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Observational studies play a critical role in evaluating the prevalence and incidence of conditions or diseases in populations as well as in defining the benefits and potential hazards of health-related interventions. There are currently no reporting guidelines for observational studies in the field of Endodontics. The Preferred Reporting Items for study Designs in Endodontology (PRIDE) team has developed and published new reporting guidelines for observational-based studies called the ‘Preferred Reporting items for OBservational studies in Endodontics (PROBE) 2023’ guidelines. The PROBE 2023 guidelines were developed exclusively for the speciality of Endodontics by integrating and adapting the ‘STrengthening the Reporting of OBservational studies in Epidemiology (STROBE)’ checklist and the ‘Clinical and Laboratory Images in Publications (CLIP)’ principles. The recommendations of the Guidance for Developers of Health Research Reporting Guidelines were adhered to throughout the process of developing the guidelines. The purpose of this document is to serve as a guide for authors by providing an explanation for each of the items in the PROBE 2023 checklist along with relevant examples from the literature. The document also offers advice to authors on how they can address each item in their manuscript before submission to a journal. The PROBE 2023 checklist is freely accessible and downloadable from the PRIDE website (http://pride-endodonticguidelines.org/probe/).

An evolving understanding of the carious process, along with new research in adhesive restorative materials, has led to a more conservative, minimally invasive and biologically-based approach to managing dental carious lesions. The growing volume of literature has also demonstrated prognostic success in the selective caries excavation technique, subsequently preventing excessive tooth structure removal and injury to the dentine-pulp complex, which maintains pulp vitality and improves the long-term prognosis of the tooth. However, at present, there remains a limited volume of high-quality evidence to support selective caries removal, which subsequently could partly explain some resistance to its use in clinical practice. This clinical technique guide aims to demonstrate the management of carious lesions of moderate-to-deep depth in permanent teeth based on current minimally invasive dental literature.

The promotion of minimally invasive treatments focussed on the maintenance of pulp vitality has become a priority area in Endodontics. These vital pulp treatments (VPT) include partial and full pulpotomy, during which diseased coronal pulp tissue is removed prior to placement of a capping biomaterial and restoration. Traditionally, pulpotomies were confined to the treatment of carious primary and traumatized permanent teeth. However, these treatments have now been proposed as definitive solutions for cariously exposed permanent teeth with mild symptoms or even symptoms indicative of irreversible disease. Until recently, it was recommended that carious exposure of mature permanent teeth be managed by root canal treatment. The promotion of pulpotomy as an alternative treatment has opened up a wave of laboratory and clinical research aimed at improving therapies or evaluating clinical outcomes. In modern evidence-based endodontics, it is imperative that the outcomes of both partial and full pulpotomy are considered and important prognostic factors identified, so that improvements can be made to aid clinical decision-making and to direct new research. In this narrative review, the outcomes of partial and full pulpotomy are discussed, before analysis of patient, intraoperative and postoperative factors that influence the outcome of the pulpotomy procedure. The review highlights that although partial and full pulpotomy for the treatment of even pulpal disease are highly successful procedures, this is based on low-quality evidence with a lack of prospective, comparative trials investigating potential prognostic factors. Based on current evidence, it appears that age, gender, tooth type, root development and intraoperative pulpal haemorrhage do not impact significantly on pulpotomy outcome, whilst others such as caries depth, inflammatory status of the pulp, capping material, level of inflammatory pulpal-biomarkers and the final restoration integrity do. Other factors, including the influence of exposure type, periodontal condition, pulpal lavage, magnification, operator experience, isolation of the operating field and type of pulpotomy, require further experimental investigation before definitive conclusions can be made relating to the success of the pulpotomy procedure. Finally, there is not only a need for future well-designed prospective research addressing these issues but also a widening of our understanding of outcome to include patient-reported as well as clinician-reported outcomes.

BackgroundRevitalization is a type of regenerative endodontic treatment (RET) that offers the exciting prospect of revitalizing damaged tissue, therefore improving outcomes for non-vital immature teeth. To evaluate its potential, there needs to be consistency in outcome reporting of clinical studies investigating revitalization to allow for evidence synthesis and inform clinical decision making.ObjectivesThe aim of this scoping review was to identify outcomes that are reported in systematic reviews on revitalization including how and when these outcomes are measured. Additionally, evidence of selective reporting bias in the reviews was assessed.MethodsA comprehensive electronic search of healthcare databases and grey literature was conducted to identify systematic reviews published in the English language reporting outcomes of revitalization in permanent immature teeth. There was no restriction on the date of publication. Outcome data was extracted by four reviewers independently and mapped with a healthcare taxonomy into five core areas: survival, clinical/physiological changes, life impact, resource use and adverse events. Selective reporting bias and how it was measured was assessed independently by two reviewers.ResultsTwenty-six systematic reviews were included in this scoping review. There was lack of standardization in reporting and significant heterogeneity across reviews in outcome endpoints. The outcomes reported could be aligned within the five core areas of the taxonomy including tooth survival which was reported in nine reviews. Patient-reported outcomes were generally limited and no review reported on Oral Health Related Quality of Life. Many of the reviews reporting on randomized control trials were at low risk of selective reporting bias whilst other study designs were at higher risk.DiscussionConsistency in outcome reporting is necessary to realize the benefits of old but particularly novel therapies. Data from this review confirmed heterogeneity in reporting outcomes of revitalization and the need for development of a core outcome set (COS).ConclusionsSeveral important outcomes including survival, root development, tooth discolouration and periapical healing have been identified in this review which could inform the development of a COS in this area.

Donation after circulatory death (DCD) is emerging as an alternative pathway to donation after brain death (DBD) to expand the cardiac organ donor pool.1 We describe the surgical technique and circuit configuration for in-situ organ reperfusion with thoracoabdominal normothermic regional perfusion (TA-NRP) using portable venoarterial extracorporeal membrane oxygenation (VA-ECMO).

Observational studies are non-interventional studies that establish the prevalence and incidence of conditions or diseases in populations or analyse the relationship between health status and other variables. They also facilitate the development of specific research questions for future randomized trials or to answer important scientific questions when trials are not possible to carry out. This article outlines the previously documented consensus-based approach by which the Preferred Reporting items for Observational studies in Endodontics (PROBE) 2023 guidelines were developed. A steering committee of nine members was formed, including the project leaders (PD, VN). The steering committee developed an initial checklist by combining and adapting items from the STrengthening the Reporting of Observational studies in Epidemiology (STROBE) checklist and the Clinical and Laboratory Images in Publications (CLIP) principles, as well as adding several new items specifically for the specialty of Endodontics. The steering committee then established a PROBE Delphi Group (PDG) and a PROBE Online Meeting Group (POMG) to obtain expert input and feedback on the preliminary draft checklist. The PDG members participated in an online Delphi process to reach consensus on the clarity and suitability of the items present in the PROBE checklist. The POMG then held detailed discussions on the PROBE checklist generated through the online Delphi process. This online meeting was held via the Zoom platform on 7th October 2022. Following this meeting, the steering committee revised the PROBE checklist, which was piloted by several authors when preparing a manuscript describing an observational study for publication. The PROBE 2023 checklist consists of 11 sections and 58 items. Authors are now encouraged to adopt the PROBE 2023 guidelines, which will improve the overall reporting quality of observational studies in Endodontics. The PROBE 2023 checklist is freely available and can be downloaded from the PRIDE website (https://pride-endodonticguidelines.org/probe/).

Evidence-informed decision-making in health care relies on the translation of research results to everyday clinical practice. A fundamental requirement is that the validity of any healthcare intervention must be supported by the resultant favourable treatment outcome. Unfortunately, differences in study design and the outcome measures evaluated often make it challenging to synthesize the available research evidence required for secondary research analysis and guideline development. Core outcome sets (COS) are defined as an agreed standardized set of outcomes, which should be measured and reported as a minimum in all clinical trials on a specific topic. The benefits of COS include less heterogeneity, a reduction in the risk of reporting bias and ensuring all trials contribute data to facilitate meta-analyses; given the engagement of key stakeholders, it also increases the chances that clinically relevant outcomes are identified. The recognition of the need for COS for assessing endodontic treatment outcomes leads to the development of Core Outcome Sets for Endodontic Treatment modalities (COSET) protocol, which is registered (No. 1879) on the Core Outcome Measures in Effectiveness Trials (COMET) website.The objectives of this scoping review are to: (1) identify the outcomes assessed in studies evaluating surgical endodontic procedures; (2) report on the method of assessment used to measure the outcomes; (3) and assess selective reporting bias in the included studies. The data obtained will be used to inform the development of COS for surgical endodontics.A structured literature search of electronic databases and the grey literature was conducted to identify systematic reviews on periradicular surgery (PS), intentional replantation (IR) and tooth/root resection (RR), published between January 1990 and December 2020. Two independent reviewers were involved in the literature selection, data extraction and the appraisal of the studies identified. The type of intervention, outcomes measured, type of outcomes reported (clinician- or patient-reported), outcome measurement method and follow-up period were recorded using a standardized form.Twenty-six systematic reviews consisting of 19 studies for PS, three studies for IR and four studies for RR were selected for inclusion. Outcome measures identified for PS and IR included pain, swelling, mobility and tenderness, outcomes related to periodontal/soft tissue healing (including sinus tract), periradicular healing, tooth survival, life impact (including oral health-related quality of life), resource use and/or adverse effects. For RR, in addition to tooth survival, endodontic complications and adverse effects, the outcome measures were primarily periodontal-related, including pocket depth reduction, attachment gain, periodontal disease and periodontic-endodontic lesions. The majority of outcome measures for PS, IR and RR were assessed clinically, radiologically and/or via patient history. Specific tools such as rating scales (Visual Analog Scale, Verbal Rating Scale, Numerical Rating Scale and other scales) were used for the assessment of pain, swelling and tenderness, and validated questionnaires were used for the assessment of oral health-related quality of life. The range of follow-up periods was variable, dependent on the outcome measure and the type of intervention.Outcome measures, method of assessment and follow-up periods for PS, IR and RR were identified and categorized to help standardize the reporting of outcomes for future research studies. Additional outcome measures that were not reported, but may be considered in the COSET consensus process, include loss of root-end filling material, number of clinic visits, surgery-related dental anxiety and mucogingival aesthetic-related measures, such as scarring, black triangles, root surface exposure and tissue discoloration.COMET (No. 1879).

COVID-19 continues to have a profound impact on infant healthcare and health outcomes. In this study, we aimed to characterize the social impact of the first COVID-19 lockdown on families in a neonatal follow-up program (NFP). Given the ongoing increased use of telehealth across the medicine, we also evaluated for patient-level differences in virtual visit rates to identify patients at risk of follow-up challenges.In order to assess the impact of virtual healthcare utilization, we conducted a retrospective cohort study to describe challenges associated with telemedicine use in this vulnerable patient population during our telemedicine epoch (March 13, 2020-July 31, 2020). We also looked for patient-level factors associated with attending NFP visits as scheduled. Finally, we summarized caregiver responses to a COVID-19 Obstacles Assessment Survey and assessed for racial disparities in these responses.When comparing patients who completed their virtual visit to those who did not, we found no differences by infants' sex, birthweight, gestational age at birth or caregiver self-reported race and ethnicity. However, infants whose visits did not occur were more often discharged with equipment or covered by public insurance. Nine percent of families endorsed food insecurity.During the initial COVID-19 lockdown, families with infants discharged from a NICU faced significant obstacles caring for their infants and attending scheduled follow-up visits. Infants in families with lower socioeconomic status or with increased medical complexity faced increased challenges in attending virtual follow-up visits during this epoch. Given the ongoing reliance on telemedicine in healthcare and the need to better prepare for future epidemics/pandemics, this study offers critical information that can assist neonatal teams in bolstering transitions to home and creating stronger safety nets for their patients after discharge.

Outcome expectations of direct pulp capping in carious teeth are obscured by a clinically unknown infiltration and breakdown of the dental pulp tissue. Histologic studies showed that this soft tissue breakdown is related to the innate immune system. We hypothesized 1) that a neutrophil biomarker could predict the outcome of direct pulp capping and 2) that using sodium hypochlorite (NaOCl) as a lavage solution to remove necrotized infected pulp tissue could improve it. In this randomized trial in mature posterior teeth causing no or mild discomfort with carious pulpal exposures, pulpal fluid was collected to assess neutrophil gelatinase (matrix metalloproteinase 9 [MMP-9]) per total protein (TP) levels as a predictive local biomarker. Subsequently, the dentin-pulp wound was randomly washed with a 2.5% NaOCl or a physiologic saline solution (1:1 allocation), capped with mineral trioxide aggregate, and the tooth was immediately restored with a resin-based composite restoration. Ninety-six patients were included, and 84 individuals could be followed up to treatment failure or clinically confirmed pulp survival after a minimum of 1 y. The entire data were fitted to a Cox proportional hazards model to assess the influence of the observational variables MMP-9/TP and discomfort with the randomized lavage treatment on pulp survival. The Kaplan-Meier pulp survival rates after 1 y were 55% for saline and 89% for NaOCl lavage. The inflammatory state of the pulp tissue as reflected by MMP-9/TP levels and NaOCl lavage had a highly significant ( P

AIM To prospectively investigate the outcome of partial pulpotomy after 1 year, using a hydraulic calcium silicate cement (HCSC) on symptomatic cariously exposed pulps in adult teeth. To compare the traditional American Association of Endodontists (AAE) pulpitis classification with the recently proposed Wolters classification system in predicting the likelihood of treatment failure. METHODOLOGY Sixty-two symptomatic adult teeth with deep and extremely deep carious lesions were classified according to the Wolters (mild/moderate/severe pulpitis) and the traditional pulpitis classification (reversible/irreversible pulpitis). Eleven teeth were excluded intraoperatively as there was no pulp exposure after non-selective caries removal. The remaining 51 teeth, regardless of diagnosis, were treated by partial pulpotomy, pulpal lavage with 2.5% sodium hypochlorite solution, haemostasis and HCSC application (Biodentine™) as a pulp capping material. A permanent restoration was placed during a second appointment 1-2 weeks later. Preoperative tenderness to percussion (TTP), bleeding time and material setting time were recorded as was preoperative and postoperative tooth colour under standardized conditions. Clinical review occurred at regular intervals with clinical/radiographic analysis at 12 months. Chi-square analysis and Fisher's exact test assessed different outcomes amongst the diagnostic categories; the Kruskal-Wallis and Wilcoxon rank-sum test assessed influence of pulp bleeding time, TTP or variation in setting time (p

Background Public mental health (PMH) aims to improve wellbeing and prevent poor mental health at the population level. It is a global challenge and a UK priority area for action. Communities play an important role in the provision of PMH interventions. However, the evidence base concerning community-based PMH interventions is limited, meaning it is challenging to compare service provision to need. Without this, the efficient and equitable provision of services is hindered. Here, we sought to map the current range of community-based interventions for improving mental health and wellbeing currently provided in England to inform priority areas for policy and service intervention. Method We adopted an established mapping exercise methodology, comparing service provision with demographic and deprivation statistics. Five local authority areas of England were selected based on differing demographics, mental health needs and wider challenging circumstances (i.e. high deprivation). Community-based interventions were identified through: 1) desk-based research 2) established professional networks 3) chain-referral sampling of individuals involved in local mental health promotion and prevention and 4) peer researchers’ insight. We included all community-based, non-clinical interventions aimed at adult residents operating between July 2019 and May 2020. Results 407 interventions were identified across the five areas addressing 16 risk/protective factors for PMH. Interventions for social isolation and loneliness were most prevalent, most commonly through social activities and/or befriending services. The most common subpopulations targeted were older adults and people from minority ethnic backgrounds. Interventions focusing on broader structural and environmental determinants were uncommon. There was some evidence of service provision being tailored to local need, though this was inconsistent, meaning some at-risk groups such as men or LGBTQ+ people from minority ethnic backgrounds were missed. Interventions were not consistently evaluated. Conclusions There was evidence of partial responsiveness to national and local prioritising. Provision was geared mainly towards addressing social and individual determinants of PMH, suggesting more integration is needed to engage wider service providers and policy-makers in PMH strategy and delivery at the community level. The lack of comprehensive evaluation of services to improve PMH needs to be urgently addressed to determine the extent of their effectiveness in communities they serve.

Objective Coronavirus disease 2019 (COVID-19) continues to have a profound impact on infant health care and health outcomes. In this study, we aimed to characterize the social impact of the first COVID-19 lockdown on families in a neonatal follow-up program (NFP). Given the ongoing increased use of telehealth across the medicine, we also evaluated for patient-level differences in virtual visit rates to identify patients at risk of follow-up challenges. Study Design To assess the impact of virtual health care utilization, we conducted a retrospective cohort study to describe challenges associated with telemedicine use in this vulnerable patient population during our telemedicine epoch (March 13, 2020–July 31, 2020). We also looked for patient-level factors associated with attending NFP visits as scheduled. Finally, we summarized caregiver responses to a COVID-19 Obstacles Assessment Survey and assessed for racial disparities in these responses. Results When comparing patients who completed their virtual visit to those who did not, we found no differences by infants' sex, birthweight, gestational age at birth, or caregiver self-reported race and ethnicity. However, infants whose visits did not occur were more often discharged with equipment or covered by public insurance. Nine percent of families reported food insecurity. Conclusion During the initial COVID-19 lockdown, families with infants discharged from a neonatal intensive care unit (NICU) faced significant obstacles caring for their infants and attending scheduled follow-up visits. Infants in families with lower socioeconomic status or with increased medical complexity faced increased challenges in attending virtual follow-up visits during this epoch. Given the ongoing reliance on telemedicine in health care and the need to better prepare for future epidemics/pandemics, this study offers critical information that can assist neonatal teams in bolstering transitions to home and creating stronger safety nets for their patients after discharge. Key Points

Histone acetylation and deacetylation of DNA-associated proteins have been shown to alter the architecture of chromatin, affecting gene expression and controlling a wide range of biological events. These events are balanced by two sets of cellular enzymes, histone-deacetylases (HDACs) and histone acetyl-transferases (HATs). Pharmacological inhibition of histone-deacetylases (HDACs) using HDAC-inhibitors (HDACis) has been shown to promote dental pulp cell reparative processes with therapeutic implications in various fields including regenerative dentistry. To date, pan-HDACi have generally been used rather than isoform-specific HDACi targeting, despite the fact that HDAC-specific inhibitors have been developed to target HDACs in several tissues. To identify potential therapeutic targets in the tooth, the expression and distribution of HDAC-isoforms need to be analyzed. This chapter focuses on techniques to analyze expression, location, and distribution of individual HDAC-isoforms under mineralizing conditions using both histology and cell biology, along with a description of basic techniques for culturing and mineralization of rodent dental pulp cells.

Recently, the central role of microRNAs (miRNAs) and epigenetic modifiers in biological and pathological processes, such as stem cell differentiation and inflammation, has stimulated interest. In particular, their influence in dental pulp stem cell (DPSC) differentiation has been highlighted as an exciting avenue of research in the field of Regenerative Endodontics. Although specific miRNAs have been shown to be altered in expression during dental pulp mineralization and repair processes, their interaction with epigenetic modifiers, such as histone deacetylase inhibitors (HDACi) or DNA methyltransferase inhibitors (DNMTi), has not been explored. Currently available next-generation sequencing (NGS) technologies offer the potential to explore in detail the miRNA expression profile of cells, and to investigate the effects of pharmacological inhibitors such as epigenetic modifiers on this profile. This chapter describes the experimental methods required to induce mineralization of DPCs in the presence and absence of epigenetic modifiers and analyze the resulting miRNA expression profiles using RNA sequencing (RNAseq), with a focus on bioinformatic analysis.

Endodontic therapy aims to preserve teeth by preventing and treating apical disease, therefore, evaluation of treatment outcome in clinical trials and outcomes studies should effectively assess if it achieves these aims. Traditionally, treatment outcomes have been reported by clinicians after history and clinical examination in what is known as clinician-reported outcomes (CROs). Much less commonly employed however, are patient-reported outcomes (PROs) in which patients directly report on their condition. Endodontic treatment outcome reporting is evolving from a focus on CROs to increasing consideration for patient and disease-focused outcomes, with different criteria being proposed for assessment of treatment outcomes. Unfortunately, this has led to considerable variability and a lack of consensus on the definition, appropriate measurement and reporting of these outcomes. Heterogeneity in outcome reporting in clinical research provides a significant major barrier to conduct meta-analysis, guidelines development, clinical decision making, and ultimately affecting patient care. These effects could, however, be reduced by the establishment of a core outcome set (COS) in endodontics, which is defined as an agreed, standardized set of outcomes that should be included, measured and reported as a minimum in all trials and outcome studies. COS development is a regulated and validated process requiring involvement of appropriate stakeholders as well as a rigorous methodology. To date, COS has been developed for the management of traumatic dental injuries, orthodontic and periodontal treatment and is currently being developed for endodontic treatment. The aim of this review is to discuss the importance of COS in endodontics with focus on the evidence for and impact of heterogeneity in reporting endodontic treatment outcomes. An overview of an ongoing process for development of COS for different endodontic treatment modalities will also be provided.

Background Public mental health (PMH) services address social determinants of mental health, such as poverty, poor housing, and job insecurity. Austerity and welfare reform in the UK has led to cuts to social and welfare support, increasing poor mental health and widening inequalities, exacerbated by COVID-19. State health services lack capacity to tackle social issues that contribute to a large proportion of expressed mental health need. Co-locating PMH services within community spaces is a potential solution to increase early access and improve quality of services. Using a realist evaluation, we sought to develop the theory on how community co-location affects PMH outcomes, who this works best for, and how this is impacted by the context of delivery. Methods We collected data from service-users and service-providers at six case study sites across England, UK, using interviews (n = 62), four focus groups (n = 40) and two stakeholder workshops (n = 19). Results We identified four overarching theories. First, community providers do not operate under the same limits as state services allowing them the flexibility and time to build trust and ongoing relationships with service users. Second, the ethos and culture of services is to empower users to access help and be independent. Third, accessing support from a shared local space allows a coordinated and holistic response reducing barriers such as distance, cost, and anxiety. Four, as they are recreational services and spaces for access by all with no predefined/required level of need they are better at promoting wellbeing and primary prevention. Conclusions Community co-location of PMH services can strengthen the overall mental health system by widening reach to people vulnerable to poor mental health and enabling earlier intervention on associated social determinants. This has potential to reduce mental health inequalities and demand on the state health system. Key messages

A large number of research reports on vital pulp treatment (VPT) has been published over the last two decades. However, heterogeneity in reporting outcomes of VPT is a significant challenge for evidence synthesis and clinical decision-making.To identify outcomes assessed in VPT studies and to evaluate how and when outcomes are measured. A subsidiary aim was to assess evidence for selective reporting bias in the included studies. The results of this review will be used to inform the development of a core outcome set (COS) for endodontic treatments.Multiple healthcare bibliographic databases, including PubMed/MEDLINE, Ovid EMBASE, Scopus, Cochrane Database of Systematic Reviews and Web of Science were searched for systematic reviews published between 1990 and 2020, reporting on VPT. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Outcomes' information was extracted and aligned with a healthcare taxonomy into five core areas: survival, clinical/physiological changes, life impact, resource use and adverse events.Thirty-six systematic reviews were included, 10 reporting on indirect pulp capping or selective caries removal, nine on direct pulp capping, eight on pulpotomy and nine on combined VPTs. There was considerable variation in the outcomes reported in these reviews and their included studies. Clinician-reported outcomes were used considerably more often than patient-reported outcomes. A range of instruments and time points were used for measuring outcomes. Several of the reviews were assessed as having low risk of selective reporting bias, but many did not specifically report this domain, whilst others did not provide risk of bias assessment at all.Considerable variation in selection of outcomes and how and when they are measured and reported was evident, and this heterogeneity has implications for evidence synthesis and clinical decision-making.Whilst there is a lack of consistency, several potentially important outcomes for VPT, including pulp survival, incidence of post-operative pain and need for further intervention, have been identified which could inform the development of a COS for endodontic treatment.Core Outcome Measures in Effectiveness Trials (COMET) (No. 1879).

Enhancer of zeste homolog 2 (EZH2) is the catalytic core of polycomb repressive complex 2 (PRC2), which primarily methylates lysine 27 on histone H3 (H2K27me3), generating transcriptionally suppressed heterochromatin. Since EZH2 suppresses expression of genes involved in dentin formation, we examined the role of EZH2 in tooth development. Intriguingly, microCT analysis of teeth from mice with conditional Ezh2 knockout in uncommitted mesenchymal cells showed hyper-mineralization of enamel, which is produced by the epithelial-lineage cells, ameloblasts. Scanning electron microscopy analysis and nano-indentation of the incisor enamel from knockout mice revealed smaller inter-rod spaces and higher hardness compared to wild type enamel, respectively. Interestingly, expression of the calcium channel subunit gene, Orai2, was decreased compared to its competitor, Orai1, both in knockout mouse incisors and the ex vivo culture of ameloblasts with the surrounding tissues under EZH2 inhibition. Moreover, histological analysis of incisor from knockout mice showed decreased ameloblastin and expedited KLK4 expression in the ameloblasts. These observations suggest that EZH2 depletion in dental mesenchymal cells reduces enamel matrix formation and increases enamel protease activity from ameloblasts, resulting in enamel hyper-mineralization. This study demonstrates the significant role of the suppressive H3K27me3 mark for heterochromatin on enamel formation.

Statement of Problem: Concerns were raised that referrals to the Dublin Dental University Hospital (DDUH) Periodontology Department often lacked sufficient information for triaging. ##Purpose of the Study: To investigate the quality of periodontal referrals when compared with a local standard and examine if the use of the existing divisional referral proforma was associated with a higher standard of referral. ##Materials and methods: Data was collected by retrospectively auditing 150 external referrals to the DDUH Periodontology Department at representative intervals over a 12-month period. Referrals were assessed to investigate if they included 22 information points as requested by our local standard (referral proforma). Data was input into a Microsoft Excel spreadsheet and analysed. Ten periodontal referrals proforma from similar Dental Institutes across Ireland and the UK were also compared to our proforma to investigate if our institution requests a similar level of information to others. ##Results: Referral analysis indicated that clinicians provided on average 12.9 out of 22 (59%) items of required information in their referral correspondence. Referrers utilised the appropriate referral proforma in 28% of cases. Use of this proforma was associated with a better standard of referral (17.9 out of 22 required information items provided, 80%) when compared with non-proforma referrals (11.2 out of 22 required information items provided, 51%). Analysis of other institutions’ proforma highlighted that DDUH requests referring practitioners to include more information than equivalent peer institutions. ##Conclusion: Periodontal referral letters to DDUH frequently fail to include sufficient information. Practitioners seldom utilise the divisional referral proforma, although its use is associated with improved referral quality. Simplification of the existing referral proforma and dissemination of referral guidelines to practitioners is recommended moving forward.

Follow-up studies are essential for understanding outcomes and informing the care of infants with high risk for medical and developmental consequences because of extreme prematurity or perinatal illness. Studies that extend to school age often identify sequelae that go unrecognized in neonatal or short-term follow-up studies. Many critical neurocognitive, behavioral, functional, and health outcomes are best assessed beginning at school age. The Eunice Kennedy Shriver National Institute of Child Health and Development Neonatal Research Network (NRN) has performed comprehensive school age evaluations of several key trial cohorts. This manuscript summarizes the important contributions of school age follow-up studies in the NRN, both historically and in ongoing research. We describe in detail the clinical questions that have been answered by the completed studies and new questions about the outcomes of high-risk infants that must be addressed by ongoing and future studies.

To demonstrate the utility of continuous-wave (CW) saturation pulses in xenon-polarization transfer contrast (XTC) MRI and MRS, to investigate the selectivity of CW pulses applied to dissolved-phase resonances, and to develop a correction method for measurement biases from saturation of the nontargeted dissolved-phase compartment.Studies were performed in six healthy Sprague-Dawley rats over a series of end-exhale breath holds. Discrete saturation schemes included a series of 30 Gaussian pulses (8 ms FWHM), spaced 25 ms apart; CW saturation schemes included single block pulses, with variable flip angle and duration. In XTC imaging, saturation pulses were applied on both dissolved-phase resonance frequencies and off-resonance, to correct for other sources of signal loss and compromised selectivity. In spectroscopy experiments, saturation pulses were applied at a set of 19 frequencies spread out between 185 and 200 ppm to map out modified z-spectra.Both modified z-spectra and imaging results showed that CW RF pulses offer sufficient depolarization and improved selectivity for generating contrast between presaturation and postsaturation acquisitions. A comparison of results obtained using a variety of saturation parameters confirms that saturation pulses applied at higher powers exhibit increased cross-contamination between dissolved-phase resonances.Using CW RF saturation pulses in XTC contrast preparation, with the proposed correction method, offers a potentially more selective alternative to traditional discrete saturation. The suppression of the red blood cell contribution to the gas-phase depolarization opens the door to a novel way of quantifying exchange time between alveolar volume and hemoglobin.

Background The association between adverse pregnancy outcomes (APOs) and maternal apical periodontitis remains unclear as it has not been examined rigorously or reviewed systematically. Objective To systematically review and critically evaluate the available evidence on the association of maternal apical periodontitis with several APOs. Methods A literature search was conducted using the following electronic databases: Clarivate Analytics' Web of Science, Scopus, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL), from inception to 25 February 2021, with no language restrictions. Observational studies including longitudinal clinical trials, cohort, case-control and cross-sectional studies of prospective and retrospective design were included. Articles with duplicate or overlapping results, abstract-only papers, case reports, case series, animal studies and reviews were excluded. Two independent reviewers were involved in study selection, data extraction and appraising the included studies; disagreements were resolved by a third reviewer. The Newcastle-Ottawa Scale (NOS) and the adapted form of the NOS were used to assess the quality for case-control and cross-sectional studies, respectively. Results Two case-control and one cross-sectional study were included in the current review. The included studies were published between 2015 and 2017, with a total of 1187 participating individuals with an approximate age range of 15 to 40 years. As the included studies reported different outcomes, the heterogeneity of data prevented a meta-analysis being undertaken. The overall quality of the evidence was 'Fair' for two out of three included studies, while one study was categorized as 'Good'. Discussion Two out of three included primary studies had a substantial number of methodological inconsistencies and flaws, and therefore caution should be exercised in interpreting the results of this systematic review because several important covariates were not considered in the original investigations. Conclusion Based on a limited volume and 'Fair' and 'Good' quality of evidence, a positive association between maternal apical periodontitis and APOs was observed. However, more 'Good' quality clinical studies are needed to confirm the results of the current review. Funding None REGISTRATION: PROSPERO database (CRD42-2191987).

BACKGROUND Mental health concerns in older adults are common, with increasing age-related risks to physical health, mobility and social isolation. Community-based approaches are a key focus of public health strategy in the UK, and may reduce the impact of these risks, protecting mental health and promoting wellbeing. We conducted a review of UK community-based interventions to understand the types of intervention studied and mental health/wellbeing impacts reported. METHOD We conducted a scoping review of the literature, systematically searching six electronic databases (2000-2020) to identify academic studies of any non-clinical community intervention to improve mental health or wellbeing outcomes for older adults. Data were extracted, grouped by population targeted, intervention type, and outcomes reported, and synthesised according to a framework categorising community actions targeting older adults. RESULTS In total, 1,131 full-text articles were assessed for eligibility and 54 included in the final synthesis. Example interventions included: link workers; telephone helplines; befriending; digital support services; group social activities. These were grouped into: connector services, gateway services/approaches, direct interventions and systems approaches. These interventions aimed to address key risk factors: loneliness, social isolation, being a caregiver and living with long-term health conditions. Outcome measurement varied greatly, confounding strong evidence in favour of particular intervention types. CONCLUSION The literature is wide-ranging in focus and methodology. Greater specificity and consistency in outcome measurement are required to evidence effectiveness - no single category of intervention yet stands out as 'promising'. More robust evidence on the active components of interventions to promote older adult's mental health is required.

OBJECTIVE: This study evaluates the 24 month follow up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial. STUDY DESIGN: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score

Background Individuals with cancer are being given increasing responsibility for the self-management of their health and illness. In other chronic diseases, individuals who experience treatment burden are at risk of poorer health outcomes. Less is known about treatment burden and its impact on individuals with cancer. This systematic review investigated perceptions of treatment burden in individuals living with and beyond cancer. Methods and findings Medline, CINAHL and EMBASE databases were searched for qualitative studies that explored treatment burden in individuals with a diagnosis of breast, prostate, colorectal, or lung cancer at any stage of their diagnostic/treatment trajectory. Descriptive and thematic analyses were conducted. Study quality was assessed using a modified CASP checklist. The review protocol was registered on PROSPERO (CRD42021145601). Forty-eight studies were included. Health management after cancer involved cognitive, practical, and relational work for patients. Individuals were motivated to perform health management work to improve life-expectancy, manage symptoms, and regain a sense of normality. Performing health care work could be empowering and gave individuals a sense of control. Treatment burden occurred when there was a mismatch between the resources needed for health management and their availability. Individuals with chronic and severe symptoms, financial challenges, language barriers, and limited social support are particularly at risk of treatment burden. For those with advanced cancer, consumption of time and energy by health care work is a significant burden. Conclusion Treatment burden could be an important mediator of inequities in cancer outcomes. Many of the factors leading to treatment burden in individuals with cancer are potentially modifiable. Clinicians should consider carefully what they are asking or expecting patients to do, and the resources required, including how much patient time will be consumed.

Within regenerative endodontics, exciting opportunities exist for the development of next-generation targeted biomaterials that harness epigenetic machinery, including microRNAs (miRNAs), histone acetylation, and DNA methylation, which are used to control pulpitis and to stimulate repair. Although histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) induce mineralisation in dental pulp cell (DPC) populations, their interaction with miRNAs during DPC mineralisation is not known. Here, small RNA sequencing and bioinformatic analysis were used to establish a miRNA expression profile for mineralising DPCs in culture. Additionally, the effects of a HDACi, suberoylanilide hydroxamic acid (SAHA), and a DNMTi, 5-aza-2′-deoxycytidine (5-AZA-CdR), on miRNA expression, as well as DPC mineralisation and proliferation, were analysed. Both inhibitors increased mineralisation. However, they reduced cell growth. Epigenetically-enhanced mineralisation was accompanied by widespread changes in miRNA expression. Bioinformatic analysis identified many differentially expressed mature miRNAs that were suggested to have roles in mineralisation and stem cell differentiation, including regulation of the Wnt and MAPK pathways. Selected candidate miRNAs were demonstrated by qRT-PCR to be differentially regulated at various time points in mineralising DPC cultures treated with SAHA or 5-AZA-CdR. These data validated the RNA sequencing analysis and highlighted an increased and dynamic interaction between miRNA and epigenetic modifiers during the DPC reparative processes.

This cross-sectional study sought to quantify the frequency of change in race category in the electronic medical record (EMR) of a pediatric population.