Vital pulp therapy-Factors influencing decision-making for permanent mature teeth with irreversible pulpitis: A systematic review.

BACKGROUND: There is an increased tendency towards adopting minimally invasive interventions in dentistry, supported by advancement in materials and techniques. However, the decision-making process in choosing conservative or invasive treatments is influenced by several factors, particularly in permanent teeth with irreversible pulpitis. OBJECTIVES: The objective of the study was to systematically review the literature regarding factors that influence decision-making for vital pulp therapy (VPT) as definitive treatment option in permanent mature teeth diagnosed with irreversible pulpitis. METHODS: Two independent reviewers searched five electronic databases (PubMed, Embase, Web of Science, Scopus and Cochrane Library). Grey literature was searched through Google Scholar and contact with experts. Defined search keys were applied, and all peer-reviewed literature published with no language nor publication date limits were included. The All studies investigating the factors influencing treatment decision-making in mature permanent teeth with irreversible pulpitis were included. The quality of included studies was assessed by two independent reviewers using the Joanna Briggs Institute quality assessment tool. RESULTS: Six articles were included in the review. All included studies used questionnaires to characterize clinician preferences and attitudes in choosing treatment options for mature permanent teeth with irreversible pulpitis. The available evidence suggests that dentist-related factors have a significant influence on the chosen treatment in teeth with irreversible pulpitis, with speciality training and years of experience influencing the choice of VPT over other treatment options. COVID-19 reportedly swayed the dentists' decision to favour VPT. Only one article studied the influence of patient-related factors, such as age and presence of spontaneous pain on decision-making. Of note, a history of cardiovascular disease moved dentists towards prescribing VPT. DISCUSSION: Collectively, the included studies demonstrated an overriding influence of dentist-related factors on choosing among treatment options for painful teeth diagnosed with irreversible pulpitis. Patient-related factors were acknowledged but there are also potential factors such as socio-economic constraints that were not included in the component studies. CONCLUSION: In teeth with irreversible pulpitis clinicians educational background influence the decision towards a specific treatment option. Further data, preferably derived from clinical records, is necessary in future investigations to explore the effect of other important factors related to both dentists and patients. REGISTRATION: PROSPERO database (CRD42022339653).

Evaluating the stress of root canal treatment in patients and dentists compared to other dental treatments: A systematic review and meta-analysis.

This systematic review aimed to investigate whether root canal treatment caused greater stress than other dental treatments for patients and dentists. All peer-reviewed literature published in English between January 1990 and January 2023 was included. This included randomized/non-randomized control trials, cohort studies, case-control studies, and cross-sectional studies. An electronic search used PubMed, Scopus, Medline, Cochrane Collaboration, and Embase. Hand searching supplemented the screening pool. Studies examining physiological or psychological stress measures within patients or providers of dental treatment (dentists, dental specialists, and dental students) were eligible. The study must have reported on the stress outcome for root canal treatment and at least one other dental procedure. After screening 3639 eligible records, there were 23 studies included, varying from very-low to low certainty of evidence. This review found that root canal treatment was more psychologically stressful for patients than routine restorative or cleaning procedures. However, the stress of root canal treatment relative to other dental procedures, especially extractions, was inconclusive for both dental patients and providers. Since patients regard root canal treatment as more stress-evoking than other routine dental procedures, providers should endeavour to minimise their own bias toward root canal treatment when providing adequate information for an informed treatment choice.

Design of an interactive system for access cavity assessment: A novel feedback tool for preclinical endodontics.

INTRODUCTION: A software program was developed to provide visual, guided feedback to students for access cavity preparations in preclinical learning. The specific aim of the study was to investigate students' overall experiences with the new learning method and compare their experiences with traditional teaching. MATERIALS AND METHODS: A workflow based on freely available software was designed to interactively register three-dimensional models of molars with access cavities, and to metrically compare these to instructor-prepared standard cavities. Third-year students practicing molar endodontics access cavity preparation in the preclinical course were then surveyed. A total of 44/79 students completed self-administered questionnaires prior and after the use of the feedback software to gauge their learning experience. RESULTS: The results of the post-training questionnaire illustrated that all surveyed students agreed/strongly agreed that the software assisted their learning in access cavity preparation. In addition, 86 and 89%, respectively, of students agreed that the use of the software improved their skills of access cavity preparation and felt more confident about their access cavity preparation skills after using the software package, 3D Dental Align. DISCUSSION: The presented software solution permitted setting and comparing access cavity preparations by students against a standard access prepared by an instructor. The process of data acquisition and registration was fast and straightforward. Student feedback was very positive and suggested the integration of this type of experiential learning into the preclinical curriculum. CONCLUSION: This feasibility study demonstrated the utility of the new technology to assist dental students' access cavity preparation learning.

Dental trauma simulation training using four splinting models: A cross sectional study.

BACKGROUND/AIM: Opportunities for dental students to obtain clinical experience in the management of traumatic dental injuries are scarce, and most dentists encounter difficulties with their first trauma patients after graduation. The aim of this study was to question students on the ease of handling of four types of flexible splints, with two common methods of bonding to the tooth. MATERIAL AND METHODS: A total of 161 fourth year dental students completed a simulated treatment of an avulsed tooth using orthodontic wire, Twistflex wire, nylon fishing line, and Powermesh as splints. The bonding materials were composite resin (Spectra ST LV) or glass ionomer cement (GC Fuji LC Ortho). The students then answered 16 questions on a 5-point Likert scale, or with an open answer field. RESULTS: Most students agreed (48.8%) or strongly agreed (31.3%) that the simulated trauma exercise assisted their learning. There was strong agreement (68.8%) and agreement (28.7%) that the simulation added value to their dental training compared to didactic training only. Similarly, 52.3% of participants strongly agreed and 40% agreed that they felt engaged in the learning activity. Only 53.8% of the participants agreed and 7.5% strongly agreed that the simulation felt realistic. Most students (56.2%) found a Powermesh/composite splint was the easiest to place, and nylon fishing line/GC Fuji LC Ortho splints was the least difficult to remove (35%). CONCLUSION: Wire-free splints with composite bonding were judged as the easiest to place by students, while glass ionomer cement was the easiest to remove.

Post-operative Outcomes and Survivorship for Shoulder Arthroplasty following Glenohumeral Tumor Resection.

A paucity of data exists for post-operative complications and survivorship in patients undergoing resection arthroplasty procedures for treatment of glenohumeral tumors. This study investigates patient and tumor characteristics, 90-day and long-term post-operative complications, and overall survivorship following glenohumeral tumor resection arthroplasty procedures. This single-center retrospective review identified 13 patients, with mean age of 51.6 ± 15.7 years, mean body mass index of 26.5 ± 6.4 kg/m2, and mean Charlson Comorbidity Index of 4.9 ± 2.4, who underwent shoulder arthroplasty procedures for glenohumeral tumors, most commonly for chondrosarcoma (n = 5) and metastatic disease (n = 3). Nine patients (69.2%) underwent revision surgeries at a median of 677 days, most commonly for prosthesis instability, dislocation (n=4) or aseptic loosening (n = 3). Seven patients (53.8%) were deceased at a median of 593.6 days. Resection arthroplasty in the treatment of glenohumeral tumors demonstrates low rates of complications during the global period but are fraught with long-term complications. This data provides pertinent information to pre-operatively counsel patients on post-operative expectations. (Journal of Surgical Orthopaedic Advances 31(4):248-251, 2022).

Phenotypic consequences of RNA polymerase dysregulation in Escherichia coli.

Many bacterial adaptive responses to changes in growth conditions due to biotic and abiotic factors involve reprogramming of gene expression at the transcription level. The bacterial RNA polymerase (RNAP), which catalyzes transcription, can thus be considered as the major mediator of cellular adaptive strategies. But how do bacteria respond if a stress factor directly compromises the activity of the RNAP? We used a phage-derived small protein to specifically perturb bacterial RNAP activity in exponentially growing Escherichia coli. Using cytological profiling, tracking RNAP behavior at single-molecule level and transcriptome analysis, we reveal that adaptation to conditions that directly perturb bacterial RNAP performance can result in a biphasic growth behavior and thereby confer the 'adapted' bacterial cells an enhanced ability to tolerate diverse antibacterial stresses. The results imply that while synthetic transcriptional rewiring may confer bacteria with the intended desirable properties, such approaches may also collaterally allow them to acquire undesirable traits.

Willard and Spackman's Enduring Legacy for Future Occupational Therapy Pathways.

Helen Willard (1894-1980) and Clare Spackman (1909-1992) paved the way for modern and future occupational therapy. This article validates the need for historical research in occupational therapy and presents a historical study on how the personal and professional collaboration of Willard and Spackman influenced occupational therapy. Data were gathered from archival documents, private papers, and 10 oral histories with colleagues, students, family, and friends. We used text analysis with triangulation to develop themes to reconstruct a proximity of the historical story. Two major themes that describe Willard's and Spackman's influence on occupational therapy are (1) Enduring Legacies and (2) Sacred Solitude and Chosen Gatherings. Subthemes within Enduring Legacies include Guiding Practice, Leaders in Service, and Educational Leadership. These women strongly influenced practitioners worldwide while maintaining the sacredness of their private lives. Their example can serve as a model for current and future occupational therapy practitioners and leaders.

Protocol for the COG-UK hospital-onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in UK NHS hospitals.

OBJECTIVES: Nosocomial transmission of SARS-CoV-2 has been a significant cause of mortality in National Health Service (NHS) hospitals during the COVID-19 pandemic. The COG-UK Consortium Hospital-Onset COVID-19 Infections (COG-UK HOCI) study aims to evaluate whether the use of rapid whole-genome sequencing of SARS-CoV-2, supported by a novel probabilistic reporting methodology, can inform infection prevention and control (IPC) practice within NHS hospital settings. DESIGN: Multicentre, prospective, interventional, superiority study. SETTING: 14 participating NHS hospitals over winter-spring 2020/2021 in the UK. PARTICIPANTS: Eligible patients must be admitted to hospital with first-confirmed SARS-CoV-2 PCR-positive test result >48 hour from time of admission, where COVID-19 diagnosis not suspected on admission. The projected sample size is 2380 patients. INTERVENTION: The intervention is the return of a sequence report, within 48 hours in one phase (rapid local lab processing) and within 5-10 days in a second phase (mimicking central lab), comparing the viral genome from an eligible study participant with others within and outside the hospital site. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes are incidence of Public Health England (PHE)/IPC-defined SARS-CoV-2 hospital-acquired infection during the baseline and two interventional phases, and proportion of hospital-onset cases with genomic evidence of transmission linkage following implementation of the intervention where such linkage was not suspected by initial IPC investigation. Secondary outcomes include incidence of hospital outbreaks, with and without sequencing data; actual and desirable changes to IPC actions; periods of healthcare worker (HCW) absence. Health economic analysis will be conducted to determine cost benefit of the intervention. A process evaluation using qualitative interviews with HCWs will be conducted alongside the study. TRIAL REGISTRATION NUMBER: ISRCTN50212645. Pre-results stage. This manuscript is based on protocol V.6.0. 2 September 2021.

Structure-function analysis of enterovirus protease 2A in complex with its essential host factor SETD3.

Enteroviruses cause a number of medically relevant and widespread human diseases with no approved antiviral therapies currently available. Host-directed therapies present an enticing option for this diverse genus of viruses. We have previously identified the actin histidine methyltransferase SETD3 as a critical host factor physically interacting with the viral protease 2A. Here, we report the 3.5 Å cryo-EM structure of SETD3 interacting with coxsackievirus B3 2A at two distinct interfaces, including the substrate-binding surface within the SET domain. Structure-function analysis revealed that mutations of key residues in the SET domain resulted in severely reduced binding to 2A and complete protection from enteroviral infection. Our findings provide insight into the molecular basis of the SETD3-2A interaction and a framework for the rational design of host-directed therapeutics against enteroviruses.

The human disease gene LYSET is essential for lysosomal enzyme transport and viral infection.

Lysosomes are key degradative compartments of the cell. Transport to lysosomes relies on GlcNAc-1-phosphotransferase-mediated tagging of soluble enzymes with mannose 6-phosphate (M6P). GlcNAc-1-phosphotransferase deficiency leads to the severe lysosomal storage disorder mucolipidosis II (MLII). Several viruses require lysosomal cathepsins to cleave structural proteins and thus depend on functional GlcNAc-1-phosphotransferase. We used genome-scale CRISPR screens to identify lysosomal enzyme trafficking factor (LYSET, also named TMEM251) as essential for infection by cathepsin-dependent viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). LYSET deficiency resulted in global loss of M6P tagging and mislocalization of GlcNAc-1-phosphotransferase from the Golgi complex to lysosomes. Lyset knockout mice exhibited MLII-like phenotypes, and human pathogenic LYSET alleles failed to restore lysosomal sorting defects. Thus, LYSET is required for correct functioning of the M6P trafficking machinery and mutations in LYSET can explain the phenotype of the associated disorder.

Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study.

Background: Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings. Methods: We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48 hr) and 4 weeks of 'longer-turnaround' (5-10 days) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital-onset COVID-19 infections (HOCIs; detected ≥48 hr from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on the incidence of probable/definite hospital-acquired infections (HAIs), was evaluated. Results: A total of 2170 HOCI cases were recorded from October 2020 to April 2021, corresponding to a period of extreme strain on the health service, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (incidence rate ratio 1.60, 95% CI 0.85-3.01; p=0.14) or rapid (0.85, 0.48-1.50; p=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8 and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2 and 11.6% of cases where the report was returned. In a 'per-protocol' sensitivity analysis, there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources. Conclusions: While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days. Funding: COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (grant code: MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute. Clinical trial number: NCT04405934.

Return of the Neurotropic Enteroviruses: Co-Opting Cellular Pathways for Infection.

Enteroviruses are among the most common human infectious agents. While infections are often mild, the severe neuropathogenesis associated with recent outbreaks of emerging non-polio enteroviruses, such as EV-A71 and EV-D68, highlights their continuing threat to public health. In recent years, our understanding of how non-polio enteroviruses co-opt cellular pathways has greatly increased, revealing intricate host-virus relationships. In this review, we focus on newly identified mechanisms by which enteroviruses hijack the cellular machinery to promote their replication and spread, and address their potential for the development of host-directed therapeutics. Specifically, we discuss newly identified cellular receptors and their contribution to neurotropism and spread, host factors required for viral entry and replication, and recent insights into lipid acquisition and replication organelle biogenesis. The comprehensive knowledge of common cellular pathways required by enteroviruses could expose vulnerabilities amenable for host-directed therapeutics against a broad spectrum of enteroviruses. Since this will likely include newly arising strains, it will better prepare us for future epidemics. Moreover, identifying host proteins specific to neurovirulent strains may allow us to better understand factors contributing to the neurotropism of these viruses.

Comparison of calcium hydroxide extrusion with syringe versus spiral filler delivery: A pilot study.

This study aimed to evaluate Ca(OH)2 extrusion in relation to delivery technique, apical size and depth of placement. Plastic blocks had j-shaped canals shaped to apical sizes #35 and #45 (n = 32 each). Amounts of calcium hydroxide extrusion was determined relative to apical taper, depth of insertion and whether syringe or spiral filler at 500 rpm was used. Blocks were immersed in pH-sensitive gel and observed for colour change. Extent of extrusion was expressed in mm2 . Extrusion occurred in 48/64 of the samples. At 3 mm from the canal terminus, the device affected the frequency of extrusion, with syringe placement causing extrusion significantly (P < 0.01) more frequently, irrespective of apical size. Extrusion was significantly greater at 2 mm short of the canal terminus (median 27.44 mm2 ) compared to 3 mm (median 19.69 mm2 ). Under in-vitro conditions, a spiral filler at 500 rpm, 3 mm short of the apex, minimised extrusion of Ca(OH)2 from root canals.

Rapid feedback on hospital onset SARS-CoV-2 infections combining epidemiological and sequencing data.

Background: Rapid identification and investigation of healthcare-associated infections (HCAIs) is important for suppression of SARS-CoV-2, but the infection source for hospital onset COVID-19 infections (HOCIs) cannot always be readily identified based only on epidemiological data. Viral sequencing data provides additional information regarding potential transmission clusters, but the low mutation rate of SARS-CoV-2 can make interpretation using standard phylogenetic methods difficult. Methods: We developed a novel statistical method and sequence reporting tool (SRT) that combines epidemiological and sequence data in order to provide a rapid assessment of the probability of HCAI among HOCI cases (defined as first positive test >48 hr following admission) and to identify infections that could plausibly constitute outbreak events. The method is designed for prospective use, but was validated using retrospective datasets from hospitals in Glasgow and Sheffield collected February-May 2020. Results: We analysed data from 326 HOCIs. Among HOCIs with time from admission ≥8 days, the SRT algorithm identified close sequence matches from the same ward for 160/244 (65.6%) and in the remainder 68/84 (81.0%) had at least one similar sequence elsewhere in the hospital, resulting in high estimated probabilities of within-ward and within-hospital transmission. For HOCIs with time from admission 3-7 days, the SRT probability of healthcare acquisition was >0.5 in 33/82 (40.2%). Conclusions: The methodology developed can provide rapid feedback on HOCIs that could be useful for infection prevention and control teams, and warrants further prospective evaluation. The integration of epidemiological and sequence data is important given the low mutation rate of SARS-CoV-2 and its variable incubation period. Funding: COG-UK HOCI funded by COG-UK consortium, supported by funding from UK Research and Innovation, National Institute of Health Research and Wellcome Sanger Institute.

Recent Advances in Cone-beam CT in Oral Medicine.

BACKGROUND: The cone-beam computed tomography (CBCT) technology has continuously evolved since its appearance in oral medicine in the early 2000s. OBJECTIVES: To present recent advances in CBCT in oral medicine: i) selection of recent and consensual evidence-based sources, ii) structured summary of the information based on an iterative framework and iii) compliance with ethical, public health and patient-centered concerns. MAIN FINDINGS: We will focus on technological advances, such as sensors and reconstruction algorithms used to improve the constant quality of the image and dosimetry. CBCT examination is now performed in almost all disciplines of oral medicine: currently, the main clinical disciplines that use CBCT acquisitions are endodontics and oral surgery, with clearly defined indications. Periodontology and ear, nose and throat medicine are more recent fields of application. For a given application and indication, the smallest possible field of view must be used. One of the major challenges in contemporary healthcare is ensuring that technological developments do not take precedence over admitted standards of care. The entire volume should be reviewed in full, with a systematic approach. All findings are noted in the patient's record and explained to the patient, including incidental findings. This presupposes the person reviewing the images is sufficiently trained to interpret such images, inform the patient and organize the clinical pathway, with referrals to other medical or oral medicine specialties as needed. CONCLUSION: A close collaboration between dentists, medical physicists, radiologists, radiographers and engineers is critical for all aspects of CBCT technology.

The double-edged sword of calcium hydroxide in endodontics: Precautions and preventive strategies for extrusion injuries into neurovascular anatomy.

BACKGROUND: Nowhere in the consideration of dental care involving endodontics does a patient become more vulnerable to potentially life-changing injuries than during a root canal procedure on the mandibular dentition that may invade and injure the neurovascular anatomy. CASE DESCRIPTION: The authors present a series of 5 cases wherein using calcium hydroxide as a disinfection strategy in endodontics caused serious neurologic injury to the treated patients. The mechanism in all cases was the inappropriate use of needle applications resulting in significant overfill into the inferior alveolar nerve space. Although calcium hydroxide has been recognized and used as a meaningful disinfectant in endodontic therapy for many years, the dangers and risks associated with a needle delivery technique are discussed and analyzed with recommendations based on current research to minimize risk. CONCLUSIONS AND PRACTICAL IMPLICATIONS: A literature search revealed that the 5 cases are not solitary cases; indeed, consequences of calcium hydroxide overfills have been described before. Therefore, a clinician initiating root canal therapy on a mandibular posterior tooth should always be mindful of the vital neurovascular anatomy, which commonly approximates the ends of these roots. Preoperative cone-beam computed tomographic imaging and the thoughtful delivery of medicaments in treatment can help the clinician manage close proximity to neural anatomy and avoid potential injuries.

Genetic ablation of serotonin receptor 2B improves aortic valve hemodynamics of Notch1 heterozygous mice in a high-cholesterol diet model.

Calcific aortic valve disease (CAVD) is a deadly disease that is rising in prevalence due to population aging. While the disease is complex and poorly understood, one well-documented driver of valvulopathy is serotonin agonism. Both serotonin overexpression, as seen with carcinoid tumors and drug-related agonism, such as with Fenfluramine use, are linked with various diseases of the valves. Thus, the objective of this study was to determine if genetic ablation or pharmacological antagonism of the 5-HT2B serotonin receptor (gene: Htr2b) could improve the hemodynamic and histological progression of calcific aortic valve disease. Htr2b mutant mice were crossed with Notch1+/- mice, an established small animal model of CAVD, to determine if genetic ablation affects CAVD progression. To assess the effect of pharmacological inhibition on CAVD progression, Notch1+/- mice were treated with the 5-HT2B receptor antagonist SB204741. Mice were analyzed using echocardiography, histology, immunofluorescence, and real-time quantitative polymerase chain reaction. Htr2b mutant mice showed lower aortic valve peak velocity and mean pressure gradient-classical hemodynamic indicators of aortic valve stenosis-without concurrent left ventricle change. 5-HT2B receptor antagonism, however, did not affect hemodynamic progression. Leaflet thickness, collagen density, and CAVD-associated transcriptional markers were not significantly different in any group. This study reveals that genetic ablation of Htr2b attenuates hemodynamic development of CAVD in the Notch1+/- mice, but pharmacological antagonism may require high doses or long-term treatment to slow progression.

Enterovirus pathogenesis requires the host methyltransferase SETD3.

Enteroviruses (EVs) comprise a large genus of positive-sense, single-stranded RNA viruses whose members cause a number of important and widespread human diseases, including poliomyelitis, myocarditis, acute flaccid myelitis and the common cold. How EVs co-opt cellular functions to promote replication and spread is incompletely understood. Here, using genome-scale CRISPR screens, we identify the actin histidine methyltransferase SET domain containing 3 (SETD3) as critically important for viral infection by a broad panel of EVs, including rhinoviruses and non-polio EVs increasingly linked to severe neurological disease such as acute flaccid myelitis (EV-D68) and viral encephalitis (EV-A71). We show that cytosolic SETD3, independent of its methylation activity, is required for the RNA replication step in the viral life cycle. Using quantitative affinity purification-mass spectrometry, we show that SETD3 specifically interacts with the viral 2A protease of multiple enteroviral species, and we map the residues in 2A that mediate this interaction. 2A mutants that retain protease activity but are unable to interact with SETD3 are severely compromised in RNA replication. These data suggest a role of the viral 2A protein in RNA replication beyond facilitating proteolytic cleavage. Finally, we show that SETD3 is essential for in vivo replication and pathogenesis in multiple mouse models for EV infection, including CV-A10, EV-A71 and EV-D68. Our results reveal a crucial role of a host protein in viral pathogenesis, and suggest targeting SETD3 as a potential mechanism for controlling viral infections.