Characterisation of myeloid cells in circulation and synovial fluid of patients with psoriatic arthritis.

OBJECTIVE: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. Adding to studies focused on the role of T cells and macrophages, we sought to investigate the systemic activation of leukocytes in PsA. METHODS: We assessed the activation state of leukocyte populations, including polymorphonuclear neutrophils (PMNs) and monocyte/macrophages, in blood and synovial fluid (SF) by multicolour flow cytometry. We also evaluated the correlation between leukocyte numbers and expression of activation markers with disease activity parameters. RESULTS: SF PMNs showed an elevated activation state compared with blood PMNs, but a reduced activation state compared with oral PMNs of non-arthritic controls. In vitro stimulation caused SF PMNs to become further activated, demonstrating that they retain a reserve capacity for activation in response to specific triggers. We found significant variability between patients in the expression of SF PMN CD activation markers, indicating a range of possible activation states across patients. However, PMN CD marker expression remained consistent over two sequential visits in a subset of patients, indicating patient-specific distinct inflammatory states during flares. We further found that markers of disease activity increased with elevated SF macrophage numbers. Expression of several CD markers on blood or SF cells, for example, PMN expression of the high-affinity Fc-receptor CD64, correlated with disease activity markers, including pain score and Disease Activity in Psoriatic Arthritis score. CONCLUSION: These preliminary findings support a potential role for surface antigens on PMNs and monocytes/macrophages as prognostic or disease activity monitoring tools.

Toward Digital Periodontal Health: Recent Advances and Future Perspectives.

Periodontal diseases, ranging from gingivitis to periodontitis, are prevalent oral diseases affecting over 50% of the global population. These diseases arise from infections and inflammation of the gums and supporting bones, significantly impacting oral health. The established link between periodontal diseases and systemic diseases, such as cardiovascular diseases, underscores their importance as a public health concern. Consequently, the early detection and prevention of periodontal diseases have become critical objectives in healthcare, particularly through the integration of advanced artificial intelligence (AI) technologies. This paper aims to bridge the gap between clinical practices and cutting-edge technologies by providing a comprehensive review of current research. We examine the identification of causative factors, disease progression, and the role of AI in enhancing early detection and treatment. Our goal is to underscore the importance of early intervention in improving patient outcomes and to stimulate further interest among researchers, bioengineers, and AI specialists in the ongoing exploration of AI applications in periodontal disease diagnosis.

Utilizing Oral Neutrophil Counts as an Indicator of Oral Inflammation Associated With Periodontal Disease: A Blinded Multicentre Study.

BACKGROUND: Periodontal diseases are chronic inflammatory conditions that require early screening for effective long-term management. Oral neutrophil counts (ONCs) correlate with periodontal inflammation. This study investigates a point-of-care test using a neutrophil enzyme activity (NEA) colorimetric strip for measuring periodontal inflammation. METHODS: This prospective study had two phases. Phase 1 validated the relationship between ONCs and periodontal inflammation with 90 participants. Phase 2 examined the test's applicability in a real-world setting through a multicentre clinical trial with 375 participants at four sites. ONCs were quantified in oral rinses using laboratory-based methods, and the NEA strip was used for ONC stratification. Clinical measures included bleeding on probing (BoP), probing depth (PD) and clinical attachment loss (CAL). RESULTS: ONCs were significantly elevated in patients with Grade B periodontitis and deep periodontal pockets (PD ≥ 5 mm, CAL ≥ 5 mm). The NEA strip accurately classified patients into high or low ONC categories, showing 80% sensitivity, 82.5% specificity and an AUC of 0.89. It also assessed the effectiveness of periodontal therapy in reducing ONC and inflammation. The test was user-friendly, with no reported discomfort among patients. CONCLUSION: The NEA strip is a user-friendly and rapid screening tool for detecting high ONCs associated with periodontal inflammation and for evaluating the effectiveness of periodontal therapy.

Mitochondrial perturbations in low-protein-diet-fed mice are associated with altered neutrophil development and effector functions.

Severe malnutrition is associated with infections, namely lower respiratory tract infections (LRTIs), diarrhea, and sepsis, and underlies the high risk of morbidity and mortality in children under 5 years of age. Dysregulations in neutrophil responses in the acute phase of infection are speculated to underlie these severe adverse outcomes; however, very little is known about their biology in this context. Here, in a lipopolysaccharide-challenged low-protein diet (LPD) mouse model, as a model of malnutrition, we show that protein deficiency disrupts neutrophil mitochondrial dynamics and ATP generation to obstruct the neutrophil differentiation cascade. This promotes the accumulation of atypical immature neutrophils that are incapable of optimal antimicrobial response and, in turn, exacerbate systemic pathogen spread and the permeability of the alveolocapillary membrane with the resultant lung damage. Thus, this perturbed response may contribute to higher mortality risk in malnutrition. We also offer a nutritional therapeutic strategy, nicotinamide, to boost neutrophil-mediated immunity in LPD-fed mice.

CBCT in Dental Implantology: A Key Tool for Preventing Peri-Implantitis and Enhancing Patient Outcomes.

(1) Introduction: Trust is a cornerstone of the patient-physician relationships. Unforeseen complications in the health care system could jeopardize patients' trust in their physicians. (2) Aim: This article presents a quantitative figure regarding foreseeing the necessity of a three-dimensional quantitative visualization of bone structure and concurrently preparing for an ancillary procedure by a dentist to successfully perform the surgery that could minimize unforeseen complications; (3) Materials and method: This retrospective study has been derived based on an analysis of 1134 patients who had received 4800 dental implants from January 2001 to August 2020, out of which 200 cases were randomly selected for this study. Each procedure during implant treatment was categorized as OPG (Orthopantomography) or OPG with CBCT as per all the procedures which included and were coded as follows, 1: Surgery & Restoration, 2: GBR (Guided Bone Regeneration), 3: GTR (Guided Tissue Regeneration), 4: Block Bone Graft, 5: Spreading, 6: Splitting, 7: Internal Sinus, 8: External Sinus, 9: PRF (Platelet Rich Fibrin). Any of the 200 cases in which implant placement could not have been performed for reasons related to a lack of CBCT were selected for this study. The surgery was aborted halfway through without implant placement in these cases due to a lack of bone quantity and/or lack of primary stability. These cases were registered for re-evaluation and statistical analysis; (4) Results: 7% of the cases that used OPG alone led the surgeon to unexpectedly abort in the middle of the surgery without implant placement. All (100%) of the patients who had CBCT during treatment planning were able to receive implants during the surgery. None of the patients left the surgery without receiving implants if CBCT was used (0%); (5) Discussion: Radiographic image quality is defined as the amount of information within the image that allows the radiologist to make a diagnostic decision with a particular level of certainty (Martin et al., 1999) and hence the importance of CBCT. The unexpected 7% of devastating situations for patients who started surgery but did not have implant placement led to [A] aborting the surgery, [B] procedural difficulties requiring an alternative treatment plan, [C] a negative impact on the patient's behavior, and [D] wanting to change doctor due to a lack of trust; (6) Conclusion: This study indicates that in implant dentistry patients' mistrust could be avoided by 7% if CBCT is obtained. It also shows the significance of cone-beam computed tomography as an adjunct to panoramic radiography during the diagnosis and treatment planning phase. The use of panoramic radiography alone can lead to a 7% likelihood of misdiagnosis. A lack of CBCT during treatment planning negatively affects the outcome of surgical procedures.

Prognosing post-treatment outcomes of head and neck cancer using structured data and machine learning: A systematic review.

BACKGROUND: This systematic review aimed to evaluate the performance of machine learning (ML) models in predicting post-treatment survival and disease progression outcomes, including recurrence and metastasis, in head and neck cancer (HNC) using clinicopathological structured data. METHODS: A systematic search was conducted across the Medline, Scopus, Embase, Web of Science, and Google Scholar databases. The methodological characteristics and performance metrics of studies that developed and validated ML models were assessed. The risk of bias was evaluated using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). RESULTS: Out of 5,560 unique records, 34 articles were included. For survival outcome, the ML model outperformed the Cox proportional hazards model in time-to-event analyses for HNC, with a concordance index of 0.70-0.79 vs. 0.66-0.76, and for all sub-sites including oral cavity (0.73-0.89 vs. 0.69-0.77) and larynx (0.71-0.85 vs. 0.57-0.74). In binary classification analysis, the area under the receiver operating characteristics (AUROC) of ML models ranged from 0.75-0.97, with an F1-score of 0.65-0.89 for HNC; AUROC of 0.61-0.91 and F1-score of 0.58-0.86 for the oral cavity; and AUROC of 0.76-0.97 and F1-score of 0.63-0.92 for the larynx. Disease-specific survival outcomes showed higher performance than overall survival outcomes, but the performance of ML models did not differ between three- and five-year follow-up durations. For disease progression outcomes, no time-to-event metrics were reported for ML models. For binary classification of the oral cavity, the only evaluated subsite, the AUROC ranged from 0.67 to 0.97, with F1-scores between 0.53 and 0.89. CONCLUSIONS: ML models have demonstrated considerable potential in predicting post-treatment survival and disease progression, consistently outperforming traditional linear models and their derived nomograms. Future research should incorporate more comprehensive treatment features, emphasize disease progression outcomes, and establish model generalizability through external validations and the use of multicenter datasets.

Development and Standardization of an Osteoradionecrosis Classification System in Head and Neck Cancer: Implementation of a Risk-Based Model.

PURPOSE: Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN. METHODS: Consecutive patients with head and neck cancer (HNC) treated with curative-intent intensity-modulated radiation therapy (IMRT) (≥45 Gy) from 2011 to 2017 were included. Occurrence of ORN was identified from in-house prospective dental and clinical databases and charts. Multivariable logistic regression model was used to identify risk factors and stratify patients into high-risk and low-risk groups. A novel ORN classification system was developed to depict ORN severity by modifying existing systems and incorporating expert opinion. The performance of the novel system was compared with 15 existing systems for their ability to identify and predict serious ORN event (jaw fracture or requiring jaw resection). RESULTS: ORN was identified in 219 of 2,732 (8%) consecutive patients with HNC. Factors associated with high risk of ORN were oral cavity or oropharyngeal primaries, received IMRT dose ≥60 Gy, current/ex-smokers, and/or stage III to IV periodontal condition. The ORN rate for high-risk versus low-risk patients was 12.7% versus 3.1% (P < .001) with an AUC of 0.71. Existing ORN systems overclassified serious ORN events and failed to recognize maxillary ORN. A novel ORN classification system, ClinRad, was proposed on the basis of vertical extent of bone necrosis and presence/absence of exposed bone/fistula. This system detected serious ORN events in 5.7% of patients and statistically outperformed existing systems. CONCLUSION: We identified risk factors for ORN and proposed a novel ORN classification system on the basis of vertical extent of bone necrosis and presence/absence of exposed bone/fistula. It outperformed existing systems in depicting the seriousness of ORN and may facilitate clinical care and clinical trials.

The dental COVID-19 paradox: Disparity in behaviors inside and outside dental schools in Canada.

OBJECTIVE: To describe the personal and professional behavior and assess the perceptions of protection and fear of contracting coronavirus disease 2019 (COVID-19) among faculty, staff, and students from all 10 Canadian dental schools during the second year of the pandemic. METHOD: Participants from a Pan-Canadian prospective study answered monthly questionnaires about their activities between April 2021 and March 2022. In May 2022, additional questions were asked about their perception of protection, fear of infection, and instances of COVID-19 testing. RESULTS: Six hundred participants were initially recruited. Over time, the participants spent less time at home and increased their participation in indoor social activities, a trend influenced by the fluctuations in COVID-19 cases (ß = â€’0.02). Over 90% of the participants were fully vaccinated, which decreased their fear of contracting the virus (χ2[4, 241‒243] = 196.07, p < 0.0001). Yet, their attitude toward protective measures did not change, and they followed them within school. CONCLUSIONS: This work shows a paradoxical behavior among dental students, staff, and faculty members in Canadian dental schools. While factors such as the vaccine's limited efficacy and a desire to protect others may contribute to stringent protective behaviors within dental schools, the mandatory nature of these measures was likely the primary motivator for the compliance. Despite potential efforts to minimize exposure to the virus during risk periods and the frequent COVID-19 testing, this paradoxical behavior raises questions about professional responsibilities extending beyond the workplace. Thus, dental schools should incorporate education about the rationale behind following different protocols and the potential consequences of outside school behaviors.

Practical 10-Color T-Cell Panel for Phenotyping Diverse Populations Using Spectral Flow Cytometry: A Beginner's Guide.

Flow cytometry stands as the most employed high-throughput single-cell analysis technique, facilitating the profiling of remarkably diverse samples, such as blood, bone marrow and body fluids. In addition, it allows for the discrimination of diverse immune cell subsets, including infrequently encountered types like T regulatory cells and exhausted CD28Null T cells. However, analyzing rare immune cell subsets with conventional flow cytometry poses challenges stemming from factors like fluorophore overlap, compensation issues, and limited flexibility in fluorophore selection. Therefore, spectral flow cytometry offers advantages over traditional flow cytometry. It measures the full emission spectrum and then separates it to identify different fluorochromes. This enables the use of fluorochromes with significant overlap in a single test, allowing for the analysis of more protein markers. Following this, spectral technology employs precise calculations to separate individual fluorochromes, thereby enabling the detection and elimination of autofluorescent signals originating from cells within the entire emission spectrum. This capability is pivotal in achieving deep phenotyping of immune cells with the requisite sensitivity and resolution essential for monitoring the immune systems of patients with compromised immunity, such as cancer and autoimmune disorders. Additionally, it allows for the exploration of interactions between distinct immune subsets. In this context, we introduce an optimized protocol utilizing spectral flow cytometry for precise T-cell characterization and differentiation, encompassing the assessment of their activation states. Furthermore, this protocol extends its applicability to the identification of less common circulating T-cell populations, notably T-regulatory and CD28Null T cells, following autofluorescence correction within the spectrum. This protocol provides a set of steps and reagents for the surface and intracellular staining of human T cells using whole peripheral blood. The spectral-based design of this panel allows for its applicability to other spectral machines, providing a versatile and efficient tool for T-cell analysis. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Achieving optimal staining through effective antibody titration Basic Protocol 2: Single-cell staining Basic Protocol 3: Comprehensive panel staining post-titration and spectral library integration.

Three-Dimensional Printing Methods for Bioceramic-Based Scaffold Fabrication for Craniomaxillofacial Bone Tissue Engineering.

Three-dimensional printing (3DP) technology has revolutionized the field of the use of bioceramics for maxillofacial and periodontal applications, offering unprecedented control over the shape, size, and structure of bioceramic implants. In addition, bioceramics have become attractive materials for these applications due to their biocompatibility, biostability, and favorable mechanical properties. However, despite their advantages, bioceramic implants are still associated with inferior biological performance issues after implantation, such as slow osseointegration, inadequate tissue response, and an increased risk of implant failure. To address these challenges, researchers have been developing strategies to improve the biological performance of 3D-printed bioceramic implants. The purpose of this review is to provide an overview of 3DP techniques and strategies for bioceramic materials designed for bone regeneration. The review also addresses the use and incorporation of active biomolecules in 3D-printed bioceramic constructs to stimulate bone regeneration. By controlling the surface roughness and chemical composition of the implant, the construct can be tailored to promote osseointegration and reduce the risk of adverse tissue reactions. Additionally, growth factors, such as bone morphogenic proteins (rhBMP-2) and pharmacologic agent (dipyridamole), can be incorporated to promote the growth of new bone tissue. Incorporating porosity into bioceramic constructs can improve bone tissue formation and the overall biological response of the implant. As such, employing surface modification, combining with other materials, and incorporating the 3DP workflow can lead to better patient healing outcomes.

Investigating the perceptions and experiences of Canadian dentists on dental regulatory bodies' communications and guidelines during the COVID-19 pandemic.

OBJECTIVE: Dental regulatory bodies aim to ensure the health and safety of dentists, dental staff patients and the public. An important responsibility during a pandemic is to communicate risk and guidelines for patient care. Limited data exist on the perceptions and experiences of dentists navigating new guidelines for mitigating risk in dental care during the pandemic. The objective of this study was to use a qualitative approach to explore how dentists in Canada experienced and perceived their regulatory bodies' communication about COVID-19 risks and guidelines during the pandemic. METHODS: Participants were Canadian dentists (N = 644) recruited through the email roster of nine provincial dental associations or regulatory bodies. This qualitative analysis was nested within a prospective longitudinal cohort study in which data were collected using online questionnaires at regular intervals from August 2020 to November 2021. To address the objective reported in this paper, a conventional qualitative content analysis method was applied to responses to three open-ended questions included in the final questionnaire. RESULTS: Participants encountered challenges and frustrations amid the COVID-19 pandemic, grappling with diverse regulations and communications from dental bodies. While some bodies offered helpful guidance, many participants felt the need for improved communication on guidelines. Dentists urged for expedited, clearer and more frequent updates, expressing difficulty in navigating overwhelming information. Negative views emerged on the vague and unclear communication of COVID-19 guidelines, contributing to confusion and frustration among participants. CONCLUSION: As COVID-19 persists and in planning for future pandemics, these experiential findings will help guide regulatory bodies in providing clear, timely and practical guidelines to protect the health and safety of dentists, dental staff, patients and the public.

Personal protective equipment during COVID-19: A natural history of dental and dental hygiene regulatory guidance in Canada.

BACKGROUND: Due to the evolving nature of COVID-19, there is evidence that COVID-19-specific infection prevention and control guideline (IPCG) documents formulated for oral health care settings are also changing rapidly. To better inform future policies, a comprehensive review of all IPCG documents across different phases of restrictions for oral health care practitioners is required. TYPES OF STUDIES REVIEWED: A search was performed for documents shared from March 2020 through January 2022 on websites of oral health regulatory authorities in Canada's 10 provinces and 3 territories. The authors performed a narrative review of the identified IPCG documents for dentists (n = 78) and dental hygienists (n = 57). RESULTS: Overall findings from more than 100 IPCG documents distributed during a period of 23 months revealed that the frequency of these updates differed among jurisdictions and between the 2 oral health care practitioners (ie, dentists and dental hygienists) within the same jurisdiction. The most notable observation was the different face-covering recommendations for dentists and dental hygienists within the same jurisdiction during the same timeframe. A common document was sometimes observed for dentists and dental hygienists, however, most jurisdictions had separate IPCG documents. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The different approaches could have been justified on the basis of prevalence of COVID-19 and availability of personal protective equipment; however, there was a risk of creating confusion about IPCG best practices. The findings of this review will support decision makers when planning future development and dissemination of regulations for all oral health care practitioners.

Dental Extractions Before Radiation Therapy and the Risk of Osteoradionecrosis in Patients With Head and Neck Cancer.

Importance: Patients with head and neck cancer undergo extraction of teeth with poor prognoses to minimize post-radiation therapy (RT) extractions, which are known to cause osteoradionecrosis (ORN). However, many patients are required to start RT before the extraction sites are completely healed. The role of pre-RT extractions in the development of ORN has been disputed in literature. Objective: To determine whether the timing of pre-RT dental extractions is associated with ORN development in patients with head and neck cancer. Design, Setting, and Participants: This retrospective cohort study was conducted at a single institution (Princess Margaret Cancer Centre, Toronto, Canada) between January 1, 2011, and January 1, 2018, and included 879 patients with head and neck cancer who underwent pre-RT dental extractions before curative RT of 45 Gy or greater. Patient demographic information and clinical characteristics (eg, primary cancer site, nodal involvement, chemotherapy, smoking status, dental pathology) were considered. Data analyses were performed from July to December 2022. Main outcomes and measures: Timing (number of days) from dental extractions to RT start date and pre-RT extractions categorized as healed, minor bone spicules (MBS), or ORN. Results: The study population consisted of 879 patients with a median (range) age of 62 (20-96) years, with 685 men (78%) and 194 women (22%). Of these, 847 (96.3%) healed from pre-RT dental extractions, 16 (1.8%) developed MBS, and 16 (1.8%) developed ORN. The median (range) time in number of days from pre-RT extraction(s) to start of RT was 9 (0-98) days in the healed cohort, 6 (3-23) days in the MBS cohort, and 6 (0-12) days in the ORN cohort. There was a large difference in the timing of pre-RT extractions between the healed and the MBS cohorts (mean 11.9 vs 7.4 days to radiation; difference 4.4; 95% CI, 1.5-7.3), and the healed and the ORN cohorts (mean 11.9 vs 7.1 days; difference 4.8 days; 95% CI, 2.6-7.1). Conclusion: The findings of this retrospective cohort study suggest that there was an important association between the timing of pre-RT dental extractions and ORN when extractions occurred within 7 days of the RT start date. Despite this, ORN after pre-RT extractions is relatively rare. These findings indicate that patients with head and neck cancer who are to undergo RT should not delay treatment for extractions when it might compromise oncologic control.

Effects of a stabilized stannous fluoride dentifrice on clinical, immunomodulatory, and microbial outcomes in a human experimental gingivitis model.

BACKGROUND: Stannous fluoride dentifrice is well established for its beneficial clinical effects. In this study, we evaluated the effects of stannous fluoride on inflammation and oral microbiome. METHODS: In this randomized, parallel-arm, double-blind, controlled clinical trial, we compared clinical resolution of experimental gingivitis by evaluating bleeding on probing, gingival index, and plaque index between stannous fluoride stabilized with zinc phosphate (test) and sodium fluoride (control) dentifrices. Further, these groups were compared for oral neutrophil counts, systemic priming of neutrophils, gingival crevicular fluid (GCF) expression of inflammatory markers, and the oral microbiome. RESULTS: We found significant reduction in bleeding on probing in the test group compared to the control group in experimental gingivitis when participants used the test dentifrice prior to induction of experimental gingivitis. The test group also showed significant reductions in GCF levels of inflammatory markers (matrix metalloproteinase 8 [MMP8], receptor activator of nuclear factor kappa-Β ligand [RANKL]), oral polymorphonuclear neutrophil (PMN) counts, and systemic neutrophil priming (CD11b expression) during experimental gingivitis. Further, significant reductions in the gram-negative genera Porphyromonas, Tannerella, and Treponema were noted in the test group. CONCLUSION: The stannous fluoride stabilized with zinc phosphate dentifrice formulation demonstrated clinical reduction in gingival inflammation and a beneficial effect on microbiome and immune markers. This intervention should be explored as a preventive aid in the progression of plaque-induced gingivitis to periodontitis.

The chemorepellent, SLIT2, bolsters innate immunity against Staphylococcus aureus.

Neutrophils are essential for host defense against Staphylococcus aureus (S. aureus). The neuro-repellent, SLIT2, potently inhibits neutrophil chemotaxis, and might, therefore, be expected to impair antibacterial responses. We report here that, unexpectedly, neutrophils exposed to the N-terminal SLIT2 (N-SLIT2) fragment kill extracellular S. aureus more efficiently. N-SLIT2 amplifies reactive oxygen species production in response to the bacteria by activating p38 mitogen-activated protein kinase that in turn phosphorylates NCF1, an essential subunit of the NADPH oxidase complex. N-SLIT2 also enhances the exocytosis of neutrophil secondary granules. In a murine model of S. aureus skin and soft tissue infection (SSTI), local SLIT2 levels fall initially but increase subsequently, peaking at 3 days after infection. Of note, the neutralization of endogenous SLIT2 worsens SSTI. Temporal fluctuations in local SLIT2 levels may promote neutrophil recruitment and retention at the infection site and hasten bacterial clearance by augmenting neutrophil oxidative burst and degranulation. Collectively, these actions of SLIT2 coordinate innate immune responses to limit susceptibility to S. aureus.

Oral inflammatory load predicts vascular function in a young adult population: a pilot study.

Background: The periodontium is a highly vascularized area of the mouth, and periodontitis initiates negative functional and structural changes in the vasculature. However, mild oral inflammation, including levels experienced by many apparently healthy individuals, has an unclear impact on cardiovascular function. The purpose of this pilot study is to investigate the effects of objectively measured whole mouth oral inflammatory load (OIL) on vascular function in apparently healthy individuals. Methods: In this cross-sectional and correlational analysis, we recruited 28 young (18-30 years) and systemically healthy participants (16 male, 12 female). Using oral neutrophil counts, a validated measure for OIL, we collected participant's mouth rinse samples and quantified OIL. Blood pressure, arterial stiffness (pulse-wave velocity) and endothelial function (brachial artery flow-mediated dilation) were also measured. Results: Only oral neutrophil count significantly predicted flow-mediated dilation % (p = 0.04; R2 = 0.16, ß = - 1.05) and those with OIL levels associated with >2.5 × 105 neutrophil counts (n = 8) had a lower flow-mediated dilation % (6.0 ± 2.3%) than those with counts associated with gingival health with less than 2.5 × 105 neutrophil counts (10.0 ± 5.2%, p = 0.05). There were no significant predictors for arterial stiffness. Conclusion: We found that OIL was a predictor of reduced flow-mediated dilation. An impairment in flow-mediated dilation is an indicator of future possible risk of cardiovascular disease-one of the leading causes of death in North America. Therefore, this study provides evidence for the importance of oral health and that OIL may impact endothelial function.

Development and Standardization of a Classification System for Osteoradionecrosis: Implementation of a Risk-Based Model.

Purpose: Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN. Methods: Consecutive head-and-neck cancer (HNC) patients treated with curative-intent IMRT (≥ 45Gy) in 2011-2018 were included. Occurrence of ORN was identified from in-house prospective dental and clinical databases and charts. Multivariable logistic regression model was used to identify risk factors and stratify patients into high-risk and low-risk groups. A novel ORN classification system was developed to depict ORN severity by modifying existing systems and incorporating expert opinion. The performance of the novel system was compared to fifteen existing systems for their ability to identify and predict serious ORN event (jaw fracture or requiring jaw resection). Results: ORN was identified in 219 out of 2732 (8%) consecutive HNC patients. Factors associated with high-risk of ORN were: oral-cavity or oropharyngeal primaries, received IMRT dose ≥60Gy, current/ex-smokers, and/or stage III-IV periodontal disease. The ORN rate for high-risk vs low-risk patients was 12.7% vs 3.1% (p<0.001) with an area-under-the-receiver-operating-curve (AUC) of 0.71. Existing ORN systems overclassified serious ORN events and failed to recognize maxillary ORN. A novel ORN classification system, RadORN, was proposed based on vertical extent of bone necrosis and presence/absence of exposed bone/fistula. This system detected serious ORN events in 5.7% of patients and statistically outperformed existing systems. Conclusion: We identified risk factors for ORN, and proposed a novel ORN classification system based on vertical extent of bone necrosis and presence/absence of exposed bone/fistula. It outperformed existing systems in depicting the seriousness of ORN, and may facilitate clinical care and clinical trials.

The Role of Bacterial, Dentinal, Salivary, and Neutrophil Degradative Activity in Caries Pathogenesis.

Until recently, it was widely accepted that bacteria participate in caries pathogenesis mainly through carbohydrate fermentation and acid production, which promote the dissolution of tooth components. Neutrophils, on the other hand, were considered white blood cells with no role in caries pathogenesis. Nevertheless, current literature suggests that both bacteria and neutrophils, among other factors, possess direct degradative activity towards both dentinal collagen type-1 and/or methacrylate resin-based restoratives and adhesives, the most common dental restoratives. Neutrophils are abundant leukocytes in the gingival sulcus, where they can readily reach adjacent tooth roots or gingival and cervical restorations and execute their degradative activity. In this review, we present the latest literature evidence for bacterial, dentinal, salivary, and neutrophil degradative action that may induce primary caries, secondary caries, and restoration failure.

Adseverin, an actin-binding protein, modulates hypertrophic chondrocyte differentiation and osteoarthritis progression.

In osteoarthritis (OA), a disease characterized by progressive articular cartilage degradation and calcification, the articular chondrocyte phenotype changes and this correlates with actin cytoskeleton alterations suggesting that it regulates gene expression essential for proper phenotype. This study reports that OA is associated with the loss of adseverin, an actin capping and severing protein. Adseverin deletion (Adseverin-/-) in mice compromised articular chondrocyte function, by reducing F-actin and aggrecan expression and increasing apoptosis, Indian hedgehog, Runx2, MMP13, and collagen type X expression, and cell proliferation. This led to stiffer cartilage and decreased hyaline and increased calcified cartilage thickness. Together, these changes predisposed the articular cartilage to enhanced OA severity in Adseverin-/- mice who underwent surgical induction of OA. Adseverin-/- chondrocyte RNA sequencing and in vitro studies together suggests that adseverin modulates cell viability and prevents mineralization. Thus, adseverin maintains articular chondrocyte phenotype and cartilage tissue homeostasis by preventing progression to hypertrophic differentiation in vivo. Adseverin may be chondroprotective and a potential therapeutic target.