowire was observed for nanowires conjugated with 4.1 nm CdTe. Addition of 3.2 nm CdTe resulted in a red-orange-green optical progression with band gaps of CdTe decreasing toward the axis of the superstructure. In this case, 4-fold luminescence enhancement of the nanowire luminescence was observed and was attributed to multistep FRET. This observation indicated the accumulation of photogenerated excitons in the cascade terminal. A simple model of multiconjugated superstructure with cascade energy transfer is developed and used to describe and understand the experimental data. The experimental data and theoretical model suggest the possibility of utilization of the prepared superstructures with radial symmetry in several classes of optoelectronic devices including nanomaterials for energy collection. They can also be a convenient model object for the investigation of methods of energy funneling in nanoscale assemblies.

title: Ankylosing spondylitis in a patient with myelodysplastic syndrome: an association with HLA-B27 or coincidence?
abstract: The authors report an unusual case of myelodysplastic syndrome (MDS) associated with ankylosing spondylitis (AS). A 40-year-old-man with MDS presented with chronic low back pain for 6 years. Four years ago, MDS was diagnosed during routine blood analysis for the work-up of his articular complaints. His initial articular complaints were attributed to extramedullary manifestations of MDS. Persistent low back pain with increasing intensity finally led the patient to seek medical attention. Radiograph of the pelvis showed bilateral asymmetric sacroiliitis. A diagnosis of AS was established on the basis of modified New York criteria. Although various autoimmune phenomena associated with MDS have been described, this is the first report of AS in the setting of MDS. Causal relationship between these two disorders is currently unknown. Increased risk of hematological diseases as well as AS in individuals with a positive HLA-B27 provides a feasible explanation for this rare observation.

title: Expression and function of sex pheromones and receptors in the homothallic ascomycete Gibberella zeae.
abstract: In heterothallic ascomycete fungi, idiomorphic alleles at the MAT locus control two sex pheromone-receptor pairs that function in the recognition and chemoattraction of strains with opposite mating types. In the ascomycete Gibberella zeae, the MAT locus is rearranged such that both alleles are adjacent on the same chromosome. Strains of G. zeae are self-fertile but can outcross facultatively. Our objective was to determine if pheromones retain a role in sexual reproduction in this homothallic fungus. Putative pheromone precursor genes (ppg1 and ppg2) and their corresponding pheromone receptor genes (pre2 and pre1) were identified in the genomic sequence of G. zeae by sequence similarity and microsynteny with other ascomycetes. ppg1, a homolog of the Saccharomyces alpha-factor pheromone precursor gene, was expressed in germinating conidia and mature ascospores. Expression of ppg2, a homolog of the a-factor pheromone precursor gene, was not detected in any cells. pre2 was expressed in all cells, but pre1 was expressed weakly and only in mature ascospores. ppg1 or pre2 deletion mutations reduced fertility in self-fertilization tests by approximately 50%. Deltappg1 reduced male fertility and Deltapre2 reduced female fertility in outcrossing tests. In contrast, Deltappg2 and Deltapre1 had no discernible effects on sexual function. Deltapre2 double mutants had the same phenotype as the Deltappg1 and Deltapre2 single mutants. Thus, one of the putative pheromone-receptor pairs (ppg1/pre2) enhances, but is not essential for, selfing and outcrossing in G. zeae whereas no functional role was found for the other pair (ppg2/pre1).

title: The composition and dynamics of cell-substratum adhesions in locomoting fish keratocytes.
abstract: Close contacts are the predominant type of cell-substratum adhesion in rapidly moving cells yet little is known about their composition and dynamics. To address these issues we have attempted to identify the molecular components of close contacts formed in rapidly moving fish epithelial keratocytes. In addition we have utilized the simple shape of keratocytes to explore the relationship between close contact formation and rapid locomotion. Beta1 integrin and talin molecules were found to be localized within a narrow rim of very close contact along the leading edge. These molecules together with vinculin were also found within small foci distributed evenly throughout the lamella, corresponding to regions of variable close contact. Alpha-actinin was found in foci within older, more posteriorly located regions of the lamella and along stress fibers. In addition to close contacts, small focal adhesion-like structures which stained positively for all antibodies tested were found at the tips of stress fibers within retracting cell margins. Interference reflection and total internal reflection microscopy of moving keratocytes showed cell-substratum contacts to be organized into distinct patterns that appear to move forwards, in concert with the leading edge. A feature common to all cells is a rim of very close contact at the leading edge. This region is specialized for the formation of new cell-substratum adhesions and is the site where patterns of close contact are generated. We have found that cell locomotion is most rapid when a uniform contact pattern is present but cell speed is progressively reduced as the contact pattern becomes more irregular. Furthermore, the local rate of lamellar extension is most rapid when underlain by regions of intermediate closeness to the substratum, but is reduced or ceases if the underlying contact is either very close or more distant, respectively. Our results suggest that close contacts and focal adhesions are related structures formed from a common hierarchy of molecular interactions. In addition the relationship between close contact formation and lamellar extension indicates a direct coupling between these two processes at the leading edge. Furthermore, we can explain the dynamic behaviour of close contacts in terms of the relative rates of trapping and release of component molecules that is initiated at the leading edge. We suggest that regulation of the molecular dynamics involved in leading edge specialization determines both the pattern of cell-substratum contacts and the net rate of actin filament assembly.

title: Is partial colectomy the operation of choice in pediatric Clostridium difficile colitis?
abstract: PurposeThis study examined the national trends in incidence and surgical management of pediatric Clostridium difficle colitis (CDC) hospitalizations.MethodsThis was a cross-sectional Nationwide Inpatient Sample (NIS) analysis of pediatric CDC from 2000 to 2008. Data analysis included patient demographics, procedures, length of stay (LOS), total hospital charges (THC), and in-hospital mortality.ResultsDuring the 9-year study period, the total number of CDC hospitalizations per year increased almost twofold, from 2,513 in 2000 to 4,817 in 2008. The rate per 100,000 discharges followed a similar trend, increasing from 38.08 in 2000 to 72.57 in 2008. Abdominal colectomy was performed in 0.35 %, with partial colectomy performed more often than total colectomy. Mortality, mean LOS, and mean THC were not statistically different between partial versus total colectomy. Children with ulcerative colitis were more likely to undergo total colectomy, (OR 35.700, CI 11.025–115.98, P < 0.001). Infants under the age of 1 year were less likely to undergo total colectomy (OR 0.568, 0.477–0.677, P < 0.001).ConclusionPediatric hospitalizations for CDC are on the rise. Partial colectomy is performed more often than total colectomy without statistical compromise of mortality, length of stay, and total hospital charges. Further studies are needed to determine the standard surgical management of pediatric CDC.