Concurrent validity of the short-form Family Impact Scale (FIS-8) in 4-year-old US children.

BACKGROUND: US data on the validity and reliability of the short-form Family Impact Scale (FIS-8; a scale for measuring the impact of a child's oral condition on his/her family) are lacking. METHODS: Cross-sectional analysis of data on four-year-old US children taking part in a multi-center cohort study. For child-caregiver dyads recruited at child age 12 months, the impact of the child's oral condition on the family was assessed at age 48 months using the FIS-8, with a subsample of 422 caregivers (from 686 who were approached). Internal consistency reliability was assessed using Cronbach's α, with concurrent validity assessed against a global family impact item ("How much are your family's daily lives affected by your child's teeth, lips, jaws or mouth?") and a global oral health item ("How would you describe the health of your child's teeth and mouth?"). RESULTS: Cronbach's alpha was 0.83. Although gradients in mean scores across ordinal response categories of the global family impact item were inconsistent, there were marked, consistent gradients across the ordinal categories of the global item on the child's oral health, with scores highest for those rating their child's oral health as 'Poor'. CONCLUSIONS: While the findings provide some evidence for the utility of the FIS in a US child sample, the study's replication in samples of preschoolers with greater disease experience would be useful.

Fluoride Use in Health Care Settings: Association with Children's Caries Risk.

Expanded partnership with the medical community is an important strategy for reducing dental caries disparities. The purpose of this study was to assess the relationship between fluoride (F) "in office" (drops/tablets and/or varnish), as prescribed or applied by a health care professional by age 1 y, and 1) caries development and 2) presence of other caries risk factors or mediators (e.g., socioeconomic status). Child-primary caregiver (PCG) pairs ( N = 1,325) were recruited in Indiana, Iowa, and North Carolina as part of a longitudinal cohort study to validate a caries risk tool for primary health care settings. PCGs completed a caries risk questionnaire, while children received caries examinations per the criteria of the International Caries Detection and Assessment System at ages 1, 2.5, and 4 y. Baseline responses regarding children's history of F in office were tested for association with other caries risk variables and caries experience at ages 2.5 and 4 y via generalized estimating equation models applied to logistic regression. The sample was 48% female, and many children (61%) were Medicaid enrolled. The prevalence of cavitated caries lesions increased from 7% at age 2.5 y to 25% by age 4 y. Children who received F in office were likely deemed at higher caries risk and indeed were significantly ( P < 0.01) more likely to develop cavitated caries lesions by ages 2.5 and 4 y, even after F application (odds ratios: 3.5 and 2.3, respectively). Factors significantly associated with receiving F included the following: child being Medicaid enrolled, not having an employed adult in the household, child and PCG often consuming sugary drinks and snacks, and PCG having recent caries experience. Increased F in office from a health care provider by age 1 y was associated with known caries risk factors. Most (69%) children had never been to the dentist, suggesting that risk factors could be alerting medical providers and/or parents, thereby affecting in-office F recommendations. Differences among states could also be related to state-specific F-varnish reimbursement policies (ClinicalTrials.gov NCT01707797).

Genome-wide association study of primary dentition pit-and-fissure and smooth surface caries.

Dental caries continues to be the most common chronic disease in children today. Despite the substantial involvement of genetics in the process of caries development, the specific genes contributing to dental caries remain largely unknown. We performed separate genome-wide association studies of smooth and pit-and-fissure tooth surface caries experience in the primary dentitions of self-reported white children in two samples from Iowa and rural Appalachia. In total, 1,006 children (ages 3-12 years) were included for smooth surface analysis, and 979 children (ages 4-14 years) for pit-and-fissure surface analysis. Associations were tested for more than 1.2 million single nucleotide polymorphisms, either genotyped or imputed. We detected genome-wide significant signals in KPNA4 (p value = 2.0E-9), and suggestive signals in ITGAL (p value = 2.1E-7) and PLUNC family genes (p value = 2.0E-6), thus nominating these novel loci as putative caries susceptibility genes. We also replicated associations observed in previous studies for MPPED2 (p value = 6.9E-6), AJAP1 (p value = 1.6E-6) and RPS6KA2 (p value = 7.3E-6). Replication of these associations in additional samples, as well as experimental studies to determine the biological functions of associated genetic variants, are warranted. Ultimately, efforts such as this may lead to a better understanding of caries etiology, and could eventually facilitate the development of new interventions and preventive measures.

Impact of Fluoride on Associations between Free Sugars Intake and Dental Caries in US Children.

OBJECTIVE: Dental caries is the most prevalent chronic disease in US children, with the highest burden among Black and Hispanic youth. Sugars are a primary risk factor, but few studies have specifically measured intakes of free sugars and related this to dental caries or explored the extent to which water fluoride mitigates the cariogenicity of free sugars. Furthermore, the cariogenicity of certain free sugars sources, such as extruded fruit and vegetable products, is unclear. METHODS: Using cross-sectional data on 4,906 children aged 2 to 19 y in the US National Health and Nutrition Examination Survey 2013-2016, we examined associations of free sugars intake with counts of decayed or filled primary tooth surfaces (dfs) and decayed, missing, or filled permanent surfaces (DMFS) in negative binomial regressions. Stratified models examined these associations in children with home water fluoride above or below the Centers for Disease Control and Prevention (CDC)-recommended level of 0.7 ppm. RESULTS: Free sugars accounted for 16.4% of energy, primarily contributed by added sugars. In adjusted models, a doubling in the percentage of energy from free sugars was associated with 22% (95% confidence interval [CI], 1%-47%) greater dfs among children aged 2 to 8. A doubling in energy from added sugars was associated with 20% (95% CI, 1%-42%) greater dfs and 10% (95% CI, 2%-20%) greater DMFS in children aged 6 to 19 y. Beverages were the most important source of added sugars associated with increased caries. Other free sugars were not associated with dfs or DMFS. Associations between free sugars and caries were diminished among children with home water fluoride of 0.7 ppm or greater. CONCLUSIONS: Free sugars intake, especially in the form of added sugars and specifically in sweetened beverages, was associated with higher dental caries. Water fluoride exposures modify these associations, reducing caries risk in the primary dentition of children whose home water meets recommended fluoride levels. KNOWLEDGE TRANSFER STATEMENT: Intake of free sugars, especially in the form of added sugars and specifically in beverages, was associated with higher dental caries in US children in this study. Water fluoride exposure at CDC-recommended levels protected against caries, especially in the primary dentition. These findings suggest that household water fluoridation at CDC-recommended levels protects against the cariogenic potential of free and added sugars during childhood.

Microbial Indicators of Dental Health, Dysbiosis, and Early Childhood Caries.

Dental caries lesions are a clinical manifestation of disease, preceded by microbial dysbiosis, which is poorly characterized and thought to be associated with saccharolytic taxa. Here, we assessed the associations between the oral microbiome of children and various caries risk factors such as demographics and behavioral and clinical data across early childhood and characterized over time the salivary and dental plaque microbiome of children before clinical diagnosis of caries lesions. Children (N = 266) were examined clinically at ~1, 2.5, 4, and 6.5 y of age. The microbiome samples were collected at 1, 2.5, and 4 y. Caries groups consisted of children who remained caries free (International Caries Detection and Assessment System [ICDAS] = 0) at all time points (CFAT) (n = 50); children diagnosed with caries (ICDAS ≥ 1) at 6.5 y (C6.5), 4 y (C4), or 2.5 y of age (C2.5); and children with early caries or advanced caries lesions at specific time points. Microbial community analyses were performed on zero-radius operational taxonomic units (zOTUs) obtained from V4 of 16S ribosomal RNA gene amplicon sequences. The oral microbiome of the children was affected by various factors, including antibiotic use, demographics, and dietary habits of the children and their caregivers. At all time points, various risk factors explained more of the variation in the dental plaque microbiome than in saliva. At 1 y, composition of saliva of the C4 group differed from that of the CFAT group, while at 2.5 y, this difference was observed only in plaque. At 4 y, multiple salivary and plaque zOTUs of genera Prevotella and Leptotrichia were significantly higher in samples of the C6.5 group than those of the CFAT group. In conclusion, up to 3 y prior to clinical caries detection, the oral microbial communities were already in a state of dysbiosis that was dominated by proteolytic taxa. Plaque discriminated dysbiotic oral ecosystems from healthy ones better than saliva.

Predicting Dental Caries in Young Children in Primary Health Care Settings.

Young children need increased access to dental prevention and care. Targeting high caries risk children first helps meet this need. The objective of this study was to develop a parent-completed, easy-to-score, short, accurate caries risk tool for screening in primary health care settings to identify children at increased risk for cavities. A longitudinal, prospective, multisite, cohort study enrolled (primarily through primary health care settings) and followed 985 (out of 1,326) 1-y-old children and their primary caregivers (PCGs) until age 4. The PCG completed a 52-item self-administered questionnaire, and children were examined using the International Caries Detection and Assessment Criteria (ICDAS) at 12 ± 3 mo (baseline), 30 ± 3 mo (80% retention), and 48 ± 3 mo of age (74% retention). Cavitated caries lesion (dmfs = decayed, missing, and filled surfaces; d = ICDAS ≥3) experience at 4 y of age was assessed and tested for associations with questionnaire items using generalized estimating equation models applied to logistic regression. Multivariable analysis used backward model selection, with a limit of 10 items. At age 4, 24% of children had cavitated-level caries experience; 49% were female; 14% were Hispanic, 41% were White, 33% were Black, 2% were other, and 10% were multiracial; 58% enrolled in Medicaid; and 95% lived in urban communities. The age 4 multivariable prediction model, using age 1 responses (area under the receiver operating characteristic curve = 0.73), included the following significant (P < 0.001) variables (odds ratios): child participating in public assistance programs such as Medicaid (1.74), being non-White (1.80-1.96), born premature (1.48), not born by caesarean section (1.28), snacking on sugary snacks (3 or more/d, 2.22; 1-2/d or weekly, 1.55), PCG cleaning the pacifier with juice/soda/honey or sweet drink (2.17), PCG daily sharing/tasting food with child using same spoon/fork/glass (1.32), PCG brushing their teeth less than daily (2.72), PCG's gums bleeding daily when brushing or PCG having no teeth (1.83-2.00), and PCG having cavities/fillings/extractions in past 2 y (1.55). A 10-item caries risk tool at age 1 shows good agreement with cavitated-level caries experience by age 4.

Genetic and environmental factors associated with dental caries in children: the Iowa Fluoride Study.

Dental caries remains the most common chronic childhood disease. Despite strong evidence of genetic components, there have been few studies of candidate genes and caries. In this analysis we tried to assess genetic and environmental factors contributing to childhood caries in the Iowa Fluoride Study. Environmental factors (age, sex, race, tooth-brushing frequencies and water fluoride level) and three dental caries scores (d(2)fs-total, d(2)fs-pit/fissure, and d(2)fs-smooth surface) were assessed in 575 unrelated children (mean age 5.2 years). Regression analyses were applied to assess environmental correlates. The Family-Based Association Test was used to test genetic associations for 23 single nucleotide polymorphism (SNP) markers in 7 caries candidate genes on 333 Caucasian parent-child trios. We evaluated the associations between caries status and the level of both single and multiple SNPs (haplotype) respectively. Permutation procedure was performed for correction of inflated type I errors due to multiple testing. Age, tooth-brushing frequency and water fluoride level were significantly correlated to at least one carious score. Caries on pit and fissure surfaces was substantially higher than on smooth surfaces (61 vs. 39%). SNPs in three genes (DSPP, KLK4 and AQP5) showed consistent associations with protection against caries. Of note, KLK4 and AQP5 were also highlighted by subsequent haplotype analysis. Our results support the concept that genes can modify the susceptibility of caries in children. Replication analysis in independent cohorts is highly needed in order to verify the validity of our findings.

Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium.

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.

Development of gold standard ion-selective electrode-based methods for fluoride analysis.

BACKGROUND/AIMS: Currently available techniques for fluoride analysis are not standardized. Therefore, this study was designed to develop standardized methods for analyzing fluoride in biological and nonbiological samples used for dental research. METHODS: A group of nine laboratories analyzed a set of standardized samples for fluoride concentration using their own methods. The group then reviewed existing analytical techniques for fluoride analysis, identified inconsistencies in the use of these techniques and conducted testing to resolve differences. Based on the results of the testing undertaken to define the best approaches for the analysis, the group developed recommendations for direct and microdiffusion methods using the fluoride ion-selective electrode. RESULTS: Initial results demonstrated that there was no consensus regarding the choice of analytical techniques for different types of samples. Although for several types of samples, the results of the fluoride analyses were similar among some laboratories, greater differences were observed for saliva, food and beverage samples. In spite of these initial differences, precise and true values of fluoride concentration, as well as smaller differences between laboratories, were obtained once the standardized methodologies were used. Intraclass correlation coefficients ranged from 0.90 to 0.93, for the analysis of a certified reference material, using the standardized methodologies. CONCLUSION: The results of this study demonstrate that the development and use of standardized protocols for F analysis significantly decreased differences among laboratories and resulted in more precise and true values.

Decline in Dental Fluorosis Severity during Adolescence: A Cohort Study.

Dental fluorosis occurs from overingestion of fluoride during tooth formation. However, there is little evidence in the literature on whether or how fluorosis prevalence and severity change over time after tooth eruption. Permanent dentition dental examinations were conducted at ages 9, 13, 17, and 23 as part of the Iowa Fluoride Study, which has followed a cohort from birth. Fluorosis was assessed using the Fluorosis Risk Index (FRI) and Russell's criteria for differential diagnosis. Measures of fluorosis severity at the person and tooth level were calculated: second highest FRI score at the person level (the maximum FRI score for each tooth was determined and the tooth with the second highest maximum FRI score was used) and highest FRI score at the tooth level. At both the person and tooth levels, a decline in mild to moderate fluorosis severity was observed across adolescence and young adulthood. Across each pair of adjacent examinations at the person level, for participants with a baseline second highest FRI of 0, most participants stayed at 0 (82% to 91%). Many participants with a baseline second highest FRI of 1 had a follow-up score of 0 (47% to 54%), while about a third had a follow-up score of 1 (34% to 38%), and a lower percentage had an increase to a score of 2 (9% to 15%). For participants with baseline second highest FRI score of 2, between 25% and 44% of participants had follow-up FRI scores each of 0, 1, and 2. Similar patterns were observed at the tooth level. These results were consistent with most of the existing, limited literature. Overall, fluorosis severity, which was initially mild to moderate, tended to decline during adolescence and young adulthood. Additional study of how this trend affects esthetic perceptions of fluorosis is warranted.

Maturation of the Oral Microbiome in Caries-Free Toddlers: A Longitudinal Study.

Understanding the development of the oral microbiota in healthy children is of great importance to oral and general health. However, limited data exist on a healthy maturation of the oral microbial ecosystem in children. Moreover, the data are biased by mislabeling "caries-free" populations. Therefore, we aimed to characterize the healthy salivary and dental plaque microbiome in young children. Caries-free (ICDAS [International Caries Detection and Assessment System] score 0) children (n = 119) and their primary caregivers were followed from 1 until 4 y of child age. Salivary and dental plaque samples were collected from the children at 3 time points (T1, ~1 y old; T2, ~2.5 y old; and T3, ~4 y old). Only saliva samples were collected from the caregivers. Bacterial V4 16S ribosomal DNA amplicons were sequenced using Illumina MiSeq. The reads were denoised and mapped to the zero-radius operational taxonomic units (zOTUs). Taxonomy was assigned using HOMD. The microbial profiles of children showed significant differences (P = 0.0001) over time. Various taxa increased, including Fusobacterium, Actinomyces, and Corynebacterium, while others showed significant decreases (e.g., Alloprevotella and Capnocytophaga) in their relative abundances over time. Microbial diversity and child-caregiver similarity increased most between 1 and 2.5 y of age while still not reaching the complexity of the caregivers at 4 y of age. The microbiome at 1 y of age differed the most from those at later time points. A single zOTU (Streptococcus) was present in all samples (n = 925) of the study. A large variation in the proportion of shared zOTUs was observed within an individual child over time (2% to 42% of zOTUs in saliva; 2.5% to 38% in dental plaque). These findings indicate that the oral ecosystem of caries-free toddlers is highly heterogeneous and dynamic with substantial changes in microbial composition over time and only few taxa persisting across the 3 y of the study. The salivary microbiome of 4-y-old children is still distinct from that of their caregivers.

Association between enamel hypoplasia and dental caries in primary second molars: a cohort study.

The purpose of this study was to assess the longitudinal relationships between enamel hypoplasia and caries experience of primary second molars. The study sample was 491 subjects who received dental examinations at both age 5 and 9 by the calibrated examiners. Four primary second molars (n = 1,892) were scored for the presence of enamel hypoplasia for each participant. Caries presence and number of decayed and filled surfaces (dfs) were determined at age 5 and 9. The relationships between enamel hypoplasia and caries experience were assessed. Among primary second molars, 3.9% of children and 1.7% of primary second molars had enamel hypoplasia. At age 5, 36.8% of children with hypoplasia had caries, while 16.9% of children without enamel hypoplasia had caries. At age 9, the corresponding numbers were 52.6% for children with hypoplasia and 34.5% for children without hypoplasia, respectively. At the tooth level, for age 5, 28.1% of teeth with hypoplasia had caries (mean dfs = 0.40), and 7.6% of teeth without hypoplasia had caries (mean dfs = 0.11). At age 9, the corresponding numbers were 41.9% (mean dfs = 0.76) for teeth with hypoplasia and 18.3% (mean dfs = 0.34) for teeth without hypoplasia. In multivariable logistic regression analyses, teeth of subjects with enamel hypoplasia had a significantly higher risk for caries at age 5 and 9 after controlling for other risk factors. Enamel hypoplasia appears to be a significant risk factor for caries and should be considered in caries risk assessment.

Predicting Caries in Medical Settings: Risk Factors in Diverse Infant Groups.

Expanded partnership with the medical community is a promising strategy for reducing disparities in dental caries among young children. However, no validated caries risk instrument exists for use in primary health care settings. To help resolve this gap, a 52-item caries risk questionnaire was developed and targeted to primary caregivers (PCGs) to test in a 3-y prospective study. To begin to understand the validity of the questionnaire items, the purpose of this study was to compare responses to the questionnaire based on key demographic characteristics known to be associated with disparities in caries experience (e.g., race/ethnicity and insurance status). A total of 1,323 one-year-old children were recruited primarily through 3 medical research networks. Baseline questionnaire responses were analyzed via logistic regression. The sample was 49% female. Its racial/ethnic makeup was as follows: 13% Hispanic, 37% White, 37% Black, and 13% other or multiracial. Sixty-one percent were enrolled in Medicaid, and 95% resided in urban communities. Mothers represented 94% of PCGs. There were significant differences ( P < 0.05) in baseline responses based on Medicaid status and race/ethnicity. As compared with those not enrolled in Medicaid, children in the Medicaid group were significantly more likely (after adjusting for race/ethnicity) to 1) go to sleep while nursing or drinking something other than water, 2) eat sugary snacks between meals, 3) consume sugary drinks between meals, 4) receive topical fluoride from a health professional, 5) visit the dentist, and 6) not have an employed adult in the household. PCGs of children enrolled in Medicaid were significantly more likely to be the mother, have bleeding gums, eat sugary snacks between meals, consume sugary drinks between meals, eat or drink something other than water before going to bed, and not get regular dental checkups. In conclusion, there are significant differences in caries risk questionnaire responses based on Medicaid status and race/ethnicity that provide construct and criterion validity to the developed caries risk tool (ClinicalTrials.gov NCT01707797).

Subjective and objective measures of physical activity in relationship to bone mineral content during late childhood: the Iowa Bone Development Study.

OBJECTIVE: This study compared accelerometry to self-report for the assessment of physical activity (PA) in relation to bone mineral content (BMC). In addition, we compared the ability of these measures to assess PA in boys versus girls. METHODS: Participants in this cross-sectional study included 449 children (mean age 11 years) from the Iowa Bone Development Study. PA was measured via 3-5 days of accelerometry using the Actigraph and 7 day self-report questionnaire using the Physical Activity Questionnaire for Children (PAQ-C). Hip, spine, and whole body BMC were measured via dual energy x ray absorptiometry (DXA). RESULTS: Partial correlation analysis (controlling for height, weight, and maturity) showed the Actigraph was significantly associated with hip (r = 0.40), spine (r = 0.20), and whole body (r = 0.33) BMC in boys, as was the PAQ-C (r = 0.28 hip, r = 0.19 spine, and r = 0.22 whole body). Among girls, only the Actigraph was significantly associated with hip (r = 0.18) and whole body (r = 0.16) BMC. Both the Actigraph and PAQ-C were significant in hip, spine, and whole body multivariable linear regression models (after controlling for body size and maturity) in boys. Only the Actigraph entered hip BMC regression model in girls. CONCLUSIONS: Our study supports previous work showing associations between everyday PA and BMC in older children. These associations are more likely to be detected with an objective versus subjective measure of PA, particularly in girls.

Examining caries aetiology in adolescence with structural equation modelling.

OBJECTIVES: This analysis examines the aetiology of caries development in adolescents using structural equation modelling to identify behavioural mediators of the relationship between socioeconomic status (SES) and caries incidence, and to investigate the role of sex on caries-preventive behaviour and caries. METHODS: This analysis was based on data from the Iowa Fluoride Study, a longitudinal study of a birth cohort. We hypothesized that socioeconomic status earlier in life has a direct effect on caries development and an indirect effect from improved behavioural variables-dental visit attendance, toothbrushing frequency and percentage of beverage intake consisting of sugar-sweetened beverages-and that sex also plays a role in behavioural variables, as well as caries. A structural equation model was developed based on these hypotheses, and direct and indirect standardized path coefficients were calculated, as well as their standard errors. RESULTS: Based on our proposed model, SES at birth significantly influences SES during adolescence, but not adolescent behaviours. The effect of SES during adolescence on caries in the permanent dentition is mediated by adolescent behaviours. Female participants have worse caries than male participants, despite lower self-reported percentages of sugar-sweetened beverage intake and more frequent brushing and dental attendance. CONCLUSIONS: This analysis models the relationships among known causal factors for caries and suggests that the role of SES in caries may not be as important as previously thought and different behaviours that affect oral health between males and females as well as differences in caries between the sexes could begin during adolescence. These findings could help improve caries prevention programmes for adolescents.

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.

Breast conservation versus mastectomy: distress sequelae as a function of choice.

Between 1981 and 1984, 93 stage I and II breast cancer patients were entered onto a trial at the National Cancer Institute (NCI) randomizing patients to excisional biopsy plus radiation v mastectomy. Between 1984 and 1987, 98 stage I and II breast cancer patients were entered onto a behavioral study in Pittsburgh, approximately 70% of whom elected to have breast conservation surgery. Patients at both sites were assessed three to five days postsurgery, and again at 3-month's follow-up, using a well-validated mood measure, the Profile of Mood States (POMS). There were no demographic or disease differences between the two samples. In the Pittsburgh sample, using a repeated measures multivariate analysis of covariance (MANCOVA) analysis, after adjusting for menopausal status and radiotherapy and chemotherapy toxicity, the conservation group was psychologically worse off (F = 2.7, P less than .03). For example, they were significantly more distressed over time (F = 5.5, P less than .02), and more depressed in general (F = 9.2, P less than .005). Using Karnofsky ratings, the two groups were identical in terms of disability at 3-month's follow-up. In contrast, for the NCI patients participating in the randomized trial, after adjusting for chemotherapy and radiotherapy treatments, reported overall distress decreased over time (F = 17.4, P less than .0001) for all patients, irrespective of treatment group, and the between-groups MANCOVA was not significant. Thus, when comparing the two samples, when "choice" played a major role, the conservation patients were psychologically worse off--at least at 3-month's follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Dimethyl sulfoxide does not trigger urine histamine release in interstitial cystitis.

OBJECTIVES: Dimethyl sulfoxide (DMSO), an agent that provides symptomatic relief in patients with interstitial cystitis (IC) works via an unknown mechanism. We investigated whether DMSO acts as a chemical stimulant of mast cell degranulation. METHODS: A radioimmunoassay (RIA) specific for histamine was used to test this hypothesis. Twelve women with strictly diagnosed IC were treated with intravesical instillations of DMSO. Treatments were repeated at varying intervals, and each patient received three to six treatments. Urine histamine levels were measured before and after each intravesical instillation of DMSO. Dilutional effects of DMSO were corrected for by conversion of urine histamine concentration to urine histamine:creatinine ratio. RESULTS: The RIA was unaffected by the addition of DMSO to urine. No consistent change in the urine histamine:creatinine ratio following DMSO instillation was found. Trend analysis revealed no trend in the histamine:creatinine ratio with time. CONCLUSIONS: The relief of symptoms reported in 50% to 77% of patients treated with intravesical DMSO is not related to detectable mast cell release of histamine. Other mechanisms of action must be investigated to explain the beneficial effect of this agent.

Mastectomy versus breast conservation surgery: mental health effects at long-term follow-up.

Between 1984 and 1989, 129 Stage 1 and Stage 2 breast cancer patients were entered into a behavioral study in Pittsburgh. Approximately 70% of these patients had elected to have breast conservation (lumpectomy) surgery, with the remainder choosing mastectomy. Using the Profile of Mood States, a measure of perceived social support, and Karnofsky ratings of physical functional status, patients were assessed 3 to 5 days following surgery and again 3 and 15 months following surgery. The data were analyzed using a repeated-measures analysis of covariance, adjusting for aggressiveness of chemotherapy. Compared to mastectomy patients, patients who received breast conservation surgery were rated as more functional by observers, but they perceived themselves as having less energy and less emotional support, especially over the first 3 months of the recovery period. Because there is accumulating evidence that emotional support may act as a stress buffer in various populations and may have survival value, these findings may be particularly troublesome. This study shows that breast conservation surgery is not a psychosocial panacea. Patients whose breasts are spared, especially younger patients, have psychological symptoms that appear acutely worse in the short run and, in the end, are similar to those of patients who elect to have mastectomies. Therefore, patients choosing lumpectomies are not necessarily psychosocially better off than those electing to have mastectomies. Additionally, these patients, particularly younger patients, may require greater social support and potential mental health interventions than they seem to be receiving.

Prognostic risk assessment in primary breast cancer by behavioral and immunological parameters.

Although findings from recent animal studies suggest that behavioral factors such as "helplessness" play a role in cancer progression, very few such studies with humans have been carried out. The study investigated the predictive power of an immunologic effector cell, the natural killer (NK) cell, as well as selected psychological and demographic factors, to breast cancer prognostic risk status. It was found that NK activity predicted the status of cancer spread to the axillary lymph nodes. Patients who had low levels of NK activity were rated as well-adjusted to their illness; patients who had higher NK activity appeared to be distressed or maladjusted. These findings are discussed in the light of recent animal findings linking environmental stress and behavioral responsiveness to biological vulnerability via endocrine and immune pathways.