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1.  Community based study of sleep bruxism during early childhood 
Sleep medicine  2012;14(2):183-188.
Objectives
The aims for this study were to determine the prevalence of sleep-bruxism among young children, explore child behavior problems that may be associated with sleep-bruxism, and identify relations among sleep-bruxism, health problems, and neurocognitive performance.
Methods
The current study was a retrospective analysis of parent report surveys, and behavioral and neurocognitive assessments. Parents of 1953 preschool and 2888 first grade children indicated their child’s frequency of bruxism during sleep. A subsample of preschool children (n = 249) had additional behavioral, as well as neurocognitive assessments. Among the subsample, parents also reported on their child’s health, and completed the Child Behavioral Checklist; children were administered the Differential Ability Scales, and Pre-Reading Abilities subtests of the Developmental Neuropsychological Assessment.
Results
36.8% of preschoolers and 49.6% of first graders were reported to brux ≥ 1 time per week. Among the preschool subsample, bruxing was independently associated with increased internalizing behaviors (β = .17). Bruxism was also associated with increased health problems (β = .19), and increased health problems were associated with decreased neurocognitive performance (β = .22).
Conclusions
The prevalence of sleep-bruxism was high. A dynamic and potentially clinically relevant relation exists among sleep-bruxism, internalizing behaviors, health, and neurocognition. Pediatric sleep-bruxism may serve as a sentinel marker for possible adverse health conditions, and signal a need for early intervention. These results support the need for an interdisciplinary approach to pediatric sleep medicine, dentistry, and psychology.
doi:10.1016/j.sleep.2012.09.027
PMCID: PMC3616318  PMID: 23219144
Parasomnia; Health; Dentistry; Behavior; Neurocognitive; Pediatrics
2.  Genome-Wide Association Study of Periodontal Health Measured by Probing Depth in Adults Ages 18−49 years 
G3: Genes|Genomes|Genetics  2013;4(2):307-314.
The etiology of chronic periodontitis clearly includes a heritable component. Our purpose was to perform a small exploratory genome-wide association study in adults ages 18–49 years to nominate genes associated with periodontal disease−related phenotypes for future consideration. Full-mouth periodontal pocket depth probing was performed on participants (N = 673), with affected status defined as two or more sextants with probing depths of 5.5 mm or greater. Two variations of this phenotype that differed in how missing teeth were treated were used in analysis. More than 1.2 million genetic markers across the genome were genotyped or imputed and tested for genetic association. We identified ten suggestive loci (p-value ≤ 1E-5), including genes/loci that have been previously implicated in chronic periodontitis: LAMA2, HAS2, CDH2, ESR1, and the genomic region on chromosome 14q21-22 between SOS2 and NIN. Moreover, we nominated novel loci not previously implicated in chronic periodontitis or related pathways, including the regions 3p22 near OSBPL10 (a lipid receptor implicated in hyperlipidemia), 4p15 near HSP90AB2P (a heat shock pseudogene), 11p15 near GVINP1 (a GTPase pseudogene), 14q31 near SEL1L (an intracellular transporter), and 18q12 in FHOD3 (an actin cytoskeleton regulator). Replication of these results in additional samples is needed. This is one of the first research efforts to identify genetic polymorphisms associated with chronic periodontitis-related phenotypes by the genome-wide association study approach. Though small, efforts such this are needed in order to nominate novel genes and generate new hypotheses for exploration and testing in future studies.
doi:10.1534/g3.113.008755
PMCID: PMC3931564  PMID: 24347629
GWAS; chronic periodontitis
3.  Hygiene Self-Care of Older Adults in West Virginia: Effects of Gender 
Purpose
This study investigated whether oral hygiene self-care behavior differs between genders in older adults in Appalachia, a geographic area with significant oral health concerns. Identifying the practices of older adults may provide valuable information for designing interventions, and improving overall oral health outcomes.
Methods
As part of a larger, on-going study on cognition and oral health in later life in Appalachia, a sample of dentate, older adults without dementia aged 70 and above (n =245, 86 men and 159 women) received an oral assessment by either a dentist or dental hygienist. Psychometricians assessed cognition using a standardized battery of neuropsychological tests. They also administered the General Oral Health Assessment Index and conducted structured interviews concerning diet, oral hygiene practices, oral health, social support, income, and years of education.
Results
Over 80% of women (n = 128) and 52.3% of men (n = 45) reported brushing their teeth twice daily. Multivariate logistic regression analysis was conducted, controlling for socioeconomic status, social support (i.e., frequency of contacting friends and relatives), general oral health assessment items, number of decayed, missing, and filled surfaces, plaque index, and having regular dental visits. The results showed that women reported more frequent toothbrushing than their male counterparts (OR=4.04, 95% CI:1.93,8.42).
Conclusion
Older women in West Virginia had significantly better oral hygiene practices than older men, particularly regarding toothbrushing. Interventions are needed to improve older men’s dental hygiene behaviors to improve overall oral health outcomes.
PMCID: PMC3607540  PMID: 22947846
aged; self-care; gender differences; preventive behavior; Appalachia; oral hygiene
4.  Effects of Smoking and Genotype on the PSR Index of Periodontal Disease in Adults Aged 18–49 
Studies have found both genetic and environmental influences on chronic periodontitis. The purpose of this study was to examine the relationships among previously identified genetic variants, smoking status, and two periodontal disease-related phenotypes (PSR1 and PSR2) in 625 Caucasian adults (aged 18–49 years). The PSR Index was used to classify participants as affected or unaffected under the PSR1 and PSR2 phenotype definitions. Using logistic regression, we found that the form of the relationship varied by single nucleotide polymorphism (SNP): For rs10457525 and rs12630931, the effects of smoking and genotype on risk were additive; whereas for rs10457526 and rs733048, smoking was not independently associated with affected status once genotype was taken into consideration. In contrast, smoking moderated the relationships of rs3870371 and rs733048 with affected status such that former and never smokers with select genotypes were at increased genetic risk. Thus, for several groups, knowledge of genotype may refine the risk prediction over that which can be determined by knowledge of smoking status alone. Future studies should replicate these findings. These findings provide the foundation for the exploration of novel pathways by which periodontitis may occur.
doi:10.3390/ijerph9082839
PMCID: PMC3447590  PMID: 23066400
adult; chronic periodontitis; genetics; genomics; smoking
5.  Thresholds and tolerance of physical pain among young adults who self-injure 
Prevalence rates of nonsuicidal self-injury among college students range from 17% to 38%. Research indicates that individuals with borderline personality disorder who self-injure sometimes report an absence of pain during self-injury. Furthermore, self-injury in the absence of pain has been associated with more frequent suicide attempts. The present study examined pain thresholds and tolerance among 44 college students (11 who engaged in self-injury and 33 who did not). Pain thresholds and tolerance were measured using an algometer pressure device that was used to produce pain in previous laboratory research. Participants who engaged in self-injury had a higher pain tolerance than those who did not. In addition, participants who engaged in self-injury rated the pain as less intense than participants who did not. ANCOVAs revealed that depression was associated with pain rating and pain tolerance.
PMCID: PMC3008662  PMID: 21165371
Pain perception; Pain tolerance; Self-harm; Self-injury
6.  Recruitment of rural and cognitively impaired older adults for dental research 
The recruitment of community-dwelling older adults, particularly those with cognitive impairment and those residing in rural areas, has been consistently challenging for researchers, especially in the dental field. This study reports on recruitment experiences from an ongoing study investigating the association between oral health and cognitive status in later life. Multiple recruitment strategies, including educational presentations and traveling to participants’ homes, were used to enroll rural elderly participants with various levels of cognitive function. In general, multi-pronged, proactive recruitment strategies were more effective than traditional, passive methods in reaching participants with varying degrees of cognitive impairment.
The outcome of this study suggests that successful recruitment of such populations involves gaining the support of staff at relevant community organizations, informing community members (including older adults and their family members) of the project and the importance of oral health, and making data collection sites accessible for older adults.
doi:10.1111/j.1754-4505.2010.00150.x
PMCID: PMC2939742  PMID: 20831737
recruitment; elders; rural; cognitive impairment; underrepresented populations
7.  PROPRANOLOL AND D-CYCLOSERINE AS ADJUNCTIVE MEDICATIONS IN REDUCING DENTAL FEAR IN SEDATION PRACTICE 
SAAD digest  2010;26:27-35.
Extensive research and clinical experience have demonstrated the usefulness of sedation in helping fearful patients receive dental treatment, particularly when they have urgent treatment needs. In addition, the efficacy of behavioural programmes for managing dental fears is well established. While often these two approaches are seen as oppositional, our work in Seattle, Morgantown and at King’s College London Dental Institute demonstrates the complementarity of the two approaches. Using the example of two compounds, one very familiar, propranolol, and one that has recently become of interest, D-cycloserine, we wish to illustrate the manner in which these medications can be used to enhance behavioural approaches to managing dental anxiety.
PMCID: PMC2893885  PMID: 20151608
8.  Human Telomere Length Correlates to the Size of the Associated Chromosome Arm 
PLoS ONE  2009;4(6):e6013.
The majority of human telomere length studies have focused on the overall length of telomeres within a cell. In fact, very few studies have examined telomere length for individual chromosome arms. The objective of this study was to examine the relationship between chromosome arm size and the relative length of the associated telomere. Quantitative Fluorescence In Situ Hybridization (Q-FISH) was used to measure the relative telomere length of each chromosome arm in metaphases from cultured lymphocytes of 17 individuals. A statistically significant positive correlation (r = 0.6) was found between telomere length and the size of the associated chromosome arm, which was estimated based on megabase pair measurements from http://www.ncbi.nlm.nih.gov/projects/mapview/.
doi:10.1371/journal.pone.0006013
PMCID: PMC2695537  PMID: 19547752
9.  Cryptic Subtelomeric Rearrangements and X Chromosome Mosaicism: A Study of 565 Apparently Normal Individuals with Fluorescent In Situ Hybridization 
PLoS ONE  2009;4(6):e5855.
Five percent of patients with unexplained mental retardation have been attributed to cryptic unbalanced subtelomeric rearrangements. Half of these affected individuals have inherited the rearrangement from a parent who is a carrier for a balanced translocation. However, the frequency of carriers for cryptic balanced translocations is unknown. To determine this frequency, 565 phenotypically normal unrelated individuals were examined for balanced subtelomeric rearrangements using Fluorescent In Situ hybridization (FISH) probes for all subtelomere regions. While no balanced subtelomeric rearrangements were identified, three females in this study were determined to be mosaic for the X chromosome. Mosaicism for XXX cell lines were observed in the lymphocyte cultures of 3 in 379 women (0.8%), which is a higher frequency than the 1 in 1000 (0.1%) reported for sex chromosome aneuploidies. Our findings suggest that numerical abnormalities of the X chromosome are more common in females than previously reported. Based on a review of the literature, the incidence of cryptic translocation carriers is estimated to be approximately 1/8,000, more than ten-fold higher than the frequency of visible reciprocal translocations.
doi:10.1371/journal.pone.0005855
PMCID: PMC2688762  PMID: 19516895
10.  Study protocol of the Center for Oral Health Research in Appalachia (COHRA) etiology study 
BMC Oral Health  2008;8:18.
Background
People in Appalachia experience some of the worst oral health in the United States. To develop effective intervention and prevention strategies in Appalachia, we must understand the complex relationships among the contributing factors and how they affect the etiology of oral diseases. To date, no such comprehensive analysis has been conducted. This report summarizes the characteristics of the sample and describes the protocol of a study determining contributions of individual, family, and community factors to oral diseases in Appalachian children and their relatives.
Methods/Design
Families participated in a comprehensive assessment protocol involving interviews, questionnaires, a clinical oral health assessment, a microbiological assessment, and collection of DNA. The design of the study is cross-sectional.
Conclusion
Due to its multilevel design and large, family-based sample, this study has the potential to greatly advance our understanding of factors that contribute to oral health in Appalachian children.
doi:10.1186/1472-6831-8-18
PMCID: PMC2443132  PMID: 18522740
11.  Genome-wide association Scan of dental caries in the permanent dentition 
BMC Oral Health  2012;12:57.
Background
Over 90% of adults aged 20 years or older with permanent teeth have suffered from dental caries leading to pain, infection, or even tooth loss. Although caries prevalence has decreased over the past decade, there are still about 23% of dentate adults who have untreated carious lesions in the US. Dental caries is a complex disorder affected by both individual susceptibility and environmental factors. Approximately 35-55% of caries phenotypic variation in the permanent dentition is attributable to genes, though few specific caries genes have been identified. Therefore, we conducted the first genome-wide association study (GWAS) to identify genes affecting susceptibility to caries in adults.
Methods
Five independent cohorts were included in this study, totaling more than 7000 participants. For each participant, dental caries was assessed and genetic markers (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Due to the heterogeneity among the five cohorts regarding age, genotyping platform, quality of dental caries assessment, and study design, we first conducted genome-wide association (GWA) analyses on each of the five independent cohorts separately. We then performed three meta-analyses to combine results for: (i) the comparatively younger, Appalachian cohorts (N = 1483) with well-assessed caries phenotype, (ii) the comparatively older, non-Appalachian cohorts (N = 5960) with inferior caries phenotypes, and (iii) all five cohorts (N = 7443). Top ranking genetic loci within and across meta-analyses were scrutinized for biologically plausible roles on caries.
Results
Different sets of genes were nominated across the three meta-analyses, especially between the younger and older age cohorts. In general, we identified several suggestive loci (P-value ≤ 10E-05) within or near genes with plausible biological roles for dental caries, including RPS6KA2 and PTK2B, involved in p38-depenedent MAPK signaling, and RHOU and FZD1, involved in the Wnt signaling cascade. Both of these pathways have been implicated in dental caries. ADMTS3 and ISL1 are involved in tooth development, and TLR2 is involved in immune response to oral pathogens.
Conclusions
As the first GWAS for dental caries in adults, this study nominated several novel caries genes for future study, which may lead to better understanding of cariogenesis, and ultimately, to improved disease predictions, prevention, and/or treatment.
doi:10.1186/1472-6831-12-57
PMCID: PMC3574042  PMID: 23259602
Dental caries; Genetics; Genome wide association; Permanent dentition; Genomics
12.  Heritable patterns of tooth decay in the permanent dentition: principal components and factor analyses 
BMC Oral Health  2012;12:7.
Background
Dental caries is the result of a complex interplay among environmental, behavioral, and genetic factors, with distinct patterns of decay likely due to specific etiologies. Therefore, global measures of decay, such as the DMFS index, may not be optimal for identifying risk factors that manifest as specific decay patterns, especially if the risk factors such as genetic susceptibility loci have small individual effects. We used two methods to extract patterns of decay from surface-level caries data in order to generate novel phenotypes with which to explore the genetic regulation of caries.
Methods
The 128 tooth surfaces of the permanent dentition were scored as carious or not by intra-oral examination for 1,068 participants aged 18 to 75 years from 664 biological families. Principal components analysis (PCA) and factor analysis (FA), two methods of identifying underlying patterns without a priori surface classifications, were applied to our data.
Results
The three strongest caries patterns identified by PCA recaptured variation represented by DMFS index (correlation, r = 0.97), pit and fissure surface caries (r = 0.95), and smooth surface caries (r = 0.89). However, together, these three patterns explained only 37% of the variability in the data, indicating that a priori caries measures are insufficient for fully quantifying caries variation. In comparison, the first pattern identified by FA was strongly correlated with pit and fissure surface caries (r = 0.81), but other identified patterns, including a second pattern representing caries of the maxillary incisors, were not representative of any previously defined caries indices. Some patterns identified by PCA and FA were heritable (h2 = 30-65%, p = 0.043-0.006), whereas other patterns were not, indicating both genetic and non-genetic etiologies of individual decay patterns.
Conclusions
This study demonstrates the use of decay patterns as novel phenotypes to assist in understanding the multifactorial nature of dental caries.
doi:10.1186/1472-6831-12-7
PMCID: PMC3328249  PMID: 22405185
Dental caries genetics; Heritability; Permanent dentition; Pit and fissure surfaces; Smooth surfaces; Tooth surfaces; Principal components analysis; Factor analysis; Patterns of tooth decay; Patterns of dental caries
13.  Detection of Streptococcus mutans Genomic DNA in Human DNA Samples Extracted from Saliva and Blood 
ISRN dentistry  2011;2011:543561.
Caries is a multifactorial disease, and studies aiming to unravel the factors modulating its etiology must consider all known predisposing factors. One major factor is bacterial colonization, and Streptococcus mutans is the main microorganism associated with the initiation of the disease. In our studies, we have access to DNA samples extracted from human saliva and blood. In this report, we tested a real-time PCR assay developed to detect copies of genomic DNA from Streptococcus mutans in 1,424 DNA samples from humans. Our results suggest that we can determine the presence of genomic DNA copies of Streptococcus mutans in both DNA samples from caries-free and caries-affected individuals. However, we were not able to detect the presence of genomic DNA copies of Streptococcus mutans in any DNA samples extracted from peripheral blood, which suggests the assay may not be sensitive enough for this goal. Values of the threshold cycle of the real-time PCR reaction correlate with higher levels of caries experience in children, but this correlation could not be detected for adults.
doi:10.5402/2011/543561
PMCID: PMC3128887  PMID: 21731912
14.  Detection of Streptococcus mutans Genomic DNA in Human DNA Samples Extracted from Saliva and Blood 
ISRN Dentistry  2011;2011:543561.
Caries is a multifactorial disease, and studies aiming to unravel the factors modulating its etiology must consider all known predisposing factors. One major factor is bacterial colonization, and Streptococcus mutans is the main microorganism associated with the initiation of the disease. In our studies, we have access to DNA samples extracted from human saliva and blood. In this report, we tested a real-time PCR assay developed to detect copies of genomic DNA from Streptococcus mutans in 1,424 DNA samples from humans. Our results suggest that we can determine the presence of genomic DNA copies of Streptococcus mutans in both DNA samples from caries-free and caries-affected individuals. However, we were not able to detect the presence of genomic DNA copies of Streptococcus mutans in any DNA samples extracted from peripheral blood, which suggests the assay may not be sensitive enough for this goal. Values of the threshold cycle of the real-time PCR reaction correlate with higher levels of caries experience in children, but this correlation could not be detected for adults.
doi:10.5402/2011/543561
PMCID: PMC3128887  PMID: 21731912
15.  Use of 16S ribosomal RNA gene analyses to characterize the bacterial signature associated with poor oral health in West Virginia 
BMC Oral Health  2011;11:7.
Background
West Virginia has the worst oral health in the United States, but the reasons for this are unclear. This pilot study explored the etiology of this disparity using culture-independent analyses to identify bacterial species associated with oral disease.
Methods
Bacteria in subgingival plaque samples from twelve participants in two independent West Virginia dental-related studies were characterized using 16S rRNA gene sequencing and Human Oral Microbe Identification Microarray (HOMIM) analysis. Unifrac analysis was used to characterize phylogenetic differences between bacterial communities obtained from plaque of participants with low or high oral disease, which was further evaluated using clustering and Principal Coordinate Analysis.
Results
Statistically different bacterial signatures (P < 0.001) were identified in subgingival plaque of individuals with low or high oral disease in West Virginia based on 16S rRNA gene sequencing. Low disease contained a high frequency of Veillonella and Streptococcus, with a moderate number of Capnocytophaga. High disease exhibited substantially increased bacterial diversity and included a large proportion of Clostridiales cluster bacteria (Selenomonas, Eubacterium, Dialister). Phylogenetic trees constructed using 16S rRNA gene sequencing revealed that Clostridiales were repeated colonizers in plaque associated with high oral disease, providing evidence that the oral environment is somehow influencing the bacterial signature linked to disease.
Conclusions
Culture-independent analyses identified an atypical bacterial signature associated with high oral disease in West Virginians and provided evidence that the oral environment influenced this signature. Both findings provide insight into the etiology of the oral disparity in West Virginia.
doi:10.1186/1472-6831-11-7
PMCID: PMC3061962  PMID: 21362199

Results 1-15 (15)