Short-term effects of repetitive transcranial magnetic stimulation on sleep bruxism:a pilot study

The purpose of this study was to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on patients with sleep bruxism (SB). Twelve patients with SB were included in an open, single-intervention pilot study. rTMS at 1 Hz and an intensity of 80% of the active motor threshold was applied to the ‘hot spot' of the masseter muscle representation at the primary motor cortex bilaterally for 20 min per side each day for 5 consecutive days. The jaw-closing muscle electromyographic (EMG) activity during sleep was recorded with a portable EMG recorder at baseline, during rTMS treatment and at follow-up for 5 days. In addition, patients scored their jaw-closing muscle soreness on a 0–10 numerical rating scale (NRS). Data were analysed with analysis of variance. The intensity of the EMG activity was suppressed during and after rTMS compared to the baseline (P = 0.04; P = 0.02, respectively). The NRS score of soreness decreased significantly during and after rTMS compared with baseline (P < 0.01). These findings indicated a significant inhibition of jaw-closing muscle activity during sleep along with a decrease of muscle soreness. This pilot study raises the possibility of therapeutic benefits from rTMS in patients with bruxism and calls for further and more controlled studies

Autocatalytic Loop, Amplification and Diffusion: A Mathematical and Computational Model of Cell Polarization in Neural Chemotaxis

The chemotactic response of cells to graded fields of chemical cues is a complex process that requires the coordination of several intracellular activities. Fundamental steps to obtain a front vs. back differentiation in the cell are the localized distribution of internal molecules and the amplification of the external signal. The goal of this work is to develop a mathematical and computational model for the quantitative study of such phenomena in the context of axon chemotactic pathfinding in neural development. In order to perform turning decisions, axons develop front-back polarization in their distal structure, the growth cone. Starting from the recent experimental findings of the biased redistribution of receptors on the growth cone membrane, driven by the interaction with the cytoskeleton, we propose a model to investigate the significance of this process. Our main contribution is to quantitatively demonstrate that the autocatalytic loop involving receptors, cytoplasmic species and cytoskeleton is adequate to give rise to the chemotactic behavior of neural cells. We assess the fact that spatial bias in receptors is a precursory key event for chemotactic response, establishing the necessity of a tight link between upstream gradient sensing and downstream cytoskeleton dynamics. We analyze further crosslinked effects and, among others, the contribution to polarization of internal enzymatic reactions, which entail the production of molecules with a one-to-more factor. The model shows that the enzymatic efficiency of such reactions must overcome a threshold in order to give rise to a sufficient amplification, another fundamental precursory step for obtaining polarization. Eventually, we address the characteristic behavior of the attraction/repulsion of axons subjected to the same cue, providing a quantitative indicator of the parameters which more critically determine this nontrivial chemotactic response

Oro-facial pain experience among symphony orchestra musicians in Finland is associated with reported stress, sleep bruxism and disrupted sleep-Independent of the instrument group

Background To evaluate whether oro-facial pain experience was related to the type of musical instrument and to learn more about the roles of sleep and sleep-related issues in the pain among professional musicians. Objectives A standard questionnaire was sent to all Finnish symphony orchestras (n = 19), with altogether 1005 professional musicians and other personnel. Methods The questionnaire covered descriptive data, instrument group, items on perceived quality of sleep, possible sleep bruxism, stress experience and oro-facial pain experience during the past 30 days. Results In the present study, which included the musicians only, the response rate was 58.7% (n = 488). All orchestras participated in the study, and there was no significant difference in the response rate between the orchestras. The mean age of men (52.3%) was 47.7 (SD 10.3) and of women (47.7%) was 43.4 (SD 9.8) years (P <0.001). Overall, current pain in the oro-facial area was reported by 28.9%, frequent bruxism by 12.1% and frequent stress by 20.8%. According to Somers' d, there were statistically significant but moderate correlations between overall pain reports in the oro-facial area and disrupted sleep (d = 0.127, P = 0.001), sleep bruxism (d = 0.241, P <0.001) and stress experiences (d = 0.193, P <0.001). Logistic regression revealed, independent of the instrument group (string, woodwind, brass wind, percussion), that current oro-facial pain experience was significantly associated with disrupted sleep (P = 0.001), frequent sleep bruxism (P <0.001) and frequent stress (P = 0.002) experiences. Conclusions Among symphony orchestra musicians, oro-facial pain experience seems to be related to perceptions of stress, sleep bruxism and disrupted sleep rather than the instrument group.Peer reviewe

Acute atomoxetine treatment of younger and older children with ADHD: A meta-analysis of tolerability and efficacy

<p>Abstract</p> <p>Background</p> <p>Atomoxetine is FDA-approved as a treatment of attention-deficit/hyperactivity disorder (ADHD) in patients aged 6 years to adult. Among pediatric clinical trials of atomoxetine to date, six with a randomized, double-blind, placebo-controlled design were used in this meta-analysis. The purpose of this article is to describe and compare the treatment response and tolerability of atomoxetine between younger children (6–7 years) and older children (8–12 years) with ADHD, as reported in these six acute treatment trials.</p> <p>Methods</p> <p>Data from six clinical trials of 6–9 weeks duration were pooled, yielding 280 subjects, ages 6–7 years, and 860 subjects, ages 8–12 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-diagnosed ADHD. Efficacy was analyzed using the ADHD Rating Scale-IV (ADHD-RS), Conners' Parent Rating Scale-revised (CPRS-R:S), and the Clinical Global Impression of ADHD Severity (CGI-ADHD-S).</p> <p>Results</p> <p>Atomoxetine was superior to placebo in both age categories for mean (SD) change in ADHD-RS total, total T, and subscale scores; 3 CPRS-R:S subscales; and CGI-ADHD-S from baseline. Although there were no significant treatment differentials between the age groups for these efficacy measures, the age groups themselves, regardless of treatment, were significantly different for ADHD-RS total (younger: ATX = -14.2 [13.8], PBO = -4.6 [10.4]; older: ATX = -15.4 [13.2], PBO = -7.3 [12.0]; p = .001), total T (younger: ATX = -15.2 [14.8], PBO = -4.9 [11.2]; older: ATX = -16.4 [14.6], PBO = -7.9 [13.1]; p = .003), and subscale scores (Inattentive: younger: ATX = -7.2 [7.5], PBO = -2.4 [5.7]; older: ATX = -8.0 [7.4], PBO = -3.9 [6.7]; p = .043; Hyperactive/Impulsive: younger: ATX = -7.0 [7.2], PBO = -2.1 [5.4]; older: ATX = -7.3 [7.0], PBO = -3.4 [6.3]; p < .001), as well as the CGI-ADHD-S score (younger: ATX = -1.2 [1.3], PBO = -0.5 [0.9]; older: ATX = -1.4 [1.3], PBO = -0.7 [1.1]; p = .010). Although few subjects discontinued from either age group due to adverse events, a significant treatment-by-age-group interaction was observed for abdominal pain (younger: ATX = 19%, PBO = 6%; older: ATX = 15%, PBO = 13%; p = .044), vomiting (younger: ATX = 14%, PBO = 2%; older: ATX = 9%, PBO = 6%; p = .053), cough (younger: ATX = 10%, PBO = 6%; older: ATX = 3%, PBO = 9%; p = .007), and pyrexia (younger: ATX = 5%, PBO = 2%; older: ATX = 3%, PBO = 5%; p = .058).</p> <p>Conclusion</p> <p>Atomoxetine is an effective and generally well-tolerated treatment of ADHD in both younger and older children as assessed by three recognized measures of symptoms in six controlled clinical trials.</p> <p>Trial Registration</p> <p>Not Applicable.</p

Associations of reported bruxism with insomnia and insufficient sleep symptoms among media personnel with or without irregular shift work

<p>Abstract</p> <p>Background</p> <p>The aims were to investigate the prevalence of perceived sleep quality and insufficient sleep complaints, and to analyze whether self-reported bruxism was associated with perceptions of sleep, and awake consequences of disturbed sleep, while controlling confounding factors relative to poor sleep.</p> <p>Methods</p> <p>A standardized questionnaire was mailed to all employees of the Finnish Broadcasting Company with irregular shift work (n = 750) and to an equal number of randomly selected controls in the same company with regular eight-hour daytime work.</p> <p>Results</p> <p>The response rate in the irregular shift work group was 82.3% (56.6% men) and in the regular daytime work group 34.3% (46.7% men). Self-reported bruxism occurred frequently (often or continually) in 10.6% of all subjects. Altogether 16.8% reported difficulties initiating sleep (DIS), 43.6% disrupted sleep (DS), and 10.3% early morning awakenings (EMA). The corresponding figures for non-restorative sleep (NRS), tiredness, and sleep deprivation (SLD) were 36.2%, 26.1%, and 23.7%, respectively. According to logistic regression, female gender was a significant independent factor for all insomnia symptoms, and older age for DS and EMA. Frequent bruxism was significantly associated with DIS (p = 0.019) and DS (p = 0.021). Dissatisfaction with current work shift schedule and frequent bruxism were both significant independent factors for all variables describing insufficient sleep consequences.</p> <p>Conclusion</p> <p>Self-reported bruxism may indicate sleep problems and their adherent awake consequences in non-patient populations.</p

A developmental approach to predicting neuronal connectivity from small biological datasets: a gradient-based neuron growth model.

PMCID: PMC3931784 Open Access article: BB/G006652/1 and BB/G006369/1.Relating structure and function of neuronal circuits is a challenging problem. It requires demonstrating how dynamical patterns of spiking activity lead to functions like cognitive behaviour and identifying the neurons and connections that lead to appropriate activity of a circuit. We apply a "developmental approach" to define the connectome of a simple nervous system, where connections between neurons are not prescribed but appear as a result of neuron growth. A gradient based mathematical model of two-dimensional axon growth from rows of undifferentiated neurons is derived for the different types of neurons in the brainstem and spinal cord of young tadpoles of the frog Xenopus. Model parameters define a two-dimensional CNS growth environment with three gradient cues and the specific responsiveness of the axons of each neuron type to these cues. The model is described by a nonlinear system of three difference equations; it includes a random variable, and takes specific neuron characteristics into account. Anatomical measurements are first used to position cell bodies in rows and define axon origins. Then a generalization procedure allows information on the axons of individual neurons from small anatomical datasets to be used to generate larger artificial datasets. To specify parameters in the axon growth model we use a stochastic optimization procedure, derive a cost function and find the optimal parameters for each type of neuron. Our biologically realistic model of axon growth starts from axon outgrowth from the cell body and generates multiple axons for each different neuron type with statistical properties matching those of real axons. We illustrate how the axon growth model works for neurons with axons which grow to the same and the opposite side of the CNS. We then show how, by adding a simple specification for dendrite morphology, our model "developmental approach" allows us to generate biologically-realistic connectomes

Identification of the occurrence and pattern of masseter muscle activities during sleep using EMG and accelerometer systems

<p>Abstract</p> <p>Background</p> <p>Sleep bruxism has been described as a combination of different orofacial motor activities that include grinding, clenching and tapping, although accurate distribution of the activities still remains to be clarified.</p> <p>Methods</p> <p>We developed a new system for analyzing sleep bruxism to examine the muscle activities and mandibular movement patterns during sleep bruxism. The system consisted of a 2-axis accelerometer, electroencephalography and electromyography. Nineteen healthy volunteers were recruited and screened to evaluate sleep bruxism in the sleep laboratory.</p> <p>Results</p> <p>The new system could easily distinguish the different patterns of bruxism movement of the mandible and the body movement. Results showed that grinding (59.5%) was most common, followed by clenching (35.6%) based on relative activity to maximum voluntary contraction (%MVC), whereas tapping was only (4.9%).</p> <p>Conclusion</p> <p>It was concluded that the tapping, clenching, and grinding movement of the mandible could be effectively differentiated by the new system and sleep bruxism was predominantly perceived as clenching and grinding, which varied between individuals.</p

The Max b-HLH-LZ Can Transduce into Cells and Inhibit c-Myc Transcriptional Activities

The inhibition of the functions of c-Myc (endogenous and oncogenic) was recently shown to provide a spectacular therapeutic index in cancer mouse models, with complete tumor regression and minimal side-effects in normal tissues. This was achieved by the systemic and conditional expression of omomyc, the cDNA of a designed mutant of the b-HLH-LZ of c-Myc named Omomyc. The overall mode of action of Omomyc consists in the sequestration of Max and the concomitant competition of the Omomyc/Max complex with the endogenous c-Myc/Max heterodimer. This leads to the inhibition of the transactivation of Myc target genes involved in proliferation and metabolism. While this body of work has provided extraordinary insights to guide the future development of new cancer therapies that target c-Myc, Omomyc itself is not a therapeutic agent. In this context, we sought to exploit the use of a b-HLH-LZ to inhibit c-Myc in a cancer cell line in a more direct fashion. We demonstrate that the b-HLH-LZ domain of Max (Max*) behaves as a bona fide protein transduction domain (PTD) that can efficiently transduce across cellular membrane via through endocytosis and translocate to the nucleus. In addition, we show that the treatment of HeLa cells with Max* leads to a reduction of metabolism and proliferation rate. Accordingly, we observe a decrease of the population of HeLa cells in S phase, an accumulation in G1/G0 and the induction of apoptosis. In agreement with these phenotypic changes, we show by q-RT-PCR that the treatment of HeLa cells with Max* leads to the activation of the transcription c-Myc repressed genes as well as the repression of the expression of c-Myc activated genes. In addition to the novel discovery that the Max b-HLH-LZ is a PTD, our findings open up new avenues and strategies for the direct inhibition of c-Myc with b-HLH-LZ analogs