Medications and Orthodontic Tooth Movement: What Accelerates and Diminishes Tooth Movement?

The biological aspect of orthodontic tooth movement is influenced by the magnitude and duration of the applied force. This initiates signaling cascades essential for bone remodeling, which involve activating various cell signaling pathways that enhance the metabolism of the periodontal ligament, leading to localized bone resorption and deposition. This process facilitates tooth movement on the pressure side and promotes healing on the tension side. The remodeling associated with orthodontic tooth movement is an inflammatory reaction involving mediators. Key components in this process include hormones, systemic influences, cyclic adenosine monophosphate, specific cytokines like interleukin 1, colony-stimulating factors, calcium, collagenase, and prostaglandins, all of which are essential for the biological adjustments necessary for tooth movement. Medications that influence molecular pathways critical for the homeostasis of periodontal tissues or that affect changes during orthodontic tooth movement and clastic cell regulation can potentially modulate tooth movement. With the recent increase in prescription medication use, it is essential for clinicians to be aware of medication consumption in prospective patients and understand its potential impact on orthodontic treatment. This review aimed to explore the effects of commonly prescribed medications on the rate of orthodontic tooth movement, thoroughly review the existing evidence on this topic, and identify potential areas for future research.

An Evaluation of the Rate and Type of Orthodontic Tooth Movement When Injecting Platelet-Rich Plasma During Mini-Implant-Based Segmented en-Masse Retraction of Upper Anterior Teeth.

INTRODUCTION: The study aimed to determine the influence of palatal injection of platelet-rich plasma (PRP) on the rate and type of orthodontic tooth movement (OTM) during the en-masse retraction of upper anterior teeth. MATERIALS AND METHODS: Two-arm parallel-group trial, in which 30 class II division 1 adult patients (7 males and 23 females) aged 16 to 27 years were recruited. The sample was randomly divided into two groups: the experimental group, in which PRP was injected in the palatal mucosa of the maxillary six anterior teeth immediately before starting the en-masse retraction of upper anterior teeth, whereas in the control group, traditional treatment was employed. Following the first premolar extraction, space closure was accomplished using frictionless mechanics for the en-masse retraction of upper anterior teeth. In both groups, a rigid segmented arch made of stainless steel with a diameter of 0.021 x 0.025 inch and an 8-mm power arm was used for the upper anterior teeth, and mini-implants were inserted between the upper second premolar and first molar at 8 mm apical from the archwire line. NiTi coil springs were used for retraction. Measurements were recorded at the onset of space closure (T0) and every 40 days till the middle of the en-masse retraction of upper anterior teeth (T1). RESULTS: Thirty patients completed the trial, and no patients were lost to follow-up in both groups. The OTM rate in the PRP group was similar to that of the control group (P = 0.596). The upper anterior teeth in the two groups were retracted mostly by controlled tipping and partially by translation. Statistically insignificant differences were observed between the two groups regarding the rest of the cephalometric variables. No serious harms were observed in either group. CONCLUSIONS: PRP was ineffective in accelerating the OTM rate during the en-masse retraction of upper anterior teeth and it did not affect the type of tooth movement.

Evaluating the efficacy of platelet-rich plasma on orthodontic tooth movement rate: A systematic review and meta-analysis.

BACKGROUND: The main objective of this study was to evaluate the effect of autologous platelet-rich plasma (PRP) on acceleration of the orthodontic tooth movement and assess the evidence based on the available literature. METHODS: The trial was registered and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic databases including PubMed, Cochrane, Scopus, Central Register of Controlled Trials, and Google Scholar were searched for randomized controlled studies of PRP on the rate of tooth movement. The search was restricted to articles published in English between January 2000 to 31 December 2023. The search was completed by two reviewers independently and the risk of bias was evaluated using the Cochrane Risk of Bias tool (RoB 2.0) and meta-analysis was performed. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was done to determine the certainty of evidence. RESULTS: Thirteen studies were included in the systematic review and 10 were included in the quantitative analysis. A random-effects model for meta-analysis of seven studies evaluating the rate of canine retraction revealed a statistically significant increase in the rate of orthodontic tooth movement of 0.38 mm/month in 1 month (121 patients; 95% confidence interval [CI] 0.27-0.49; I2 = 35%; P < 0.001) which decreased to 0.09mm/month in the fourth month (80 patients; 95% CI 0.02-0.17; I2 = 0%; P < 0.02). Three studies that considered en masse retraction revealed a mean difference of 0.36mm over 3 months (40 patients; 95% CI -0.23 to 0.94; I2 = 74%; P < 0.23). CONCLUSIONS: The study suggests that PRP application can accelerate tooth movement, but its effects decreased over 4 months. The results should be interpreted cautiously due to the study's inherent limitations.

Exploring biological mechanisms in orthodontic tooth movement: Bridging the gap between basic research experiments and clinical applications - A comprehensive review.

OBJECTIVES: The molecular mechanisms behind orthodontic tooth movements (OTM) were investigated by clarifying the role of chemical messengers released by cells. METHODS: Using the Cochrane library, Google scholar, and PubMed databases, a literature search was conducted, and studies published from 1984 to 2024 were considered. RESULTS: Both bone growth and remodeling may occur when a tooth is subjected to mechanical stress. These chemicals have a significant effect on the stimulation and regulation of osteoblasts, osteoclasts, and osteocytes during alveolar bone remodeling. This regulation can take place in pathological conditions, such as periodontal diseases, or during OTM alone. This comprehensive review outlines key molecular mechanisms underlying OTM and explores various clinical assumptions associated with specific molecules and their functional domains during this process. Furthermore, clinical applications of certain molecules such as relaxin, prostaglandin E (PGE), and interleukin-1ß (IL-1ß) in accelerating OTM have been reported. Our findings underscore the existing gap between OTM clinical applications and basic research investigations. CONCLUSION: A comprehensive understanding of orthodontic treatment is enriched by insights into biological systems. We reported the activation of osteoblasts, osteoclast precursor cells, osteoclasts, and osteocytes in response to mechanical stress, leading to targeted cellular and molecular interventions and facilitating rapid and regulated alveolar bone remodeling during tooth movement. Despite the shortcomings of clinical studies in accelerating OTM, this review highlights the crucial role of biological agents in this process and advocates for prioritizing high-quality human studies in future research to gain further insights from clinical trials.

SDF-1 involvement in orthodontic tooth movement after tooth extraction.

The stromal cell-derived factor 1 (SDF-1)/chemokine receptor type 4 (CXCR4) axis plays a key role in alveolar bone metabolism during orthodontic tooth movement (OTM). Herein, the effects of the SDF-1/CXCR4 axis on the regional acceleratory phenomenon (RAP) in OTM velocity and on changes in the surrounding periodontium after adjacent tooth extraction in rats were investigated. Six-week-old male Wistar/ST rats underwent left maxillary first molar (M1) extraction and mesial OTM of the left maxillary second molar (M2) with a 10-g force closed-coil spring. Phosphate-buffered saline, immunoglobulin G (IgG) isotype control antibody, or anti-SDF-1 neutralizing monoclonal antibody were injected at the M1 and M2 interproximal areas (10 µg/0.1 mL) for the first three days. Analyses were performed after 1, 3, and 7 days (n = 7). The results demonstrated a significant increase in SDF-1 expression from day 1, which was effectively blocked via anti-SDF-1 neutralizing monoclonal antibody injection. On day 3, the M2 OTM distance and the number of positively stained osteoclasts significantly reduced alongside a reduction in inflammatory markers in the experimental group. Our results demonstrated that serial local injection of the anti-SDF-1 neutralizing monoclonal antibody reduces M2 OTM, osteoclast accumulation, and localized inflammatory responses in an OTM model with tooth extraction-induced RAP.

3D printed models are an accurate, cost-effective, and reproducible tool for quantifying terrestrial thermal environments.

Predicting ecological responses to rapid environmental change has become one of the greatest challenges of modern biology. One of the major hurdles in forecasting these responses is accurately quantifying the thermal environments that organisms experience. The distribution of temperatures available within an organism's habitat is typically measured using data loggers called operative temperature models (OTMs) that are designed to mimic certain properties of heat exchange in the focal organism. The gold standard for OTM construction in studies of terrestrial ectotherms has been the use of copper electroforming which creates anatomically accurate models that equilibrate quickly to ambient thermal conditions. However, electroformed models require the use of caustic chemicals, are often brittle, and their production is expensive and time intensive. This has resulted in many researchers resorting to the use of simplified OTMs that can yield substantial measurement errors. 3D printing offers the prospect of robust, easily replicated, morphologically accurate, and cost-effective OTMs that capture the benefits but alleviate the problems associated with electroforming. Here, we validate the use of OTMs that were 3D printed using several materials across eight lizard species of different body sizes and living in habitats ranging from deserts to tropical forests. We show that 3D printed OTMs have low thermal inertia and predict the live animal's equilibration temperature with high accuracy across a wide range of body sizes and microhabitats. Finally, we developed a free online repository and database of 3D scans (https://www.3dotm.org/) to increase the accessibility of this tool to researchers around the world and facilitate ease of production of 3D printed models. 3D printing of OTMs is generalizable to taxa beyond lizards. If widely adopted, this approach promises greater accuracy and reproducibility in studies of terrestrial thermal ecology and should lead to improved forecasts of the biological impacts of climate change.

The tooth movement efficiency of different orthodontic thermoplastics for clear aligners: study protocol for a randomized controlled clinical trial.

INTRODUCTION: With regard to the esthetics and comfort of orthodontic treatment, the requirement for removable clear aligners (CAs) is increasing. Unlike conventional fixed orthodontic appliances, CAs were made of thermoplastic film by thermoforming on the personalized dental models. The construction of orthodontic thermoplastic is a critical factor for orthodontic tooth movement (OTM). Polyethylene terephthalate glycol-modified (PETG) and thermoplastic polyurethane (TPU) are the most commonly orthodontic thermoplastics; however, the evidence of the differences between different orthodontic thermoplastic are limited to vitro environment and the evidence in vivo environment is not available. Therefore, this trial aims to provide reliable evidence for orthodontists' personalized treatment plans whether the two most commonly used orthodontic thermoplastics of PETG and TPU have differences in the efficiency of OTM. METHODS AND ANALYSIS: This randomized controlled clinical study will recruit 44 orthodontic patients for orthodontic treatment. All the subjects will be randomized into two groups (PETG and TPU, n = 22 for each group). In the first stage (M0 to M1), clear aligners will be made of two orthodontic thermoplastics and move the maxillary first or second premolars 2 mm. In the second stage, patients will take the standard orthodontic treatments. The primary outcome will be the efficiency of clear aligners made of different materials on the digital models. The secondary outcome will be the efficiency of clear aligners made of different materials on the cone-beam computed tomography (CBCT). The efficiency will be calculated through the superimposition of the digital models and CBCT. DISCUSSION: The results from this trial will serve as evidence for orthodontists and manufacturers and clarify whether the difference in orthodontic thermoplastics significantly impacts the efficiency of OTM. TRIAL REGISTRATION NUMBER: ChiCTR2300070980. Registered on 27 April 2023. https://www.chictr.org.cn/showproj.html?proj=186253.

Knockout of bone sialoprotein in cementoblasts cell lines affects specific gene expression in unstimulated and mechanically stimulated conditions.

One of the major components in cementum extracellular matrix is bone sialoprotein (BSP). BSP knockout (Ibsp) mice were reported to have a nonfunctional hypo-mineralized cementum, as well as detachment and disorganization of the periodontal ligament tissue. However, studies investigating the influence of Ibsp in cementoblasts are missing yet. This study investigates the influences of Bsp in three cementoblasts cell lines (OCCM.30-WT,IbspΔNterm, and IbspKAE). The mRNA expression of cementoblast and osteoclast markers (Col1a1, Alpl, Ocn, Runx2, Ctsk, Rankl and Opg) and the cell morphology were compared. Additionally, a functional monocyte adhesion assay was performed. To understand the influence of external stimuli, the effect of Ibsp was investigated under static compressive force, mimicking the compression side of orthodontic tooth movement. Cementoblasts with genotype IbspΔNterm and IbspKAE showed slight differences in cell morphology compared to OCCM.30-WT, as well as different gene expression. Under compressive force, the Ibsp cell lines presented expression pattern markers similar to the OCCM.30-WT cell line. However, Cathepsin K was strongly upregulated in IbspΔNterm cementoblasts under compressive force. This study provides insight into the role of BSP in cementoblasts and explores the influence of BSP on periodontal ligament tissues. BSP markers in cementoblasts seem to be involved in the regulation of cementum organization as an important factor for a functional periodontium. In summary, our findings provide a basis for investigations regarding molecular biology interactions of BSP in cementoblasts, and a supporting input for understanding the periodontal and cellular cementum remodeling.

Evaluation of systemic Omega-3 PUFAs effect on orthodontic tooth movement in a rabbit model: RCT.

OBJECTIVES: To evaluate the effect of systemic administration of omega-3 fatty acids on orthodontic tooth movement (OTM) with histological analysis. MATERIALS AND METHODS: OTM was induced in 20 adult albino New Zealand rabbits, divided into omega-3 and control groups, with nickel-titanium coil springs for 21 days. Omega-3 or saline was given every day via oral gavage during the experimental period. Animals were sacrificed for histomorphometric analysis of alveolar bone remodeling after 21 days of OTM. RESULTS: A significant difference in OTM amount was found in the third week of OTM with means of 1.445 ± 0.13 and 1.72 ± 0.15 for the experimental and control groups, respectively. Histomorphometric analysis showed a significant reduction in the area of active bone-resorptive lacunae and a significant increase in osteoblastic activity in the omega-3 group after 3 weeks. CONCLUSIONS: Strong evidence of the osteoclastic inhibitory effect of systemic omega-3 was found, which reduced the percentage and amount of OTM.

The Emerging Role of MMP12 in the Oral Environment.

Matrix metalloproteinase-12 (MMP12), or macrophage metalloelastase, plays important roles in extracellular matrix (ECM) component degradation. Recent reports show MMP12 has been implicated in the pathogenesis of periodontal diseases. To date, this review represents the latest comprehensive overview of MMP12 in various oral diseases, such as periodontitis, temporomandibular joint dysfunction (TMD), orthodontic tooth movement (OTM), and oral squamous cell carcinoma (OSCC). Furthermore, the current knowledge regarding the distribution of MMP12 in different tissues is also illustrated in this review. Studies have implicated the association of MMP12 expression with the pathogenesis of several representative oral diseases, including periodontitis, TMD, OSCC, OTM, and bone remodelling. Although there may be a potential role of MMP12 in oral diseases, the exact pathophysiological role of MMP12 remains to be elucidated. Understanding the cellular and molecular biology of MMP12 is essential, as MMP12 could be a potential target for developing therapeutic strategies targeting inflammatory and immunologically related oral diseases.

Machine learning techniques to increase the performance of indirect methane quantification from a single, stationary sensor.

Researchers are searching for ways to better quantify methane emissions from natural gas infrastructure. Current indirect quantification techniques (IQTs) allow for more frequent or continuous measurements with fewer personnel resources than direct methods but lack accuracy and repeatability. Two IQTs are Other Test Method (OTM) 33A and Eddy Covariance (EC). We examined a novel approach to improve the accuracy of single sensor IQT whereby the results from both OTM and EC were combined with two machine learning (ML) models, a random forest (RF) and a neural network (NN). Then, models were enhanced with feature reduction and hyper-parameter tuning and compared to traditional quantification methods. The NN and RF improved upon the default OTM by an average of 44% and 78%, respectively. When compared to traditional OTM estimates with low Data Quality Indicators (DQIs), RF and NN models reduced 1σ errors from ±66% to ±13% and ±34%, respectively. Models also reduced the standard deviation of estimates with 93% and 85% of estimates falling within ±50% of the known release rate. This approach can be deployed with single sensor systems at well sites to improve confidence in reported emissions, reducing the number of anomalous overestimates that would trigger unnecessary site evaluations. Additional improvements could be realized by expanding training datasets with more methane release rates. Further, deployment of such models in a variety of situations could enhance their ability help close the gap between bottom-up inventory and top-down studies by enabling continuous monitoring of temporal emissions that could identify with improved confidence, atypically higher emissions. Accurate remote single sensor systems are key in developing an improved understanding of methane emissions to enable industry to identify and reduce methane emissions.

Failure Mechanisms of Ba0.5Sr0.5Co0.8Fe0.2O3-δ Membranes after Pilot Module Operation.

The step from the testing of oxygen transport membranes on a lab scale to long-term operation on a large scale is a challenge. In a previous study, membrane failure was observed at defined positions of one end of the cooled tubular Ba0.5Sr0.5Co0.8Fe0.2O3-δ membranes after an emergency shutdown. To understand the failure mechanisms, strength degradation and transient stress distribution were investigated by brittle-ring tests and finite element simulations, respectively. A 15% decrease in the characteristic strength of 162 MPa was proven after aging at 850 °C and was attributed to grain coarsening. The reduction in characteristic strength after thermal shock ranged from 5 to 90% depending on the cooling rates, and from 5 to 40% after the first and 20th soft thermal cycling. Simulations indicated the chemical strains induced by a 10-bar feed air and 50 mbar permeate pressure, which caused tensile stresses of up to 70 MPa at the outer surface. These stresses relaxed to 43 MPa by creep within a 1000 h operation. A remaining local stress maximum seemed to be responsible for the fracture. It evolved near the experimentally observed fracture position during a 1000 h permeation and exceeded the temperature and time-dependent strength. The maximum stress was formed by a chemical strain at temperatures above 500 °C but effective creep relaxation needed temperatures above 750 °C.

Relative Bioavailability of Trace Minerals in Production Animal Nutrition: A Review.

The importance of dietary supplementation of animal feeds with trace minerals is irrefutable, with various forms of both organic and inorganic products commercially available. With advances in research techniques, and data obtained from both in-vitro and in-vivo studies in recent years, differences between inorganic and organic trace minerals have become more apparent. Furthermore, differences between specific organic mineral types can now be identified. Adhering to PRISMA guidelines for systematic reviews, we carried out an extensive literature search on previously published studies detailing performance responses to trace minerals, in addition to their corresponding relative bioavailability values. This review covers four of the main trace minerals included in feed: copper, iron, manganese and zinc, and encompasses the different types of organic and inorganic products commercially available. Their impact from environmental, economic, and nutritional perspectives are discussed, along with the biological availability of various mineral forms in production animals. Species-specific sections cover ruminants, poultry, and swine. Extensive relative bioavailability tables cover values for all trace mineral products commercially available, including those not previously reviewed in earlier studies, thereby providing a comprehensive industry reference guide. Additionally, we examine reasons for variance in reported relative bioavailability values, with an emphasis on accounting for data misinterpretation.

Effects of vitamin D deficiency on the rate of orthodontic tooth movement: An animal study.

Bone remodeling and orthodontic tooth movement (OTM) are controlled by certain essential molecules, one of which is vitamin D. Increased levels of vitamin D have been associated with increased rates of OTM. The purpose of this study was to determine the effect of vitamin D deficiency on the rate of OTM, and to determine their association after applying orthodontic forces. MATERIALS AND METHODS: Wistar rats were divided into two groups: control group with average vitamin D levels and experimental group with induced vitamin D deficiency. Orthodontic appliances were fixed to initiate tooth movement. Distance between the reference teeth were measured in millimeters on day zero, and repeated every 7 days, till day 21. RESULTS: A significant difference within the experimental group was found; as well as within the control group, there was also no significant interaction between time and the type of group. CONCLUSION: The rate of Orthodontic tooth movement was not affected by induced vitamin D deficiency in rats.

Evaluation of image-guided and surface-guided radiotherapy for breast cancer patients treated in deep inspiration breath-hold: A single institution experience.

INTRODUCTION: Nowadays, deep inspiratory breath-hold is a common technique to reduce heart dose in left-sided breast radiotherapy. This study evaluates the evolution of the breath-hold technique in our institute, from portal imaging during dose delivery to continuous monitoring with surface-guided radiotherapy (SGRT). MATERIALS AND METHODS: Setup data and portal imaging results were analyzed for 98 patients treated before 2014, and SGRT data for 228 patients treated between 2018 and 2020. For the pre-SGRT group, systematic and random setup errors were calculated for different correction protocols. Residual errors and reproducibility of breath-holds were evaluated for both groups. The benefit of using SGRT for initial positioning was evaluated for another cohort of 47 patients. RESULTS: Online correction reduced the population mean error from 3.9 mm (no corrections) to 1.4 mm. Despite online setup correction, deviations greater than 3 mm were observed in about 10% and 20% of the treatment beams in ventral-dorsal and cranial-caudal directions, respectively. However, these percentages were much smaller than with offline protocols or no corrections. Mean absolute differences between breath-holds within a fraction were smaller in the SGRT-group (1.69 mm) than in the pre-SGRT-group (2.10 mm), and further improved with addition of visual feedback (1.30 mm). SGRT for positioning did not improve setup accuracy, but slightly reduced the time for imaging and setup correction, allowing completion within 3.5 min for 95% of fractions. CONCLUSION: For accurate radiotherapy breast treatments using deep inspiration breath-hold, daily imaging and correction is required. SGRT provides accurate information on patient positioning during treatment and improves patient compliance with visual feedback.

Comparative assessment of corticotomy facilitated rapid canine retraction using piezo versus bur: A randomized clinical study.

PURPOSE: The leading concern of orthodontic patients is prolonged treatment with fixed appliances and demand speedy treatment from the orthodontists. Piezocision is a relatively innovative, safe and reliable technique of corticotomy in the domain of surgically-accelerated orthodontic treatment. Our aim was to compare the efficiency of piezo corticotomy (piezocision) and conventional bur in rapid orthodontic tooth movement (OTM). SUBJECTS AND METHOD: The study employed a randomized, double-blind, split-mouth design. 24 subjects with Class II div 1 malocclusion were randomly assigned to the two interventions, viz; piezo and bur group. The primary parameters evaluated were the rate and amount of tooth movement and total treatment time required for canine retraction. Additionally, the duration of surgery and postoperative complications were also evaluated. OBSERVATIONS AND RESULTS: Rate and amount of tooth movement were significantly higher with reduction in total treatment time in piezo compared to bur group. The duration of surgery was significantly longer in piezo group with no significant difference observed in post-operative complications. CONCLUSION: Piezo-guided corticotomy was effective in providing rapid OTM with profound reduction in total treatment time and may be proposed as a suitable adjuvant to conventional corticotomy having comparable post-operative complications.

Formulations for Effective Detoxification Derived from Three Medicinal Plants: Thunbergia laurifolia, Clerodendrum disparifolium and Rotheca serrata.

BACKGROUND: Based on the long history of the medicinal use of Thunbergia laurifolia, Clerodendrum disparifolium and Rotheca serrata, the extract formulations of these species: T. laurifolia and C. disparifolium; T. laurifolia and R. serrata; and T. laurifolia, C. disparifolium and R. serrata, called formulas 1, 2 and 3, were created for detoxification testing to take more advantage of each species. OBJECTIVE: The objective of this study is to estimate the detoxifying effects of studied extract formulations on human cell and tissue culture as a preclinical trial. METHODS: The major phytochemicals were derived by GC-MS. The detoxification efficacy of these formulations in cells and DNA levels were derived by MTT and comet assays in toxic PBMCs (incubated with rice whisky or bathroom cleaner). RESULTS: The phytochemical constituents were detected at 23.48% phytol and 43.03% oleamide in T. laurifolia; 12.88% oleamide, 20.93% 9,12,15-octadecatrien, 25.52% squalene, 22.19% butylated hydroxy toluene and 15.36% vitamin E in C. disparifolium; and 30.41% phytol, 32.78% oleamide, and 12.20%, 9,12,15-octadecatrien-1-ol in R. serrata. The toxic cells treated with the plant formulas 1, 2 and 3 showed no IC50 values, but formulas 1 and 2 displayed higher efficacies than formula 3 did. The comet assay indicated that the experiments (the treatment on toxic cells with the plant formulas) induced significant (p < 0.05) DNA damage compared to the negative control due to poisoning occurring before administration of the plant formulas. The OTM of the controls was significantly (p < 0.05) longer than the experimental samples showing significantly reduce the toxicity of the created formulations. CONCLUSION: The formulas showed high detoxification efficacies and formulations 1 and 2 resulted in higher levels of detoxification than formulation 3, especially in immediate treatment after receiving toxic substances.

Pharmacokinetics of cannabidiol following single oral and oral transmucosal administration in dogs.

Introduction: In the last few years, different formulations containing cannabidiol (CBD) were tested with regard to its efficacy on chronic pain, refractory epilepsy, anxiety, aggressive behavior and atopic dermatitis in dogs. CBD is generally administered orally, but its low bioavailability, probably due to a first-pass metabolism, represents a great limitation. The aim of this study was to evaluate if CBD bioavailability increases after oral transmucosal administration (OTM) compared to oral treatment. Methods: Twelve dogs diagnosed with mild chronic pain were enrolled in the study and treated once orally or OTM (6 dogs/group) with a pure CBD in oil formulation at a dosing rate of 1 mg/kg b.w. At prefixed time points, blood samples were collected to define CBD plasma concentrations vs. time profiles, and the main pharmacokinetics parameters were obtained by non-compartmental model. Results: CBD Cmax, Tmax, terminal half-life and AUC0 - t were 206.77 ± 167 and 200.33 ± 158.33 ng/mL, 2.17 ± 0.98 and 1.92 ± 1.11 h, 2.67 ± 0.53 and 2.62 ± 0.64 h, 647.51 ± 453.17, and 536.05 ± 370.21 h*ng/mL, following oral and OTM administration, respectively. No significant difference in pharmacokinetic parameters were observed between treatments. Discussion: The OTM administration did not increase cannabidiol bioavailability compared to oral treatment. The almost perfectly superimposable mean plasma concentrations of cannabidiol following the two treatments suggests that CBD is not able to be adsorbed by the oral mucosa or that its absorption is very scarce, and that CBD is swallowed and absorbed in the gastrointestinal tract.

FAIRification of nanosafety data to improve applicability of (Q)SAR approaches: A case study on in vitro Comet assay genotoxicity data.

(Quantitative) structure-activity relationship ([Q]SAR) methodologies are widely applied to predict the (eco)toxicological effects of chemicals, and their use is envisaged in different regulatory frameworks for filling data gaps of untested substances. However, their application to the risk assessment of nanomaterials is still limited, also due to the scarcity of large and curated experimental datasets. Despite a great amount of nanosafety data having been produced over the last decade in international collaborative initiatives, their interpretation, integration and reuse has been hampered by several obstacles, such as poorly described (meta)data, non-standard terminology, lack of harmonized reporting formats and criteria. Recently, the FAIR (Findable, Accessible, Interoperable, and Reusable) principles have been established to guide the scientific community in good data management and stewardship. The EU H2020 Gov4Nano project, together with other international projects and initiatives, is addressing the challenge of improving nanosafety data FAIRness, for maximizing their availability, understanding, exchange and ultimately their reuse. These efforts are largely supported by the creation of a common Nanosafety Data Interface, which connects a row of project-specific databases applying the eNanoMapper data model. A wide variety of experimental data relating to characterization and effects of nanomaterials are stored in the database; however, the methods, protocols and parameters driving their generation are not fully mature. This article reports the progress of an ongoing case study in the Gov4nano project on the reuse of in vitro Comet genotoxicity data, focusing on the issues and challenges encountered in their FAIRification through the eNanoMapper data model. The case study is part of an iterative process in which the FAIRification of data supports the understanding of the phenomena underlying their generation and, ultimately, improves their reusability.

IPEM topical report: results of a 2020 UK survey on the use of online treatment monitoring solutions for IMRT/VMAT.

Numerous commercial technologies for online treatment monitoring (OTM) in radiotherapy (RT) are currently available including electronic portal imaging device (EPID)in vivodosimetry (IVD), transmission detectors and log files analysis. Despite this, in the UK there exists limited guidance on how to implement and commission a system for clinical use or information about the resources required to set up and maintain a service. A Radiotherapy Special Interest Group working party, established by Institute of Physics and Engineering in Medicine was formed with a view to reassess the current practice for OTM in the UK and an aim to develop consensus guidelines for the implementation of a system. A survey distributed to Heads of Medical Physics at 71 UK RT departments investigated: availability of OTM in the UK; estimates of workload; clinical implementation; methods of analysis; quality assurance; and opinions on future directions. The survey achieved a 76% response rate and demonstrated that OTM is widely supported in the UK, with 87% of respondents indicating all patients should undergo OTM. EPID IVD (EIVD) was the most popular form of OTM. An active EIVD service was reported by 37% of respondents, with 84% believing it was the optimal solution. This demonstrates a steady increase in adoption since 2012. Other forms of OTM were in use but they had only been adopted by a minority of centres. Financial barriers and the increase of staff workload continue to hinder wider implementation in other centres. Device automation and integration is a key factor for successful future adoption and requires support between treatment machine and OTM manufacturers. The survey has provided an updated analysis on the use of OTM methods across the UK. Future guidance is recommended on commissioning, adoption of local tolerances and root-cause analysis strategies to assist departments intending to implement OTM.