The receptor activator of NF-κB ligand-osteoprotegerin system in pulpal and periapical disease

AIM: To summarize the collective in vitro, in vivo and clinical evidence of the involvement of the receptor activator of NF-κB ligand (RANKL)-osteoprotegerin (OPG) system, a system of two molecules controlling osteoclast differentiation and hard-tissue resorption, in pulpal and periapical pathophysiology. METHODOLOGY: A systematic search related to RANKL and/or OPG and pulp or periapical disease was conducted on Medline, Biosis, Cochrane, Embase and Web of Science databases using keywords and controlled vocabulary. No language restriction was applied. Two independent reviewers first screened titles and abstracts and then the full texts that were initially included. The reference lists of the identified publications were examined for additional titles. RESULTS: A total of 33 papers were identified. In vitro studies (N = 11) revealed that pulpal cells can be stimulated by various inflammatory agents to produce RANKL, whilst many studies did not consider the RANKL/OPG ratio. Animal studies (N = 9) mostly focused on the time course and development of periapical lesions in relation to the RANKL-OPG system. Levels of RANKL and OPG in the necrotizing pulp were not investigated. Human studies (N = 13) showed a steady-state expression of OPG in the odontoblast layer. Conflicting results have been reported regarding the role of RANKL in active apical periodontitis, again because the correlation of this molecule with its inhibitor (OPG) was often disregarded. CONCLUSIONS: There is relatively little information currently available that would highlight the specific role of RANKL and OPG in pulpal and periapical disease. OPG may play a protective role against internal resorption, whilst an increased periapical RANKL/OPG ratio might indicate bone resorption

Analysis of the Hydrogen-rich Magnetic White Dwarfs in the SDSS

We have calculated optical spectra of hydrogen-rich (DA) white dwarfs with magnetic field strengths between 1 MG and 1000 MG for temperatures between 7000 K and 50000 K. Through a least-squares minimization scheme with an evolutionary algorithm, we have analyzed the spectra of 114 magnetic DAs from the SDSS (95 previously published plus 14 newly discovered within SDSS, and five discovered by SEGUE). Since we were limited to a single spectrum for each object we used only centered magnetic dipoles or dipoles which were shifted along the magnetic dipole axis. We also statistically investigated the distribution of magnetic-field strengths and geometries of our sample.Comment: to appear in the proceedings of the 16th European Workshop on White Dwarfs, Barcelona, 200

PRIRATE 2020 guidelines for reporting randomized trials in endodontics: a consensus-based development

In evidence-based healthcare, randomized clinical trials provide the most accurate and reliable information on the effectiveness of an intervention. This project aimed to develop reporting guidelines, exclusively for randomized clinical trials in the dental specialty of Endodontology, using a well-documented, validated consensus-based methodology. The guidelines have been named: Preferred Reporting Items for RAndomized Trials in Endodontics (PRIRATE) 2020. A total of eight individuals (PD, VN, HD, LB, TK, JJ, EP, SP), including the project leaders (PD, VN) formed a steering committee. The committee developed a checklist based on the items in the Consolidated Standards for Reporting Trials (CONSORT) guidelines and Clinical and Laboratory Images in Publications (CLIP) principles. A PRIRATE Delphi Group (PDG) and PRIRATE Face-to-Face Meeting group (PFMG) were also formed. Thirty PDG members participated in the online Delphi process and achieved consensus on the checklist items and flowchart that make up the PRIRATE guidelines. The guidelines were discussed at a meeting of the PFMG at the 19th European Society of Endodontology (ESE) Biennial congress, held on 13th September 2019 in Vienna, Austria. A total of 21 individuals from across the globe and four steering committee members (PD, VN, HD, LB) attended the meeting. As a consequence of the discussions, the guidelines were modified and then piloted by several authors whilst writing a manuscript. The PRIRATE 2020 guidelines contain a checklist consisting of 11 sections and 58 individual items as well as a flowchart, considered essential for authors to include when writing manuscripts for randomized clinical trials in Endodontics

An overview of population-based algorithms for multi-objective optimisation

In this work we present an overview of the most prominent population-based algorithms and the methodologies used to extend them to multiple objective problems. Although not exact in the mathematical sense, it has long been recognised that population-based multi-objective optimisation techniques for real-world applications are immensely valuable and versatile. These techniques are usually employed when exact optimisation methods are not easily applicable or simply when, due to sheer complexity, such techniques could potentially be very costly. Another advantage is that since a population of decision vectors is considered in each generation these algorithms are implicitly parallelisable and can generate an approximation of the entire Pareto front at each iteration. A critique of their capabilities is also provided

An Ultrasound Assisted Anchoring Technique (BoneWelding® Technology) for Fixation of Implants to Bone – A Histological Pilot Study in Sheep

The BoneWelding® Technology offers new opportunities to anchor implants within bone. The technology melted the surface of biodegradable polymer pins by means of ultrasound energy to mould material into the structures of the predrilled bone. Temperature changes were measured at the sites of implantation in an in vitro experiment. In the in vivo part of the study two types of implants were implanted in the limb of sheep to investigate the biocompatibility of the method. One implant type was made of PL-DL-lactide (PLA), the second one was a titanium core partially covered with PLA. Healing period was 2 and 6 months, with 3 sheep per group. Bone samples were evaluated radiologically, histologically and histomorphometrically for bone remodeling and inflammatory reactions. Results demonstrated mild and short temperature increase during insertion. New bone formed at the implant without evidence of inflammatory reaction. The amount of adjacent bone was increased compared to normal cancellous bone. It was concluded that the BoneWelding® Technology proved to be a biocompatible technology to anchor biodegradable as well as titanium-PLA implants in bone

Biocompatibility and Bone Formation of Flexible, Cotton Wool-like PLGA/Calcium Phosphate Nanocomposites in Sheep

BACKGROUND: The purpose of this preliminary study was to assess the in vivo performance of synthetic, cotton wool-like nanocomposites consisting of a biodegradable poly(lactide-co-glycolide) fibrous matrix and containing either calcium phosphate nanoparticles (PLGA/CaP 60:40) or silver doped CaP nanoparticles (PLGA/Ag-CaP 60:40). Besides its extraordinary in vitro bioactivity the latter biomaterial (0.4 wt% total silver concentration) provides additional antimicrobial properties for treating bone defects exposed to microorganisms. MATERIALS AND METHODS: Both flexible artificial bone substitutes were implanted into totally 16 epiphyseal and metaphyseal drill hole defects of long bone in sheep and followed for 8 weeks. Histological and histomorphological analyses were conducted to evaluate the biocompatibility and bone formation applying a score system. The influence of silver on the in vivo performance was further investigated. RESULTS: Semi-quantitative evaluation of histology sections showed for both implant materials an excellent biocompatibility and bone healing with no resorption in the adjacent bone. No signs of inflammation were detectable, either macroscopically or microscopically, as was evident in 5 µm plastic sections by the minimal amount of inflammatory cells. The fibrous biomaterials enabled bone formation directly in the centre of the former defect. The area fraction of new bone formation as determined histomorphometrically after 8 weeks implantation was very similar with 20.5 ± 11.2 % and 22.5 ± 9.2 % for PLGA/CaP and PLGA/Ag-CaP, respectively. CONCLUSIONS: The cotton wool-like bone substitute material is easily applicable, biocompatible and might be beneficial in minimal invasive surgery for treating bone defects

Harvesting Candidate Genes Responsible for Serious Adverse Drug Reactions from a Chemical-Protein Interactome

Identifying genetic factors responsible for serious adverse drug reaction (SADR) is of critical importance to personalized medicine. However, genome-wide association studies are hampered due to the lack of case-control samples, and the selection of candidate genes is limited by the lack of understanding of the underlying mechanisms of SADRs. We hypothesize that drugs causing the same type of SADR might share a common mechanism by targeting unexpectedly the same SADR-mediating protein. Hence we propose an approach of identifying the common SADR-targets through constructing and mining an in silico chemical-protein interactome (CPI), a matrix of binding strengths among 162 drug molecules known to cause at least one type of SADR and 845 proteins. Drugs sharing the same SADR outcome were also found to possess similarities in their CPI profiles towards this 845 protein set. This methodology identified the candidate gene of sulfonamide-induced toxic epidermal necrolysis (TEN): all nine sulfonamides that cause TEN were found to bind strongly to MHC I (Cw*4), whereas none of the 17 control drugs that do not cause TEN were found to bind to it. Through an insight into the CPI, we found the Y116S substitution of MHC I (B*5703) enhances the unexpected binding of abacavir to its antigen presentation groove, which explains why B*5701, not B*5703, is the risk allele of abacavir-induced hypersensitivity. In conclusion, SADR targets and the patient-specific off-targets could be identified through a systematic investigation of the CPI, generating important hypotheses for prospective experimental validation of the candidate genes