Immunogenicity and protective efficacy of adenoviral and subunit RSV vaccines based on stabilized prefusion F protein in pre-clinical models

Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development.     

Are risk factors necessary for pretest probability assessment of coronary artery disease? A patient similarity network analysis of the PROMISE trial

BackgroundPretest probability (PTP) calculators utilize epidemiological-level findings to provide patient-level risk assessment of obstructive coronary artery disease (CAD). However, their limited accuracies question whether dissimilarities in risk factors necessarily result in differences in CAD. Using patient similarity network (PSN) analyses, we wished to assess the accuracy of risk factors and imaging markers to identify ≥50% luminal narrowing on coronary CT angiography (CCTA) in stable chest-pain patients.MethodsWe created four PSNs representing: patient characteristics, risk factors, non-coronary imaging markers and calcium score. We used spectral clustering to group individuals with similar risk profiles. We compared PSNs to a contemporary PTP score incorporating calcium score and risk factors to identify ≥50% luminal narrowing on CCTA in the CT-arm of the PROMISE trial. We also conducted subanalyses in different age and sex groups.ResultsIn 3556 individuals, the calcium score PSN significantly outperformed patient characteristic, risk factor, and non-coronary imaging marker PSNs (AUC: 0.81 vs. 0.57, 0.55, 0.54; respectively, p ?< ?0.001 for all). The calcium score PSN significantly outperformed the contemporary PTP score (AUC: 0.81 vs. 0.78, p ?< ?0.001), and using 0, 1–100 and ?> ?100 cut-offs provided comparable results (AUC: 0.81 vs. 0.81, p ?= ?0.06). Similar results were found in all subanalyses.ConclusionCalcium score on its own provides better individualized obstructive CAD prediction than contemporary PTP scores incorporating calcium score and risk factors. Risk factors may not be able to improve the diagnostic accuracy of calcium score to predict ≥50% luminal narrowing on CCTA.     

Effects of ambient particulate matter on vascular tissue: a review

ABSTRACT

Fine and ultra-fine particulate matter (PM) are major constituents of urban air pollution and recognized risk factors for cardiovascular diseases. This review examined the effects of PM exposure on vascular tissue. Specific mechanisms by which PM affects the vasculature include inflammation, oxidative stress, actions on vascular tone and vasomotor responses, as well as atherosclerotic plaque formation. Further, there appears to be a greater PM exposure effect on susceptible individuals with pre-existing cardiovascular conditions.     

Dental anxiety in relation to torture experiences and symptoms of post‐traumatic stress disorder

Torture victims often show symptoms of dental anxiety when receiving dental care, but little systematic research is available. The purpose of this study was to explore torture experiences, symptoms of post‐traumatic stress disorder (PTSD), and dental anxiety in refugees in Norway and to test the hypothesis that refugees with torture experiences are more prone to dental anxiety than refugees with no such experiences. A total of 173 refugees were interviewed shortly after an oral examination. The Modified Dental Anxiety Scale (MDAS) and the Harvard Trauma Questionnaire‐PTSS16 were administered verbally through attending interpreters. Among torture victims (47%, n = 81), the prevalence of torture experiences involving mouth or teeth was 35% and 23%, respectively. Harvard Trauma Questionnaire mean sum scores were statistically significantly higher in torture victims (34.3 vs. 24.8). Torture survivors report a larger number of symptoms of PTSD, and dental anxiety shows a higher prevalence in refugees reporting PTSD symptoms than in refugees who do not report such symptoms. When analysed using logistic regression models, the data showed the odds of high levels of dental anxiety being 6.1 times higher in refugees with torture experiences compared with other refugees and 9.3 times higher in torture victims with PTSD symptoms. Oral health professionals should be aware of these associations when providing dental care to refugees. The hypothesis that tortured refugees are more prone to dental anxiety is supported.     

Lymphoplasmacytic plaque in children: Case report and literature review

We report a case of benign lymphoplasmacytic plaque (LPP) in a child. These asymptomatic erythematous papulonodular lesions are an emerging clinicopathological entity. Herein, we describe a previously unreported site for LPP lesions, namely, the volar wrist and the distal ipsilateral palm.     

Dual-Energy Computed Tomography as an Adjunct in the Evaluation of Peripheral Chronic Total Occlusions: A Feasibility Study

This study investigated the role of dual-energy computed tomography (CT) for lesion characterization in patients with peripheral arterial disease manifesting with chronic total occlusions (CTOs). Forty-one symptomatic patients with CTOs underwent dual-energy CT angiography before endovascular treatment. The lesions were subsequently analyzed in a dedicated workstation, and 2 indexes—dual-energy index (DEI) and effective Z (Z_eff)—were calculated, ranging from 0.0027 to 0.321 and from 6.89 to 13.02, respectively. Statistical analysis showed a significant correlation between the DEI and Z_eff values (P < .001). The interobserver intraclass correlation coefficient was 0.91 for the mean Z_eff values and 0.86 for the mean DEI values. This technique could potentially provide useful information regarding the composition of a CTO.     

Oral biosciences: The annual review 2021

BackgroundThe Journal of Oral Biosciences is devoted to advancing and disseminating fundamental knowledge concerning every aspect of oral biosciences.HighlightThis review features review articles in the fields of “Extracellular Vesicles,” “Propolis,” “Odontogenic Tumors,” “Periodontitis,” “Periodontium,” “Flavonoids,” “Lactoferrin,” “Dental Plaque,” “Anatomy,” “Induced Pluripotent Stem Cells,” “Bone Cell Biology,” “Dysgeusia,” “Dental Caries,” and “Dental Pulp Cavity,” in addition to the review article by the winners of the “Lion Award” (“Sox9 function in salivary gland development”) presented by the Japanese Association for Oral Biology.ConclusionThese reviews in the Journal of Oral Biosciences have inspired its readers to broaden their knowledge regarding various aspects of oral biosciences. The current editorial review introduces these exciting review articles.     

Effect of Gum Arabic on plaque-induced gingivitis: A randomised controlled trial

New approaches to treating periodontal diseases aim to balance sustaining the natural oral microbiota and modifying the host immune response. Gum Arabic (GA) is a natural polysaccharide rich in prebiotics.The aim of this study was to assess the effect of GA on clinical (Plaque Index (PI), Gingival Index (GI)) and immunological (Gingival Crevicular Fluid Interleukin 1 Beta (GCF IL-1 β)) parameters in patients with plaque-induced gingivitis.Materials and methodsThis placebo-controlled, double-blinded randomised clinical trial was conducted at the Department of Periodontology at Khartoum Dental Teaching Hospital, Khartoum, Sudan, from July to October 2016. Patients diagnosed with plaque-induced gingivitis meeting the study eligibility criteria were enrolled. At baseline, PI, GI and GCF IL-1β were measured. Patients received full-mouth scaling and were randomly assigned to receive either GA powder (intervention group) or Microcrystalline cellulose powder (placebo group). The patients were instructed to apply the treatment twice a day throughout the study. The PI, GI and GCF IL-1β were reassessed after 30 and 60 days.ResultsA total of 60 patients were enrolled (30 in each group). Compared to the placebo group, the intervention group showed a statistically significant reduction in GI scores after 30 days and improved PI scores at 30 and 60 days. Between baseline and 60 days, patients who received GA exhibited a significant reduction in GCF IL-1β levels compared to the placebo group.ConclusionGA was found to be effective in controlling plaque and gingivitis.Clinical Trial Registration. ISRCTN registry ISRCTN14209449.