Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism

The absence of phytoestrogens in the diet during pregnancy has been reported to result in obesity later in adulthood. We investigated whether phytoestrogen withdrawal in adult life could alter the hypothalamic signals that regulate food intake and affect body weight and glucose homeostasis. Male Wistar rats fed from conception to adulthood with a high phytoestrogen diet were submitted to phytoestrogen withdrawal by feeding a low phytoestrogen diet, or a high phytoestrogen-high fat diet. Withdrawal of dietary phytoestrogens increased body weight, adiposity and energy intake through an orexigenic hypothalamic response characterized by upregulation of AGRP and downregulation of POMC. This was associated with elevated leptin and T4, reduced TSH, testosterone and estradiol, and diminished hypothalamic ERα expression, concomitant with alterations in glucose tolerance. Removing dietary phytoestrogens caused manifestations of obesity and diabetes that were more pronounced than those induced by the high phytoestrogen-high fat diet intake

Estimation of Subglottal Pressure, Vocal Fold Collision Pressure, and Intrinsic Laryngeal Muscle Activation From Neck-Surface Vibration Using a Neural Network Framework and a Voice Production Model

The ambulatory assessment of vocal function can be significantly enhanced by having access to physiologically based features that describe underlying pathophysiological mechanisms in individuals with voice disorders. This type of enhancement can improve methods for the prevention, diagnosis, and treatment of behaviorally based voice disorders. Unfortunately, the direct measurement of important vocal features such as subglottal pressure, vocal fold collision pressure, and laryngeal muscle activation is impractical in laboratory and ambulatory settings. In this study, we introduce a method to estimate these features during phonation from a neck-surface vibration signal through a framework that integrates a physiologically relevant model of voice production and machine learning tools. The signal from a neck-surface accelerometer is first processed using subglottal impedance-based inverse filtering to yield an estimate of the unsteady glottal airflow. Seven aerodynamic and acoustic features are extracted from the neck surface accelerometer and an optional microphone signal. A neural network architecture is selected to provide a mapping between the seven input features and subglottal pressure, vocal fold collision pressure, and cricothyroid and thyroarytenoid muscle activation. This non-linear mapping is trained solely with 13,000 Monte Carlo simulations of a voice production model that utilizes a symmetric triangular body-cover model of the vocal folds. The performance of the method was compared against laboratory data from synchronous recordings of oral airflow, intraoral pressure, microphone, and neck-surface vibration in 79 vocally healthy female participants uttering consecutive /pæ/ syllable strings at comfortable, loud, and soft levels. The mean absolute error and root-mean-square error for estimating the mean subglottal pressure were 191 Pa (1.95 cm H2O) and 243 Pa (2.48 cm H2O), respectively, which are comparable with previous studies but with the key advantage of not requiring subject-specific training and yielding more output measures. The validation of vocal fold collision pressure and laryngeal muscle activation was performed with synthetic values as reference. These initial results provide valuable insight for further vocal fold model refinement and constitute a proof of concept that the proposed machine learning method is a feasible option for providing physiologically relevant measures for laboratory and ambulatory assessment of vocal function.Fil: Ibarra, Emiro J.. Universidad Tecnica Federico Santa Maria.; ChileFil: Parra, Jesús A.. Universidad Tecnica Federico Santa Maria.; ChileFil: Alzamendi, Gabriel Alejandro. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Cortés, Juan P.. Universidad Tecnica Federico Santa Maria.; ChileFil: Espinoza, Víctor M.. Universidad de Chile; ChileFil: Mehta, Daryush D.. Center For Laryngeal Surgery And Voice Rehabilitation; Estados UnidosFil: Hillman, Robert E.. Center For Laryngeal Surgery And Voice Rehabilitation; Estados UnidosFil: Zañartu, Matías. Universidad Tecnica Federico Santa Maria.; Chil

Procesamiento, análisis y modelado de señales biomédicas: un enfoque integrador

Este proyecto se centra en el estudio, desarrollo y aplicación de técnicas de procesamiento, modelado y análisis de señales que permitan abordar los casos de señales biomédicas. Abordaremos métodos adaptativos de análisis de señales, principalmente la descomposición empírica en modos y sus variantes. Se avanzará en el desarrollo de modelos de las señales relacionadas con el aparato fonador. Se continuará el estudio de modelos en espacio de estados que permiten extraer información sobre el estado instantáneo del tracto vocal y de la fuente glótica. Se estudiará la factibilidad de extraer nuevos parámetros acústicos de utilidad clínica. Investigaremos técnicas y herramientas provenientes de la teoría de la información estudiando medidas basadas en la integral de correlación asistida por ruido y la integral de correlación U, propuestas por nuestro grupo, para la estimación de los invariantes dimensión, entropía y ruido, en sistemas simulados y reales de variadas dimensiones. Finalmente, se continuará con la formación de recursos humanos, a través de la realización de becas postdoctorales y doctorales CONICET, y el fortalecimiento de un grupo de investigación en el área de las TICs en el procesamiento de señales biomédicas, en el contexto del Instituto de Bioinformática y Bioingeniería en vías de creación. ARK/CAICYT: http://id.caicyt.gov.ar/ark:/s22504559/rd18ww2h

Parametrial adipose tissue and metabolic dysfunctions induced by fructose-rich diet in normal and neonatal-androgenized adult female rats.

Hyperandrogenemia predisposes an organism toward developing impaired insulin sensitivity. The aim of our study was to evaluate endocrine and metabolic effects during early allostasis induced by a fructose-rich diet (FRD) in normal (control; CT) and neonatal-androgenized (testosterone propionate; TP) female adult rats. CT and TP rats were fed either a normal diet (ND) or an FRD for 3 weeks immediately before the day of study, which was at age 100 days. Energy intake, body weight (BW), parametrial (PM) fat characteristics, and endocrine/metabolic biomarkers were then evaluated. Daily energy intake was similar in CT and TP rats regardless of the differences in diet. When compared with CT-ND rats, the TP-ND rats were heavier, had larger PM fat, and were characterized by basal hypoadiponectinemia and enhanced plasma levels of non-esterified fatty acid (NEFA), plasminogen activator inhibitor-1 (PAI-1), and leptin. FRD-fed CT rats, when compared with CT-ND rats, had high plasma levels of NEFA, triglyceride (TG), PAI-1, leptin, and adiponectin. The TP-FRD rats, when compared with TP-ND rats, displayed enhanced leptinemia and triglyceridemia, and were hyperinsulinemic, with glucose intolerance. The PM fat taken from TP rats displayed increase in the size of adipocytes, decrease in adiponectin (protein/gene), and a greater abundance of the leptin gene. PM adipocyte response to insulin was impaired in CT-FRD, TP-ND, and TP-FRD rats. A very short duration of isocaloric FRD intake in TP rats induced severe metabolic dysfunction at the reproductive age. Our study supports the hypothesis that the early-androgenized female rat phenotype is highly susceptible to developing endocrine/metabolic dysfunction. In turn, these abnormalities enhance the risk of metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease

Modeling the influence of the extrinsic musculature on phonation

Neck muscles play important roles in various physiological tasks, including swallowing, head stabilization, and phonation. The mechanisms by which neck muscles influence phonation are not well understood, with conflicting reports on the change in fundamental frequency for ostensibly the same neck muscle activation scenarios. In this work, we introduce a reduced-order muscle-controlled vocal fold model, comprising both intrinsic muscle control and extrinsic muscle effects. The model predicts that when the neck muscles pull the thyroid cartilage in the superior–anterior direction (with a sufficiently large anterior component), inferior direction, or inferior–anterior direction, tension in the vocal folds increases, leading to fundamental frequency rise during sustained phonation. On the other hand, pulling in the superior direction, superior–posterior direction, or inferior–posterior direction (with a sufficiently large posterior component) tends to decrease vocal fold tension and phonation fundamental frequency. Varying the pulling force location alters the posture and phonation biomechanics, depending on the force direction. These findings suggest potential roles of particular neck muscles in modulating phonation fundamental frequency, with implications for vocal hyperfunction.Fil: Serry, Mohamed A.. University of Waterloo; CanadáFil: Alzamendi, Gabriel Alejandro. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Zañartu, Matías. Universidad Tecnica Federico Santa Maria.; ChileFil: Peterson, Sean D.. University of Waterloo; Canad

An Euler–Bernoulli-type beam model of the vocal folds for describing curved and incomplete glottal closure patterns

Incomplete glottal closure is a laryngeal configuration wherein the glottis is not fully obstructed prior to phonation. It has been linked to inefficient voice production and voice disorders. Various incomplete glottal closure patterns can arise and the mechanisms driving them are not well understood. In this work, we introduce an Euler–Bernoulli composite beam vocal fold (VF) model that produces qualitatively similar incomplete glottal closure patterns as those observed in experimental and high-fidelity numerical studies, thus offering insights into the potential underlying physical mechanisms. Refined physiological insights are pursued by incorporating the beam model into a VF posturing model that embeds the five intrinsic laryngeal muscles. Analysis of the combined model shows that co-activating the lateral cricoarytenoid (LCA) and interarytenoid (IA) muscles without activating the thyroarytenoid (TA) muscle results in a bowed (convex) VF geometry with closure at the posterior margin only; this is primarily attributed to the reactive moments at the anterior VF margin. This bowed pattern can also arise during VF compression (due to extrinsic laryngeal muscle activation for example), wherein the internal moment induced passively by the TA muscle tissue is the predominant mechanism. On the other hand, activating the TA muscle without incorporating other adductory muscles results in anterior and mid-membranous glottal closure, a concave VF geometry, and a posterior glottal opening driven by internal moments induced by TA muscle activation. In the case of initial full glottal closure, the posterior cricoarytenoid (PCA) muscle activation cancels the adductory effects of the LCA and IA muscles, resulting in a concave VF geometry and posterior glottal opening. Furthermore, certain maneuvers involving co-activation of all adductory muscles result in an hourglass glottal shape due to a reactive moment at the anterior VF margin and moderate internal moment induced by TA muscle activation. These findings have implications regarding potential laryngeal maneuvers in patients with voice disorders involving imbalances or excessive tension in the laryngeal muscles such as muscle tension dysphonia.Fil: Serry, Mohamed A.. University of Waterloo; CanadáFil: Alzamendi, Gabriel Alejandro. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Zañartu, Matías. Universidad Tecnica Federico Santa Maria.; ChileFil: Peterson, Sean D.. University of Waterloo; Canad

Kalman Filter Implementation of Subglottal Impedance-Based Inverse Filtering to Estimate Glottal Airflow during Phonation

Subglottal Impedance-Based Inverse Filtering (IBIF) allows for the continuous, non-invasive estimation of glottal airflow from a surface accelerometer placed over the anterior neck skin below the larynx. It has been shown to be advantageous for the ambulatory monitoring of vocal function, specifically in the use of high-order statistics to understand long-term vocal behavior. However, during long-term ambulatory recordings over several days, conditions may drift from the laboratory environment where the IBIF parameters were initially estimated due to sensor positioning, skin attachment, or temperature, among other factors. Observation uncertainties and model mismatch may result in significant deviations in the glottal airflow estimates; unfortunately, they are very difficult to quantify in ambulatory conditions due to a lack of a reference signal. To address this issue, we propose a Kalman filter implementation of the IBIF filter, which allows for both estimating the model uncertainty and adapting the airflow estimates to correct for signal deviations. One-way analysis of variance (ANOVA) results from laboratory experiments using the Rainbow Passage indicate an improvement using the modified Kalman filter on amplitude-based measures for phonotraumatic vocal hyperfunction (PVH) subjects compared to the standard IBIF; the latter showing a statistically difference (p-value =0.02, F=4.1) with respect to a reference glottal volume velocity signal estimated from a single notch filter used here as ground-truth in this work. In contrast, maximum flow declination rates from subjects with vocal phonotrauma exhibit a small but statistically difference between the ground-truth signal and the modified Kalman filter when using one-way ANOVA (p-value =0.04, F=3.3). Other measures did not have significant differences with either the modified Kalman filter or IBIF compared to ground-truth, with the exception of H1-H2, whose performance deteriorates for both methods. Overall, both methods (modified Kalman filter and IBIF) show similar glottal airflow measures, with the advantage of the modified Kalman filter to improve amplitude estimation. Moreover, Kalman filter deviations from the IBIF output airflow might suggest a better representation of some fine details in the ground-truth glottal airflow signal. Other applications may take more advantage from the adaptation offered by the modified Kalman filter implementation

Fructose-rich diet-induced abdominal adipose tissue endocrine dysfunction in normal male rats.

We have currently studied the changes induced by administration of a fructose-rich diet (FRD) to normal rats in the mass and the endocrine function of abdominal (omental) adipose tissue (AAT). Rats were fed ad libitum a standard commercial chow and tap water, either alone (control diet, CD) or containing fructose (10%, w/vol) (FRD). Three weeks after treatment, circulating metabolic markers and leptin release from adipocytes of AAT were measured. Plasma free fatty acids (FFAs), leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in FRD than in CD rats. AAT mass was greater in FRD than in CD rats and their adipocytes were larger, they secreted more leptin and showed impaired insulin sensitivity. While leptin mRNA expression increased in AAT from FRD rats, gene expression of insulin receptor substrate, IRS1 and IRS2 was significantly reduced. Our study demonstrates that administration of a FRD significantly affects insulin sensitivity and several AAT endocrine/metabolic functions. These alterations could be part of a network of interacting abnormalities triggered by FRD-induced oxidative stress at the AAT level. In view of the impaired glucose tolerance observed in FRD rats, these alterations could play a key role in both the development of metabolic syndrome (MS) and beta-cell failure