Electrophysiologic Biomarkers for Assessing Disease Progression and the Effect of Riluzole in SOD1 G93A ALS Mice

Objective: To compare electrical impedance myography (EIM) 50 kHz phase to weight, motor score, paw grip endurance (PGE), CMAP amplitude, and MUNE for the identification of disease progression and the effect of riluzole in the SOD1 G93A mouse. Methods: Twenty-three animals received 8 mg/kg/day riluzole in the drinking water starting at 6 weeks of age; 22 animals served as controls. Weight, motor score, PGE, CMAP, MUNE, and EIM were performed weekly to evaluate disease progression. Results: No difference in clinical disease onset or survival was found between treated and untreated groups. In addition, all methods failed to identify any beneficial effect of riluzole. Thus, data from all animals were combined for additional analyses. Of the 4 parameters, EIM phase showed the earliest change from baseline and the most linear decline throughout the entire measurement period. In addition, EIM phase correlated with PGE, CMAP amplitude, and MUNE (Spearman r = 0.92, 0.90, and 0.72, respectively, p<0.01 for all). The rate of EIM phase decline also correlated with individual animal survival (Spearman r = −0.31, p<0.05). Conclusions: At this dose, riluzole is ineffective in slowing progression of ALS. However, EIM phase shows early linear declines, supporting its potential as a useful new biomarker for preclinical drug testing

Developing a Low-Cost Force Treadmill via Dynamic Modeling

By incorporating force transducers into treadmills, force platform-instrumented treadmills (commonly called force treadmills) can collect large amounts of gait data and enable the ground reaction force (GRF) to be calculated. However, the high cost of force treadmills has limited their adoption. This paper proposes a low-cost force treadmill system with force sensors installed underneath a standard exercise treadmill. It identifies and compensates for the force transmission dynamics from the actual GRF applied on the treadmill track surface to the force transmitted to the force sensors underneath the treadmill body. This study also proposes a testing procedure to assess the GRF measurement accuracy of force treadmills. Using this procedure in estimating the GRF of “walk-on-the-spot motion,” it was found that the total harmonic distortion of the tested force treadmill system was about 1.69%, demonstrating the effectiveness of the approach

Assessing Postural Stability Via the Correlation Patterns of Vertical Ground Reaction Force Components

Background Many methods have been proposed to assess the stability of human postural balance by using a force plate. While most of these approaches characterize postural stability by extracting features from the trajectory of the center of pressure (COP), this work develops stability measures derived from components of the ground reaction force (GRF). Methods In comparison with previous GRF-based approaches that extract stability features from the GRF resultant force, this study proposes three feature sets derived from the correlation patterns among the vertical GRF (VGRF) components. The first and second feature sets quantitatively assess the strength and changing speed of the correlation patterns, respectively. The third feature set is used to quantify the stabilizing effect of the GRF coordination patterns on the COP. Results In addition to experimentally demonstrating the reliability of the proposed features, the efficacy of the proposed features has also been tested by using them to classify two age groups (18–24 and 65–73 years) in quiet standing. The experimental results show that the proposed features are considerably more sensitive to aging than one of the most effective conventional COP features and two recently proposed COM features. Conclusions By extracting information from the correlation patterns of the VGRF components, this study proposes three sets of features to assess human postural stability during quiet standing. As demonstrated by the experimental results, the proposed features are not only robust to inter-trial variability but also more accurate than the tested COP and COM features in classifying the older and younger age groups. An additional advantage of the proposed approach is that it reduces the force sensing requirement from 3D to 1D, substantially reducing the cost of the force plate measurement system

Shaping the Emerging Norms of Using Large Language Models in Social Computing Research

The emergence of Large Language Models (LLMs) has brought both excitement and concerns to social computing research. On the one hand, LLMs offer unprecedented capabilities in analyzing vast amounts of textual data and generating human-like responses, enabling researchers to delve into complex social phenomena. On the other hand, concerns are emerging regarding the validity, privacy, and ethics of the research when LLMs are involved. This SIG aims at offering an open space for social computing researchers who are interested in understanding the impacts of LLMs to discuss their current practices, perspectives, challenges when engaging with LLMs in their everyday work and collectively shaping the emerging norms of using LLMs in social computing research

A Technique for Performing Electrical Impedance Myography in the Mouse Hind Limb: Data in Normal and ALS SOD1 G93A Animals

Objective: To test a method for performing electrical impedance myography (EIM) in the mouse hind limb for the assessment of disease status in neuromuscular disease models. Methods: An impedance measuring device consisting of a frame with electrodes embedded within an acrylic head was developed. The head was rotatable such that data longitudinal and transverse to the major muscle fiber direction could be obtained. EIM measurements were made with this device on 16 healthy mice and 14 amyotrophic lateral sclerosis (ALS) animals. Repeatability was assessed in both groups. Results: The technique was easy to perform and provided good repeatability in both healthy and ALS animals, with intra-session repeatability (mean ± SEM) of 5% ±1% and 12% ±2%, respectively. Significant differences between healthy and ALS animals were also identified (e.g., longitudinal mean 50 kHz phase was 18±0.6° for the healthy animals and 14±1.0° for the ALS animals, p = 0.0025). Conclusions: With this simple device, the EIM data obtained is highly repeatable and can differentiate healthy from ALS animals. Significance: EIM can now be applied to mouse models of neuromuscular disease to assess disease status and the effects of therapy

Epigenetic Modifiers Are Necessary but Not Sufficient for Reprogramming Non-Myelinating Cells into Myelin Gene-Expressing Cells

Modifications on specific histone residues and DNA methylation play an essential role in lineage choice and cellular reprogramming. We have previously shown that histone modifications or combinatorial codes of transcription factors (TFs) are critical for the differentiation of multipotential progenitors into myelinating oligodendrocytes. In this study we asked whether combining global manipulation of DNA methylation and histone acetylation together with the expression of oligodendrocyte-specific TFs, was sufficient to switch the identity of fibroblasts into myelin gene-expressing cells.Transfection of six oligodendrocyte-specific TFs (Olig1, Olig2, Sox10, Mash1, E47 and Nkx2.2) into NIH3T3 fibroblasts was capable of inducing expression of myelin gene promoter-driven reporters, but did not activate endogenous myelin gene expression. These results suggested the existence of a transcriptionally incompetent chromatin conformation in NIH3T3 fibroblasts. Using chromatin immunoprecipitation (ChIP) analysis, we compared the histone code on the conserved regions of myelin genes (i.e. Mbp and Mag) in differentiating oligodendrocyte progenitors and NIH3T3 fibroblasts. Chromatin at myelin gene loci was characterized by the presence of repressive histone modifications (me3K9H3 and me3K27H3) in NIH3T3 fibroblasts and active histone marks (me3K4H3 and AcH3) in oligodendrocyte lineage cells. To induce a transcriptionally competent chromatin signature, NIH3T3 fibroblasts were treated with 5-azadeoxy-citidine (5-AzaC) to decrease DNA methylation, and trichostatin A (TSA) or sirtinol, to favor histone acetylation. Treatment with 5-AzaC/TSA but not sirtinol, resulted in the detection of endogenous myelin gene transcripts in fibroblasts, although not to the levels detected in myelinating cells. Transfection of oligodendrocyte-specific TFs after 5-AzaC/TSA treatment did not further increase myelin gene expression, nor did it reprogram the transcriptional network of NIH3T3 fibroblasts into that of oligodendrocytes.These results suggest that reprogramming of fibroblasts into myelin gene-expressing cells not only requires transcriptional activation, but also chromatin manipulations that go beyond histone acetylation and DNA methylation

Impact of gastroesophageal reflux disease on daily life: the Systematic Investigation of Gastrointestinal Diseases in China (SILC) epidemiological study

<p>Abstract</p> <p>Background</p> <p>Gastroesophageal reflux disease imposes a significant burden of illness in Western populations. However, data on the impact of reflux symptoms on daily life in Asian populations are scarce. The current study aimed to evaluate the impact of GERD (defined on the basis of symptoms) on health-related quality-of-life (HRQoL) in individuals from five regions in China, as part of the Systematic Investigation of Gastrointestinal Diseases in China (SILC) study.</p> <p>Methods</p> <p>In total, 18 000 residents were randomly selected from across five regions of China and asked to complete a general information questionnaire and a Chinese version of the Reflux Disease Questionnaire (RDQ). A randomly selected subsample of one-fifth of subjects (20% from each region) completed Chinese versions of the 36-item self-administered (SF-36) questionnaire and Epworth Sleepiness Scale (ESS) questionnaire. Reflux symptoms were defined as the presence of heartburn and/or regurgitation. Symptom-defined GERD was diagnosed as mild heartburn and/or regurgitation ≥2 days per week, or moderate/severe heartburn and/or regurgitation ≥1 day a week, based on the Montreal Definition of GERD for population-based studies.</p> <p>Results</p> <p>The response rate was 89.4% for the total sample (16 091/18 000), and for the 20% subsample (3219/3600). Meaningful impairment was observed in all 8 SF-36 dimensions in participants with symptom-defined GERD, in 7 of the 8 SF-36 dimensions in participants with troublesome reflux symptoms, and in 6 of the 8 SF-36 dimensions in participants with reflux symptoms below the threshold for symptom-defined GERD. Meaningful daytime sleepiness was also observed in each of these groups. The proportion of individuals reporting troublesome symptoms increased as reflux symptom frequency and severity approached the threshold for symptom-defined GERD, and this was associated with concomitant decreases in all HRQoL measures. Troublesome symptoms were reported by 68.2% (75/110) of individuals with symptom-defined GERD.</p> <p>Conclusions</p> <p>GERD diagnosed using symptom/frequency criteria (recommended for population-based studies), or based on troublesome reflux symptoms (recommended for the clinic), is associated with significantly impaired HRQoL in Chinese individuals. However, patient groups identified using these definitions do not overlap completely, suggesting that they capture slightly different, though clinically relevant, GERD populations.</p