Signal acquisition and analysis of ambulatory electromyographic recordings for the assessment of sleep bruxism : A scoping review

Background Ambulatory electromyographic (EMG) devices are increasingly being used in sleep bruxism studies. EMG signal acquisition, analysis and scoring methods vary between studies. This may impact comparability of studies and the assessment of sleep bruxism in patients. Objectives (a) To provide an overview of EMG signal acquisition and analysis methods of recordings from limited-channel ambulatory EMG devices for the assessment of sleep bruxism; and (b) to provide an overview of outcome measures used in sleep bruxism literature utilising such devices. Method A scoping review of the literature was performed. Online databases PubMed and Semantics Scholar were searched for studies published in English until 7 October 2020. Data on five categories were extracted: recording hardware, recording logistics, signal acquisition, signal analysis and sleep bruxism outcomes. Results Seventy-eight studies were included, published between 1977 and 2020. Recording hardware was generally well described. Reports of participant instructions in device handling and of dealing with failed recordings were often lacking. Basic elements of signal acquisition, for example amplifications factors, impedance and bandpass settings, and signal analysis, for example rectification, signal processing and additional filtering, were underreported. Extensive variability was found for thresholds used to characterise sleep bruxism events. Sleep bruxism outcomes varied, but typically represented frequency, duration and/or intensity of masticatory muscle activity (MMA). Conclusion Adequate and standardised reporting of recording procedures is highly recommended. In future studies utilising ambulatory EMG devices, the focus may need to shift from the concept of scoring sleep bruxism events to that of scoring the whole spectrum of MMA.Peer reviewe

The Structural Features of Trask That Mediate Its Anti-Adhesive Functions

Trask/CDCP1 is a transmembrane protein with a large extracellular and small intracellular domains. The intracellular domain (ICD) undergoes tyrosine phosphorylation by Src kinases during anchorage loss and, when phosphorylated, Trask functions to inhibit cell adhesion. The extracellular domain (ECD) undergoes proteolytic cleavage by serine proteases, although the functional significance of this remains unknown. There is conflicting evidence regarding whether it functions to signal the phosphorylation of the ICD. To better define the structural determinants that mediate the anti-adhesive functions of Trask, we generated a series of deletion mutants of Trask and expressed them in tet-inducible cell models to define the structural elements involved in cell adhesion signaling. We find that the ECD is dispensable for the phosphorylation of the ICD or for the inhibition of cell adhesion. The anti-adhesive functions of Trask are entirely embodied within its ICD and are specifically due to tyrosine phosphorylation of the ICD as this function is completely lost in a phosphorylation-defective tyrosine-phenylalanine mutant. Both full length and cleaved ECDs are fully capable of phosphorylation and undergo phosphorylation during anchorage loss and cleavage is not an upstream signal for ICD phosphorylation. These data establish that the anti-adhesive functions of Trask are mediated entirely through its tyrosine phosphorylation. It remains to be defined what role, if any, the Trask ECD plays in its adhesion functions

On the use of the group SO(4,2) in atomic and molecular physics

In this paper the dynamical noninvariance group SO(4,2) for a hydrogen-like atom is derived through two different approaches. The first one is by an established traditional ascent process starting from the symmetry group SO(3). This approach is presented in a mathematically oriented original way with a special emphasis on maximally superintegrable systems, N-dimensional extension and little groups. The second approach is by a new symmetry descent process starting from the noninvariance dynamical group Sp(8,R) for a four-dimensional harmonic oscillator. It is based on the little known concept of a Lie algebra under constraints and corresponds in some sense to a symmetry breaking mechanism. This paper ends with a brief discussion of the interest of SO(4,2) for a new group-theoretical approach to the periodic table of chemical elements. In this connection, a general ongoing programme based on the use of a complete set of commuting operators is briefly described. It is believed that the present paper could be useful not only to the atomic and molecular community but also to people working in theoretical and mathematical physics.Comment: 31 page

Screening of DUB activity and specificity by MALDI-TOF mass spectrometry

Deubiquitylases (DUBs) are key regulators of the ubiquitin system which cleave ubiquitin moieties from proteins and polyubiquitin chains. Several DUBs have been implicated in various diseases and are attractive drug targets. We have developed a sensitive and fast assay to quantify in vitro DUB enzyme activity using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Unlike other current assays, this method uses unmodified substrates, such as diubiquitin topoisomers. By analyzing 42 human DUBs against all diubiquitin topoisomers we provide an extensive characterization of DUB activity and specificity. Our results confirm the high specificity of many members of the OTU and JAMM DUB families and highlight that all USPs tested display low linkage selectivity. We also demonstrate that this assay can be deployed to assess the potency and specificity of DUB inhibitors by profiling 11 compounds against a panel of 32 DUBs

Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Virtual Patients and Sensitivity Analysis of the Guyton Model of Blood Pressure Regulation: Towards Individualized Models of Whole-Body Physiology

Mathematical models that integrate multi-scale physiological data can offer insight into physiological and pathophysiological function, and may eventually assist in individualized predictive medicine. We present a methodology for performing systematic analyses of multi-parameter interactions in such complex, multi-scale models. Human physiology models are often based on or inspired by Arthur Guyton's whole-body circulatory regulation model. Despite the significance of this model, it has not been the subject of a systematic and comprehensive sensitivity study. Therefore, we use this model as a case study for our methodology. Our analysis of the Guyton model reveals how the multitude of model parameters combine to affect the model dynamics, and how interesting combinations of parameters may be identified. It also includes a “virtual population” from which “virtual individuals” can be chosen, on the basis of exhibiting conditions similar to those of a real-world patient. This lays the groundwork for using the Guyton model for in silico exploration of pathophysiological states and treatment strategies. The results presented here illustrate several potential uses for the entire dataset of sensitivity results and the “virtual individuals” that we have generated, which are included in the supplementary material. More generally, the presented methodology is applicable to modern, more complex multi-scale physiological models

Dynamic simulations on the mitochondrial fatty acid Beta-oxidation network

<p>Abstract</p> <p>Background</p> <p>The oxidation of fatty acids in mitochondria plays an important role in energy metabolism and genetic disorders of this pathway may cause metabolic diseases. Enzyme deficiencies can block the metabolism at defined reactions in the mitochondrion and lead to accumulation of specific substrates causing severe clinical manifestations. Ten of the disorders directly affecting mitochondrial fatty acid oxidation have been well-defined, implicating episodic hypoketotic hypoglycemia provoked by catabolic stress, multiple organ failure, muscle weakness, or hypertrophic cardiomyopathy. Additionally, syndromes of severe maternal illness (HELLP syndrome and AFLP) have been associated with pregnancies carrying a fetus affected by fatty acid oxidation deficiencies. However, little is known about fatty acids kinetics, especially during fasting or exercise when the demand for fatty acid oxidation is increased (catabolic stress).</p> <p>Results</p> <p>A computational kinetic network of 64 reactions with 91 compounds and 301 parameters was constructed to study dynamic properties of mitochondrial fatty acid β-oxidation. Various deficiencies of acyl-CoA dehydrogenase were simulated and verified with measured concentrations of indicative metabolites of screened newborns in Middle Europe and South Australia. The simulated accumulation of specific acyl-CoAs according to the investigated enzyme deficiencies are in agreement with experimental data and findings in literature. Investigation of the dynamic properties of the fatty acid β-oxidation reveals that the formation of acetyl-CoA – substrate for energy production – is highly impaired within the first hours of fasting corresponding to the rapid progress to coma within 1–2 hours. LCAD deficiency exhibits the highest accumulation of fatty acids along with marked increase of these substrates during catabolic stress and the lowest production rate of acetyl-CoA. These findings might confirm gestational loss to be the explanation that no human cases of LCAD deficiency have been described.</p> <p>Conclusion</p> <p>In summary, this work provides a detailed kinetic model of mitochondrial metabolism with specific focus on fatty acid β-oxidation to simulate and predict the dynamic response of that metabolic network in the context of human disease. Our findings offer insight into the disease process (e.g. rapid progress to coma) and might confirm new explanations (no human cases of LCAD deficiency), which can hardly be obtained from experimental data alone.</p