RESIL MOJARES AND THE CRISIS OF COMPARATIVE LITERATURE IN THE PHILIPPINES

After its heyday from the 1950s until the early 1970s, a crisis in the field of comparative literature was declared present by its practitioners during the 1980s. The effects of the perceived crisis were felt not only during conferences but also through brutal budget cuts and the downsizing of comparative literature departments across the world.   In the decades that followed, various attempts to address the crisis were made by critics such as Franco Moretti, Pascale Casanova, Alexander Beecroft, among many others. As a result, methods and concepts such as “distant reading,” “evolutionary literary history,” “literary ecologies,” and “world republic of letters” easily became the theoretical and methodological bulwark of numerous comparative literature departments against the perceived effects of the crisis.  Incidentally, in his seminal Origins and Rise of the Filipino Novel, Resil Mojares deployed similar ideas and concepts, however, to different ends.  This paper, then, is first an attempt to analyze Mojares’ deployment of the said concepts and methods vis-à-vis to that of Beecroft, Casanova, and Moretti’s. Finally, the paper also seeks to identify and elaborate on specific implications and possibilities made visible by Mojares’ methodological interventions in the field and practice of comparative literature in the Philippines.Keywords: Crisis, comparative literature, literary history, Mojares, methodological intervention, Philippines.Cite as: Mendoza III, A.A.G. (2018). Resil Mojares and the crisis of comparative literature in the Philippines. Journal of Nusantara Studies, 3(2), 80-91. http://dx.doi.org/10.24200/jonus.vol3iss2pp80-9

El régimen probatorio en el nuevo procedimiento administrativo

En el año 2011 el régimen de procedimiento en materia administrativa fue modificado con la implementación del Código de Procedimiento Administrativo y de lo Contencioso Administrativo, en el que se contempla un nuevo régimen probatorio, con observancia de la citada modificación y su entrada en vigencia, se pretende realizar un acercamiento de la estructura del régimen probatorio contenida en el nuevo Código, con el fin de identificar los lineamientos y propósitos del procedimiento administrativo. A lo largo de la investigación, se abordaron temas como los principios que rigen la práctica probatoria, los medios probatorios contenidos tanto en el Código de Procedimiento Administrativo y de lo Contencioso Administrativo como en las normas que por remisión señala el Código de Procedimiento Civil y, por último, un tema que en la actualidad no se puede dejar de lado, el uso de los medios electrónicos en la práctica de pruebas.In 2011 the regime in administrative procedure was modified due to the implementation of the Code of Administrative Procedure and Administrative Disputes, which contains one new probation, in compliance with that amendment and its effective date, is to conduct research on the structure of the rules of evidence contained in the new Code and identify the guidelines and purpose of the administrative procedure. Throughout the research, covering issues such as the principles that govern the practice of evidence, the evidence contained both in the Code of Administrative Procedure and Administrative Disputes as standards for reference states that the Code of Civil Procedure and finally a topic that currently can not be put aside, as is the use of electronic media in the practice of evidence

Hybrid thermoresponsive nanoparticles containing drug nanocrystals for NIR-triggered remote release

The on-demand administration of anaesthetic drugs can be a promising alternative for chronic pain management. To further improve the efficacy of drug delivery vectors, high drug loadings combined with a spatiotemporal control on the release can not only relief the pain according to patient''s needs, but also improve the drawbacks of conventional burst release delivery systems. In this study, a hybrid nanomaterial was developed by loading bupivacaine nanocrystals (BNCs) into oligo(ethylene glycol) methyl ether methacrylate (OEGMA)-based thermoresponsive nanogels and coupling them to NIR-absorbing biodegradable copper sulphide nanoparticles (CuS NPs). Those CuS NPs were surface modified with polyelectrolytes using layer-by-layer techniques to be efficiently attached to the surface of nanogels by means of supramolecular interactions. The encapsulation of bupivacaine in the form of nanocrystals allowed to achieve CuS@BNC-nanogels having drug loadings as high as 65.5 wt%. The nanocrystals acted as longlasting drug reservoirs, leading to an elevated localized drug content, which was useful for their application in prolonged pain relief. The CuS@BNC-nanogels exhibited favorable photothermal transducing properties upon NIR-light irradiation. The photothermal effect granted by the CuS NPs triggered the nano-crystallized drug release to be boosted by the collapse of the thermoresponsive nanogels upon heating. Remote control was achieved for on-demand release at a specific time and place, indicating their potential use as an externally activated triggerable drug-delivery system. Furthermore, cell viability tests and flow cytometry analysis were performed showing satisfactory cytocompatibility in the dose-ranging study having a subcytotoxic concentration of 0.05 mg/mL for CuS@BNC-nanogels. This remotely activated nanoplatform is a promising strategy for long-lasting controlled analgesia and a potential alternative for clinical pain management. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND licens

Smart dressings based on nanostructured fibers containing natural origin antimicrobial and anti-inflammatory compounds

La presente tesis doctoral denominada “Apósitos inteligentes basados en la encapsulación de compuestos antimicrobianos y anti-inflamatorios de origen natural en fibras nanoestructuradas” ha sido desarrollada en el Departamento de Ingeniería Química y Tecnologías del Medioambiente (Universidad de Zaragoza, España) en el Grupo de Películas y Partículas Nanoestructuradas (NFP), miembro del Instituto de Nanociencia de Aragón (INA). Parte de la investigación ha sido desarrollada en el Centro de Investigación Biomédica de Aragón (CIBA). Durante este periodo, se ha realizado una estancia de 6 meses en el Methodist Hospital Research Institute en Houston (Texas, US), supervisada por el Profesor Ennio Tasciotti. La tesis ha sido financiada por el Programa de Formación de Personal Investigador (FPI) proporcionado por el Ministerio de Economía y Competitividad de España (CTQ2014-52384-R). La estancia fue co-financiada por el Centro de Investigación Biomédica en Red en el campo de la Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN). Debido al desarrollo de resistencias bacterianas, el interés en la búsqueda de nuevos compuestos para abordar infecciones ha crecido exponencialmente para los investigadores. Por este motivo, esta tesis doctoral está enfocada en el diseño de un apósito basado en nanofibras de policaprolactona (PCL) sintetizadas mediante electrospinning, que encapsulen compuestos naturales que actúen como anti-inflamatorios y antimicrobianos para el tratamiento de heridas. Con este objetivo, se ha llevado a cabo un profundo estudio de los aceites esenciales con propiedades bactericidas y anti-inflamatorias. El primer objetivo de la tesis doctoral fue abordar la infección de heridas con compuestos naturales derivados de plantas. Para esto, se estudiaron las propiedades y los mecanismos de acción de diferentes compuestos en bacterias planctónicas utilizando dos modelos bacterianos, uno Gram-positivo, como S. aureus (ATCC 25923) y otro Gram-negativo, como E. coli-S17. Teniendo en cuenta que la formación de biofilm es un problema en las infecciones de heridas, se estudió el efecto de los compuestos naturales en un modelo de biofilm de S. aureus. El carácter volátil de los EOs y la posibilidad de oxidarse cuando están en contacto con luz ultravioleta o el aire, hacen difícil su aplicación. La encapsulación de estos compuestos ayuda a proteger sus propiedades y facilitar así su aplicación final. Así, el timol (THY) demostró ser el compuesto con mejor actividad antimicrobiana en ambos modelos bacterianos, de modo que fue encapsulado en nanofibras de PCL. La síntesis de nanofibras y la encapsulación del THY se llevaron a cabo mediante la técnica de electrospinning. Este método permite la fabricación de nanofibras con encapsulación de compuestos volátiles, como el THY, gracias a la rápida formación de las fibras. Las propiedades bactericidas de los apósitos de PCL cargado con THY se estudiaron utilizando un modelo de S. aureus que expresaba GFP y así poder realizar ensayos cuantitativos y mediante microscopía confocal. El segundo objetivo de la tesis ha sido encontrar un compuesto natural anti-inflamatorio para el tratamiento de heridas. Para ello, se ha optimizado un modelo inflamatorio in vitro en macrófagos J774 activados con lipopolisacárido (LPS). Estos experimentos se llevaron a cabo en el Methodist Hospital Research Institute en Houston (Texas, US), donde se determinaron los niveles de citoquinas inflamatorias lo que nos permitió determinar entre los testados los mejores compuestos naturales anti-inflamatorios. Además, las membranas de PCL-THY demostraron ser los mejores apósitos reduciendo la inflamación, entre los distintos tratamientos de estudio. Tras concluir que el THY encapsulado en nanofibras de PCL mantiene las propiedades antimicrobianas y anti-inflamatorias, se desarrolló un modelo in vivo para determinar la efectividad de los apósitos en heridas de piel infectadas. Para ello, se utilizaron ratones sin pelo SKH1 para analizar las propiedades bactericidas e inflamatorias para su potencial aplicación clínica. El documento está estructurado en diferentes capítulos que abordan cada uno de los objetivos de la tesis doctoral: o El Capítulo I corresponde con la parte introductoria, donde se explican los conceptos generales. El capítulo incluye una descripción del proceso de curación de una herida, resaltando factores que afectan al mismo, como por ejemplo la infección e inflamación. Se explican también los diferentes tipos de tratamientos que existen, como los antibióticos, poniendo especial atención en el desarrollo de resistencias bacterianas a los mismos, como la razón principal de elección de compuestos naturales para el tratamiento de heridas. La técnica de electrospinning se detalla para entender la síntesis de fibras de PCL y la encapsulación de los principios activos. o El Capítulo II se centra en la actividad antimicrobiana de los compuestos libres para abordar la infección de heridas. Se calculó la Concentración Mínima Inhibitoria (MIC) y la Concentración Mínima Bactericida (MBC) de diferentes compuestos derivados de plantas en una cepa de S. aureus (ATCC 25923) y otra de E. coli-S17. Además, se desarrolló un modelo de biofilm en S. aureus para determinar el efecto de los compuestos libres en estas estructuras bacterianas. El mecanismo de acción de los aceites esenciales en las bacterias fue estudiado mediante microscopía electrónica de barrido (SEM) y citometría de flujo. Por último, se estudió la citotoxicidad de los compuestos en tres tipos celulares relacionados con la piel: fibroblastos, queratinocitos y macrófagos. Carvacrol (CAR), cinamaldehido (CIN) y THY demostraron tener la mayor actividad antimicrobiana en un modelo in vitro de S. aureus y E. coli. a través de la disrupción de la membrana bacteriana. Estos resultados están incluidos en el artículo publicado titulado “Evaluation of the antimicrobial activity and cytotoxicity of different components of natural origin present in essential oils”. García-Salinas, S.; Elizondo-Castillo, H.; Arruebo, M.; Mendoza, G.; Irusta, S. Molecules 2018, 23 (6), 1–18.https://doi.org/10.3390/molecules23061399.o Capítulo III: Teniendo en cuenta los resultados obtenidos en el Capítulo II, el THY fue elegido para ser encapsulado en nanofibras de PCL, dada su capacidad antimicrobiana y su baja citotoxicidad comparada con el resto de los compuestos. Se midió el efecto del PCL-THY en contacto con cGFP-expressing S. aureus en suspensión y en forma de biofilm. Por último, se diseñó un modelo de co-cultivo con cGFP-expressing S. aureus y macrófagos J774 para estudiar el efecto del PCL-THY en células infectadas. Los apósitos de PCL-THY eliminaron el crecimiento bacteriano en un modelo de infección de macrófagos J774. Además, los estudios corroboraron la inhibición de la formación de biofilm. Los resultados están incluidos en el artículo titulado “Antimicrobial Wound Dressings Against Fluorescent and Methicillin-Sensitive Intracellular Pathogenic Bacteria” Garcia-Salinas, S.; Gamez-Herrera, E.; Landa, G.; Arruebo, M.; Irusta, S.; Mendoza, G. enviado para su publicación a ACS Applied Materials & Interfaces. Manuscript ID: am-2020-05668q.o El Capítulo IV describe la actividad anti-inflamatoria de los aceites esenciales con el objetivo de reducir y controlar el proceso inflamatorio en la curación de heridas. La abundante inflamación puede causar la activación de células o citoquinas innecesarias que generan efectos deletéreos y retrasan el proceso de curación. Por esta razón, se optimizó un modelo inflamatorio con macrófagos J774 activados con LPS y se estudió el efecto de diferentes compuestos naturales reportados como anti-inflamatorios. Los macrófagos infectados se trataron y se analizaron a nivel genético, midiendo los niveles de expresión de Il (Interleucina) 1b, iNos (óxido nítrico sintasa inducible) e Il10 por RT-PCR (Real Time-Polymerase Chain Reaction). Los aceites esenciales con mejor resultado se encapsularon en nanofibras de PCL y se estudió el efecto de los mismos, confirmando los resultados previamente obtenidos. Además, se realizaron experimentos en los que se evaluó la morfología celular, comparando las células tratadas con controles positivos (células activadas con LPS sin tratamiento) y negativos (células no activadas con LPS). Este experimento demostró la similitud entre las células tratadas y las no activadas, confirmando los efectos anti-inflamatorios del tratamiento. Los resultados están incluidos en el artículo publicado titulado “Electrospun Anti-Inflammatory Patch Loaded with Essential Oils for Wound Healing”. García-Salinas, S.; Evangelopoulos, M.; Gámez-Herrera, E.; Arruebo, M.; Irusta, S.; Taraballi, F.; Mendoza, G.; Tasciotti, E. Int. J. Pharm.2020, 577 (January), 119067. https://doi.org/10.1016/j.ijpharm.2020.119067o El Capítulo V unifica toda la investigación realizada durante la tesis en un modelo in vivo de infección de heridas con S. aureus (ATCC 25923) en ratones sin pelo SKH1. Se analizaron las propiedades bactericidas y antiinflamatorias de los apósitos diseñados. Además, se realizaron controles del compuesto libre y de clorhexidina (compuesto utilizado en la clínica) para conocer las ventajas de nuestros apósitos frente a otros tratamientos. En cuanto al control de la infección, se realizaron medidas cuantitativas y cualitativas de las bacterias presentes en la herida a diferentes tiempos post-infección. En cuanto al control de la inflamación, se realizaron análisis histológicos de las heridas evaluando la reacción de células inflamatorias y la formación de nuevos vasos sanguíneos. Los estudios demostraron que los apósitos de PCL-THY pueden prevenir la infección, además de promover la regeneración en heridas. Los resultados están incluidos en el artículo titulado “Efficiency of Antimicrobial Electrospun Thymol-Loaded Polycaprolactone Mats in vivo” Garcia-Salinas, S.; Gamez-Herrera, E.; Asin, J.; de Miguel, R.; Andreu, V.; Sancho-Albero, M.; Mendoza, G.; Irusta, S.; Arruebo, M.: aceptado para su publicación en ACS Applied Biomaterials. Manuscript ID: mt-2020-002706.o El Capítulo VI resume las principales conclusiones obtenidas en este trabajo. o El Apéndice I describe las técnicas de caracterización y métodos biológicos utilizados para evaluar la actividad antimicrobiana y anti-inflamatoria de los compuestos libres y encapsulados. o El Apéndice II indica las referencias utilizadas en este trabajo o El Apéndice III señala los artículos publicados y la participación en congresos que se han llevado a cabo durante la tesis The current Doctoral Thesis, named “Smart dressings based on nanostructured fibers containing natural origin antimicrobial and anti-inflammatory compounds” has been developed in the Department of Chemical Engineering and Environmental Technology (University of Zaragoza, Spain) in the group of Nanostructured Films and Particles (NFP), which is a member of the Aragon Institute of Nanoscience (INA). This research has been developed in this institute and also in the Biomedical Research Center of Aragon (CIBA). A predoctoral stay of 6 months was performed in the Methodist Hospital Research Institute in Houston (Texas, US) supervised by Professor Ennio Tasciotti. This research was supported by a FPI predoctoral fellowship, funded by the Spanish Ministry of Economy and Competitiveness (CTQ2014-52384-R). The short stay was also funded by the Network of Biomedical Research Center in the field of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). Due to the development of bacterial resistances, the search of new compounds to treat infections is in the spotlight of researchers. In this scenario, this thesis is focused on the design of a bioactive dressing based on electrospun polycaprolactone (PCL) nanofibers loading natural compounds obtained from essential oils (EOs) acting as anti-inflammatory and antimicrobial compounds for wound healing treatment. For this aim, a deep research on the bactericidal and anti-inflammatory EOs compounds properties was carried out. The first purpose of the thesis was to tackle wound infection with plant-derived natural compounds. For this goal, the bactericidal properties and mechanisms of different free EOs in planktonic bacteria cultures using a Gram-positive strain, Staphylococcus aureus (ATCC 25923) and a Gram-negative strain, Escherichia coli S17 were studied. In addition, since biofilm formation is a challenge in wound infections, the effect of natural compounds was studied on S. aureus biofilm. The high volatility character of EOs and the fact that they can be oxidized in contact with air or ultraviolet light, make difficult their application. Encapsulation of EOs is a good technique to protect their properties. Thus, thymol (THY), the compound that demonstrated the best antimicrobial activity against planktonic bacteria and biofilm, was encapsulated into PCL nanofibers. Nanofibers synthesis and THY encapsulation were carried out using the electrospinning technique. This method allows the fabrication of patches with high load of those volatile compounds such as THY. The bactericidal properties of these patches were studied using a cGFP-expressing S. aureus strain through quantitative assays and confocal microscopy. In order to use these natural compounds for wound healing applications, free-compound cytotoxicity assays were carried out in three different cell types: fibroblast, keratinocytes and macrophages. Moreover, a co-culture model using J774 macrophages and cGFP-expressing S. aureus was developed to study and monitoring the effect of THY loaded PCL patches in intracellular bacteria. The second goal in the thesis was to find an anti-inflammatory natural compound effective for wound treatment. For these assays, an in vitro inflammatory model was optimized in lipopolysaccharide (LPS) -activated J774 macrophages. These experiments were developed in the Methodist Hospital Research Institute in Houston (Texas, US). The study of the increase or reduction levels of inflammatory cytokines allowed us to determine the best anti-inflammatory natural compounds evaluated in our studies. Among them, PCL-THY patches demonstrated to be the wound dressings that better reduced inflammation in an in vitro inflammatory model. After concluding that THY had superior antimicrobial and anti-inflammatory properties when loaded in PCL nanofibers, an in vivo experiment to determine the effectiveness of the designed patches in an infected skin wound model was developed. SKH1 hairless mice were used to analyze the in vivo bactericidal and anti-inflammatory properties of PCL-THY patches for their potential clinical application. The document is structured in different chapters that address each of the goals of this doctoral thesis: Chapter I corresponds with the introductory part where general concepts are exposed. The chapter includes a description of the wound healing processes, pointing the factors affecting the procedure such as infection and inflammation. Different types of wound healing treatments such as antibiotics are described, highlighting antibiotic resistance as the reason to choose plant-derived compounds as a wound healing treatment. Electrospinning technique is explained to understand the synthesis of PCL nanofibers and the encapsulation of the active principle. Chapter II focuses on antimicrobial activity of free EOs to tackle wound infection. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were measured for different plant-derived natural compounds in S. aureus (ATCC 25923) and E. coli S17 strains. In addition, a S. aureus biofilm model was optimized to determine the effect of EOs in these bacterial formations. The mechanism of action of EOs against bacteria was studied by scanning electron microscopy (SEM) and flow cytometry. Cytotoxicity of EOs treatment was also evaluated in skin-related cell types such as fibroblasts, keratinocytes and macrophages. Carvacrol (CAR), cinnamaldehyde (CIN) and THY exhibited the highest in vitro antimicrobial activities against E. coli and S. aureus by disrupting the bacteria membrane. These results are included in the published article entitled “Evaluation of the antimicrobial activity and cytotoxicity of different components of natural origin present in essential oils”. García-Salinas, S.; Elizondo-Castillo, H.; Arruebo, M.; Mendoza, G.; Irusta, S. Molecules 2018, 23 (6), 1–18. https://doi.org/10.3390/molecules23061399. Chapter III considering the results obtained in Chapter II, THY was chosen as the compound to be loaded into electrospun PCL nanofibers due to its antimicrobial activity and low cytotoxicity compared with the other EOs tested. PCL-THY patches were synthetized, and their bactericidal properties were measured against both, planktonic culture and biofilm of cGFP-expressing S. aureus. A co-culture model using cGFP-expressing S. aureus and J774 macrophages was developed to study the effect of PCL-THY patches on infected cells. Compared to non-loaded dressings, PCL-THY dressings were able to eliminate the pathogenic bacteria in coculture models using infected murine macrophages. In addition, it was corroborated the successful ability of the developed patch in preventing biofilm formation. These results are included in the recently submitted article entitled “Antimicrobial Wound Dressings Against Fluorescent and Methicillin-Sensitive Intracellular Pathogenic Bacteria” Garcia-Salinas, S.; Gamez-Herrera, E.; Landa, G.; Arruebo, M.; Irusta, S.; Mendoza, G. ACS Applied Materials & Interfaces Manuscript ID: am-2020-05668q. Chapter IV describes the anti-inflammatory activity of EOs with the aim of reducing and controlling the inflammatory process during wound healing. Excessive inflammation can cause the activation of unnecessary cells or cytokines, generating deleterious effects, limiting healing. To develop this goal, an inflammatory model of J774 macrophages activated with LPS was carried out. Different free natural compounds reported as anti-inflammatory molecules were assessed. Thus, infected macrophages were treated and analyzed at the genetic level, measuring interleukin (Il) 1b, iNos (inducible Nitric oxide synthase) and Il10 cytokines by RT-PCR (Reverse Transcription-Polymerase Chain Reaction). PCL patches loaded with EOs were tested using the same in vitro model, confirming previous results. In addition, it was assessed cell morphology and average cell area comparing treated cells with positive (LPS-activated cells without treatment) and negative (non LPS-activated cells) controls. This experiment demonstrated the similarity among treated cells and non-activated cells, confirming the anti-inflammatory effect of THY loaded PCL patches. These results are included in the published article entitled “Electrospun Anti-Inflammatory Patch Loaded with Essential Oils for Wound Healing”. García-Salinas, S.; Evangelopoulos, M.; Gámez-Herrera, E.; Arruebo, M.; Irusta, S.; Taraballi, F.; Mendoza, G.; Tasciotti, E. Int. J. Pharm. 2020, 577 (January), 119067. https://doi.org/10.1016/j.ijpharm.2020.119067. Chapter V joins all the research performed during the thesis related to an S. aureus (ATCC 25923) infected wound in vivo model using SHK1 hairless mice. Thus, it was analyzed the in vivo bactericidal and inflammatory properties of the designed dressings. In addition, controls of free EO and a clinical compound (chlorhexidine) were added to assess the advantages of our patch against other treatments. Starting by infection, quantitative and qualitative measurements of bacteria present in the wound were collected at different dpi (days post infection). Moreover, the histological analysis of skin wounds was carried out to evaluate the inflammatory reaction and new vessel formation. Studies demonstrated that PCL-THY can prevent infection, promote wound healing and prompt regeneration. These results are included in the recently accepted article entitled “Efficiency of Antimicrobial Electrospun Thymol-Loaded Polycaprolactone Mats in vivo” Garcia-Salinas, S.; Gamez-Herrera, E.; Asin, J.; de Miguel, R.; Andreu, V.; Sancho-Albero, M.; Mendoza, G.; Irusta, S.; Arruebo, M. ACS Applied Biomaterials. ACS Appl. Bio Mater. 2020, 3 (5), 3430–3439. https://doi.org/10.1021/acsabm.0c00419 Chapter VI summarizes the main conclusions obtained during this doctoral thesis. Appendix I describes the main characterization techniques and biological methods in order to evaluate the antimicrobial and anti-inflammatory ability of free and loaded compounds. Appendix II compiles the references used to write this work. Appendix III points out the published scientific papers and the participation in conferences during this thesis.<br /

PoseGraphNet++: Enriching 3D Human Pose with Orientation Estimation

Existing kinematic skeleton-based 3D human pose estimation methods only predict joint positions. Although this is sufficient to compute the yaw and pitch of the bone rotations, the roll around the axis of the bones remains unresolved by these methods. In this paper, we propose a novel 2D-to-3D lifting Graph Convolution Network named PoseGraphNet++ to predict the complete human pose including the joint positions and the bone orientations. We employ node and edge convolutions to utilize the joint and bone features. Our model is evaluated on multiple benchmark datasets, and its performance is either on par with or better than the state-of-the-art in terms of both position and rotation metrics. Through extensive ablation studies, we show that PoseGraphNet++ benefits from exploiting the mutual relationship between the joints and the bones.Comment: 9 page

Targeted release of probiotics from enteric microparticulated formulations

The development of advanced probiotic delivery systems, which preserve bacteria from degradation of the gastrointestinal tract and achieve a targeted release mediated by pH-independent swelling, is of great interest to improve the eficient delivery of probiotic bacteria to the target tissue. Gram-positive and Gram-negative bacteria models (Lactobacillus acidophilus (Moro) Hansen and Mocquot (ATCC®4356™) and Escherichia coli S17, respectively) have been successfully encapsulated for the first time in pH-independent microparticulate polymethacrylates (i.e., Eudraguard biotic) used for the targeted delivery of nutraceuticals to the colon. These bacteria have also been encapsulated within the mucoadhesive polymethacrylate Eudragit RS 100 widely used as targeted release formulation for active pharmaceutical ingredients. The enteric microparticles remained unaltered under simulated gastric conditions and released the contained viable microbial cargo under simulated intestinal conditions. Buoyancies of 90.2% and 57.3% for Eudragit and Eudraguard microparticles, respectively, and long-term stability (5 months) for the encapsulated microorganisms were found. Cytotoxicity of the microparticles formulated with both polymers was evaluated (0.5-20 mg/mL) on Caco-2 cells, showing high cytocompatibility. These results underline the suitability of the synthesized materials for the successful delivery of probiotic formulations to the target organ, highlighting for the first time the potential use of Eudraguard biotic as an effective enteric coating for the targeted delivery of probiotics

New insights in osteoarthritis diagnosis and treatment: Nano-strategies for an improved disease management

Osteoarthritis (OA) is a common chronic joint pathology that has become a predominant cause of disability worldwide. Even though the origin and evolution of OA rely on different factors that are not yet elucidated nor understood, the development of novel strategies to treat OA has emerged in the last years. Cartilage degradation is the main hallmark of the pathology though alterations in bone and synovial inflammation, among other comorbidities, are also involved during OA progression. From a molecular point of view, a vast amount of signaling pathways are implicated in the progression of the disease, opening up a wide plethora of targets to attenuate or even halt OA. The main purpose of this review is to shed light on the recent strategies published based on nanotechnology for the early diagnosis of the disease as well as the most promising nano-enabling therapeutic approaches validated in preclinical models. To address the clinical issue, the key pathways involved in OA initiation and progression are described as the main potential targets for OA prevention and early treatment. Furthermore, an overview of current therapeutic strategies is depicted. Finally, to solve the drawbacks of current treatments, nanobiomedicine has shown demonstrated benefits when using drug delivery systems compared with the administration of the equivalent doses of the free drugs and the potential of disease-modifying OA drugs when using nanosystems. We anticipate that the development of smart and specific bioresponsive and biocompatible nanosystems will provide a solid and promising basis for effective OA early diagnosis and treatment. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacemen

Development of microfluidic devices with 3D collagen gels for traction force microscopy

In the past few decades, it has been widely demonstrated that cells constantly exert traction forces on the cells and matrix surrounding them. This behavior is fundamental in physiological and pathological processes such as embryogenesis and metastasis, therefore studying how cells interact with their environment is vitally important to understand these processes. To contribute to this research field, the present master project aims to adapt a given microfluidic device to the traction force microscopy technique, which is currently the most reliable approach for measuring cell forces. It is of great interest to quantify the forces exerted by cells seeded inside this microfluidic device because this specific device allows the deposition of collagen in a 3D arrangement, which resembles better the cell’s physiological environment than traditional 2D cell cultures. Device adaptation consisted in introduction of fluorescent microbeads into the collagen matrix, and subsequent confocal microscopy imaging of the cultured cells. Both stages required optimization of diverse features, for example: bead size and concentration, cell viability and labeling, fluorescence staining complications, etc. After numerous experiments and information search, the aforementioned features were improved, and ultimately, the microfluidic device was successfully adapted to traction force microscopy. Thus, the final assays produced useful data for performing the cell force calculation

Antimicrobial Wound Dressings against Fluorescent and Methicillin-Sensitive Intracellular Pathogenic Bacteria

There is limited evidence indicating that drug-eluting dressings are clinically more effective than simple conventional dressings. To shed light on this concern, we have performed evidence-based research to evaluate the antimicrobial action of thymol (THY)-loaded antimicrobial dressings having antibiofilm forming ability, able to eradicate intracellular and extracellular pathogenic bacteria. We have used four different Staphylococcus aureus strains, including the ATCC 25923 strain, the Newman strain (methicillin-sensitive strain, MSSA) expressing the coral green fluorescent protein from the vector pCN47, and two clinical reference strains, Newman-(MSSA) and USA300-(methicillin-resistant strain), as traceable models of pathogenic bacteria commonly infecting skin and soft tissues. Compared to non-loaded dressings, THY-loaded polycaprolactone-based electrospun dressings were also able to eliminate pathogenic bacteria in coculture models based on infected murine macrophages. In addition, by using confocal microscopy and the conventional microdilution plating method, we corroborated the successful ability of THY in preventing also biofilm formation. Herein, we demonstrated that the use of wound dressings loaded with the natural monoterpenoid phenol derivative THY are able to eliminate biofilm formation and intracellular methicillin-sensitive S aureus more efficiently than with their corresponding THY-free counterparts

Revisión de técnicas para una correcta inducción hipotérmica postparada cardíaca en una unidad de cuidados intensivos

La parada cardiorrespiratoria es una situación sanitaria problemática que lleva asociada una alta mortalidad pero son sus consecuencias neurológicas las que han obligado a buscar alternativas para mejorar la recuperación funcional de los pacientes. La optimización de las maniobras de reanimación y la aparición de la denominada cadena de supervivencia han aumentado la tasa de individuos que recuperan la circulación espontánea. El último eslabón corresponde a los cuidados postresucitación, entre los cuales se incluye la hipotermia inducida o terapéutica. Varios ensayos clínicos demostraron que el descenso controlado de la temperatura corporal a 32-34ºC durante 12-24 horas en individuos inconscientes tras una parada cardíaca mejoraba los daños neurológicos y disminuía la mortalidad. No obstante, en la actualidad, las distintas sociedades científicas buscan fomentar un entrenamiento profesional y crear protocolos de actuación, ya que aun existen interrogantes sin resolver y la escasa familiarización con la metodología de actuación por parte del personal sanitario especializado obstaculiza la implantación de la técnica en las unidades de cuidados intensivos