Evaluation of nano-technology-modified zirconia oral implants: a study in rabbits.
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: Enhancedex vivo buccal transport of propranolol: Evaluation of phospholipids as permeation enhancers
abstract: The aim of the present study was to evaluate the effects of two phospholipid permeation enhancers, lysophosphatidylcholine (LPC) and didecanoylphosphatidylcholine (DDPC), along with a fusidic acid derivative, sodium taurodihydrofusidate (STDHF) and ethanol (EtOH) on the buccal transport of propranolol hydrochloride (PPL) using anex vivo buccal diffusion model. The permeation rate of [3H]PPL as measured by steady-state fluxes increased with increasing EtOH concentration. A significant flux enhancement (P<0.05) was achieved by EtOH at 20 and 30 %v/v concentrations. At a 0.5 %w/v permeation enhancer concentration, the buccal permeation of [3H]PPL was significantly enhanced by all the enhancers studied (i.e., LPC, DDPC and STDHF) compared to the control (phosphate-buffered saline pH 7.4, PBS). LPC and DDPC displayed a greater degree of permeation enhancement compared with STDHF and EtOH-PBS mixtures with an enhancement ratio of 3.2 and 2.9 for LPC and DDPC, respectively compared with 2.0 and 1.5 for STDHF and EtOH:PBS 30:70 %v/v mixture, respectively. There was no significant difference between LPC and DDPC for the flux values and apparent permeability coefficients of [3H]PPL. These results suggest that phospholipids are suitable as permeation enhancers for the buccal delivery of drugs.

title: The contribution of myelin to magnetic susceptibility-weighted contrasts in high-field MRI of the brain
abstract: T(2)*-weighted gradient-echo MRI images at high field (≥ 7T) have shown rich image contrast within and between brain regions. The source for these contrast variations has been primarily attributed to tissue magnetic susceptibility differences. In this study, the contribution of myelin to both T(2)* and frequency contrasts is investigated using a mouse model of demyelination based on a cuprizone diet. The demyelinated brains showed significantly increased T(2)* in white matter and a substantial reduction in gray-white matter frequency contrast, suggesting that myelin is a primary source for these contrasts. Comparison of in-vivo and in-vitro data showed that, although tissue T(2)* values were reduced by formalin fixation, gray-white matter frequency contrast was relatively unaffected and fixation had a negligible effect on cuprizone-induced changes in T(2)* and frequency contrasts.

title: Korean nurses' perceived facilitators and barriers in provision of end-of-life care.
abstract: This study examined nurses' perceived facilitators and barriers to end-of-life (EOL) care in clinical settings. The study participants were 383 Korean nurses working at tertiary hospitals. The nurses had an average of 7.6 years of clinical experience. The three highest-scoring facilitating items were 'family member acceptance of patient death', 'having time to prepare the family for the patient's expected death' and 'having the physician meet with the family after the patient's death to offer support and validate the given care'. The top two perceived barriers were 'families not accepting what the physician is telling them about the patient's prognosis' and 'dealing with angry family members'. Nurses who had received EOL care education showed a higher score in perception of facilitators than nurses who did not receive that education. EOL care for patients and their families is a challenge; thus, continuing education should be provided to improve nursing practice.

title: Traction forces generated by locomoting keratocytes
abstract: Traction forces produced by moving fibroblasts have been observed as distortions in flexible substrata including wrinkling of thin, silicone rubber films. Traction forces generated by fibroblast lamellae were thought to represent the forces required to move the cell forwards. However, traction forces could not be detected with faster moving cell types such as leukocytes and growth cones (Harris, A. K., D. Stopak, and P. Wild. 1981.  ). We have developed a new assay in which traction forces produced by rapidly locomoting fish keratocytes can be detected by the two-dimensional displacements of small beads embedded in the plane of an elastic substratum. Traction forces were not detected at the rapidly extending front edge of the cell. Instead the largest traction forces were exerted perpendicular to the left and right cell margins. The maximum traction forces exerted by keratocytes were estimated to be approximately 2 x 10(-8) N. The pattern of traction forces can be related to the locomotion of a single keratocyte in terms of lamellar contractility and area of close cell- substratum contact.

title: CIP2A expression is associated with synovial hyperplasia and invasive function of fibroblast-like synoviocytes in rheumatoid arthritis
abstract: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that leads to cellular proliferation in cancer cells. We aim to investigate CIP2A expression in fibroblast-like synoviocytes (FLS) and its association with the histopathological grade of synovitis and the invasive function of FLS in rheumatoid arthritis (RA). CIP2A protein expression was measured in 8 RA FLS and 8 OA FLS using Western blot analysis. CIP2A mRNA expression from 19 RA FLS and 7 OA FLS was measured using real-time PCR. Synovitis score of RA FLS-matched synovial tissues was semiquantitatively measured by two independent pathologists. An in vitro cell invasion assay was performed using RA FLS treated with CIP2A small interfering RNA (siRNA) or with control vector. Western blot analysis showed that CIP2A is more frequently overexpressed in RA FLS compared with OA FLS. CIP2A mRNA expression was higher in RA FLS compared with those in OA FLS, but did not reach statistical significance (P = 0.076). In RA, total synovitis score was strongly correlated with FLS CIP2A mRNA expression (rs = 0.849, P = 0.043). TNF-α treatment induced a robust increase in the invasive function of control FLS (P = 0.0021), but no significant effect was observed in CIP2A siRNA-treated FLS. Our data demonstrate that CIP2A expression is closely associated with the histopathological score of synovitis and invasive function of FLS in RA. These results suggest that CIP2A may play a critical role in the destructive process in RA and warrant further investigation of CIP2A as a therapeutic target.