Faculty Bibliography

The field of "salivary diagnostics" includes studies utilizing samples obtained from a variety of sources within the oral cavity. These samples include; whole unstimulated saliva, stimulated whole saliva, duct saliva collected directly from the parotid, submandibular/sublingual glands or minor salivary glands, swabs of the buccal mucosa, tongue or tonsils, and gingival crevicular fluid. Many publications state "we collected saliva from subjects" without fully describing the process or source of the oral fluid. Factors that need to be documented in any study include the time of day of the collection, the method used to stimulate and collect the fluid, and how much fluid is being collected and for how long. The handling of the oral fluid during and post-collection is also critical and may include addition of protease or nuclease inhibitors, centrifugation, and cold or frozen storage prior to assay. In an effort to create a standard protocol for determining a biomarker's origin we carried out a pilot study collecting oral fluid from 5 different sites in the mouth and monitoring the concentrations of pro-and anti-inflammatory cytokines detected using MesoScaleDiscovery (MSD) electrochemiluminesence assays. Our data suggested that 3 of the cytokines are primarily derived from the submandibular gland, while 7 of the cytokines come from a source other than the major salivary glands such as the minor salivary glands or cells in the oral mucosae. Here we review the literature on monitoring biomarkers in oral samples and stress the need for determining the blood/saliva ratio when a quantitative determination is needed and suggest that the term oral diagnostic be used if the source of an analyte in the oral cavity is unknown.

OBJECTIVE: Late preterm birth confers increased risk of developmental delay, academic difficulties and social deficits. The late third trimester may represent a critical period of development of neural networks including the default mode network (DMN), which is essential to normal cognition. Our objective is to identify functional and structural connectivity differences in the posteromedial cortex related to late preterm birth. METHODS: Thirty-eight preadolescents (ages 9-13; 19 born in the late preterm period (>/=32 weeks gestational age) and 19 at term) without access to advanced neonatal care were recruited from a low socioeconomic status community in Brazil. Participants underwent neurocognitive testing, 3-dimensional T1-weighted imaging, diffusion-weighted imaging and resting state functional MRI (RS-fMRI). Seed-based probabilistic diffusion tractography and RS-fMRI analyses were performed using unilateral seeds within the posterior DMN (posterior cingulate cortex, precuneus) and lateral parietal DMN (superior marginal and angular gyri). RESULTS: Late preterm children demonstrated increased functional connectivity within the posterior default mode networks and increased anti-correlation with the central-executive network when seeded from the posteromedial cortex (PMC). Key differences were demonstrated between PMC components with increased anti-correlation with the salience network seen only with posterior cingulate cortex seeding but not with precuneus seeding. Probabilistic tractography showed increased streamlines within the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus within late preterm children while decreased intrahemispheric streamlines were also observed. No significant differences in neurocognitive testing were demonstrated between groups. CONCLUSION: Late preterm preadolescence is associated with altered functional connectivity from the PMC and lateral parietal cortex to known distributed functional cortical networks despite no significant executive neurocognitive differences. Selective increased structural connectivity was observed in the setting of decreased posterior interhemispheric connections. Future work is needed to determine if these findings represent a compensatory adaptation employing alternate neural circuitry or could reflect subtle pathology resulting in emotional processing deficits not seen with neurocognitive testing.

OBJECTIVES: To determine the effectiveness of a novel sonic toothbrush in reducing plaque and in maintenance of gingival health when compared to a standard manual brush. METHODS: This study was a block-randomized, examiner-blind, two-treatment, parallel group, single centre clinical investigation. A total of 84 subjects were enrolled and randomly assigned to receive either the Panasonic EW-DL90 or an American Dental Association-endorsed manual toothbrush. Subjects were instructed to follow a twice-daily brushing regimen without flossing. Plaque levels and gingival health were assessed at baseline and after 1 and 3 weeks of treatment using the Turesky Modification of the Quigley-Hein Plaque Index and the Papillary Bleeding Score. RESULTS: Subjects assigned to the EW-DL90 group had significantly lower plaque levels after 1 and 3 weeks of treatment than those in the manual group (P = 0.003 and 0.0035, respectively). Both groups showed a reduction in plaque levels at Week 3 relative to baseline. The EW-DL90 group had significantly lower gingival inflammation scores after 1 week of treatment (P = 0.0293), but there was no difference between groups after 3 weeks of treatment. CONCLUSION: The EW-DL90 toothbrush safely and effectively removes more plaque than a standard manual toothbrush. Improvement in gingival inflammation was observed after 1 week of treatment. There was no difference in Papillary Bleeding Score between the two groups after 3 weeks of treatment. CLINICAL SIGNIFICANCE: The newly developed sonic brush (Panasonic EW-DL90) tested in this study was found to be more effective than a manual toothbrush at plaque removal. The papillary bleeding scores were significantly lower in the sonic brush group after 1 week of product use. After 3 weeks of product use, both treatment groups had similar papillary bleeding scores almost returning to baseline values.

Oral mucositis is a significant problem in cancer patients treated with radiation or chemotherapy, often hindering definitive cancer treatment. For patients with oral mucositis, pain is the most distressing symptom, leading to loss of orofacial function and poor quality of life. While oral mucositis has been well-described, its pathophysiology is poorly understood. Oral health professionals treating patients with mucositis have almost no effective therapies to treat or prevent oral mucositis. The purpose of this review is to (1) describe the current preclinical models of oral mucositis and their contribution to the understanding of mucositis pathophysiology, (2) explore preclinical studies on therapies targeting mucositis and discuss the clinical trials that have resulted from these preclinical studies, and (3) describe the proposed pathophysiology of oral mucositis pain and preclinical modeling of oral mucositis pain.

The purpose of this study was to radiographically evaluate, then analyze, bone height, volume, and density with reference to percentage of vital bone after maxillary sinuses were grafted using two different doses of recombinant human bone morphogenetic protein 2/acellular collagen sponge (rhBMP-2/ACS) combined with mineralized cancellous bone allograft (MCBA) and a control sinus grafted with MCBA only. A total of 18 patients (36 sinuses) were used for analysis of height and volume measurements, having two of three graft combinations (one in each sinus): (1) control, MCBA only; (2) test 1, MCBA + 5.6 mL of rhBMP-2/ACS (containing 8.4 mg of rhBMP-2); and (3) test 2, MCBA + 2.8 mL of rhBMP-2/ACS (containing 4.2 mg of rhBMP-2). The study was completed with 16 patients who also had bilateral cores removed 6 to 9 months following sinus augmentation. A computer software system was used to evaluate 36 computed tomography scans. Two time points where selected for measurements of height: The results indicated that height of the grafted sinus was significantly greater in the treatment groups compared with the control. However, by the second time point, there were no statistically significant differences. Three weeks post-surgery bone volume measurements showed similar statistically significant differences between test and controls. However, prior to core removal, test group 1 with the greater dose of rhBMP-2 showed a statistically significant greater increase compared with test group 2 and the control. There was no statistically significant difference between the latter two groups. All three groups had similar volume and shrinkage. Density measurements varied from the above results, with the control showing statistically significant greater density at both time points. By contrast, the density increase over time in both rhBMP groups was similar and statistically higher than in the control group. There were strong associations between height and volume in all groups and between volume and new vital bone only in the control group. There were no statistically significant relationships observed between height and bone density or between volume and bone density for any parameter measured. More cases and monitoring of the future survival of implants placed in these augmented sinuses are needed to verify these results.

Limited information is available about the effect of human immunodeficiency virus (HIV) and subsequent antiretroviral treatment on host-microbe interaction. This study aimed to determine the salivary microbial composition in 10 HIV-seropositive subjects, before and 6 months after highly active antiretroviral therapy (HAART), compared with that of 10 HIV-seronegative subjects. Both a conventional culture and two culture-independent analyses were used and consistently demonstrated differences in microbial composition among the three sets of samples. HIV+ subjects had higher levels of total cultivable microbes, including oral streptococci, lactobacilli, S. mutans, and Candida, in saliva as compared to HIV- subjects. The total cultivable microbial level was significantly correlated with CD4+ T cell counts. Denaturing gradient gel electrophoresis (DGGE), which compared the overall microbial profiles, showed distinct fingerprinting profiles for each group. Human oral microbe identification microarray (HOMIM), which compared the 16S rRNA genes, showed a clear separation among the three sample groups. Veillonella, Synergistetes, and Streptococcus, were present in all 30 saliva samples. Only minor changes or no changes were observed in the prevalence of Neisseria, Haemophilus, Gemella, Leptotrichia, Solobacterium, Parvimonas and RothiaI. Severn genera were detected only in HIV- samples, including Capnocytophaga, Slackia, Porphyromonas, Kingella, Peptostreptococcaceae, Lactobacillus, and Atopobium. The prevalence of Fusobacterium, Campylobacter, Prevotella, Capnocytophaga, Selenomonas, Actinomyces, and Atopobium was increased after therapy with HAART. In contrast, the prevalence of Aggregatibacter was significantly decreased after HAART. Findings of this study suggest that HIV infection and therapy with HAART could have a significant effect on salivary microbial colonization and composition.

The aim of this study was to determine heritability estimates of treatment responses to a 10% hydrogen peroxide strip-based whitening system in twins. Eighty-five twin pairs were randomly assigned to 10% hydrogen peroxide whitening strips or placebo strips without peroxide. Both twins (monozygotic or dizygotic) received the same treatment. Maxillary teeth were treated for 30 minutes twice daily for 7 days. Efficacy was measured objectively as L* (light-dark), a* (red-green), and b* (yellow-blue) color change from digital images at baseline () and day 8. Heritability estimates for tooth whitening treatment responses for changes from day 8 to baseline were obtained using variance-component methodologies. Whitening treatment responses were highly heritable (h2 = 71.0) for b* and a*(p < .0001), but not for L* (h2 = 27.0), which was essentially modulated by environmental factors. This study has demonstrated that both genetic and environmental factors significantly contributed to seven-day whitening treatment responses achieved with 10% hydrogen peroxide strips.

OBJECTIVE:The objective of this study was to assess the ability of a dentifrice containing 8% arginine and calcium carbonate (Pro-Argin' Technology), and 1450 ppm fluoride as sodium monofluorophosphate (MFP) to prevent enamel loss from an erosive acid challenge in comparison to a silica-based dentifrice with 1450 ppm fluoride as MFP using an intra-oral erosion model. METHODS:The intra-oral clinical study used a double blind, two-treatment, crossover design. A palatal retainer was used to expose the enamel specimens to the oral environment during the five-day treatment period. The retainer was designed to house three partially demineralized bovine enamel samples. The study population was composed of 24 adults, ages 18 to 70 years. The study consisted of two treatment periods, with a washout period lasting seven (+/- three) days preceding each treatment phase. A silica-based dentifrice without fluoride was used during the washout period. The Test Dentifrice used in this study contained 8% arginine and calcium carbonate (Pro-Argin Technology), and 1450 ppm fluoride as sodium monofluorophosphate (MFP). The Control Dentifrice was silica-based and contained 1450 ppm fluoride as MFP. The treatment period lasted five days, during which the panelists wore the retainer 24 hours a day (except during meals and the ex vivo acid challenges) and brushed with their assigned product while wearing the retainer. The panelists brushed once in the morning and once in the evening each day for one minute, followed by a one-minute swish with the slurry and a rinse with 15 ml of water. The panelists brushed only their teeth and not the specimens directly. There were four ex vivo challenges with 1% citric acid dispersed throughout the day: two in the morning, one in the afternoon, and one in the evening. Mineral loss was monitored by a quantitative light fluorescence (QLF) technique. RESULTS:Twenty-three of 24 subjects successfully completed the study. The one subject who did not complete the study did so for reasons unrelated to the study or products used. The average percent mineral loss for the Test Dentifrice and Control Dentifrice was 9.74 +/- 13.23 and 18.36 +/- 14.14, respectively. The statistical analysis showed that the observed product differences were statistically significant (p < 0.001). CONCLUSION/CONCLUSIONS:The Test Dentifrice with 8% arginine, calcium carbonate, and 1450 ppm fluoride as MFP provided significantly better protection against erosive challenges in comparison to the Control Dentifrice with 1450 ppm fluoride as MFP.

OBJECTIVE:An intra-oral remineralization study was conducted to compare the ability of a dentifrice containing 8% arginine and calcium carbonate (Pro-Argin Technology), and 1450 ppm fluoride as sodium monofluorophosphate (MFP) to remineralize acid-softened bovine enamel specimens compared to a silica-based dentifrice with 1450 ppm fluoride as MFP. METHODS:The intra-oral clinical study employed a double blind, two-treatment, crossover design, and used an upper palatal retainer to expose the enamel specimens to the oral environment during product use and periods of remineralization. The retainer was designed to house three partially demineralized bovine enamel samples. The study population was comprised of 30 adults, ages 18 to 70 years. The study consisted of two treatment phases with a washout period lasting seven (+/- three) days preceding each treatment phase. A silica-based dentifrice without fluoride was used during the washout period. The Test Dentifrice used in this study contained 8% arginine, calcium carbonate, and 1450 ppm fluoride as sodium monofluorophosphate (MFP). The Control Dentifrice was silica-based and contained 1450 ppm fluoride as MFP. The treatment period consisted of a three-day lead-in period with the assigned product. The panelists brushed two times per day during the three-day lead-in period with the assigned product. On the fourth day, the panelists began brushing with the assigned product with the retainer in their mouth. The panelists brushed for one minute, followed by a one-minute swish with the slurry and a rinse with 15 ml of water in the morning, in the afternoon, and night with the retainer in the mouth. The panelists brushed only their teeth and not the specimens directly. Changes in mineral content before and after treatment were measured using a Knoop microhardness tester. RESULTS:The results of the study showed that percent remineralization values for the Test Dentifrice and Control Dentifrice were 14.99% and 8.66%, respectively. A statistical analysis showed that the Test Dentifrice was statistically significantly more effective at remineralizing acid-softened enamel in comparison to the Control Dentifrice (p < 0.05). CONCLUSION/CONCLUSIONS:This study demonstrated that the Test Dentifrice with 8% arginine, calcium carbonate, and 1450 ppm fluoride as MFP is highly effective treatment for promoting remineralization of enamel that has been softened by an erosive challenge.