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The development of high-filled 3D printing resin necessitates a bonding protocol for dental indirect restorations to achieve optimal bond strength after cementation. This study evaluates shear bond strengths of high-filler 3D printed materials for permanent restorations with various surface treatments. Rodin Sculpture 1.0 (50% lithium disilicate fillers) and 2.0 Ceramic Nanohybrid (>60% zirconia and lithium disilicate fillers) were tested, with Aelite All-Purpose Body composite resin as control. Samples were prepared, post-cured, and sandblasted with alumina (25 µm). Surface roughness was analyzed using an optical profilometer. Two bonding protocols were compared. First, groups were treated with lithium disilicate silane (Porcelain Primer) or zirconia primer (Z-Prime Plus) or left untreated without a bonding agent. Beam-shaped resin cement (DuoLink Universal) specimens were bonded and stored in a 37 °C water bath. Second, additional sets of materials were coated with a bonding agent (All-Bond Universal), either followed by silane application or left untreated. These sets were then similarly stored alongside resin cement specimens. Shear bond tests were performed after 24 h. SEM images were taken after debonding. One-Way ANOVA and post hoc Duncan were performed for the statistical analysis. Rodin 1.0 exhibited increased adhesive failure with silane or zirconia primer coating, but significantly improved bond strengths with bonding agent application. Rodin 2.0 showed consistent bond strengths regardless of bonding agent application, but cohesive failure rates increased with bonding agent and filler coating. In all groups, except for Rodin 1.0 without bonding agent, silane coating increased cohesive failure rate. In conclusion, optimal shear bond strength for high-filler 3D printing materials can be achieved with silane coating and bonding agent application.

Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40-69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment. The adoption of multifactorial risk assessment, the effectiveness of methods for collecting risk factor information and the costs of risk assessment were examined. Associations between participant characteristics and study sites, as well as data collection methods, were assessed using logistic regression; all p -values are two-sided. Of the 4246 participants recruited, 88.4% completed a risk assessment, with 79.8%, 15.7% and 4.4% estimated at average, higher than average and high risk, respectively. The total per-participant cost for risk assessment was CAD 315. Participants who chose to provide risk factor information on paper/telephone (27.2%) vs. online were more likely to be older ( p = 0.021), not born in Canada ( p = 0.043), visible minorities ( p = 0.01) and have a lower attained education ( p < 0.0001) and perceived fair/poor health ( p < 0.001). The 34.4% of participants requiring risk factor verification for missing/unusual values were more likely to be visible minorities ( p = 0.009) and have a lower attained education ( p ≤ 0.006). This study demonstrates the feasibility of risk assessment for risk-stratified screening at the population level. Implementation should incorporate an equity lens to ensure cancer-screening disparities are not widened.

The Depression, Anxiety, and Stress Scale-21 (DASS-21) has been used in various countries to assess the mental states of individuals. The objectives of this study were to validate the DASS-21 for use in Guam, an island that endures a high burden of mental health challenges, such as suicide, and examine the predictive impact of selected health indicators on DASS-21 variables. Three years of data (2017-2019) were pooled from the Pacific Islands Cohort of College Students (PICCS) study conducted annually at the University of Guam. In total, 726 students were included in the secondary data analysis. MPlus statistical software was used to perform a confirmatory factor analysis (CFA) for the validation and structural equation modeling (SEM) for the predictive modeling. The results from the CFA suggested an acceptable model fit (RMSEA: 0.073, CFI: 0.901, TLI: 0.889, RMR: 0.044), while SEM suggested that sleep quality and physical activity were significant predictors of DASS-21 variables. Therefore, the DASS-21 is a valid instrument for measuring depression, anxiety, and stress among emerging adults in Guam., Competing Interests: The authors declare no conflicts of interest.

Emerging evidence indicates that intracellular calcium (Ca 2+ ) levels and their regulatory proteins play essential roles in normal stem cell proliferation and differentiation. Cancer stem-like cells (CSCs) are subpopulations of cancer cells that retain characteristics similar to stem cells and play an essential role in cancer progression. Recent studies have reported that the Orai3 calcium channel plays an oncogenic role in human cancer. However, its role in CSCs remains underexplored. In this study, we explored the effects of Orai3 in the progression and stemness of oral/oropharyngeal squamous cell carcinoma (OSCC). During the course of OSCC progression, the expression of Orai3 exhibited a stepwise augmentation. Notably, Orai3 was highly enriched in CSC populations of OSCC. Ectopic Orai3 expression in non-tumorigenic immortalized oral epithelial cells increased the intracellular Ca 2+ levels, acquiring malignant growth and CSC properties. Conversely, silencing of the endogenous Orai3 in OSCC cells suppressed the CSC phenotype, indicating a pivotal role of Orai3 in CSC regulation. Moreover, Orai3 markedly increased the expression of inhibitor of DNA binding 1 (ID1), a stemness transcription factor. Orai3 and ID1 exhibited elevated expression within CSCs compared to their non-CSC counterparts, implying the functional importance of the Orai3/ID1 axis in CSC regulation. Furthermore, suppression of ID1 abrogated the CSC phenotype in the cell with ectopic Orai3 overexpression and OSCC. Our study reveals that Orai3 is a novel functional CSC regulator in OSCC and further suggests that Orai3 plays an oncogenic role in OSCC by promoting cancer stemness via ID1 upregulation.

GV1001, a 16 amino acid peptide derived from the catalytic segment of human telomerase reverse transcriptase, was developed as an anti-cancer vaccine. Subsequently, it was found to exhibit anti-inflammatory and anti-Alzheimer's disease properties. Periodontitis is a risk factor for a variety of systemic diseases, including atherosclerosis, a process in which chronic systemic and vascular inflammation results in the formation of plaques containing lipids, macrophages, foam cells, and tissue debris on the vascular intima. Thus, we investigated the effect of GV1001 on the severity of ligature-induced periodontitis, vascular inflammation, and arterial lipid deposition in mice. GV1001 notably reduced the severity of ligature-induced periodontitis by inhibiting gingival and systemic inflammation, alveolar bone loss, and vascular inflammation in wild-type mice. It also significantly lowered the amount of lipid deposition in the arterial wall in ApoE -deficient mice receiving ligature placement without changing the serum lipid profile. In vitro, we found that GV1001 inhibited the Receptor Activator of NF-κB ligand (RANKL)-induced osteoclast formation and tumor necrosis factor-α (TNF-α)-induced phenotypic changes in endothelial cells. In conclusion, our study suggests that GV1001 prevents the exacerbation of periodontitis and atherosclerosis associated with periodontitis partly by inhibiting local, systemic, and vascular inflammation and phenotypic changes of vascular endothelial cells.

Alcohol consumption is associated with an increased risk of several cancers, including oral/oropharyngeal squamous cell carcinoma (OSCC). Alcohol also enhances the progression and aggressiveness of existing cancers; however, its underlying molecular mechanism remains elusive. Especially, the local carcinogenic effects of alcohol on OSCC in closest contact with ingestion of alcohol are poorly understood. We demonstrated that chronic ethanol exposure to OSCC increased cancer stem cell (CSC) populations and their stemness features, including self-renewal capacity, expression of stem cell markers, ALDH activity, and migration ability. The ethanol exposure also led to a significant increase in aerobic glycolysis. Moreover, increased aerobic glycolytic activity was required to support the stemness phenotype of ethanol-exposed OSCC, suggesting a molecular coupling between cancer stemness and metabolic reprogramming. We further demonstrated that chronic ethanol exposure activated NFAT (nuclear factor of activated T cells) signaling in OSCC. Functional studies revealed that pharmacological and genetic inhibition of NFAT suppressed CSC phenotype and aerobic glycolysis in ethanol-exposed OSCC. Collectively, chronic ethanol exposure promotes cancer stemness and aerobic glycolysis via activation of NFAT signaling. Our study provides a novel insight into the roles of cancer stemness and metabolic reprogramming in the molecular mechanism of alcohol-mediated carcinogenesis.

The purpose of this randomized controlled clinical trial was to assess the short-term clinical effectiveness of sealer-based root canal obturation using calcium-silicate-based sealer (CSBS) and epoxy-resin-based sealer (ERBS). A total of eighty patients (eighty teeth) were enrolled and seventy-two patients (seventy-two teeth) were randomly assigned into four different sealer groups: AH Plus (AH, Dentsply Sirona), ADseal (AD, Meta Biomed), CeraSeal (CS, Meta Biomed), or EndoSeal TCS (ES, Maruchi). At the first visit, root canal treatment was performed using ProTaper. Next, the NiTi file system and passive ultrasonic irritation was applied with 2.5% NaOCl. At the second visit, the teeth were obturated with a sealer-based obturation technique using the assigned sealer. The quality of filling obturation was evaluated with postoperative radiographs in terms of the presence of voids and sealer extrusion. The patients were recalled at 1-week, 1-month, and 3-month intervals, and pain levels were measured using visual analog scales (VAS), and clinical examination performed with percussion and palpation. Radiographs were also taken. The results were statistically compared by using the χ2 test or Fisher exact test. Among the 80 teeth included, 72 teeth received allocated intervention and 71 teeth were included in the analysis (98.6% recall). There was no significant difference among the sealers in void and sealer extrusion (p > 0.05). Postoperative pain was not indicated prominently regardless of the type of sealer. For a 3-month follow-up period, all cases were maintained successfully except for one case from AD. According to the findings, there was no significant difference between CSBS and ERBS in terms of postoperative pain or the healing process, and the variation in filling quality appears to be linked to the properties of each product.

This in vitro study aimed to examine the shear bond strength of composite on the dentin and enamel substrates when mixed with different composite-handling agents (CHAs). Eighty extracted molars were embedded into acrylic resin and sectioned sagittally. On the prepared specimens, four groups of resin mixtures were bonded onto the enamel or dentin surfaces—composite only, composite mixed with Composite Wetting Resin (CWR), composite mixed with Brush and Sculpt (BS), and composite mixed with Modeling Resin (MR). All groups were prepared by mixing at a 1:1 ratio by weight. Each specimen was subjected to the shear bond strength test. After the test, adhesive or cohesive failures were examined at the fractured sites. Data were analyzed using one-way and two-way analysis of variance (ANOVA) and the Tukey post hoc test. All composite groups mixed with CHAs displayed a reduced shear bond strength on dentin and enamel substrates compared to composite alone (p < 0.05). The shear bond strength on dentin decreased in the following order: CWR > BS > MR. A similar pattern was observed on enamel, except that there was no statistically significant difference between BS and MR. Statistically significant interactions between resin mixtures and substrates were found (p < 0.001). On the dentin substrate, adhesive failure dominated while adhesive/cohesive failure dominated on the enamel substrate. Conclusions: The shear bonding strength of composite decreases when mixed with CHAs on both dentin and enamel substrates.

The development of direct pulp-capping materials with favorable biological and structural properties is an important goal in restorative dentistry. Fucoidan is a sulfated, fucose-containing polysaccharide obtained from brown seaweed, with a wide range of applications; however, its use as a direct pulp-capping material has not been examined. This study aimed to evaluate the mechanical, physical, and biological effects of fucoidan combined with conventional mineral trioxide aggregate (MTA) for direct pulp capping. The capping materials were created using Portland cement (80 wt%) and zirconium oxide (20 wt%) as base components, compared with base components plus 5 wt% fucoidan (PZF5) and base components plus 10 wt% fucoidan (PZF10). The initial and final setting time, compressive strength, chemical components, cell viability, adhesion, migration, osteogenesis, and gene expression were analyzed. Fucoidan significantly reduced the initial and final setting time, regardless of quantity. However, the compressive strength was lower for PZF5. Sulfur levels increased with fucoidan. The biological activity improved, especially in the PZF5 group. Cell migration, Alizarin Red S staining, and alkaline phosphatase activity were upregulated in the PZF5 group. Fucoidan is a useful regenerative additive for conventional pulp-capping materials because it reduces the setting time and improves cell migration and osteogenic ability.

The tensile bond strength between zirconia subjected to different surface-pretreatment methods and methacryloyloxydecyl-dihydrogen-phosphate (MDP)-containing self-adhesive resin cement was evaluated herein. Eighty-eight cylindrical zirconia specimens were randomly divided into the following four groups based on the pretreatment method: (1) no treatment, (2) air abrasion, (3) HNO3/HF etching, and (4) zirconia-nanoparticle coating. The tensile bond strength of the zirconia−resin-cement complexes was investigated. One-way ANOVA and post hoc tests were performed at a 95% significance level, and the Weibull modulus was calculated. Fracture patterns were visualized by SEM. The surface roughness of the specimens without resin bonding was evaluated by AFM. The tensile bond strength of the specimens decreased as follows: Groups 3 > 4 > 2 > 1 (28.2 ± 6.6, 26.1 ± 5.7, 16.6 ± 3.3, and 13.9 ± 3.0 MPa, respectively). Groups 3 and 4 had significantly higher tensile bond strengths (p < 0.05) and lower fracture probabilities than those of Groups 1 and 2. They also showed both mixed failure and resin-cement cohesive failure, whereas Groups 1 and 2 showed mixed failure exclusively. The zirconia−resin tensile bond was stronger after HNO3/HF etching or ZrO2-nanoparticle coating than after air abrasion or no treatment. The estimated surface roughness decreased as follows: Groups 3 > 4 > 2 > 1. The combination of zirconia pretreated with HNO3/HF etching or ZrO2-nanoparticle coating and an MDP-containing self-adhesive resin cement can increase the clinical longevity of zirconia restorations by preventing their decementation.

The objective of this study was to determine reactive oxygen species (ROS) produced by fagopyrin F-rich fraction (FFF) separated from Tartary buckwheat flower extract exposed to lights and to investigate its antibacterial photodynamic inactivation (PDI) against Streptococcus mutans and its biofilm. ROS producing mechanisms involving FFF with light exposure were determined using a spectrophotometer and a fluorometer. S. mutans and its biofilm inactivation after PDI treatment of FFF using blue light (BL; 450 nm) were determined by plate count method and crystal violet assay, respectively. The biofilm destruction by ROS produced from FFF after exposure to BL was visualized using confocal laser scanning microscopy (CLSM) and field emission scanning electron microscope (FE-SEM). BL among 3 light sources produced type 1 ROS the most when applying FFF as a photosensitizer. FFF exposed to BL (5 and 10 J/cm 2 ) significantly more inhibited S. mutans viability and biofilm formation than FFF without the light exposure ( p < 0.05). In the PDI of FFF exposed to BL (10 J/cm 2 ), an apparent destruction of S. mutans and its biofilm were observed by the CLSM and FE-SEM. Antibacterial PDI effect of FFF was determined for the first time in this study.

This study compares knowledge, experience and understanding of genetic testing, and psychological outcomes among breast and ovarian cancer patients undergoing multi-gene panel testing via genetic counselor-mediated (GMT) or oncologist-mediated (OMT) testing models. A pragmatic, prospective survey of breast and ovarian cancer patients pursuing genetic testing between January 2017 and August 2019 was conducted at the Princess Margaret Cancer Centre in Toronto, Canada. A total of 120 (80 GMT; 40 OMT) individuals completed a survey administered one week following consent to genetic testing. Compared to OMT, the GMT cohort had higher median knowledge (8 vs. 9; p = 0.025) and experience/understanding scores (8.5 vs. 10; p < 0.001) at the time of genetic testing. Significant differences were noted in the potential psychological concerns experienced, with individuals in the GMT cohort more likely to screen positive in the hereditary predisposition domain of the Psychosocial Aspects of Hereditary Cancer tool (55% vs. 27.5%; p = 0.005), and individuals in the OMT cohort more likely to screen positive in the general emotions domain (65.0% vs. 38.8%; p = 0.007). The results of this study suggest that OMT can be implemented to streamline genetic testing; however, post-test genetic counseling should remain available to all individuals undergoing genetic testing, to ensure any psychologic concerns are addressed and that individuals have a clear understanding of relevant implications and limitations of their test results.

The Genomics of Malignant Peripheral Nerve Sheath Tumor (GeM) Consortium is an international collaboration focusing on multi-omic analysis of malignant peripheral nerve sheath tumors (MPNSTs), the most aggressive tumor associated with neurofibromatosis type 1 (NF1). Here we present a summary of current knowledge gaps, a description of our consortium and the cohort we have assembled, and an overview of our plans for multi-omic analysis of these tumors. We propose that our analysis will lead to a better understanding of the order and timing of genetic events related to MPNST initiation and progression. Our ten institutions have assembled 96 fresh frozen NF1-related (63%) and sporadic MPNST specimens from 86 subjects with corresponding clinical and pathological data. Clinical data have been collected as part of the International MPNST Registry. We will characterize these tumors with bulk whole genome sequencing, RNAseq, and DNA methylation profiling. In addition, we will perform multiregional analysis and temporal sampling, with the same methodologies, on a subset of nine subjects with NF1-related MPNSTs to assess tumor heterogeneity and cancer evolution. Subsequent multi-omic analyses of additional archival specimens will include deep exome sequencing (500×) and high density copy number arrays for both validation of results based on fresh frozen tumors, and to assess further tumor heterogeneity and evolution. Digital pathology images are being collected in a cloud-based platform for consensus review. The result of these efforts will be the largest MPNST multi-omic dataset with correlated clinical and pathological information ever assembled.

Background: CDH1 pathogenic variants (pvs) cause most cases of inherited diffuse gastric cancer (dgc), but have low detection rates and vary geographically. In the present study, we examined hereditary causes of dgc in patients in Ontario., Methods: CDH1 testing through single-site or multi-gene panels was conducted for patients with dgc meeting the 2015 International Gastric Cancer Linkage Consortium (igclc) criteria, or with isolated dgc at less than 50 years of age, or with a strong family history of cancer identified at the Zane Cohen Centre (zcc). All CDH1- positive patients at zcc, regardless of cancer history, were summarized., Results: In 15 of 85 patients with dgc (17.6%), a pv or likely pv was identified through CDH1 single-site ( n = 43) or multi-gene panel ( n = 42) testing. The detection rate was 9.4% overall (8 of 85) and 11% using igclc criteria (7 of 65). No CDH1 pvs were identified in patients with isolated dgc at less than 40 years of age, but 1 pv was identified in a patient with isolated dgc at less than 50 years of age. Multi-gene panels identified 9 pvs (21.4%), including CDH1, STK11, ATM , BRCA2, MLH1 , and MSH2 . Review of 81 CDH1 carriers identified 10% with dgc (median age: 48 years; range: 38-59 years); 41% were unaffected (median age: 53 years; range: 26-89 years). Observed malignancies other than dgc or lobular breast cancer (lbc) included colorectal, gynecologic, kidney or bladder, prostate, testicular, and ductal breast cancers. Lobular-breast cancer was seen only in 3 families., Conclusions: In Ontario, the detection rate of CDH1 pvs in patients with dgc was low: no pvs were identified in patients with isolated dgc at less than 40 years of age, and 1 was identified in a patient with isolated dgc at less than 50 years of age. Isolated lbc with no dgc was observed in CDH1- positive families, as were pathology-confirmed nondgc or non-lbc malignancies, which had not previously been reported. Given a phenotype that overlaps with other hereditary conditions, multi-gene panels are recommended for all patients with dgc at less than 50 years of age and for those meeting igclc criteria., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none., (2020 Multimed Inc.)

Neurofibromatosis Type I (NF1) is caused by variants in neurofibromin ( NF1 ). NF1 predisposes to a variety of benign and malignant tumor types, including breast cancer. Women with NF1 <50 years of age possess an up to five-fold increased risk of developing breast cancer compared with the general population. Impaired emotional functioning is reported as a comorbidity that may influence the participation of NF1 patients in regular clinical surveillance despite their increased risk of breast and other cancers. Despite emphasis on breast cancer surveillance in women with NF1, the uptake and feasibility of high-risk screening programs in this population remains unclear. A retrospective chart review between 2014-2018 of female NF1 patients seen at the Elizabeth Raab Neurofibromatosis Clinic (ERNC) in Ontario was conducted to examine the uptake of high-risk breast cancer screening, radiologic findings, and breast cancer characteristics. 61 women with pathogenic variants in NF1 enrolled in the high-risk Ontario breast screening program (HR-OBSP); 95% completed at least one high-risk breast screening modality, and four were diagnosed with invasive breast cancer. Our findings support the integration of a formal breast screening programs in clinical management of NF1 patients.

The combination of increased referral for genetic testing and the current shortage of genetic counselors has necessitated the development and implementation of alternative models of genetic counseling and testing for hereditary cancer assessment. The purpose of this scoping review is to provide an overview of the patient outcomes that are associated with alternative models of genetic testing and genetic counseling for hereditary cancer, including germline-only and tumor testing models. Seven databases were searched, selecting studies that were: (1) full-text articles published ≥2007 or conference abstracts published ≥2015, and (2) assessing patient outcomes of an alternative model of genetic counseling or testing. A total of 79 publications were included for review and synthesis. Data-charting was completed using a data-charting form that was developed by the study team for this review. Seven alternative models were identified, including four models that involved a genetic counselor: telephone, telegenic, group, and embedded genetic counseling models; and three models that did not: mainstreaming, direct, and tumor-first genetic testing models. Overall, these models may be an acceptable alternative to traditional models on knowledge, patient satisfaction, psychosocial measures, and the uptake of genetic testing; however, particular populations may be better served by traditional in-person genetic counseling. As precision medicine initiatives continue to advance, institutions should consider the implementation of new models of genetic service delivery, utilizing a model that will best serve the needs of their unique patient populations.