Nonrestorative Treatments for Caries: Systematic Review and Network Meta-analysis.

The goal of nonrestorative or non- and microinvasive caries treatment (fluoride- and nonfluoride-based interventions) is to manage the caries disease process at a lesion level and minimize the loss of sound tooth structure. The purpose of this systematic review and network meta-analysis was to summarize the available evidence on nonrestorative treatments for the outcomes of 1) arrest or reversal of noncavitated and cavitated carious lesions on primary and permanent teeth and 2) adverse events. We included parallel and split-mouth randomized controlled trials where patients were followed for any length of time. Studies were identified with MEDLINE and Embase via Ovid, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews. Pairs of reviewers independently conducted the selection of studies, data extraction, risk-of-bias assessments, and assessment of the certainty in the evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Data were synthesized with a random effects model and a frequentist approach. Forty-four trials (48 reports) were eligible, which included 7,378 participants and assessed the effect of 22 interventions in arresting or reversing noncavitated or cavitated carious lesions. Four network meta-analyses suggested that sealants + 5% sodium fluoride (NaF) varnish, resin infiltration + 5% NaF varnish, and 5,000-ppm F (1.1% NaF) toothpaste or gel were the most effective for arresting or reversing noncavitated occlusal, approximal, and noncavitated and cavitated root carious lesions on primary and/or permanent teeth, respectively (low- to moderate-certainty evidence). Study-level data indicated that 5% NaF varnish was the most effective for arresting or reversing noncavitated facial/lingual carious lesions (low certainty) and that 38% silver diamine fluoride solution applied biannually was the most effective for arresting advanced cavitated carious lesions on any coronal surface (moderate to high certainty). Preventing the onset of caries is the ultimate goal of a caries management plan. However, if the disease is present, there is a variety of effective interventions to treat carious lesions nonrestoratively.

Genetic Association of MMP10, MMP14, and MMP16 with Dental Caries.

Matrix metalloproteinases (MMPs), which degrade extracellular proteins as part of a variety of physiological processes, and their inhibitors have been implicated in the dental caries process. Here we investigated 28 genetic variants spanning the MMP10, MMP14, and MMP16 genes to detect association with dental caries experience in 13 age- and race-stratified (n = 3,587) samples from 6 parent studies. Analyses were performed separately for each sample, and results were combined across samples by meta-analysis. Two SNPs (rs2046315 and rs10429371) upstream of MMP16 were significantly associated with caries in an individual sample of white adults and via meta-analysis across 8 adult samples after gene-wise adjustment for multiple comparisons. Noteworthy is SNP rs2046315 (p = 8.14 × 10-8) association with caries in white adults. This SNP was originally nominated in a genome-wide-association study (GWAS) of dental caries in a sample of white adults and yielded associations in a subsequent GWAS of surface level caries in white adults as well. Therefore, in our study, we were able to recapture the association between rs2046315 and dental caries in white adults. Although we did not strengthen evidence that MMPs 10, 14, and 16 influence caries risk, MMP16 is still a likely candidate gene to pursue.

Genetic Association of MPPED2 and ACTN2 with Dental Caries.

The first genome-wide association study of dental caries focused on primary teeth in children aged 3 to 12 yr and nominated several novel genes: ACTN2, EDARADD, EPHA7, LPO, MPPED2, MTR, and ZMPSTE24. Here we interrogated 156 single-nucleotide polymorphisms (SNPs) within these candidate genes for evidence of association with dental caries experience in 13 race- and age-stratified samples from 6 independent studies (n = 3600). Analysis was performed separately for each sample, and results were combined across samples via meta-analysis. MPPED2 was significantly associated with caries via meta-analysis across the 5 childhood samples, with 4 SNPs showing significant associations after gene-wise adjustment for multiple comparisons (p < .0026). These results corroborate the previous genome-wide association study, although the functional role of MPPED2 in caries etiology remains unknown. ACTN2 also showed significant association via meta-analysis across childhood samples (p = .0014). Moreover, in adults, genetic association was observed for ACTN2 SNPs in individual samples (p < .0025), but no single SNP was significant via meta-analysis across all 8 adult samples. Given its compelling biological role in organizing ameloblasts during amelogenesis, this study strengthens the hypothesis that ACTN2 influences caries risk. Results for the other candidate genes neither proved nor precluded their associations with dental caries.

Clam-associated vibriosis, USA, 1988-2010.

Infections with Vibrio spp. have frequently been associated with consumption of bivalve molluscs, especially oysters, but illness associated with clams has also been well documented. We describe the 2312 domestically acquired foodborne Vibrio infections reported to the Cholera and Other Vibrio Illness Surveillance system from 1988 to 2010. Clams were associated with at least 4% (93 persons, 'only clams') and possibly as many as 24% (556 persons, 'any clams') of foodborne cases. Of those who consumed 'only clams', 77% of infections were caused by V. parahaemolyticus. Clam-associated illnesses were generally similar to those associated with other seafood consumption. Clams associated with these illnesses were most frequently harvested from the Atlantic coastal states and eaten raw. Our study describes the contribution of clams to the overall burden of foodborne vibriosis and indicates that a comprehensive programme to prevent foodborne vibriosis need to address the risks associated with clams.

Increased enamel hypoplasia and very low birthweight infants.

Birth cohort studies of developmental defects of enamel (DDE) and early childhood caries (ECC) in very low birthweight (VLBW) and normal birthweight (NBW) infants are rare. In this birth cohort of 234 VLBW and 234 NBW infants, we report the incidence of ECC and DDE at 8 and 18-20 mos of corrected age. Infant medical and maternal socio-demographic data were abstracted from medical records at birth. Dental assessments for ECC and DDE (enamel hypoplasia, demarcated and diffuse opacities) were completed at 8 and 18-20 mos. The incidence of hypoplasia was significantly higher in VLBW compared with NBW infants (8 mos, 19% vs. 2%; 18 mos, 31% vs. 8%). The incidence of ECC (International Caries Detection and Assessment System: ICDAS ≥ 2) was 1.4% (8 mos) and 12% (18-20 mos) and was similar between the VLBW and NBW groups. At both ages, using a beta-binomial regression model to control for potential confounders (maternal and infant characteristics), we found increased risk for enamel hypoplasia among the VLBW infants compared with the NBW infants. African Americans had a lower risk for enamel hypoplasia at 18-20 mos. The VLBW infants should be monitored for ECC due to the presence of enamel hypoplasia.

The economic burden of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA).

The economic impact of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) remains unclear. We developed an economic simulation model to quantify the costs associated with CA-MRSA infection from the societal and third-party payer perspectives. A single CA-MRSA case costs third-party payers $2277-$3200 and society $7070-$20 489, depending on patient age. In the United States (US), CA-MRSA imposes an annual burden of $478 million to 2.2 billion on third-party payers and $1.4-13.8 billion on society, depending on the CA-MRSA definitions and incidences. The US jail system and Army may be experiencing annual total costs of $7-11 million ($6-10 million direct medical costs) and $15-36 million ($14-32 million direct costs), respectively. Hospitalization rates and mortality are important cost drivers. CA-MRSA confers a substantial economic burden on third-party payers and society, with CA-MRSA-attributable productivity losses being major contributors to the total societal economic burden. Although decreasing transmission and infection incidence would decrease costs, even if transmission were to continue at present levels, early identification and appropriate treatment of CA-MRSA infections before they progress could save considerable costs.

Genome-wide association scan for childhood caries implicates novel genes.

Dental caries is the most common chronic disease in children and a major public health concern due to its increasing incidence, serious health and social co-morbidities, and socio-demographic disparities in disease burden. We performed the first genome-wide association scan for dental caries to identify associated genetic loci and nominate candidate genes affecting tooth decay in 1305 US children ages 3-12 yrs. Affection status was defined as 1 or more primary teeth with evidence of decay based on intra-oral examination. No associations met strict criteria for genome-wide significance (p < 10E-7); however, several loci (ACTN2, MTR, and EDARADD, MPPED2, and LPO) with plausible biological roles in dental caries exhibited suggestive evidence for association. Analyses stratified by home fluoride level yielded additional suggestive loci, including TFIP11 in the low-fluoride group, and EPHA7 and ZMPSTE24 in the sufficient-fluoride group. Suggestive loci were tested but not significantly replicated in an independent sample (N = 1695, ages 2-7 yrs) after adjustment for multiple comparisons. This study reinforces the complexity of dental caries, suggesting that numerous loci, mostly having small effects, are involved in cariogenesis. Verification/replication of suggestive loci may highlight biological mechanisms and/or pathways leading to a fuller understanding of the genetic risks for dental caries.

Id3 is a novel atheroprotective factor containing a functionally significant single-nucleotide polymorphism associated with intima-media thickness in humans.

RATIONALE: The gene encoding the helix-loop-helix transcription factor Id3 (inhibitor of differentiation-3) is located within atherosclerosis susceptibility loci of both mice and humans, yet its influence on atherosclerosis is not known. OBJECTIVE: The present study sought to determine whether polymorphisms in the ID3 gene were associated with indices of atherosclerosis in humans and if loss of Id3 function modulated atherogenesis in mice. METHODS AND RESULTS: Six tagging single-nucleotide polymorphisms (SNPs) (tagSNPs) in the human ID3 gene were assessed in participants of the Diabetes Heart Study. One tagSNP, rs11574, was independently associated with carotid intima-media thickness (IMT). The human ID3 variant at rs11574 results in an alanine to threonine substitution in the C terminus. To determine the effect of this polymorphism on the basic function of Id3, site-directed mutagenesis of the human ID3 gene at rs11574 was performed. Results demonstrated a significant reduction in coimmunoprecipitation of the known E-protein partner, E12, with Id3 when it contains the sequence encoded by the risk allele (Id3105T). Further, Id3105T had an attenuated ability to modulate E12-mediated transcriptional activation compared to Id3 containing the ancestral allele (Id3105A). Microarray analysis of vascular smooth muscle cells from WT and Id3(-/-) mice revealed significant modulation of multiple gene pathways implicated in atherogenesis. Moreover, Id3(-/-)ApoE(-/-) mice developed significantly more atherosclerosis in response to 32 weeks of Chow or Western diet feeding than Id3(+/+)ApoE(-/-) mice. CONCLUSIONS: Taken together, results provide novel evidence that Id3 is an atheroprotective factor and link a common SNP in the human ID3 gene to loss of Id3 function and increased IMT.

The helix-loop-helix factors Id3 and E47 are novel regulators of adiponectin.

Adiponectin is an adipocyte-derived cytokine with beneficial effects on insulin sensitivity and the development of atherosclerosis. Id3 is a helix-loop-helix factor that binds to E-proteins such as E47 and inhibits their binding to DNA. Although the helix-loop-helix factor sterol regulatory element binding protein (SREBP)-1c is a known activator of adiponectin transcription, this study provides the first evidence of a role for Id3 and E47 in adiponectin expression. Decreased Id3 in differentiating adipocytes correlates with increased adiponectin expression and forced expression of Id3 inhibits adiponectin expression. Moreover, Id3-null mice have increased adiponectin expression in visceral fat tissue and in serum. We demonstrate that E47 potentiates SREBP-1c-mediated adiponectin promoter activation and that Id3 can dose-dependently inhibit this action via interaction with E47. Mutation of a consensus E47 binding site results in nearly complete loss of promoter activation. Furthermore, we demonstrate E47 binding to the endogenous adiponectin promoter both in vitro and in vivo by chromatin immunoprecipitation analysis. Binding is not detected in undifferentiated cells which express Id3 but peaks during differentiation in parallel with Id3 decline. This promoter binding can be completely abolished by the overexpression of Id3 and is enhanced in adipose tissue null for Id3. These data establish Id3 and E47 as novel regulators of SREBP-1c-mediated adiponectin expression in differentiating adipocytes and provide evidence that Id3 regulates adiponectin expression in vivo.

Acidic proline-rich protein Db and caries in young children.

Polymorphic, acidic proline-rich proteins (PRPs) in saliva influence the attachment of bacteria associated with caries. Our aims were to detect one of three acidic PRP alleles of the PRH1 locus (Db) using polymerase chain-reaction (PCR) on genomic DNA, and to determine its association with caries. DNA was obtained from buccal swabs from Caucasian and African-American children, and their caries experience was recorded. PCR primers designed around exon 3 of the PRH1 locus gave a 416-base product representing Db and a 353-base product representing the other two alleles (Pa or Pif). In Caucasians, Db gene frequency was 14%, similar to Db protein from parotid saliva. In African-Americans, however, it was 37%, 18% lower than Db from parotid saliva (reported previously). Compared with African-Americans, all Caucasians had significantly greater Streptococcus mutans colonization, but only Db-negative Caucasians had significantly more caries. Alleles linked to Db may explain racial differences in caries experience.

Tuftelin, mutans streptococci, and dental caries susceptibility.

The purpose of this study was to identify genetic factors that contribute to dental caries susceptibility, either alone or in combination with environmental factors. Dental examinations were performed and buccal swab samples collected from 3- to 5-year-old children with at least 4 surfaces of decay, or with no evidence of decay. SNP assays for each of 6 candidate genes were performed for all cases and controls. Chi-square analysis and regression analysis were used for the evaluation of individual gene effects, environmental effects, and gene-environment interactions. There were no significant associations between single candidate genes and caries susceptibility. Levels of S. mutans were positively and Lactobacilli were negatively associated with caries. Regression analysis revealed a significant interaction between tuftelin and S. mutans, with 26.8% of the variation in dmfs explained by the interaction. Future research will focus on the identification of these additional factors and the development of functional assays so that these interactions can be better understood.

Perceived dental needs of children enrolled in Iowa's Medicaid Supplemental Security Income (SSI) health plan.

The purpose of this study was to determine parental perception of the oral health needs of children with disabilities and whether or not they had difficulty obtaining dental care. A survey of parents of children enrolled in the Medicaid Supplemental Security Income (SSI) health plan in Iowa showed that 68 percent of children had dental needs during the previous year. Of these children, parents reported that 9.4 percent had a 'big problem' getting that care, 8.1 percent had a 'small problem' getting care and 82.5 percent stated that getting dental care was 'not a problem.' There were significantly more dental needs reported in children in the older age groups (> or = 5 years) and those with more years of experience in the program (p < 0.01). Further study is necessary to determine the types of barriers faced by those in the SSI program seeking dental care.

Prevalence of enamel hypoplasia and isolated opacities in the primary dentition.

PURPOSE: Enamel hypoplasia is of interest to both the clinician and the basic scientist because it may indicate an increased risk for caries and can contribute to the understanding of enamel development. The purpose of this paper is to report the prevalence of enamel hypoplasia and isolated enamel opacities in a cohort of healthy, well-nourished children in Iowa. METHODS: The study sample consisted of 698 children examined at 4-5 years of age. Individual tooth surfaces were scored for the presence of enamel hypoplasia (EH) and isolated enamel opacities. Prevalence of EH and isolated opacities were determined by tooth type and by gender. RESULTS: Six percent of the children examined had at least one tooth with EH; 27% had at least one tooth with isolated enamel opacities. There was no difference in the prevalence of EH between boys and girls, but significantly more boys than girls had enamel opacities. CONCLUSIONS: The prevalence of enamel defects in this study group is comparable to that seen in other studies of normally developed children except that in this study, the primary tooth types most commonly affected with enamel hypoplasia or isolated opacities were mandibular second molars and maxillary second molars, respectively.

Adapalene gel 0.1% is effective and well tolerated in acne patients in a dermatology practice setting.

The US Food and Drug Administration has approved adapalene gel 0.1% for use in the treatment of acne vulgaris. The objective of our study was to evaluate the efficacy and tolerability of adapalene gel 0.1% in the treatment of acne vulgaris in a clinical practice. We used a 12-week, multicenter, open-label, noncomparative phase 4 study of adapalene gel 0.1%. The study involved approximately 600 dermatologists in the United States and included 2,545 healthy men and nonpregnant women older than 14 years who had mild or moderate acne vulgaris. Of the patients enrolled, 75% completed the study and most of them (89%) showed an improvement in their acne (clear of acne or marked, definite, or minimal improvement) from baseline. Most patients (69%) were satisfied or very satisfied with adapalene therapy, and most (80%) wished to continue treatment. Only 3.7% of patients enrolled reported treatment-related adverse events (n=94), the most common being skin irritation (2.2%). We conclude from this open-label trial in a dermatology practice setting that adapalene gel 0.1% was effective and well tolerated and had a favorable safety profile. Furthermore, compliance with once-daily application of adapalene was rated as high by 92% of patients who responded to a self-assessment questionnaire.

Treatment alternatives for sublingual traumatic ulceration (Riga-Fede disease).

The term Riga-Fede disease has been used historically to describe a traumatic ulceration that occurs on the ventral surface of the tongue in neonates and infants. It is frequently associated with natal or neonatal teeth but may also occur in older infants after the eruption of primary lower incisors. Failure to diagnose and properly treat this lesion can result in dehydration and inadequate nutrient intake for the infant. Treatment should begin conservatively and should focus on eliminating the source of trauma. A case is presented in which modification of sharp tooth surfaces by the Pediatric Dentist and changes in feeding techniques by the parent were used successfully to resolve this lesion. By working together, the parent and the Pediatric Dentist can achieve positive results in a short period of time with minimal trauma to the infant.

Results of a nationwide survey of chest radiography: comparison with results of a previous study.

PURPOSE: To provide public health information by means of measurement of the radiation exposures that patients undergoing chest radiography would receive and to compare the results with those of a similar previous survey. MATERIALS AND METHODS: Surveyed facilities were randomly selected from each state. Patient exposure was evaluated along with film processing, half-value layer, and image quality. Additional information obtained concerned type of equipment, facility work load, radiographic technique, screen-film system, and grid type. RESULTS: Mean entrance air kerma in all facilities was 141 microGy (16.1 mR). Mean kilovoltage in all facilities was 101 kV. In 1994, 140 (90%) of 156 hospitals (vs 71% in 1984) and 92 (58%; nearly double the percentage in 1984) of 159 nonhospital sites were using grids. Scoring with the imaging test tool resulted in a mean spatial resolution of 2.3 cycles per millimeter, and a mean low-contrast sensitivity of about 3%. Two hundred fifty-three (80%) of 315 facilities surveyed were processing film at minimum acceptable performance levels. CONCLUSION: Mean entrance air kerma for all facilities did not substantially change. Although increased grid usage would lead to the expectation of higher measured exposures, this was offset by an increase in the use of faster screen-film combinations.

Nonsense mutations in the COL1A1 gene preferentially reduce nuclear levels of mRNA but not hnRNA in osteogenesis imperfecta type I cell strains.

Osteogenesis imperfecta (OI) is a heterogeneous disorder of type I collagen resulting in varying degrees of severity. The mildest form of OI (Type I) is associated with bone fragility, normal or near normal stature and blue sclerae. All forms of OI are the result of mutations in COL1A1 or COL1A2, the genes that encode the proalpha1(I) and proalpha2(I) chains of type I collagen, respectively. Mutations identified in patients with OI type I lead to premature termination codons and allele-specific reductions of nuclear mRNA (termed nonsense-mediated mRNA decay or NMD), resulting in a COL1A1 null allele. In mammals, this process primarily effects RNA that co-purifies with the nuclear fraction of the cell. Using a semi-quantitative RT-PCR assay, we compare the relative amounts of normal and mutant transcripts in unprocessed hnRNA and mature mRNA isolated from the nuclear fraction of cells from 11 OI type I individuals with previously identified mutations distributed throughout the COL1A1 gene. While we detect about equal amounts of normal and mutant hnRNA from each cell strain, there is preferential reduction in the relative amount of mutant mRNA when compared to normal; only the cell strain with a mutation in the last exon escapes the major effects of NMD. Our data indicate that NMD targets mRNA rather than hnRNA for degradation, and that this occurs either during or after splicing but prior to cytoplasmic translation.

Time-resolved mid-infrared spectroscopy: methods and biological applications.

Recent developments in time-resolved infrared spectroscopy have paved the way to probe transient intermediates with a high degree of functional group specificity on timescales as short as femtoseconds. This capability has been exploited in studies of biophysical phenomena ranging from protein folding/unfolding to ligand migration in proteins.

Nationwide survey of fluoroscopy: radiation dose and image quality.

PURPOSE: To determine the average abdominal entrance air kerma, low-contrast sensitivity, and spatial resolution in upper gastrointestinal tract fluoroscopy in the United States. MATERIALS AND METHODS: A random sample of fluoroscopic facilities was selected to be surveyed for the Nationwide Evaluation of X-ray Trends program. Measurements were performed by using a newly developed fluoroscopic phantom. The surveys were conducted by state radiation control personnel. RESULTS: Average air kerma rates 1 cm above the tabletop, free in air, were 43 mGy/min (n = 340). The rate increased to 64 mGy/min when a 1.6-mm-thick copper filter, which simulated the use of barium contrast medium, was added to increase attenuation. The average entrance air kerma, free in air, for radiographs was 3.4 mGy, and an average of 12 radiographs were obtained per examination. Of 352 facilities surveyed, 306 (87%) were able to resolve wire mesh with 20 or more lines per inch. Of 339 facilities for which percentage contrast could be calculated, 192 (57%) had minimum percentage contrast values of 4% or more. CONCLUSION: Spatial resolution for fluoroscopy is adequate for most of the facilities surveyed, but a substantial proportion of facilities could not visualize low-contrast test objects, which strongly suggests image quality problems.

Premature chain termination is a unifying mechanism for COL1A1 null alleles in osteogenesis imperfecta type I cell strains.

Nonsense and frameshift mutations, which predict premature termination of translation, often cause a dramatic reduction in the amount of transcript from the mutant allele (nonsense-mediated mRNA decay). In some genes, these mutations also influence RNA splicing and induce skipping of the exon that contains the nonsense codon. To begin to dissect how premature termination alters the metabolism of RNA from the COL1A1 gene, we studied nonsense and frameshift mutations distributed over exons 11-49 of the gene. These mutations were originally identified in 10 unrelated families with osteogenesis imperfecta (OI) type 1. We observed marked reduction in steady-state amounts of mRNA from the mutant allele in both total cellular and nuclear RNA extracts of cells from affected individuals, suggesting that nonsense-mediated decay of COL1A1 RNA is a nuclear phenomenon. Position of the mutation within the gene did not influence this observation. None of the mutations induced skipping of either the exon containing the mutation or, for the frameshifts, the downstream exons with the new termination sites. Our data suggest that nonsense and frameshift mutations throughout most of the COL1A1 gene result in a null allele, which is associated with the predictable mild clinical phenotype, OI type 1.