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Almici E, Chiappini V, López-Márquez A, Badosa C, Blázquez B, Caballero D, Montero J, Natera-de Benito D, Nascimento A, Roldán M, Lagunas A, Jiménez-Mallebrera C, Samitier J, (2022). Personalized in vitro Extracellular Matrix Models of Collagen VI-Related Muscular Dystrophies Frontiers In Bioengineering And Biotechnology 10,

Collagen VI-related dystrophies (COL6-RDs) are a group of rare congenital neuromuscular dystrophies that represent a continuum of overlapping clinical phenotypes that go from the milder Bethlem myopathy (BM) to the severe Ullrich congenital muscular dystrophy, for which there is no effective treatment. Mutations in one of the three Collagen VI genes alter the incorporation of this protein into the extracellular matrix (ECM), affecting the assembly and the structural integrity of the whole fibrillar network. Clinical hallmarks of COL6-RDs are secondary to the ECM disruption and include muscle weakness, proximal joint contractures, and distal hyperlaxity. Although some traits have been identified in patients’ ECMs, a correlation between the ECM features and the clinical phenotype has not been established, mainly due to the lack of predictive and reliable models of the pathology. Herein, we engineered a new personalized pre-clinical model of COL6-RDs using cell-derived matrices (CDMs) technology to better recapitulate the complexity of the native scenario. We found that CDMs from COL6-RD patients presented alterations in ECM structure and composition, showing a significantly decreased Collagen VI secretion, especially in the more severe phenotypes, and a decrease in Fibrillin-1 inclusion. Next, we examined the Collagen VI-mediated deposition of Fibronectin in the ECM, finding a higher alignment, length, width, and straightness than in patients with COL6-RDs. Overall, these results indicate that CDMs models are promising tools to explore the alterations that arise in the composition and fibrillar architecture due to mutations in Collagen VI genes, especially in early stages of matrix organization. Ultimately, CDMs derived from COL6-RD patients may become relevant pre-clinical models, which may help identifying novel biomarkers to be employed in the clinics and to investigate novel therapeutic targets and treatments. Copyright © 2022 Almici, Chiappini, López-Márquez, Badosa, Blázquez, Caballero, Montero, Natera-de Benito, Nascimento, Roldán, Lagunas, Jiménez-Mallebrera and Samitier.

Keywords: alpha-3 chain, binding, collagen vi related muscular dystrophy, decellularisation, decellularized matrices, deficiency, expression, fibroblasts, fibronectin, in vitro model, patient-derived ecms, skeletal-muscle, ullrich, Cell-derived matrices, Collagen, Collagen vi related muscular dystrophy, Decellularisation, Decellularization, Extracellular matrices, Extracellular matrix, Genes, In vitro model, In-vitro, In-vitro models, Matrix, Matrix model, Muscular dystrophy, Pathology, Patient-derived ecm, Patient-derived ecms, Pre-clinical


Lozano-Garcia M, Estrada-Petrocelli L, Blanco-Almazan D, Tas B, Cho PS, Moxham J, Rafferty GF, Torres A, Jane R, Jolley CJ, (2022). Noninvasive Assessment of Neuromechanical and Neuroventilatory Coupling in COPD Ieee Journal Of Biomedical And Health Informatics ,

This study explored the use of parasternal second intercostal space and lower intercostal space surface electromyogram (sEMG) and surface mechanomyogram (sMMG) recordings (sEMGpara and sMMGpara, and sEMGlic and sMMGlic, respectively) to assess neural respiratory drive (NRD), neuromechanical (NMC) and neuroventilatory (NVC) coupling, and mechanical efficiency (MEff) noninvasively in healthy subjects and chronic obstructive pulmonary disease (COPD) patients. sEMGpara, sMMGpara, sEMGlic, sMMGlic, mouth pressure (Pmo), and volume (Vi) were measured at rest, and during an inspiratory loading protocol, in 16 COPD patients (8 moderate and 8 severe) and 9 healthy subjects. Myographic signals were analyzed using fixed sample entropy and normalized to their largest values (fSEsEMGpara%max, fSEsMMGpara%max, fSEsEMGlic%max, and fSEsMMGlic%max). fSEsMMGpara%max, fSEsEMGpara%max, and fSEsEMGlic%max were significantly higher in COPD than in healthy participants at rest. Parasternal intercostal muscle NMC was significantly higher in healthy than in COPD participants at rest, but not during threshold loading. Pmo-derived NMC and MEff ratios were lower in severe patients than in mild patients or healthy subjects during threshold loading, but differences were not consistently significant. During resting breathing and threshold loading, Vi-derived NVC and MEff ratios were significantly lower in severe patients than in mild patients or healthy subjects. sMMG is a potential noninvasive alternative to sEMG for assessing NRD in COPD. The ratios of Pmo and Vi to sMMG and sEMG measurements provide wholly noninvasive NMC, NVC, and MEff indices that are sensitive to impaired respiratory mechanics in COPD and are therefore of potential value to assess disease severity in clinical practice. Author

Keywords: At rests, Biomedical measurement, Biomedical measurements, Chronic obstructive pulmonary disease, Couplings, Disease severity, Efficiency ratio, Electromyography, Healthy subjects, Healthy volunteers, Loading, Mechanical efficiency, Mechanomyogram, Muscle, Muscles, Noninvasive medical procedures, Pressure measurement, Protocols, Pulmonary diseases, Surface electromyogram, Volume measurement


Arboleda A, Amado L, Rodriguez J, Naranjo F, Giraldo BF, (2021). A new protocol to compare successful versus failed patients using the electromyographic diaphragm signal in extubation process Conference Proceedings : ... Annual International Conference Of The Ieee Engineering In Medicine And Biology Society. Ieee Engineering In Medicine And Biology Society. Conference , 5646-5649

In clinical practice, when a patient is undergoing mechanical ventilation, it is important to identify the optimal moment for extubation, minimizing the risk of failure. However, this prediction remains a challenge in the clinical process. In this work, we propose a new protocol to study the extubation process, including the electromyographic diaphragm signal (diaEMG) recorded through 5-channels with surface electrodes around the diaphragm muscle. First channel corresponds to the electrode on the right. A total of 40 patients in process of withdrawal of mechanical ventilation, undergoing spontaneous breathing tests (SBT), were studied. According to the outcome of the SBT, the patients were classified into two groups: successful (SG: 19 patients) and failure (FG: 21 patients) groups. Parameters extracted from the envelope of each channel of diaEMG in time and frequency domain were studied. After analyzing all channels, the second presented maximum differences when comparing the two groups of patients, with parameters related to root mean square (p = 0.005), moving average (p = 0.001), and upward slope (p = 0.017). The third channel also presented maximum differences in parameters as the time between maximum peak (p = 0.004), and the skewness (p = 0.027). These results suggest that diaphragm EMG signal could contribute to increase the knowledge of the behaviour of respiratory system in these patients and improve the extubation process.Clinical Relevance - This establishes the characterization of success and failure patients in the extubation process. © 2021 IEEE.

Keywords: Airway extubation, Artificial ventilation, Clinical practices, Clinical process, Diaphragm, Diaphragm muscle, Diaphragms, Electrodes, Electromyographic, Extubation, Frequency domain analysis, Human, Humans, Maximum differences, Mechanical ventilation, New protocol, Respiration, artificial, Respiratory system, Risk of failure, Spontaneous breathing, Surface electrode, Thorax, Ventilation, Ventilator weaning


Guallar-Garrido, S, Campo-Perez, V, Perez-Trujillo, M, Cabrera, C, Senserrich, J, Sanchez-Chardi, A, Rabanal, RM, Gomez-Mora, E, Noguera-Ortega, E, Luquin, M, Julian, E, (2022). Mycobacterial surface characters remodeled by growth conditions drive different tumor-infiltrating cells and systemic IFN-gamma/IL-17 release in bladder cancer treatment Oncoimmunology 11, 2051845

The mechanism of action of intravesical Mycobacterium bovis BCG immunotherapy treatment for bladder cancer is not completely known, leading to misinterpretation of BCG-unresponsive patients, who have scarce further therapeutic options. BCG is grown under diverse culture conditions worldwide, which can impact the antitumor effect of BCG strains and could be a key parameter of treatment success. Here, BCG and the nonpathogenic Mycobacterium brumae were grown in four culture media currently used by research laboratories and BCG manufacturers: Sauton-A60, -G15 and -G60 and Middlebrook 7H10, and used as therapies in the orthotopic murine BC model. Our data reveal that each mycobacterium requires specific culture conditions to induce an effective antitumor response. since higher survival rates of tumor-bearing mice were achieved using M. brumae-A60 and BCG-G15 than the rest of the treatments. M. brumae-A60 was the most efficacious among all tested treatments in terms of mouse survival, cytotoxic activity of splenocytes against tumor cells, higher systemic production of IL-17 and IFN-gamma, and bladder infiltration of selected immune cells such as ILCs and CD4(TEM). BCG-G15 triggered an antitumor activity based on a massive infiltration of immune cells, mainly CD3(+) (CD4(+) and CD8(+)) T cells, together with high systemic IFN-gamma release. Finally, a reduced variety of lipids was strikingly observed in the outermost layer of M. brumae-A60 and BCG-G15 compared to the rest of the cultures, suggesting an influence on the antitumor immune response triggered. These findings contribute to understand how mycobacteria create an adequate niche to help the host subvert immunosuppressive tumor actions.

Keywords: Bcg, Calmette-guerin bcg, Glycerol, Identification, Immune-response, Innate immune response, Innate-lymphoid cells, Lipid, Lipids, Mycolic acids, Neutral-red, Non-muscle invasive, Phenolic glycolipids, Tuberculosis, Tumor microenvironment, Virulence


Ballester, BR, Antenucci, F, Maier, M, Coolen, ACC, Verschure, PFMJ, (2021). Estimating upper-extremity function from kinematics in stroke patients following goal-oriented computer-based training Journal Of Neuroengineering And Rehabilitation 18,

Introduction: After a stroke, a wide range of deficits can occur with varying onset latencies. As a result, assessing impairment and recovery are enormous challenges in neurorehabilitation. Although several clinical scales are generally accepted, they are time-consuming, show high inter-rater variability, have low ecological validity, and are vulnerable to biases introduced by compensatory movements and action modifications. Alternative methods need to be developed for efficient and objective assessment. In this study, we explore the potential of computer-based body tracking systems and classification tools to estimate the motor impairment of the more affected arm in stroke patients. Methods: We present a method for estimating clinical scores from movement parameters that are extracted from kinematic data recorded during unsupervised computer-based rehabilitation sessions. We identify a number of kinematic descriptors that characterise the patients' hemiparesis (e.g., movement smoothness, work area), we implement a double-noise model and perform a multivariate regression using clinical data from 98 stroke patients who completed a total of 191 sessions with RGS. Results: Our results reveal a new digital biomarker of arm function, the Total Goal-Directed Movement (TGDM), which relates to the patients work area during the execution of goal-oriented reaching movements. The model's performance to estimate FM-UE scores reaches an accuracy of R-2: 0.38 with an error (sigma: 12.8). Next, we evaluate its reliability (r = 0.89 for test-retest), longitudinal external validity (95% true positive rate), sensitivity, and generalisation to other tasks that involve planar reaching movements (R-2: 0.39). The model achieves comparable accuracy also for the Chedoke Arm and Hand Activity Inventory (R-2: 0.40) and Barthel Index (R-2: 0.35). Conclusions: Our results highlight the clinical value of kinematic data collected during unsupervised goal-oriented motor training with the RGS combined with data science techniques, and provide new insight into factors underlying recovery and its biomarkers.

Keywords: interactive feedback, motion classification, motion sensing, multivariate regression, posture monitoring, rehabilitation, stroke, Adult, Aged, Analytic method, Arm movement, Article, Barthel index, Brain hemorrhage, Cerebrovascular accident, Chedoke arm and hand activity inventory, Clinical protocol, Cognitive defect, Computer analysis, Controlled study, Convergent validity, Correlation coefficient, Disease severity, External validity, Female, Fugl meyer assessment for the upper extremity, Functional assessment, Functional status assessment, General health status assessment, Hemiparesis, Human, Interactive feedback, Ischemic stroke, Kinematics, Major clinical study, Male, Mini mental state examination, Motion classification, Motion sensing, Motor analog scale, Movement, Multivariate regression, Muscle function, Posture monitoring, Probability, Recovery, Rehabilitation, Reliability, Retrospective study, Stroke, Stroke patient, Test retest reliability, Therapy, Total goal directed movement, Upper extremities, Upper limb, Upper-limb, Wolf motor function test


Dulay, S, Rivas, L, Pla, L, Berdun, S, Eixarch, E, Gratacos, E, Illa, M, Mir, M, Samitier, J, (2021). Fetal ischemia monitoring with in vivo implanted electrochemical multiparametric microsensors Journal Of Biological Engineering 15, 28

Under intrauterine growth restriction (IUGR), abnormal attainment of the nutrients and oxygen by the fetus restricts the normal evolution of the prenatal causing in many cases high morbidity being one of the top-ten causes of neonatal death. The current gold standards in hospitals to detect this relevant problem is the clinical observation by echography, cardiotocography and Doppler. These qualitative techniques are not conclusive and requires risky invasive fetal scalp blood testing and/or amniocentesis. We developed micro-implantable multiparametric electrochemical sensors for measuring ischemia in real time in fetal tissue and vascular. This implantable technology is designed to continuous monitoring for an early detection of ischemia to avoid potential fetal injury. Two miniaturized electrochemical sensors were developed based on oxygen and pH detection. The sensors were optimized in vitro under controlled concentration, to assess the selectivity and sensitivity required. The sensors were then validated in vivo in the ewe fetus model, by means of their insertion in the muscle leg and inside the iliac artery of the fetus. Ischemia was achieved by gradually obstructing the umbilical cord to regulate the amount of blood reaching the fetus. An important challenge in fetal monitoring is the detection of low levels of oxygen and pH changes under ischemic conditions, requiring high sensitivity sensors. Significant differences were observed in both; pH and pO(2) sensors under changes from normoxia to hypoxia states in the fetus tissue and vascular with both sensors. Herein, we demonstrate the feasibility of the developed sensors for future fetal monitoring in medical applications.

Keywords: electrochemical biosensor, implantable sensor, in vivo validation, ischemia detection, tissue and vascular monitoring, Animal experiment, Animal model, Animal tissue, Article, Blood-gases, Brain, Classification, Controlled study, Diagnosis, Doppler, Early diagnosis, Electrochemical analysis, Electrochemical biosensor, Ewe, Feasibility study, Female, Fetus, Fetus disease, Fetus monitoring, Gestational age, Hypoxemia, Iliac artery, Implantable sensor, In vivo validation, Intrauterine growth restriction, Intrauterine growth retardation, Ischemia detection, Leg muscle, Management, Nonhuman, Oxygen consumption, Ph, Ph and oxygen detection, Ph measurement, Process optimization, Sheep, Tissue and vascular monitoring, Umbilical-cord occlusion


Tantai, Xinxing, Liu, Yi, Yeo, Yee Hui, Praktiknjo, Michael, Mauro, Ezequiel, Hamaguchi, Yuhei, Engelmann, Cornelius, Zhang, Peng, Jeong, Jae Yoon, van Vugt, Jeroen Laurens Ad, Xiao, Huijuan, Deng, Huan, Gao, Xu, Ye, Qing, Zhang, Jiayuan, Yang, Longbao, Cai, Yaqin, Liu, Yixin, Liu, Na, Li, Zongfang, Han, Tao, Kaido, Toshimi, Sohn, Joo Hyun, Strassburg, Christian, Berg, Thomas, Trebicka, Jonel, Hsu, Yao-Chun, IJzermans, Jan Nicolaas Maria, Wang, Jinhai, Su, Grace L., Ji, Fanpu, Nguyen, Mindie H., (2021). Effect of sarcopenia on survival of patients with cirrhosis: A meta-analysis Journal Of Hepatology 76, 588-599

The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, by sex, underlying liver disease etiology, and severity of hepatic dysfunction.PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with additional manual search of bibliographies of relevant articles. Cohort studies of ?100 patients with cirrhosis and ?12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included.22 studies with 6965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), higher in male patients, patients with alcohol associated liver disease (ALD), patients with CTP grade C, and when sarcopenia was defined in patients by lumbar 3- skeletal muscle index (L3-SMI). Sarcopenia was associated with the increased risk of mortality in patients with cirrhosis (adjusted-hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in sensitivity analysis of cirrhosis patients without HCC (aHR 2.35, 95% CI 1.95-2.83) and in subgroup analysis by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the poor prognosis for patients with sarcopenia (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in all analyses.Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis.The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% in patients with ALD or Child's class C cirrhosis. Sarcopenia was independently associated with about 2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer period of having sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.Copyright © 2021. Published by Elsevier B.V.

Keywords: alcohol associated liver disease, cirrhosis, prognosis, sarcopenia, Alcohol-associated liver disease, Cirrhosis, Prognosis, Sarcopenia, Skeletal muscle index


Lopez-Muñoz, Gerardo A, Fernández-Costa, Juan M, Ortega, Maria Alejandra, Balaguer-Trias, Jordina, Martin-Lasierra, Eduard, Ramón-Azcón, Javier, (2021). Plasmonic nanocrystals on polycarbonate substrates for direct and label-free biodetection of Interleukin-6 in bioengineered 3D skeletal muscles Nanophotonics 10, 4477-4488

Abstract The development of nanostructured plasmonic biosensors has been widely widespread in the last years, motivated by the potential benefits they can offer in integration, miniaturization, multiplexing opportunities, and enhanced performance label-free biodetection in a wide field of applications. Between them, engineering tissues represent a novel, challenging, and prolific application field for nanostructured plasmonic biosensors considering the previously described benefits and the low levels of secreted biomarkers (?pM–nM) to detect. Here, we present an integrated plasmonic nanocrystals-based biosensor using high throughput nanostructured polycarbonate substrates. Metallic film thickness and incident angle of light for reflectance measurements were optimized to enhance the detection of antibody–antigen biorecognition events using numerical simulations. We achieved an enhancement in biodetection up to 3× as the incident angle of light decreases, which can be related to shorter evanescent decay lengths. We achieved a high reproducibility between channels with a coefficient of variation below 2% in bulk refractive index measurements, demonstrating a high potential for multiplexed sensing. Finally, biosensing potential was demonstrated by the direct and label-free detection of interleukin-6 biomarker in undiluted cell culture media supernatants from bioengineered 3D skeletal muscle tissues stimulated with different concentrations of endotoxins achieving a limit of detection (LOD) of ? 0.03 ng/mL (1.4 pM).

Keywords: assay, crystals, drug, label-free biosensing, molecules, plasmonic nanostructures, sensors, skeletal muscle, tissue engineering, Biodetection, Biomarkers, Biosensors, Cell culture, Cells, Chemical detection, Histology, Interleukin-6, Interleukin6 (il6), Label free, Label-free biosensing, Muscle, Nano-structured, Nanocrystals, Plasmonic nanocrystals, Plasmonic nanostructures, Plasmonics, Polycarbonate substrates, Polycarbonates, Refractive index, Sensitivity, Skeletal muscle, Tissue engineering, Tissues engineerings


Soblechero-Martín P, Albiasu-Arteta E, Anton-Martinez A, de la Puente-Ovejero L, Garcia-Jimenez I, González-Iglesias G, Larrañaga-Aiestaran I, López-Martínez A, Poyatos-García J, Ruiz-Del-Yerro E, Gonzalez F, Arechavala-Gomeza V, (2021). Duchenne muscular dystrophy cell culture models created by CRISPR/Cas9 gene editing and their application in drug screening Scientific Reports 11, 18188

Gene editing methods are an attractive therapeutic option for Duchenne muscular dystrophy, and they have an immediate application in the generation of research models. To generate myoblast cultures that could be useful in in vitro drug screening, we have optimised a CRISPR/Cas9 gene edition protocol. We have successfully used it in wild type immortalised myoblasts to delete exon 52 of the dystrophin gene, modelling a common Duchenne muscular dystrophy mutation; and in patient’s immortalised cultures we have deleted an inhibitory microRNA target region of the utrophin UTR, leading to utrophin upregulation. We have characterised these cultures by demonstrating, respectively, inhibition of dystrophin expression and overexpression of utrophin, and evaluating the expression of myogenic factors (Myf5 and MyH3) and components of the dystrophin associated glycoprotein complex (α-sarcoglycan and β-dystroglycan). To demonstrate their use in the assessment of DMD treatments, we have performed exon skipping on the DMDΔ52-Model and have used the unedited DMD cultures/ DMD-UTRN-Model combo to assess utrophin overexpression after drug treatment. While the practical use of DMDΔ52-Model is limited to the validation to our gene editing protocol, DMD-UTRN-Model presents a possible therapeutic gene edition target as well as a useful positive control in the screening of utrophin overexpression drugs.

Keywords: expression, in-vitro, mouse model, muscle, mutations, phenotype, quantification, sarcolemma, therapy, Utrophin up-regulation


Mestre R, García N, Patiño T, Guix M, Fuentes J, Valerio-Santiago M, Almiñana N, Sánchez S, (2021). 3D-bioengineered model of human skeletal muscle tissue with phenotypic features of aging for drug testing purposes Biofabrication 13,

Three-dimensional engineering of skeletal muscle is becoming increasingly relevant for tissue engineering, disease modeling and bio-hybrid robotics, where flexible, versatile and multidisciplinary approaches for the evaluation of tissue differentiation, functionality and force measurement are required. This works presents a 3D-printed platform of bioengineered human skeletal muscle which can efficiently model the three-dimensional structure of native tissue, while providing information about force generation and contraction profiles. Proper differentiation and maturation of myocytes is demonstrated by the expression of key myo-proteins using immunocytochemistry and analyzed by confocal microscopy, and the functionality assessed via electrical stimulation and analysis of contraction kinetics. To validate the flexibility of this platform for complex tissue modeling, the bioengineered muscle is treated with tumor necrosis factor α to mimic the conditions of aging, which is supported by morphological and functional changes. Moreover, as a proof of concept, the effects of Argireline® Amplified peptide, a cosmetic ingredient that causes muscle relaxation, are evaluated in both healthy and aged tissue models. Therefore, the results demonstrate that this 3D-bioengineered human muscle platform could be used to assess morphological and functional changes in the aging process of muscular tissue with potential applications in biomedicine, cosmetics and bio-hybrid robotics.

Keywords: 3d bioprinting, bio-actuator, drug testing, human skeletal muscle, muscle ageing, platform, tnf-alpha, 3d bioprinting, Bio-actuator, Drug testing, Human skeletal muscle, Muscle ageing, Necrosis-factor-alpha


Guix M, Mestre R, Patiño T, de Corato M, Fuentes J, Zarpellon G, Sánchez S, (2021). Biohybrid soft robots with self-stimulating skeletons Science Robotics 6,

Bioinspired hybrid soft robots that combine living and synthetic components are an emerging field in the development of advanced actuators and other robotic platforms (i.e., swimmers, crawlers, and walkers). The integration of biological components offers unique characteristics that artificial materials cannot precisely replicate, such as adaptability and response to external stimuli. Here, we present a skeletal muscle–based swimming biobot with a three-dimensional (3D)–printed serpentine spring skeleton that provides mechanical integrity and self-stimulation during the cell maturation process. The restoring force inherent to the spring system allows a dynamic skeleton compliance upon spontaneous muscle contraction, leading to a cyclic mechanical stimulation process that improves the muscle force output without external stimuli. Optimization of the 3D-printed skeletons is carried out by studying the geometrical stiffnesses of different designs via finite element analysis. Upon electrical actuation of the muscle tissue, two types of motion mechanisms are experimentally observed: directional swimming when the biobot is at the liquid-air interface and coasting motion when it is near the bottom surface. The integrated compliant skeleton provides both the mechanical self-stimulation and the required asymmetry for directional motion, displaying its maximum velocity at 5 hertz (800 micrometers per second, 3 body lengths per second). This skeletal muscle–based biohybrid swimmer attains speeds comparable with those of cardiac-based biohybrid robots and outperforms other muscle-based swimmers. The integration of serpentine-like structures in hybrid robotic systems allows self-stimulation processes that could lead to higher force outputs in current and future biomimetic robotic platforms. Copyright © 2021 The Authors, some rights reserved;

Keywords: actuators, design, fabrication, mechanics, mems, myotubes, platform, tissue, 3d printers, Agricultural robots, Biological components, Biomimetic processes, Electrical actuation, Geometrical stiffness, Intelligent robots, Liquefied gases, Liquid-air interface, Mechanical integrity, Mechanical stimulation, Muscle, Muscle contractions, Phase interfaces, Robotics, Serpentine, Springs (components), Threedimensional (3-d)


Fernández-Garibay X, Ortega MA, Cerro-Herreros E, Comelles J, Martínez E, Artero R, Fernández-Costa JM, Ramón-Azcón J, (2021). Bioengineered in vitro 3D model of myotonic dystrophy type 1 human skeletal muscle Biofabrication 13,

Myotonic dystrophy type 1 (DM1) is the most common hereditary myopathy in the adult population. The disease is characterized by progressive skeletal muscle degeneration that produces severe disability. At present, there is still no effective treatment for DM1 patients, but the breakthroughs in understanding the molecular pathogenic mechanisms in DM1 have allowed the testing of new therapeutic strategies. Animal models and in vitro two-dimensional cell cultures have been essential for these advances. However, serious concerns exist regarding how faithfully these models reproduce the biological complexity of the disease. Biofabrication tools can be applied to engineer human three-dimensional (3D) culture systems that complement current preclinical research models. Here, we describe the development of the first in vitro 3D model of DM1 human skeletal muscle. Transdifferentiated myoblasts from patient-derived fibroblasts were encapsulated in micromolded gelatin methacryloyl-carboxymethyl cellulose methacrylate hydrogels through photomold patterning on functionalized glass coverslips. These hydrogels present a microstructured topography that promotes myoblasts alignment and differentiation resulting in highly aligned myotubes from both healthy and DM1 cells in a long-lasting cell culture. The DM1 3D microtissues recapitulate the molecular alterations detected in patient biopsies. Importantly, fusion index analyses demonstrate that 3D micropatterning significantly improved DM1 cell differentiation into multinucleated myotubes compared to standard cell cultures. Moreover, the characterization of the 3D cultures of DM1 myotubes detects phenotypes as the reduced thickness of myotubes that can be used for drug testing. Finally, we evaluated the therapeutic effect of antagomiR-23b administration on bioengineered DM1 skeletal muscle microtissues. AntagomiR-23b treatment rescues both molecular DM1 hallmarks and structural phenotype, restoring myotube diameter to healthy control sizes. Overall, these new microtissues represent an improvement over conventional cell culture models and can be used as biomimetic platforms to establish preclinical studies for myotonic dystrophy.

Keywords: 3d cell culture, hydrogel micropatterning, myotonic dystrophy, skeletal muscle, tissue engineering, 3d cell culture, Hydrogel micropatterning, Myotonic dystrophy, Skeletal muscle, Tissue engineering


Estrada-Petrocelli L, Torres A, Sarlabous L, Rafols-De-Urquia M, Ye-Lin Y, Prats-Boluda G, Jane R, Garcia-Casado J, (2021). Evaluation of Respiratory Muscle Activity by Means of Concentric Ring Electrodes IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING 68, 1005-1014

© 1964-2012 IEEE. Surface electromyography (sEMG) can be used for the evaluation of respiratory muscle activity. Recording sEMG involves the use of surface electrodes in a bipolar configuration. However, electrocardiographic (ECG) interference and electrode orientation represent considerable drawbacks to bipolar acquisition. As an alternative, concentric ring electrodes (CREs) can be used for sEMG acquisition and offer great potential for the evaluation of respiratory muscle activity due to their enhanced spatial resolution and simple placement protocol, which does not depend on muscle fiber orientation. The aim of this work was to analyze the performance of CREs during respiratory sEMG acquisitions. Respiratory muscle sEMG was applied to the diaphragm and sternocleidomastoid muscles using a bipolar and a CRE configuration. Thirty-two subjects underwent four inspiratory load spontaneous breathing tests which was repeated after interchanging the electrode positions. We calculated parameters such as (1) spectral power and (2) median frequency during inspiration, and power ratios of inspiratory sEMG without ECG in relation to (3) basal sEMG without ECG (Rins/noise), (4) basal sEMG with ECG (Rins/cardio) and (5) expiratory sEMG without ECG (Rins/exp). Spectral power, Rins/noise and Rins/cardio increased with the inspiratory load. Significantly higher values (p < 0.05) of Rins/cardio and significantly higher median frequencies were obtained for CREs. Rins/noise and Rins/exp were higher for the bipolar configuration only in diaphragm sEMG recordings, whereas no significant differences were found in the sternocleidomastoid recordings. Our results suggest that the evaluation of respiratory muscle activity by means of sEMG can benefit from the remarkably reduced influence of cardiac activity, the enhanced detection of the shift in frequency content and the axial isotropy of CREs which facilitates its placement.

Keywords: atmospheric measurements, concentric ring electrodes, electrocardiography, electrodes, electromyography, laplacian potential, non-invasive respiratory monitoring, particle measurements, respiratory muscles, surface electromyography, Concentric ring electrodes, Laplacian potential, Muscles, Non-invasive respiratory monitoring, Respiratory muscles, Surface electromyography


Lozano-García M, Estrada-Petrocelli L, Torres A, Rafferty GF, Moxham J, Jolley CJ, Jané R, (2021). Noninvasive assessment of neuromechanical coupling and mechanical efficiency of parasternal intercostal muscle during inspiratory threshold loading Sensors 21, 1-15

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This study aims to investigate noninvasive indices of neuromechanical coupling (NMC) and mechanical efficiency (MEff) of parasternal intercostal muscles. Gold standard assessment of diaphragm NMC requires using invasive techniques, limiting the utility of this procedure. Nonin-vasive NMC indices of parasternal intercostal muscles can be calculated using surface mechano-myography (sMMGpara) and electromyography (sEMGpara). However, the use of sMMGpara as an in-spiratory muscle mechanical output measure, and the relationships between sMMGpara, sEMGpara, and simultaneous invasive and noninvasive pressure measurements have not previously been eval-uated. sEMGpara, sMMGpara, and both invasive and noninvasive measurements of pressures were recorded in twelve healthy subjects during an inspiratory loading protocol. The ratios of sMMGpara to sEMGpara, which provided muscle-specific noninvasive NMC indices of parasternal intercostal muscles, showed nonsignificant changes with increasing load, since the relationships between sMMGpara and sEMGpara were linear (R2 = 0.85 (0.75–0.9)). The ratios of mouth pressure (Pmo) to sEMGpara and sMMGpara were also proposed as noninvasive indices of parasternal intercostal muscle NMC and MEff, respectively. These indices, similar to the analogous indices calculated using invasive transdiaphragmatic and esophageal pressures, showed nonsignificant changes during threshold loading, since the relationships between Pmo and both sEMGpara (R2 = 0.84 (0.77–0.93)) and sMMGpara (R2 = 0.89 (0.85–0.91)) were linear. The proposed noninvasive NMC and MEff indices of parasternal intercostal muscles may be of potential clinical value, particularly for the regular assessment of patients with disordered respiratory mechanics using noninvasive wearable and wireless devices.

Keywords: inspiratory threshold loading, neuromechanical coupling, parasternal intercostal muscles, respiratory pressure, surface electromyography, surface mechanomyography, Inspiratory threshold loading, Neuromechanical coupling, Parasternal intercostal mus-cles, Respiratory pressure, Surface electromyography, Surface mechanomyography


Fernández-Costa JM, Fernández-Garibay X, Velasco-Mallorquí F, Ramón-Azcón J, (2021). Bioengineered in vitro skeletal muscles as new tools for muscular dystrophies preclinical studies Journal of Tissue Engineering 12,

© The Author(s) 2021. Muscular dystrophies are a group of highly disabling disorders that share degenerative muscle weakness and wasting as common symptoms. To date, there is not an effective cure for these diseases. In the last years, bioengineered tissues have emerged as powerful tools for preclinical studies. In this review, we summarize the recent technological advances in skeletal muscle tissue engineering. We identify several ground-breaking techniques to fabricate in vitro bioartificial muscles. Accumulating evidence shows that scaffold-based tissue engineering provides topographical cues that enhance the viability and maturation of skeletal muscle. Functional bioartificial muscles have been developed using human myoblasts. These tissues accurately responded to electrical and biological stimulation. Moreover, advanced drug screening tools can be fabricated integrating these tissues in electrical stimulation platforms. However, more work introducing patient-derived cells and integrating these tissues in microdevices is needed to promote the clinical translation of bioengineered skeletal muscle as preclinical tools for muscular dystrophies.

Keywords: biomaterials, drug screening platforms, muscular dystrophy, skeletal muscle, tissue engineering, Biomaterials, Drug screening platforms, Muscular dystrophy, Skeletal muscle, Tissue engineering


Mestre R, Patiño T, Sánchez S, (2021). Biohybrid robotics: From the nanoscale to the macroscale Wiley Interdisciplinary Reviews-Nanomedicine and Nanobiotechnology 13

© 2021 Wiley Periodicals LLC. Biohybrid robotics is a field in which biological entities are combined with artificial materials in order to obtain improved performance or features that are difficult to mimic with hand-made materials. Three main level of integration can be envisioned depending on the complexity of the biological entity, ranging from the nanoscale to the macroscale. At the nanoscale, enzymes that catalyze biocompatible reactions can be used as power sources for self-propelled nanoparticles of different geometries and compositions, obtaining rather interesting active matter systems that acquire importance in the biomedical field as drug delivery systems. At the microscale, single enzymes are substituted by complete cells, such as bacteria or spermatozoa, whose self-propelling capabilities can be used to transport cargo and can also be used as drug delivery systems, for in vitro fertilization practices or for biofilm removal. Finally, at the macroscale, the combinations of millions of cells forming tissues can be used to power biorobotic devices or bioactuators by using muscle cells. Both cardiac and skeletal muscle tissue have been part of remarkable examples of untethered biorobots that can crawl or swim due to the contractions of the tissue and current developments aim at the integration of several types of tissue to obtain more realistic biomimetic devices, which could lead to the next generation of hybrid robotics. Tethered bioactuators, however, result in excellent candidates for tissue models for drug screening purposes or the study of muscle myopathies due to their three-dimensional architecture. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Keywords: bacteria-bots, based biorobots, biorobots, bots, enzymatic nanomotors, hybrid robotics, muscle‐, Bacteria‐, Bacteria-bots, Biorobots, Enzymatic nanomotors, Hybrid robotics, Muscle-based biorobots


Ben Hamouda S, Vargas A, Boivin R, Miglino MA, da Palma RK, Lavoie JP, (2021). Recellularization of Bronchial Extracellular Matrix With Primary Bronchial Smooth Muscle Cells Journal Of Equine Veterinary Science 96, 103313

© 2020 Elsevier Inc. Severe asthma is associated with an increased airway smooth muscle (ASM) mass and altered composition of the extracellular matrix (ECM). Studies have indicated that ECM-ASM cell interactions contribute to this remodeling and its limited reversibility with current therapy. Three-dimensional matrices allow the study of complex cellular responses to different stimuli in an almost natural environment. Our goal was to obtain acellular bronchial matrices and then develop a recellularization protocol with ASM cells. We studied equine bronchi as horses spontaneously develop a human asthma-like disease. The bronchi were decellularized using Triton/Sodium Deoxycholate. The obtained scaffolds retained their anatomical and histological properties. Using immunohistochemistry and a semi-quantitative score to compare native bronchi to scaffolds revealed no significant variation for matrixial proteins. DNA quantification and electrophoresis revealed that most DNA was 29.6 ng/mg of tissue ± 5.6, with remaining fragments of less than 100 bp. Primary ASM cells were seeded on the scaffolds. Histological analysis of the recellularizations showed that ASM cells migrated and proliferated primarily in the decellularized smooth muscle matrix, suggesting a chemotactic effect of the scaffolds. This is the first report of primary ASM cells preferentially repopulating the smooth muscle matrix layer in bronchial matrices. This protocol is now being used to study the molecular interactions occurring between the asthmatic ECMs and ASM to identify effectors of asthmatic bronchial remodeling.

Keywords: 2d, airway smooth muscle cells, asthma, decellularization, disease, elastin, extracellular matrix, lung scaffolds, migration, peptide, recellularization, tissues, Airway smooth muscle cells, Asthma, Culture-systems, Decellularization, Extracellular matrix, Recellularization


Castillo-Escario, Y., Rodríguez-Cañón, M., García-Alías, G., Jané, R., (2020). Identifying muscle synergies from reaching and grasping movements in rats IEEE Access 8, 62517-62530

Reaching and grasping (R&G) is a skilled voluntary movement which is critical for animals. In this work, we aim to identify muscle synergy patterns from R&G movements in rats and show how these patterns can be used to characterize such movements and investigate their consistency and repeatability. For that purpose, we analyzed the electromyographic (EMG) activity of five forelimb muscles recorded while the animals were engaged in R&G tasks. Our dataset included 200 R&G attempts from three different rats. Non-negative matrix factorization was used to decompose EMG signals and extract muscle synergies. We compared all pairs of attempts and created cross-validated models to study intra- and inter-subject variability. We found that three synergies were enough to accurately reconstruct the EMG envelopes. These muscle synergies and their corresponding activation coefficients were very similar for all the attempts in the database, providing a general pattern to describe the movement. Results suggested that the movement strategy adopted by an individual in its different attempts was highly repetitive, but also resembled the strategies adopted by the other animals. Inter-subject variability was not much higher than intra-subject variability. This study is a proof-of-concept, but the proposed approaches can help to establish whether there is a stereotyped pattern of neuromuscular activity in R&G movement in healthy rats, and the changes that occur in animal models of acute neurological injuries. Research on muscle synergies could elucidate motor control mechanisms, and lead to quantitative tools for evaluating upper limb motor impairment after an injury.

Keywords: Electromyography, Motor control, Muscle synergies, Reaching and grasping, Upper limb


Estrada-Petrocelli, L., Jané, R., Torres, A., (2020). Neural respiratory drive estimation in respiratory sEMG with cardiac arrhythmias Engineering in Medicine & Biology Society (EMBC) 42nd Annual International Conference of the IEEE , IEEE (Montreal, Canada) , 2748-2751

Neural respiratory drive as measured by the electromyography allows the study of the imbalance between the load on respiratory muscles and its capacity. Surface respiratory electromyography (sEMG) is a non-invasive tool used for indirectly assessment of NRD. It also provides a way to evaluate the level and pattern of respiratory muscle activation. The prevalence of electrocardiographic activity (ECG) in respiratory sEMG signals hinders its proper evaluation. Moreover, the occurrence of abnormal heartbeats or cardiac arrhythmias in respiratory sEMG measures can make even more challenging the NRD estimation. Respiratory sEMG can be evaluated using the fixed sample entropy (fSampEn), a technique which is less affected by cardiac artefacts. The aim of this work was to investigate the performance of the fSampEn, the root mean square (RMS) and the average rectified value (ARV) on respiratory sEMG signals with supraventricular arrhythmias (SVA) for NRD estimation. fSampEn, ARV and RMS parameters increased as the inspiratory load increased during the test. fSampEn was less influenced by ECG with SVAs for the NRD estimation showing a greater response to respiratory sEMG, reflected with a higher percentage increase with increasing load (228 % total increase, compared to 142 % and 135 % for ARV and RMS, respectively).

Keywords: Electrocardiography, Muscles, Electrodes, Estimation, Band-pass filters, Electromyography, Heart beat


Hernández-Albors, Alejandro, Castaño, Albert G., Fernández-Garibay, Xiomara, Ortega, María Alejandra, Balaguer, Jordina, Ramón-Azcón, Javier, (2019). Microphysiological sensing platform for an in-situ detection of tissue-secreted cytokines Biosensors and Bioelectronics: X 2, 100025

Understanding the protein-secretion dynamics from single, specific tissues is critical toward the advancement of disease detection and treatments. However, such secretion dynamics remain difficult to measure in vivo due to the uncontrolled contributions from other tissue populations. Here, we describe an integrated platform designed for the reliable, near real-time measurements of cytokines secreted from an in vitro single-tissue model. In our setup, we grow 3D biomimetic tissues to discretize cytokine source, and we separate them from a magnetic microbead-based biosensing system using a Transwell insert. This design integrates physiochemically controlled biological activity, high-sensitivity protein detection (LOD < 20 pg mL−1), and rapid protein diffusion to enable non-invasive, near real-time measurements. To showcase the specificity and sensitivity of the system, we use our setup to probe the inflammatory process related to the protein Interleukine 6 (IL-6) and to the Tumor Necrosis Factor (TNF-α). We show that our setup can monitor the time-dependence profile of IL-6 and TNF-α secretion that results from the electrical and chemical stimulation of 3D skeletal muscle tissues. We demonstrate a novel and affordable methodology for discretizing the secretion kinetics of specific tissues for advancing metabolic-disorder studies and drug-screening applications.

Keywords: Microphysiological tissues, Tissue engineering, Electrochemical, biosensors, Magnetic particles, Skeletal muscle, Electric stimulation


Molina, B. G., Cuesta, S., Besharatloo, H., Roa, J. J., Armelin, E., Alemán, C., (2019). Free-standing taradaic motors based on biocompatible nanoperforated poly(lactic acid) layers and electropolymerized poly(3,4-ethylenedioxythiophene) ACS Applied Materials and Interfaces 11, (32), 29427-29435

The electro-chemo-mechanical response of robust and flexible free-standing films made of three nanoperforated poly(lactic acid) (pPLA) layers separated by two anodically polymerized poly(3,4-ethylenedioxythiophene) (PEDOT) layers has been demonstrated. The mechanical and electrochemical properties of these films, which are provided by pPLA and PEDOT, respectively, have been studied by nanoindentation, cyclic voltammetry, and galvanostatic charge-discharge assays. The unprecedented combination of properties obtained for this system is appropriated for its utilization as a Faradaic motor, also named artificial muscle. Application of square potential waves has shown important bending movements in the films, which can be repeated for more than 500 cycles without damaging its mechanical integrity. Furthermore, the actuator is able to push a huge amount of mass, as it has been proved by increasing the mass of the passive pPLA up to 328% while keeping the mass of electroactive PEDOT unaltered.

Keywords: Actuator, Artificial muscle, Conducting polymer, Nanoindentation


Lozano-García, M., Estrada-Petrocelli, L., Moxham, J., Rafferty, G. F., Torres, A., Jolley, C. J., Jané, R. , (2019). Noninvasive assessment of inspiratory muscle neuromechanical coupling during inspiratory threshold loading IEEE Access 7, 183634-183646

Diaphragm neuromechanical coupling (NMC), which reflects the efficiency of conversion of neural activation to transdiaphragmatic pressure (Pdi), is increasingly recognized to be a useful clinical index of diaphragm function and respiratory mechanics in neuromuscular weakness and cardiorespiratory disease. However, the current gold standard assessment of diaphragm NMC requires invasive measurements of Pdi and crural diaphragm electromyography (oesEMGdi), which complicates the measurement of diaphragm NMC in clinical practice. This is the first study to compare invasive measurements of diaphragm NMC (iNMC) using the relationship between Pdi and oesEMGdi, with noninvasive assessment of NMC (nNMC) using surface mechanomyography (sMMGlic) and electromyography (sEMGlic) of lower chest wall inspiratory muscles. Both invasive and noninvasive measurements were recorded in twelve healthy adult subjects during an inspiratory threshold loading protocol. A linear relationship between noninvasive sMMGlic and sEMGlic measurements was found, resulting in little change in nNMC with increasing inspiratory load. By contrast, a curvilinear relationship between invasive Pdi and oesEMGdi measurements was observed, such that there was a progressive increase in iNMC with increasing inspiratory threshold load. Progressive recruitment of lower ribcage muscles, serving to enhance the mechanical advantage of the diaphragm, may explain the more linear relationship between sMMGlic and sEMGlic (both representing lower intercostal plus costal diaphragm activity) than between Pdi and crural oesEMGdi. Noninvasive indices of NMC derived from sEMGlic and sMMGlic may prove to be useful indices of lower chest wall inspiratory muscle NMC, particularly in settings that do not have access to invasive measures of diaphragm function.

Keywords: Cardiovascular system, Diaphragms, Diseases, Electromyography, Medical signal processing, Neurophysiology, Patient monitoring, Pneumodynamics, Inspiratory muscle neuromechanical coupling, Diaphragm neuromechanical coupling, Neural activation, Transdiaphragmatic pressure, Diaphragm function, Respiratory mechanics, Diaphragm NMC, Invasive measurements, Crural diaphragm electromyography, iNMC, Noninvasive assessment, nNMC, Lower chest wall inspiratory muscles, Inspiratory threshold loading protocol, Noninvasive sMMGlic measurements, sEMGlic measurements, oesEMGdi measurements, Inspiratory threshold load, Lower ribcage muscles, Lower intercostal plus costal diaphragm activity, Crural oesEMGdi, Noninvasive indices, sEMGlic sMMGlic, Lower chest wall inspiratory muscle NMC, Surface mechanomyography, Electromyography, Inspiratory threshold loading, Mechanomyography, Neuromechanical coupling, Respiratory muscles


Lozano-García, M., Estrada, L., Jané, R., (2019). Performance evaluation of fixed sample entropy in myographic signals for inspiratory muscle activity estimation Entropy 21, (2), 183

Fixed sample entropy (fSampEn) has been successfully applied to myographic signals for inspiratory muscle activity estimation, attenuating interference from cardiac activity. However, several values have been suggested for fSampEn parameters depending on the application, and there is no consensus standard for optimum values. This study aimed to perform a thorough evaluation of the performance of the most relevant fSampEn parameters in myographic respiratory signals, and to propose, for the first time, a set of optimal general fSampEn parameters for a proper estimation of inspiratory muscle activity. Different combinations of fSampEn parameters were used to calculate fSampEn in both non-invasive and the gold standard invasive myographic respiratory signals. All signals were recorded in a heterogeneous population of healthy subjects and chronic obstructive pulmonary disease patients during loaded breathing, thus allowing the performance of fSampEn to be evaluated for a variety of inspiratory muscle activation levels. The performance of fSampEn was assessed by means of the cross-covariance of fSampEn time-series and both mouth and transdiaphragmatic pressures generated by inspiratory muscles. A set of optimal general fSampEn parameters was proposed, allowing fSampEn of different subjects to be compared and contributing to improving the assessment of inspiratory muscle activity in health and disease.

Keywords: Electromyography, Fixed sample entropy, Mechanomyography, Non-invasive physiological measurements, Oesophageal electromyography, Respiratory muscle


Mestre, R., Patiño, T., Guix, M., Barceló, X., Sánchez, S., (2019). Design, optimization and characterization of bio-hybrid actuators based on 3D-bioprinted skeletal muscle tissue Biomimetic and Biohybrid Systems 8th International Conference, Living Machines 2019 (Lecture Notes in Computer Science) , Springer International Publishing (Nara, Japan) 11556, 205-215

The field of bio-hybrid robotics aims at the integration of biological components with artificial materials in order to take advantage of many unique features occurring in nature, such as adaptability, self-healing or resilience. In particular, skeletal muscle tissue has been used to fabricate bio-actuators or bio-robots that can perform simple actions. In this paper, we present 3D bioprinting as a versatile technique to develop these kinds of actuators and we focus on the importance of optimizing the designs and properly characterizing their performance. For that, we introduce a method to calculate the force generated by the bio-actuators based on the deflection of two posts included in the bio-actuator design by means of image processing algorithms. Finally, we present some results related to the adaptation, controllability and force modulation of our bio-actuators, paving the way towards a design- and optimization-driven development of more complex 3D-bioprinted bio-actuators.

Keywords: 3D bioprinting, Bio-hybrid robotics, Muscle-based bio-actuators


Estrada, L., Sarlabous, L., Lozano-García, M., Jané, R., Torres, A., (2019). Neural offset time evaluation in surface respiratory signals during controlled respiration Engineering in Medicine and Biology Society (EMBC) 41st Annual International Conference of the IEEE , IEEE (Berlín, Germany) , 2344-2347

The electrical activity of the diaphragm measured by surface electromyography (sEMGdi) provides indirect information on neural respiratory drive. Moreover, it allows evaluating the ventilatory pattern from the onset and offset (ntoff) estimation of the neural inspiratory time. sEMGdi amplitude variation was quantified using the fixed sample entropy (fSampEn), a less sensitive method to the interference from cardiac activity. The detection of the ntoff is controversial, since it is located in an intermediate point between the maximum value and the cessation of sEMGdi inspiratory activity, evaluated by the fSampEn. In this work ntoff detection has been analyzed using thresholds between 40% and 100 % of the fSampEn peak. Furthermore, fSampEn was evaluated analyzing the r parameter from 0.05 to 0.6, using a m equal to 1 and a sliding window size equal to 250 ms. The ntoff has been compared to the offset time (toff) obtained from the airflow during a controlled respiratory protocol varying the fractional inspiratory time from 0.54 to 0.18 whilst the respiratory rate was constant at 16 bpm. Results show that the optimal threshold values were between 66.0 % to 77.0 % of the fSampEn peak value. r values between 0.25 to 0.50 were found suitable to be used with the fSampEn.

Keywords: Protocols, Low pass filters, Electrodes, Standards, Band-pass filters, Muscles, Cutoff frequency


Castillo-Escario, Y., Rodríguez-Cañón, M., García-Alías, G., Jané, R., (2019). Onset detection to study muscle activity in reaching and grasping movements in rats Engineering in Medicine and Biology Society (EMBC) 41st Annual International Conference of the IEEE , IEEE (Berlín, Germany) , 5113-5116

EMG signals reflect the neuromuscular activation patterns related to the execution of a certain movement or task. In this work, we focus on reaching and grasping (R&G) movements in rats. Our objective is to develop an automatic algorithm to detect the onsets and offsets of muscle activity and use it to study muscle latencies in R&G maneuvers. We had a dataset of intramuscular EMG signals containing 51 R&G attempts from 2 different animals. Simultaneous video recordings were used for segmentation and comparison. We developed an automatic onset/offset detector based on the ratio of local maxima of Teager-Kaiser Energy (TKE). Then, we applied it to compute muscle latencies and other features related to the muscle activation pattern during R&G cycles. The automatic onsets that we found were consistent with visual inspection and video labels. Despite the variability between attempts and animals, the two rats shared a sequential pattern of muscle activations. Statistical tests confirmed the differences between the latencies of the studied muscles during R&G tasks. This work provides an automatic tool to detect EMG onsets and offsets and conducts a preliminary characterization of muscle activation during R&G movements in rats. This kind of approaches and data processing algorithms can facilitate the studies on upper limb motor control and motor impairment after spinal cord injury or stroke.

Keywords: Muscles, Electromyography, Rats, Low pass filters, Microsoft Windows, Band-pass filters


Mohammadi, M. H., Obregón, R., Ahadian, S., Ramón-Azcón, J., Radisic, M., (2017). Engineered muscle tissues for disease modeling and drug screening applications Current Pharmaceutical Design , 23, (20), 2991-3004

Animal models have been the main resources for drug discovery and prediction of drugs’ pharmacokinetic responses in the body. However, noticeable drawbacks associated with animal models include high cost, low reproducibility, low physiological similarity to humans, and ethical problems. Engineered tissue models have recently emerged as an alternative or substitute for animal models in drug discovery and testing and disease modeling. In this review, we focus on skeletal muscle and cardiac muscle tissues by first describing their characterization and physiology. Major fabrication technologies (i.e., electrospinning, bioprinting, dielectrophoresis, textile technology, and microfluidics) to make functional muscle tissues are then described. Finally, currently used muscle tissue models in drug screening are reviewed and discussed.

Keywords: Cardiac muscle, Drug screening, Engineering muscle, Human pharmacological response, Physiological similarity, Skeletal muscle


Estrada, L., Torres, A., Sarlabous, L., Jané, R., (2016). Improvement in neural respiratory drive estimation from diaphragm electromyographic signals using fixed sample entropy IEEE Journal of Biomedical and Health Informatics 20, (2), 476-485

Diaphragm electromyography is a valuable technique for the recording of electrical activity of the diaphragm. The analysis of diaphragm electromyographic (EMGdi) signal amplitude is an alternative approach for the quantification of neural respiratory drive (NRD). The EMGdi signal is, however, corrupted by electrocardiographic (ECG) activity, and this presence of cardiac activity can make the EMGdi interpretation more difficult. Traditionally, the EMGdi amplitude has been estimated using the average rectified value (ARV) and the root mean square (RMS). In this work, surface EMGdi signals were analyzed using the fixed sample entropy (fSampEn) algorithm, and compared to traditional ARV and RMS methods. The fSampEn is calculated using a tolerance value fixed and independent of the standard deviation of the analysis window. Thus, this method quantifies the amplitude of the complex components of stochastic signals (such as EMGdi), and being less affected by changes in amplitude due to less complex components (such as ECG). The proposed method was tested in synthetic and recorded EMGdi signals. fSampEn was less sensitive to the effect of cardiac activity on EMGdi signals with different levels of NRD than ARV and RMS amplitude parameters. The mean and standard deviation of the Pearson’s correlation values between inspiratory mouth pressure (an indirect measure of the respiratory muscle activity) and fSampEn, ARV and RMS parameters, estimated in the recorded EMGdi signal at tidal volume (without inspiratory load), were 0.38???0.12, 0.27???0.11 and 0.11???0.13, respectively. Whereas at 33 cmH2O (maximum inspiratory load) were 0.83???0.02, 0.76???0.07 and 0.61???0.19, respectively. Our findings suggest that the proposed method may improve the evaluation of NRD.

Keywords: Electromyography, diaphragm muscle, neural respiratory drive


Estrada, L., Torres, A., Sarlabous, L., Jané, R., (2016). Evaluating respiratory muscle activity using a wireless sensor platform Engineering in Medicine and Biology Society (EMBC) 38th Annual International Conference of the IEEE , IEEE (Orlando, USA) , 5769-5772

Wireless sensors are an emerging technology that allows to assist physicians in the monitoring of patients health status. This approach can be used for the non-invasive recording of the electrical respiratory muscle activity of the diaphragm (EMGdi). In this work, we acquired the EMGdi signal of a healthy subject performing an inspiratory load test. To this end, the EMGdi activity was captured from a single channel of electromyography using a wireless platform which was compared with the EMGdi and the inspiratory mouth pressure (Pmouth) recorded with a conventional lab equipment. From the EMGdi signal we were able to evaluate the neural respiratory drive, a biomarker used for assessing the respiratory muscle function. In addition, we evaluated the breathing movement and the cardiac activity, estimating two cardio-respiratory parameters: the respiratory rate and the heart rate. The correlation between the two EMGdi signals and the Pmouth improved with increasing the respiratory load (Pearson's correlation coefficient ranges from 0.33 to 0.85). The neural respiratory drive estimated from both EMGdi signals showed a positive trend with an increase of the inspiratory load and being higher in the conventional EMGdi recording. The respiratory rate comparison between measurements revealed similar values of around 16 breaths per minute. The heart rate comparison showed a root mean error of less than 0.2 beats per minute which increased when incrementing the inspiratory load. In summary, this preliminary work explores the use of wireless devices to record the muscle respiratory activity to derive several physiological parameters. Its use can be an alternative to conventional measuring systems with the advantage of being portable, lightweight, flexible and operating at low energy. This technology can be attractive for medical staff and may have a positive impact in the way healthcare is being delivered.

Keywords: Biomedical monitoring, Electrodes, Medical services, Monitoring, Muscles, Wireless communication, Wireless sensor networks


Estrada, L., Torres, A., Garcia-Casado, J., Sarlabous, L., Prats-Boluda, G., Jané, R., (2016). Time-frequency representations of the sternocleidomastoid muscle electromyographic signal recorded with concentric ring electrodes Engineering in Medicine and Biology Society (EMBC) 38th Annual International Conference of the IEEE , IEEE (Orlando, USA) , 3785-3788

The use of non-invasive methods for the study of respiratory muscle signals can provide clinical information for the evaluation of the respiratory muscle function. The aim of this study was to evaluate time-frequency characteristics of the electrical activity of the sternocleidomastoid muscle recorded superficially by means of concentric ring electrodes (CREs) in a bipolar configuration. The CREs enhance the spatial resolution, attenuate interferences, as the cardiac activity, and also simplify the orientation problem associated to the electrode location. Five healthy subjects underwent a respiratory load test in which an inspiratory load was imposed during the inspiratory phase. During the test, the electromyographic signal of the sternocleidomastoid muscle (EMGsc) and the inspiratory mouth pressure (Pmouth) were acquired. Time-frequency characteristics of the EMGsc signal were analyzed by means of eight time-frequency representations (TFRs): the spectrogram (SPEC), the Morlet scalogram (SCAL), the Wigner-Ville distribution (WVD), the Choi-Williams distribution (CHWD), two generalized exponential distributions (GED1 and GED2), the Born-Jordan distribution (BJD) and the Cone-Kernel distribution (CKD). The instantaneous central frequency of the EMGsc showed an increasing behavior during the inspiratory cycle and with the increase of the inspiratory load. The bilinear TFRs (WVD, CHWD, GEDs and BJD) were less sensitive to cardiac activity interference than classical TFRs (SPEC and SCAL). The GED2 was the TFR that shown the best results for the characterization of the instantaneous central frequency of the EMGsc.

Keywords: Electrodes, Interference, Kernel, Mouth, Muscles, Spectrogram, Time-frequency analysis


Estrada, L., Torres, A., Sarlabous, L., Jané, R., (2015). EMG-derived respiration signal using the fixed sample entropy during an Inspiratory load protocol Engineering in Medicine and Biology Society (EMBC) 37th Annual International Conference of the IEEE , IEEE (Milan, Italy) , 1703-1706

Extracting clinical information from one single measurement represents a step forward in the assessment of the respiratory muscle function. This attracting idea entails the reduction of the instrumentation and fosters to develop new medical integrated technologies. We present the use of the fixed sample entropy (fSampEn) as a more direct method to non-invasively derive the breathing activity from the diaphragm electromyographic (EMGdi) signal, and thus to extract the respiratory rate, an important vital sign which is cumbersome and time-consuming to be measured by clinicians. fSampEn is a method to evaluate the EMGdi activity that is less sensitive to the cardiac activity (ECG) and its application has proven to be useful to evaluate the load of the respiratory muscles. The behavior of the proposed method was tested in signals from two subjects that performed an inspiratory load protocol, which consists of increments in the inspiratory mouth pressure (Pmouth). Two respiratory signals were derived and compared to the Pmouth signal: the ECG-derived respiration (EDR) signal from the lead-I configuration, and the EMG-derived respiration (EMGDR) signal by applying the fSampEn method over the EMGdi signal. The similitude and the lag between signals were calculated through the cross-correlation between each derived respiratory signal and the Pmouth. The EMGDR signal showed higher correlation and lower lag values (≥ 0.91 and ≤ 0.70 s, respectively) than the EDR signal (≥ 0.83 and ≤0.99 s, respectively). Additionally, the respiratory rate was estimated with the Pmouth, EDR and EMGDR signals showing very similar values. The results from this preliminary work suggest that the fSampEn method can be used to derive the respiration waveform from the respiratory muscle electrical activity.

Keywords: Band-pass filters, Electrocardiography, Electromyography, Entropy, Mouth, Muscles, Protocols


Urra, O., Casals, A., Jané, R., (2015). The impact of visual feedback on the motor control of the upper-limb Engineering in Medicine and Biology Society (EMBC) 37th Annual International Conference of the IEEE , IEEE (Milan, Italy) , 3945-3948

Stroke is a leading cause of adult disability with upper-limb hemiparesis being one of the most frequent consequences. Given that stroke only affects the paretic arm's control structure (the set of synergies and activation vectors needed to perform a movement), we propose that the control structure of the non-affected arm can serve as a physiological reference to rehabilitate the paretic arm. However, it is unclear how rehabilitation can effectively tune the control structure of a patient. The use of Visual Feedback (VF) is recommended to boost stroke rehabilitation, as it is able to positively modify neural mechanisms and improve motor performance. Thus, in this study we investigate whether VF can effectively modify the control structure of the upper-limb. We asked six neurologically intact subjects to perform a complete upper-limb rehabilitation routine comprised of 12 movements in absence and presence of VF. Our results indicate that VF significantly increases interlimb similarity both in terms of synergies and activation coefficients. However, the magnitude of improvement depended upon each subject. In general, VF brings the control structure of the nondominant side closer to the control structure of dominant side, suggesting that VF modifies the control structure towards more optimized motor patterns. This is especially interesting because stroke mainly affects the activation coefficients of patients and because it has been shown that the control of the affected side resembles that of the nondominant side. In conclusion, VF may enhance motor performance by effectively tuning the control-structure. Notably, this finding offers new insights to design improved stroke rehabilitation.

Keywords: Bars, Biomedical engineering, Electrodes, Electromyography, Mirrors, Muscles, Visualization


Estrada, L., Torres, A., Garcia-Casado, J., Prats-Boluda, G., Yiyao, Ye-Lin, Jané, R., (2014). Evaluation of Laplacian diaphragm electromyographic recording in a dynamic inspiratory maneuver Engineering in Medicine and Biology Society (EMBC) 36th Annual International Conference of the IEEE , IEEE (Chicago, USA) , 2201-2204

The analysis of the electromyographic signal of the diaphragm muscle (EMGdi) can provide important information for evaluating the respiratory muscular function. The EMGdi can be recorded using surface Ag/AgCl disc electrodes in monopolar or bipolar configuration. However, these non-invasive EMGdi recordings are usually contaminated by the electrocardiographic (ECG) signal. EMGdi signal can also be noninvasively recorded using concentric ring electrodes in bipolar configuration (CRE) that estimate Laplacian surface potential. Laplacian recordings increase spatial resolution and attenuate distant bioelectric interferences, such as the ECG. Thus, the objective of this work is to compare and to evaluate CRE and traditional bipolar EMGdi recordings in a healthy subject during a dynamic inspiratory maneuver with incremental inspiratory loads. In the conducted study, it was calculated the cumulative percentage of power spectrum of EMGdi recordings to determine the signal bandwidth, and the power ratio between the EMGdi signal segments with and without cardiac activity. The results of this study suggest that EMGdi acquired with CRE electrodes is less affected by the ECG interference, achieves a wider bandwidth and a higher power ratio between segments without cardiac activity and with cardiac activity.

Keywords: Bandwidth, Electric potential, Electrocardiography, Electrodes, Interference, Laplace equations, Muscles


Estrada, L., Torres, A., Sarlabous, L., Fiz, J. A., Jané, R., (2014). Respiratory rate detection by empirical mode decomposition method applied to diaphragm mechanomyographic signals Engineering in Medicine and Biology Society (EMBC) 36th Annual International Conference of the IEEE , IEEE (Chicago, USA) , 3204-3207

Non-invasive evaluation of respiratory activity is an area of increasing research interest, resulting in the appearance of new monitoring techniques, ones of these being based on the analysis of the diaphragm mechanomyographic (MMGdi) signal. The MMGdi signal can be decomposed into two parts: (1) a high frequency activity corresponding to lateral vibration of respiratory muscles, and (2) a low frequency activity related to excursion of the thoracic cage. The purpose of this study was to apply the empirical mode decomposition (EMD) method to obtain the low frequency of MMGdi signal and selecting the intrinsic mode functions related to the respiratory movement. With this intention, MMGdi signals were acquired from a healthy subject, during an incremental load respiratory test, by means of two capacitive accelerometers located at left and right sides of rib cage. Subsequently, both signals were combined to obtain a new signal which contains the contribution of both sides of thoracic cage. Respiratory rate (RR) measured from the mechanical activity (RRMmg) was compared with that measured from inspiratory pressure signal (RRP). Results showed a Pearson's correlation coefficient (r = 0.87) and a good agreement (mean bias = -0.21 with lower and upper limits of -2.33 and 1.89 breaths per minute, respectively) between RRmmg and RRP measurements. In conclusion, this study suggests that RR can be estimated using EMD for extracting respiratory movement from low mechanical activity, during an inspiratory test protocol.

Keywords: Accelerometers, Band-pass filters, Biomedical measurement, Empirical mode decomposition, Estimation, IP networks, Muscles


Torres, A., Fiz, J. A., Jané, R., (2014). Cancellation of cardiac interference in diaphragm EMG signals using an estimate of ECG reference signal IFMBE Proceedings XIII Mediterranean Conference on Medical and Biological Engineering and Computing 2013 (ed. Roa Romero, Laura M.), Springer International Publishing (London, UK) 41, 1000-1004

The analysis of the electromyographic signal of the diaphragm muscle (EMGdi) can provide important information in order to evaluate the respiratory muscular function. However, EMGdi signals are usually contaminated by the electrocardiographic (ECG) signal. An adaptive noise cancellation (ANC) based on event-synchronous cancellation can be used to reduce the ECG interference in the recorded EMGdi activity. In this paper, it is proposed an ANC scheme for cancelling the ECG interference in EMGdi signals using only the EMGdi signal (without acquiring the ECG signal). In this case the detection of the QRS complex has been performed directly in the EMGdi signal, and the ANC algorithm must be robust to false or missing QRS detections. Furthermore, an automatic criterion to select the adaptive constant of the LMS algorithm has been proposed (μ). The μ constant is selected automatically so that the canceling signal energy equals the energy of the reference signal (which is an estimation of the ECG interference present in the EMGdi signal). This approach optimizes the tradeoff between cancellation of ECG interference and attenuation of EMG component. A number of weights equivalent of a time window that contains several QRS complexes is selected in order to make the algorithm robust to QRS detection errors.

Keywords: Adaptive Canceller, EMG, Diaphragm muscle


Estrada, L., Torres, A., Garcia-Casado, J., Ye-Lin, Y., Jané, R., (2014). Evaluation of Laplacian diaphragm electromyographic recordings in a static inspiratory maneuver IFMBE Proceedings XIII Mediterranean Conference on Medical and Biological Engineering and Computing 2013 (ed. Roa Romero, Laura M.), Springer International Publishing (London, UK) 41, 977-980

Diaphragm electromyography (EMGdi) provides important information on diaphragm activity, to detect neuromuscular disorders of the most important muscle in the breathing inspiratory phase. EMGdi is habitually recorded using needles or esophageal catheters, with the implication of being invasive for patients. Surface electrodes offer an alternative for the non-invasive assessment of diaphragm activity. Ag/AgCl surface disc electrodes are used in monopolar or bipolar configuration to record EMGdi signals. On the other hand, Laplacian surface potential can be estimated by signal recording through active concentric ring electrodes. This kind of recording could reduce physiological interferences, increase the spatial selectivity and reduce orientation problems in the electrode location. The aim of this work is to compare EMGdi signals recorded simultaneously with disc electrodes in bipolar configuration and a Laplacian ring electrode over chest wall. EMGdi signal was recorded in one healthy subject during a breath hold maneuver and a static inspiratory maneuver based on Mueller’s technique. In order to estimate the covered frequency range and the degree of noise contamination in both bipolar and Laplacian EMGdi signals, the cumulative percentage of the power spectrum and the signal to noise ratio in sub-bands were determined. Furthermore, diaphragm fatigue was evaluated by means of amplitude and frequency parameters. Our findings suggest that Laplacian EMGdi recording covers a broader frequency range although with higher noise contamination compared to bipolar EMGdi recording. Finally, in Laplacian recording fatigue indexes showed a clearer trend for muscle fatigue detection and also a reduced cardiac interference, providing an alternative to bipolar recording for diaphragm fatigue studies.

Keywords: Laplacian electrode, Diaphragm muscle, Fatigue, Surface electromyography


Sarlabous, L., Torres, A., Fiz, J. A., Morera, J., Jané, R., (2013). Index for estimation of muscle force from mechanomyography based on the Lempel-Ziv algorithm Journal of Electromyography and Kinesiology , 23, (3), 548-557

The study of the amplitude of respiratory muscle mechanomyographic (MMG) signals could be useful in clinical practice as an alternative non-invasive technique to assess respiratory muscle strength. The MMG signal is stochastic in nature, and its amplitude is usually estimated by means of the average rectified value (ARV) or the root mean square (RMS) of the signal. Both parameters can be used to estimate MMG activity, as they correlate well with muscle force. These estimations are, however, greatly affected by the presence of structured impulsive noise that overlaps in frequency with the MMG signal. In this paper, we present a method for assessing muscle activity based on the Lempel-Ziv algorithm: the Multistate Lempel-Ziv (MLZ) index. The behaviour of the MLZ index was tested with synthesised signals, with various amplitude distributions and degrees of complexity, and with recorded diaphragm MMG signals. We found that this index, like the ARV and RMS parameters, is positively correlated with changes in amplitude of the diaphragm MMG components, but is less affected by components that have non-random behaviour (like structured impulsive noise). Therefore, the MLZ index could provide more information to assess the MMG-force relationship.

Keywords: Diaphragm, Electromyography, Lempel-Ziv, Mechanomyography, Muscle force, Respiratory muscles


Sarlabous, L., Torres, A., Fiz, J. A., Morera, J., Jané, R., (2012). Evaluation and adaptive attenuation of the cardiac vibration interference in mechanomyographic signals Engineering in Medicine and Biology Society (EMBC) 34th Annual International Conference of the IEEE , IEEE (San Diego, USA) , 3400-3403

The study of the mechanomyographic signal of the diaphragm muscle (MMGdi) is a promising technique in order to evaluate the respiratory muscles effort. The relationship between amplitude and frequency parameters of this signal with the respiratory effort performed during respiration is of great interest for researchers and physicians due to its diagnostic potentials. However, MMGdi signals are frequently contaminated by a cardiac vibration or mechanocardiographic (MCG) signal. An adaptive noise cancellation (ANC) can be used to reduce the MCG interference in the recorded MMGdi activity. In this paper, it is evaluated the proposed ANC scheme by means of a synthetic MMGdi signal with a controlled MCG interference. The Pearson's correlation coefficient (PCC) between both root mean square (RMS) and mean frequency (fm) of the synthetic MMGdi signal are considerably reduced with the presence of cardiac vibration noise (from 0.95 to 0.87, and from 0.97 to 0.76, respectively). With the ANC algorithm proposed the effect of the MCG noise on the amplitude and frequency of MMG parameters is reduced considerably (PCC of 0.93 and 0.97 for the RMS and fm, respectively). The ANC method proposed in this work is an interesting technique to attenuate the cardiac interference in respiratory MMG signals. Further investigation should be carried out to evaluate the performance of the ANC algorithm in real MMGdi signals.

Keywords: Adaptive filters, Frequency modulation, Interference, Muscles, Noise cancellation, Vibrations, Cardiology, Medical signal processing, Muscle, Signal denoising, ANC algorithm, MCG interference, Pearson correlation coefficient, Adaptive noise cancellation, Cardiac vibration interference, Cardiac vibration noise, Diaphragm muscle, Mechanocardiographic signal, Mechanomyographic signals, Respiratory muscles effort


Moore, S. W., Roca-Cusachs, P., Sheetz, M. P., (2010). Stretchy proteins on stretchy substrates: The important elements of integrin-mediated rigidity sensing Developmental Cell 19, (2), 194-206

Matrix and tissue rigidity guides many cellular processes, including the differentiation of stem cells and the migration of cells in health and disease. Cells actively and transiently test rigidity using mechanisms limited by inherent physical parameters that include the strength of extracellular attachments, the pulling capacity on these attachments, and the sensitivity of the mechanotransduction system. Here, we focus on rigidity sensing mediated through the integrin family of extracellular matrix receptors and linked proteins and discuss the evidence supporting these proteins as mechanosensors.

Keywords: Focal adhesion kinase, Atomic Force Microscopy, Smooth-muscle cells, Traction forces, Living cells, Mechanical force, Locomoting cells


Sarlabous, L., Torres, A., Fiz, J. A., Gea, J., Marti nez-Llorens, J. M., Morera, J., Jané, R., (2010). Interpretation of the approximate entropy using fixed tolerance values as a measure of amplitude variations in biomedical signals Engineering in Medicine and Biology Society (EMBC) 32nd Annual International Conference of the IEEE , IEEE (Buenos Aires, Argentina) , 5967-5970

A new method for the quantification of amplitude variations in biomedical signals through moving approximate entropy is presented. Unlike the usual method to calculate the approximate entropy (ApEn), in which the tolerance value (r) varies based on the standard deviation of each moving window, in this work ApEn has been computed using a fixed value of r. We called this method, moving approximate entropy with fixed tolerance values: ApEn/sub f/. The obtained results indicate that ApEn/sub f/ allows determining amplitude variations in biomedical data series. These amplitude variations are better determined when intermediate values of tolerance are used. The study performed in diaphragmatic mechanomyographic signals shows that the ApEn/sub f/ curve is more correlated with the respiratory effort than the standard RMS amplitude parameter. Furthermore, it has been observed that the ApEn/sub f/ parameter is less affected by the existence of impulsive, sinusoidal, constant and Gaussian noises in comparison with the RMS amplitude parameter.

Keywords: Practical, Theoretical or Mathematical/ biomechanics, Entropy, Gaussian noise, Medical signal processing, Muscle, Random processes/ approximate entropy interpretation, Fixed tolerance values, Diaphragmatic mechanomyographic signals, ApEnf curve, Respiratory effort, Gaussian noises


Torres, A., Sarlabous, L., Fiz, j A., Gea, J., Marti nez-Llorens, J. M., Morera, J., Jané, R., (2010). Noninvasive measurement of inspiratory muscle performance by means of diaphragm muscle mechanomyographic signals in COPD patients during an incremental load respiratory test Engineering in Medicine and Biology Society (EMBC) 32nd Annual International Conference of the IEEE , IEEE (Buenos Aires, Argentina) , 2493-2496

The study of mechanomyographic (MMG) signals of respiratory muscles is a promising noninvasive technique in order to evaluate the respiratory muscular effort and efficiency. In this work, the MMG signal of the diaphragm muscle it is evaluated in order to assess the respiratory muscular function in Chronic Obstructive Pulmonary Disease (COPD) patients. The MMG signals from left and right hemidiaphragm were acquired using two capacitive accelerometers placed on both left and right sides of the costal wall surface. The MMG signals and the inspiratory pressure signal were acquired while the COPD patients carried out an inspiratory load respiratory test. The population of study is composed of a group of 6 patients with severe COPD (FEV1>50% ref and DLCO<50% ref). We have found high positive correlation coefficients between the maximum inspiratory pressure (IPmax) developed in a respiratory cycle and different amplitude parameters of both left and right MMG signals (RMS, left: 0.68+/-0.11 - right: 0.69+/-0.12; Re nyi entropy, left: - 0.73+/-0.10 - right: 0.77+/-0.08; Multistate Lempel-Ziv, left: 0.73+/-0.17 - right: 0.74+/-0.08), and negative correlation between the Pmax and the maximum frequency of the MMG signal spectrum (left: -0.39+/-0.19 - right: -0.65+/-0.09). Furthermore, we found that the slope of the evolution of the MMG amplitude parameters, as the load increases during the respiratory test, has positive correlation with the %FEV1/FVC pulmonary function test parameter of the six COPD patients analyzed (RMS, left: 0.38 - right: 0.41; Re nyi entropy, left: 0.45 - right: 0.63; Multistate Lempel-Ziv, left: 0.39 - right: 0.64). These results suggest that the information provided by MMG signals could be used in order to evaluate the respiratory effort and the muscular efficiency in COPD patients.

Keywords: Accelerometers, Biomechanics, Biomedical measurement, Diseases, Medical signal processing, Muscle


Sunyer, R., Trepat, X., Fredberg, J. J., Farre, R., Navajas, D., (2009). The temperature dependence of cell mechanics measured by atomic force microscopy Physical Biology 6, (2), 25009

The cytoskeleton is a complex polymer network that regulates the structural stability of living cells. Although the cytoskeleton plays a key role in many important cell functions, the mechanisms that regulate its mechanical behaviour are poorly understood. Potential mechanisms include the entropic elasticity of cytoskeletal filaments, glassy-like inelastic rearrangements of cross-linking proteins and the activity of contractile molecular motors that sets the tensional stress (prestress) borne by the cytoskeleton filaments. The contribution of these mechanisms can be assessed by studying how cell mechanics depends on temperature. The aim of this work was to elucidate the effect of temperature on cell mechanics using atomic force microscopy. We measured the complex shear modulus (G*) of human alveolar epithelial cells over a wide frequency range (0.1-25.6 Hz) at different temperatures (13-37 degrees C). In addition, we probed cell prestress by mapping the contractile forces that cells exert on the substrate by means of traction microscopy. To assess the role of actomyosin contraction in the temperature-induced changes in G* and cell prestress, we inhibited the Rho kinase pathway of the myosin light chain phosphorylation with Y-27632. Our results show that with increasing temperature, cells become stiffer and more solid-like. Cell prestress also increases with temperature. Inhibiting actomyosin contraction attenuated the temperature dependence of G* and prestress. We conclude that the dependence of cell mechanics with temperature is dominated by the contractile activity of molecular motors.

Keywords: Membrane Stress Failure, Frog Skeletal-Muscle, Extracellular-Matrix, Glass-Transition, Energy Landscape, Actin-Filaments, Living Cell, Single, Traction, Cytoskeleton


Orini, Michele, Giraldo, Beatriz F., Bailon, Raquel, Vallverdu, Montserrat, Mainardi, Luca, Benito, Salvador, Diaz, Ivan, Caminal, Pere, (2008). Time-frequency analysis of cardiac and respiratory parameters for the prediction of ventilator weaning IEEE Engineering in Medicine and Biology Society Conference Proceedings 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (ed. IEEE), IEEE (Vancouver, Canada) 1-8, 2793-2796

Mechanical ventilators are used to provide life support in patients with respiratory failure. Assessing autonomic control during the ventilator weaning provides information about physiopathological imbalances. Autonomic parameters can be derived and used to predict success in discontinuing from the mechanical support. Time-frequency analysis is used to derive cardiac and respiratory parameters, as well as their evolution in time, during ventilator weaning in 130 patients. Statistically significant differences have been observed in autonomic parameters between patients who are considered ready for spontaneous breathing and patients who are not. A classification based on respiratory frequency, heart rate and heart rate variability spectral components has been proposed and has been able to correctly classify more than 80% of the cases.

Keywords: Automatic Data Processing, Databases, Factual, Electrocardiography, Humans, Models, Statistical, Respiration, Respiration, Artificial, Respiratory Insufficiency, Respiratory Mechanics, Respiratory Muscles, Signal Processing, Computer-Assisted, Time Factors, Ventilator Weaning, Ventilators, Mechanical, Work of Breathing