Associations of Patient Mood, Modulators of Quality of Life, and Pharmaceuticals with Amyotrophic Lateral Sclerosis Survival Duration.

Associations of modulators of quality of life (QoL) and survival duration are assessed in the fatal motor neuron disease, Amyotrophic Lateral Sclerosis. Major categories include clinical impression of mood (CIM); physical health; patient social support; and usage of interventions, pharmaceuticals, and supplements. Associations were assessed at p < 0.05 and p < 0.001 significance thresholds using applicable methods (Chi-square, t-test, ANOVA, logistical regression, random forests, Fisher's exact test) within a retrospective cohort of 1585 patients. Factors significantly correlated with positive (happy or normal) mood included family support and usage of bi-level positive airway pressure (Bi-PAP) and/or cough assist. Decline in physical factors like presence of dysphagia, drooling, general pain, and decrease in ALSFRS-R total score or forced vital capacity (FVC) significantly correlated with negative (depressed or anxious) mood (p < 0.05). Use of antidepressants or pain medications had no association with ALS patient mood (p > 0.05), but were significantly associated with increased survival (p < 0.05). Positive patient mood, Bi-PAP, cough assist, percutaneous endoscopic gastrostomy (PEG), and accompaniment to clinic visits associated with increased survival duration (p < 0.001). Of the 47 most prevalent pharmaceutical and supplement categories, 17 associated with significant survival duration increases ranging +4.5 to +16.5 months. Tricyclic antidepressants, non-opioids, muscle relaxants, and vitamin E had the highest associative increases in survival duration (p < 0.05). Random forests, which examined complex interactions, identified the following pharmaceuticals and supplements as most predictive to survival duration: Vitamin A, multivitamin, PEG supplements, alternative herbs, antihistamines, muscle relaxants, stimulant laxatives, and antispastics. Statins, metformin, and thiazide diuretics had insignificant associations with decreased survival.

Design, characterization and optimization of a soft fluidic actuator for minimally invasive surgery.

PURPOSE: In minimally invasive surgery and endoscopy, the rise of soft robotics, using materials of similar softness as biological soft tissues, opens many new opportunities. Soft actuated catheters could become an alternative to current steerable catheters, by minimizing the risk of damage to surrounding tissues while enhancing the possibilities to navigate in confined space and to reach remote locations. Fluidic actuators present the advantage to be safe, since they do not require rigid parts nor voltage, to be lightweight, and to allow the reduction of the number of parts needed for a given movement. This work presents the design, development and characterization of a soft fluidic bending actuator for a steerable catheter. METHODS: A silicone prototype of 5 mm diameter has been designed. It has one degree of freedom in bending and achieves a radius of curvature below 10 mm. A numerical model has been developed and compared to the experimental results. RESULTS: Despite an overestimation of the bending, the numerical model properly captures the behaviour of the actuator. This allowed to identify and validate the key design parameters of the actuator, namely the ratio between the pressure channel surface and the actuator cross-section surface. Based on the results, an optimized design has been developed and numerically implemented. The miniaturization and the potential to carry devices with non-negligible bending stiffness have also been discussed. CONCLUSION: In this work, a proof of concept of a soft fluidic actuator for a steerable catheter has been designed, developed and characterized. It showed promising results concerning the feasibility of a miniaturized actuator with two degrees of freedom.

The larynx ruler to measure height and profile of vocal folds: a proof of concept.

INTRODUCTION: Glottic leakage during phonation is a direct consequence of unilateral vocal fold (VF) paralysis. This air leakage can be in the horizontal plane and in the vertical plane. Presently, there is no easily applicable medical device allowing noninvasive, office-based measurement of the relative vertical position of the VFs. The larynx ruler (LR) is a laser-based measuring device that could meet the previously stated need, using a flexible endoscope. This study represents a proof of concept regarding the use of the LR in assessing VF relative positions in the vertical plane. MATERIALS AND METHODS: One fresh male human cadaver larynx, free of neurologic and anatomic disease, was explored with the LR system through the operative channel of a flexible gastroenterology video-endoscope. The tip of the video-endoscope was located in the laryngeal vestibule. The right crico-arytenoid joint was posteriorly disarticulated. Tilting of the VF was obtained by pulling or pushing the arytenoid cartilage with a mosquito forceps fixed to the stump of the previously sectioned superior tip of the posterior crico-arytenoid muscle allowing anterior and posterior tilting of the arytenoid cartilage in order to induce an elevation or a depression of the VF process. Ten "push" and ten "pull" sessions were performed. The distance from the tip of the video-endoscope to each illuminated pixel of the laser beam was recorded. The level difference between the left and right VFs was measured for each recording. RESULTS: Data provided by the LR were consistently in accordance with the movements applied on the VFs. The accuracy of 0.2 mm of the LR is compatible with the envisioned applications for the human larynx. CONCLUSION: The LR system represents a feasible technique to evaluate respective vertical position of VFs in the human larynx. Technical limitations were identified that will require improvements before experimental use on human beings.

Type I Vs. Type II Cytokine Levels as a Function of SOD1 G93A Mouse Amyotrophic Lateral Sclerosis Disease Progression.

Amyotrophic Lateral Sclerosis (ALS) is a fatal motoneuron disease that is characterized by the degradation of neurons throughout the central nervous system. Inflammation have been cited a key contributor to ALS neurodegeneration, but the timeline of cytokine upregulation remains unresolved. The goal of this study was to temporally examine the correlation between the varying levels of pro-inflammatory type I cytokines (IL-1ß, IL-1α, IL-12, TNF-α, and GFAP) and anti-inflammatory type II cytokines (IL-4, IL-6, IL-10) throughout the progression of ALS in the SOD1 G93A mouse model. Cytokine level data from high copy SOD1 G93A transgenic mice was collected from 66 peer-reviewed studies. For each corresponding experimental time point, the ratio of transgenic to wild type (TG/WT) cytokine was calculated. One-way ANOVA and t-tests with Bonferonni correction were used to analyze the data. Meta-analysis was performed for four discrete stages: early, pre-onset, post-onset, and end stage. A significant increase in TG cytokine levels was found when compared to WT cytokine levels across the entire SOD1 G93A lifespan for majority of the cytokines. The rates of change of the individual cytokines, and type I and type II were not significantly different; however, the mean fold change of type I was expressed at significantly higher levels than type II levels across all stages with the difference between the means becoming more pronounced at the end stage. An overexpression of cytokines occurred both before and after the onset of ALS symptoms. The trend between pro-inflammatory type I and type II cytokine mean levels indicate a progressive instability of the dynamic balance between pro- and anti-inflammatory cytokines as anti-inflammatory cytokines fail to mediate the pronounced increase in pro-inflammatory cytokines. Very early immunoregulatory treatment is necessary to successfully interrupt ALS-induced neuroinflammation.

In vitro study of the effects of ELF electric fields on gene expression in human epidermal cells.

An acceleration of differentiation, at the expense of proliferation, is observed after exposure of various biological models to low frequency and low amplitude electric and electromagnetic fields. Following these results showing significant modifications, we try to identify the biological mechanism involved at the cell level through microarray screening. For this study, we use epidermis cultures harvested from human abdominoplasty. Two platinum electrodes are used to apply the electric signal. The gene expressions of 38,500 well-characterized human genes are analyzed using Affymetrix(®) microarray U133 Plus 2.0 chips. The protocol is repeated on three different patients. After three periods of exposure, a total of 24 chips have been processed. After the application of ELF electric fields, the microarray analysis confirms a modification of the gene expression of epidermis cells. Particularly, four up-regulated genes (DKK1, TXNRD1, ATF3, and MME) and one down-regulated gene (MACF1) are involved in the regulation of proliferation and differentiation. Expression of these five genes was also confirmed by real-time rtPCR in all samples used for microarray analysis. These results corroborate an acceleration of cell differentiation at the expense of cell proliferation.