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The capacity of dental clinicians and researchers to assess oral health and to advocate for dental care has been hampered by limitations in measurements of the levels of dysfunction, discomfort and disability associated with oral disorders. The purpose of this research was to develop and test the Oral Health Impact Profile (OHIP), a scaled index of the social impact of oral disorders which draws on a theoretical hierarchy of oral health outcomes. Forty nine unique statements describing the consequences of oral disorders were initially derived from 535 statements obtained in interviews with 64 dental patients. The relative importance of statements within each of seven conceptual subscales was assessed by 328 persons using Thurstone's method of paired comparisons. The consistency of their judgements was confirmed (Kendall's mu, P < 0.05). The reliability of the instrument was evaluated in a cohort of 122 persons aged 60 years and over. Internal reliability of six subscales was high (Cronbach's alpha, 0.70-0.83) and test-retest reliability (intraclass correlation coefficient, 0.42-0.77) demonstrated stability. Validity was examined using longitudinal data from the 60 years and over cohort where the OHIP's capacity to detect previously observed associations with perceived need for a dental visit (ANOVA, p < 0.05 in five subscales) provided evidence of its construct validity. The Oral Health Impact Profile offers a reliable and valid instrument for detailed measurement of the social impact of oral disorders and has potential benefits for clinical decision-making and research.

A case-control study of oral and pharyngeal cancer conducted in four areas of the United States provided information on the tobacco and alcohol use of 1114 patients and 1268 population-based controls. Because of the large study size, it could be shown that the risks of these cancers among nondrinkers increased with amount smoked, and conversely that the risks among nonsmokers increased with the level of alcohol intake. Among consumers of both products, risks of oropharyngeal cancer tended to combine more in a multiplicative than additive fashion and were increased more than 35-fold among those who consumed two or more packs of cigarettes and more than four alcoholic drinks/day. Cigarette, cigar, and pipe smoking were separately implicated, although it was shown for the first time that risk was not as high among male lifelong filter cigarette smokers. Cessation of smoking was associated with a sharply reduced risk of this cancer, with no excess detected among those having quit for 10 or more years, suggesting that smoking affects primarily a late stage in the process of oropharyngeal carcinogenesis. The risks varied by type of alcoholic beverage, being higher among those consuming hard liquor or beer than wine. The relative risk patterns were generally similar among whites and blacks, and among males and females, and showed little difference when oral and pharyngeal cancers were analyzed separately. From calculations of attributable risk, we estimate that tobacco smoking and alcohol drinking combine to account for approximately three-fourths of all oral and pharyngeal cancers in the United States.

The proportion of older people continues to grow worldwide, especially in developing countries. Non-communicable diseases are fast becoming the leading causes of disability and mortality, and in coming decades health and social policy-makers will face tremendous challenges posed by the rapidly changing burden of chronic diseases in old age. Chronic disease and most oral diseases share common risk factors. Globally, poor oral health amongst older people has been particularly evident in high levels of tooth loss, dental caries experience, and the prevalence rates of periodontal disease, xerostomia and oral precancer/cancer. The negative impact of poor oral conditions on the quality of life of older adults is an important public health issue, which must be addressed by policy-makers. The means for strengthening oral health programme implementation are available; the major challenge is therefore to translate knowledge into action programmes for the oral health of older people. The World Health Organization recommends that countries adopt certain strategies for improving the oral health of the elderly. National health authorities should develop policies and measurable goals and targets for oral health. National public health programmes should incorporate oral health promotion and disease prevention based on the common risk factors approach. Control of oral disease and illness in older adults should be strengthened through organization of affordable oral health services, which meet their needs. The needs for care are highest among disadvantaged, vulnerable groups in both developed and developing countries. In developing countries the challenges to provision of primary oral health care are particularly high because of a shortage of dental manpower. In developed countries reorientation of oral health services towards prevention should consider oral care needs of older people. Education and continuous training must ensure that oral health care providers have skills in and a profound understanding of the biomedical and psychosocial aspects of care for older people. Research for better oral health should not just focus on the biomedical and clinical aspects of oral health care; public health research needs to be strengthened particularly in developing countries. Operational research and efforts to translate science into practice are to be encouraged. WHO supports national capacity building in the oral health of older people through intercountry and interregional exchange of experiences.

Oral diseases are among the most prevalent diseases globally and have serious health and economic burdens, greatly reducing quality of life for those affected. The most prevalent and consequential oral diseases globally are dental caries (tooth decay), periodontal disease, tooth loss, and cancers of the lips and oral cavity. In this first of two papers in a Series on oral health, we describe the scope of the global oral disease epidemic, its origins in terms of social and commercial determinants, and its costs in terms of population wellbeing and societal impact. Although oral diseases are largely preventable, they persist with high prevalence, reflecting widespread social and economic inequalities and inadequate funding for prevention and treatment, particularly in low-income and middle-income countries (LMICs). As with most non-communicable diseases (NCDs), oral conditions are chronic and strongly socially patterned. Children living in poverty, socially marginalised groups, and older people are the most affected by oral diseases, and have poor access to dental care. In many LMICs, oral diseases remain largely untreated because the treatment costs exceed available resources. The personal consequences of chronic untreated oral diseases are often severe and can include unremitting pain, sepsis, reduced quality of life, lost school days, disruption to family life, and decreased work productivity. The costs of treating oral diseases impose large economic burdens to families and health-care systems. Oral diseases are undoubtedly a global public health problem, with particular concern over their rising prevalence in many LMICs linked to wider social, economic, and commercial changes. By describing the extent and consequences of oral diseases, their social and commercial determinants, and their ongoing neglect in global health policy, we aim to highlight the urgent need to address oral diseases among other NCDs as a global health priority.

For millions of years, our resident microbes have coevolved and coexisted with us in a mostly harmonious symbiotic relationship. We are not distinct entities from our microbiome, but together we form a 'superorganism' or holobiont, with the microbiome playing a significant role in our physiology and health. The mouth houses the second most diverse microbial community in the body, harbouring over 700 species of bacteria that colonise the hard surfaces of teeth and the soft tissues of the oral mucosa. Through recent advances in technology, we have started to unravel the complexities of the oral microbiome and gained new insights into its role during both health and disease. Perturbations of the oral microbiome through modern-day lifestyles can have detrimental consequences for our general and oral health. In dysbiosis, the finely-tuned equilibrium of the oral ecosystem is disrupted, allowing disease-promoting bacteria to manifest and cause conditions such as caries, gingivitis and periodontitis. For practitioners and patients alike, promoting a balanced microbiome is therefore important to effectively maintain or restore oral health. This article aims to give an update on our current knowledge of the oral microbiome in health and disease and to discuss implications for modern-day oral healthcare.

At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the UK issues related to terminology, definitions and classification of oral precancer were discussed by an expert group. The consensus views of the Working Group are presented here. The term, 'potentially malignant disorders', was recommended to refer to precancer as it conveys that not all disorders described under this term may transform into cancer. Critically evaluating all definitions proposed so far for oral leukoplakia, the Working Group agreed that the term leukoplakia should be used to recognize 'white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer'. An outline was proposed for diagnosing oral leukoplakia that will prevent other oral white disorders being misclassified as leukoplakia. The Working Group discussed the caveats involved in the current use of terminology and classification of oral potentially malignant disorders, deficiencies of these complex systems, and how they have evolved over the past several decades. The terminology presented in this report reflects our best understanding of multi-step carcinogenesis in the oral mucosa, and aspires to engender consistency in use.

Oral bioavailability measurements in rats for over 1100 drug candidates studied at SmithKline Beecham Pharmaceuticals (now GlaxoSmithKline) have allowed us to analyze the relative importance of molecular properties considered to influence that drug property. Reduced molecular flexibility, as measured by the number of rotatable bonds, and low polar surface area or total hydrogen bond count (sum of donors and acceptors) are found to be important predictors of good oral bioavailability, independent of molecular weight. That on average both the number of rotatable bonds and polar surface area or hydrogen bond count tend to increase with molecular weight may in part explain the success of the molecular weight parameter in predicting oral bioavailability. The commonly applied molecular weight cutoff at 500 does not itself significantly separate compounds with poor oral bioavailability from those with acceptable values in this extensive data set. Our observations suggest that compounds which meet only the two criteria of (1) 10 or fewer rotatable bonds and (2) polar surface area equal to or less than 140 A(2) (or 12 or fewer H-bond donors and acceptors) will have a high probability of good oral bioavailability in the rat. Data sets for the artificial membrane permeation rate and for clearance in the rat were also examined. Reduced polar surface area correlates better with increased permeation rate than does lipophilicity (C log P), and increased rotatable bond count has a negative effect on the permeation rate. A threshold permeation rate is a prerequisite of oral bioavailability. The rotatable bond count does not correlate with the data examined here for the in vivo clearance rate in the rat.

In the United States, cancers of the oral cavity and oropharynx represent approximately three percent of all malignancies in men and two percent of all malignancies in women. The American Cancer Society estimates that 28,900 new cases of oral cancer will be diagnosed in 2002, and nearly 7,400 people will die from this disease. Over 90 percent of these tumors are squamous cell carcinomas, which arise from the oral mucosal lining. In spite of the ready accessibility of the oral cavity to direct examination, these malignancies still are often not detected until a late stage, and the survival rate for oral cancer has remained essentially unchanged over the past three decades. The purpose of this article is to review the clinical features of oral cancer and premalignant oral lesions, with an emphasis on early detection.

List of figures and tables Preface Acknowledgements Part I. Writing and the Alphabet: 1. The historical development of writing Part II. The Influence of Early Forms of Writing: 2. Literacy and achievement in the Ancient World 3. Africa, Greece and oral poetry 4. Oral composition and oral transmission: the case of the Vedas Part III. Written and Oral Cultures in West Africa: 5. The impact of Islamic writing on oral cultures 6. Literacy and the non-literate: the impact of European schooling 7. Alternative paths to knowledge in oral and literate cultures 8. Memory and learning in oral and literate cultures: the reproduction of the Bagre 9. Writing and formal operations: a case study among the Vai Part IV. Writing and its Impact on Individuals in Society: 10. The interface between the sociological and psychological analysis of literacy 11. Language and writing 12. Recapitulations Notes Bibliography Index.

The human oral cavity contains a number of different habitats, including the teeth, gingival sulcus, tongue, cheeks, hard and soft palates, and tonsils, which are colonized by bacteria. The oral microbiome is comprised of over 600 prevalent taxa at the species level, with distinct subsets predominating at different habitats. The oral microbiome has been extensively characterized by cultivation and culture-independent molecular methods such as 16S rRNA cloning. Unfortunately, the vast majority of unnamed oral taxa are referenced by clone numbers or 16S rRNA GenBank accession numbers, often without taxonomic anchors. The first aim of this research was to collect 16S rRNA gene sequences into a curated phylogeny-based database, the Human Oral Microbiome Database (HOMD), and make it web accessible (www.homd.org). The HOMD includes 619 taxa in 13 phyla, as follows: Actinobacteria, Bacteroidetes, Chlamydiae, Chloroflexi, Euryarchaeota, Firmicutes, Fusobacteria, Proteobacteria, Spirochaetes, SR1, Synergistetes, Tenericutes, and TM7. The second aim was to analyze 36,043 16S rRNA gene clones isolated from studies of the oral microbiota to determine the relative abundance of taxa and identify novel candidate taxa. The analysis identified 1,179 taxa, of which 24% were named, 8% were cultivated but unnamed, and 68% were uncultivated phylotypes. Upon validation, 434 novel, nonsingleton taxa will be added to the HOMD. The number of taxa needed to account for 90%, 95%, or 99% of the clones examined is 259, 413, and 875, respectively. The HOMD is the first curated description of a human-associated microbiome and provides tools for use in understanding the role of the microbiome in health and disease.

Chronic diseases and injuries are the leading health problems in all but a few parts of the world. The rapidly changing disease patterns throughout the world are closely linked to changing lifestyles, which include diets rich in sugars, widespread use of tobacco, and increased consumption of alcohol. In addition to socio-environmental determinants, oral disease is highly related to these lifestyle factors, which are risks to most chronic diseases as well as protective factors such as appropriate exposure to fluoride and good oral hygiene. Oral diseases qualify as major public health problems owing to their high prevalence and incidence in all regions of the world, and as for all diseases, the greatest burden of oral diseases is on disadvantaged and socially marginalized populations. The severe impact in terms of pain and suffering, impairment of function and effect on quality of life must also be considered. Traditional treatment of oral diseases is extremely costly in several industrialized countries, and not feasible in most low-income and middle-income countries. The WHO Global Strategy for Prevention and Control of Noncommunicable Diseases, added to the common risk factor approach is a new strategy for managing prevention and control of oral diseases. The WHO Oral Health Programme has also strengthened its work for improved oral health globally through links with other technical programmes within the Department for Noncommunicable Disease Prevention and Health Promotion. The current oral health situation and development trends at global level are described and WHO strategies and approaches for better oral health in the 21st century are outlined.

More than 700 bacterial species or phylotypes, of which over 50% have not been cultivated, have been detected in the oral cavity. Our purposes were (i) to utilize culture-independent molecular techniques to extend our knowledge on the breadth of bacterial diversity in the healthy human oral cavity, including not-yet-cultivated bacteria species, and (ii) to determine the site and subject specificity of bacterial colonization. Nine sites from five clinically healthy subjects were analyzed. Sites included tongue dorsum, lateral sides of tongue, buccal epithelium, hard palate, soft palate, supragingival plaque of tooth surfaces, subgingival plaque, maxillary anterior vestibule, and tonsils. 16S rRNA genes from sample DNA were amplified, cloned, and transformed into Escherichia coli. Sequences of 16S rRNA genes were used to determine species identity or closest relatives. In 2,589 clones, 141 predominant species were detected, of which over 60% have not been cultivated. Thirteen new phylotypes were identified. Species common to all sites belonged to the genera Gemella, Granulicatella, Streptococcus, and Veillonella. While some species were subject specific and detected in most sites, other species were site specific. Most sites possessed 20 to 30 different predominant species, and the number of predominant species from all nine sites per individual ranged from 34 to 72. Species typically associated with periodontitis and caries were not detected. There is a distinctive predominant bacterial flora of the healthy oral cavity that is highly diverse and site and subject specific. It is important to fully define the human microflora of the healthy oral cavity before we can understand the role of bacteria in oral disease.

It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-nCov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.

Growing recognition that quality of life is an important outcome of dental care has created a need for a range of instruments to measure oral health-related quality of life. This study aimed to derive a subset of items from the Oral Health Impact Profile (OHIP-49)-a 49-item questionnaire that measures people's perceptions of the impact of oral conditions on their well-being. Secondary analysis was conducted using data from an epidemiologic study of 1217 people aged 60+ years in South Australia. Internal reliability analysis, factor analysis and regression analysis were undertaken to derive a subset (OHIP-14) questionnaire and its validity was evaluated by assessing associations with sociodemographic and clinical oral status variables. Internal reliability of the OHIP-14 was evaluated using Cronbach's coefficient alpha. Regression analysis yielded an optimal set of 14 questions. The OHIP-14 accounted for 94% of variance in the OHIP-49; had high reliability (alpha = 0.88); contained questions from each of the seven conceptual dimensions of the OHIP-49; and had a good distribution of prevalence for individual questions. OHIP-14 scores and OHIP-49 scores displayed the same pattern of variation among sociodemographic groups of older adults. In a multivariate analysis of dentate people, eight oral status and sociodemographic variables were associated (P < 0.05) with both the OHIP-49 and the OHIP-14. While it will be important to replicate these findings in other populations, the findings suggest that the OHIP-14 has good reliability, validity and precision.

Overexpression of the prosurvival Bcl-2 family members (Bcl-2, Bcl-xL, and Mcl-1) is commonly associated with tumor maintenance, progression, and chemoresistance. We previously reported the discovery of ABT-737, a potent, small-molecule Bcl-2 family protein inhibitor. A major limitation of ABT-737 is that it is not orally bioavailable, which would limit chronic single agent therapy and flexibility to dose in combination regimens. Here we report the biological properties of ABT-263, a potent, orally bioavailable Bad-like BH3 mimetic (K(i)'s of <1 nmol/L for Bcl-2, Bcl-xL, and Bcl-w). The oral bioavailability of ABT-263 in preclinical animal models is 20% to 50%, depending on formulation. ABT-263 disrupts Bcl-2/Bcl-xL interactions with pro-death proteins (e.g., Bim), leading to the initiation of apoptosis within 2 hours posttreatment. In human tumor cells, ABT-263 induces Bax translocation, cytochrome c release, and subsequent apoptosis. Oral administration of ABT-263 alone induces complete tumor regressions in xenograft models of small-cell lung cancer and acute lymphoblastic leukemia. In xenograft models of aggressive B-cell lymphoma and multiple myeloma where ABT-263 exhibits modest or no single agent activity, it significantly enhances the efficacy of clinically relevant therapeutic regimens. These data provide the rationale for clinical trials evaluating ABT-263 in small-cell lung cancer and B-cell malignancies. The oral efficacy of ABT-263 should provide dosing flexibility to maximize clinical utility both as a single agent and in combination regimens.

Despite its relatively recent emergence over the past few decades, oral health-related quality of life (OHRQoL) has important implications for the clinical practice of dentistry and dental research. OHRQoL is a multidimensional construct that includes a subjective evaluation of the individual's oral health, functional well-being, emotional well-being, expectations and satisfaction with care, and sense of self. It has wide-reaching applications in survey and clinical research. OHRQoL is an integral part of general health and well-being. In fact, it is recognized by the World Health Organization (WHO) as an important segment of the Global Oral Health Program (2003). This paper identifies the what, why, and how of OHRQoL and presents an oral health theoretical model. The relevance of OHRQoL for dental practitioners and patients in community-based dental practices is presented. Implications for health policy and related oral health disparities are also discussed. A supplemental Appendix contains a Medline and ProQuest literature search regarding OHRQoL research from 1990-2010 by discipline and research design (e.g., descriptive, longitudinal, clinical trial, etc.). The search identified 300 articles with a notable surge in OHRQoL research in pediatrics and orthodontics in recent years.

The Global Burden of Disease (GBD) 2010 Study produced comparable estimates of the burden of 291 diseases and injuries in 1990, 2005, and 2010. This article reports on the global burden of untreated caries, severe periodontitis, and severe tooth loss in 2010 and compares those figures with new estimates for 1990. We used disability-adjusted life-years (DALYs) and years lived with disability (YLDs) metrics to quantify burden. Oral conditions affected 3.9 billion people, and untreated caries in permanent teeth was the most prevalent condition evaluated for the entire GBD 2010 Study (global prevalence of 35% for all ages combined). Oral conditions combined accounted for 15 million DALYs globally (1.9% of all YLDs; 0.6% of all DALYs), implying an average health loss of 224 years per 100,000 population. DALYs due to oral conditions increased 20.8% between 1990 and 2010, mainly due to population growth and aging. While DALYs due to severe periodontitis and untreated caries increased, those due to severe tooth loss decreased. DALYs differed by age groups and regions, but not by genders. The findings highlight the challenge in responding to the diversity of urgent oral health needs worldwide, particularly in developing communities.

1. Structure of the Oral Tissues 2. General Embryology 3. Embryology of the Head, Face, and Oral Cavity 4. Cytoskeleton, Junctions, and Fibroblasts 5. Development of the Tooth and Its Supporting Tissues 6. Bone 7. Enamel: Composition, Formation, and Structure 8. Dentin-pulp Complex 9. The Periodontium 10. Physiologic Tooth Movement: Eruption and Shedding 11. Salivary Glands 12. Oral Mucosa 13. Temporomandibular Joint 14. Repair and Regeneration of Oral Tissues

BACKGROUND: Oral fingolimod, a sphingosine-1-phosphate-receptor modulator that prevents the egress of lymphocytes from lymph nodes, significantly improved relapse rates and end points measured on magnetic resonance imaging (MRI), as compared with either placebo or intramuscular interferon beta-1a, in phase 2 and 3 studies of multiple sclerosis. METHODS: In our 24-month, double-blind, randomized study, we enrolled patients who had relapsing-remitting multiple sclerosis, were 18 to 55 years of age, had a score of 0 to 5.5 on the Expanded Disability Status Scale (which ranges from 0 to 10, with higher scores indicating greater disability), and had had one or more relapses in the previous year or two or more in the previous 2 years. Patients received oral fingolimod at a dose of 0.5 mg or 1.25 mg daily or placebo. End points included the annualized relapse rate (the primary end point) and the time to disability progression (a secondary end point). RESULTS: A total of 1033 of the 1272 patients (81.2%) completed the study. The annualized relapse rate was 0.18 with 0.5 mg of fingolimod, 0.16 with 1.25 mg of fingolimod, and 0.40 with placebo (P<0.001 for either dose vs. placebo). Fingolimod at doses of 0.5 mg and 1.25 mg significantly reduced the risk of disability progression over the 24-month period (hazard ratio, 0.70 and 0.68, respectively; P=0.02 vs. placebo, for both comparisons). The cumulative probability of disability progression (confirmed after 3 months) was 17.7% with 0.5 mg of fingolimod, 16.6% with 1.25 mg of fingolimod, and 24.1% with placebo. Both fingolimod doses were superior to placebo with regard to MRI-related measures (number of new or enlarged lesions on T(2)-weighted images, gadolinium-enhancing lesions, and brain-volume loss; P<0.001 for all comparisons at 24 months). Causes of study discontinuation and adverse events related to fingolimod included bradycardia and atrioventricular conduction block at the time of fingolimod initiation, macular edema, elevated liver-enzyme levels, and mild hypertension. CONCLUSIONS: As compared with placebo, both doses of oral fingolimod improved the relapse rate, the risk of disability progression, and end points on MRI. These benefits will need to be weighed against possible long-term risks. (ClinicalTrials.gov number, NCT00289978.)