Perceptions regarding the use of a three-dimensionally-printed manufactured educational simulator for periodontal treatment of intraosseous and interradicular lesions.

PURPOSE/OBJECTIVES: Treating intraosseous lesions (IOLs) and interradicular bone lesions (IRLs) is an extremely technical dental procedure in periodontics. Instrumentation of these lesions is often perceived as difficult by students and inexperienced dentists before they perform a certain number of procedures on patients in the clinic. The aim of this article is to evaluate a cost-effective three-dimensional (3D)-printed educational simulator for the periodontal treatment of IOLs/IRLs (including scaling, incisions and sutures). METHODS: The simulators were first developed digitally, and then manufactured using printable resins and specific materials; finally, they were assembled using different bonding systems. To evaluate the simulators, assessments were gathered from two target populations: undergraduate students and periodontics experts. These individuals tested the simulator and completed a cross-sectional questionnaire based on a Likert scale with comparative and pedagogical items scored from one to five. The purpose of the questionnaire was to compare our simulator to clinical reality (i.e., operation on human jaws) and to an animal simulator (i.e., simulation of porcine jaws). The results are expressed as the mean and standard deviation and were statistically analyzed with the Wilcoxon signed-rank test. RESULTS: Overall, the results were satisfactory for both groups of testers (4.70 and 4.61 out of five for students and experts, respectively, for global satisfaction). CONCLUSIONS: The overall educational relevance of the simulator designed herein highlights the fact that 3D-printed educational simulators could enable efficient cognitive-functional learning for clinical IOL/IRL treatment.

Machine learning insights into thrombo-ischemic risks and bleeding events through platelet lysophospholipids and acylcarnitine species.

Coronary artery disease (CAD) often leads to adverse events resulting in significant disease burdens. Underlying risk factors often remain inapparent prior to disease incidence and the cardiovascular (CV) risk is not exclusively explained by traditional risk factors. Platelets inherently promote atheroprogression and enhanced platelet functions and distinct platelet lipid species are associated with disease severity in patients with CAD. Lipidomics data were acquired using mass spectrometry and processed alongside clinical data applying machine learning to model estimates of an increased CV risk in a consecutive CAD cohort (n = 595). By training machine learning models on CV risk measurements, stratification of CAD patients resulted in a phenotyping of risk groups. We found that distinct platelet lipids are associated with an increased CV or bleeding risk and independently predict adverse events. Notably, the addition of platelet lipids to conventional risk factors resulted in an increased diagnostic accuracy of patients with adverse CV events. Thus, patients with aberrant platelet lipid signatures and platelet functions are at elevated risk to develop adverse CV events. Machine learning combining platelet lipidome data and common clinical parameters demonstrated an increased diagnostic value in patients with CAD and might improve early risk discrimination and classification for CV events.

Periodontitis in ischemic stroke: impact of Porphyromonas gingivalis on thrombus composition and ischemic stroke outcomes.

Background: Periodontitis is associated with an increased risk of ischemic stroke, but the mechanisms underlying this association remain unclear. Objectives: Our objective was to determine whether Porphyromonas gingivalis (Pg), a periodontal bacterium, could be detected within thrombus aspirates, modify thrombus composition, and endovascular therapy responses. Methods: The presence of Pg gingipain in 175 consecutive thrombi from patients with large vessel occlusion stroke enrolled in the multicenter research cohort compoCLOT was investigated by immunostaining. Thrombus blood cell composition according to gingipain status was analyzed in a subset of 63 patients. Results: Pg gingipain immunostaining was positive in 33.7% of thrombi (95% CI, 26.7%-40.8%). The percentage of near to complete reperfusion (modified Thrombolysis in Cerebral Infarction Score 2c/3) at the end of the procedure was lower in the Pgpos group than the Pgneg group (39.0% vs 57.8% respectively; adjusted odds ratio, 0.38; 95% CI, 0.19-0.77). At 3 months, 35.7% of patients in the Pgpos group had a favorable neurological outcome vs 49.5% in the Pgneg group (odds ratio, 0.65; 95% CI, 0.30-1.40). Quantitative analysis of a subset of 63 thrombi showed that neutrophil elastase content was significantly (P < .05) higher in Pgpos thrombi than in Pgneg thrombi. Conclusion: Our results indicate that intrathrombus Pg gingipain is associated with increased neutrophil content and resistance to endovascular therapy.

[Periodontitis : An underestimated risk of cardiovascular diseases]. / La parodontite : un risque sous-estimé des maladies cardiovasculaires.

Epidemiological studies have identified periodontitis as a contributing factor to cardiovascular risk. Periodontitis is a chronic inflammatory disease that affects the tissues supporting the teeth. Although the nature of the association between periodontitis and cardiovascular disease (CVD) remains to be defined, the low-grade systemic inflammation and chronic bacteremia associated with periodontitis appear to be involved in the development of atherosclerosis and associated cardiovascular pathologies. Periodontal treatment has been shown to improve cardiovascular health parameters. A bidirectional preventive approach, involving the management of both periodontitis and cardiovascular risk factors, could lead to a reduction in morbidity and mortality related to cardiovascular disease.

Title: La parodontite : un risque sous-estimé des maladies cardiovasculaires. Abstract: Les études épidémiologiques identifient la parodontite, maladie inflammatoire chronique des tissus de soutien des dents, comme un facteur contribuant au risque cardiovasculaire. Bien que la nature de l'association entre parodontite et maladies cardio-vasculaires (MCV) reste à définir (causalité ou corrélation), l'inflammation systémique de bas grade et les bactériémies chroniques qui sont associées aux parodontites apparaissent impliquées dans le développement de l'athérosclérose et des maladies cardio-vasculaires associées. Le traitement parodontal semble contribuer à l'amélioration des paramètres de la santé cardiovasculaire. Dès lors, une approche de prévention bidirectionnelle, impliquant à la fois la gestion de la parodontite et des facteurs de risque cardiovasculaire, pourrait permettre une réduction de la morbidité et de la mortalité liées aux MCV.

Large-scale lipidomics profiling reveals characteristic lipid signatures associated with an increased cardiovascular risk.

BACKGROUND AND AIMS: Patients with cardiovascular disease (CVD) are at high risk to develop adverse events. The distinct risk of developing adverse cardiovascular (CV) events is not solely explained by traditional risk factors. Platelets are essentially involved in progression of CVD including coronary artery disease (CAD) and platelet hyperreactivity leads to development of adverse CV events. Alterations in the platelet lipidome lead to platelet hyperresponsiveness and thus might alter the individual risk profile. In this study, we investigate the platelet lipidome of CAD patients by untargeted lipidomics and elucidate alterations in the lipid composition of patients with adverse CV events. METHODS: We characterized the platelet lipidome in a large consecutive CAD cohort (n = 1057) by an untargeted lipidomics approach using liquid chromatography coupled to mass spectrometry. RESULTS: The platelet lipidome in this study identified 767 lipids and characteristic changes occurred in patients with adverse CV events. The most prominent upregulated lipids in patients with cardiovascular events primarily belong to the class of phospholipids and fatty acyls. Further, upregulated platelet lipids are associated with an increased cardiovascular or bleeding risk and independently associated with adverse events. In addition, alterations of the platelet lipidome are associated with modulation of in vitro platelet functions. CONCLUSIONS: Our results reveal that the composition of the platelet lipidome is altered in CVD patients with an increased cardiovascular risk and distinct platelet lipids may indicate adverse events. Results of this study may contribute to improved risk discrimination and classification for cardiovascular events in patients with CVD. Main findings of this study and hypothetical impact of altered platelet lipid signatures in patients with adverse cardiovascular events on platelet function and clinical outcome. LPE lysophosphatidylethanolamines, CAR acylcarnitines, FA fatty acids.

Statin Treatment Is Associated with Alterations in the Platelet Lipidome.

BACKGROUND: Platelets are key players in the pathophysiology of coronary artery disease (CAD) and platelet hyperreactivity leads to increased risk of developing adverse cardiovascular events. Further, significant changes in the platelet lipidome occur in patients with acute coronary syndrome (ACS) and critically regulated lipids lead to platelet hyperresponsiveness. Statin treatment is crucial in the treatment and prevention of patients with CAD by remodeling lipid metabolism. OBJECTIVE: In this study, we investigate the platelet lipidome of CAD patients by untargeted lipidomics, highlighting significant changes between statin-treated and naïve patients. METHODS: We characterized the platelet lipidome in a CAD cohort (n = 105) by an untargeted lipidomics approach using liquid chromatography coupled to mass spectrometry. RESULTS: Among the annotated lipids, 41 lipids were significantly upregulated in statin-treated patients, whereas 6 lipids were downregulated compared to naïve patients. The most prominent upregulated lipids in statin-treated patients belong to the class of triglycerides, cholesteryl esters, palmitic acid, and oxidized phospholipids, whereas mainly glycerophospholipids were downregulated compared to untreated patients. A more pronounced effect of statin treatment on the platelet lipidome was observed in ACS patients. We further highlight a dose-dependent influence on the platelet lipidome. CONCLUSION: Our results reveal that the platelet lipidome is altered in CAD patients with statin treatment and upregulated lipids embody mainly characteristic triglycerides, whereas downregulated lipids mostly compromise glycerophospholipids, which may play a role in the pathophysiology of CAD. Results of this study may contribute to the understanding of statin treatment softening the lipid phenotype.

Oral microbiota and atherothrombotic carotid plaque vulnerability in periodontitis patients. A cross-sectional study.

BACKGROUND: An increased risk of atherothrombotic vascular events has been reported in periodontitis patients. Periodontitis is associated with dysbiotic subgingival biofilms and bacteremia. OBJECTIVE: We hypothesized (a) that the oral microbiome is associated with the carotid microbiome and (b) that periodontitis could contribute to plaque vulnerability. The aim of this study was to determine the associations between periodontitis, the carotid microbiome, and the local innate immune response in carotid atherothrombotic plaques vulnerable to rupture. METHODS: In this cross-sectional study, 45 patients admitted for carotid endarterectomy underwent a preoperative periodontal examination. The volume of intraplaque hemorrhage reflected by the hemoglobin level released in carotid-conditioned media was considered as a criterion of carotid plaque vulnerability. Levels of antibodies against periodontal bacteria were determined in sera. The signature of the oral microbiota was assessed by microbial whole-genome sequencing, nested PCR, and immunostaining in carotid plaque samples. Markers of neutrophil recruitment (leukotriene B4), neutrophil activation (myeloperoxidase, defensins), and cytokines were measured in carotid-conditioned media and/or plasma. RESULTS: All patients exhibited periodontitis. One hundred and forty-four bacterial genera were detected in the carotid microbiome. While Streptococcus was found in 84% of the carotid samples, periodontitis-associated genera were detected in 21%. P. gingivalis DNA and gingipains were also identified in carotid samples. There were significant inverse correlations between periodontal attachment loss/serum anti-P. gingivalis Immunoglobulin A and cytokine inhibiting neutrophils (all P < .01). There were also significant positive correlations between lipopolysaccharides, myeloperoxidase/human neutrophil peptides1-3, and hemoglobin levels (all P < .01). CONCLUSIONS: In patients at risk of stroke, the carotid plaque microbiome was highly diverse and compatible with an oral origin. Periodontitis was significantly associated with neutrophil activation markers and plaque vulnerability to rupture.

Emerging Nanotechnology in Non-Surgical Periodontal Therapy in Animal Models: A Systematic Review.

Periodontitis is one of the most prevalent inflammatory diseases. Its treatment, mostly mechanical and non-surgical, shows limitations. The aim of this systematic review was to investigate the effect of nanoparticles as a treatment alone in non-surgical periodontal therapy in animal models. A systematic search was conducted in Medline/PubMed, Web of Science, The Cochrane Library and Science Direct. The eligibility criteria were: studies (i) using nanoparticles as chemotherapeutic agent or as delivery system; (ii) including preclinical controlled animal model (experimental periodontitis); (iii) reporting alveolar bone loss; (iv) written in English; and (v) published up to June 2019. Risk of bias was evaluated according to the SYstematic Review Centre for Laboratory Animal Experimentation. On the 1324 eligible studies, 11 were included. All reported advantages in using nanoparticles for the treatment of periodontitis, highlighted by a reduction in bone loss. Agents modulating inflammation seem to be more relevant than antibiotics, in terms of efficiency and risk of antibiotic resistance. In addition, poly(lactic-co-glycolic acid) or drugs used as their own carrier appear to be the most interesting nanoparticles in terms of biocompatibility. Risk of bias assessment highlighted many criteria scored as unclear. There are encouraging preclinical data of using nanoparticles as a contribution to the treatment of periodontitis.

Innovative application of nested PCR for detection of Porphyromonas gingivalis in human highly calcified atherothrombotic plaques.

Atherothrombosis, leading to stroke and myocardial infarction, is responsible for most of the deaths in the world. An increased risk of atherothrombotic vascular events has been reported in patients with periodontitis. Periodontitis is a chronic multifactorial inflammatory disease, which involves a dysbiotic microbiota, and leads to a progressive destruction of the tooth-supporting apparatus. Transcient periodontal pathogen blood translocation, mainly bacteremia, has been associated with the severity of gingival inflammation. The identification of periodontal bacteria within atherothrombotic plaques is challenging and unpredictable. This review aims to summarize existing molecular technics for identifying periodontal microbiota in human atherothrombotic samples. A secondary objective is to describe a protocol for the identification of Porphyromonas gingivalis from highly calcified, atherothrombotic human samples that is based on our experience in translational cardiovascular research. Compared to direct real-time PCR, our protocol based on nested PCR has increased the detection of Porphyromonas gingivalis by 22.2% with good specificity.

Intraplaque hemorrhage, a potential consequence of periodontal bacteria gathering in human carotid atherothrombosis.

Periodontal diseases are multifactorial inflammatory diseases, caused by a bacterial biofilm involving both innate and adaptative immunity, characterized by the destruction of tooth-supporting tissues. In the context of periodontitis, the spread of weak pathogenic bacteria into the bloodstream has been described. These bacteria will preferentially localize to existing clot within the circulation. Atherothrombosis of the carotid arteries is a local pathology and a common cause of cerebral infarction. Intraplaque hemorrhages render the lesion more prone to clinical complications such as stroke. The main objective of this study is to explore the biological relationship between carotid intraplaque hemorrhage and periodontal diseases. This study included consecutive patients with symptomatic or asymptomatic carotid stenosis, admitted for endarterectomy surgical procedure (n=41). In conditioned media of the carotid samples collected, markers of neutrophil activation (myeloperoxidase or MPO, DNA-MPO complexes) and hemoglobin were quantified. To investigate the presence of DNA from periodontal bacteria in atherosclerotic plaque, PCR analysis using specific primers was performed. Our preliminary results indicate an association between neutrophil activation and intraplaque hemorrhages, reflected by the release of MPO (p<0,01) and MPO-DNA complexes (p<0,05). Presence of DNA from periodontitis-associated bacteria was found in 32/41 (78%) atheromatous plaque samples. More specifically, DNA from Pg, Tf, Pi, Aa was found in 46%, 24%, 34% and 68% of the samples, respectively. Hemoglobin levels were higher in conditioned media in carotid samples where the bacteria were found, but this was not statistically significant. Our data confirm the relationship between intraplaque hemorrhage and neutrophil activation. In addition, the presence of periodontal bacteria DNA in carotid atheromatous plaque, may contribute to this activation. Further analysis is needed to fully explore the raw data and specimens.

Different sympathetic pathways control the metabolism of distinct bone envelopes.

Bone remodeling, the mechanism that modulates bone mass adaptation, is controlled by the sympathetic nervous system through the catecholaminergic pathway. However, resorption in the mandible periosteum envelope is associated with cholinergic Vasoactive Intestinal Peptide (VIP)-positive nerve fibers sensitive to sympathetic neurotoxics, suggesting that different sympathetic pathways may control distinct bone envelopes. In this study, we assessed the role of distinct sympathetic pathways on rat femur and mandible envelopes. To this goal, adult male Wistar rats were chemically sympathectomized or treated with agonists/antagonists of the catecholaminergic and cholinergic pathways; femora and mandibles were sampled. Histomorphometric analysis showed that sympathectomy decreased the number of preosteoclasts and RANKL-expressing osteoblasts in mandible periosteum but had no effect on femur trabecular bone. In contrast, pharmacological stimulation or repression of the catecholaminergic cell receptors impacted the femur trabecular bone and mandible endosteal retromolar zone. VIP treatment of sympathectomized rats rescued the disturbances of the mandible periosteum and alveolar wall whereas the cholinergic pathway had no effect on the catecholaminergic-dependent envelopes. We also found that VIP receptor-1 was weakly expressed in periosteal osteoblasts in the mandible and was increased by VIP treatment, whereas osteoblasts of the retromolar envelope that was innervated only by tyrosine hydroxylase-immunoreactive fibers, constitutively expressed beta-2 adrenergic receptors. These data highlight the complexity of the sympathetic control of bone metabolism. Both the embryological origin of the bone (endochondral for the femur, membranous for the mandibular periosteum and the socket wall) and environmental factors specific to the innervated envelope may influence the phenotype of the sympathetic innervation. We suggest that an origin-dependent imprint of bone cells through osteoblast-nerve interactions determines the type of autonomous system innervating a particular bone envelope.