Development of a Personalised Device for Systemic Magnetic Drug Targeting to Brain Tumours.

Delivering therapies to deeply seated brain tumours (BT) is a major clinical challenge. Magnetic drug targeting (MDT) could overcome this by rapidly transporting magnetised drugs directly into BT. We have developed a magnetic device for application in murine BT models using an array of neodymium magnets with a combined strength of 0.7T. In a closed fluidic system, the magnetic device trapped magnetic nanoparticles (MNP) up to distances of 0.8cm. In mice, the magnetic device guided intravenously administered MNP (<50nm) from the circulation into the brain where they localised within mouse BT. Furthermore, MDT of magnetised Temozolomide (TMZmag+) significantly reduced tumour growth and extended mouse survival to 48 days compared to the other treatment groups. Using the same principles, we built a proof of principle scalable magnetic device for human use with a strength of 1.1T. This magnetic device demonstrated trapping of MNP undergoing flow at distances up to 5cm. MDT using our magnetic device provides an opportunity for targeted delivery of magnetised drugs to human BT.

Surface Characteristics and Adhesion of Veneering Composite Resin to PAEK-Based Substructure Restorative Materials.

PURPOSE: To evaluate and compare the shear bond strength (SBS) of composite veneering material to polyetherketoneketone (PEKK), polyetheretherketone (PEEK), zirconia (YZ), and nickel-chromium alloy (NiCr) substructure restorative materials. MATERIALS AND METHODS: Forty samples (12 × 2 mm) were prepared from four materials: PEKK, PEEK, zirconia, and NiCr alloy (n = 10). The Vickers hardness was evaluated before preparing the surface for bonding by shot-blasting using 110 µm Al2 O3 particles. The surface roughness (Ra) of each sample was determined using a noncontact optical profilometer. The veneering resin was bonded onto each sample following primer application. The prepared samples were then subjected to an SBS test using a universal testing machine at 0.5 mm/min crosshead speed. Failure modes and surface topography following debonding were assessed. The data were statistically analyzed using ANOVA and Tukey's post-hoc comparison test (p < 0.05).  RESULTS: The highest and lowest mean surface roughness was observed in PEEK (3.45 ±0.13 µm) and NiCr (1.87 ±0.07 µm) materials, respectively. A significant difference in roughness values was observed between the materials except for NiCr and YZ (p = 0.547). Concerning SBS, PEEK and NiCr exhibited the highest (16.23 ±0.96 MPa) and lowest (10.1 ±0.63 MPa) values. The mean difference in SBS indicated a statistically significant difference between the material groups (p < 0.01). CONCLUSIONS: PEKK materials demonstrated significantly lower SBS than PEEK and significantly higher SBS values than conventional zirconia and alloy materials. A positive and significant correlation between mean roughness and SBS was observed, but the causality could be either intrinsic to the material or the roughness.

Laboratory Evaluation of Production Efficiency for Removable Partial Denture Frameworks Using In-House Casting vs Outsourced Additive Manufacturing Techniques

PURPOSE: To compare the production efficiency of selective laser sintering (SLS) to traditional casting for the fabrication of metal prosthodontic frameworks in a prospective pilot evaluation in a hospital prosthodontic laboratory setting. MATERIALS AND METHODS: The time taken to complete each of the identified stages in the production of 50 removable partial denture frameworks made using either SLS (n = 25) or casting (n = 25) workflows was measured. The mean time for production was calculated for each workflow, and the difference was tested for statistical significance. RESULTS/CONCLUSION: The results indicate that an SLS workflow may be more time-efficient, and further cost-effectiveness research is indicated.

Fatigue behavior and damage modes of high performance poly-ether-ketone-ketone PEKK bilayered crowns.

OBJECTIVES: To evaluate and compare the fatigue behavior (fatigue limit and fatigue life) and damage modes of high-performance poly-ether-ketone-ketone (PEKK), zirconia and alloy bilayered crowns. MATERIALS AND METHODS: A total of 110 crowns (n = 50 for fatigue limit and n = 60 for fatigue life) were fabricated and used in this study. Pekkton® ivory discs, yttrium stabilized zirconia blanks and NiCr casting alloy were used to produce the respective PEKK, zirconia and alloy copings for crown fabrication. The prepared crowns were veneered with composite resin and subjected to fatigue tests. The fatigue limit was evaluated using the staircase method and the fatigue life of the samples was evaluated by subjecting the crowns to a load lower than the fatigue limit of that particular group, and also with an intermediate load of 522 N. A graphical plot was generated from the shape parameter (ß) and life parameter (α) values obtained through the Weibull analysis method. Kruskal-Wallis and Mann-Whitney tests were applied to determine the significance differences in the recorded fracture mode between the study groups. The damage modes of the samples were assessed using Burke's classification. RESULTS: The recorded fatigue limits of the groups were 442.8 ± 42.1 N, 608.7 ± 7.6 N, and 790.4 ± 29.2 N for zirconia, NiCr and PEKK, respectively. A significant difference in the fatigue limit of the groups was observed (p < 0.05). PEKK samples demonstrated the highest survival cycles of 1,170,000 and the lowest survival cycles was observed with zirconia samples at 100,000 under 522 N loading. The fracture modes in PEKK samples were largely distributed between code 1 and 2 whereas the fracture modes in NiCr group was distributed between code 1 and 4 and YZ crowns exhibited more of code 5 fractures. The difference in fracture modes among the groups was statistically significant (p < 0.05). CONCLUSION: The PEKK group demonstrated better results compared to zirconia and NiCr based crowns. The PEKK group demonstrated high fatigue limit and survived the highest fatigue life cycles among the tested groups.

Determination of Polyetheretherketone (PEEK) mechanical properties as a denture material.

PURPOSE: To optimize the gypsum mold temperatures for pressed PEEK, and to estimate the impact, tensile strength and flexural properties of pressed and milled PEEK. Where appropriate, these properties were compared with those of PMMA. MATERIALS AND METHODS: Since the mold temperature could affect the properties of the injected parts, the temperature of 20 gypsum specimens was monitored using the multi-thermocouple system (n = 5). A total of 210 specimens were prepared for mechanical tests according to the ISO standard for denture base polymer (n = 10). The Izod impact, tensile strength, and flexural behavior were assessed. PEEK-OptimaNI1 (PEEK-pressed) was tested after processing via the pressing method at4 different mold temperatures. Machining PEEK-Juvora (PEEK-milled) specimens were prepared using the CAD-CAM production method. Data were analyzed via one-way ANOVA performed at a confidence level of 95% and a significant P-value of (P ≤ 0.05). RESULTS: In comparison to the furnace temperature more heat was required to preheat the gypsum mold up to 100, 150, 175 and 200 °C for pressing purposes. The highest impact strength was 5.7 kJ/m2 for PEEK-pressed at 100 °C mold temperature and 4 kJ/m2 for PEEK-milled. The latter had a higher tensile strength of 118 MPa. The best result for PEEK-pressed was 97 MPa at 200 °C mold temperature. Under a 4-point bending test, Young's modulus of PEEK-milled was 5591 MPa, while the highest for PEEK-pressed was 4936 MPa at 200 °C mold temperature. CONCLUSIONS: Compared to PMMA, given the superior mechanical properties of PEEK, it may become the material of choice for future use. Dentures constructed from PEEK polymer could well be routinely constructed in the near future.

Comparing the optical and mechanical properties of PEKK polymer when CAD/CAM milled and pressed using a ceramic pressing furnace.

The aim was to optimise the hot pressing parameters for processing PEKK polymer using a standard ceramic pressing furnace and compare the optical and mechanical properties of pressed samples to PEKK samples produced via CAD/CAM milling. The samples were compared using a spectrophotometer to determine the CIE L*a*b* colour values and ΔE colour difference. A universal testing machine was used for biaxial flexural strength testing and Vickers Hardness machine for measuring the hardness. It was concluded that hot pressed and milled PEKK samples showed no significant difference in the colour values, biaxial flexural strength or hardness.

Characterisation of machinable structural polymers in restorative dentistry.

OBJECTIVES: To characterise the mechanical properties of the machinable polymers Pekkton® (Cendres-Meteaux, Biel/Bienne, Switzerland), Lava Ultimate® (3MESPE, Seefeld, Germany), Vita Enamic® (Ivoclar Vivadent, Schaan, Liechtenstein) and the ceramic IPS e.Max Press® (Ivoclar Vivadent, Schaan, Liechtenstein). To determine the structural integrity of full coverage crowns fabricated from these materials. METHODS: The following tests were conducted: Biaxial flexural strength (BFS) using the piston on 3 balls jig (n=10); Vickers Hardness (VH) 10 indentations per sample with 10kg load & 20s dwell time (n=5); Hygroscopic Expansion Change (HEC) in artificial saliva over 68 days (n=5). Structural Strength (SS) of teeth analogues (n=20) restored with monolithic crowns from the four materials. Mean values and standard deviations for BFS, VH, HEC and SS tests were calculated and compared using one-way ANOVA with post-hoc Tukey's test at a level of 5% significance. RESULTS: BFS: IPS e.Max Press® (317MPa±37MPa), Pekkton® (227MPa±18MPa), Lava Ultimate® (145MPa±18MPa) and Vita Enamic® (137MPa±7MPa) with a significance between groups of p<0.0001. VH: IPS e.Max Press® (5064MPa±131MPa), Vita Enamic® (1976MPa±12MPa), Lava Ultimate® (924MPa±27MPa) and Pekkton® (445MPa±21MPa) with a significance between groups of p<0.0001. HEC (%vol change): Pekkton® (0.14%±0.14%), Vita Enamic® (0.38%±0.16%) and Lava Ultimate® (1.06%±0.17%). SS for full-coverage crowns: Pekkton® (2037N±49N no fracture), IPS e.Max Press® (1497N±165N), Lava Ultimate® (1476N±142N) and Vita Enamic® (1127N±108N). SIGNIFICANCE: The properties investigated suggest that full coverage monolithic PEKK crowns possess adequate mechanical and physical properties for use in the posterior region of the mouth. These results must be considered alongside other data including clinical studies.

The effects of different opacifiers on the translucency of experimental dental composite resins.

OBJECTIVE: The aim of this study was to evaluate the effects of different opacifiers on the translucency of experimental dental composite-resins. METHODS: Three metal oxides that are used as opacifiers were tested in this study: titanium oxide (TiO2), aluminium oxide (Al2O3) and zirconium oxide (ZrO2). Experimental composite-resins were fabricated containing 25wt.% urethane dimethacrylate (UDMA)-based resin matrix and 75% total filler including different concentrations of metal oxides (0, 0.25, 0.5, 0.75 and 1wt.%) blended into silane treated barium-silicate filler. The specimens (15.5mm diameter and 1mm thickness) were light-cured and tested in the transmittance mode using a UV/VIS spectrophotometer at wavelengths from 380 to 700nm under a standard illuminant D65. The color differences (ΔE* ab) between different concentrations of opacifiers were also measured in transmittance mode based on their Lab values. RESULTS: Statistical analysis by ANOVA and Tukey's test showed a significant decrease (p<0.05) in light transmittance with the addition of opacifiers to the experimental composite-resins. There was a linear correlation between different concentrations of TiO2 and Al2O3 and total transmittance. Total transmittance was also found to be wavelength dependent. The color differences for the concentrations of 0-1wt.% of the opacifiers were above 1 ΔE* unit, with Al2O3 showing the smallest color shift. SIGNIFICANCE: The type and the amount of the opacifiers used in this study had a significant effect on the translucency of the experimental UDMA-based dental composite resins. The most effective opacifier was TiO2, followed by ZrO2 and Al2O3 in decreasing order, respectively.

Fracture resistance of zirconia-composite veneered crowns in comparison with zirconia-porcelain crowns.

The objectives were to evaluate the fracture resistance and stress concentration in zirconia/composite veneered crowns in comparison to zirconia/porcelain crowns using occlusal fracture resistance and by stress analysis using finite element analysis method. Zirconia substructures were divided into two groups based on the veneering material. A static load was applied occlusally using a ball indenter and the load to fracture was recorded in Newtons (N). The same crown design was used to create 3D crown models and evaluated using FEA. The zirconia/composite crowns subjected to static occlusal load showed comparable results to the zirconia/porcelain crowns. Zirconia/composite crowns showed higher stress on the zirconia substructure at 63.6 and 50.9 MPa on the zirconia substructure veneered with porcelain. In conclusion, zirconia/composite crowns withstood high occlusal loads similar to zirconia/porcelain crowns with no significant difference. However, the zirconia/composite crowns showed higher stress values than the zirconia/porcelain crowns at the zirconia substructure.

Validity of the UKCAT in applicant selection and predicting exam performance in UK dental students.

The United Kingdom's Clinical Aptitude Test (UKCAT) aims to assess candidates' "natural talent" for dentistry. The aim of this study was to determine the validity of the UKCAT for dental school applicant selection. The relationship of the UKCAT with demographic and academic variables was examined, assessing if the likelihood of being offered a place at a UK dental school was predicted by demographic factors and academic selection tools (predicted grades and existing school results). Finally, the validity of these selection tools in predicting first-year dental exam performance was assessed. Correlational and regression analyses showed that females and poorer students were more likely to have lower UKCAT scores. Gender and social class did not, however, predict first-year dental exam performance. UKCAT scores predicted the likelihood of the candidate being offered a place in the dental course; however, they did not predict exam performance during the first year of the course. Indeed, the only predictor of dental exam performance was existing school results. These findings argue against the use of the UKCAT as the sole determinant in dental applicant selection, instead highlighting the value of using existing school results.

Assessment of the risk of bias in rehabilitation reviews.

Systematic reviews are used to inform practice, and develop guidelines and protocols. A questionnaire to quantify the risk of bias in systematic reviews, the review paper assessment (RPA) tool, was developed and tested. A search of electronic databases provided a data set of review articles that were then independently reviewed by two assessors using the RPA. The inter-rater reliability was between moderate and good (κ scores 0.46-0.95). Many reviews did not describe the purpose in terms of population, intervention, comparator and outcome measure (i.e. PICO format), making inter-rater agreement on this question difficult. The RPA discriminated between high-quality reviews and those with a risk of bias (e.g. inadequate reporting of search terms, lack of independent reviewing or inclusion of non-randomized-controlled trials). The RPA questionnaire was revised to ensure that questions (on the basis of clarity of purpose, extent of search, independence of reviewers, randomized-controlled trial inclusion and availability of data) had dichotomous answers so that the positive responses scored one. The risk of bias increases as the score reduces.

Relationship between Color and Translucency of Multishaded Dental Composite Resins.

The aim of the present study was to compare the translucency of different shades of two highly aesthetic multilayered restorative composite resins. In total nine shades from Esthet.X and ten shades from Filtek Supreme composite resins were chosen. Discs of each shade were prepared (N = 3) and light-cured. Total and diffuse transmittance values for each sample were measured. Statistical analysis showed that the opaque dentine shades of both composites were the least translucent and the enamel shades had the highest translucency. There was a significant decrease in translucency from A2 to C2 of regular body shades and also from A4 to C4 of opaque dentine shades of Esthet.X composite resin. Grey enamel shade had a significantly higher diffuse translucency compared to clear and yellow enamel shades. There was a significant decrease in translucency from A2B to D2B and also in diffuse translucency from A4D to C6D shades of Filtek Supreme composite resin. It can be concluded that the color of the composite resins tested in this study had a significant effect on their translucency. Information on the translucency of different shades of composite resins can be very useful for the clinicians in achieving optimal esthetic restorative outcome.

Optical properties of base dentin ceramics for all-ceramic restorations.

OBJECTIVES: The study was conducted to compare the optical parameters of VM7(®) M-shade base dentin ceramics (VITA, Germany) for all ceramic restorations to the chemical composition across the 3D-MASTER(®) shade system. METHODS: Three disc samples, 13 mm diameter and 1.4 mm thickness, were produced for each M-shade following the manufacturer's instructions. Each disc was ground and polished to a thickness of 1.0 mm. Spectral light transmittance and reflectance data were recorded in the visible spectrum under the standard illuminant D65 and 2° observer at 10 nm intervals by using a computer-controlled spectrophotometer. Opacity, translucency and opalescence parameters were determined for each sample. RESULTS: (1) Spectral transmittance and reflectance in the short-wavelength range systematically decreased with increasing chroma number (M1, M2, M3) when compared within the same value (lightness) group. (2) Spectral transmittance and reflectance decreased systematically across the whole visible spectrum with increasing value group number when compared within the same chroma group. (3) Analysis of relationship between chemical composition and various optical parameters for all the samples showed the significant contribution of ZrO2 and Y2O3 substances to optical properties of the present material. SIGNIFICANCE: Systematic variations in optical properties of VM7(®) M-shade base dentin ceramics were observed throughout the 3D-MASTER(®) shade system and were suggested to be caused by the fine structure of the sample which can interfere with shorter wavelengths in the visible spectrum.

Effect of resin matrix composition on the translucency of experimental dental composite resins.

OBJECTIVES: The purpose of this study was to investigate the effect of the resin matrix composition on the translucency of experimental dental composite resins. METHODS: Three types of unfilled resin matrices (TEGDMA-, UDMA- and BisGMA-based) were formulated and light cured. In addition, six different experimental dental composite resins with constant filler loading but varying in the type of monomer and the content of BisGMA were fabricated. Discs of each test material with 15.5mm diameter and 1.0mm thickness were prepared (N=3) and light cured. Total and diffuse transmittance values for each sample were measured using a UV/VIS spectrophotometer with the range of readings from 380 to 700nm. Difference in color was measured using the CIE Lab system. RESULTS: Statistical analysis by one-way ANOVA followed by Tukey's test showed that there was no statistically significant difference in transmittance values between the three unfilled resins. However, with the addition of filler, BisGMA-containing composite resins showed significantly higher transmittance values than the UDMA- and TEGDMA-based composite resins. Regression analysis revealed that there was a linear correlation between the percentage of BisGMA in the resin matrix and the total and diffuse translucency. SIGNIFICANCE: The amount of BisGMA used in the resin matrix has a significant effect on the translucency of silica filler-containing dental composite resins.

Spectral reflectance and color of dentin ceramics for all-ceramic restorations.

OBJECTIVE: The study was conducted to observe the spectral reflectance curves, and evaluate the color coordinates (CIELAB) of VM7 dentin ceramics (VITA, Germany) across the whole 3D-MASTER shade system. METHODS: Three disc samples, 13 mm in diameter and 1.4mm in thickness, were produced for each shade by firing following the manufacturer's instructions. Each fired disc was ground to a thickness of 1.0 mm and both faces were polished. Spectral reflectance data in the visible spectrum under the standard illuminant D65 were collected at 1 nm intervals by using a computer-controlled spectrophotometer. Color coordinates, L*, a*, b*, C*, h, in the three-dimensional CIELAB color space were obtained. RESULTS: (1) Spectral reflectance in the short-wavelength range systematically decreased with increasing chroma number (M1, M2, and M3) when compared within the same value (lightness) group (1M, 2M, 3M, 4M, and 5M). (2) Spectral reflectance decreased systematically across the whole visible spectrum with increasing value group when compared within the same chroma group. (3) A negative relationship was recognized between lightness (L*) and chromaticity index a* (red-green direction). That is, a* coordinate increases from approximately 1 for the 1M1 sample to approximately 13 for the 5M3 sample, the corresponding lightness systematically decreased from 87 to 69. (4) With increasing a* coordinate, hue angle (h) significantly decreased from 85 degrees for the 1M1 sample to 69 degrees for the 5M3 sample. (5) Lightness apparently increased with increasing hue angle (h) throughout the whole range of the 3D-MASTER shade system. (6) A strong positive relationship between chroma (C*) and chromaticity index b* (yellow-blue direction) was found, demonstrating that the chroma of the present ceramic is mainly controlled by the b* coordinate. SIGNIFICANCE: Systematic variations in spectral reflectance and color coordinates of VM7 dentin were observed throughout the 3D-MASTER shade system and were suggested to be caused by the fine structure of the sample which can interfere with shorter wavelengths in the visible spectrum.

The effect of combined use of botulinum toxin type A and functional electric stimulation in the treatment of spastic drop foot after stroke: a preliminary investigation.

OBJECTIVE: To investigate the effect of combined botulinum toxin type A (BTX) and functional electric stimulation (FES) treatment on spastic drop foot in stroke. DESIGN: Nonblinded randomized controlled trial. SETTING: Hospitals. PARTICIPANTS: Consecutive sample of 21 ambulant adults within 1 year after stroke with a spastic drop foot, of whom 18 completed the study. INTERVENTIONS: The treatment group received BTX injections (Dysport) on 1 occasion into the medial and lateral heads of the gastrocnemius (200U each) and tibialis posterior (400U each) muscles and FES, used on a daily basis for 16 weeks to assist walking. Both groups continued with physiotherapy at the same rate. MAIN OUTCOME MEASURES: Walking speed, Physiological Cost Index, Modified Ashworth Scale, Rivermead Motor Assessment, and Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: Walking speed increased over 12 weeks in both control (P=.020) and treatment groups (nonstimulated, P=.004; stimulated, P=.042). The baseline corrected (analysis of covariance) increase in mean walking speed at 12 weeks, relative to controls, was.04m/s (95% confidence interval [CI],.003-.090) without stimulation, and.09m/s (95% CI,.031-.150) with stimulation. CONCLUSIONS: Combined treatment effectively improved walking and function. A larger study is needed to quantify the treatment effect and to investigate its impact on quality of life.

New results in feedback control of unsupported standing in paraplegia.

The aim of this study was to implement a new approach to feedback control of unsupported standing and to evaluate it in tests with an intact and a paraplegic subject. In our setup, all joints above the ankles are braced and stabilizing torque at the ankle is generated by electrical stimulation of the plantarflexor muscles. A previous study showed that short periods of unsupported standing with a paraplegic subject could be achieved. In order to improve consistency and reliability and to prolong the duration of standing, we have implemented several modifications to the control strategy. These include a simplified control structure and a different controller design method. While the reliability of standing is mainly limited by the muscle characteristics such as reduced strength and progressive fatigue, the results presented here show that the new strategy allows much longer periods (up to several minutes) of unsupported standing in paraplegia.

Is the spinal cord the generator of 16-Hz orthostatic tremor?

Primary orthostatic tremor is characterized by 16-Hz motor activity that is coherent between muscles. It has been suggested that this tremor originates in the brain. This view is questioned by findings from a patient with complete paraplegia who experiences intermittent leg spasms at rest. The EMG activity within the spasms showed a 16-Hz component that was coherent between muscles unilaterally and bilaterally. This raises the possibility that the spinal cord could be the source of orthostatic tremor.

Spinally generated electromyographic oscillations and spasms in a low-thoracic complete paraplegic.

We have measured some oscillatory properties of severe lower limb spasms experienced by a low-thoracic complete paraplegic during assisted standing. Electromyograms (EMG) were recorded from the leg muscles while the patient stood passively in a standing frame. The patient also stood using functional electrical stimulation (FES) while ground and handle reaction force vectors were measured together with EMG activity. During passive standing, spasms appeared simultaneously in all leg muscle groups on one side. The interval between spasms varied between 3 and 30 seconds. Within the spasms, there was a tendency of repetitive grouped discharge of motor units as well as a strong 10-Hz component in the EMG that was coherent across ipsilateral muscle groups. Thus, the spasms were inherently oscillatory. During FES-assisted standing, clinically similar spasms were observed. However, the interspasm interval became relatively fixed at around 16 seconds, which may indicate entraining of the spasm cycle by FES. There are similarities between this patient's spasms and the pathological motor activities seen in other movement disorders that may also be of spinal origin.

Control of leg-powered paraplegic cycling using stimulation of the lumbo-sacral anterior spinal nerve roots.

We investigated leg-powered cycling in a recumbent tricycle for a paraplegic using functional electrical stimulation (FES) with the lumbo-sacral anterior root stimulator implant (LARSI). A female complete T9 paraplegic had a stimulator for the anterior L2 to S2 spinal roots (bilaterally) implanted in 1994. She was provided with equipment for daily FES cycling exercise at home. The cycling controller applies a pattern of stimulation in each of 16 crank angle phases. A 7-bit shaft encoder measures the crank angle with adequate precision. Each pattern was originally chosen to give the greatest propulsive force in that position when there was no motion. However, dynamically, some reduction in co-contraction is needed; also the patterns are applied with a preset advance time. Maximal power is obtained with an advance of 250 ms, which compensates for muscle response delay and accommodates changes in cadence (from about 25 to 85 rpm). With this system, she has cycled 1.2 km at a time on gently undulating road. We found that spinal root stimulation gives sufficient control over the muscles in the legs to produce a fluid cycling gait. We propose that root stimulation for leg cycling exercise may be a practicable and valuable function for paraplegics following spinal cord injury.