Project Tooth Fairy: a pan-London initiative from conception to delivery to patient-reported experience measures.

Pressure on paediatric dental general anaesthetic (GA) waiting lists has recently been at its highest, further compounded by the COVID-19 pandemic. Project Tooth Fairy (PTF), a pan-London collaborative project, was conceived in response to this backlog. A dedicated day case GA suite was established within The Royal London Dental Hospital (Barts Health NHS Trust) for use by multiple trusts to enhance elective recovery.Over ten months, 895 patients were treated and discharged by PTF, averaging 101 patients per month. The majority required simple exodontia and comprehensive care and some patients were treated for surgery related to orthodontic treatment. Patient-reported experience measures highlighted an overall positive experience and appreciation for the service.Several governance domains were considered in the service development, including risk management, workforce recruitment and information governance. Training opportunities have arisen for team members to develop their skills. Patient-reported experience measures have guided the provision of service focusing on paediatric dentistry and paediatric GA.PTF has demonstrated the creation of a service centred around collaboration to successfully reduce GA waiting lists and therefore improving patient outcomes. The development of this service can be used as a template for the establishment of similar regional collaborative projects.

More than the Eye Can See: Shedding New Light on SARS-CoV-2 Lateral Flow Device-Based Immunoassays.

Containing the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been an unprecedented challenge due to high horizontal transmissivity and asymptomatic carriage rates. Lateral flow device (LFD) immunoassays were introduced in late 2020 to detect SARS-CoV-2 infection in asymptomatic or presymptomatic individuals rapidly. While LFD technologies have been used for over 60 years, their widespread use as a public health tool during a pandemic is unprecedented. By the end of 2020, data from studies into the efficacy of the LFDs emerged and showed these point-of-care devices to have very high specificity (ability to identify true negatives) but inadequate sensitivity with high false-negative rates. The low sensitivity (<50%) shown in several studies is a critical public health concern, as asymptomatic or presymptomatic carriers may wrongly be assumed to be noninfectious, posing a significant risk of further spread in the community. Here, we show that the direct visual readout of SARS-CoV-2 LFDs is an inadequate approach to discriminate a potentially infective viral concentration in a biosample. We quantified significant immobilized antigen-antibody-labeled conjugate complexes within the LFDs visually scored as negative using high-sensitivity synchrotron X-ray fluorescence imaging. Correlating quantitative X-ray fluorescence measurements and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) determined numbers of viral copies, we identified that negatively scored samples could contain up to 100 PFU (equivalent here to ∼10 000 RNA copies/test). The study demonstrates where the shortcomings arise in many of the current direct-readout SARS-CoV-2 LFDs, namely, being a deficiency in the readout as opposed to the potential level of detection of the test, which is orders of magnitude higher. The present findings are of importance both to public health monitoring during the Coronavirus Disease 2019 (COVID-19) pandemic and to the rapid refinement of these tools for immediate and future applications.

Adherence to RCS recommendations for extraction of first permanent molars in a teaching hospital: To compensate or not to compensate?

OBJECTIVE: To observe whether paediatric dentists and orthodontists balance and compensate the extraction of first permanent molars (FPMs) in children aged 7-11 years. DESIGN: Service evaluation. SETTING: UK dental teaching hospital. METHODS: Retrospective analysis of FPM extraction patterns in patients aged 7-11 years that attended for extraction of FPMs from 1 January 2019 to 31 January 2020 (13-month period). RESULTS: A total of 194 patients were included and they collectively had 435 FPMs extracted. No balancing extractions to prevent dental centreline shifts and no lower FPM compensatory extractions were performed. Compensatory extraction of good prognosis upper FPMs were performed in 64% (94/146) of cases to avoid overeruption. Orthodontic input was sought for poor prognosis lower FPMs in 76% of cases compared to 51% for poor prognosis upper FPMs. CONCLUSION: Compensatory extraction of good prognosis upper FPMs to avoid overeruption appears to be a common practice at Guy's and St Thomas' Hospitals. There was also higher demand for orthodontic advice for cases presenting with poor prognosis lower FPMs compared to poor prognosis upper FPMs, which suggests that paediatric dentists may prefer for the final decision on upper FPM compensatory extractions to be made by an orthodontist, even with national guidelines available. More high-quality research on the topic is required to determine the necessity of this practice for achieving optimal long-term oral health in children.

Loss of the tumor suppressor BIN1 enables ATM Ser/Thr kinase activation by the nuclear protein E2F1 and renders cancer cells resistant to cisplatin.

The tumor suppressor bridging integrator 1 (BIN1) is a corepressor of the transcription factor E2F1 and inhibits cell-cycle progression. BIN1 also curbs cellular poly(ADP-ribosyl)ation (PARylation) and increases sensitivity of cancer cells to DNA-damaging therapeutic agents such as cisplatin. However, how BIN1 deficiency, a hallmark of advanced cancer cells, increases cisplatin resistance remains elusive. Here, we report that BIN1 inactivates ataxia telangiectasia-mutated (ATM) serine/threonine kinase, particularly when BIN1 binds E2F1. BIN1 + 12A (a cancer-associated BIN1 splicing variant) also inhibited cellular PARylation, but only BIN1 increased cisplatin sensitivity. BIN1 prevented E2F1 from transcriptionally activating the human ATM promoter, whereas BIN1 + 12A did not physically interact with E2F1. Conversely, BIN1 loss significantly increased E2F1-dependent formation of MRE11A/RAD50/NBS1 DNA end-binding protein complex and efficiently promoted ATM autophosphorylation. Even in the absence of dsDNA breaks (DSBs), BIN1 loss promoted ATM-dependent phosphorylation of histone H2A family member X (forming γH2AX, a DSB biomarker) and mediator of DNA damage checkpoint 1 (MDC1, a γH2AX-binding adaptor protein for DSB repair). Of note, even in the presence of transcriptionally active (i.e. proapoptotic) TP53 tumor suppressor, BIN1 loss generally increased cisplatin resistance, which was conversely alleviated by ATM inactivation or E2F1 reduction. However, E2F2 or E2F3 depletion did not recapitulate the cisplatin sensitivity elicited by E2F1 elimination. Our study unveils an E2F1-specific signaling circuit that constitutively activates ATM and provokes cisplatin resistance in BIN1-deficient cancer cells and further reveals that γH2AX emergence may not always reflect DSBs if BIN1 is absent.

A Bag of Marbles: A Fascinating Compound Odontoma of the Maxilla.

Odontomas are the most common odontogenic tumors, typically diagnosed during the first two decades of life. 1 The purpose of this paper was to report an interesting case of an eight-year-old Caucasian boy who presented with an asymptomatic, progressive, firm swelling of the right maxilla with no eruption of the permanent maxillary right lateral incisor. Radiographic investigation revealed a mixed radiolucent and radiopaque lesion measuring 28 by 24 by 17 mm with a corticated border causing expansion and thinning of the buccal cortical plate. This large bag-of-marbles-like appearance representing odontoids was impeding his adult teeth from erupting; hence, complete surgical removal under general anesthesia was the treatment of choice. Removal of the lesion resulted in an unexpected loss of the embedded permanent maxillary right lateral incisor. Histopathological investigations gave a diagnosis of compound odontoma; due to their low growth potential, recurrence after removal is not expected.

The Prosthetic Management of an Infra-Occluded First Permanent Molar: Case Report.

This report describes the prosthetic management of a 15-year-old patient with an infra-occluded first permanent molar due to primary failure of eruption (secondary retention). An indirect composite onlay restoration was used to stimulate the periodontal fibres, improve function and restore occlusal stability. This paper describes the clinical technique involved. CPD/Clinical Relevance: Early detection, diagnosis and management of infra-occluded permanent molar teeth is important to avoid occlusal complications, in addition to improving function and stimulating the periodontal fibres.

"Watching time tick by ": Decision making for Duchenne muscular dystrophy trials.

OBJECTIVE: This interview study explored clinicians' perspectives and parents' decision making about children's participation in Duchenne muscular dystrophy (DMD) clinical trials. METHODS: Data from semi-structured interviews conducted with clinicians and parents in U.S. or Canada were assessed using thematic analysis. RESULTS: Eleven clinicians involved in ten trials and fifteen parents involved in six trials were interviewed. Parents described benefit-risk assessments using information from advocacy, peers, professionals, and sponsors. Strong influence was attributed to the progressive nature of DMD. Most expected direct benefit. Few considered the possibility of trial failure. Most made decisions to participate before the informed consent (IC) process, but none-the-less perceived informed choice with little to lose for potential gain. Clinicians described more influence on parental decisions than attributed by parents. Clinicians felt responsible to facilitate IC while maintaining hope. Both clinicians and parents reported criticisms about the IC process and regulatory barriers. CONCLUSIONS: The majority of parents described undertaking benefit-risk assessments that led to informed choices that offered psychological and potential disease benefits. Parents' high expectations influenced their decisions while also reflecting optimism. Clinicians felt challenged in balancing parents' expectations and likely outcomes. Prognosis-related pressures coupled with decision making prior to IC suggest an obligation to ensure educational materials are understandable and accurate, and to consider an expanded notion of IC timeframes. Anticipatory guidance about potential trial failure might facilitate parents' deliberations while aiding clinicians in moderating overly-optimistic motivations. Regulators and industry should appreciate special challenges in progressive disorders, where doing nothing was equated with doing harm.

Simplified basic periodontal examination (BPE) in children and adolescents: a guide for general dental practitioners.

UNLABELLED: Dental plaque-induced periodontal diseases are common in children and adults. Guidelines were previously not available for the periodontal screening of under 18s. However, new guidelines have been introduced by the British Society of Periodontology and the British Society of Paediatric Dentistry which set out recommendations for the periodontal screening and management of under 18s in primary dental care. This article provides a practical guide for general dental practitioners on how to use the BPE in children and adolescents, and highlights the importance of early detection and management of periodontal diseases in this age group. A failure to use the modified BPE in a young patient who is later diagnosed with periodontitis may leave a dentist vulnerable to a medico-legal complaint or claim. CLINICAL RELEVANCE: New BPE guidelines for children and adolescents have been introduced by the BSPD and BSP; it is important that all dentists are aware of these guidelines and how to implement them in general practice.

Adenovirus E1A oncoprotein liberates c-Myc activity to promote cell proliferation through abating Bin1 expression via an Rb/E2F1-dependent mechanism.

Adenovirus E1A oncogene transforms primary rodent fibroblasts in cooperation with activated Ras. Conversely, the c-Myc oncoprotein-binding tumor suppressor, Bin1, inhibits Ras/E1A-mediated cell transformation. Since E1A does not directly bind to and inhibit Bin1, the primary mechanism by which E1A counteracts Bin1 to liberate oncogenic c-Myc activity is poorly understood. Here we show that wild-type E1A, but not an Rb binding-defective E1A mutant, suppresses endogenous Bin1 expression in cultured rodent fibroblasts. Similarly, other anti-Rb agents, such as human papillomavirus E7, mitogenic stimuli, and small interfering RNA (siRNA) for Rb, consistently decrease Bin1 promoter activity. In contrast, serum starvation, which activates Rb, enhances endogenous Bin1 levels. These findings suggest that Bin1 may be a novel component of Rb-mediated G1 arrest. Consistent with this premise, chromatin immunoprecipitation assays demonstrate that Rb protein directly interacts with the Bin1 promoter only upon removal of serum. Furthermore, ectopically expressed E2F1, which is primarily inhibited by Rb under serum-starved condition, represses Bin1 promoter activity in a manner that is dependent on the DNA-binding and transactivation domains of E2F1. Lastly, depletion of endogenous Bin1 per se is biologically meaningful since antisense or siRNA of Bin1 transfection releases endogenous c-Myc transcriptional activity and, concomitantly, accelerates cell proliferation. Our results suggest that Bin1 gene suppression caused by oncogenic E1A via Rb inactivation is an essential step in cell cycle progression promoted by c-Myc, and subsequently, E1A transformation. We propose a novel G1 arrest signaling mechanism by which Rb indirectly curbs oncogenic c-Myc activity via sustaining Bin1 expression.

The use of multidirectional cross-sectional tomography for localizing an odontome.

BACKGROUND: A 7-year old boy was referred with retained maxillary right primary central and lateral incisors. Radiographic exam revealed a large calcified radio-opaque mass overlying the roots of these primary teeth preventing the permanent teeth from erupting. CASE REPORT: The purpose of this paper is to describe the pre-operative use of multi-directional cross-sectional tomography in establishing the relationship between a large complex odontome that was preventing the eruption of a maxillary permanent central incisor. CONCLUSION: Low dose, multi-directional cross-sectional tomography was beneficial in visualisation of the precise relationship between the large complex odontome and the unerupted permanent incisor. This allowed correct judgement of the position on the odontome prior to its surgical removal.