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Background: CP-X is an opioid antagonist evaluated in a thorough QT (TQT) study to investigate the potential effect of CP-X concentration on the QTc interval following repeated oral administration.Methods: This was a multiple-dose, randomized, 4-period crossover, double-blind study investigating 10 mg and 40 mg QD of CP-X and placebo on Days 1 through 7, and open-label moxifloxacin 400 mg single dose on Day 7 in 64 healthy volunteers. Plasma samples were analyzed for CP-X using solid phase extraction followed by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) analysis. Time-matched ECG measurements and pharmacokinetic data were analyzed using NONMEM V, Level 1.1.Results: The QTcF-concentration relationship was characterized with a linear model that accounted for effects of placebo, sex, and study day on intercept and the effect of study day on slope. The mean (95% CI) slope describing the QTcF-concentration relationship was 0.0866 (0.0476, 0.126) msec/(ng/mL) on Day 1, which translates to mean prolongations of 1.33 msec and 6.51 msec at mean Cmax following the initial 10 mg and 40 mg doses, respectively. The mean (95% CI) slope on Day 7 was 0.0480 (0.0300, 0.0670) msec/(ng/mL), producing expected prolongations of 1.80 msec and 7.49 msec at mean steady state Cmax following multiple 10 mg and 40 mg doses.Conclusions: Exposure-response modeling allowed for quantification of concentration and time-dependent changes in the QTcF interval-concentration relationship in a TQT study.Clinical Pharmacology & Therapeutics (2005) 79, P29–P29; doi: 10.1016/j.clpt.2005.12.109 [ABSTRACT FROM AUTHOR]

Objectives: To assess the effective and organ/tissue equivalent radiation doses of different scout projection protocols in four CBCT units., Methods: Optically stimulated luminescence dosimeters (OSLD) were placed in reference anatomical locations in the head and neck segments of an anthropomorphic phantom representing an average adult male. Ten repeated exposures were obtained from each of the twelve scout projections studied, acquired from four maxillofacial cone beam computed tomography (CBCT) units (Midmark EIOS, 3D Accuitomo F170, Veraviewepocs 3D R100, and Veraview X800). The effective and organ/tissue equivalent doses were calculated for each protocol., Results: Effective doses ranged from 0.7 µSv (Accuitomo F170 60 × 60 mm-anterior maxilla) to 6.9 µSv (Midmark 50 × 50 mm-anterior maxilla). The highest organ/tissue equivalent doses were recorded for the oral mucosa and salivary glands; however, the thyroid was the highest contributor to the effective dose, followed by the salivary glands., Conclusions: Despite some variability among CBCT machines and protocols, the acquisition of scout projections is a low-dose procedure. The use of scout projections to ensure an adequate position of the region of interest within the field of view is highly desirable as they contribute minimally to overall CBCT patient dose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study aimed to assess the performance of a convolutional neural network (CNN) model in detecting the pubertal growth spurt by analyzing cervical vertebrae maturation (CVM) in lateral cephalometric radiographs (LCRs)., Study Design: In total, 600 LCRs of patients from 6 to 17 years old were selected. Three radiologists independently and blindly classified the maturation stages of the LCRs and defined the difficulty of each classification. Subsequently, the stage and level of difficulty were determined by consensus. LCRs were distributed between training, validation, and test datasets across 4 CNN-based models. The models' responses were compared with the radiologists' reference standard, and the architecture with the highest success rate was selected for evaluation. Models were developed using full and cropped LCRs with original and simplified maturation classifications., Results: In the simplified classification, the Inception-v3 CNN yielded an accuracy of 74% and 75%, with recall and precision values of 61% and 62%, for full and cropped LCRs, respectively. It achieved 61% and 62% total success rates with full and cropped LCRs, respectively, reaching 72.7% for easy-to-classify cropped cases., Conclusion: Overall, the CNN model demonstrated potential for determining the maturation status regarding the pubertal growth spurt through images of the cervical vertebrae. It may be useful as an initial assessment tool or as an aid for optimizing the assessment and treatment decisions of the clinician., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: We investigated the influence of voxel and field of view (FOV) sizes on expression of the volumetric alteration artifact (VAA) of 5 high-density materials in 2 cone beam computed tomography (CBCT) devices., Study Design: Cylinders of amalgam, cobalt-chromium, gutta-percha, titanium, and zirconium were individually positioned in a polymethyl methacrylate phantom. OP300 Maxio and ProMax 3D Classic CBCT devices were used to acquire images with varying voxel and FOV sizes, totaling 585 scans. Two evaluators segmented the high-density cylinder images to obtain the tomographic volumes. The difference between the tomographic and physical volume of each cylinder (i.e., volumetric alteration) was calculated. Statistical analysis was conducted with multiway ANOVA and the Tukey post hoc test (α = 5%). Evaluator reliability was measured with the intraclass correlation coefficient (ICC)., Results: All studied parameters and nearly all interactions influenced the VAA (P < .05). The post hoc test demonstrated less volumetric alteration for the smallest voxel sizes, 61 × 78 mm FOV, and gutta-percha for OP300, and for the smallest voxel sizes, 80 × 80 mm FOV, and gutta-percha and titanium for ProMax 3D (P < .05). The ICC demonstrated perfect reliability (1.00)., Conclusions: Voxel and FOV sizes influenced VAA expression. Using smaller voxel sizes, the 61 × 78 mm FOV for OP300 and the 80 × 80 mm FOV for ProMax 3D, and materials with lower density and lower atomic number reduced VAA expression., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the effect of the presence and the number of high-density objects in the exomass on the volume of a high-density object in cone-beam CT (CBCT)., Methods: Cylinders of cobalt-chromium (Co-Cr), titanium (Ti), and zirconium (Zi) were inserted into a polymethylmethacrylate phantom in five different combinations of number and position: 1-no cylinder; 2-one cylinder in a posterior region; 3-one cylinder in an anterior region; 4-two cylinders in posterior regions; and 5-three cylinders in anterior and posterior regions. The phantom underwent CBCT scanning using OP300 and X800 systems, with the afore mentioned cylinders of the same composition placed in the exomass and an additional high-density cylinder placed in the centre of the field of view (FOV), corresponding to the left-anterior region. The tomographic volume of the cylinder inside the FOV was measured using semi-automatic segmentation. The volumetric alteration (VA) between the segmented and physical volumes, in percentage, was compared among the experimental groups using repeated measures ANOVA and Tukey post-hoc (α = 5%)., Results: The factors material, combination, and their interaction affected the volume or both CBCT systems. In OP300, more cylinders in the exomass reduced the VA, mainly for Co-Cr. In X800, more cylinders in the exomass tended to increase the VA inside the FOV, except for Zi., Conclusions: In general, the presence of high-density objects in the exomass influences the VA of the object inside the FOV, although this oscillates according to object composition, number and position in the exomass, and CBCT system., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology and the International Association of Dentomaxillofacial Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To compare the dosimetry between convex triangular fields of view (FOV) and similar dimension cylindrical FOVs of two cone-beam computed tomography (CBCT) models., Methods: Optically stimulated luminescence dosimeters (OSLDs) were placed in fiducial anatomical locations in an anthropomorphic phantom representing an adult head male for dosimetry scans. Convex triangular FOVs (100 × 80 mm/maxilla-mandible; 100 × 50 mm mandible; 100 × 50 mm/maxilla) from Veraviewepocs 3D R100 (J. Morita, Kyoto, Japan) (R100) and Veraview® X800 (J. Morita, Kyoto, Japan) (X800) and cylindrical FOVs from R100 and X800 (80 × 80 mm/maxilla-mandible; 80 × 50 mm/mandible; 80 × 50 mm/maxilla) were obtained, resulting in 12 different scan protocols. Equivalent doses for each relevant organ/tissue and the effective dose for each protocol were calculated. Mean effective doses were compared by the two-way analysis of variance (ANOVA) with Tukey's post hoc test to evaluate the effect of the FOV and device (α = 0.05)., Results: The effective doses ranged between 69 and 324 μSv for the convex triangular FOVs and 76 and 332 μSv for the cylindrical FOVs. Convex triangular FOVs from the R100 device had effective doses 2.3 to 15.3% lower than their corresponding cylindrical FOVs with similar height (p < 0.05), and that difference ranged between 8.8 and 11.8% for the X800 device (p < 0.05)., Conclusion: Convex triangular fields of view delivered slightly lower effective doses than the cylindrical fields of view of similar dimensions in the R100 and X800 CBCT devices., Clinical Relevance: Understanding the influence of the image geometry formation in effective dose allows optimization to reduce patient dose., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To assess the distortion of high-density materials using two CBCT devices presenting convex triangular and cylindrical fields of view (FOVs)., Methods and Materials: Four high-density cylinders were individually placed in a polymethylmethacrylate phantom. 192 CBCT scans were acquired using the convex triangular and cylindrical FOVs of Veraviewepocs ® R100 (R100) and Veraview ® X800 (X800) devices. Using Horos TM 's software, two oral radiologists determined the cylinders' horizontal and vertical dimensional alterations. Nine oral radiologists subjectively identified each cylinder's axial shape distortion. Statistical analysis comprised Multiway ANOVA (α = 5%), and the Kruskal-Wallis test., Results: The distortion in the axial plane was greater in the convex triangular FOVs for both devices in almost all the materials ( p < 0.05). The evaluators subjectively identified a shape distortion in both FOVs for R100 device ( p < 0.001), while no distortion was identified for X800 device ( p = 0.620). A vertical magnification of all materials was observed in both FOVs for both devices ( p < 0.05). No differences among vertical regions ( p = 0.988) nor FOVs ( p = 0.544) were found for the R100 device, while all materials showed higher magnification in all regions in the cylindrical FOV ( p < 0.001) of the X800 device., Conclusions: The convex triangular FOV influenced the axial distortion of the high-density materials in both devices. A vertical magnification was observed in both FOVs of both devices, but it was greater in the cylindrical FOV of the X800 device.

Objective: To compare cylindrical and convex triangular field-of-views (FOVs) concerning the magnitude of artefacts from high-density materials in cone-beam CT (CBCT)., Methods and Materials: Cylinders of amalgam, chromium-cobalt, titanium, and zirconia were individually placed in the anterior and posterior regions of a polymethylmethacrylate phantom and scanned using cylindrical and convex triangular FOVs of the Veraview X800 CBCT device. Using the Image J software, 15 square regions of interest (ROIs) were placed in the axial reconstruction around the middle level of the cylinder and at distances of 0.5, 1.0, and 1.5 cm from the centre of the cylinder. Mean grey value and standard deviation of each ROI were averaged for each distance and subtracted from the values of a control ROI to calculate the magnitude of the artefacts by the grey value mean difference (GVMD) and grey value standard deviation (GVSD). Multiway analysis of variance with Tukey post-hoc test with a significance level of 5% evaluated the effect of the shape of the FOV, position inside the FOV, high-density material, and the distance of the artefact from the material., Results: The convex triangular FOV increased the GVSD for all materials in the anterior and posterior regions at 0.5 cm compared to the cylindrical FOV ( p < 0.0001). The convex triangular FOV showed greater GVMD for chromium-cobalt and zirconium in the anterior region and all materials in the posterior region at all distances ( p < 0.0001)., Conclusion: The FOV shape influences the magnitude of artefacts from high-density materials. The convex triangular FOV showed greater artefact magnitude with variability among the high-density materials, region in the FOV, and distance from the material.

Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of rats: Sham, CCI-alone and CCI-BMMNCs (AUTO). One hundred twenty days after injury, rodents were imaged with PBR28 and their cognitive behavior assessed utilizing the Morris Water Maze. Subsequent ex vivo analysis included brain volume and immunohistochemistry. BMMNCs therapy attenuated PBR28suv in comparison to CCI alone and it improved spatial learning as measured by the Morris Water Maze. Ex vivo analysis demonstrated preservation of brain volume, a decrease in amoeboid-shaped microglia in the dentate gyrus and an increase in the ratio of ramified to amoeboid microglia in the thalamus. PBR28suv is a viable option to measure efficacy of BMMNCs therapy after TBI., (© 2023. Springer Nature Limited.)

Human prion diseases are remarkable for long incubation times followed typically by rapid clinical decline. Seed amplification assays and neurodegeneration biofluid biomarkers are remarkably useful in the clinical phase, but their potential to predict clinical onset in healthy people remains unclear. This is relevant not only to the design of preventive strategies in those at-risk of prion diseases, but more broadly, because prion-like mechanisms are thought to underpin many neurodegenerative disorders. Here, we report the accrual of a longitudinal biofluid resource in patients, controls and healthy people at risk of prion diseases, to which ultrasensitive techniques such as real-time quaking-induced conversion (RT-QuIC) and single molecule array (Simoa) digital immunoassays were applied for preclinical biomarker discovery. We studied 648 CSF and plasma samples, including 16 people who had samples taken when healthy but later developed inherited prion disease (IPD) ('converters'; range from 9.9 prior to, and 7.4 years after onset). Symptomatic IPD CSF samples were screened by RT-QuIC assay variations, before testing the entire collection of at-risk samples using the most sensitive assay. Glial fibrillary acidic protein (GFAP), neurofilament light (NfL), tau and UCH-L1 levels were measured in plasma and CSF. Second generation (IQ-CSF) RT-QuIC proved 100% sensitive and specific for sporadic Creutzfeldt-Jakob disease (CJD), iatrogenic and familial CJD phenotypes, and subsequently detected seeding activity in four presymptomatic CSF samples from three E200K carriers; one converted in under 2 months while two remain asymptomatic after at least 3 years' follow-up. A bespoke HuPrP P102L RT-QuIC showed partial sensitivity for P102L disease. No compatible RT-QuIC assay was discovered for classical 6-OPRI, A117V and D178N, and these at-risk samples tested negative with bank vole RT-QuIC. Plasma GFAP and NfL, and CSF NfL levels emerged as proximity markers of neurodegeneration in the typically slow IPDs (e.g. P102L), with significant differences in mean values segregating healthy control from IPD carriers (within 2 years to onset) and symptomatic IPD cohorts; plasma GFAP appears to change before NfL, and before clinical conversion. In conclusion, we show distinct biomarker trajectories in fast and slow IPDs. Specifically, we identify several years of presymptomatic seeding positivity in E200K, a new proximity marker (plasma GFAP) and sequential neurodegenerative marker evolution (plasma GFAP followed by NfL) in slow IPDs. We suggest a new preclinical staging system featuring clinical, seeding and neurodegeneration aspects, for validation with larger prion at-risk cohorts, and with potential application to other neurodegenerative proteopathies., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Network automation promises to reduce costs while guaranteeing the required performance; this is paramount when dealing with the forecasted highly dynamic traffic that will be generated by new 5G/6G applications. In optical networks, autonomous lightpath operation entails that the optical receiver can identify the configuration of a received optical signal without necessarily being configured from the network controller. This provides relief for the network controller from real-time operation, and it can simplify the operation in multi-domain scenarios, where an optical connection spans across more than one domain. Consequently, in this work, we propose a blind and low complex modulation format (MF) and symbol rate (SR) identification algorithm. The algorithm is based on studying the effects of decoding an optical signal with different MFs and SRs. Extensive MATLAB-based simulations have been carried out which consider a coherent wavelength division multiplexed system based on 32 and 64 quadrature amplitude modulated signals at up to 96 GBd, thus enabling bit rates of up to 800 Gb/s/channel. The results show remarkable identification accuracy in the presence of linear and nonlinear noise for a wide range of feasible configurations.

Background: Using data from electronic health registries, this study intended to estimate the COVID-19 vaccine effectiveness (VE) in the population aged 65 years and more, against symptomatic infection, COVID-19-related hospitalizations, and deaths, overall and by time since complete vaccination for the period February to September 2021., Methods: We established a cohort of individuals aged 65 and more years old, resident in Portugal mainland, using the National Health Service User number to link eight electronic health registries. Outcomes included were symptomatic SARS-CoV-2 infections, COVID-19-related hospitalizations or deaths. The exposures of interest were the mRNA vaccines (Comirnaty or Spikevax) and the viral vector (Vaxzevria) vaccine. Complete schedule VE was estimated as one minus the confounder adjusted hazard ratio, for each outcome, estimated by time-dependent Cox regression with time-dependent vaccine exposure., Results: For the cohort of individuals aged 65-79 years, complete scheme VE against symptomatic infection varied 43 (95%CI: 37-49) (Vaxzevria) and 65 (95%CI: 62-68) (mRNA vaccines). This estimate was slightly lower in the ≥80 years cohort (53, 95%CI: 45-60) for mRNA vaccines). VE against COVID-19 hospitalization varied between 89% (95%CI: 52-94) for Vaxzevria and 95% (95%CI: 93-97) for mRNA vaccines for the cohort aged 65-79 years and was 76% (95%CI: 67-83) for mRNA vaccines in the ≥80 years cohort. High VE against COVID-19-related deaths was estimated, for both vaccine types, 95% and 81 (95%CI:76-86) for the 65-79 years and the ≥80 years cohort, respectively. We observed a significant waning of VE against symptomatic infection, with VE estimates reaching approximately 34% for both vaccine types and cohorts. Significant waning was observed for the COVID-19 hospitalizations in the ≥80 years cohort (decay from 83% (95%CI:68 to 91) 14-41 days to 63% (95%CI:37 to 78) 124 days after mRNA second dose). No significant waning effect was observed for COVID-19-related deaths in the period of follow-up of either cohort., Conclusions: In a population with a high risk of SARS-CoV-2 complications, we observed higher overall VE estimates against more severe outcomes for both age cohorts when compared to symptomatic infections. Considering the analysis of VE according to time since complete vaccination, the results showed a waning effect for both age cohorts in symptomatic infection and COVID-19 hospitalization for the 80 and more years cohort., Competing Interests: The authors have declared that no competing interests exist.

Background: Prion diseases cause a range of movement disorders involving the cortical, extrapyramidal, and cerebellar systems, and yet there are no large systematic studies of their prevalence, features, associations, and responses to commonly used treatments., Objectives: We sought to describe the natural history and pharmacological management of movement disorders in prion diseases., Methods: We studied the serial examination findings, investigation results, and symptomatic treatment recorded for 700 patients with prion diseases and 51 mimics who had been enrolled onto the prospective longitudinal National Prion Monitoring Cohort study between 2008 and 2020. We performed an analysis to identify whether there were patterns of movement disorders associated with disease aetiology, PRNP codon 129 polymorphism, disease severity rating scales, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) findings., Results: Gait disturbances, myoclonus, and increased tone are the most frequently observed movement disorders in patients with prion diseases. The typical pattern of early motor dysfunction involves gait disturbance, limb ataxia, impaired smooth pursuit, myoclonus, tremor, and increased limb tone. Disturbances of gait, increased tone, and myoclonus become more prevalent and severe as the disease progresses. Chorea, alien limb phenomenon, and nystagmus were the least frequently observed movement disorders, with these symptoms showing spontaneous resolution in approximately half of symptomatic patients. Disease severity and PRNP codon 129 polymorphism were associated with different movement disorder phenotypes. Antiepileptics and benzodiazepines were found to be effective in treating myoclonus., Conclusions: We describe the prevalence, severity, evolution, treatment, and associated features of movement disorders in prion diseases based on a prospective cohort study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: MRI is invaluable for the pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), demonstrating characteristic diffusion abnormalities. Previous work showed these changes were often not reported (low sensitivity), leading to eventual diagnosis at a more advanced state. Here, we reviewed the situation a decade later, on the presumption of improved access and awareness over time., Methods: We reviewed initial MRI scans of 102 consecutive suspected sCJD patients recruited to the National Prion Monitoring Cohort study between 2015 and 2019, assessing for characteristic signal changes in the striatum, thalamus and cortical ribbon. We compared our findings to formal reports from referring centres. Requesting indications were studied to assess if they were suggestive of CJD. Patients were examined and their MRC Prion Disease Rating Scale scores recorded., Results: We identified characteristic MRI abnormalities in 101 cases (99% sensitivity), whilst referring centres reported changes in 70 cases (69% sensitivity), which was a significant improvement in reporting sensitivity from 2012. Reporting sensitivity was associated with signal change in the cerebral cortex, and with the number of regions involved, but not significantly affected by clinical information on request forms, or referring centres being regional neuroscience/non-neuroscience centres. Similar to a previous study, patients with missed abnormalities on initial reporting possessed lower MRC Scale scores when referred to the NPC than those correctly identified., Conclusions: Whilst local MRI reporting of sCJD has improved with time, characteristic abnormalities remain significantly under detected on initial scans. Sensitivity is better when the cerebral cortex and multiple regions are involved. We re-emphasize the utility of MRI and encourage further efforts to improve awareness and sensitivity in the assessment of patients with rapidly progressive dementia., (© 2022. The Author(s).)

Objectives: To assess the influence of sagittal and vertical skeletal patterns, and sex in the angulation and relationship between the maxillary central incisors and the nasopalatine canal., Materials and Methods: Cone-beam computed tomography (CBCT) exams of 172 patients were classified into sagittal (class I, II, and III) and vertical skeletal patterns (mesofacial, brachyfacial and dolichofacial). Hard palate-nasopalatine canal and hard palate-long axis of maxillary central incisors angles were measured in sagittal reconstructions. The obtained angles were used to calculate the angulation between maxillary central incisors and nasopalatine canal by triangle geometric relationship. Analysis of variance (multi-way ANOVA) and Tukey post-hoc test were used for data analysis (α=5%)., Results: Sagittal and vertical skeletal patterns, and sex presented a low influence on the angulation of maxillary central incisors and nasopalatine canal. Dolichofacial class II women showed the greatest hard palate-nasopalatine canal angulations (P<0.05) and maxillary central incisors and nasopalatine canal angulations (P<0.05). Mesofacial class II and III men presented the lowest maxillary central incisors and nasopalatine canal angulations (P<0.05)., Conclusions: The sagittal and vertical skeletal patterns, and sex have a low influence on the angulation of the maxillary central incisors and the nasopalatine canal., (Copyright © 2022 CEO. Published by Elsevier Masson SAS. All rights reserved.)

This study aimed to estimate chronic daily intake (CDI) and to predict the attributable lifetime cancer risk (LCR) and hazard index (HI) from concurrent exposure to four trihalomethanes (THMs; chloroform, bromodichloromethane, dibromochloromethane and bromoform), via multiple exposure routes (oral ingestion, dermal contact and inhalation), among 238 non-competitive attendees of 10 Portuguese public indoor swimming pools (SPs), using a probabilistic approach based on Monte Carlo simulations. Exposure parameters of study participants were collected via questionnaires and THMs levels in SPs water were determined according the respective normative standards. The CDI for total THMs calculated for male and female participants considering all routes was 7.52 and 8.97 mg/kg/day, respectively. SP attendees presented higher CDI through inhalation than via the other two exposure routes, and chloroform was the compound contributing the most to total THMs CDI. The risk analysis indicated that the total LCR and HI from the targeted THMs were higher than the negligible risk levels (1 × 10 -6 and 1, respectively) in the scenarios examined (central tendency exposure and reasonable maximum exposure), and the health risk for females was slightly higher than for males. This study suggests that there are possible adverse health risks, thus, to protect pool attendees, adequate mitigation measures, and comprehensive regulatory guidelines on individual THMs concentrations are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To assess the reproducibility of a wedge-guided bitewing image receptor-holding device (IRHD-WG) compared to a commercially available bitewing image receptor-holding device (IRHD-XCP)., Methods and Materials: Ten operators randomly acquired bitewing radiographs of four posterior regions (Premolar, Molar 1, Molar 2, Molar 3) distributed in two dry bone skulls and mandibles using 2 IRHDs (IRHD-WG and IRHD-XCP). The radiographs corresponding to the same region and IRHD but acquired by different operators were paired for reproducibility comparison. A total of 360 pairs of radiographs were randomized for analysis. Objective analysis consisted of extracting the pixel values from each radiograph and comparing the values between each pair by intraclass correlation coefficient. For subjective analysis, the IRHDs images were digitally removed. Five oral radiologists blinded for the study conditions classified the radiograph pairs according to their similarity and diagnostic value. The answers' relative frequencies were compared by the chi-square test (α = 0.05)., Results: The IRHD-WG presented a higher reproducibility (Mean = 0.850; SD = 0.144) than the IRHD-XCP (Mean = 0.615; SD = 0.287) in the objective analysis. Radiographs acquired with the IRHD-WG were more similar than those acquired with the IRHD-XCP ( p < 0.001). The diagnostic value of bitewing radiographs acquired with the IRHD-WG was considered superior to those acquired with the IRHD-XCP ( p < 0.001)., Conclusion: For the objective and subjective analyses of reproducibility, the IRHD-WG performed better than the commercial IRHD-XCP.

Objective: To compare the expression of the volumetric alteration (VA) artifact between cylindrical and convex triangular fields of view (FOVs) using high-density materials in different positions in two cone-beam computed tomography (CBCT) devices., Materials and Methods: Cylinders of five high-density materials (amalgam, chromium-cobalt, gutta-percha, titanium, and zirconium) with known physical volume were individually submitted to CBCT acquisition in four positions inside a polymethylmethacrylate phantom using two different FOV shapes (convex triangular and cylindrical) on the Veraviewepocs® R100 (R100) and Veraview® X800 (X800) devices. Two oral radiologists obtained the tomographic volumes by segmenting each cylinder. The difference between the tomographic and physical volumes corresponded to the VA. These values were analyzed by intraclass correlation coefficient and analysis of variance for repeated measures with Tukey post hoc test (α = 5%)., Results: The FOV influenced the VA only in the X800 device (p = 0.014): the VA in the triangular FOV was greater than in the cylindrical FOV. The VA in the triangular FOV of the X800 device was greater than the R100 device (p < 0.0001). The material influenced the expression of the VA only in the R100 device (p < 0.0001); gutta-percha presented the highest VA, being underestimated, and differing from the other materials (p < 0.01)., Conclusion: The triangular FOV increased the VA of high-density materials in the X800 device., Clinical Relevance: It is important to know if there is an influence on the volumetric alteration artifact of dental materials due to the different image formation geometry in the convex triangular FOV., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Endemic human coronaviruses (hCoVs) 229E and OC43 cause respiratory disease with recurrent infections, while severe acute respiratory syndrome (SARS)-CoV-2 spreads across the world with impact on health and societies. Here, we report an image-based multicycle infection procedure with α-coronavirus hCoV-229E-eGFP in an arrayed chemical library screen of 5440 clinical and preclinical compounds. Toxicity counter selection and challenge with the β-coronaviruses OC43 and SARS-CoV-2 in tissue culture and human airway epithelial explant cultures (HAEEC) identified four FDA-approved compounds with oral availability. Methylene blue (MB, used for the treatment of methemoglobinemia), Mycophenolic acid (MPA, used in organ transplantation) and the anti-fungal agent Posaconazole (POS) had the broadest anti-CoV spectrum. They inhibited the shedding of SARS-CoV-2 and variants-of-concern (alpha, beta, gamma, delta) from HAEEC in either pre- or post exposure regimens at clinically relevant concentrations. Co-treatment of cultured cells with MB and the FDA-approved SARS-CoV-2 RNA-polymerase inhibitor Remdesivir reduced the effective anti-viral concentrations of MB by 2-fold, and Remdesivir by 4 to 10-fold, indicated by BLISS independence synergy modelling. Neither MB, nor MPA, nor POS affected the cell delivery of SARS-CoV-2 or OC43 (+)sense RNA, but blocked subsequent viral RNA accumulation in cells. Unlike Remdesivir, MB, MPA or POS did not reduce the release of viral RNA in post exposure regimen, thus indicating infection inhibition at a post-replicating step as well. In summary, the data emphasize the power of unbiased, full cycle compound screens to identify and repurpose broadly acting drugs against coronaviruses., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: UFG has been a consultant and stock owner in 3V-Biosciences (now Sagimet Biosciences), a consultant to F. Hoffmann-La Roche Ltd and to Union Therapeutics A/S. The authors filed a patent application on the use of MPA for the treatment of COVID-19 (EP20213904, European Patent Office, University of Zurich)., (© 2022 The Authors.)

Introduction: This study aimed to evaluate the impact of preoperative pulp inflammation on the histologic outcome of full pulpotomy performed in mature permanent posterior teeth using 4 different biomaterials., Methods: Five beagle dogs (providing a total of 120 roots) were selected. Dentin exposure was performed in teeth from the second and third quadrants. One week later, full pulpotomy procedures were performed using 4 different bioactive materials (ProRoot MTA [MTA], TotalFill BC Putty [BC], Biodentine [BIO], and an experimental cement [ie, pulp capping material]). The hemostasis time was registered. After 14 weeks, the animals were killed. Pulp-dentin tissues were histologically and radiographically assessed. The significance level was set at .05., Results: Teeth with previously exposed dentin revealed a statistically significant increase in the time required to achieve hemostasis (P < .001), therefore confirming the pulp inflammation status induced by 1-week exposure of occlusal dentin before performing full pulpotomy. There was no radiographic evidence of root resorption, periapical radiolucency, or lamina dura alterations. No statistically significant differences were observed between normal and inflamed pulp regardless of the evaluated histologic parameters. Moreover, histologic data concerning calcified barrier formation and the pulp tissue response show better results for BIO without statistical differences compared with MTA or BC (P > .05). The pulp capping material presented a lower performance, with statistically significant differences being detected in regard to the remaining 3 tested materials (P < .001)., Conclusions: Radiographic and histologic outcomes of full pulpotomy are not jeopardized by short-term preoperative pulp inflammation. Moreover, BIO, MTA, and BC cements present suitable alternatives to be used as pulp capping agents., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Through deterministic data linkage of health registries, mRNA vaccine effectiveness (VE) against COVID-19-related hospitalisations and deaths was measured in 1,880,351 older adults. VE against hospitalisations was 94% (95% confidence interval (CI): 88-97) and 82% (95% CI: 72-89) for those 65-79 and ≥ 80 years old, with no evidence of waning 98 days after dose two. VE against mortality was 96% (95% CI: 92-98) and 81% (95% CI: 74-87) in these two age groups.

Objectives: The aim of this study was to evaluate the shear bond strength inherent to immediate and delayed definitive composite resin restorations, over three different biomaterials., Methods: Fifty-four aluminum blocks were randomly assigned to six experimental groups (n = 9) according to the biomaterial (Biodentine, TotalFill BC Putty, or PCM) and restoration timing (immediate or 7 days delayed). Regarding the restorative procedures, a two-step self-etch bonding system (Clearfil SE Bond) was applied and subsequently restored using a flowable composite resin (SDR). After shear bond strength testing, fracture pattern analysis was performed. The significance level was set at α = 0.05., Results: Within the immediate groups, Biodentine showed the highest mean shear bond strength value, with no statistically significant differences (P > 0.05) being detected when compared with both TotalFill (P = 0.072) and PCM (P = 0.232) groups. Regarding the delayed restoration groups, Biodentine and TotalFill presented the highest mean shear bond strength value, with statistical differences when compared with PCM (P = 0.002 and P = 0.043, respectively). No statistically significant differences (P > 0.05) were verified between both immediate and delayed groups for each tested biomaterial. Also, a statistically significant association was found between the fracture type and the biomaterial (P < 0.001)., Conclusions and Clinical Relevance: Our findings suggest that all tested biomaterials present suitable alternatives which allow to perform restorative procedures immediately after pulp capping biomaterial placement (3 or 12 min, depending on the bioactive cement), therefore requiring one single appointment to complete the procedure. Biodentine and TotalFill BC Putty have shown superior shear bond strength results when compared with PCM, within a delayed timeframe (7 days).