Host-Microbiome Cross-talk in Oral Mucositis.

Oral mucositis (OM) is among the most common, painful, and debilitating toxicities of cancer regimen-related treatment, resulting in the formation of ulcers, which are susceptible to increased colonization of microorganisms. Novel discoveries in OM have focused on understanding the host-microbial interactions, because current pathways have shown that major virulence factors from microorganisms have the potential to contribute to the development of OM and may even prolong the existence of already established ulcerations, affecting tissue healing. Additional comprehensive and disciplined clinical investigation is needed to carefully characterize the relationship between the clinical trajectory of OM, the local levels of inflammatory changes (both clinical and molecular), and the ebb and flow of the oral microbiota. Answering such questions will increase our knowledge of the mechanisms engaged by the oral immune system in response to mucositis, facilitating their translation into novel therapeutic approaches. In doing so, directed clinical strategies can be developed that specifically target those times and tissues that are most susceptible to intervention.

Modulation of the orodigestive tract microbiome in HIV-infected patients.

More than 37 million people are living with human immunodeficiency virus 1 (HIV), and more people than ever received lifesaving antiretroviral therapy worldwide. HIV-1 infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the GI microbiome and its association with host immune activation. The data indicated that the microbiome was different in HIV-positive and HIV-negative individuals. The initial sequence analysis of saliva indicated that there were major differences in the phyla of Bacteroidetes, Firmicutes, Proteobacteria, and TM7. Phylum Tenericutes was only seen in HIV-positive saliva. At the family level, we identified differences in Streptococcacea, Prevotellaceae, Porphyromonadaceae, and Neisseriaceae, whereas data from various sites in GI tract indicated that Prevotella melaninigencia, Fusobacterium necrophorum, Burkholderia, Bradyrhizobium, Ralstonia, and Eubacterium biforme were predominant but differentially present at various sites. Furthermore, there was a decrease in seven proteins associated with the alternative complement pathway and an increase in 6 proteins associated with the lectin and classical complement pathways. The correlation with a shift in complement pathways suggests that compromised immunity could be responsible for the observed dysbiosis in the GI microbiome.

Comparison of two mouthrinses in relation to salivary flow and perceived dryness.

OBJECTIVE: To compare measures of dry mouth following extended use of an alcohol-based mouthrinse (LISTERINE Antiseptic [LA]) and a non-alcohol-based mouthrinse (Crest Pro-Health Rinse [CPH]) on healthy adults with "normal" salivary flow. METHODS: This single-site, randomized, observer-blinded, parallel study compared unstimulated whole salivary flow and perceived dryness following daily use at weeks 4 and 12 versus baseline. Noninferiority, between-treatment flow comparisons (0.15 mL/min margin), and between-treatment comparisons of the mean Bluestone Mouthfeel Questionnaire (BMQ) visual analog scale scores were made using analysis of covariance. RESULTS: Measures of dry mouth were comparable between mouthrinses, as demonstrated by both noninferiority of LA versus CPH flow (P < .001) and no significant differences between groups in the BMQ measures at 4 or 12 weeks. CONCLUSIONS: Extended use of an alcohol-based mouthrinse is no more likely to cause reduction in salivary flow or perceived dryness in individuals with normal salivary flow compared with a non-alcohol-based mouthrinse (CPH).

Evaluation of a dentifrice containing 8% arginine, calcium carbonate, and sodium monofluorophosphate to prevent enamel loss after erosive challenges using an intra-oral erosion model.

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: 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.

Evaluation of a dentifrice containing 8% arginine, calcium carbonate, and sodium monofluorophosphate to repair acid-softened enamel using an intra-oral remineralization model.

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: 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.

Review of preclinical studies on treatment of mucositis and associated pain.

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.

Toothbrush efficacy for plaque removal.

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.

A dermatology outpatient waiting list initiative.

Skin disease is the most common reason for people to present to their general practitioner (GP) with a new episode of disease. In April 2010 there were estimated 23,000 patients on dermatology outpatient waiting lists in Ireland, including almost 11,000 patients waiting over 6 months. We analysed the data of 200 dermatology outpatient visits scheduled under an initiative to target patients waiting more than 120 days for a new dermatology outpatient appointment. There were 171 (85.5%) patients seen, 29 (14.5%) patients did not attend the appointment. The data from 161 patients seen under the initiative was included in the analysis. Skin lesions accounted for 81 (50%) referrals, of these 71 (44%) patients had benign skin lesions and 10 (6%) patients were considered to have suspicious skin lesions. There was no case of malignant melanoma. After the initial consultation, 66% (106) of the patients were discharged to their primary care physician.

In vivo effects of a new dentifrice containing 1.5% arginine and 1450 ppm fluoride on plaque metabolism.

OBJECTIVE: This paper presents the results of a clinical study assessing the in vivo effects on plaque metabolism of a new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride compared to a commercially available dentifrice containing 1450 ppm fluoride alone. METHODS: A four-week, parallel, randomized, double-blind clinical study using 54 subjects was conducted at the New York University College of Dentistry Bluestone Center for Clinical Research. Two study groups used the following products for two weeks: 1) a dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride as sodium monofluorophosphate (MFP; test); and 2) a commercial silica dentifrice with 1450 ppm fluoride as sodium fluoride (NaF; control). In the following two-week period, all subjects used the control product. The effects of product use on plaque metabolism in vivo were assessed by conducting ex vivo analyses at baseline, after two weeks of assigned product use, and after two weeks of control product use. These plaque analyses comprised pH measurements before and after an in vivo sucrose rinse, and measurements of ammonia production and lactate production. RESULTS: The study showed that subjects using the test dentifrice, containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride, had significantly higher plaque pH values before the sucrose challenge than those using the commercially available control dentifrice (p < or = 0.01). Plaque samples from subjects using the arginine-containing dentifrice also produced significantly higher levels of ammonia (p < or = 0.01). Subjects using the arginine-containing dentifrice also had a directionally higher plaque pH after the sucrose challenge, and their plaque samples produced a directionally lower level of lactate during the two-week treatment period compared to subjects using the control dentifrice. Following two weeks of subsequent use of the control product, there were no significant differences in plaque metabolism measures between groups. CONCLUSION: A new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride has been shown in this study to modulate plaque metabolism, increasing ammonia production and decreasing lactate production, thereby increasing plaque pH to help restore a pH-neutral environment.

HIV infection affects Streptococcus mutans levels, but not genotypes.

We report a clinical study that examines whether HIV infection affects Streptococcus mutans colonization in the oral cavity. Whole stimulated saliva samples were collected from 46 HIV-seropositive individuals and 69 HIV-seronegative control individuals. The level of S. mutans colonization was determined by conventional culture methods. The genotype of S. mutans was compared between 10 HIV-positive individuals before and after highly active antiretroviral therapy (HAART) and 10 non-HIV-infected control individuals. The results were analyzed against viral load, CD4+ and CD8+ T-cell counts, salivary flow rate, and caries status. We observed that S. mutans levels were higher in HIV-infected individuals than in the non-HIV-infected control individuals (p = 0.013). No significant differences in S. mutans genotypes were found between the two groups over the six-month study period, even after HAART. There was a bivariate linear relationship between S. mutans levels and CD8+ counts (r = 0.412; p = 0.007), but not between S. mutans levels and either CD4+ counts or viral load. Furthermore, compared with non-HIV-infected control individuals, HIV-infected individuals experienced lower salivary secretion (p = 0.009) and a positive trend toward more decayed tooth surfaces (p = 0.027). These findings suggest that HIV infection can have a significant effect on the level of S. mutans, but not genotypes.

Inheritance of occlusal topography: a twin study.

AIM: This was to determine the relative contribution of genetic factors on the morphology of occlusal surfaces of mandibular primary first molars by employing the twin study model. METHODS: The occlusal morphology of mandibular primary first molar teeth from dental casts of 9 monozygotic (MZ) twin pairs and 12 dizygotic (DZ) twin pairs 4 to 7 years old, were digitized by contact-type three-dimensional (3D) scanner. To compare the similarity of occlusal morphology between twin sets, each twin pair of occlusal surfaces was superimposed to establish the best fit by using computerized least squared techniques. Heritability was computed using a variance component model, adjusted for age and gender. RESULTS: DZ pairs demonstrated a greater degree of occlusal morphology variance. The total amount of difference in surface overlap was 0.0508 mm (0.0018 (inches) for the MZ (n=18) sample and 0.095 mm (0.0034 inches) for the DZ (n=24) sample and were not statistically significant (p=0.2203). The transformed mean differences were not statistically significantly different (p=0.2203). Heritability estimates of occlusal surface areas for right and left mandibular primary first molars were 97.5% and 98.2% (p<0.0001), respectively. CONCLUSIONS: Occlusal morphology of DZ twin pairs was more variable than that of MZ twin pairs. Heritability estimates revealed that genetic factors strongly influence occlusal morphology of mandibular primary first molars.

Microbial acid production (Clinpro Cario L-Pop) and dental caries in infants and children.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic utility of the Clinpro Cario-L-Pop test as it relates to dental caries rates and severity in infants and children. METHOD AND MATERIALS: The study population was comprised of 771 infants and children who were on average 5.2 years of age (range of 1.5 to 8 years of age). Examiners conducted dental caries clinical examination using established criteria. In addition, lesion severity was determined be measuring its depth. An indicator swab was applied to the tongue dorsum until completely moistened with saliva. The indicator swab was processed according to the manufacturer's instructions, and acid production was assessed with the aid of a color chart. RESULTS: Twenty-three percent of children were caries free, and 7% (n = 50) of participants were categorized as having low production of lactic acid (scores 1 to 3), 17% (n = 135) moderate production of lactic acid (scores 4 to 6), and 76% (n = 586) high production of lactic acid (scores 7 to 9). There was a tendency for moderate and high lactic acid formers to exhibit higher surface-based caries prevalence rates, higher rates for deep dentinal lesions, and increased lesion severity. There was a linear increase of white spot surface-based lesions from low to high lactic acid formers and for initial dentinal lesions. Clinpro Cario-L-Pop test results, when controlling for age and gender, significantly distinguished caries-free participants from those exhibiting any form of decay. CONCLUSION: These results suggest that Clinpro Cario-L-Pop test was useful in explaining elevated frequency and severity of dental caries in spite of the high levels of decay and of microbial acid production observed in this population.

Microbial risk indicators of early childhood caries.

The aim of this study was to use molecular identification methods, such as 16S RNA gene sequence and reverse-capture checkerboard hybridization, for identification of the bacteria associated with dental caries and with dental health in a subset of 204 twins aged 1.5 to 7 years old. A total of 448 plaque samples (118 collected from caries-free subjects and 330 from caries-active subjects) were used for analysis. We compared the bacteria found in biofilms of children exhibiting severe dental caries, with different degrees of lesion severity, with those found in biofilms of caries-free children. A panel of 82 bacterial species was selected, and a PCR-based reverse-capture checkerboard method was used for detection. A simple univariate test was used to determine the overabundance and underabundance of bacterial species in the diseased and in the healthy groups. Features identified with this univariate test were used to construct a probabilistic disease prediction model. Furthermore, a method for the analysis of global patterns of gene expression was performed to permit simultaneous analysis of the abundance of significant species by allowing cross-bacterial comparisons of abundance profiles between caries-active and caries-free subjects. Our results suggested that global patterns of microbial abundance in this population are very distinctive. The top bacterial species found to be overabundant in the caries-active group were Actinomyces sp. strain B19SC, Streptococcus mutans, and Lactobacillus spp., which exhibited an inverse relationship to beneficial bacterial species, such as Streptococcus parasanguinis, Abiotrophia defectiva, Streptococcus mitis, Streptococcus oralis, and Streptococcus sanguinis.

Longitudinal analysis of heritability for dental caries traits.

The role of genetic and environmental factors on dental caries progression in young children was determined. A detailed caries assessment was performed in 2 examinations on 314 pairs of twins initially 1.5 to 8 years old. Surface-based caries prevalence rates (SBCPR) and lesion severity (LSI) were computed. Heritability estimates were calculated by SOLAR software. Analyses were performed on all ages combined and by age group (1.5-< 4; 4-6; > 6). Overall heritability estimates (H) of net increments SBCPRs were H = 30.0 (p < 0.0001), and were greatest for the youngest (H = 30.0) and oldest groups (H = 46.3). Overall LSI heritability estimates [H = 36.1 (p < 0.0001)] were also greatest for the youngest (H = 51.2) and oldest groups (H = 50.6). Similar findings were found for net increments of occlusal surfaces and deep dentinal lesions SBCPRs (H = 46.4-56.2). These findings are consistent with a significant genetic contribution to dental caries progression and severity in both emerging primary and permanent dentitions.

Dental caries and microbial acid production in twins.

OBJECTIVE: To determine the relative contribution of genetic and environmental stimuli on dental caries traits and microbial acid production in a twin model. METHODS: Dental caries examinations and microbial acid production assays were performed on 388 pairs of twins 1.5-8 years old from the city of Montes Claros, Brazil. Genotyping 8 polymorphic DNA markers determined zygosity. Caries exams followed NIDCR criteria modified to distinguish white spot lesions from cavitated lesions. Surface-based caries prevalence rates (SBCPR) were computed and lesion severity was determined by a weighted index (LSI). Biofilm samples were collected from the tongue using a lactic acid indicator swab. Assay scores were categorized based on acid formation as 1 = low, 2 = medium, and 3 = high. Heritability analyses were performed using the SOLAR software package. RESULTS: Heritability estimates for SBCPRs, LSI and for microbial acid production were H = 76.3 (p < 0.001), H = 70.6 (p < 0.001), H = 16.2 (p = 0.0078), respectively. Treating microbial acid production as a covariate in the SBCPR and LSI models did not significantly alter the heritability estimates, i.e. H = 76.5 (p < 0.001) and H = 70.8 (p < 0.001), respectively. CONCLUSIONS: These results suggest that variation in dental caries surface traits has a significant genetic contribution and that microbial acid production is modulated by the environment.

Mutans streptococci in preschool twins.

OBJECTIVE: The purpose of this study was to determine whether genetic factors influence variation in salivary levels of the mutans streptococci (MS) in preschool twins. DESIGN: The study population consisted of 48 pairs of monozygotic (MZ) twins and 54 pairs of dizygotic (DZ) twins. Genotyping eight highly polymorphic DNA markers determined zygosity. Demographic data and antibiotic exposure as reported by mothers were obtained by a face-to-face interview. Salivary levels of MS were determined by the Stripmutanstrade mark test. Test results are reported on a scale of 0-3. Regression analysis, two sample t-tests and structural equation modeling were applied to analyse the data. RESULTS: Only 6% of the participants ever visited a dentist (F component of the DMFS was 0 for this population). Average salivary scores for the mutans streptococci were significantly different between MZ (1.1+/-0.1) and DZ (0.8+/-0.1) twins (p=0.021). High salivary levels of MS (scores 2 and 3) were observed in 42% of MZ twins and in 26% of DZ twins. Regression analysis on the MS salivary levels revealed no significant effects of age, gender and antibiotic intake for MZ or DZ twins. The heritability of mutans streptococci colonisation in 48 pairs MZ and in 26 pairs of DZ twins was estimated to be 52%. The non-shared environment contribution was estimated to be 48%. CONCLUSIONS: These results suggest that variation in the salivary levels of the mutans streptococci is significantly contributed by genetic factors.

A preliminary analysis of the dental informatics literature.

Dental informatics is an emerging discipline applying computer and information science to dental practice, research, education, and management. To date, the dental informatics research literature has not been comprehensively reviewed. This study reports an initial analysis of the dental informatics literature. We developed an initial, comprehensive retrieval strategy to locate dental informatics citations in MEDLINE (1966-April 2003), including three concepts: dentistry, computers, and research. After refinement of the search, we manually classified the final set into four categories: (1) non-dental; (2) dental, but neither dental informatics nor IT-related; (3) dental informatics; and (4) IT in dentistry. We analyzed informatics and IT-related citations regarding their distribution across journals, growth rate, the number of authors and their publication frequency, and content as expressed by Medical Subject Headings (MeSH). The final set of citations (n = 3872) consisted of: 12% non-dental articles; 59% dental, but not informatics- or IT-related articles; 16% informatics-related articles; and 13% IT-related articles. Informatics-related citations appeared in 176 journals, and IT-related citations in 206 journals. Approximately 50 papers are currently published in both categories yearly. While a great many authors have contributed to this literature, very few have published more than three papers. Main topics of articles included "Imaging and Image Processing", "Computer-aided Diagnosis and Therapy", "Computer-aided Instruction", and "Other". The dental informatics literature is small, but growing. Imaging and image processing predominate as research topics.

Medication usage and dental caries outcome-related variables in HIV/AIDS patients.

The purpose of this study was to access current medication usage by HIV/AIDS patients and its effects on dental caries and on unstimulated salivary flow rates. Thirty females and 127 males (mean age = 39.6 +/- 7.4 years), of whom 46% were White/Non-Hispanic, 39% African-American, and 15% Hispanic, were examined and interviewed at the Bering Dental Clinic, Houston, Texas. The mean time in years after seroconversion was 5.4 +/- 4.1. Calibrated examiners performed dental caries examination (DMFS) with dental explorers and bitewing radiographs. Interviews were carried out with pretested questionnaires, and medication usage was assessed by illustrative examples of HIV/AIDS medications. Salivary flow rates were determined gravimetrically (mL/min). Bivariate analysis and analysis of variance (ANOVA) were used to analyze the data. Because there were no race or gender effects on dental caries outcome variables or salivary flow rates, separate logistic regression models for medication usage were generated, which were adjusted for age and CD4+ cell counts. Patients who, currently, were receiving antiretroviral therapy (ART) had a lower occurrence of dental caries than patients not taking these medications. An unexpected finding in the lower caries rate group was a decrease in salivary flow rates, which was a probable oral side effect of ART. It appears from this cross-sectional study that systemic medication for the management of HIV disease has no significant detrimental effect on the dentition.