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Importance: Development of myocardial fibrosis in patients with aortic stenosis precedes left ventricular decompensation and is associated with an adverse long-term prognosis., Objective: To investigate whether early valve intervention reduced the incidence of all-cause death or unplanned aortic stenosis-related hospitalization in asymptomatic patients with severe aortic stenosis and myocardial fibrosis., Design, Setting, and Participants: This prospective, randomized, open-label, masked end point trial was conducted between August 2017 and October 2022 at 24 cardiac centers across the UK and Australia. Asymptomatic patients with severe aortic stenosis and myocardial fibrosis were included. The final date of follow-up was July 26, 2024., Intervention: Early valve intervention with transcatheter or surgical aortic valve replacement or guideline-directed conservative management., Main Outcomes and Measures: The primary outcome was a composite of all-cause death or unplanned aortic stenosis-related hospitalization in a time-to-first-event intention-to-treat analysis. There were 9 secondary outcomes, including the components of the primary outcome and symptom status at 12 months., Results: The trial enrolled 224 eligible patients (mean [SD] age, 73 [9] years; 63 women [28%]; mean [SD] aortic valve peak velocity of 4.3 [0.5] m/s) of the originally planned sample size of 356 patients. The primary end point occurred in 20 of 113 patients (18%) in the early intervention group and 25 of 111 patients (23%) in the guideline-directed conservative management group (hazard ratio, 0.79 [95% CI, 0.44-1.43]; P = .44; between-group difference, -4.82% [95% CI, -15.31% to 5.66%]). Of 9 prespecified secondary end points, 7 showed no significant difference. All-cause death occurred in 16 of 113 patients (14%) in the early intervention group and 14 of 111 (13%) in the guideline-directed group (hazard ratio, 1.22 [95% CI, 0.59-2.51]) and unplanned aortic stenosis hospitalization occurred in 7 of 113 patients (6%) and 19 of 111 patients (17%), respectively (hazard ratio, 0.37 [95% CI, 0.16-0.88]). Early intervention was associated with a lower 12-month rate of New York Heart Association class II-IV symptoms than guideline-directed conservative management (21 [19.7%] vs 39 [37.9%]; odds ratio, 0.37 [95% CI, 0.20-0.70])., Conclusions and Relevance: In asymptomatic patients with severe aortic stenosis and myocardial fibrosis, early aortic valve intervention had no demonstrable effect on all-cause death or unplanned aortic stenosis-related hospitalization. The trial had a wide 95% CI around the primary end point, with further research needed to confirm these findings., Trial Registration: ClinicalTrials.gov Identifier: NCT03094143.

Introduction: Placement of an implant in the maxillary anterior region is challenging due to the angulation of bone in this area. Angled abutments may be used to achieve proper restorative contours. The present study was undertaken to examine and compare the stress levels of implants in the maxillary anterior region having different types of internal connections and different abutment angulations., Material and Methods: Implants with three types of abutment connections, internal conical, Morse taper, and internal hex, were modeled using SolidWorks software. Three abutment angulations of 0, 15, and 30 degrees were used for each type of implant. A 100 N axial load was applied to the implants, and the stresses on the implant, abutment, and bone were analyzed by finite element analysis., Results: Among the straight abutments, the most stress was in model 3A (62.60 MPa). The stress value among angled abutments was highest with 30-degree angled abutments. The value was highest in model 3C (94.83 MPa). Internal hex connection showed the highest stress levels in all degrees of angulation of the abutment, and Morse taper connection showed the least amount of stress in all three abutment angles. The most stress concentration was seen in the cortical bone on the buccal surface in the implant-abutment junction., Conclusion: The Morse taper design of implant exhibited the least-highest stress levels on the alveolar bone. The stress levels increased with the increasing angulation of the implant or implant-abutment connection.

The placenta, composed of chorionic villi, changes dramatically across gestation. Understanding differences in ongoing pregnancies are essential to identify the role of chorionic villi at specific times in gestation and develop biomarkers and prognostic indicators of maternal-fetal health. The normative mRNA profile is established using next-generation sequencing of 124 first trimester and 43 third trimester human placentas from ongoing healthy pregnancies. Stably expressed genes (SEGs) not different between trimesters and with low variability are identified. Differential expression analysis of first versus third trimester adjusted for fetal sex is performed, followed by a subanalysis with 23 matched pregnancies to control for subject variability using the same genetic and environmental background. Placenta expresses 14,979 polyadenylated genes above sequencing noise (transcripts per million > 0.66), with 10.7% SEGs across gestation. Differentially expressed genes (DEGs) account for 86.7% of genes in the full cohort [false discovery rate (FDR) < 0.05]. Fold changes highly correlate between the full cohort and subanalysis (Pearson = 0.98). At stricter thresholds (FDR < 0.001, fold change > 1.5), there remains 50.1% DEGs (3353 upregulated in first and 4155 upregulated in third trimester). This is the largest mRNA atlas of healthy human placenta across gestation, controlling for genetic and environmental factors, demonstrating substantial changes from first to third trimester in chorionic villi. Specific differences and SEGs may be used to understand the specific role of the chorionic villi throughout gestation and develop first trimester biomarkers of placental health that transpire across gestation, which can be used for future development of biomarkers for maternal-fetal health., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Fetal sex affects fetal and maternal health outcomes in pregnancy, but this connection remains poorly understood. As the placenta is the route of fetomaternal communication and derives from the fetal genome, placental gene expression sex differences may explain these outcomes., Objectives: We utilized next generation sequencing to study the normal human placenta in both sexes in first and third trimester to generate a normative transcriptome based on sex and gestation., Study Design: We analyzed 124 first trimester (T1, 59 female and 65 male) and 43 third trimester (T3, 18 female and 25 male) samples for sex differences within each trimester and sex-specific gestational differences., Results: Placenta shows more significant sexual dimorphism in T1, with 94 T1 and 26 T3 differentially expressed genes (DEGs). The sex chromosomes contributed 60.6% of DEGs in T1 and 80.8% of DEGs in T3, excluding X/Y pseudoautosomal regions. There were 6 DEGs from the pseudoautosomal regions, only significant in T1 and all upregulated in males. The distribution of DEGs on the X chromosome suggests genes on Xp (the short arm) may be particularly important in placental sex differences. Dosage compensation analysis of X/Y homolog genes shows expression is primarily contributed by the X chromosome. In sex-specific analyses of first versus third trimester, there were 2815 DEGs common to both sexes upregulated in T1, and 3263 common DEGs upregulated in T3. There were 7 female-exclusive DEGs upregulated in T1, 15 female-exclusive DEGs upregulated in T3, 10 male-exclusive DEGs upregulated in T1, and 20 male-exclusive DEGs upregulated in T3., Discussion: This is the largest cohort of placentas across gestation from healthy pregnancies defining the normative sex dimorphic gene expression and sex common, sex specific and sex exclusive gene expression across gestation. The first trimester has the most sexually dimorphic transcripts, and the majority were upregulated in females compared to males in both trimesters. The short arm of the X chromosome and the pseudoautosomal region is particularly critical in defining sex differences in the first trimester placenta. As pregnancy is a dynamic state, sex specific DEGs across gestation may contribute to sex dimorphic changes in overall outcomes., Competing Interests: Declaration of competing interest The authors report no conflict of interest, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Out-of-hospital cardiac arrest (OHCA) is associated with very poor clinical outcomes. An optimal pathway of care is yet to be defined, but prognostication is likely to assist in the challenging decision-making required for treatment of this high-risk patient cohort. The MIRACLE 2 score provides a simple method of neuro-prognostication but as yet it has not been externally validated. The aim of this study was therefore to retrospectively apply the score to a cohort of OHCA patients to assess the predictive ability and accuracy in the identification of neurological outcome., Methods: Retrospective data of patients identified by hospital coding, over a period of 18 months, were collected from a large tertiary-level cardiac centre with a mature, multidisciplinary OHCA service. MIRACLE 2 score performance was assessed against three existing OHCA prognostication scores., Results: Patients with all-comer OHCA, of presumed cardiac origin, with and without evidence of ST-elevation MI (43.4% versus 56.6%, respectively) were included. Regardless of presentation, the MIRACLE 2 score performed well in neuro-prognostication, with a low MIRACLE 2 score (≤2) providing a negative predictive value of 94% for poor neurological outcome at discharge, while a high score (≥5) had a positive predictive value of 95%. A high MIRACLE 2 score performed well regardless of presenting ECG, with 91% of patients receiving early coronary angiography having a poor outcome., Conclusion: The MIRACLE 2 score has good prognostic performance and is easily applicable to cardiac-origin OHCA presentation at the hospital front door. Prognostic scoring may assist decision-making regarding early angiographic assessment., Competing Interests: Disclosure: The authors have no conflicts of interest to declare. Consent: This study involves the secondary use of data collected by the clinical team as part of the patients’ normal care; specific patient consent was not sought. Only members of the patients’ direct clinical care team were involved in processing the raw data. Data availability: The data that support the findings of this study are available from the corresponding author upon reasonable request and subject to ethics approval. Ethics: This study falls outside the scope of the UK policy framework for health and social care research and was registered with University Hospitals Bristol and Weston NHS Foundation Trust as a service evaluation. It is a retrospective analysis of routinely collected anonymised data. The study was carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). Authors' contributions: Conceptualisation: TWJ, NS, FC, ZL; data curation: NS, FC, ZL; formal analysis: NS; investigation: TWJ, NVJ, MM, IF, SB, GD, AD, SA, DM, RK, AK, HR, CB, KR, MG, MT, SD, JS; supervision: TWJ; writing – original draft preparation: NS, FC, ZL; writing – review & editing: NS, FC, ZL, TWJ, NVJ, MM, IF, SB, GD, AD, SA, DM, RK, AK, HR, CB, KR, MG, MT, SD, JS., (Copyright © The Author(s), 2023. Published by Radcliffe Group Ltd.)

Background: Assessments of coronary disease activity with 18 F-sodium fluoride positron emission tomography and radiomics-based precision coronary plaque phenotyping derived from coronary computed tomography angiography may enhance risk stratification in patients with coronary artery disease. We sought to investigate whether the prognostic information provided by these 2 approaches is complementary in the prediction of myocardial infarction., Methods: Patients with known coronary artery disease underwent coronary 18 F-sodium fluoride positron emission tomography and coronary computed tomography angiography on a hybrid positron emission tomography/computed tomography scanner. Coronary 18 F-NaF uptake was determined by the coronary microcalcification activity. We performed quantitative plaque analysis of coronary computed tomography angiography datasets and extracted 1103 radiomic features for each plaque. Using weighted correlation network analysis, we derived latent morphological features of coronary lesions which were aggregated to patient-level radiomics nomograms to predict myocardial infarction., Results: Among 260 patients with established coronary artery disease (age, 65±9 years; 83% men), 179 (69%) participants showed increased coronary 18 F-NaF activity (coronary microcalcification activity>0). Over 53 (40-59) months of follow-up, 18 patients had a myocardial infarction. Using weighted correlation network analysis, we derived 15 distinct eigen radiomic features representing latent morphological coronary plaque patterns in an unsupervised fashion. Following adjustments for calcified, noncalcified, and low-density noncalcified plaque volumes and 18 F-NaF coronary microcalcification activity, 4 radiomic features remained independent predictors of myocardial infarction (hazard ratio, 1.46 [95% CI, 1.03-2.08]; P =0.03; hazard ratio, 1.62 [95% CI, 1.04-2.54]; P =0.02; hazard ratio, 1.49 [95% CI, 1.07-2.06]; P =0.01; and hazard ratio, 1.50 (95% CI, 1.05-2.13); P =0.02)., Conclusions: In patients with established coronary artery disease, latent coronary plaque morphological features, quantitative plaque volumes, and disease activity on 18 F-sodium fluoride positron emission tomography are additive predictors of myocardial infarction., Competing Interests: Disclosures None.

Coronary artery disease (CAD) remains a leading cause of mortality and morbidity worldwide, and it is associated with considerable economic burden. In an ageing, multimorbid population, it has become increasingly important to develop reliable, consistent, low-risk, non-invasive means of diagnosing CAD. The evolution of multiple cardiac modalities in this field has addressed this dilemma to a large extent, not only in providing information regarding anatomical disease, as is the case with coronary computed tomography angiography (CCTA), but also in contributing critical details about functional assessment, for instance, using stress cardiac magnetic resonance (S-CMR). The field of artificial intelligence (AI) is developing at an astounding pace, especially in healthcare. In healthcare, key milestones have been achieved using AI and machine learning (ML) in various clinical settings, from smartwatches detecting arrhythmias to retinal image analysis and skin cancer prediction. In recent times, we have seen an emerging interest in developing AI-based technology in the field of cardiovascular imaging, as it is felt that ML methods have potential to overcome some limitations of current risk models by applying computer algorithms to large databases with multidimensional variables, thus enabling the inclusion of complex relationships to predict outcomes. In this paper, we review the current literature on the various applications of AI in the assessment of CAD, with a focus on multimodality imaging, followed by a discussion on future perspectives and critical challenges that this field is likely to encounter as it continues to evolve in cardiology.

Background: Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke., Objectives: The purpose of this study was to investigate whether thoracic 18 F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke., Methods: In a post hoc observational cohort study, we quantified thoracic aortic and coronary 18 F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of 18 F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable Cox regression., Results: After 12.7 ± 2.7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic 18 F-sodium fluoride activity (n = 140; r = 0.31; P = 0.00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6.1 ± 2.3 years of follow-up. High thoracic aortic 18 F-sodium fluoride activity was strongly associated with ischemic stroke (HR: 10.3 [95% CI: 3.1-34.8]; P = 0.00017), but not myocardial infarction (P = 0.40). Conversely, high coronary 18 F-sodium fluoride activity was associated with myocardial infarction (HR: 4.8 [95% CI: 1.9-12.2]; P = 0.00095) but not ischemic stroke (P = 0.39). In a multivariable Cox regression model including imaging and clinical risk factors, thoracic aortic 18 F-sodium fluoride activity was the only variable associated with ischemic stroke (HR: 8.19 [95% CI: 2.33-28.7], P = 0.0010)., Conclusions: In patients with established cardiovascular disease, thoracic aortic 18 F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial 18 F-sodium fluoride activity identifies localized areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events. (DIAMOND-Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND], NCT02110303; Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis [SALTIRE II], NCT02132026; Novel Imaging Approaches To Identify Unstable Coronary Plaques, NCT01749254; and Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis, NCT01358513)., Competing Interests: Funding Support and Author Disclosures Drs Fletcher (FS/19/15/34155), Tzolos (FS/17/51/33096), Syed (FS/18/31/33676), Moss (AA/18/3/34220), Walker (FS/19/15/34155), Williams (FS/ICRF/20/26002), Newby (CH/09/002, RG/16/10/32375, RE/18/5/34216), and Dweck (FS/14/78/31020) are supported by the British Heart Foundation. Dr Lembo is supported by the International PhD programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh). Dr van Beek is supported by SINAPSE. Dr Adamson is supported by a Heart Foundation of New Zealand Senior Fellowship (1844). Dr Wardlaw is supported by the UK Dementia Research Institute (funded by the MRC, Alzheimer Society and Alzheimer Research UK). Dr Slomka and FusionQuant Development are supported by the National Institute of Health Grant HL135557 (PI: Dr Slomka); and his laboratory is supported by National Institutes of Health R01HL135557. Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA); and holds investigator-initiated research grants from Siemens Healthineers. Dr Dweck is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA). The Edinburgh Imaging facility QMRI (Edinburgh) is supported by the National Health Service Research Scotland through National Health Service Lothian Health Board. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Dentin hypersensitivity (DH) is a rising concern in clinical dentistry that causes pain and discomfort and negatively affects the quality of life of patients. Indian Society of Periodontology conducted a nationwide survey, involving 3000 dentists in December 2020, which revealed significant knowledge gaps regarding DH, viz., under-diagnosis, incorrect differential diagnosis, and treatment strategies/recommendations for the management of DH patients in daily clinical practice. The current paper has been envisioned and conceptualized to update the practicing Indian dentists regarding the so-called enigma of dentistry "Dentin Hypersensitivity," based on the best available contemporary evidence. An expert panel was constituted comprising 30 subject experts from across the country, which after extensive literature review and group discussions formulated these recommendations. The panel advocated routine screening of all dentate patients for exposed dentin areas and DH to avoid under-diagnosis of the condition and suggested an early preventive management. Consensus guidelines/recommendations for the use of desensitizing agents (DAs) at home, including the use of herbal agents, are also provided within the backdrop of the Indian context. The guidelines recommend that active management of DH shall be accomplished by a combination of at home and in-office therapies, starting with the simplest and cost-effective home use of desensitizing toothpastes. A diagnostic decision tree and a flowchart for application in daily practice are designed to manage the patients suffering from DH or presenting with exposed dentin areas in dentition. Various treatment methods to manage DH have been discussed in the paper, including the insights from previously published treatment guidelines. Further, a novel system of classification of DH patients based on specific case definitions has been developed for the first time. Explicit charts regarding the available treatment options and the chronology of institution of the agent, for the management in different case categories of DH, have been provided for quick reference. The management strategy takes into account a decision algorithm based on hierarchy of complexity of treatment options and intends to improve the quality of life of the patient by long-term maintenance with an innovatively defined triple C's or 3Cs approach., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Society of Periodontology.)

Maternal and fetal pregnancy outcomes related to placental function vary based on fetal sex, which may be due to sexually dimorphic epigenetic regulation of RNA expression. We identified sexually dimorphic miRNA expression throughout gestation in human placentae. Next-generation sequencing identified miRNA expression profiles in first and third trimester uncomplicated pregnancies using tissue obtained at chorionic villous sampling (n = 113) and parturition (n = 47). Sequencing analysis identified 986 expressed mature miRNAs from female and male placentae at first and third trimester (baseMean>10). Of these, 11 sexually dimorphic (FDR < 0.05) miRNAs were identified in the first and 4 in the third trimester, all upregulated in females, including miR-361-5p, significant in both trimesters. Sex-specific analyses across gestation identified 677 differentially expressed (DE) miRNAs at FDR < 0.05 and baseMean>10, with 508 DE miRNAs in common between female-specific and male-specific analysis (269 upregulated in first trimester, 239 upregulated in third trimester). Of those, miR-4483 had the highest fold changes across gestation. There were 62.5% more female exclusive differences with fold change>2 across gestation than male exclusive (52 miRNAs vs 32 miRNAs), indicating miRNA expression across human gestation is sexually dimorphic. Pathway enrichment analysis identified significant pathways that were differentially regulated in first and third trimester as well as across gestation. This work provides the normative sex dimorphic miRNA atlas in first and third trimester, as well as the sex-independent and sex-specific placenta miRNA atlas across gestation, which may be used to identify biomarkers of placental function and direct functional studies investigating placental sex differences., (© The Author(s) 2021. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Tooth surface polishing is an integral part of periodontal therapy. Enamel and cementum show a smooth surface clinically after debridement with the naked eye, but numerous surface irregularities can be detected microscopically. Air polishing is safe and effective when used by trained professionals., Aims: The aim of the study is to evaluate and compare the surface roughness of cementum by using an air polishing device and conventional root planing with hand instruments., Materials and Methods: A total of 45 extracted teeth stored in saline were divided into three groups randomly - Group A (conventional root planing), Group B (hand instrumentation and air polishing), and Group C (air polishing alone) - with 15 samples each. Samples were evaluated for surface roughness by using profilometer. Six parameters were checked for surface roughness., Statistical Analysis Used: The data were collected, charted, and analyzed using one-way ANOVA with post hoc LSD method for pairwise comparisons., Results: Least amount of surface roughness was achieved with Group C when compared with Group A and Group B. These differences were statistical significant ( P < 0.0001)., Conclusions: Air polishing can effectively smoothen the root surface by removing surface irregularities which are produced hand/ultrasonic instruments. Profilometer can be effectively used to measure the surface roughness., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Society of Periodontology.)

Coronary 18 F-sodium fluoride ( 18 F-NaF) PET and CT angiography-based quantitative plaque analysis have shown promise in refining risk stratification in patients with coronary artery disease. We combined both of these novel imaging approaches to develop an optimal machine-learning model for the future risk of myocardial infarction in patients with stable coronary disease. Methods: Patients with known coronary artery disease underwent coronary 18 F-NaF PET and CT angiography on a hybrid PET/CT scanner. Machine-learning by extreme gradient boosting was trained using clinical data, CT quantitative plaque analysis, measures and 18 F-NaF PET, and it was tested using repeated 10-fold hold-out testing. Results: Among 293 study participants (65 ± 9 y; 84% male), 22 subjects experienced a myocardial infarction over the 53 (40-59) months of follow-up. On univariable receiver-operator-curve analysis, only 18 F-NaF coronary uptake emerged as a predictor of myocardial infarction (c-statistic 0.76, 95% CI 0.68-0.83). When incorporated into machine-learning models, clinical characteristics showed limited predictive performance (c-statistic 0.64, 95% CI 0.53-0.76) and were outperformed by a quantitative plaque analysis-based machine-learning model (c-statistic 0.72, 95% CI 0.60-0.84). After inclusion of all available data (clinical, quantitative plaque and 18 F-NaF PET), we achieved a substantial improvement ( P = 0.008 versus 18 F-NaF PET alone) in the model performance (c-statistic 0.85, 95% CI 0.79-0.91). Conclusion: Both 18 F-NaF uptake and quantitative plaque analysis measures are additive and strong predictors of outcome in patients with established coronary artery disease. Optimal risk stratification can be achieved by combining clinical data with these approaches in a machine-learning model., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)