A survey of patient contact shielding in dental teaching hospitals in the UK.

A high volume of dental imaging is carried out each year. In the UK, guidance on the use of patient contact shielding for these investigations is published by the British Institute of Radiology (BIR) and in a document jointly produced by the Faculty of General Dental Practice and Public Health England (FGDP/PHE). Both these sources of guidance have been updated recently and patient contact shielding is no longer recommended for most imaging settings in dental radiology. It is unclear whether radiology departments at dental teaching hospitals in the UK are aware of these sources of guidance, and how this relates to clinical practice within these departments. A survey was carried out exploring the awareness of current guidelines and clinical practice at dental teaching hospitals in the UK. The survey was sent to a representative at 17 different dental teaching hospital radiology departments. Responses were received from 11 departments. The range of intra-oral and extra-oral imaging carried out at these departments was comparable. Ten departments were aware of the existence of national guidelines for patient contact shielding, however only four were specifically aware of the recent BIR guidelines and only four were specifically aware of the FGDP/PHE guidelines. No department was aware of both sets of guidelines. No departments used thyroid protection for bitewing, periapical, lower 45 degree occlusal, panoramic or lateral cephalometric radiographs. Six departments sometimes or always used thyroid protection for upper standard occlusal imaging. Two departments used thyroid protection for cone beam CT imaging. No departments routinely used lead aprons on patients for dental imaging. In conclusion, radiology departments at dental teaching hospitals in the UK do not use patient contact shielding for most imaging situations in dental radiology. There is mixed awareness of current national guidelines, but the reported clinical practice aligns well with the current guidelines.

Core information set for informed consent to surgery for oral or oropharyngeal cancer: A mixed-methods study.

OBJECTIVES: To develop a core information set for informed consent to surgery for oral/oropharyngeal surgery. A core information set is baseline information rated important by patients and surgeons and is intended to improve patients' understanding of the intended procedure. DESIGN: A mixed-methods study. Systematic reviews of scientific and written healthcare literature, qualitative interviews and observations, Delphi surveys, and group consensus meetings identified information domains of importance for consent. SETTING: A regional head and neck clinic in the United Kingdom. Questionnaire participants were recruited from around the UK. PARTICIPANTS: Patients about to undergo, or who had previously undergone, surgery for oral/oropharyngeal cancer. Healthcare professionals involved in the management of head and neck cancer. MAIN OUTCOME MEASURES: The main outcome was a core information set. RESULTS: Systematic reviews, interviews and consultation observations yielded 887 pieces of information that were categorised into 87 information domains. Survey response rates were 67% (n = 50) and 71% (n = 52) for patient and healthcare professional groups in round one. More than 90% responded in each group in the second round. Healthcare professionals were more likely to rate information about short-term or peri-operative events as important while patients rated longer term issues about survival and quality of life. The consensus-building process resulted in an agreed core information set of 13 domains plus two procedure-specific domains about tracheostomy and free-flap surgery. CONCLUSION: This study produced a core information set for surgeons and patients to discuss before surgery for oral/oropharyngeal cancer. Future work will optimise ways to integrate core information into routine consultations.

A Polygenic Score Predicts Caries Experience in Elderly Swedish Adults.

Caries is a partially heritable disease, raising the possibility that a polygenic score (PS, a summary of an individual's genetic propensity for disease) might be a useful tool for risk assessment. To date, PS for some diseases have shown clinical utility, although no PS for caries has been evaluated. The objective of the study was to test whether a PS for caries is associated with disease experience or increment in a cohort of Swedish adults. A genome-wide PS for caries was trained using the results of a published genome-wide association meta-analysis and constructed in an independent cohort of 15,460 Swedish adults. Electronic dental records from the Swedish Quality Registry for Caries and Periodontitis (SKaPa) were used to compute the decayed, missing, and filled tooth surfaces (DMFS) index and the number of remaining teeth. The performance of the PS was evaluated by testing the association between the PS and DMFS at a single dental examination, as well as between the PS and the rate of change in DMFS. Participants in the highest and lowest deciles of PS had a mean DMFS of 63.5 and 46.3, respectively. A regression analysis confirmed this association where a 1 standard deviation increase in PS was associated with approximately 4-unit higher DMFS (P < 2 × 10-16). Participants with the highest decile of PS also had greater change in DMFS during follow-up. Results were robust to sensitivity analysis, which adjusted for age, age squared, sex, and the first 20 genetic principal components. Mediation analysis suggested that tooth loss was a strong mediating factor in the association between PS and DMFS but also supported a direct genetic effect on caries. In this cohort, there are clinically meaningful differences in DMFS between participants with high and low PS for caries. The results highlight the potential role of genomic data in improving caries risk assessment.

Novel Genetic Determinants of Dental Maturation in Children.

Dental occlusion requires harmonious development of teeth, jaws, and other elements of the craniofacial complex, which are regulated by environmental and genetic factors. We performed the first genome-wide association study (GWAS) on dental development (DD) using the Demirjian radiographic method. Radiographic assessments from participants of the Generation R Study (primary study population, N1 = 2,793; mean age of 9.8 y) were correlated with ~30 million genetic variants while adjusting for age, sex, and genomic principal components (proxy for population stratification). Variants associated with DD at genome-wide significant level (P < 5 × 10-8) mapped to 16q12.2 (IRX5) (lead variant rs3922616, B = 0.16; P = 2.2 × 10-8). We used Fisher's combined probability tests weighted by sample size to perform a meta-analysis (N = 14,805) combining radiographic DD at a mean age of 9.8 y from Generation R with data from a previous GWAS (N2 = 12,012) on number of teeth (NT) in infants used as proxy of DD at a mean age of 9.8 y (including the ALSPAC and NFBC1966). This GWAS meta-analysis revealed 3 novel loci mapping to 7p15.3 (IGF2BP3: P = 3.2 × 10-8), 14q13.3 (PAX9: P = 1.9 × 10-8), and 16q12.2 (IRX5: P = 1.2 × 10-9) and validated 8 previously reported NT loci. A polygenic allele score constructed from these 11 loci was associated with radiographic DD in an independent Generation R set of children (N = 703; B = 0.05, P = 0.004). Furthermore, profiling of the identified genes across an atlas of murine and human stem cells observed expression in the cells involved in the formation of bone and/or dental tissues (>0.3 frequency per kilobase of transcript per million mapped reads), likely reflecting functional specialization. Our findings provide biological insight into the polygenic architecture of the pediatric dental maturation process.

Genome-wide Scan of Dental Fear and Anxiety Nominates Novel Genes.

Dental care-related fear and anxiety (DFA) is prevalent, affects oral health care utilization, and is related to poor oral health and decreased quality of life. In addition to learned and cultural factors, genetics is hypothesized to contribute to DFA. Therefore, we performed a genome-wide association study to identify genetic variants contributing to DFA. Adult and adolescent participants were from 4 cohorts (3 from the US-based Center for Oral Health Research in Appalachia, n = 1,144, 1,164, and 535, and the UK-based Avon Longitudinal Study of Parents and Children [ALSPAC], n = 2,078). Two self-report instruments were used to assess DFA: the Dental Fear Survey (US cohorts) and Corah's Dental Anxiety Scale (ALSPAC). Genome-wide scans were performed for the DFA total scores and subscale scores (avoidance, physiological arousal, fear of dental treatment-specific stimuli), adjusting for age, sex, educational attainment, recruitment site, and genetic ancestry. Results across cohorts were combined using meta-analysis. Heritability estimates for DFA total and subscale scores were similar across cohorts and ranged from 23% to 59%. The meta-analysis revealed 3 significant (P < 5E-8) associations between genetic loci and 2 DFA subscales: physiological arousal and avoidance. Nearby genes included NTSR1 (P = 3.05E-8), DMRTA1 (P = 4.40E-8), and FAM84A (P = 7.72E-9). Of these, NTSR1, which was associated with the avoidance subscale, mediates neurotensin function, and its deficiency may lead to altered fear memory in mice. Gene enrichment analyses indicated that loci associated with the DFA total score and physiological arousal subscale score were enriched for genes associated with severe and persistent mental health (e.g., schizophrenia) and neurocognitive (e.g., autism) disorders. Heritability analysis indicated that DFA is partly explained by genetic factors, and our association results suggested shared genetic underpinnings with other psychological conditions.

Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium.

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.

Endothelin receptor expression in idiopathic pulmonary arterial hypertension: effect of bosentan and epoprostenol treatment.

Endothelin receptor antagonists are used to treat idiopathic pulmonary arterial hypertension (IPAH), but human pulmonary arterial endothelin receptor expression is not well defined. We hypothesised that disease and treatment would modify normal receptor distribution in pulmonary resistance arteries of children. Using immunohistochemistry and semiquantitative analysis, we investigated endothelin receptor subtypes A and B (ET(A) and ET(B), respectively), and endothelial nitric oxide synthase (eNOS) expression in peripheral pulmonary arteries of tissue from untreated children with IPAH (n=7), following extended combined bosentan and epoprostenol therapy (n=5) and from normal subjects (n=5). Clinical, haemodynamic and pathological abnormalities were severe and advanced in all IPAH cases. ET(A) was detected in pulmonary arterial endothelial cells of all normal and diseased tissue and cultured cells. Endothelial ET(A), ET(B) and eNOS expression was reduced in patent, plexiform and dilatation lesions of untreated cases, but in treated cases, ET(A) and ET(B) were normal and eNOS increased. In smooth muscle, ET(A) expression was reduced in treated cases but ET(B) expression increased in all arteries of both treated and untreated cases. In summary, ET(A) is expressed on human pulmonary arterial endothelium. In IPAH, combination treatment with bosentan and epoprostenol had a more marked influence on endothelin receptor expression of endothelial than smooth muscle cells.

Long-term efficacy of bosentan in treatment of pulmonary arterial hypertension in children.

The aim of the present study was to evaluate a 5-yr experience of bosentan in children with pulmonary arterial hypertension (PAH). A retrospective, observational study was made of children in the UK Pulmonary Hypertension Service for Children (Great Ormond Street Hospital for Children, London, UK) who were given bosentan as monotherapy or in combination, from February 2002 to May 2008 and followed up for ≥ 6 months. Detailed studies were made of 101 children with idiopathic PAH (IPAH) (n = 42) and PAH associated with congenital heart disease (n = 59). Before treatment, World Health Organization (WHO) functional class, 6-min walk distance (6MWD), height, weight and haemodynamic data were determined. Evaluations were analysed after 6 months and annually to a maximum of 5 yrs. Median duration of treatment was 31.5 months. Initial improvement in WHO functional class and 6MWD was maintained for up to 3 yrs. Height and weight increased but the z-scores did not improve. After 3 yrs, bosentan was continued as monotherapy in only 21% of children with IPAH, but in 69% of repaired cases and 56% of those with Eisenmenger syndrome. The Kaplan-Meier survival estimates for the 101 patients were 96, 89, 83 and 60% at 1, 2, 3 and 5 yrs, respectively. A treatment regime that includes bosentan is safe and appears to be effective in slowing disease progression in children with PAH.

Can we justify the continued use of botulinum toxin A in the management of myofascial pain?

We initially conducted a pilot study to evaluate the impact of botulinum toxin A (BtA) on increased masseteric mass associated with pain. After injection we assessed its impact on the muscle mass and the impact, if any, on reported pain, in a group of 10 patients who were refractory to conservative management. Results of this pilot study indicated that clenched and unclenched muscle dimensions showed no significant reduction (-0.82 clenched and -1mm unclenched). However, what did prove to be significant was an improvement in their pain scores as measured on a visual analogue scale (VAS). The mean VAS score before the injection was 8.2, and at six weeks after the injection it was 1.8. Following the pilot study we focused only on patients' pain scores. Our main study included 48 patients (81 muscles) who suffered with pain secondary to increased masseteric size, and had recorded their pain score out of 10 on the VAS before placement of BtA into each affected muscle and again six weeks after the injection. Results showed a mean pre-injection pain score of 7.9 and a mean post-injection pain score of 2.9. Following the results of this study on reported pain alone, our Trust has allowed funding to provide the intramuscular injection of BtA in appropriately selected patients.

Heritability of Caries Scores, Trajectories, and Disease Subtypes.

Previous studies report that dental caries is partially heritable, but there is uncertainty in the magnitude of genetic effects and little understanding of how genetic factors might influence caries progression or caries subtypes. This study aimed to estimate the relative importance of genetic and environmental factors in the etiology of different caries outcomes using a twin-based design. Analysis included up to 41,678 twins in the Swedish Twin Register aged 7 to 97 y, and dental data were obtained from preexisting dental records. The outcome measures were 1) summary indices of caries experience, 2) parameters representing trajectory in caries progression derived from longitudinal modeling, and 3) caries scores in groups of biologically similar tooth surfaces derived from hierarchical clustering of tooth surfaces (termed caries clusters). Additive genetic factors explained between 49.1% and 62.7% of variation in caries scores and between 50.0% and 60.5% of variation in caries trajectories. Seven caries clusters were identified, which had estimates of heritability lying between 41.9% and 54.3%. Shared environmental factors were important for only some of these clusters and explained 16% of variation in fissure caries in molar teeth but little variation in other clusters of caries presentation. The genetic factors influencing these clusters were only partially overlapping, suggesting that different biological processes are important in different groups of tooth surfaces and that innate liability to some patterns of caries presentation may partially explain why groups of tooth surfaces form clusters within the mouth. These results provide 1) improved quantification of genetic factors in the etiology of caries and 2) new data about the role of genetics in terms of longitudinal changes in caries status and specific patterns of disease presentation, and they may help lay the foundations for personalized interventions in the future.

Dietary nitrate attenuates high-fat diet-induced obesity via mechanisms involving higher adipocyte respiration and alterations in inflammatory status.

Emerging evidence indicates that dietary nitrate can reverse several features of the metabolic syndrome, but the underlying molecular mechanisms still remain elusive. The aim of the present study was to explore mechanisms involved in the effects of dietary nitrate on the metabolic dysfunctions induced by high-fat diet (HFD) in mice. Four weeks old C57BL/6 male mice, exposed to HFD for ten weeks, were characterised by increased body weight, fat content, increased fasting glucose and impaired glucose clearance. All these metabolic abnormalities were significantly attenuated by dietary nitrate. Mechanistically, subcutaneous primary mouse adipocytes exposed to palmitate (PA) and treated with nitrite exhibited higher mitochondrial respiration, increased protein expression of total mitochondrial complexes and elevated gene expression of the thermogenesis gene UCP-1, as well as of the creatine transporter SLC6A8. Finally, dietary nitrate increased the expression of anti-inflammatory markers in visceral fat, plasma and bone marrow-derived macrophages (Arginase-1, Egr-2, IL-10), which was associated with reduction of NADPH oxidase-derived superoxide production in macrophages. In conclusion, dietary nitrate may have therapeutic utility against obesity and associated metabolic complications possibly by increasing adipocyte mitochondrial respiration and by dampening inflammation and oxidative stress.

Contribution of inflammation to the pathology of idiopathic pulmonary arterial hypertension in children.

Idiopathic pulmonary arterial hypertension (IPAH) is an incurable disease of multifactorial origin. Inflammation is frequently observed in IPAH, but its role in the pathobiology is unclear. In this study the distribution, nature and number of inflammatory cells in periarterial infiltrates in lungs of children with IPAH, pulmonary arterial hypertension associated with congenital heart disease (APAH) and in normal lung tissue were characterised and compared using immunohistochemistry The influence of treatment with combined prostacyclin and endothelin receptor blockers was also studied. In children with IPAH, both treated and untreated, but not in children with APAH or normal children, extensive periarterial infiltrates were present comprising macrophages and T lymphocytes with S100A4- and bone morphogenetic protein receptor type-2 (BMPR2)-positive cells. Although rarely co-expressing macrophage-specific antigens, BMPR2-positive cells were frequently closely associated with macrophages and lymphocytes. They were more abundant around peripheral arteries of children with IPAH than in APAH or normal lungs (15.1 (3.5), 2.3 (0.9) and 2.3 (0.9) cells/mm external elastic lamina, respectively; p<0.01 for IPAH vs APAH or normal lungs). Prostacyclin with endothelin receptor blockade resulted in a significant reduction in endothelial cell activation as indicated by human leucocyte antigen (HLA)-DR expression (treated 17% vs untreated 100%, p<0.002). This study shows that pulmonary inflammation is present in the lungs of children with IPAH. This may indicate a role for inflammation in the pathobiology of IPAH and provide the rationale for novel therapeutic intervention.

Carbonic Anhydrase 6 Gene Variation influences Oral Microbiota Composition and Caries Risk in Swedish adolescents.

Carbonic anhydrase VI (CA6) catalyses the reversible hydration of carbon dioxide in saliva with possible pH regulation, taste perception, and tooth formation effects. This study assessed effects of variation in the CA6 gene on oral microbiota and specifically the acidophilic and caries-associated Streptococcus mutans in 17-year old Swedish adolescents (n = 154). Associations with caries status and secreted CA6 protein were also evaluated. Single Nucleotide Polymorphisms (27 SNPs in 5 haploblocks) and saliva and tooth biofilm microbiota from Illumina MiSeq 16S rDNA (V3-V4) sequencing and culturing were analysed. Haploblock 4 (rs10864376, rs3737665, rs12138897) CCC associated with low prevalence of S. mutans (OR (95% CI): 0.5 (0.3, 0.8)), and caries (OR 0.6 (0.3, 0.9)), whereas haploblock 4 TTG associated with high prevalence of S. mutans (OR: 2.7 (1.2, 5.9)) and caries (OR: 2.3 (1.2, 4.4)). The TTG-haploblock 4 (represented by rs12138897(G)) was characterized by S. mutans, Scardovia wiggsiae, Treponema sp. HOT268, Tannerella sp. HOT286, Veillonella gp.1 compared with the CCC-haploblock 4 (represented by rs12138897(C)). Secreted CA6 in saliva was weakly linked to CA6 gene variation. In conclusion, the results indicate that CA6 gene polymorphisms influence S. mutans colonization, tooth biofilm microbiota composition and risk of dental caries in Swedish adolescents.

Early-life pulmonary arterial hypertension with subsequent development of diffuse pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia type 1.

The case history is presented of a male infant who was thought to have idiopathic pulmonary arterial hypertension (PAH) at 3 months of age. Subsequently the PAH decreased unexpectedly and diffuse pulmonary arteriovenous malformations (PAVMs) were seen at 6.9 years of age for the first time. Hereditary haemorrhagic telangiectasia type 1 (HHT1) related to an endoglin mutation was diagnosed. At 10.3 years of age a lung biopsy showed diffuse PAVMs as well as pulmonary arteriopathy with medial hypertrophy. This is the first case of HHT1 presenting with PAH at such a young age. The subsequent decrease in pulmonary arterial pressure (PAP) was probably caused by the development of PAVMs. In the presence of PAVMs, measurement of the PAP may underestimate the extent of PAH-related vasculopathy.

Effect of a domiciliary facial cooling system on generic quality of life after removal of mandibular third molars.

To evaluate quality of life (QoL) and patients' perceptions of a domiciliary facial cooling system (Hilotherm®, Hilotherapy UK Ltd, Coventry, UK), we asked 30 patients to complete a paper-based EQ-5D-3L QoL questionnaire (EuroQol Group 1990, Rotterdam, The Netherlands) each day for seven days after the removal of mandibular third molars. They were returned by 14 of the 20 patients who had not used the system and by all 10 who had. Patients aged between 18 and 25 who had their teeth removed in outpatients (in accordance with National Institute for Health and Care Excellence guidelines) under general anaesthesia (American Association of Anesthesiologists (ASA) class I or II) and did not smoke, were included. They were all treated by the same surgeon in the day surgery unit of a district general hospital. Patients found the system helpful and easy to use. They had no complications, their QoL was significantly improved (p<0.001), and the time taken to return to normal activities was reduced. The Hilotherm® domiciliary facial cooling system is safe and helps in the management of postoperative pain and swelling. Our findings confirm recently published meta-analyses that show the effectiveness of hilotherapy after facial surgery.

Vascular endothelium summary statement V: Pulmonary hypertension and acute lung injury: public health implications.

Although relatively rare, pulmonary hypertension can be devastating for those individuals who are affected and has significant societal implications. The 2003 WHO classification separates PAH (idiopathic, specific disease linked) from pulmonary hypertension related to lung disease, thromboembolic disease, and pulmonary venous hypertension. Another form of pulmonary hypertension, persistent pulmonary hypertension (PPHN), occurs in the newborn. In general, PPHN is thought to be responsible for approximately 10% of admissions to neonatal intensive care units and can be a complicating factor in 5 of 1000 live births. Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are complex disorders that pose a significant threat to critically ill patients. They are usually related to direct lung injury or indirect injury from sepsis, trauma, and other disorders. Although these pulmonary disorders reflect distinct pathophysiologic mechanisms, current evidence strongly suggests that a common denominator underlying many of the established molecular and cellular elements is endothelial cell activation and dysfunction. This summary statement briefly summarizes the state of the science and suggests future avenues of public health research.

Measurement of generic compared with disease-specific quality of life after removal of mandibular third molars: a patient-centred evaluation.

Our aim was to evaluate patients' perceptions and their responsiveness to a generic quality of life (QoL) scale after removal of mandibular third molars. We asked 40 consecutive patients who met NICE guidelines for removal of third molars to rank items from the generic EuroQuol three-dimensional questionnaire (EQ 5D 3L) and the disease-specific Oral Health Impact Profile (OHIP-14) based on what they perceived to be important outcomes. Each item was then assigned a numerical value that depended on its rank, and an overall score calculated. Fifty consecutive patients were then invited to complete a paper-based EQ 5D 3L QoL questionnaire daily for seven days after removal of third molars. Most of the generic QoL items ranked more highly than disease-specific ones. The generic EQ 5D 3L questionnaire indicated an initial fall in QoL after removal of the teeth, before improving for all participants over the first seven postoperative days. The responses to questions about "overall QoL", "pain/discomfort", and "anxiety/depression" in the EQ 5D 3L tool were strongly correlated. The EQ 5D 3L is used to assess fluctuations in QoL during the early postoperative period after removal of third molars, and describes items that are perceived by patients to be more important than those recorded by the disease-specific OHIP-14 QoL questionnaire. It is therefore more relevant for counselling patients preoperatively. Development of measures of early outcomes after removal of third molars should incorporate generic items to remain useful.

Ten years on: Is dental general anaesthesia in childhood a risk factor for caries and anxiety?

Objectives To identify whether dental general anaesthesia (DGA) status is informative in assessing risk of caries or dental anxiety by (a) describing long-term oral health and dental anxiety for people who underwent DGA in childhood and (b) testing whether DGA status in childhood is associated with incident future dental caries or anxiety independently of preconceived risk factors.Design Analysis of prospectively obtained data.Setting An established population based cohort in the UK, the Avon Longitudinal Study of Parents and Children.Participants and methods In total 1,695 participants with dental data in childhood and adolescence were included in analysis. DGA status by age 7 and oral health measures at age 17 were identified from questionnaire data.Main outcome measures Filled or extracted permanent teeth at age 17, Corah Dental Anxiety Scale.Results One hundred and twenty-eight (7.6%) participants underwent DGA in childhood. Individuals who underwent DGA had higher measures of filled or extracted permanent teeth in adolescence (0.36 more affected teeth in fully-adjusted model [95% confidence interval: 0.27, 0.55; P <0.001]).Conclusions DGA in childhood predicts burden of treated caries in adolescence, independently of other risk factors. DGA status may be a clinically useful adjunct in identifying young people at high risk of further disease.

Role of the endothelium in pulmonary arterial hypertension.

Pulmonary hypertension represents a significant disease burden in both the developed and developing worlds. Certain forms of pulmonary hypertension are more common in some countries than others but people of all races, all ages and both sexes are affected. Treatment options are limited and expensive. The development of new therapies will be determined by improved understanding of endothelial cell biology.