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by Keyword: Humans

González J-E, Rodríguez MA, Caballero E, Pardo A, Marco S, Farré R, (2024). Open-source, low-cost App-driven Internet of Things approach to facilitate respiratory oscillometry at home and in developing countries Pulmonology 30, 180-183

Humbert, P, Kampleitner, C, De Lima, J, Brennan, MA, Lodoso-Torrecilla, I, Sadowska, JM, Blanchard, F, Canal, C, Ginebra, MP, Hoffmann, O, Layrolle, P, (2024). Phase composition of calcium phosphate materials affects bone formation by modulating osteoclastogenesis Acta Biomaterialia 176, 417-431

Human mesenchymal stromal cells (hMSCs) seeded on calcium phosphate (CaP) bioceramics are extensively explored in bone tissue engineering and have recently shown effective clinical outcomes. In previous pre-clinical studies, hMSCs-CaP-mediated bone formation was preceded by osteoclastogenesis at the implantation site. The current study evaluates to what extent phase composition of CaPs affects the osteoclast response and ultimately influence bone formation. To this end, four different CaP bioceramics were used, hydroxyapatite (HA), beta-tricalcium phosphate (beta-TCP) and two biphasic composites of HA/beta- TCP ratios of 60/40 and 20/80 respectively, for in vitro osteoclast differentiation and correlation with in vivo osteoclastogenesis and bone formation. All ceramics allowed osteoclast formation in vitro from mouse and human precursors, except for pure HA, which significantly impaired their maturation. Ectopic implantation alongside hMSCs in subcutis sites of nude mice revealed new bone formation at 8 weeks in all conditions with relative amounts for beta-TCP > biphasic CaPs > HA. Surprisingly, while hMSCs were essential for osteoinduction, their survival did not correlate with bone formation. By contrast, the degree of early osteoclastogenesis (2 weeks) seemed to define the extent of subsequent bone formation. Together, our findings suggest that the osteoclastic response could be used as a predictive marker in hMSC-CaPbased bone regeneration and strengthens the need to understand the underlying mechanisms for future biomaterial development. Statement of significance The combination of mesenchymal stromal cells (MSCs) and calcium phosphate (CaP) materials has demonstrated its safety and efficacy for bone regeneration in clinical trials, despite our insufficient understanding of the underlying biological mechanisms. Osteoclasts were previously suggested as key mediators between the early inflammatory phase following biomaterial implantation and the subsequent bone formation. Here we compared the affinity of osteoclasts for various CaP materials with different ratios of hydroxyapatite to beta-tricalcium phosphate. We found that osteoclast formation, both in vitro and at early stages in vivo, correlates with bone formation when the materials were implanted alongside MSCs in mice. Surprisingly, MSC survival did not correlate with bone formation, suggesting that the number or phenotype of osteoclasts formed was more important. (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

JTD Keywords: Acid phosphatase tartrate resistant isoenzyme, Animal, Animal cell, Animal experiment, Animal tissue, Animals, Article, Beta-tricalcium phosphate, Bioceramics, Biocompatible materials, Biomaterial, Bone, Bone development, Bone formation, Bone regeneration, Calcium phosphate, Calcium phosphate materials, Calcium phosphates, Cd14 antigen, Cell differentiation, Cell engineering, Cell maturation, Cell survival, Ceramics, Chemical composition, Controlled study, Correlation analysis, Correlation coefficient, Data correlation, Durapatite, Engraftment, Flowcharting, Human, Human cell, Human mesenchymal stromal cell, Human mesenchymal stromal cells, Humans, Hydroxyapatite, Hydroxyapatites, In vitro study, In vivo study, In-vitro, In-vivo, Mammals, Marrow stromal cells, Material composition, Material compositions, Mesenchymal stroma cell, Mesenchymal stromal cells, Mice, Mice, nude, Monocyte, Mouse, Nonhuman, Nude mouse, Ossification, Osteoclast, Osteoclastogenesis, Osteoclasts, Osteogenesis, Osteoinduction, Phase composition, Regeneration strategies, Resorption, Scaffolds, Stem-cells, Subcutaneous tissue, Tissue engineering, Transmission control protocol, Tri-calcium phosphates, Vimentin


Avalos-Padilla, Y, Fernandez-Busquets, X, (2024). Nanotherapeutics against malaria: A decade of advancements in experimental models Wiley Interdisciplinary Reviews-Nanomedicine And Nanobiotechnology 16, e1943

Malaria, caused by different species of protists of the genus Plasmodium, remains among the most common causes of death due to parasitic diseases worldwide, mainly for children aged under 5. One of the main obstacles to malaria eradication is the speed with which the pathogen evolves resistance to the drug schemes developed against it. For this reason, it remains urgent to find innovative therapeutic strategies offering sufficient specificity against the parasite to minimize resistance evolution and drug side effects. In this context, nanotechnology-based approaches are now being explored for their use as antimalarial drug delivery platforms due to the wide range of advantages and tuneable properties that they offer. However, major challenges remain to be addressed to provide a cost-efficient and targeted therapeutic strategy contributing to malaria eradication. The present work contains a systematic review of nanotechnology-based antimalarial drug delivery systems generated during the last 10 years. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

JTD Keywords: Adjuvant system, Antimalarial activities, Antimalarial agent, Antimalarial drug, Antimalarial drugs, Antimalarials, Artemisinin resistance, Causes of death, Child, Controlled drug delivery, Diseases, Drug delivery system, Drug delivery systems, Drug interactions, Drug side-effects, Drug-delivery, Experimental modelling, Heparan-sulfate, Human, Humans, In-vitro, Malaria, Malaria vaccine, Mannosylated liposomes, Medical nanotechnology, Models, theoretical, Nanocarriers, Nanomedicine, Nanotechnology, Parasite-, Parasitics, Plasmodium, Plasmodium-falciparum malaria, Red-blood-cells, Targeted delivery, Targeted drug delivery, Theoretical model, Therapeutic strategy


Hafa, L, Breideband, L, Posada, LR, Torras, N, Martinez, E, Stelzer, EHK, Pampaloni, F, (2024). Light Sheet-Based Laser Patterning Bioprinting Produces Long-Term Viable Full-Thickness Skin Constructs Advanced Materials 36, e2306258

Tissue engineering holds great promise for biomedical research and healthcare, offering alternatives to animal models and enabling tissue regeneration and organ transplantation. Three-dimensional (3D) bioprinting stands out for its design flexibility and reproducibility. Here, we present an integrated fluorescent light sheet bioprinting and imaging system that combines high printing speed (0.66 mm3 /s) and resolution (9 μm) with light sheet-based imaging. This approach employs direct laser patterning and a static light sheet for confined voxel crosslinking in photocrosslinkable materials. The developed bioprinter enables real-time monitoring of hydrogel crosslinking using fluorescent recovery after photobleaching (FRAP) and brightfield imaging as well as in situ light sheet imaging of cells. Human fibroblasts encapsulated in a thiol-ene click chemistry-based hydrogel exhibited high viability (83% ± 4.34%) and functionality. Furthermore, full-thickness skin constructs displayed characteristics of both epidermal and dermal layers and remained viable for 41 days. The integrated approach demonstrates the capabilities of light sheet bioprinting, offering high speed, resolution, and real-time characterization. Future enhancements involving solid-state laser scanning devices such as acousto-optic deflectors and modulators will further enhance resolution and speed, opening new opportunities in light-based bioprinting and advancing tissue engineering. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.

JTD Keywords: cadherin, collagen, culture, differentiation, fluorescence microscopy, full-thickness skin model, hydrogels, light sheet bioprinter, light sheet fluorescence microscopy, proliferation, survival, tissue engineering, Animal, Animals, Biofabrication, Bioprinting, Cell culture, Crosslinking, Fluorescence, Fluorescence microscopy, Full-thickness skin model, Hair follicle, Human, Humans, Hydrogel, Hydrogels, Image resolution, Laser patterning, Light sheet, Light sheet bioprinter, Light sheet fluorescence microscopy, Molecular biology, Photobleaching, Printing, three-dimensional, Procedures, Reproducibility, Reproducibility of results, Skin model, Three dimensional printing, Tissue, Tissue engineering, Tissue regeneration, Tissue scaffolds, Tissues engineerings


Román-Alamo, L, Avalos-Padilla, Y, Bouzón-Arnáiz, I, Iglesias, V, Fernández-Lajo, J, Monteiro, JM, Rivas, L, Fisa, R, Riera, C, Andreu, D, Pintado-Grima, C, Ventura, S, Arce, EM, Muñoz-Torrero, D, Fernàndez-Busquets, X, (2024). Effect of the aggregated protein dye YAT2150 on Leishmania parasite viability Antimicrobial Agents And Chemotherapy 68, e01127-23

The problems associated with the drugs currently used to treat leishmaniasis, including resistance, toxicity, and the high cost of some formulations, call for the urgent identification of new therapeutic agents with novel modes of action. The aggregated protein dye YAT2150 has been found to be a potent antileishmanial compound, with a half-maximal inhibitory concentration (IC50) of approximately 0.5 mu M against promastigote and amastigote stages of Leishmania infantum. The encapsulation in liposomes of YAT2150 significantly improved its in vitro IC50 to 0.37 and 0.19 mu M in promastigotes and amastigotes, respectively, and increased the half-maximal cytotoxic concentration in human umbilical vein endothelial cells to >50 mu M. YAT2150 became strongly fluorescent when binding intracellular protein deposits in Leishmania cells. This fluorescence pattern aligns with the proposed mode of action of this drug in the malaria parasite Plasmodium falciparum, the inhibition of protein aggregation. In Leishmania major, YAT2150 rapidly reduced ATP levels, suggesting an alternative antileishmanial mechanism. To the best of our knowledge, this first-in-class compound is the only one described so far having significant activity against both Plasmodium and Leishmania, thus being a potential drug for the treatment of co-infections of both parasites.

JTD Keywords: Animal, Animals, Antileishmanial drugs, Antiprotozoal agent, Antiprotozoal agents, Axenic amastigotes, Colocalization, Differentiation, Discovery, Endothelial cells, Endothelium cell, Human, Humans, Identification, Leishmania, Leishmania infantum, Leishmaniasis, Parasite, Parasites, Protein aggregation, Yat2150, Yeast


Pahuja, A, Corredera, IG, Moya-Rull, D, Garreta, E, Montserrat, N, (2024). Engineering physiological environments to advance kidney organoid models from human pluripotent stem cells Current Opinion In Cell Biology 86, 102306

During embryogenesis, the mammalian kidney arises because of reciprocal interactions between the ureteric bud (UB) and the metanephric mesenchyme (MM), driving UB branching and nephron induction. These morphogenetic processes involve a series of cellular rearrangements that are tightly controlled by gene regulatory networks and signaling cascades. Here, we discuss how kidney developmental studies have informed the definition of procedures to obtain kidney organoids from human pluripotent stem cells (hPSCs). Moreover, bioengineering techniques have emerged as potential solutions to externally impose controlled microenvironments for organoid generation from hPSCs. Next, we summarize some of these advances with major focus On recent works merging hPSC-derived kidney organoids (hPSC-kidney organoids) with organ-on-chip to develop robust models for drug discovery and disease modeling applications. We foresee that, in the near future, coupling of different organoid models through bioengineering approaches will help advancing to recreate organ-to-organ crosstalk to increase our understanding on kidney disease progression in the human context and search for new therapeutics.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

JTD Keywords: Animal, Animals, Bioengineering, Cell differentiation, Embryo development, Embryology, Embryonic structures, Gene regulatory network, Human, Humans, Kidney, Kidney development, Kidney mesenchyme cell, Kidney organoid, Mammal, Mammals, Mesenchyme, Metanephric mesenchyme, Microenvironment, Nephron, Nephrons, Organoid, Organoids, Physiology, Pluripotent stem cell, Pluripotent stem cells, Review, Signal transduction, Ureteric bud


Cassani, M, Fernandes, S, Cruz, JOD, Durikova, H, Vrbsky, J, Patocka, M, Hegrova, V, Klimovic, S, Pribyl, J, Debellis, D, Skladal, P, Cavalieri, F, Caruso, F, Forte, G, (2024). YAP Signaling Regulates the Cellular Uptake and Therapeutic Effect of Nanoparticles Advanced Science 11, e2302965

Interactions between living cells and nanoparticles are extensively studied to enhance the delivery of therapeutics. Nanoparticles size, shape, stiffness, and surface charge are regarded as the main features able to control the fate of cell-nanoparticle interactions. However, the clinical translation of nanotherapies has so far been limited, and there is a need to better understand the biology of cell-nanoparticle interactions. This study investigates the role of cellular mechanosensitive components in cell-nanoparticle interactions. It is demonstrated that the genetic and pharmacologic inhibition of yes-associated protein (YAP), a key component of cancer cell mechanosensing apparatus and Hippo pathway effector, improves nanoparticle internalization in triple-negative breast cancer cells regardless of nanoparticle properties or substrate characteristics. This process occurs through YAP-dependent regulation of endocytic pathways, cell mechanics, and membrane organization. Hence, the study proposes targeting YAP may sensitize triple-negative breast cancer cells to chemotherapy and increase the selectivity of nanotherapy.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

JTD Keywords: cancer treatment, cells, differentiation, hippo pathway, mechanics, mechanobiology, mechanotransduction, nanoparticles, progression, protein, resistance, yap-signaling, yap/taz, Adaptor proteins, signal transducing, Bio-nano interaction, Bio-nano interactions, Breast cancer cells, Cancer cells, Cancer treatment, Cells, Cellular therapeutics, Cellular uptake, Chemotherapy, Cytology, Diseases, Extracellular-matrix, Human, Humans, Mechano-biology, Mechanobiology, Metabolism, Nanoparticle, Nanoparticle interaction, Nanoparticles, Physiology, Protein serine threonine kinase, Protein serine-threonine kinases, Protein signaling, Signal transducing adaptor protein, Signal transduction, Therapeutic effects, Triple negative breast cancer, Triple negative breast neoplasms, Triple-negative breast cancers, Yap-signaling, Yes-associated protein-signaling


Liu, M, Zhang, C, Gong, XM, Zhang, T, Lian, MM, Chew, EGY, Cardilla, A, Suzuki, K, Wang, HM, Yuan, Y, Li, Y, Naik, MY, Wang, YX, Zhou, BR, Soon, WZ, Aizawa, E, Li, P, Low, JH, Tandiono, M, Montagud, E, Moya-Rull, D, Esteban, CR, Luque, Y, Fang, ML, Khor, CC, Montserrat, N, Campistol, JM, Belmonte, JCI, Foo, JN, Xia, Y, (2024). Kidney organoid models reveal cilium-autophagy metabolic axis as a therapeutic target for PKD both in vitro and in vivo Cell Stem Cell 31, 52-70.e8

Human pluripotent stem cell -derived kidney organoids offer unprecedented opportunities for studying polycystic kidney disease (PKD), which still has no effective cure. Here, we developed both in vitro and in vivo organoid models of PKD that manifested tubular injury and aberrant upregulation of renin-angiotensin aldosterone system. Single -cell analysis revealed that a myriad of metabolic changes occurred during cystogenesis, including defective autophagy. Experimental activation of autophagy via ATG5 overexpression or primary cilia ablation significantly inhibited cystogenesis in PKD kidney organoids. Employing the organoid xenograft model of PKD, which spontaneously developed tubular cysts, we demonstrate that minoxidil, a potent autophagy activator and an FDA -approved drug, effectively attenuated cyst formation in vivo. This in vivo organoid model of PKD will enhance our capability to discover novel disease mechanisms and validate candidate drugs for clinical translation.

JTD Keywords: Adenylate kinase, Adult, Animal cell, Animal experiment, Animal model, Animal tissue, Article, Autophagosome, Autophagy, Autophagy (cellular), Autosomal-dominant, Calcium homeostasis, Cilia, Cilium, Cohort analysis, Controlled study, Cyclic amp, Disease, Dominant polycystic kidney, Enzyme linked immunosorbent assay, Epithelium, Exon, Expression, Female, Food and drug administration, Framework, Generation, Growth, Hepatitis a virus cellular receptor 1, Human, Human cell, Humans, Immunohistochemistry, In vitro study, In vivo study, Kidney, Kidney organoid, Kidney polycystic disease, Male, Minoxidil, Mouse, Mutations, Nonhuman, Organoid, Organoids, Platelet derived growth factor beta receptor, Pluripotent stem-cells, Polycystic kidney diseases, Protein kinase lkb1, Renin, Sequestosome 1, Single cell analysis, Single cell rna seq, Small nuclear rna, Tunel assay, Upregulation, Western blotting, Whole exome sequencing


Jonkman, AH, Warnaar, RSP, Baccinelli, W, Carbon, NM, D'Cruz, RF, Doorduin, J, van Doorn, JLM, Elshof, J, Estrada-Petrocelli, L, Grasshoff, J, Heunks, LMA, Koopman, AA, Langer, D, Moore, CM, Silveira, JMN, Petersen, E, Poddighe, D, Ramsay, M, Rodrigues, A, Roesthuis, LH, Rossel, A, Torres, A, Duiverman, ML, Oppersma, E, (2024). Analysis and applications of respiratory surface EMG: report of a round table meeting Critical Care 28, 2

Surface electromyography (sEMG) can be used to measure the electrical activity of the respiratory muscles. The possible applications of sEMG span from patients suffering from acute respiratory failure to patients receiving chronic home mechanical ventilation, to evaluate muscle function, titrate ventilatory support and guide treatment. However, sEMG is mainly used as a monitoring tool for research and its use in clinical practice is still limited-in part due to a lack of standardization and transparent reporting. During this round table meeting, recommendations on data acquisition, processing, interpretation, and potential clinical applications of respiratory sEMG were discussed. This paper informs the clinical researcher interested in respiratory muscle monitoring about the current state of the art on sEMG, knowledge gaps and potential future applications for patients with respiratory failure.

JTD Keywords: Acute respiratory failure, Artificial ventilation, Asthmatic-children, Breathing muscle, Clinical monitoring, Clinical practice, Clinical research, Consensus development, Data interpretation, Disease exacerbation, Drive, Electrode positioning, Electrode removal, Electromyography, Force, Home care, Human, Human diaphragm, Humans, Information processing, Inspiratory muscle training, Inspiratory muscles, Intensive care unit, Knowledge gap, Long term care, Mechanical ventilation, Medical procedures, Muscle contraction, Muscle fatigue, Muscle function, Muscle training, Muscle, skeletal, Muscle-activity, Noninvasive ventilation, Patient monitoring, Patient-ventilator asynchrony, Physiology, Prognosis, Quality of life, Reporting and data system, Respiratory failure, Respiratory muscles, Review, Severe exacerbations, Signal processing, Skeletal muscle, Standardization, Surface electromyography, Time factor


Garcia-de-Albeniz, N, Ginebra, MP, Jimenez-Piqué, E, Roa, JJ, Mas-Moruno, C, (2024). Influence of nanosecond laser surface patterning on dental 3Y-TZP: Effects on the topography, hydrothermal degradation and cell response Dental Materials 40, 139-150

Laser surface micropatterning of dental-grade zirconia (3Y-TZP) was explored with the objective of providing defined linear patterns capable of guiding bone-cell response.A nanosecond (ns-) laser was employed to fabricate microgrooves on the surface of 3Y-TZP discs, yielding three different groove periodicities (i.e., 30, 50 and 100 µm). The resulting topography and surface damage were characterized by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). X-Ray diffraction (XRD) and Raman spectroscopy techniques were employed to assess the hydrothermal degradation resistance of the modified topographies. Preliminary biological studies were conducted to evaluate adhesion (6 h) of human mesenchymal stem cells (hMSC) to the patterns in terms of cell number and morphology. Finally, Staphylococcus aureus adhesion (4 h) to the microgrooves was investigated.The surface analysis showed grooves of approximately 1.8 µm height that exhibited surface damage in the form of pile-up at the edge of the microgrooves, microcracks and cavities. Accelerated aging tests revealed a slight decrease of the hydrothermal degradation resistance after laser patterning, and the Raman mapping showed the presence of monoclinic phase heterogeneously distributed along the patterned surfaces. An increase of the hMSC area was identified on all the microgrooved surfaces, although only the 50 µm periodicity, which is closer to the cell size, significantly favored cell elongation and alignment along the grooves. A decrease in Staphylococcus aureus adhesion was observed on the investigated micropatterns.The study suggests that linear microgrooves of 50 µm periodicity may help in promoting hMSC adhesion and alignment, while reducing bacterial cell attachment.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

JTD Keywords: abutment material, alumina toughened zirconia, antibacterial, bacterial adhesion, biofilm growth, cell adhesion, dental implants, hydrothermal degradation, implant surfaces, in-vitro, laser patterning, osseointegration, osteogenic differentiation, part 1, surface topography, y-tzp ceramics, Antibacterial, Antibacterials, Bacteria, Bone, Cell adhesion, Cell culture, Cells adhesion, Ceramics, Chemistry, Degradation resistance, Dental implants, Dental material, Dental materials, Dental prostheses, Human, Human mesenchymal stem cells, Humans, Hydrothermal degradation, Laser patterning, Laser surface, Lasers, Low-temperature degradation, Materials testing, Microscopy, electron, scanning, Nanosecond lasers, Osseointegration, Piles, Scanning electron microscopy, Staphylococcus aureus, Stem cells, Surface analysis, Surface damages, Surface properties, Surface property, Surface topography, Topography, Yttrium, Zirconia, Zirconium


Gregori-Pla, C, Zirak, P, Cotta, G, Bramon, P, Blanco, I, Serra, I, Mola, A, Fortuna, A, Solà-Soler, J, Giraldo, BFG, Durduran, T, Mayos, M, (2023). How does obstructive sleep apnea alter cerebral hemodynamics? Sleep 46, zsad122

We aimed to characterize the cerebral hemodynamic response to obstructive sleep apnea/hypopnea events, and evaluate their association to polysomnographic parameters. The characterization of the cerebral hemodynamics in obstructive sleep apnea (OSA) may add complementary information to further the understanding of the severity of the syndrome beyond the conventional polysomnography.Severe OSA patients were studied during night sleep while monitored by polysomnography. Transcranial, bed-side diffuse correlation spectroscopy (DCS) and frequency-domain near-infrared diffuse correlation spectroscopy (NIRS-DOS) were used to follow microvascular cerebral hemodynamics in the frontal lobes of the cerebral cortex. Changes in cerebral blood flow (CBF), total hemoglobin concentration (THC), and cerebral blood oxygen saturation (StO2) were analyzed.We considered 3283 obstructive apnea/hypopnea events from sixteen OSA patients (Age (median, interquartile range) 57 (52-64.5); females 25%; AHI (apnea-hypopnea index) 84.4 (76.1-93.7)). A biphasic response (maximum/minimum followed by a minimum/maximum) was observed for each cerebral hemodynamic variable (CBF, THC, StO2), heart rate and peripheral arterial oxygen saturation (SpO2). Changes of the StO2 followed the dynamics of the SpO2, and were out of phase from the THC and CBF. Longer events were associated with larger CBF changes, faster responses and slower recoveries. Moreover, the extrema of the response to obstructive hypopneas were lower compared to apneas (p < .001).Obstructive apneas/hypopneas cause profound, periodic changes in cerebral hemodynamics, including periods of hyper- and hypo-perfusion and intermittent cerebral hypoxia. The duration of the events is a strong determinant of the cerebral hemodynamic response, which is more pronounced in apnea than hypopnea events.© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society.

JTD Keywords: cerebral hemodynamics, desaturation, diffuse correlation spectroscopy, duration, hypopnea, hypoxemia, near-infrared spectroscopy, optical pathlength, oxygenation, severity, sleep disorder, spectroscopy, tissue, Adult, Airway obstruction, Apnea hypopnea index, Arterial oxygen saturation, Article, Blood oxygen tension, Blood-flow, Brain blood flow, Brain cortex, Cerebral hemodynamics, Controlled study, Diffuse correlation spectroscopy, Disease severity, Female, Frequency, Frontal lobe, Heart rate, Hemodynamics, Hemoglobin, Hemoglobin determination, Human, Humans, Major clinical study, Male, Near infrared spectroscopy, Near-infrared spectroscopy, Obstructive sleep apnea, Oxygen, Periodicity, Polysomnography, Sleep apnea syndromes, Sleep apnea, obstructive, Sleep disorder, Spectroscopy, near-infrared


Cañellas-Socias, A, Cortina, C, Hernando-Momblona, X, Palomo-Ponce, S, Mulholland, EJ, Turon, G, Mateo, L, Conti, S, Roman, O, Sevillano, M, Slebe, F, Stork, D, Caballé-Mestres, A, Berenguer-Llergo, A, Alvarez-Varela, A, Fenderico, N, Novellasdemunt, L, Jiménez-Gracia, L, Sipka, T, Bardia, L, Lorden, P, Colombelli, J, Heyn, H, Trepat, X, Tejpar, S, Sancho, E, Tauriello, DVF, Leedham, S, Attolini, CSO, Batlle, E, (2022). Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells Nature 611, 603-613

Around 30-40% of patients with colorectal cancer (CRC) undergoing curative resection of the primary tumour will develop metastases in the subsequent years1. Therapies to prevent disease relapse remain an unmet medical need. Here we uncover the identity and features of the residual tumour cells responsible for CRC relapse. An analysis of single-cell transcriptomes of samples from patients with CRC revealed that the majority of genes associated with a poor prognosis are expressed by a unique tumour cell population that we named high-relapse cells (HRCs). We established a human-like mouse model of microsatellite-stable CRC that undergoes metastatic relapse after surgical resection of the primary tumour. Residual HRCs occult in mouse livers after primary CRC surgery gave rise to multiple cell types over time, including LGR5+ stem-like tumour cells2-4, and caused overt metastatic disease. Using Emp1 (encoding epithelial membrane protein 1) as a marker gene for HRCs, we tracked and selectively eliminated this cell population. Genetic ablation of EMP1high cells prevented metastatic recurrence and mice remained disease-free after surgery. We also found that HRC-rich micrometastases were infiltrated with T cells, yet became progressively immune-excluded during outgrowth. Treatment with neoadjuvant immunotherapy eliminated residual metastatic cells and prevented mice from relapsing after surgery. Together, our findings reveal the cell-state dynamics of residual disease in CRC and anticipate that therapies targeting HRCs may help to avoid metastatic relapse.© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

JTD Keywords: colonization, defines, human colon, mutations, plasticity, retrieval, stem-cells, subtypes, underlie, Animal, Animal cell, Animal experiment, Animal model, Animal tissue, Animals, Article, Cancer, Cancer growth, Cancer immunotherapy, Cancer inhibition, Cancer recurrence, Cancer staging, Cell, Cell adhesion, Cell migration, Cell population, Cell surface receptor, Cohort analysis, Colorectal cancer, Colorectal neoplasms, Colorectal tumor, Comprehensive molecular characterization, Controlled study, Crispr-cas9 system, Cytoskeleton, Disease exacerbation, Disease progression, Dynamics, Emp1 gene, Epithelial membrane protein-1, Extracellular matrix, Flow cytometry, Fluorescence intensity, Gene expression, Genetics, Human, Human cell, Humans, Immune response, Immunofluorescence, In situ hybridization, Marker gene, Metastasis potential, Mice, Minimal residual disease, Mouse, Neoplasm proteins, Neoplasm recurrence, local, Neoplasm, residual, Nonhuman, Pathology, Phenotype, Prevention and control, Protein, Receptors, cell surface, Single cell rna seq, Tumor, Tumor protein, Tumor recurrence


Amil, AF, Ballester, BR, Maier, M, Verschure, PFMJ, (2022). Chronic use of cannabis might impair sensory error processing in the cerebellum through endocannabinoid dysregulation Addictive Behaviors 131, 107297

Chronic use of cannabis leads to both motor deficits and the downregulation of CB1 receptors (CB1R) in the cerebellum. In turn, cerebellar damage is often related to impairments in motor learning and control. Further, a recent motor learning task that measures cerebellar-dependent adaptation has been shown to distinguish well between healthy subjects and chronic cannabis users. Thus, the deteriorating effects of chronic cannabis use in motor performance point to cerebellar adaptation as a key process to explain such deficits. We review the literature relating chronic cannabis use, the endocannabinoid system in the cerebellum, and different forms of cerebellar-dependent motor learning, to suggest that CB1R downregulation leads to a generalized underestimation and misprocessing of the sensory errors driving synaptic updates in the cerebellar cortex. Further, we test our hypothesis with a computational model performing a motor adaptation task and reproduce the behavioral effect of decreased implicit adaptation that appears to be a sign of chronic cannabis use. Finally, we discuss the potential of our hypothesis to explain similar phenomena related to motor impairments following chronic alcohol dependency. © 2022

JTD Keywords: adaptation, addiction, alcohol-abuse, cerebellum, chronic cannabis use, cognition, deficits, endocannabinoid system, error processing, explicit, modulation, motor learning, release, synaptic plasticity, Adaptation, Adaptation, physiological, Alcoholism, Article, Behavioral science, Cannabinoid 1 receptor, Cannabis, Cannabis addiction, Cerebellum, Cerebellum cortex, Cerebellum disease, Chronic cannabis use, Computer model, Down regulation, Endocannabinoid, Endocannabinoid system, Endocannabinoids, Error processing, Hallucinogens, Human, Humans, Motor dysfunction, Motor learning, Nerve cell plasticity, Nonhuman, Physiology, Psychedelic agent, Purkinje-cells, Regulatory mechanism, Sensation, Sensory dysfunction, Sensory error processing impairment, Synaptic transmission, Task performance


Marte, L, Boronat, S, Barrios, R, Barcons-Simon, A, Bolognesi, B, Cabrera, M, Ayté, J, Hidalgo, E, (2022). Expression of Huntingtin and TDP-43 Derivatives in Fission Yeast Can Cause Both Beneficial and Toxic Effects International Journal Of Molecular Sciences 23, 3950

Many neurodegenerative disorders display protein aggregation as a hallmark, Huntingtin and TDP-43 aggregates being characteristic of Huntington disease and amyotrophic lateral sclerosis, respectively. However, whether these aggregates cause the diseases, are secondary by-products, or even have protective effects, is a matter of debate. Mutations in both human proteins can modulate the structure, number and type of aggregates, as well as their toxicity. To study the role of protein aggregates in cellular fitness, we have expressed in a highly tractable unicellular model different variants of Huntingtin and TDP-43. They each display specific patterns of aggregation and toxicity, even though in both cases proteins have to be very highly expressed to affect cell fitness. The aggregation properties of Huntingtin, but not of TDP-43, are affected by chaperones such as Hsp104 and the Hsp40 couple Mas5, suggesting that the TDP-43, but not Huntingtin, derivatives have intrinsic aggregation propensity. Importantly, expression of the aggregating form of Huntingtin causes a significant extension of fission yeast lifespan, probably as a consequence of kidnapping chaperones required for maintaining stress responses off. Our study demonstrates that in general these prion-like proteins do not cause toxicity under normal conditions, and in fact they can protect cells through indirect mechanisms which up-regulate cellular defense pathways. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

JTD Keywords: aggregation, antioxidant, degradation, features, fission yeast, gene, huntingtin, neurodegenerative diseases, pap1, polyglutamine toxicity, protein aggregation, proteins, stress, tdp-43, Amyotrophic-lateral-sclerosis, Chaperone, Chemistry, Dna binding protein, Dna-binding proteins, Fission yeast, Genetics, Human, Humans, Huntingtin, Metabolism, Molecular chaperones, Neurodegenerative diseases, Prion, Prions, Protein aggregate, Protein aggregates, Protein aggregation, Schizosaccharomyces, Tdp-43


Boda, SK, Aparicio, C, (2022). Dual keratinocyte-attachment and anti-inflammatory coatings for soft tissue sealing around transmucosal oral implants Biomaterials Science 10, 665-677

Unlike the attachment of soft epithelial skin tissue to penetrating solid natural structures like fingernails and teeth, sealing around percutaneous/permucosal devices such as dental implants is hindered by inflammation and epidermal down growth. Here, we employed a dual keratinocyte-adhesive peptide and anti-inflammatory biomolecule coating on titanium to promote oral epithelial tissue attachment. For minimizing inflammation-triggered epidermal down growth, we coated pristine and oxygen plasma pre-treated polished titanium (pTi) with conjugated linoleic acid (CLA). Further, in order to aid in soft tissue attachment via the formation of hemidesmosomes, adhesive structures by oral keratinocytes, we coated the anionic linoleic acid (LA) adsorbed titanium with cationic cell adhesive peptides (CAP), LamLG3, a peptide derived from Laminin 332, the major extracellular matrix component of the basement membrane in skin tissue and Net1, derived from Netrin-1, a neural chemoattractant capable of epithelial cell attachment via alpha 6 beta 4 integrins. The dual CLA-CAP coatings on pTi were characterized by X-ray photoelectron spectroscopy and dynamic water contact angle measurements. The proliferation of human oral keratinocytes (TERT-2/OKF6) was accelerated on the peptide coated titanium while also promoting the expression of Col XVII and beta-4 integrin, two markers for hemidesmosomes. Simultaneously, CLA coating suppressed the production of inducible nitric oxide synthase (anti-iNOS); a pro-inflammatory M1 marker expressed in lipopolysaccharide (LPS) stimulated murine macrophages (RAW 264.7) and elevated expression of anti-CD206, associated to an anti-inflammatory M2 macrophage phenotype. Taken together, the dual keratinocyte-adhesive peptide and anti-inflammatory biomolecule coating on titanium can help reduce inflammation and promote permucosal/peri-implant soft tissue sealing.

JTD Keywords: Adhesives, Animal, Animals, Anti-inflammatories, Anti-inflammatory agents, Antiinflammatory agent, Biomolecules, Bone, Cell adhesion, Cell-adhesives, Coatings, Conjugated linoleic acid, Conjugated linoleic-acid, Contact angle, Hemidesmosome, Hemidesmosomes, Human, Humans, Hydroxyapatite, Inflammation, Integrins, Keratinocyte, Keratinocytes, Linoleic acid, Macrophages, Mice, Mouse, Nitric oxide, Oral implants, Pathology, Peptides, Skin tissue, Soft tissue, Supplementation, Surface properties, Surface property, Tissue, Titania, Titanium, X ray photoelectron spectroscopy


Ferrer-Lluis, I, Castillo-Escario, Y, Glos, M, Fietze, I, Penzel, T, Jane, R, (2021). Sleep Apnea & Chronic Obstructive Pulmonary Disease: Overlap Syndrome Dynamics in Patients from an Epidemiological Study Conference Proceedings : ... Annual International Conference Of The Ieee Engineering In Medicine And Biology Society. Ieee Engineering In Medicine And Biology Society. Conference 2021, 5574-5577

Obstructive sleep apnea (OSA) is a sleep disorder in which repetitive upper airway obstructive events occur during sleep. These events can induce hypoxia, which is a risk factor for multiple cardiovascular and cerebrovascular diseases. Chronic obstructive pulmonary disease (COPD) is a disorder which induces a persistent inflammation of the lungs. This condition produces hypoventilation, affecting the blood oxygenation, and leads to an increased risk of developing lung cancer and heart disease. In this study, we evaluated how COPD affects the severity and characteristics of OSA in a multivariate demographic database including polysomnographic signals. Results showed SpO2 subtle variations, such as more non-recovered desaturations and increased time below a 90% SpO2 level, which, in the long term, could worsen the risk to suffer cardiovascular and cerebrovascular diseases.Clinical Relevance - COPD increases the OSA risk due to hypoventilation and altered SpO2 behavior. © 2021 IEEE.

JTD Keywords: Chronic obstructive lung disease, Complication, Epidemiologic studies, Epidemiology, Human, Humans, Oxygen saturation, Pulmonary disease, chronic obstructive, Sleep apnea, obstructive, Sleep disordered breathing, Syndrome


Romero, D, Jane, R, (2021). Relationship between Sleep Stages and HRV response in Obstructive Sleep Apnea Patients Conference Proceedings : ... Annual International Conference Of The Ieee Engineering In Medicine And Biology Society. Ieee Engineering In Medicine And Biology Society. Conference 2021, 5535-5538

Patients suffering from obstructive sleep apnea (OSA) usually present an increased sympathetic activity caused by the intermittent hypoxia effect on autonomic control. This study evaluated the relationship between sleep stages and the apnea duration, frequency, and type, as well as their impact on HRV markers in different groups of disease severity. The hypnogram and R-R interval signals were extracted in 81 OSA patients from night polysomnographic (PSG) recordings. The apnea-hypopnea index (AHI) defined patient classification as mild-moderate (AHI< 30, n 44) or severe (AHI>30, n 37). The normalized power in VLH, LF, and HF bands of RR series were estimated by a time-frequency approach and averaged in 1-min epochs of normal and apnea segments. The autonomic response and the impact of sleep stages were assessed in both segments to compare patient groups. Deeper sleep stages (particularly S2) concentrated the shorter and mild apnea episodes (from 10 to 40 s) compared to light (SWS) and REM sleep. Longer episodes (>50 s) although less frequent, were of similar incidence in all stages. This pattern was more pronounced for the group of severe patients. Moreover, during apnea segments, LF nu was higher (p 0.044) for the severe group, since V LF nu and HF nu presented the greatest changes when compared to normal segments. The non-REM sleep seems to better differentiate OSA patients groups, particularly through VLF nu and HF nu (p<0.001). A significant difference in both sympathetic and vagal modulation between REM and non-REM sleep was only found within the severe group. These results confirm the importance of considering sleep stages for HRV analysis to further assess OSA disease severity, beyond the traditional and clinically limited AHI values.Clinical relevance - Accounting for sleep stages during HRV analysis could better assess disease severity in OSA patients. © 2021 IEEE.

JTD Keywords: blood-pressure, genomic consequences, intermittent hypoxia, rapid-eye-movement, sympathetic activity, Heart rate, Heart-rate-variability, Human, Humans, Polysomnography, Rem sleep, Sleep apnea, obstructive, Sleep disordered breathing, Sleep stage, Sleep stages, Sleep, rem


Rodriguez, J, Schulz, S, Voss, A, Giraldo, BF, (2021). Classification of ischemic and dilated cardiomyopathy patients based on the analysis of the pulse transit time Conference Proceedings : ... Annual International Conference Of The Ieee Engineering In Medicine And Biology Society. Ieee Engineering In Medicine And Biology Society. Conference , 5527-5530

Cardiomyopathies diseases affects a great number of the elderly population. An adequate identification of the etiology of a cardiomyopathy patient is still a challenge. The aim of this study was to classify patients by their etiology in function of indexes extracted from the characterization of the pulse transit time (PTT). This time series represents the time taken by the pulse pressure to propagate through the length of the arterial tree and corresponding to the time between R peak of ECG and the mid-point of the diastolic to systolic slope in the blood pressure signal. For each patient, the PTT time series was extracted. Thirty cardiomyopathy patients (CMP) classified as ischemic (ICM - 15 patients) and dilated (DCM - 15 patients) were analyzed. Forty-three healthy subjects (CON) were used as a reference. The PTT time series was characterized through statistical descriptive indices and the joint symbolic dynamics method. The best indices were used to build support vector machine models. The optimal model to classify ICM versus DCM patients achieved 89.6% accuracy, 78.5% sensitivity, and 100% specificity. When comparing CMP patients and CON subjects, the best model achieved 91.3% accuracy, 91.3% sensitivity, and 88.3% specificity. Our results suggests a significantly lower pulse transit time in ischemic patients.Clinical relevance - This study analyzed the suitability of the pulse transit time for the classification of ICM and DCM patients. © 2021 IEEE.

JTD Keywords: Aged, Blood pressure, Cardiomyopathies, Cardiomyopathy, Cardiomyopathy, dilated, Congestive cardiomyopathy, Human, Humans, Pulse wave, Pulse wave analysis, Support vector machine


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.

JTD Keywords: classification, recognition, 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, Surface emg signals, Thorax, Ventilation, Ventilator weaning


Estrada-Petrocelli, L, Lozano-Garcia, M, Jane, R, Torres, A, (2021). Assessment of the Non-linear Response of the fSampEn on Simulated EMG Signals Conference Proceedings : ... Annual International Conference Of The Ieee Engineering In Medicine And Biology Society. Ieee Engineering In Medicine And Biology Society. Conference 2021, 5582-5585

Fixed sample entropy (fSampEn) is a promising technique for the analysis of respiratory electromyographic (EMG) signals. Its use has shown outperformance of amplitude-based estimators such as the root mean square (RMS) in the evaluation of respiratory EMG signals with cardiac noise and a high correlation with respiratory signals, allowing changes in respiratory muscle activity to be tracked. However, the relationship between the fSampEn response to a given muscle activation has not been investigated. The aim of this study was to analyze the nature of the fSampEn measurements that are produced as the EMG activity increases linearly. Simulated EMG signals were generated and increased linearly. The effect of the parameters r and the size of the moving window N of the fSampEn were evaluated and compared with those obtained using the RMS. The RMS showed a linear trend throughout the study. A non-linear, sigmoidal-like behavior was found when analyzing the EMG signals using the fSampEn. The lower the values of r, the higher the non-linearity observed in the fSampEn results. Greater moving windows reduced the variation produced by too small values of r.Clinical Relevance - Understanding the inherent non-linear relationship produced when using the fSampEn in EMG recordings will contribute to the improvement of the respiratory muscle activation assessment at different levels of respiratory effort in patients with respiratory conditions, particularly during the inspiratory phase © 2021 IEEE.

JTD Keywords: Breathing muscle, Breathing rate, Electromyography, Entropy, Heart, Human, Humans, Respiratory muscles, Respiratory rate


Blanco-Almazán, D, Groenendaal, W, Catthoor, F, Jané, R, (2021). Detection of Respiratory Phases to Estimate Breathing Pattern Parameters using Wearable Bioimpendace Conference Proceedings : ... Annual International Conference Of The Ieee Engineering In Medicine And Biology Society. Ieee Engineering In Medicine And Biology Society. Conference 2021, 5508-5511

Many studies have focused on novel noninvasive techniques to monitor respiratory rate such as bioimpedance. We propose an algorithm to detect respiratory phases using wearable bioimpedance to compute time parameters like respiratory rate, inspiratory and expiratory times, and duty cycle. The proposed algorithm was compared with two other algorithms from literature designed to estimate the respiratory rate using physiological signals like bioimpedance. We acquired bioimpedance and airflow from 50 chronic obstructive pulmonary disease (COPD) patients during an inspiratory loading protocol. We compared performance of the algorithms by computing accuracy and mean average percentage error (MAPE) between the bioimpedance parameters and the reference parameters from airflow. We found similar performance for the three algorithms in terms of accuracy (>0.96) and respiratory time and rate errors (<3.42 %). However, the proposed algorithm showed lower MAPE in duty cycle (10.18 %), inspiratory time (10.65 %) and expiratory time (8.61 %). Furthermore, only the proposed algorithm kept the statistical differences in duty cycle between COPD severity levels that were observed using airflow. Accordingly, we suggest bioimpedance to monitor breathing pattern parameters in home situations.Clinical relevance - This study exhibits the suitability of wearable thoracic bioimpedance to detect respiratory phases and to compute accurate breathing pattern parameters. © 2021 IEEE.

JTD Keywords: algorithms, copd, signals, Algorithm, Algorithms, Bioimpedance, Breathing rate, Chronic obstructive lung disease, Electronic device, Human, Humans, Lung, Pulmonary disease, chronic obstructive, Respiratory rate, Wearable electronic devices


Fernandez, Javier G., Mills, C. A., Samitier, J., (2009). Complex microstructured 3D surfaces using chitosan biopolymer Small 5, (5), 614-620

A technique for producing micrometer-scale structures over large, nonplanar chitosan surfaces is described. The technique makes use of the rheological characteristics (deformability) of the chitosan to create freestanding, three-dimensional scaffolds with controlled shapes, incorporating defined microtopography. The results of an investigation into the technical limits of molding different combinations of shapes and microtopographies are presented, highlighting the versatility of the technique when used irrespectively with inorganic or delicate organic moulds. The final, replicated scaffolds presented here are patterned with arrays of one-micrometer-tall microstructures over large areas. Structural integrity is characterized by the measurement of structural degradation. Human umbilical vein endothelial cells cultured on a tubular scaffold show that early cell growth is conditioned by the microtopography and indicate possible uses for the structures in biomedical applications. For those applications requiring improved chemical and mechanical resistance, the structures can be replicated in poly(dimethyl siloxane).

JTD Keywords: Biocompatible Materials/ chemistry, Cell Adhesion, Cell Culture Techniques/ methods, Cell Proliferation, Cells, Cultured, Chitosan/ chemistry, Crystallization/methods, Endothelial Cells/ cytology/ physiology, Humans, Materials Testing, Nanostructures/ chemistry/ ultrastructure, Nanotechnology/methods, Particle Size, Surface Properties, Tissue Engineering/methods


Engel, E., Michiardi, A., Navarro, M., Lacroix, D., Planell, J. A., (2008). Nanotechnology in regenerative medicine: the materials side Trends in Biotechnology , 26, (1), 39-47

Regenerative medicine is an emerging multidisciplinary field that aims to restore, maintain or enhance tissues and hence organ functions. Regeneration of tissues can be achieved by the combination of living cells, which will provide biological functionality, and materials, which act as scaffolds to support cell proliferation. Mammalian cells behave in vivo in response to the biological signals they receive from the surrounding environment, which is structured by nanometre-scaled components. Therefore, materials used in repairing the human body have to reproduce the correct signals that guide the cells towards a desirable behaviour. Nanotechnology is not only an excellent tool to produce material structures that mimic the biological ones but also holds the promise of providing efficient delivery systems. The application of nanotechnology to regenerative medicine is a wide issue and this short review will only focus on aspects of nanotechnology relevant to biomaterials science. Specifically, the fabrication of materials, such as nanoparticles and scaffolds for tissue engineering, and the nanopatterning of surfaces aimed at eliciting specific biological responses from the host tissue will be addressed.

JTD Keywords: Animals, Biocompatible Materials/ metabolism, Humans, Nanoparticles, Nanotechnology/ methods, Regenerative Medicine/ methods, Tissue Scaffolds


Engel, E., Del Valle, S., Aparicio, C., Altankov, G., Asin, L., Planell, J. A., Ginebra, M. P., (2008). Discerning the role of topography and ion exchange in cell response of bioactive tissue engineering scaffolds Tissue Engineering Part A , 14, (8), 1341-1351

Surface topography is known to have an influence on osteoblast activity. However, in the case of bioactive materials, topographical changes can affect also ion exchange properties. This makes the problem more complex, since it is often difficult to separate the strictly topographical effects from the effects of ionic fluctuations in the medium. The scope of this paper is to analyze the simultaneous effect of topography and topography-mediated ion exchange on the initial cellular behavior of osteoblastic-like cells cultured on bioactive tissue engineering substrates. Two apatitic substrates with identical chemical composition but different micro/nanostructural features were obtained by low-temperature setting of a calcium phosphate cement. MG63 osteoblastic-like cells were cultured either in direct contact with the substrates or with their extracts. A strong and permanent decrease of calcium concentration in the culture medium, dependent on substrate topography, was detected. A major effect of the substrate microstructure on cell proliferation was observed, explained in part by the topography-mediated ion exchange, but not specifically by the ionic Ca(2+) fluctuations. Cell differentiation was strongly enhanced when cells were cultured on the finer substrate. This effect was not explained by the chemical modification of the medium, but rather suggested a strictly topographical effect.

JTD Keywords: Alkaline Phosphatase/metabolism, Bone Cements/pharmacology, Calcium/metabolism, Calcium Phosphates/pharmacology, Cell Adhesion/drug effects, Cell Differentiation/drug effects, Cell Proliferation/drug effects, Cell Shape/drug effects, Cells, Cultured, Culture Media, Durapatite/pharmacology, Humans, Interferometry, Ion Exchange, Materials Testing, Osteoblasts/ cytology/drug effects/enzymology/ultrastructure, Phosphorus/metabolism, Powders, Tissue Engineering, Tissue Scaffolds


Gavara, N., Roca-Cusachs, P., Sunyer, R., Farre, R., Navajas, D., (2008). Mapping cell-matrix stresses during stretch reveals inelastic reorganization of the cytoskeleton Biophysical Journal , 95, (1), 464-471

The mechanical properties of the living cell are intimately related to cell signaling biology through cytoskeletal tension. The tension borne by the cytoskeleton (CSK) is in part generated internally by the actomyosin machinery and externally by stretch. Here we studied how cytoskeletal tension is modified during stretch and the tensional changes undergone by the sites of cell-matrix interaction. To this end we developed a novel technique to map cell-matrix stresses during application of stretch. We found that cell-matrix stresses increased with imposition of stretch but dropped below baseline levels on stretch release. Inhibition of the actomyosin machinery resulted in a larger relative increase in CSK tension with stretch and in a smaller drop in tension after stretch release. Cell-matrix stress maps showed that the loci of cell adhesion initially bearing greater stress also exhibited larger drops in traction forces after stretch removal. Our results suggest that stretch partially disrupts the actin-myosin apparatus and the cytoskeletal structures that support the largest CSK tension. These findings indicate that cells use the mechanical energy injected by stretch to rapidly reorganize their structure and redistribute tension.

JTD Keywords: Cell Line, Computer Simulation, Cytoskeleton/ physiology, Elasticity, Epithelial Cells/ physiology, Extracellular Matrix/ physiology, Humans, Mechanotransduction, Cellular/ physiology, Models, Biological, Stress, Mechanical


Roca-Cusachs, P., Alcaraz, J., Sunyer, R., Samitier, J., Farre, R., Navajas, D., (2008). Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation Biophysical Journal , 94, (12), 4984-4995

Shape-dependent local differentials in cell proliferation are considered to be a major driving mechanism of structuring processes in vivo, such as embryogenesis, wound healing, and angiogenesis. However, the specific biophysical signaling by which changes in cell shape contribute to cell cycle regulation remains poorly understood. Here, we describe our study of the roles of nuclear volume and cytoskeletal mechanics in mediating shape control of proliferation in single endothelial cells. Micropatterned adhesive islands were used to independently control cell spreading and elongation. We show that, irrespective of elongation, nuclear volume and apparent chromatin decondensation of cells in G1 systematically increased with cell spreading and highly correlated with DNA synthesis (percent of cells in the S phase). In contrast, cell elongation dramatically affected the organization of the actin cytoskeleton, markedly reduced both cytoskeletal stiffness (measured dorsally with atomic force microscopy) and contractility (measured ventrally with traction microscopy), and increased mechanical anisotropy, without affecting either DNA synthesis or nuclear volume. Our results reveal that the nuclear volume in G1 is predictive of the proliferative status of single endothelial cells within a population, whereas cell stiffness and contractility are not. These findings show that the effects of cell mechanics in shape control of proliferation are far more complex than a linear or straightforward relationship. Our data are consistent with a mechanism by which spreading of cells in G1 partially enhances proliferation by inducing nuclear swelling and decreasing chromatin condensation, thereby rendering DNA more accessible to the replication machinery.

JTD Keywords: Cell Line, Cell Nucleus/ physiology, Cell Proliferation, Cell Size, Computer Simulation, Endothelial Cells/ cytology/ physiology, G1 Phase/ physiology, Humans, Mechanotransduction, Cellular/ physiology, Models, Biological, Statistics as Topic


Charles-Harris, M., Koch, M. A., Navarro, M., Lacroix, D., Engel, E., Planell, J. A., (2008). A PLA/calcium phosphate degradable composite material for bone tissue engineering: an in vitro study Journal of Materials Science-Materials in Medicine , 19, (4), 1503-1513

Biodegradable polymers reinforced with an inorganic phase such as calcium phosphate glasses may be a promising approach to fulfil the challenging requirements presented by 3D porous scaffolds for tissue engineering. Scaffolds' success depends mainly on their biological behaviour. This work is aimed to the in vitro study of polylactic acid (PLA)/CaP glass 3D porous constructs for bone regeneration. The scaffolds were elaborated using two different techniques, namely solvent-casting and phase-separation. The effect of scaffolds' micro and macrostructure on the biological response of these scaffolds was assayed. Cell proliferation, differentiation and morphology within the scaffolds were studied. Furthermore, polymer/glass scaffolds were seeded under dynamic conditions in a custom-made perfusion bioreactor. Results indicate that the final architecture of the solvent-cast or phase separated scaffolds have a significant effect on cells' behaviour. Solvent-cast scaffolds seem to be the best candidates for bone tissue engineering. Besides, dynamic seeding yielded a higher seeding efficiency in comparison with the static method.

JTD Keywords: Biocompatible Materials/ chemistry, Bone and Bones/ metabolism, Calcium Phosphates/ chemistry, Cell Differentiation, Cell Proliferation, Humans, Lactic Acid/ chemistry, Microscopy, Confocal, Microscopy, Electron, Scanning, Osteoblasts/metabolism, Permeability, Polymers/ chemistry, Porosity, Solvents/chemistry, Tissue Engineering/ methods


Gustavsson, J., Altankov, G., Errachid, A., Samitier, J., Planell, J. A., Engel, E., (2008). Surface modifications of silicon nitride for cellular biosensor applications Journal of Materials Science-Materials in Medicine , 19, (4), 1839-1850

Thin films of silicon nitride (Si3N4) can be used in several kinds of micro-sized biosensors as a material to monitor fine environmental changes related to the process of bone formation in vitro. We found however that Si3N4 does not provide optimal conditions for osseointegration as osteoblast-like MG-63 cells tend to detach from the surface when cultured over confluence. Therefore Si3N4 was modified with self-assembled monolayers bearing functional end groups of primary amine (NH2) and carboxyl (COOH) respectively. Both these modifications enhanced the interaction with confluent cell layers and thus improve osseointegration over Si3N4. Furthermore it was observed that the NH2 functionality increased the adsorption of fibronectin (FN), promoted cell proliferation, but delayed the differentiation. We also studied the fate of pre-adsorbed and secreted FN from cells to learn more about the impact of above functionalities for the development of provisional extracellular matrix on materials interface. Taken together our data supports that Si3N4 has low tissue integration but good cellular biocompatibility and thus is appropriate in cellular biosensor applications such as the ion-sensitive field effect transistor (ISFET). COOH and NH2 chemistries generally improve the interfacial tissue interaction with the sensor and they are therefore suitable substrates for monitoring cellular growth or matrix deposition using electrical impedance spectroscopy.

JTD Keywords: Adsorption, Amines/chemistry, Biocompatible Materials/ chemistry, Biosensing Techniques, Cell Differentiation, Cell Line, Cell Proliferation, Electric Impedance, Extracellular Matrix/metabolism, Fibronectins/chemistry, Humans, Materials Testing, Osteoblasts/ cytology, Silicon Compounds/ chemistry, Surface Properties


Diez, Pablo F., Laciar, Eric, Mut, Vicente, Avila, Enrique, Torres, Abel, (2008). A comparative study of the performance of different spectral estimation methods for classification of mental tasks 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, 1155-1158

In this paper we compare three different spectral estimation techniques for the classification of mental tasks. These techniques are the standard periodogram, the Welch periodogram and the Burg method, applied to electroencephalographic (EEG) signals. For each one of these methods we compute two parameters: the mean power and the root mean square (RMS), in various frequency bands. The classification of the mental tasks was conducted with a linear discriminate analysis. The Welch periodogram and the Burg method performed better than the standard periodogram. The use of the RMS allows better classification accuracy than the obtained with the power of EEG signals.

JTD Keywords: Adult, Algorithms, Artificial Intelligence, Cognition, Electroencephalography, Female, Humans, Male, Pattern Recognition, Automated, Reproducibility of Results, Sensitivity and Specificity, Task Performance and Analysis, User-Computer Interface


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.

JTD 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