by Keyword: Guide

Sergi Rey-Viñolas, Laura Valls-Lacalle, Soledad Pérez-Amodio, Oscar Castaño, Miguel Angel Mateos-Timoneda, Elisabeth Engel, (2023). Biodegradable and bioactive personalized implant for guided bone regeneration (94238135204) Tissue Engineering Part a 29, 177-178

Andrés-Benito P, Carmona M, Pirla MJ, Torrejón-Escribano B, del Rio JA, Ferrer I, (2023). Dysregulated Protein Phosphorylation as Main Contributor of Granulovacuolar Degeneration at the First Stages of Neurofibrillary Tangles Pathology Neuroscience 518, 119-140

The hippocampus of cases with neurofibrillary tangles (NFT) pathology classified as stages I–II, III–IV, and V–VI without comorbidities, and middle-aged (MA) individuals with no NFT pathology, were examined to learn about the composition of granulovacuolar degeneration (GVD). Our results confirm the presence of CK1-?, p38-P Thr180/Tyr182, SAPK/JNK-P Thr183/Thr185, GSK-3?/?-P Tyr279/Tyr216, and GSK-3? Ser9 in the cytoplasmic granules in a subset of neurons of the CA1 and CA2 subfields of the hippocampus. Also, we identify the presence of PKA ?/?-P Thr197, SRC-P Tyr416, PAK1-P Ser199/Ser204, CAMK2A-P Tyr197, and PKCG-P Thr655 in cytoplasmic granules in cases with NFT pathology, but not in MA cases. Our results also confirm the presence of ?-catenin-P Ser45/Thr41, IRE?-P Ser274, eIF2?-P Ser51, TDP-43-P Ser403-404 (but absent TDP-43), and ubiquitin in cytoplasmic granules. Other components of the cytoplasmic granules are MAP2-P Thr1620/1623, MAP1B-P Thr1265, ADD1-P Ser726, and ADD1/ADD1-P Ser726/Ser713, in addition to several tau species including 3Rtau, 4Rtau, and tau-P Ser262. The analysis of GVD at progressive stages of NFT pathology reveals the early appearance of phosphorylated kinases and proteins in cytoplasmic granules at stages I–II, before the appearance of pre-tangles and NFTs. Most of these granules are not surrounded by LAMP1-positive membranes. Markers of impaired ubiquitin-protesome system, abnormal reticulum stress response, and altered endocytic and autophagic pathways occur in a subpopulation of neurons containing cytoplasmic granules, and they appear later. These observations suggest early phosphorylation of kinases leading to their activation, and resulting in the abnormal phosphorylation of various substrates, including tau, as a main alteration at the first stages of GVD. © 2021 The Author(s)

JTD Keywords: alzheimer's disease, alzheimers association guidelines, alzheimer’s disease, brain aging, cyclin-dependent kinase-5, granulovacuolar degeneration, kinases, national institute, neuropathologic assessment, p38 kinase, progressive supranuclear palsy, protein phosphorylation, tau, tau pathology, up-regulation, upstream activator, Alzheimer's disease, Brain aging, Glycogen-synthase kinase-3, Granulovacuolar degeneration, Kinases, Protein phosphorylation, Tau

Li, Jiahui, Tiberi, Riccardo, Canals, Pere, Vargas, Daniel, Castaño, Oscar, Molina, Marc, Tomasello, Alejandro, Ribo, Marc, (2023). Double stent-retriever as the first-line approach in mechanical thrombectomy: a randomized in vitro evaluation Journal Of Neurointerventional Surgery ,

BackgroundA repeated number of passes during mechanical thrombectomy leads to worse clinical outcomes in acute ischemic stroke. Initial experiences with the simultaneous double stent-retriever (double-SR) technique as the first-line treatment showed promising safety and efficacy results.ObjectiveTo characterize the potential benefits of using the double-SR as first-line technique as compared with the traditional single-SR approach.MethodsThree types of clot analogs (soft, moderately stiff, and stiff) were used to create terminal internal carotid artery (T-ICA=44) and middle cerebral artery (MCA=88) occlusions in an in vitro neurovascular model. Sixty-six cases were randomized into each treatment arm: single-SR or double-SR, in combination with a 0.071" distal aspiration catheter. A total of 132 in vitro thrombectomies were performed. Primary endpoints were the rate of first-pass recanalization (%FPR) and procedural-related distal emboli.ResultsFPR was achieved in 42% of the cases. Overall, double-SR achieved a significantly higher %FPR than single-SR (52% vs 33%, P=0.035). Both techniques showed similar %FPR in T-ICA occlusions (single vs double: 23% vs 27%, P=0.728). Double-SR significantly outperformed single-SR in MCA occlusions (63% vs 38%, P=0.019), most notably in saddle occlusions (64% vs 14%, P=0.011), although no significant differences were found in single-branch occlusions (64% vs 50%, P=0.275). Double-SR reduced the maximal size of the clot fragments migrating distally (Feret diameter=1.08±0.65 mm vs 2.05±1.14 mm, P=0.038).ConclusionsThis randomized in vitro evaluation demonstrates that the front-line double-SR technique is more effective than single-SR in achieving FPR when treating MCA bifurcation occlusions that present saddle thrombus.

JTD Keywords: endovascular treatment, guidelines, health, stroke, technique, thrombectomy, Acute ischemic-stroke, Stroke, Thrombectomy

Cillo U, Weissenbacher A, Pengel L, Jochmans I, Roppolo D, Amarelli C, Belli LS, Berenguer M, De Vries A, Ferrer J, Friedewald J, Furian L, Greenwood S, Monbaliu D, Nadalin S, Neyrinck A, Strazzabosco M, Toso C, Zaza G, Thuraisingham R, Berney T, Potena L, Montserrat N, Selzner N, (2022). ESOT Consensus Platform for Organ Transplantation: Setting the Stage for a Rigorous, Regularly Updated Development Process Transplant International 35, 10915

The European Society for Organ Transplantation (ESOT) has created a platform for the development of rigorous and regularly updated evidence based guidelines for clinical practice in the transplantation field. A dedicated Guideline Taskforce, including ESOT-council members, a representative from the Centre for Evidence in Transplantation, editors of the journal Transplant International has developed transparent procedures to guide the development of guidelines, recommendations, and consensus statements. During ESOT's first Consensus Conference in November 2022, leading experts will present in-depth evidence based reviews of nine themes and will propose recommendations aimed at reaching a consensus after public discussion and assessment by an independent jury. All recommendations and consensus statements produced for the nine selected topics will be published including the entire evidence-based consensus-finding process. An extensive literature review of each topic was conducted to provide final evidence and/or expert opinion.Copyright © 2022 Cillo, Weissenbacher, Pengel, Jochmans, Roppolo, Amarelli, Belli, Berenguer, De Vries, Ferrer, Friedewald, Furian, Greenwood, Monbaliu, Nadalin, Neyrinck, Strazzabosco, Toso, Zaza, Thuraisingham, Berney, Potena, Montserrat and Selzner.

JTD Keywords: consensus conference, guidelines, methodology, platform, Consensus conference, Guidelines, Methodology, Organ transplantation, Platform, Quality

Fuentes E, Gabaldón Y, Collado M, Dhiman S, Berrocal JA, Pujals S, Albertazzi L, (2022). Supramolecular Stability of Benzene-1,3,5-tricarboxamide Supramolecular Polymers in Biological Media: Beyond the Stability-Responsiveness Trade-off Journal Of The American Chemical Society 144, 21196-21205

Supramolecular assemblies have been gaining attention in recent years in the field of drug delivery because of their unique formulation possibilities and adaptive behavior. Their non-covalent nature allows for their self-assembly formulation and responsiveness to stimuli, an appealing feature to trigger a therapeutic action with spatiotemporal control. However, facing in vivo conditions is very challenging for non-covalent structures. Dilution and proteins in blood can have a direct impact on self assembly, destabilizing the supramolecules and leading to a premature and uncontrolled cargo release. To rationalize this behavior, we designed three monomers exhibiting distinct hydrophobic cores that self-assemble into photo-responsive fibers. We estimated their stability-responsiveness tradeoff in vitro, finding two well-separated regimes. These are low-robustness regime, in which the system equilibrates quickly and responds readily to stimuli, and high-robustness regime, in which the system equilibrates slowly and is quite insensitive to stimuli. We probed the performance of both regimes in a complex environment using Fo''rster resonance energy transfer (FRET). Interestingly, the stability-responsiveness trade-off defines perfectly the extent of disassembly caused by dilution but not the one caused by protein interaction. This identifies a disconnection between intrinsic supramolecular robustness and supramolecular stability in the biological environment, strongly influenced by the disassembly pathway upon protein interaction. These findings shed light on the key features to address for supramolecular stability in the biological environment.

JTD Keywords: Azobenzene, Critical micellization, Fret, Guide, Nanoparticles, Ph, Photoisomerization, Polymerization, Shape, Water

Ferrer I, Andrés-Benito P, Ausín K, Pamplona R, del Rio JA, Fernández-Irigoyen J, Santamaría E, (2021). Dysregulated protein phosphorylation: A determining condition in the continuum of brain aging and Alzheimer's disease Brain Pathology 31, e12996

Tau hyperphosphorylation is the first step of neurofibrillary tangle (NFT) formation. In the present study, samples of the entorhinal cortex (EC) and frontal cortex area 8 (FC) of cases with NFT pathology classified as stages I–II, III–IV, and V–VI without comorbidities, and of middle-aged (MA) individuals with no NFT pathology, were analyzed by conventional label-free and SWATH-MS (sequential window acquisition of all theoretical fragment ion spectra mass spectrometry) to assess the (phospho)proteomes. The total number of identified dysregulated phosphoproteins was 214 in the EC, 65 of which were dysregulated at the first stages (I–II) of NFT pathology; 167 phosphoproteins were dysregulated in the FC, 81 of them at stages I–II of NFT pathology. A large percentage of dysregulated phosphoproteins were identified in the two regions and at different stages of NFT progression. The main group of dysregulated phosphoproteins was made up of components of the membranes, cytoskeleton, synapses, proteins linked to membrane transport and ion channels, and kinases. The present results show abnormal phosphorylation of proteins at the first stages of NFT pathology in the elderly (in individuals clinically considered representative of normal aging) and sporadic Alzheimer's disease (sAD). Dysregulated protein phosphorylation in the FC precedes the formation of NFTs and SPs. The most active period of dysregulated phosphorylation is at stages III–IV when a subpopulation of individuals might be clinically categorized as suffering from mild cognitive impairment which is a preceding determinant stage in the progression to dementia. Altered phosphorylation of selected proteins, carried out by activation of several kinases, may alter membrane and cytoskeletal functions, among them synaptic transmission and membrane/cytoskeleton signaling. Besides their implications in sAD, the present observations suggest a molecular substrate for “benign” cognitive deterioration in “normal” brain aging.

JTD Keywords: (phospho)proteomics, alzheimer's disease, amyloid-beta, association guidelines, brain aging, cytoskeleton, frontal-cortex, kinases, lipid rafts, membranes, national institute, neuropathologic assessment, pathological process, protein phosphorylation, synapse pathology, synapses, tau, tau pathology, (phospho)proteomics, Age-related tauopathy, Alzheimer's disease, Brain aging, Cytoskeleton, Kinases, Membranes, Protein phosphorylation, Synapses, Tau

Grob, M, Anselmetti, D, Fernandez-Busquets, X, (2021). In memory of Max Burger Journal Of Cellular Biochemistry 122, 1259-1261

Hyun I, Clayton EW, Cong Y, Fujita M, Goldman SA, Hill LR, Monserrat N, Nakauchi H, Pedersen RA, Rooke HM, Takahashi J, Knoblich JA, (2021). ISSCR guidelines for the transfer of human pluripotent stem cells and their direct derivatives into animal hosts Stem Cell Reports 16, 1409-1415

The newly revised 2021 ISSCR Guidelines for Stem Cell Research and Clinical Translation includes scientific and ethical guidance for the transfer of human pluripotent stem cells and their direct derivatives into animal models. In this white paper, the ISSCR subcommittee that drafted these guidelines for research involving the use of nonhuman embryos and postnatal animals explains and summarizes their recommendations.

JTD Keywords: animal research, chimeric embryos, isscr guidelines, Animal research, Chimeric embryos, Isscr guidelines, Stem cell chimeras

Ebrahimi N, Bi C, Cappelleri DJ, Ciuti G, Conn AT, Faivre D, Habibi N, Hošovský A, Iacovacci V, Khalil ISM, Magdanz V, Misra S, Pawashe C, Rashidifar R, Soto-Rodriguez PED, Fekete Z, Jafari A, (2021). Magnetic Actuation Methods in Bio/Soft Robotics Advanced Functional Materials 31, 2005137

© 2020 Wiley-VCH GmbH In recent years, magnetism has gained an enormous amount of interest among researchers for actuating different sizes and types of bio/soft robots, which can be via an electromagnetic-coil system, or a system of moving permanent magnets. Different actuation strategies are used in robots with magnetic actuation having a number of advantages in possible realization of microscale robots such as bioinspired microrobots, tetherless microrobots, cellular microrobots, or even normal size soft robots such as electromagnetic soft robots and medical robots. This review provides a summary of recent research in magnetically actuated bio/soft robots, discussing fabrication processes and actuation methods together with relevant applications in biomedical area and discusses future prospects of this way of actuation for possible improvements in performance of different types of bio/soft robots.

JTD Keywords: capsule endoscope, controlled propulsion, conventional gastroscopy, digital microfluidics, guided capsule, liquid-metal, magnetic drug delivery, magnetic microrobots, magnetically guided capsule endoscopy, magnetotactic bacteria, nanoscribe ip-dip, navigation system, Gallium-indium egain, Magnetic bioinspired micromanipulation, Magnetic drug delivery, Magnetic microrobots, Magnetically guided capsule endoscopy, Magnetotactic bacteria

Gugutkov, D., Gustavsson, J., Cantini, M., Salmeron-Sánchez, M., Altankov, G., (2017). Electrospun fibrinogen-PLA nanofibres for vascular tissue engineering Journal of Tissue Engineering and Regenerative Medicine 11, (10), 2774-2784

Here we report on the development of a new type of hybrid fibrinogen-polylactic acid (FBG-PLA) nanofibres (NFs) with improved stiffness, combining the good mechanical properties of PLA with the excellent cell recognition properties of native FBG. We were particularly interested in the dorsal and ventral cell response to the nanofibres' organization (random or aligned), using human umbilical endothelial cells (HUVECs) as a model system. Upon ventral contact with random NFs, the cells developed a stellate-like morphology with multiple projections. The well-developed focal adhesion complexes suggested a successful cellular interaction. However, time-lapse analysis shows significantly lowered cell movements, resulting in the cells traversing a relatively short distance in multiple directions. Conversely, an elongated cell shape and significantly increased cell mobility were observed in aligned NFs. To follow the dorsal cell response, artificial wounds were created on confluent cell layers previously grown on glass slides and covered with either random or aligned NFs. Time-lapse analysis showed significantly faster wound coverage (within 12 h) of HUVECs on aligned samples vs. almost absent directional migration on random ones. However, nitric oxide (NO) release shows that endothelial cells possess lowered functionality on aligned NFs compared to random ones, where significantly higher NO production was found. Collectively, our studies show that randomly organized NFs could support the endothelization of implants while aligned NFs would rather direct cell locomotion for guided neovascularization.

JTD Keywords: Electrospun nanofibers, Endothelial cells, Fibrinogen, Guided cellular behavior, Polylactic acid, Vascular tissue engineering

Diéguez, Lorena, Caballero, David, Calderer, Josep, Moreno, Mauricio, Martínez, Elena, Samitier, Josep, (2012). Optical gratings coated with thin Si3N4 layer for efficient immunosensing by optical waveguide lightmode spectroscopy Biosensors , 2, (2), 114-126

New silicon nitride coated optical gratings were tested by means of Optical Waveguide Lightmode Spectroscopy (OWLS). A thin layer of 10 nm of transparent silicon nitride was deposited on commercial optical gratings by means of sputtering. The quality of the layer was tested by x-ray photoelectron spectroscopy and atomic force microscopy. As a proof of concept, the sensors were successfully tested with OWLS by monitoring the concentration dependence on the detection of an antibody-protein pair. The potential of the Si3N4 as functional layer in a real-time biosensor opens new ways for the integration of optical waveguides with microelectronics.

JTD Keywords: Silicon nitride, Optical gratings, Waveguide, Biosensor

Mattotti, Marta, Alvarez, Zaida, Ortega, Juan A., Planell, Josep A., Engel, Elisabeth, Alcántara, Soledad, (2012). Inducing functional radial glia-like progenitors from cortical astrocyte cultures using micropatterned PMMA Biomaterials 33, (6), 1759-1770

Radial glia cells (RGC) are multipotent progenitors that generate neurons and glia during CNS development, and which also served as substrate for neuronal migration. After a lesion, reactive glia are the main contributor to CNS regenerative blockage, although some reactive astrocytes are also able to de-differentiate in situ into radial glia-like cells (RGLC), providing beneficial effects in terms of CNS recovery. Thus, the identification of substrate properties that potentiate the ability of astrocytes to transform into RGLC in response to a lesion might help in the development of implantable devices that improve endogenous CNS regeneration. Here we demonstrate that functional RGLC can be induced from in vitro matured astrocytes by using a precisely-sized micropatterned PMMA grooved scaffold, without added soluble or substrate adsorbed biochemical factors. RGLC were extremely organized and aligned on 2 μm line patterned PMMA and, like their embryonic counterparts, express nestin, the neuron-glial progenitor marker Pax6, and also proliferate, generate different intermediate progenitors and support and direct axonal growth and neuronal migration. Our results suggest that the introduction of line patterns in the size range of the RGC processes in implantable scaffolds might mimic the topography of the embryonic neural stem cell niche, driving endogenous astrocytes into an RGLC phenotype, and thus favoring the regenerative response in situ.

JTD Keywords: Polymethylmethacrylate, Micropatterning, Surface topography, Astrocyte, Nerve guide, Co-culture

Azevedo, S., Diéguez, L., Carvalho, P., Carneiro, J. O., Teixeira, V., Martínez, Elena, Samitier, J., (2012). Deposition of ITO thin films onto PMMA substrates for waveguide based biosensing devices Journal of Nano Research , 17, 75-83

Biosensors' research filed has clearly been changing towards the production of multifunctional and innovative design concepts to address the needs related with sensitivity and selectivity of the devices. More recently, waveguide biosensors, that do not require any label procedure to detect biomolecules adsorbed on its surface, have been pointed out as one of the most promising technologies for the production of biosensing devices with enhanced performance. Moreover the combination of optical and electrochemical measurements through the integration of transparent and conducting oxides in the multilayer structures can greatly enhance the biosensors' sensitivity. Furthermore, the integration of polymeric substrates may bring powerful advantages in comparison with silicon based ones. The biosensors will have a lower production costs being possible to disposable them after use ("one use sensor chip"). This research work represents a preliminary study about the influence of substrate temperature on the overall properties of ITO thin films deposited by DC magnetron sputtering onto 0,5 mm thick PMMA sheets.

JTD Keywords: ITO thin films, PMMA sheets, Waveguide biosensing devices, Biosensing devices, Conducting oxides, Dc magnetron sputtering, Electrochemical measurements, Enhanced performance, Innovative design, ITO thin films, Multilayer structures, Overall properties, PMMA sheets, Polymeric substrate, Production cost, Sensor chips, Silicon-based, Substrate temperature, Biosensors, Deposition, Design, Film preparation, Optical multilayers, Thin films, Vapor deposition, Waveguides, Substrates

Manzo, C., van Zanten, T. S., Garcia-Parajo, M. F., (2011). Nanoscale fluorescence correlation spectroscopy on intact living cell membranes with NSOM probes Biophysical Journal , 100, (2), L8-L10

Characterization of molecular dynamics on living cell membranes at the nanoscale is fundamental to unravel the mechanisms of membrane organization and compartmentalization. Here we demonstrate the feasibility of fluorescence correlation spectroscopy (FCS) based on the nanometric illumination of near-field scanning optical microscopy (NSOM) probes on intact living cells. NSOM-FCS applied to fluorescent lipid analogs allowed us to reveal details of the diffusion hidden by larger illumination areas. Moreover, the technique offers the unique, advantages of evanescent axial illumination and straightforward implementation of multiple color excitation. As such, NSOM-FCS represents a powerful tool to study a variety of dynamic processes occurring at the nanometer scale on cell membranes.

JTD Keywords: Mode wave-guides, Lipid rafts, Difussion, Organization, Aperture