Birmingham Community Healthcare NHS Trust

BACKGROUND: The recently introduced 2017 World Workshop on the classification of periodontitis, incorporating stages and grades of disease, aims to link disease classification with approaches to prevention and treatment, as it describes not only disease severity and extent but also the degree of complexity and an individual's risk. There is, therefore, a need for evidence-based clinical guidelines providing recommendations to treat periodontitis. AIM: The objective of the current project was to develop a S3 Level Clinical Practice Guideline (CPG) for the treatment of Stage I-III periodontitis. MATERIAL AND METHODS: This S3 CPG was developed under the auspices of the European Federation of Periodontology (EFP), following the methodological guidance of the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation (GRADE). The rigorous and transparent process included synthesis of relevant research in 15 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, the formulation of specific recommendations and consensus, on those recommendations, by leading experts and a broad base of stakeholders. RESULTS: The S3 CPG approaches the treatment of periodontitis (stages I, II and III) using a pre-established stepwise approach to therapy that, depending on the disease stage, should be incremental, each including different interventions. Consensus was achieved on recommendations covering different interventions, aimed at (a) behavioural changes, supragingival biofilm, gingival inflammation and risk factor control; (b) supra- and sub-gingival instrumentation, with and without adjunctive therapies; (c) different types of periodontal surgical interventions; and (d) the necessary supportive periodontal care to extend benefits over time. CONCLUSION: This S3 guideline informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to treat periodontitis and to maintain a healthy dentition for a lifetime, according to the available evidence at the time of publication.

The CONSORT 2010 statement provides minimum guidelines for reporting randomized trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.

The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.

The PAS-ADD Checklist is a screening instrument specifically designed to help staff recognize mental health problems in the people with intellectual disability for whom they care, and to make informed referral decisions. The instrument consists of a life-events checklist and 29 symptom items scored on a four-point scale. Scores are combined to provide three threshold scores. The crossing of any of these thresholds indicates the need for a fuller assessment. The items are worded in everyday language, making the Checklist suitable for use by individuals who do not have a background in psychopathology. The present paper presents the results of a number of studies evaluating the reliability and validity of the Checklist. Factor analysis of Checklists completed on a community sample of 201 individuals yielded eight factors, of which seven were readily interpretable in diagnostic terms. Internal consistency of the scales was generally acceptable. Inter-rater reliability in respect to individual items gave a fairly low average Kappa of 0.42. However, agreement on case identification, the main purpose of the Checklist, was quite good, with 83% of the decision being in agreement. Validity in relation to clinical opinion was also satisfactory, case detection rising appropriately with the clinically judged severity of disorder. The PAS-ADD Checklist is published and distributed by the Hester Adrian Research Centre, Manchester, England, from where further information and order forms are available on request.

BACKGROUND: Sedentary behaviour (SB) is a risk factor for chronic disease and premature mortality. While many individual studies have examined the reliability and validity of various self-report measures for assessing SB, it is not clear, in general, how self-reported SB (e.g., questionnaires, logs, ecological momentary assessments (EMAs)) compares to device measures (e.g., accelerometers, inclinometers). OBJECTIVE: The primary objective of this systematic review was to compare self-report versus device measures of SB in adults. METHODS: Six bibliographic databases were searched to identify all studies which included a comparable self-report and device measure of SB in adults. Risk of bias within and across studies was assessed. Results were synthesized using meta-analyses. RESULTS: The review included 185 unique studies. A total of 123 studies comprising 173 comparisons and data from 55,199 participants were used to examine general criterion validity. The average mean difference was -105.19 minutes/day (95% CI: -127.21, -83.17); self-report underestimated sedentary time by ~1.74 hours/day compared to device measures. Self-reported time spent sedentary at work was ~40 minutes higher than when assessed by devices. Single item measures performed more poorly than multi-item questionnaires, EMAs and logs/diaries. On average, when compared to inclinometers, multi-item questionnaires, EMAs and logs/diaries were not significantly different, but had substantial amount of variability (up to 6 hours/day within individual studies) with approximately half over-reporting and half under-reporting. A total of 54 studies provided an assessment of reliability of a self-report measure, on average the reliability was good (ICC = 0.66). CONCLUSIONS: Evidence from this review suggests that single-item self-report measures generally underestimate sedentary time when compared to device measures. For accuracy, multi-item questionnaires, EMAs and logs/diaries with a shorter recall period should be encouraged above single item questions and longer recall periods if sedentary time is a primary outcome of study. Users should also be aware of the high degree of variability between and within tools. Studies should exert caution when comparing associations between different self-report and device measures with health outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019118755.

A summary of the latest evidence-based nutrition guidelines for the prevention and management of diabetes is presented. These guidelines are based on existing recommendations last published in 2011, and were formulated by an expert panel of specialist dietitians after a literature review of recent evidence. Recommendations have been made in terms of foods rather than nutrients wherever possible. Guidelines for education and care delivery, prevention of Type 2 diabetes, glycaemic control for Type 1 and Type 2 diabetes, cardiovascular disease risk management, management of diabetes-related complications, other considerations including comorbidities, nutrition support, pregnancy and lactation, eating disorders, micronutrients, food supplements, functional foods, commercial diabetic foods and nutritive and non-nutritive sweeteners are included. The sections on pregnancy and prevention of Type 2 diabetes have been enlarged and the weight management section modified to include considerations of remission of Type 2 diabetes. A section evaluating detailed considerations in ethnic minorities has been included as a new topic. The guidelines were graded using adapted 'GRADE' methodology and, where strong evidence was lacking, grading was not allocated. These 2018 guidelines emphasize a flexible, individualized approach to diabetes management and weight loss and highlight the emerging evidence for remission of Type 2 diabetes. The full guideline document is available at www.diabetes.org.uk/nutrition-guidelines.

BACKGROUND: The recently published Clinical Practice Guidelines (CPGs) for the treatment of stages I-IV periodontitis provided evidence-based recommendations for treating periodontitis patients, defined according to the 2018 classification. Peri-implant diseases were also re-defined in the 2018 classification. It is well established that both peri-implant mucositis and peri-implantitis are highly prevalent. In addition, peri-implantitis is particularly challenging to manage and is accompanied by significant morbidity. AIM: To develop an S3 level CPG for the prevention and treatment of peri-implant diseases, focusing on the implementation of interdisciplinary approaches required to prevent the development of peri-implant diseases or their recurrence, and to treat/rehabilitate patients with dental implants following the development of peri-implant diseases. MATERIALS AND METHODS: This S3 level CPG was developed by the European Federation of Periodontology, following methodological guidance from the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation process. A rigorous and transparent process included synthesis of relevant research in 13 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, formulation of specific recommendations, and a structured consensus process involving leading experts and a broad base of stakeholders. RESULTS: The S3 level CPG for the prevention and treatment of peri-implant diseases culminated in the recommendation for implementation of various different interventions before, during and after implant placement/loading. Prevention of peri-implant diseases should commence when dental implants are planned, surgically placed and prosthetically loaded. Once the implants are loaded and in function, a supportive peri-implant care programme should be structured, including periodical assessment of peri-implant tissue health. If peri-implant mucositis or peri-implantitis are detected, appropriate treatments for their management must be rendered. CONCLUSION: The present S3 level CPG informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to maintain healthy peri-implant tissues, and to manage peri-implant diseases, according to the available evidence at the time of publication.

BACKGROUND: The recently published clinical practice guideline (CPG) for the treatment of periodontitis in stages I-III provided evidence-based recommendations for the treatment of periodontitis patients, defined according to the 2018 classification. Stage IV periodontitis shares the severity and complexity characteristics of stage III periodontitis, but includes the anatomical and functional sequelae of tooth and periodontal attachment loss (tooth flaring and drifting, bite collapse, etc.), which require additional interventions following completion of active periodontal therapy. AIM: To develop an S3 Level CPG for the treatment of stage IV periodontitis, focusing on the implementation of inter-disciplinary treatment approaches required to treat/rehabilitate patients following associated sequelae and tooth loss. MATERIALS AND METHODS: This S3 Level CPG was developed by the European Federation of Periodontology (EFP), following methodological guidance from the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process. A rigorous and transparent process included synthesis of relevant research in 13 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, the formulation of specific recommendations and a structured consensus process with leading experts and a broad base of stakeholders. RESULTS: The S3 Level CPG for the treatment of stage IV periodontitis culminated in recommendations for different interventions, including orthodontic tooth movement, tooth splinting, occlusal adjustment, tooth- or implant-supported fixed or removable dental prostheses and supportive periodontal care. Prior to treatment planning, it is critically important to undertake a definitive and comprehensive diagnosis and case evaluation, obtain relevant patient information, and engage in frequent re-evaluations during and after treatment. The periodontal component of therapy should follow the CPG for the treatment of periodontitis in stages I-III. CONCLUSIONS: The present S3 Level CPG informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to treat patients with stage IV periodontitis and to maintain a healthy dentition over lifetime, according to the available evidence at the time of publication.

OBJECTIVES: The objective of this study was to systematically review the epidemiological evidence for an association between periodontitis (PD) and incident atherosclerotic cardiovascular disease (ACVD), including coronary heart disease (CHD), cerebrovascular disease and peripheral arterial disease. METHODS: Systematic review of cohort and case-control studies on the association of clinically or radiographically diagnosed PD and ACVD. RESULTS: Overall, 12 studies were included in this study (six studies on CHD, three studies on cerebrovascular disease, two studies on both coronary heart and cerebrovascular disease mortality and one study on peripheral arterial disease).All but one study reported positive associations between various periodontal disease measures and the incidence of ACVD, at least in specific subgroups. The association was stronger in younger adults and there was no evidence for an association between PD and incident CHD in subjects older than 65 years. Only one study evaluated the association between PD and secondary cardiovascular events. CONCLUSIONS: There is evidence for an increased risk of ACVD in patients with PD compared to patients without. However, this may not apply to all groups of the population. There is insufficient evidence for an association between PD and the incidence of secondary cardiovascular events.

AIM: To explore the implications for dentists and family doctors of the association between periodontal and systemic diseases and the role of dentists and family doctors in managing non-communicable diseases (NCDs) and promoting healthy lifestyles. MATERIALS AND METHODS: The consensus reports of the previous Focused Workshops on the associations between periodontitis and diabetes (2017) and periodontitis and cardiovascular diseases (2019) formed the technical reviews to underpin discussions on both topics. For the association with respiratory diseases, a systematic review was specifically commissioned for the Workshop discussions. Working groups prepared proposals independently, and then the proposals were discussed and approved at plenary meetings. RESULTS: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea and COVID-19 complications. Dentists and family doctors should collaborate in managing NCDs, implementing strategies for early detection of periodontitis in primary care centres and of cardiovascular diseases or diabetes in dental settings. Family doctors should be informed about periodontal diseases and their consequences, and oral health professionals (OHPs) should be informed about the relevance of NCDs and the associated risk factors. CONCLUSIONS: Closer collaboration between OHPs and family doctors is important in the early detection and management of NCDs and in promoting healthy lifestyles. Pathways for early case detection of periodontitis in family medicine practices and of NCDs in dental practices should be developed and evaluated.

Abstract Objectives The objective of this study was to systematically review the epidemiological evidence for an association between periodontitis ( PD ) and incident atherosclerotic cardiovascular disease ( ACVD ), including coronary heart disease (CHD), cerebrovascular disease and peripheral arterial disease. Methods Systematic review of cohort and case‐control studies on the association of clinically or radiographically diagnosed PD and ACVD . Results Overall, 12 studies were included in this study (six studies on CHD, three studies on cerebrovascular disease, two studies on both coronary heart and cerebrovascular disease mortality and one study on peripheral arterial disease). All but one study reported positive associations between various periodontal disease measures and the incidence of ACVD , at least in specific subgroups. The association was stronger in younger adults and there was no evidence for an association between PD and incident CHD in subjects older than 65 years. Only one study evaluated the association between PD and secondary cardiovascular events. Conclusions There is evidence for an increased risk of ACVD in patients with PD compared to patients without. However, this may not apply to all groups of the population. There is insufficient evidence for an association between PD and the incidence of secondary cardiovascular events.

BACKGROUND: The ESE previously published quality guidelines for endodontic treatment in 2006; however, there have been significant changes since not only in clinical endodontics but also in consensus and guideline development processes. In the development of the inaugural S3-level clinical practice guidelines (CPG), a comprehensive systematic and methodologically robust guideline consultation process was followed in order to produce evidence-based recommendations for the management of patients presenting with pulpal and apical disease. AIM: To develop an S3-level CPG for the treatment of pulpal and apical disease, focusing on diagnosis and the implementation of the treatment approaches required to manage patients presenting with pulpitis and apical periodontitis (AP) with the ultimate goal of preventing tooth loss. METHODS: This S3-level CPG was developed by the ESE, with the assistance of independent methodological guidance provided by the Association of Scientific Medical Societies in Germany and utilizing the GRADE process. A robust, rigorous and transparent process included the analysis of relevant comparative research in 14 specifically commissioned systematic reviews, prior to evaluation of the quality and strength of evidence, the formulation of specific evidence and expert-based recommendations in a structured consensus process with leading endodontic experts and a broad base of external stakeholders. RESULTS: The S3-level CPG for the treatment of pulpal and apical disease describes in a series of clinical recommendations the effectiveness of diagnosing pulpitis and AP, prior to investigating the effectiveness of endodontic treatments in managing those diseases. Therapeutic strategies include the effectiveness of deep caries management in cases with, and without, spontaneous pain and pulp exposure, vital versus nonvital teeth, the effectiveness of root canal instrumentation, irrigation, dressing, root canal filling materials and adjunct intracanal procedures in the management of AP. Prior to treatment planning, the critical importance of history and case evaluation, aseptic techniques, appropriate training and re-evaluations during and after treatment is stressed. CONCLUSION: The first S3-level CPG in endodontics informs clinical practice, health systems, policymakers, other stakeholders and patients on the available and most effective treatments to manage patients with pulpitis and AP in order to preserve teeth over a patient's lifetime, according to the best comparative evidence currently available.

SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3-11 years) and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Neutralization of viral variants was comparable between children and adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens.

OBJECTIVE: To assess the effectiveness of a school and family based healthy lifestyle programme (WAVES intervention) compared with usual practice, in preventing childhood obesity. DESIGN: Cluster randomised controlled trial. SETTING: UK primary schools from the West Midlands. PARTICIPANTS: 200 schools were randomly selected from all state run primary schools within 35 miles of the study centre (n=980), oversampling those with high minority ethnic populations. These schools were randomly ordered and sequentially invited to participate. 144 eligible schools were approached to achieve the target recruitment of 54 schools. After baseline measurements 1467 year 1 pupils aged 5 and 6 years (control: 28 schools, 778 pupils) were randomised, using a blocked balancing algorithm. 53 schools remained in the trial and data on 1287 (87.7%) and 1169 (79.7%) pupils were available at first follow-up (15 month) and second follow-up (30 month), respectively. INTERVENTIONS: The 12 month intervention encouraged healthy eating and physical activity, including a daily additional 30 minute school time physical activity opportunity, a six week interactive skill based programme in conjunction with Aston Villa football club, signposting of local family physical activity opportunities through mail-outs every six months, and termly school led family workshops on healthy cooking skills. MAIN OUTCOME MEASURES: The protocol defined primary outcomes, assessed blind to allocation, were between arm difference in body mass index (BMI) z score at 15 and 30 months. Secondary outcomes were further anthropometric, dietary, physical activity, and psychological measurements, and difference in BMI z score at 39 months in a subset. RESULTS: Data for primary outcome analyses were: baseline, 54 schools: 1392 pupils (732 controls); first follow-up (15 months post-baseline), 53 schools: 1249 pupils (675 controls); second follow-up (30 months post-baseline), 53 schools: 1145 pupils (621 controls). The mean BMI z score was non-significantly lower in the intervention arm compared with the control arm at 15 months (mean difference -0.075 (95% confidence interval -0.183 to 0.033, P=0.18) in the baseline adjusted models. At 30 months the mean difference was -0.027 (-0.137 to 0.083, P=0.63). There was no statistically significant difference between groups for other anthropometric, dietary, physical activity, or psychological measurements (including assessment of harm). CONCLUSIONS: The primary analyses suggest that this experiential focused intervention had no statistically significant effect on BMI z score or on preventing childhood obesity. Schools are unlikely to impact on the childhood obesity epidemic by incorporating such interventions without wider support across multiple sectors and environments. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97000586.

<h3>Abstract</h3> We introduce the dynseq genome browser track, which displays DNA nucleotide characters scaled by user-specified, base-resolution scores provided in the BigWig file format. The dynseq track enables visualization of context-specific, informative genomic sequence features. We demonstrate its utility in three popular genome browsers for interpreting cis-regulatory sequence syntax and regulatory variant interpretation by visualizing nucleotide importance scores derived from machine learning models of regulatory DNA trained on protein-DNA binding and chromatin accessibility experiments.

While post mortem studies have identified the major cell types and functional systems affected in Alzheimer's disease (AD) the initial sites and molecular characteristics of pathology are still unclear. Because individuals with Down syndrome (DS) (trisomy 21) develop the full pathological changes of AD in a predictable way by the time they reach middle to late age, a study of the brains of such persons at different ages makes an ideal 'model system' in which the sites of earliest onset of pathology can be detected and the subsequent progression of changes be monitored. In the present study we have examined the brains of 56 individuals with DS ranging from new-born to 76 years for the presence of amyloid and tau pathology in key cortical and subcortical regions. Amyloid pathology was found to commence in the late teens to twenties as a deposition of diffuse plaques initially within the temporal neocortex, quickly involving other neocortical regions but only reaching subcortical regions and cerebellum by the late forties. Cerebral amyloid angiopathy did not regularly commence until after 45-50 years of age. Tau pathology usually commenced after 35 years of age, initially involving not only entorhinal areas and hippocampus but also subcortical regions such as locus caeruleus (LC) and dorsal raphe nucleus (DRN). Later, tau pathology spread throughout the neocortex reaching occipital lobes in most instances by mid-50 years of age. Such a pattern of spread is consistent with that seen in typical AD. We found no evidence that tau pathology might commence within the brain in DS before amyloid deposition had occurred, but there was limited data that suggests tau pathology in LC or DRN might predate that in entorhinal areas and hippocampus or at least be coincident.

ABSTRACT Background The COVID-19 pandemic caused &gt;1 million infections during January-March 2020. There is an urgent need for reliable antibody detection approaches to support diagnosis, vaccine development, safe release of individuals from quarantine, and population lock-down exit strategies. We set out to evaluate the performance of ELISA and lateral flow immunoassay (LFIA) devices. Methods We tested plasma for COVID (SARS-CoV-2) IgM and IgG antibodies by ELISA and using nine different LFIA devices. We used a panel of plasma samples from individuals who have had confirmed COVID infection based on a PCR result (n=40), and pre-pandemic negative control samples banked in the UK prior to December-2019 (n=142). Results ELISA detected IgM or IgG in 34/40 individuals with a confirmed history of COVID infection (sensitivity 85%, 95%CI 70-94%), vs. 0/50 pre-pandemic controls (specificity 100% [95%CI 93-100%]). IgG levels were detected in 31/31 COVID-positive individuals tested ≥10 days after symptom onset (sensitivity 100%, 95%CI 89-100%). IgG titres rose during the 3 weeks post symptom onset and began to fall by 8 weeks, but remained above the detection threshold. Point estimates for the sensitivity of LFIA devices ranged from 55-70% versus RT-PCR and 65-85% versus ELISA, with specificity 95-100% and 93-100% respectively. Within the limits of the study size, the performance of most LFIA devices was similar. Conclusions Currently available commercial LFIA devices do not perform sufficiently well for individual patient applications. However, ELISA can be calibrated to be specific for detecting and quantifying SARS-CoV-2 IgM and IgG and is highly sensitive for IgG from 10 days following first symptoms.

Periodontitis is a complex chronic inflammatory noncommunicable disease, initiated by the development of a dysbiotic microbial plaque biofilm below the gingival margin. Whilst the pathogenic biofilm is a "necessary cause" of periodontitis, it is insufficient on its own to cause the disease, and a destructive immune-inflammatory response is a key to the translation of risk to destructive events. Other exposures or "component causes" include individual genetic predisposition, lifestyle (including smoking and nutrition), and environmental factors. Dietary nutrients are essential for life as they provide crucial energy sources in the form of macronutrients, as well as important cofactors in the form of micronutrients, which regulate the functionality of enzymes during the regulation of anabolic and catabolic processes in human cells. Moreover, micronutrients can regulate gene transcription factors, such as the proinflammatory nuclear factor kappa B and the anti-inflammatory nuclear factor (erythroid-derived 2)-like 2. This review focuses on the role of vitamins (vitamin A, carotenoids, the vitamin B complex, vitamins C, D, and E, and coenzyme Q10) and minerals (calcium, magnesium, iron, zinc, potassium, copper, manganese, and selenium) in human physiology and the impact of their deficiencies upon periodontal health and disease.

It is common knowledge that materials used in endodontics may cause discoloration and thus impair the aesthetic outcome of the treated tooth. The purpose of this review is to summarise the existing knowledge on the discoloration potential of materials used for endodontic procedures. A comprehensive literature search covering the period from 1966 to 2011 was conducted on Pubmed and the Cochrane Library using different keyword combinations including 'tooth', 'colour', 'discoloration', 'staining', 'endodontic''root canal''sealer', 'dressing', 'medicament', 'obturation', 'filling', 'treatment', 'portland cement', 'MTA' and 'antibiotic paste'. Any relevant work published in the English language in peer-reviewed journals and presenting pertinent information related to the purpose of this overview was considered for inclusion. In addition, bibliographies of all relevant papers and previous review articles were hand searched and the reference lists from endodontic textbooks were also reviewed. Articles were excluded if an English abstract was unavailable, if only single clinical reports or conference reports were included, or if the topic was unrelated to the subject. Ten in-vitro studies, one randomized controlled trial and one multicenter randomized controlled trial met the inclusion criteria. There were not any recently used endodontic materials that would not induce at least measurable colour changes. For a wide range of materials currently available on the market there is only scarce or no evidence available on their staining ability. Endodontic therapy should not focus solely on biological and functional aspects, but take aesthetic considerations into account as well. To reduce the risk of material-induced tooth discoloration all materials should be applied carefully in areas of aesthetic concern. The need for further research in this field and for the development of non-staining endodontic materials is evident.

A survey of West Midlands paediatricians in 2001 identified 24 cases of symptomatic vitamin D deficiency in children less than 5 years of age. The overall incidence was 7.5 per 100 000 children per year with notable differences in incidence per ethnic group.