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.

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.

Streptococcus mutans and Streptococcus sanguinis colonization correlated with caries experience in children.

The aim of this study was to examine the colonization of Streptococcus mutans and Streptococcus sanguinis in the oral cavity and the association with severe early childhood caries (S-ECC). Saliva and plaque samples were collected from 14 S-ECC children and 8 caries-free (CF) children. All S-ECC children were S. mutans positive; 100% of CF children and 93% of S-ECC children were S. sanguinis positive. The children's caries severity was positively correlated with levels of S. mutans (p < 0.001), total oral streptococci (p < 0.01), total cultivable oral bacteria (p < 0.05), and children's age (p < 0.05). Logistic regression analysis showed that the interaction of S. sanguinis with S. mutans was a significant factor associated with the caries status in children, suggesting that the relative levels of these two microorganisms in the oral cavity play an important role in caries development.

Evaluating data from behavioral analysis: visual inspection or statistical models?

Traditional behavior analysis relies upon single-subject study designs and visual inspection of graphed data to evaluate the efficacy of experimental manipulations. Attempts to apply statistical inferential procedures to analyze data have been successfully opposed for many decades, despite problems with visual inspection and increasingly cogent arguments to utilize inferential statistics. In a series of experiments, we show that trained behavior analysts often identify level shifts in responding during intervention phases ('treatment effect') in modestly autocorrelated data, but trends are either misconstrued as level treatment effects or go completely unnoticed. Errors in trend detection illustrate the liabilities of using visual inspection as the sole means by which to analyze behavioral data. Meanwhile, because of greatly increased computer power and advanced mathematical techniques, previously undeveloped or underutilized statistical methods have become far more sophisticated and have been brought to bear on a variety of problems associated with repeated measures data. I present several nonparametric procedures and other statistical techniques to evaluate traditional behavioral data to augment, not replace, visual inspection procedures.

Psychological assessment in XLMR: a proposal for setting international standards.

The need for an agreed upon set of standards for assessing individuals with XLMR was made quite evident this past year at the Fragile X and XLMR Workshop in Strasbourg. Several affected individuals from different families may have been incorrectly diagnosed as MR. Many factors can have a negative affect on IQ testing. As a result, evaluating individuals with cognitive deficits can be problematic. To be effective, psychological assessments must produce uniform results that are consistent with the definition of MR. Therefore, to foster international research in XLMR. I propose a two-stage standardized protocol. To determine which tests may be suitable. I review an assortment of instruments for psychological assessment at each stage, noting their strengths and weaknesses. Afterward, I present a set of standardized protocols based on age and language ability.

FMR1 gene and fragile X syndrome.

Taxonomic features of fragile X syndrome (FXS) associated with the fragile X mutation have evolved over several decades. Males are more severely impacted cognitively than females, but both show declines in IQ scores as they age. Although many males with FXS exhibit autistic-like features, autism does not occur more frequently in males with FXS than among males with mental retardation (MR). FXS is caused by inactivation of the FMR1 gene located on Xq27.3. FMRP, the protein produced by FMR1, has been detected in most organs and in brain. In cells, it is located primarily in cytoplasm and contains motifs found in RNA-binding proteins. The FMRP N-terminal contains a functional nuclear localization signal which permits the protein to shuttle between cytoplasm and nucleus. FMR1 knockout mice show subtle behavioral and visual-spatial difficulties. Analysis of their brain tissue suggests absence of FMRP impairs synaptic maturation. Individuals with the fragile premutation produce FMRP, and the phenotype associated with the premutation has been controversial. However, there seems to be a higher incidence of premature ovarian failure in women with the premutation than is found in the general female population. This may be related to unusual increases in mRNA levels in premutation carriers.

Learning and memory in the FMR1 knockout mouse.

The fragile X [fra(X)] syndrome is manifested phenotypically as a developmental disability comprised mainly of moderate-to-severe mental retardation (MR). Deficits are especially evident in auditory and visual short-term memory. Recently, an FMR1 knockout mouse developed by the Dutch-Belgian Fragile X Consortium demonstrated significantly lower visual-spatial abilities than littermate controls. We wondered if these results were associated with learning per se or to performance deficits only. Thus, we examined learning and memory in male FMR1 knockout mice crossbred from Fvb and E129 strains, and in male Fvb control mice, using operant conditioning techniques. In Experiment 1, we demonstrated that two aged male FMR1 knockouts could acquire the necessary bar-press response to discriminate visual (L+) and auditory (N+) stimuli. In Experiment 2, we showed that three naive male knockouts and two naive male controls, all 12 weeks old, also learned to discriminate L+ and N+. A third component, a complex discrimination task, during which light and noise were presented concurrently without reinforcement (LN-) was added to each session. All knockouts acquired both L+ and N+ discriminative responses in fewer sessions and with higher discrimination ratios than either control. Moreover, all knockouts exhibited the typical response pattern associated with complex discrimination (LN-) tasks. However, neither control made the complex discrimination. Our findings were unexpected and raise issues concerning FMR1 mouse strains and their cognitive-behavioral testing.

Age-related language characteristics of children and adolescents with fragile X syndrome.

In addition to moderate-to-severe mental retardation (MR), the fragile X [fra(X)] mutation produces significant impediments in speech and language. Severe delays in speech and language have been demonstrated in both adult males and young individuals with the fra(X) mutation. Having observed longitudinal declines in IQ scores in young males with fra(X) and given the relationship between cognitive ability and language skill, we wanted to determine whether speech-language deficits in young males with fra(X) were age-related in ways comparable with those observed in cognitive deficits. We examined a small sample (n = 16) of children and adolescents, ages 6-17 years, using the Clinical Evaluation of Language Fundamental-Preschool (CELF-P). The CELF-P is used to evaluate language deficits in preschool children and assesses receptive and expressive language ability. It is standardized for children ages 3-7 years and provides age-normed standard scores. To evaluate changes in language scores, we converted raw scores into age-equivalents. Results indicate that males with fra(X) have significantly lower age equivalent scores compared with females. A cross-sectional analysis of males' age-equivalent scores reveals that a plateau is reached at approximately 48 months. Our findings suggest that, as with IQ and adaptive behavior scores, language development in young, fully mutated fra(X) individuals appears to reach a plateau as they age.

Longitudinal assessment of adaptive and maladaptive behaviors in fragile X males: growth, development, and profiles.

As young fully mutated fragile X [fra(X)] males age, cognitive levels (IQ scores) and adaptive behavior levels (DQ scores) decline. Given the variable behavioral profiles reported previously, we wondered whether changes in specific attributes of adaptive behavior are related to declines in composite adaptive behavior levels. We also examined maladaptive behavior to determine if changes are related to age. Therefore, we evaluated three areas of adaptive behavior, as well as maladaptive behavior, in 28 fully mutated fra(X) males, ages 4-14 years. To develop a profile of adaptive behavior, we analyzed nine subscale scores from the Vine-land Adaptive Behavior Scale (VABS). To assess maladaptive behavior, we graded part I of the VABS Maladaptive Behavior Scale. Subjects were sorted into three age cohorts, according to their initial test age: younger than 6 years; 6 to 9 years; older than 9 years. Results indicate that, in all age groups, the communications domain is the most severely impacted compared with either the socialization domain or daily living skills and that, in all age groups, the socialization domain is a relative strength compared with either the communications domain or daily living skills. The youngest cohort manifested significant increases in age-equivalent community living skills. Significant differences in age-equivalent scores between cohorts were observed in written language and play skills. Maladaptive behavior scores were available from cross-sectional data only. Twenty males (74%) showed significantly higher maladaptive scores than expected from other children their age. Our data analysis also revealed a moderate and significant negative correlation between maladaptive behavior levels and age (r = -0.54; P < 0.01). Curiously, adaptive and maladaptive behaviors did not correlate with each other.

Longitudinal changes in cognitive and adaptive behavior in fragile X females: a prospective multicenter analysis.

In prospective studies of young, fragile X [fra(X)] males with the full mutation, cognitive abilities (IQ scores) and adaptive behavior levels (DQ scores) declined in most subjects tested. Little is known about longitudinal changes in IQ and DQ scores in young fra(X) females, although one earlier retrospective study showed declines in IQ scores in 8 of 11 subjects. To examine fra(X) females prospectively, we tested and retested 13 females with the full mutation, age 4 to 15 years. Nine were tested and retested in North America, and four were evaluated at the Catholic University in Leuven, Belgium. Cognitive abilities of North American females were measured using the Stanford-Binet 4th Edition. Adaptive behavior levels were ascertained from the Vineland Adaptive Behavior Scales. For Belgians, test-retest scores from the Wechsler Intelligence Scales for Children-Revised were used. Subjects were subsequently separated into two age cohorts: those tested initially before age 7 years and those tested initially after age 7 years. Compared with young males with the full mutation and of the same age, females expectedly display a wider range of IQ scores. Test-retest IQ scores showed statistically significant decreases (P < 0.03). Analysis of individual test-retest scores indicate that declines in eight females were statistically significant. Adaptive behavior scores were available only for North American females. Five of nine (55%) showed significant declines in DQ. Like young males with the full mutation, all females with the full mutation attained higher adaptive behavior levels than cognitive scores, i.e., DQ > IQ.

Visual inspection of data revisited: Do the eyes still have it?

In behavior analysis, visual inspection of graphic information is the standard by which data are evaluated. Efforts to supplement visual inspection using inferential statistical procedures to assess intervention effects (e.g., analysis of variance or time-series analysis) have met with opposition. However, when serial dependence is present in the data, the use of visual inspection by itself may prove to be problematic. Previously published reports demonstrate that autocorrelated data influence trained observers' ability to identify level treatment effects and trends that occur in the intervention phase of experiments. In this report, four recent studies are presented in which autoregressive equations were used to produce point-to-point functions to simulate experimental data. In each study, various parameters were manipulated to assess trained observers' responses to changes in point-to-point functions from the baseline condition to intervention. Level shifts over baseline behavior (treatment effect), as well as no change from baseline (no treatment effect or trend), were most readily identified by observers, but trends were rarely recognized. Furthermore, other factors previously thought to augment and improve observers' responses had no impact. Results are discussed in terms of the use of visual inspection and the training of behavior analysts.

Rater reliability of fragile X mutation size estimates: a multilaboratory analysis.

Notwithstanding the use of comparable molecular protocols, description and measurement of the fra(X) (fragile X) mutation may vary according to its appearance as a discrete band, smear, multiple bands, or mosaic. Estimation of mutation size may also differ from one laboratory to another. We report on the description of an mutation size estimate for a large sample of individuals tested for the fra(X) pre- or full mutation. Of 63 DNA samples evaluated, 45 were identified previously as fra(X) pre- or full mutations. DNA from 18 unaffected individuals was used as control. Genomic DNA was extracted from peripheral blood, and DNA fragments from each of four laboratories were sent to a single center where Southern blots were prepared and hybridized with the pE5.1 probe. Photographs from autoradiographs were returned to each site, and raters blind to the identity of the specimens were asked to evaluate them. Raters' estimates of mutation size compared favorably with a reference test. Intrarater reliability was good to excellent. Variability in mutation size estimates was comparable across band types. Variability in estimates was moderate, and was significantly correlated with absolute mutation size and band type.

Longitudinal study of cognitive abilities and adaptive behavior levels in fragile X males: a prospective multicenter analysis.

Retrospective longitudinal studies have noted declines in IQ scores in many but not all fra(X) (fragile X) males and females. We report on a prospective investigation of longitudinal changes in cognitive ability (IQ) and adaptive behavior (DQ) in 24 fra(X) males from four test sites. Individuals who were tested ranged in age from 3-15 years. To determine cognitive ability, all males were administered the Stanford-Binet test (4th Edition). To assess adaptive behavior, all males were evaluated using the Vineland Adaptive Behavior Scales. Mean interest interval was 2.3 years. Using identical DNA protocols, all subjects were identified as bearing the fra(X) mutation. Results showed declines in IQ scores in 18/24 (75%) males. Four males showed no change in scores. Declines in DQ scores were noted in 22/24 (92%) of those tested. DQ scores were higher than IQ scores in 20/24 (83%) subjects. From a descriptive cohort analysis, decreases in IQ scores appear to follow a well-defined, negatively decelerating function. Declines in DQ were steeper and more nearly linear. Declining scores are not indicative of regression of intellectual and/or social skills, but of a relative inability to keep pace with their age-normed cohort. We conclude that the fra(X) mutation affects cognitive abilities in a uniform, nonlinear manner comparable to outcomes observed in earlier retrospective studies. Adaptive behavior also declines, but in a more linear fashion.

Lack of association between mutation size and cognitive/behavior deficits in fragile X males: a brief report.

Previously, researchers reported molecular-neurobehavioral or molecular-cognitive associations in individuals with fra(X) (fragile X) mutation. However, not all investigators have noted molecular-behavioral relationships. Consequently, we examined prospectively 30 fra(X) males age 3-15 years from four testing sites to determine whether there was a relationship between mutation size and degree of either cognitive or adaptive behavior deficit. To measure cognitive abilities, all individuals were administered the Stanford-Binet (4th edition) IQ test. To evaluate adaptive behavior (DQ) skills, all individuals were assessed using the Vineland Adaptive Behavior Scale. To determine fra(X) status, genomic DNA from all individuals was extracted and digested with EcoRI and EagI restriction enzymes. Southern blots were prepared and hybridized with the pE5.1 probe. The Pearson correlation coefficient between full mutation size and composite IQ score revealed a nonsignificant, near-zero association (r = 0.06; P > .76). The Pearson coefficient between mutation size and DQ also showed a nonsignificant, near-zero association (r = 0.06; P > .73). We conclude that while fra(X) mutation produces cognitive and behavior deficits in males who inherit the defective gene, there is no relationship between mutation size and degree of deficit.

The fragile X premutation in carriers and its effect on mutation size in offspring.

The pattern of inheritance in the fragile X (fra(X)) mutation follows a multistage intergenerational process in which the premutation evolves into the full mutation and the characteristic phenotype of the fra(X) syndrome after passing through oogenesis or a postzygotic event. Findings from our multicenter study confirm a strong direct relationship between fra(X) premutation size in the mother and probability of a full mutation in offspring with the mutation. Remarkably, the best-fitting equations are nonlinear asymptotic functions. The close approximation to both the logistic model and Gompertz suggests a process of accumulation of errors in DNA synthesis, as has been proposed previously. We also note that a larger-than-expected number of daughters of transmitting males have premutations that are smaller than their fathers', and that proportion is significantly higher than the proportion of daughters whose premutations are smaller than their mothers'. Intergenerational decreases in premutation size have been reported in other trinucleotide-repeat disorders and also appear to be parent-of-origin specific. Thus, while intergenerational expansion to the full mutation in fra(X) may manifest a postzygotic event, decreases in mutation size may occur during or prior to meiosis.