Adjunctive therapies for in vitro carious lesions: Antimicrobial activity,activation of dentin metalloproteinases and effects on dental pulp cells

BackgroundAdjunctive therapies used before dental restorative procedures may encourage carious tissue removal. Beyond promising antimicrobial properties, treatments could positively modulate the dentin-pulp complex while not interfering with restoration survival. Herein, we evaluated a set of substances and their effects on carious lesions and the underlying dentin or pulp cells.MethodsArtificial caries lesions were developed in bovine teeth cavities immersed in Streptococcus mutans and Lactobacillus casei co-cultures. The cavities were treated according to the following groups: Phosphate Buffer Saline (PBS), Chlorhexidine (CHX), Papacárie® (Papain gel), Ozone (O₃), and antimicrobial Photodynamic Therapy (aPDT). After treatments, samples were cultivated to count isolated microbial colonies. The zymography assay evaluated the activity of dentin metalloproteinases (MMP-2 and MMP-9). Cell viability was indirectly assessed on human dental pulp cells after 24, 72, or 120 h, whereas the odontodifferentiation potential was evaluated after ten days of cell culture.ResultsCHX and aPDT led to around 1 log bacterial load reduction. PBS, CHX, and aPDT showed the eventual expression of MMP-2 and MMP-9. Cell viability was reduced (< 30%) after 120 h for all groups compared to the control. CHX, O3, and aPDT induced greater odontodifferentiation (≈ 20% higher) than PBS and papain gel.ConclusionAdjunctive therapies presented little or no biological significance in reducing bacterial load in artificial carious lesions. Although the activation of endogenous metalloproteinases may represent a possible concern for adhesive restorations, some of these treatments may have a positive role in dental pulp tissue repair.     

Skin3D: Detection and longitudinal tracking of pigmented skin lesions in 3D total-body textured meshes

We present an automated approach to detect and longitudinally track skin lesions on 3D total-body skin surface scans. The acquired 3D mesh of the subject is unwrapped to a 2D texture image, where a trained objected detection model, Faster R-CNN, localizes the lesions within the 2D domain. These detected skin lesions are mapped back to the 3D surface of the subject and, for subjects imaged multiple times, we construct a graph-based matching procedure to longitudinally track lesions that considers the anatomical correspondences among pairs of meshes and the geodesic proximity of corresponding lesions and the inter-lesion geodesic distances.We evaluated the proposed approach using 3DBodyTex, a publicly available dataset composed of 3D scans imaging the coloured skin (textured meshes) of 200 human subjects. We manually annotated locations that appeared to the human eye to contain a pigmented skin lesion as well as tracked a subset of lesions occurring on the same subject imaged in different poses. Our results, when compared to three human annotators, suggest that the trained Faster R-CNN detects lesions at a similar performance level as the human annotators. Our lesion tracking algorithm achieves an average matching accuracy of 88% on a set of detected corresponding pairs of prominent lesions of subjects imaged in different poses, and an average longitudinal accuracy of 71% when encompassing additional errors due to lesion detection. As there currently is no other large-scale publicly available dataset of 3D total-body skin lesions, we publicly release over 25,000 3DBodyTex manual annotations, which we hope will further research on total-body skin lesion analysis.     

Aqueous outflow channels and its lymphatic association: A review

The human eye has a unique immune architecture and behavior. While the conjunctiva is known to have a well-defined lymphatic drainage system, the cornea, sclera, and uveal tissues were historically considered “alymphatic” and thought to be immune privileged. The very fact that the aqueous outflow channels carry a clear fluid (aqueous humor) along the outflow pathway makes it hard to ignore its lymphatic-like characteristics. The development of novel lymphatic lineage markers and expression of these markers in aqueous outflow channels and improved imaging capabilities has sparked a renewed interest in the study of ocular lymphatics. Ophthalmic lymphatic research has had a directional shift over the last decade, offering an exciting new physiological platform that needs further in-depth understanding. The evidence of a presence of distinct lymphatic channels in the human ciliary body is gaining significant traction. The uveolymphatic pathway is an alternative new route for aqueous outflow and adds a new dimension to pathophysiology and management of glaucoma. Developing novel animal models, markers, and non-invasive imaging tools to delineate the core anatomical structure and physiological functions may help pave some crucial pathways to understand disease pathophysiology and help develop novel targeted therapeutic approaches for glaucoma.     

Plectin ensures intestinal epithelial integrity and protects colon against colitis

Plectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in an intestinal epithelial cell (IEC; Ple^ΔIEC) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in the colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and the formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal α6β4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with the effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacity in vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in the Ple^ΔIEC colon.     

A comprehensive method for calculating total body irradiation

PurposeTo provide means for calculating the dose received by various tissues of the patient, calculate lung shield, and verify received dose using a phantom as a tool for quality assurance for a planned Total Body Irradiation (TBI) procedure in radiotherapy.MethodUsing Microsoft Visual Basic, MATLAB, and Python, a program for Total Body Irradiation Calculation in Radiotherapy (TBICR) is constructed. It uses patient translation and beam zone method for total body irradiation calculations to compute the proper dose received by the patient and determine the lung shield thickness. There are three main user-friendly interfaces in the application. The first one allows the user to upload the TBI topography and estimate the distances needed for TBI calculations. The second one enables the user to count the number of beam zones needed for each point and estimate the effective area (A_eff) for each level. The third interface estimates the velocity required to deliver the relative dose depending on patient separation, Monitor Units (MU), couch speed and travel distance. It allows the user to compute the required lung shield thickness, read any patient's CT DICOM file and acquire dose in any distinct location using machine learning model to predict the dose.ResultsThe TBICR software has been successfully validated by reproducing all of the manual calculations in an exact and timely manner. TBICR generated more accurate results and confirmed the absorbed dose to patient through measurements on Anderson phantom.ConclusionsA computer program for the calculation of total body irradiation (TBI) is described in full. The dose received at each point on the patient, the calculation of lung shield and the determination of the velocity and time required for the couch movement are all made possible using the software. The ease of use, precision, data storage and printing are some important features of the present software.     

Patient engagement in the Continuing Professional Development programs within the department of radiation oncology at the University of Toronto (UTDRO): A qualitative study

IntroductionThere is little research regarding patient engagement (PE) in Continuing Professional Development (CPD) programs in radiation oncology. This study aims to understand the barriers and enablers to PE in the design and implementation process of CPD programs, and advance PE in these programs moving forward.MethodsThis qualitative study involved 17 semi-structured interviews, with 5 cancer patients and 12 educators, conducted from June 2019 to April 2020. Interview data identified common themes, such as: the current state of PE in CPD programming, and key barriers and recommendations on how to engage patients in meaningful and practical ways.ResultsSix themes were identified related to PE: the concept of PE, ethical considerations, barriers, key considerations in planning resources, and the anticipated impact of PE on curriculum planning.ConclusionBoth patients and educators emphasized that creating and sustaining meaningful educator-patient relationships and giving patients an active and effective role in CPD planning would improve curriculum content. The University of Toronto Department of Radiation Oncology (UTDRO) should consider building this initiative into its strategic CPD priorities and ensure the appropriate infrastructure is in place.