Specificity of protein kinases and phosphatases may be achieved through compartmentalization with preferred substrates. In neurons, adenosine 3', 5'-monophosphate (cAMP)-dependent protein kinase (PKA) is localized at postsynaptic densities by association of its regulatory subunit with an A kinase anchor protein, AKAP79. Interaction cloning experiments demonstrated that AKAP79 also binds protein phosphatase 2B, or calcineurin (CaN). A ternary complex of PKA, AKAP, and CaN was isolated from bovine brain, and colocalization of the kinase and the phosphatase was established in neurites of cultured hippocampal neurons. The putative CaN-binding domain of AKAP79 is similar to that of the immunophilin FKBP-12, and AKAP79 inhibited CaN phosphatase activity. These results suggest that both PKA and CaN are targeted to subcellular sites by association with a common anchor protein and thereby regulate the phosphorylation state of key neuronal substrates.

Ethnic associations with PAD remained significant even after adjustment for traditional and novel risk factors. This suggests that unknown factors may account for the residual ethnic differences in PAD.

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Background The prevalence of dentin hypersensitivity is uncertain, yet appropriate diagnosis and treatment of dentin hypersensitivity require accurate knowledge regarding its prevalence. The authors conducted a study to estimate the prevalence of dentin hypersensitivity in general dental practices and to investigate associated risk factors. Methods The authors conducted a cross-sectional survey of 787 adult patients from 37 general dental practices within Northwest Practice-based Research Collaborative in Evidence-based DENTistry (PRECEDENT). Dentin hypersensitivity was diagnosed by means of participants’ responses to a question regarding pain in their teeth and gingivae, and practitioner-investigators conducted a clinical examination to rule out alternative causes of pain. Participants recorded their pain level on a visual analog scale and the Seattle Scales in response to a one-second air blast. The authors used generalized estimating equation log-linear models to estimate the prevalence and the prevalence ratios. Results The prevalence of dentin hypersensitivity was 12.3 percent; patients with hypersensitivity had, on average, 3.5 hypersensitive teeth. The prevalence of dentin hypersensitivity was higher among 18- to 44-year olds than among participants 65 years or older; it also was higher in women than in men, in participants with gingival recession than in those without gingival recession and in participants who underwent at-home tooth whitening than in those who did not. Hypersensitivity was not associated with obvious occlusal trauma, noncarious cervical lesions or aggressive toothbrushing habits. Conclusions One in eight participants from general practices had dentin hypersensitivity, which was a chronic condition causing intermittent, low-level pain. Patients with hypersensitivity were more likely to be younger, to be female and to have a high prevalence of gingival recession and at-home tooth whitening. Practical Implications Given dentin hypersensitivity’s prevalence, clinicians should diagnose it only after investigating all other possible sources of pain.

Stepped wedge designs are increasingly commonplace and advantageous for cluster randomized trials (CRTs) when it is both unethical to assign placebo and it is logistically difficult to allocate an intervention simultaneously to many clusters. We study marginal mean models fit with generalized estimating equations (GEE) for assessing treatment effectiveness in stepped wedge CRTs. This approach has advantages over the more commonly used mixed models that (1) the population-average parameters have an important interpretation for public health applications and (2) they avoid untestable assumptions on latent variable distributions and avoid parametric assumptions about error distributions, therefore providing more robust evidence on treatment effects. However, CRTs typically have a small number of clusters, rendering the standard GEE sandwich variance estimator biased and highly variable and hence yielding incorrect inferences. We study the usual asymptotic GEE inferences (i.e., using sandwich variance estimators and asymptotic normality) and four small-sample corrections to GEE for stepped wedge CRTs and for parallel CRTs as a comparison. We show by simulation that the small-sample corrections provide improvement, with one correction appearing to provide at least nominal coverage even with only 10 clusters per group. These results demonstrate the viability of the marginal mean approach for both stepped wedge and parallel CRTs. We also study the comparative performance of the corrected methods for stepped wedge and parallel designs, and describe how the methods can accommodate interval censoring of individual failure times and incorporate semiparametric efficient estimators.

Background Temporomandibular disorder (TMD) incidences are believed to be related to parafunctional behaviors like teeth clenching. Objectives This pilot study aimed to (i) develop an automated clench-detection algorithm, and (ii) apply the algorithm to test for differences in nocturnal clenching in women with and without TMD. Methods Subjects gave informed consent to participate. Adult women were categorized using Diagnostic Criteria for TMD according to presence/absence (+/-) of both TM joint disc placement (DD) and chronic pain (P) into two groups (+DD+P, -DD-P) with 12 subjects each. Surface temporalis electromyography was recorded during oral tasks performed by subjects at two laboratory sessions. The data were used to characterize muscle activity per N of bite-force (μV/N) for each subject, develop the clench-detection algorithm and test its accuracy. Ambulatory surface temporalis electromyography was self-recorded by each subject over three nights and analyzed using the algorithm and bite-force (N) vs muscle activity μV/N calibrations. Bonferroni-adjusted homoscedastic t-tests assessed for significant between-group differences in clenching (p<0.05). Results Sensitivity, specificity, and accuracy of algorithm-detected laboratory clenches were all ≥96%. During self-recordings 95% of clenches had durations of <4 seconds and peak forces of <10 N in both groups. Mean clench durations were significantly longer (p=0.042) in +DD+P (1.9±0.8 seconds) than -DD-P subjects (1.4±0.4 seconds). Mean temporalis duty factors (%clench time/total recording time) were significantly larger (p=0.041) in +DD+P (0.47±0.34%) than -DD-P (0.26±0.22%) subjects. Conclusions Nocturnal temporalis muscle activities detected by a validated algorithm were longer per clench and recording time in +DD+P compared to -DD-P women.

Objective Unmet dental need in children with autism spectrum disorder (ASD) is common. We tested hypotheses that lacking a medical home or having characteristics of more severe ASD is positively associated with having unmet dental need among children with ASD. Methods Using data from the 2009–2010 National Survey of Children with Special Health Care Needs, we analyzed 2,772 children 5–17 years old with ASD. We theorized unmet dental need would be positively associated with not having a medical home and having characteristics of more severe ASD (e.g. parent reported severe ASD, an intellectual disability, communication or behavior difficulties). Prevalence of unmet dental need was estimated, and unadjusted and adjusted odds ratios (ORs), 95% confidence intervals (CIs), and p-values were computed using survey methods for logistic regression. Results Nationally, 15.1% of children with ASD had unmet dental need. Among children with ASD, those without a medical home were more apt to have unmet dental need than those with a medical home (adjusted OR 4.46, 95% CI: 2.59, 7.69). Children with ASD with intellectual disability or greater communication or behavioral difficulties had greater odds of unmet dental need than those with ASD without these characteristics. Parent reported ASD severity was not associated with unmet dental need. Conclusions Children with ASD without a medical home and with characteristics suggestive of increased ASD-related difficulties are more apt to have unmet dental need. Pediatricians may use these findings to aid in identifying children with ASD who may not receive all needed dental care.

SYNOPSIS Excess added sugars, particularly in the form of sugar sweetened beverages, is a leading cause of tooth decay in U.S. children. While added sugar intake is rooted behavioral and social factors, few evidence-based, theory-driven sociobehavioral strategies are currently available to address added sugar intake. Dental health professionals are in a position to help identify and address problematic sugar-related behaviors in pediatric patients and advocate for broader upstream approaches including taxes, warning labels, and policy changes that can help to reduce added sugar intake, prevent tooth decay, and improve health outcomes in vulnerable child populations.