Public Dental Services, Queensland: Alan Thomas Robertson.

Alan Thomas Robertson's career as Assistant Superintendent Brisbane Dental Hospital [1927-1945] and Acting Superintendent [1945-1946] spanned difficult times. In Victoria, against a backdrop of family tragedy and World War I, Robertson achieved distinguished academic and war-service records. Following the move to Queensland, Robertson either experienced or witnessed the Great Depression, World War II and affiliated paradigm shifts in government policy, dental education and the system of the delivery of dental services. Within this context, the actions of Hanlon, Vidgen and Hoole overshadowed Robertson's brief but meaningful contribution to the Australian Dental Association Queensland Branch, his diligent nineteen years of service to the Brisbane Dental Hospital [BDH] and its patients, his pioneering of general anesthesia and his perennial commitment to undergraduate and continuing dental education. Robertson's career was neither financially lucrative nor acclaimed. Despite his overt patriotism, leadership potential, academic profile and experience, seniority and service, Robertson's appointment as Superintendent at the BDH was only an interim measure. A brief career in an entrepreneurial private practice ended in professional isolation followed by tragedy. The authors present a revisionist interpretation of Robertson's career. This narrative conveys messages for human resource managers in both academe and health departments.

Public Dental Services, Queensland, Australia: Charles Octavius Vidgen.

Charles Octavius Vidgen was the Superintendent of the Brisbane Dental Hospital, c1917-1945. Hitherto, commentators' reviews rely on imposing but narrow streams of evidence to either ignore Vidgen's influence on the dental profession or portray it as both peripheral and controversial. In this account, the authors use historical method to provide a revisionist account of Vidgen's professional profile and, to a lesser extent, a character resurrection. Vidgen was probably introverted. His orientation relating to dental education became obsolete, inappropriate and disruptive. Vidgen's actions, beliefs and values incurred sustained and organized opposition from academe, the Australian Dental Association Queensland Branch, the Odontological Society of Queensland and some private practitioners. The sociopolitical context, namely the Great Depression and affiliated reconstruction, the community's demand for government-administered dental services, World War II, twenty-five years of continuous Australian Labor Party government in Queensland, Edward Hanlon's authoritarianism and the emergence of a welfare state were also relevant to Vidgen's becoming a nonconformist, nonjoiner and an outcast. However, the authors posit that, for the socially disadvantaged and the regionally and remotely domiciled, Vidgen was a humanitarian and a quiet social reformer who, under Hanlon's authority and tutelage, pioneered enduring changes to the delivery of dental services across Queensland.

Brisbane Dental Hospital and Queensland University Dental College Building Alias The Palace: Heritage Listing.

The National Trust of Queensland placed the Brisbane Dental Hospital and Queensland College of Dentistry Building, alias The Palace, on the National Trust of Queensland Register in April 1997. This action generated no statutory consequences. Within days, the trust nominated The Palace for listing on the Queensland Heritage Register. Under the terms of the Queensland Heritage Act 1992, this nomination could have impeded an imminent $2-million redevelopment within The Palace. Two years later, the Queensland Heritage Council entered The Palace on the Queensland Heritage Register. This procedural delay was unusual and occurred in an era of post-Fitzgerald bureaucratic reform, federal cutbacks to funding for public dental services, tenuous political control of state government and widespread community support for heritage protection. The authors use historical methods to disclose and analyze hitherto inaccessible evidence relating to the delay in the listing. They argue that, against a backdrop of potential controversy, a small band of networked, organized and resolute administrators and Palace-based personnel, achieved the redevelopment. Astute tactics, concurrent rebuilding of health infrastructure, ministerial resolve, the nature of the act, public demand for dental services, the timing of the redevelopment and the political circumstances influenced the outcome.

Public Dental Services, Queensland: Alfred James Hoole.

Historians have given limited attention to the genesis and evolution of public dental services across Queensland. The Secretary [Minister] for Home Affairs and later Premier, Edward 'Ned' Hanlon, was the political architect of accessible public hospital and dental facilities. However it was administrator and dentist, Alfred James Hoole, who orchestrated the practical details in the field. Hoole developed an extensive and successful government-administered, hospital-based dental service that, in terms of reach and workforce, was the contemporaneous leader in Australia. These clinics and affiliated school dental services delivered treatment to a disproportionately high percentage of socially disadvantaged and remotely domiciled Queenslanders. Hoole's career progression from Superintendent of the Brisbane Dental Hospital to Director of Dental Services is remarkable for its achievements, consequences, competency and duration. It originated from a limited secondary education and traversed the bitter political split of 1957, changes of government, minister and fiscal policy, health adversity and opposition from private practitioners. Hoole, an anointed leader, a ministerial confidant and a pragmatist, served on authorities and institutions that shaped the future of dental education and dental practice across the state. Forty-five years after his death, Hoole's contribution to the administration of public dental services in Queensland remains unrivalled.

Public Dental Services, Queensland: Edward "Ned" Michael Hanlon.

Within the Australian context, commentators often portray the Queensland system of delivery of public dental services as state-specific. A poorly explored dimension within this narrative is the contribution from Ned Hanlon. The authors use historical methods to address this inadequacy in the literature. The implementation of Hanlon's vision of a statewide government-administered dental service required dentists and infrastructure; both implicated legislative and administrative changes to dental education, hospital organization and local authority. In this way, there was an inexorable link between the genesis and evolution of the public hospital and public dental systems. Hanlon's motive was initially humanitarian but later implicated pragmatism, state development and Queensland chauvinism. Hanlon's actions were autocratic, authoritarian and populist. He pursued regionalism, states rights and state development. The post-depression and post-war timing, together with the ubiquity of dental caries and the nature of the dental profession, facilitated Hanlon's success. A nascent and emerging dental profession was powerless, out of touch with public thinking and hindered by the legislative framework that controlled dentists' registration. The Hanlon-dentist encounters became an intersection of conflicting values; idealism and tradition versus pragmatism and innovation. Whatever the perceived inadequacies in Hanlon's methods, his contribution to public dentistry across Queensland remains remarkable.

PAK4 promotes kinase-independent stabilization of RhoU to modulate cell adhesion.

P21-activated kinase 4 (PAK4) is a Cdc42 effector protein thought to regulate cell adhesion disassembly in a kinase-dependent manner. We found that PAK4 expression is significantly higher in high-grade human breast cancer patient samples, whereas depletion of PAK4 modifies cell adhesion dynamics of breast cancer cells. Surprisingly, systematic analysis of PAK4 functionality revealed that PAK4-driven adhesion turnover is neither dependent on Cdc42 binding nor kinase activity. Rather, reduced expression of PAK4 leads to a concomitant loss of RhoU expression. We report that RhoU is targeted for ubiquitination by the Rab40A-Cullin 5 complex and demonstrate that PAK4 protects RhoU from ubiquitination in a kinase-independent manner. Overexpression of RhoU rescues the PAK4 depletion phenotype, whereas loss of RhoU expression reduces cell adhesion turnover and migration. These data support a new kinase-independent mechanism for PAK4 function, where an important role of PAK4 in cellular adhesions is to stabilize RhoU protein levels. Thus, PAK4 and RhoU cooperate to drive adhesion turnover and promote cell migration.

Digital imaging in the immunohistochemical evaluation of the proliferation markers Ki67, MCM2 and Geminin, in early breast cancer, and their putative prognostic value.

BACKGROUND: Immunohistochemical assessment of proliferation may provide additional prognostic information in early breast cancer. However, due to a lack of methodological standards proliferation markers are still not routinely used for determining therapy. Even for Ki67, one of the most widely-studied markers, disagreements over the optimal cutoff exist. Improvements in digital microscopy may provide new avenues to standardise and make data more reproducible. METHODS: We studied the immunohistochemical expression of three markers of proliferation: Ki67, Mini-Chromosome Maintenance protein 2 and Geminin, by conventional light microscope and digital imaging on triplicate TMAs from 309 consecutive cases of primary breast cancers. Differences between the average and the maximum percentage reactivity in tumour cell nuclei from the three TMA cores were investigated to assess the validity of the approach. Time-dependent Receiver Operating Characteristic curves were utilized to obtain optimal expression level cut-offs, which were then correlated with clinico-pathological features and survival. RESULTS: High concordance between conventional and digital scores was observed for all 3 markers (Ki67: rs = 0.87, P < 0.001; MCM2: rs = 0.94, P < 0.001; and Geminin: rs = 0.86, P < 0.001; Spearman's rank). There was no significant difference according to the number of TMA cores included for either Ki67 or MCM2; analysis of two or three cores produced comparable results. Higher levels of all three proliferation markers were significantly associated with higher grade (P < 0.001) and ER-negativity (P < 0.001). Optimal prognostic cut-offs for percentage expression in the tumour were 8 %, 12 and 2.33 % for Ki67, MCM2 and Geminin respectively. All 3 proliferation marker cutoffs were predictive of 15-year breast cancer-specific survival in univariable Cox regression analyses. In multivariable analysis only lymph node status (HR = 3.9, 95 % CI = 1.79-8.5, P = 0.0006) and histological grade (HR = 1.84, 95 % CI = 1-3.38, P = 0.05) remained significantly prognostic. CONCLUSIONS: Here we show that. MCM2 is a more sensitive marker of proliferation than Ki67 and should be examined in future studies, especially in the lymph node-negative, hormone receptor-positive subgroup. Further, digital microscopy can be used effectively as a high-throughput method to evaluate immunohistochemical expression.

The dynamic behavior of the early dental caries lesion in caries-active adults and implications.

OBJECTIVE: To describe the full range of behavior of the visible, noncavitated, early caries lesion in caries-active adults with substantial fluoride exposure, and to consider implications. METHODS: The data were from the Xylitol for Adult Caries Trial (X-ACT) collected annually for 33 months using condensed ICDAS caries threshold criteria. Individual tooth surfaces having a noncavitated caries lesion were included, and the patterns of transition to each subsequent annual clinical examination to sound, noncavitated or cavitated, filled or crowned were determined. The resulting sets of patterns for an individual tooth surface, looking forward from its first appearance as a noncavitated lesion, were combined into one of four behavior profiles classified as reversing, stable, oscillating, or continuously progressing, or were excluded if not part of the caries continuum. The distributions of profile types were assessed using the Rao-Scott chi-square test, which adjusts for clustering of tooth surfaces within teeth. RESULTS: Inter- and intra-examiner kappa scores demonstrated acceptable calibration at baseline and annually. 8084 tooth surfaces from 543 subjects were included. The distribution of profile types differed significantly between coronal and root surfaces. Overall, two-thirds of all coronal noncavitated lesions were first seen at baseline, half reversed, over a fifth were stable, 15% oscillated, and only 8.3% progressed to cavitation, filled, or crowned in 33 months or less (6.3% consistently Progressed plus 2.0% inconsistently, a subset of oscillating, which oscillated before progressing to cavitation). Approximal, smooth, and occlusal coronal surfaces each were significantly different in their individual distributions of profile types. Xylitol showed no significant and consistent effect on this distribution by tooth surface type. This was in keeping with the X-ACT's lack of effect of xylitol at the noncavitated plus cavitated lesion thresholds combined. CONCLUSIONS: This study demonstrated the full dynamic range of early caries lesion behavior. The great majority were not progressive, and few (8.3%) became cavitated over 33 months in caries-active adults using fluorides. Important caries management implications favoring recorded longitudinal monitoring, prevention of active risks, and minimal restoration only after direct visual determination of cavitation are discussed.

The Brisbane Dental Hospital Building: "The Palace" An Era Ends.

Constitutional, educational, humanitarian and political considerations underpinned the design and construction of the Brisbane Dental Hospital Building, often colloquially referred to as "The Palace." The Queensland Heritage Council's listing of the Brisbane Dental Hospital Building on The Queensland Heritage Register in 1999 confirms the cultural significance of Nowland's architectural signature, the historical importance of the Wickham Park precinct and prior students' connection with the building. Influences on decisions determining the location, grand design and timing of construction of the Brisbane Dental Hospital Building emanated from a far bigger and largely unrecorded political picture. The authors argue that the political context in two tiers of government, the timing and nature of the proposal, town planning issues, the exigencies of the caries epidemic and Forgan Smith's post-Depression economic reconstruction across Queensland underpinned the project. Hanlon's personal attributes and disdain for the autonomy of the dental profession, together with his desire to reform dental education and to establish statewide government-administred dental clinics, were also relevant. Accordingly, the BDHD portrayed aspiration, purpose, symbolism, and vision. This paper, essentially an integration of dental and mainstream history, assembles and analyzes hitherto scattered and unpublished evidence to fill a gap in the current literature.

Visual scoring of non cavitated caries lesions and clinical trial efficiency, testing xylitol in caries-active adults.

OBJECTIVES: To better understand the effectiveness of xylitol in caries prevention in adults and to attempt improved clinical trial efficiency. METHODS: As part of the Xylitol for Adult Caries Trial (X-ACT), non cavitated and cavitated caries lesions were assessed in subjects who were experiencing the disease. The trial was a test of the effectiveness of 5 g/day of xylitol, consumed by dissolving in the mouth five 1 g lozenges spaced across each day, compared with a sucralose placebo. For this analysis, seeking trial efficiency, 538 subjects aged 21-80, with complete data for four dental examinations, were selected from the 691 randomized into the 3-year trial, conducted at three sites. Acceptable inter- and intra-examiner reliability before and during the trial was quantified using the kappa statistic. RESULTS: The mean annualized noncavitated plus cavitated lesion transition scores in coronal and root surfaces, from sound to carious favoured xylitol over placebo, during the three cumulative periods of 12, 24, and 33 months, but these clinically and statistically nonsignificant differences declined in magnitude over time. Restricting the present assessment to those subjects with a higher baseline lifetime caries experience showed possible but inconsistent benefit. CONCLUSIONS: There was no clear and clinically relevant preventive effect of xylitol on caries in adults with adequate fluoride exposure when non cavitated plus cavitated lesions were assessed. This conformed to the X-ACT trial result assessing cavitated lesions. Including non cavitated lesion assessment in this full-scale, placebo-controlled, multisite, randomized, double-blinded clinical trial in adults experiencing dental caries did not achieve added trial efficiency or demonstrate practical benefit of xylitol. TRIAL REGISTRATION: ClinicalTrials.Gov NCT00393055.

Comparison of basal-like triple-negative breast cancer defined by morphology, immunohistochemistry and transcriptional profiles.

Basal-like invasive breast cancer is an important clinical group because of its association with a triple-negative phenotype defined by the lack of expression of estrogen, progesterone and human epidermal growth factor receptors 2, relative lack of therapeutic options and poor prognosis. However, depending on the method used to define these lesions, morphological assessment, immunohistochemical markers or gene expression, a different set of tumors is captured. The aim of this study was to investigate the consequences of using different methodological approaches to define basal-like lesions among triple-negative breast carcinomas with regard to their clinicopathological features and patient outcome. The cohort consisted of 142 invasive breast cancers with a triple-negative receptor status. First, each was reviewed histologically and those with morphological basal-like features were characterized as 'Path-Basal'. Second, the 'Core Basal' immunohistochemical lesions, defined as cytokeratin 5/6 and/or epidermal growth factor receptor 1 positive, within the triple-negative breast cancers were identified, and third their classification based on gene expression profiling was retrieved and those in the molecular 'PAM50 basal-like' subtype recorded. A total of 116 basal-like breast cancers were identified among the 142 triple-negative breast cancers by at least one of these three classifications (80%), but only 13 samples were defined as basal-like with all three methods. None of these 13 tumors were associated with lymphovascular invasion. The 34 morphological 'Path-Basal' lesions were significantly associated with a lack of nodal metastases. Comparing the estimates of death in the three classifications, the highest risk of death was seen for the 'Core Basal' group. In this study, we highlight that the definition of basal-like breast cancer based on different methodologies varies significantly and does not identify the same lesions. This incomplete overlap of cases emphasizes the need for consistent or new approaches to improve precise identification.

Results from the Xylitol for Adult Caries Trial (X-ACT).

BACKGROUND: Although caries is prevalent in adults, investigators have tested few preventive therapies in adult populations. In a randomized controlled trial, the authors evaluated the effectiveness of xylitol lozenges in preventing caries in adults at elevated risk of developing caries. METHODS: The Xylitol for Adult Caries Trial (X-ACT) was a three-site placebo-controlled randomized trial. Participants (n = 691) aged 21 through 80 years consumed five 1.0-gram xylitol or placebo lozenges daily for 33 months. They underwent clinical examinations at baseline and at 12, 24 and 33 months. RESULTS: Xylitol lozenges reduced the caries increment 10 percent. This reduction, which represented less than one-third of a surface per year, was not statistically significant. There was no indication of a dose-response effect. CONCLUSIONS: Daily use of xylitol lozenges did not result in a statistically or clinically significant reduction in 33-month caries increment among adults at an elevated risk of developing caries. CLINICAL IMPLICATIONS: These results suggest that xylitol used as a supplement in adults does not reduce their caries experience significantly.

The manufacture and assessment of tissue microarrays: suggestions and criteria for analysis, with breast cancer as an example.

Tissue microarray (TMA) is an established and valuable tool, particularly in translational research and clinical trials, allowing resource-efficient use, and high-throughput profiling, of large numbers of tumours. Despite this, there is little evidence, or guidance, on the optimum manufacture, use and assessment of TMAs. Here we review some of the literature, using breast cancer as an example, to highlight good practice and pitfalls in the design and manufacture of TMAs. Issues, such as the size, number, spacing and layout of cores, as well as the assessment and reporting of studies using TMAs are addressed. We make some suggestions regarding these challenges, and propose a checklist of features that should be considered in order to stimulate debate and improve the quality of data produced by TMA analysis.

Dental caries prediction to target high-risk individuals in community-based preventive programs is problematic.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Life course dental caries determinants and predictors in children aged 12 years: a population-based birth cohort. Peres MA, Barros AJ, et al. Community Dent Oral Epidemiol 2009;37:123-33. REVIEWER: John P. Brown, BDS, MS, PhD. PURPOSE/QUESTION: To define selected life course social, biological, and behavioral exposures as determinants and predictors of dental caries in children at 12 years of age. SOURCE OF FUNDING: Brazilian National Council for Scientific and Technological Development CNPq Grant No. 403362/2004-0. TYPE OF STUDY/DESIGN: Cohort study. LEVEL OF EVIDENCE: Level 2: limited-quality patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Not applicable.

Design of the xylitol for adult caries trial (X-ACT).

BACKGROUND: Dental caries incidence in adults is similar to that in children and adolescents, but few caries preventive agents have been evaluated for effectiveness in adults populations. In addition, dentists direct fewer preventive services to their adult patients. Xylitol, an over-the-counter sweetener, has shown some potential as a caries preventive agent, but the evidence for its effectiveness is not yet conclusive and is based largely on studies in child populations. METHODS/DESIGN: X-ACT is a three-year, multi-center, placebo controlled, double-blind, randomized clinical trial that tests the effects of daily use of xylitol lozenges versus placebo lozenges on the prevention of adult caries. The trial has randomized 691 participants (ages 21-80) to the two arms. The primary outcome is the increment of cavitated lesions. DISCUSSION: This trial should help resolve the overall issue of the effectiveness of xylitol in preventing caries by contributing evidence with a low risk of bias. Just as importantly, the trial will provide much-needed information about the effectiveness of a promising caries prevention agent in adults. An effective xylitol-based caries prevention intervention would represent an easily disseminated method to extend caries prevention to individuals not receiving caries preventive treatment in the dental office. TRIAL REGISTRATION: ClinicalTrials.Gov NCT00393055.

Epidemiologic survey of erosive tooth wear in San Antonio, Texas.

OBJECTIVES: To estimate the prevalence of erosive tooth wear in children aged 12-17 years in the southwest region of San Antonio, Texas, within Bexar County. METHODS: A convenience sample of 307 children aged 12-17 years was selected from two junior high schools. The population consisted predominantly of Hispanic Mexican Americans. The true prevalence of erosive tooth wear within the US is known from only one study, and then only for limited sectors of the population. The Tooth Wear Index, Screening for Oral Health using the Association of State and Territorial Dental Directors (ASTDD) criteria and oral health and dietary assessment questionnaires were used as survey parameters. The questionnaire included data on detailed dietary habits relating primarily to the consumption of acidic beverages and foods. RESULTS: The overall prevalence of erosion within our convenience sample was 5.5 percent. All affected children showed erosive tooth wear low in severity and confined to the enamel with no exposed dentin. A chi-square test was performed to test for associations between the presence of erosion and consumption level of certain acidic foods at a significance level of 5 percent. Few significant and consistent associations were found between erosive tooth wear and consumption frequency categories of groups of acidic foods and beverages using a non-validated food intake questionnaire on purported risk foods. Soda drinks were associated. Mexican acidic foods were not. CONCLUSION: This study indicated a low prevalence and low severity of dental erosion in a convenience sample of children aged 12-17 years in southwest San Antonio, Texas. Issues of sampling and response bias preclude these findings being generalized to other populations and regions.The results should be viewed with caution. Because the local consumption of some purported risk foods appears to be increasing, this study provides a base-line for future assessments of erosive tooth wear in this population.

A novel CD11c monoclonal antibody effective in formalin-fixed tissue for the diagnosis of hairy cell leukemia.

OBJECTIVE: The diagnosis of hairy cell leukemia (HCL) and its distinction from other B-cell lymphomas can be difficult in formalin-fixed tissue. This is because the histology is not always classical, and despite having a characteristic phenotype, there are few relevant monoclonal antibodies with sufficient sensitivity and specificity that can be applied to fixed material. In this study, we assessed the utility of a newly developed antibody against a formalin-resistant CD11c epitope (5D11) for the diagnosis and monitoring of HCL in formalin-fixed tissue. METHODS: We performed immunohistochemical staining for CD11c expression in formalin-fixed and also decalcified tissue of 196 small B-cell lymphomas, including 104 cases of HCL showing extensive to minimal infiltrates. RESULTS: The CD11c antibody was both sensitive and specific for HCL, even in cases with minimal infiltration. CONCLUSION: We recommend that this CD11c antibody be added to a panel of antibodies for immunostaining of formalin-fixed material, for differentiation of HCL from other small B-cell lymphomas, and for detection of residual disease following therapy.

Alpha-6 integrin is necessary for the tumourigenicity of a stem cell-like subpopulation within the MCF7 breast cancer cell line.

The identification of mammary epithelial stem cells raises the hypothesis that these cells may be crucial in the pathogenesis of breast cancer. To further support this, a highly tumourigenic sub-population of cancer cells has recently been identified in primary and metastatic breast cancer samples. In this study, a sub-population of cells displaying features normally attributed to stem cells was identified within the breast cancer cell line MCF-7. This sub-population is capable of growth in anchorage-independent conditions as spherical organoids, displays resistance to proapoptotic agents and significantly greater tumourigenicity than its parental line, with as few as 1,000 cells able to form tumours in immunodeficient mice. Cells within this sub-population can be enriched by serial passages in anchorage-independence, and are characterized by over-expression of the adhesion molecule alpha6-integrin. Alpha-6 integrin proves to be required for the growth and survival of these cells, as the knockdown of ITGA6 causes mammosphere-derived cells to lose their ability to grow as mammospheres and abrogates their tumourigenicity in mice. These findings support the existence of a highly tumourigenic sub-population in breast cancer cells. Furthermore, it shows alpha6-integrin as a potential therapeutic target aimed at tumour-generating subsets of breast cancer cells.

Interaction of age and specific saliva component output on caries.

BACKGROUND AND AIMS: The purpose of this study was to explore the relationship between individual salivary components, dental caries and age, utilizing the data from the Oral Health: San Antonio Longitudinal Study of Aging (OH:SALSA). METHODS: The study population comprised a well-defined stratified sample of 811 dentate men and women. Subjects were divided into four age groups from 35 to 75+ years old. Unstimulated and stimulated submandibular/sublingual saliva flow rates, unstimulated and stimulated parotid saliva flow rates, total protein, 6 individual proteins and 4 inorganic constituents were measured. Specific salivary components were lactoferrin, secretory IgA, albumin, lysozyme, mucin, cystatin, K+, Ca2+, Na+ and Cl-. Caries measurements were the DMFT Index for crowns and for roots, Tooth Health Index for crowns and roots, Tooth caries, Root caries and Tooth restoration. The data on saliva components were square root transformed for linearity prior to analysis. Analysis was carried out in two stages. Partial correlation was performed, in order to identify significant relationships between specific salivary components and caries measurements, controlling for age group. In the second stage, using caries measurement as the dependant variable, the effects of age, flow rate and specific salivary component output (product of flow rate and concentration) were examined. RESULTS: Significant associations were found between caries, age and specific individual submandibular/sublingual salivary proteins (lactoferrin, albumin, lysozyme, mucin and cystatin) and specific inorganic constituents (K+, Ca2+, Na+ and Cl-). CONCLUSIONS: Changes in submandibular/ sublingual salivary component output during aging are correlated with high caries prevalence. These changes in saliva components over age may represent caries risk indicators.