Accuracy assessment of 3D-printed tooth replicas.

AIM: The production of individual tooth replicas has two applications in dental practice: tooth autotransplantations and dental root analogue implants. These applications require a particularly high degree of precision. The purpose of this study was to establish and evaluate a method for fabricating individual 3D-printed tooth replicas. MATERIALS AND METHODS: 10 patients requiring extraction of a wisdom tooth and a preoperative cone beam computed tomography (CBCT) scan were included; exclusion criteria were intraoperative fragmentation or fracture of the tooth. 3D Slicer 4.6.2 was used for tooth segmentation and model generation based on CBCT data. The tooth replicas were manufactured by selective laser melting (SLM). The extracted teeth and 3D-printed replicas were scanned and tested for surface deviations in CloudCompare 2.8.1. RESULTS: The mean absolute surface deviation between the 3D-printed teeth and the corresponding extracted teeth ranged from 0.13 to 0.25 mm, with standard deviations of 0.10 to 0.21 mm; 95% of the measured surface points deviated less than 0.474 mm; the surface area was reduced by -6.0% and the volume by -3.4%. The root mean square was 0.238 mm and the mean maximum absolute surface deviation was 0.927 mm. The SLM technique showed a high precision with a mean absolute deviation of 0.045 mm and a standard deviation of 0.04 mm. CONCLUSION: 3D-printed tooth replicas with a very high accuracy could be produced based on CBCT data. The described method is suitable for manufacturing tooth replicas for use in tooth autotransplantations or for fabricating root analogue implants.

Techno-economic feasibility of waste biorefinery: Using slaughtering waste streams as starting material for biopolyester production.

The utilization of industrial waste streams as input materials for bio-mediated production processes constitutes a current R&D objective not only to reduce process costs at the input side but in parallel, to minimize hazardous environmental emissions. In this context, the EU-funded project ANIMPOL elaborated a process for the production of polyhydroxyalkanoate (PHA) biopolymers starting from diverse waste streams of the animal processing industry. This article provides a detailed economic analysis of PHA production from this waste biorefinery concept, encompassing the utilization of low-quality biodiesel, offal material and meat and bone meal (MBM). Techno-economic analysis reveals that PHA production cost varies from 1.41 €/kg to 1.64 €/kg when considering offal on the one hand as waste, or, on the other hand, accounting its market price, while calculating with fixed costs for the co-products biodiesel (0.97 €/L) and MBM (350 €/t), respectively. The effect of fluctuating market prices for offal materials, biodiesel, and MBM on the final PHA production cost as well as the investment payback time have been evaluated. Depending on the current market situation, the calculated investment payback time varies from 3.25 to 4.5years.

First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers.

BACKGROUND: α-Synuclein is a major component of pathologic inclusions that characterize Parkinson's disease. PRX002 is an antibody that targets α-synuclein, and its murine parent antibody 9E4 has been shown in preclinical studies to reduce α-synuclein pathology and to protect against cognitive and motor deteriorations and progressive neurodegeneration in human α-synuclein transgenic mice. METHODS: This first-in-human, randomized, double-blind, placebo-controlled, phase 1 study assessed the impact of PRX002 administered to 40 healthy participants in 5 ascending-dose cohorts (n = 8/cohort) in which participants were randomly assigned to receive a single intravenous infusion of study drug (0.3, 1, 3, 10, or 30 mg/kg; n = 6/cohort) or placebo (n = 2/cohort). RESULTS: PRX002 demonstrated favorable safety, tolerability, and pharmacokinetic profiles at all doses tested, with no immunogenicity. No serious adverse events, discontinuations as a result of adverse events, or dose-limiting toxicities were reported. Serum PRX002 exposure was dose proportional; the average terminal half-life across all doses was 18.2 days. A significant dose-dependent reduction in free serum α-synuclein (unbound to PRX002) was apparent within 1 hour after PRX002 administration, whereas total α-synuclein (free plus bound) increased dose-dependently, presumably because of the expected change in kinetics following antibody binding. CONCLUSIONS: This study demonstrates that serum α-synuclein can be safely modulated in a dose-dependent manner after single intravenous infusions of an anti-α-synuclein antibody. These findings support continued development of PRX002, including further characterization of its safety, tolerability, pharmacokinetics, and pharmacodynamic effects in the central nervous system in patients with Parkinson's disease. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study.

BACKGROUND: Carbon-11-labelled Pittsburgh compound B ((11)C-PiB) PET is a marker of cortical fibrillar amyloid-beta load in vivo. We used (11)C-PiB PET to investigate whether bapineuzumab, a humanised anti-amyloid-beta monoclonal antibody, would reduce cortical fibrillar amyloid-beta load in patients with Alzheimer's disease. METHODS: Patients with mild-to-moderate Alzheimer's disease were randomly assigned to receive intravenous bapineuzumab or placebo in a ratio of seven to three in three ascending dose groups (0.5, 1.0, or 2.0 mg/kg). Each dose group was enrolled after safety review of the previous group. Randomisation was by interactive voice response system; masking was achieved with numbered kit allocation. Patients, investigators, study site personnel, sponsor staff, and carers were masked to treatment. Patients received up to six infusions, 13 weeks apart, and had (11)C-PiB PET scans at baseline and at weeks 20, 45, and 78. The primary outcome was the difference between the pooled bapineuzumab group and the pooled placebo group in mean change from screening to week 78 in (11)C-PiB cortical to cerebellar retention ratio averaged across six cortical regions of interest. Analysis was by modified intention to treat. This study is registered with EudraCT, number 2004-004120-12; ISRCTN17517446. FINDINGS: 28 patients were assigned to bapineuzumab (n=20) or placebo (n=8). 19 patients in the bapineuzumab group and seven in the placebo group were included in the modified intention-to-treat analysis. Estimated mean (11)C-PiB retention ratio change from baseline to week 78 was -0.09 (95% CI -0.16 to -0.02; p=0.014) in the bapineuzumab group and 0.15 (95% CI 0.02 to 0.28; p=0.022) in the placebo group. Estimated mean difference in (11)C-PiB retention ratio change from baseline to week 78 between the bapineuzumab group and the placebo group was -0.24 (95% CI -0.39 to -0.09; p=0.003). Differences between the bapineuzumab group and the placebo group in the individual regions of interest were similar to the overall mean difference. Adverse events were typically mild to moderate in severity and transient. Two patients in the 2.0 mg/kg bapineuzumab group had transient cerebral vasogenic oedema. INTERPRETATION: Treatment with bapineuzumab for 78 weeks reduced cortical (11)C-PiB retention compared with both baseline and placebo. (11)C-PiB PET seems to be useful in assessing the effects of potential Alzheimer's disease treatments on cortical fibrillar amyloid-beta load in vivo. FUNDING: Elan Pharmaceuticals and Wyeth Research.

Assessment of formal and low structured kinetic modeling of polyhydroxyalkanoate synthesis from complex substrates.

A formal kinetic mathematical model for poly-(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxybutyrate) [P(3HB-co-3HV-co-4HB)] terpolyester synthesis from glucose and galactose derived from whey permeate supplemented with gamma-butyrolactone by the archaeon Haloferax mediterranei was created. Further, a low structured mathematical model for poly-3-hydroxybutyrate synthesis from whey permeate by Pseudomonas hydrogenovora was developed. In both cases, biosyntheses for obtaining the experimental data used for compiling the models were performed via fed-batch cultivations. The model developed for H. mediterranei consists of 10 differential and 11 algebraic equations, including 27 kinetic constants. The model compiled for P. hydrogenovora encompasses 10 differential and 3 algebraic equations, including 36 kinetic constants. Both models were solved by Runge-Kuta variable step numerical integration with Monte Carlo parameter optimization procedure. Difficulties arising from the modeling of redirection of metabolic fluxes from biomass growth toward polyhydroxyalkanoate synthesis and byproducts are discussed.