by Keyword: Rage

Loeck, M, Placci, M, Muro, S, (2023). Effect of acid sphingomyelinase deficiency in type A Niemann-Pick disease on the transport of therapeutic nanocarriers across the blood-brain barrier Drug Delivery And Translational Research 13, 3077-3093

ASM deficiency in Niemann-Pick disease type A results in aberrant cellular accumulation of sphingomyelin, neuroinflammation, neurodegeneration, and early death. There is no available treatment because enzyme replacement therapy cannot surmount the blood-brain barrier (BBB). Nanocarriers (NCs) targeted across the BBB via transcytosis might help; yet, whether ASM deficiency alters transcytosis remains poorly characterized. We investigated this using model NCs targeted to intracellular adhesion molecule-1 (ICAM-1), transferrin receptor (TfR), or plasmalemma vesicle-associated protein-1 (PV1) in ASM-normal vs. ASM-deficient BBB models. Disease differentially changed the expression of all three targets, with ICAM-1 becoming the highest. Apical binding and uptake of anti-TfR NCs and anti-PV1 NCs were unaffected by disease, while anti-ICAM-1 NCs had increased apical binding and decreased uptake rate, resulting in unchanged intracellular NCs. Additionally, anti-ICAM-1 NCs underwent basolateral reuptake after transcytosis, whose rate was decreased by disease, as for apical uptake. Consequently, disease increased the effective transcytosis rate for anti-ICAM-1 NCs. Increased transcytosis was also observed for anti-PV1 NCs, while anti-TfR NCs remained unaffected. A fraction of each formulation trafficked to endothelial lysosomes. This was decreased in disease for anti-ICAM-1 NCs and anti-PV1 NCs, agreeing with opposite transcytosis changes, while it increased for anti-TfR NCs. Overall, these variations in receptor expression and NC transport resulted in anti-ICAM-1 NCs displaying the highest absolute transcytosis in the disease condition. Furthermore, these results revealed that ASM deficiency can differently alter these processes depending on the particular target, for which this type of study is key to guide the design of therapeutic NCs.© 2023. Controlled Release Society.

JTD Keywords: asm deficiency, blood-brain barrier, delivery, determines, drug, endocytosis, enzymes, icam-1, lysosomal storage disease, mechanisms, nanoparticles, natural-history, niemann-pick disease type a, pv-1, receptor-mediated transcytosis, trafficking, transferrin receptor, Asm deficiency, Blood-brain barrier, Blood–brain barrier, Drug carriers, Drug nanocarriers, Humans, Icam-1, Icam-1-targeted nanocarriers, Intercellular adhesion molecule-1, Lysosomal storage disease, Niemann-pick disease type a, Niemann-pick disease, type a, Niemann-pick diseases, Pv-1, Receptor-mediated transcytosis, Transferrin receptor

del Moral, M, Loeck, M, Muntimadugu, E, Vives, G, Pham, V, Pfeifer, P, Battaglia, G, Muro, S, Andrianov, AK, (2023). Role of the Lactide:Glycolide Ratio in PLGA Nanoparticle Stability and Release under Lysosomal Conditions for Enzyme Replacement Therapy of Lysosomal Storage Disorders J Funct Biomater 14, 440

Prior studies demonstrated that encapsulation in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) enhanced the delivery of enzymes used for replacement therapy (ERT) of lysosomal storage disorders (LSDs). This study examined how the copolymer lactide:glycolide ratio impacts encapsulation, physicochemical characteristics, stability, and release under lysosomal conditions. Hyaluronidase, deficient in mucopolysaccharidosis IX, was encapsulated in NPs synthesized using 50:50, 60:40, or 75:25 lactide:glycolide copolymers. All NPs had diameters compatible with cellular transport (≤168 nm) and polydispersity indexes (≤0.16) and ζ-potentials (≤-35 mV) compatible with colloidal stability. Yet, their encapsulation efficiency varied, with 75:25 NPs and 60:40 NPs having the lowest and highest EE, respectively (15% vs. 28%). Under lysosomal conditions, the 50:50 copolymer degraded fastest (41% in 1 week), as expected, and the presence of a targeting antibody coat did not alter this result. Additionally, 60:40 NPs destabilized fastest (<1 week) because of their smaller diameter, and 75:25 NPs did not destabilize in 4 weeks. All formulations presented burst release under lysosomal conditions (56-78% of the original load within 30 min), with 50:50 and 60:40 NPs releasing an additional small fraction after week 1. This provided 4 weeks of sustained catalytic activity, sufficient to fully degrade a substrate. Altogether, the 60:40 NP formulation is preferred given its higher EE, and 50:50 NPs represent a valid alternative, while the highest stability of 75:25 NPs may impair lysosomes. These results can guide future studies aiming to translate PLGA NP-based ERT for this and other LSDs.

JTD Keywords: biodegradation, copolymer ratio, degradation, drug-delivery, emulsification, enzyme release, enzyme replacement therapy, hyaluronidase, mechanisms, microspheres, nanoparticle stability, poly(lactide-co-glycolide) nanoparticles, size, sphingomyelinase, transport, Central-nervous-system, Copolymer ratio, Enzyme release, Enzyme replacement therapy, Hyaluronidase, Lysosomal storage disorder, Nanoparticle stability, Poly(lactide-co-glycolide) nanoparticles

Placci, M, Giannotti, MI, Muro, S, (2023). Polymer-based drug delivery systems under investigation for enzyme replacement and other therapies of lysosomal storage disorders Advanced Drug Delivery Reviews 197, 114683

Lysosomes play a central role in cellular homeostasis and alterations in this compartment associate with many diseases. The most studied example is that of lysosomal storage disorders (LSDs), a group of 60 + maladies due to genetic mutations affecting lysosomal components, mostly enzymes. This leads to aberrant intracellular storage of macromolecules, altering normal cell function and causing multiorgan syndromes, often fatal within the first years of life. Several treatment modalities are available for a dozen LSDs, mostly consisting of enzyme replacement therapy (ERT) strategies. Yet, poor biodistribution to main targets such as the central nervous system, musculoskeletal tissue, and others, as well as generation of blocking antibodies and adverse effects hinder effective LSD treatment. Drug delivery systems are being studied to surmount these obstacles, including polymeric constructs and nanoparticles that consti-tute the focus of this article. We provide an overview of the formulations being tested, the diseases they aim to treat, and the results observed from respective in vitro and in vivo studies. We also discuss the advantages and disadvantages of these strategies, the remaining gaps of knowledge regarding their per-formance, and important items to consider for their clinical translation. Overall, polymeric nanocon-structs hold considerable promise to advance treatment for LSDs.(c) 2023 Elsevier B.V. All rights reserved.

JTD Keywords: cellular and animal models, enzyme replacement therapy, lysosomal storage disorders, nanoemulsions, nanoparticles, Beta-glucuronidase deficiency, Blood-brain-barrier, Cellular and animal models, Central-nervous-system, Drug delivery systems, Enzyme replacement therapy, Feline gm1 gangliosidosis, Human acid sphingomyelinase, Human alpha-galactosidase, Humans, Lysosomal storage diseases, Lysosomal storage disorders, Lysosomes, Mucopolysaccharidosis type-ii, Nanoemulsions, Nanoparticles, Neuronal ceroid-lipofuscinosis, Niemann-pick-disease, Pluripotent stem-cells, Polymer-based drug delivery systems, Polymers, Tissue distribution

Bouras, A, Gutierrez-Galvez, A, Burgués, J, Bouzid, Y, Pardo, A, Guiatni, M, Marco, S, (2023). Concentration map reconstruction for gas source location using nano quadcopters: Metal oxide semiconductor sensor implementation and indoor experiments validation Measurement 213, 112638

Solomon, M, Loeck, M, Silva-Abreu, M, Moscoso, R, Bautista, R, Vigo, M, Muro, S, (2022). Altered blood-brain barrier transport of nanotherapeutics in lysosomal storage diseases Journal Of Controlled Release 349, 1031-1044

Treatment of neurological lysosomal storage disorders (LSDs) are limited because of impermeability of the blood-brain barrier (BBB) to macromolecules. Nanoformulations targeting BBB transcytosis are being explored, but the status of these routes in LSDs is unknown. We studied nanocarriers (NCs) targeted to the transferrin receptor (TfR), ganglioside GM1 or ICAM1, associated to the clathrin, caveolar or cell adhesion molecule (CAM) routes, respectively. We used brain endothelial cells and mouse models of acid sphingomyelinase-deficient Niemann Pick disease (NPD), and postmortem LSD patients' brains, all compared to respective controls. NC transcytosis across brain endothelial cells and brain distribution in mice were affected, yet through different mechanisms. Reduced TfR and clathrin expression were found, along with decreased transcytosis in cells and mouse brain distribution. Caveolin-1 expression and GM1 transcytosis were also reduced, yet increased GM1 levels seemed to compensate, providing similar NC brain distribution in NPD vs. control mice. A tendency to lower NHE-1 levels was seen, but highly increased ICAM1 expression in cells and human brains correlated with increased transcytosis and brain distribution in mice. Thus, transcytosis-related alterations in NPD and likely other LSDs may impact therapeutic access to the brain, illustrating the need for these mechanistic studies.Copyright © 2022 Elsevier B.V. All rights reserved.

JTD Keywords: acid sphingomyelinase, antibody-affinity, blood -brain barrier, drug-delivery, icam-1-targeted nanocarriers, in-vivo, mediated endocytosis, model, neurological diseases, niemann-pick, targeted nanocarriers, trafficking, transcytosis pathways, Blood-brain barrier, Central-nervous-system, Lysosomal storage disorders, Neurological diseases, Targeted nanocarriers, Transcytosis pathways

Rial-Hermida, MI, Rey-Rico, A, Blanco-Fernandez, B, Carballo-Pedrares, N, Byrne, EM, Mano, JF, (2021). Recent Progress on Polysaccharide-Based Hydrogels for Controlled Delivery of Therapeutic Biomolecules Acs Biomaterials Science & Engineering 7, 4102-4127

A plethora of applications using polysaccharides have been developed in recent years due to their availability as well as their frequent nontoxicity and biodegradability. These polymers are usually obtained from renewable sources or are byproducts of industrial processes, thus, their use is collaborative in waste management and shows promise for an enhanced sustainable circular economy. Regarding the development of novel delivery systems for biotherapeutics, the potential of polysaccharides is attractive for the previously mentioned properties and also for the possibility of chemical modification of their structures, their ability to form matrixes of diverse architectures and mechanical properties, as well as for their ability to maintain bioactivity following incorporation of the biomolecules into the matrix. Biotherapeutics, such as proteins, growth factors, gene vectors, enzymes, hormones, DNA/RNA, and antibodies are currently in use as major therapeutics in a wide range of pathologies. In the present review, we summarize recent progress in the development of polysaccharide-based hydrogels of diverse nature, alone or in combination with other polymers or drug delivery systems, which have been implemented in the delivery of biotherapeutics in the pharmaceutical and biomedical fields. © 2021 American Chemical Society.

JTD Keywords: biodegradable dextran hydrogels, biotherapeutics, bone morphogenetic protein-2, carrageenan-based hydrogels, chitosan-based hydrogels, controlled delivery, controlled-release, cross-linked hydrogels, growth-factor delivery, hydrogels, in-vitro characterization, polysaccharides, self-healing hydrogel, stimuli-responsiveness, tissue engineering, Antibodies, Bioactivity, Biodegradability, Biomedical fields, Biomolecules, Biotherapeutics, Chemical modification, Circular economy, Controlled delivery, Controlled drug delivery, Delivery systems, Drug delivery system, Functional polymers, Hyaluronic-acid hydrogels, Hydrogels, Industrial processs, Polysaccharides, Recent progress, Renewable sources, Stimuli-responsiveness, Targeted drug delivery, Tissue engineering, Waste management

Seras-Franzoso, J, Diaz-Riascos, ZV, Corchero, JL, González, P, Garcia-Aranda, N, Mandaña, M, Riera, R, Boullosa, A, Mancilla, S, Grayston, A, Moltó-Abad, M, Garcia-Fruitós, E, Mendoza, R, Pintos-Morell, G, Albertazzi, L, Rosell, A, Casas, J, Villaverde, A, Schwartz, S, Abasolo, I, (2021). Extracellular vesicles from recombinant cell factories improve the activity and efficacy of enzymes defective in lysosomal storage disorders Journal Of Extracellular Vesicles 10, e12058

In the present study the use of extracellular vesicles (EVs) as vehicles for therapeutic enzymes in lysosomal storage disorders was explored. EVs were isolated from mammalian cells overexpressing alpha-galactosidase A (GLA) or N-sulfoglucosamine sulfohydrolase (SGSH) enzymes, defective in Fabry and Sanfilippo A diseases, respectively. Direct purification of EVs from cell supernatants was found to be a simple and efficient method to obtain highly active GLA and SGSH proteins, even after EV lyophilization. Likewise, EVs carrying GLA (EV-GLA) were rapidly uptaken and reached the lysosomes in cellular models of Fabry disease, restoring lysosomal functionality much more efficiently than the recombinant enzyme in clinical use. In vivo, EVs were well tolerated and distributed among all main organs, including the brain. DiR-labelled EVs were localized in brain parenchyma 1 h after intra-arterial (internal carotid artery) or intravenous (tail vein) administrations. Moreover, a single intravenous administration of EV-GLA was able to reduce globotriaosylceramide (Gb3) substrate levels in clinically relevant tissues, such kidneys and brain. Overall, our results demonstrate that EVs from cells overexpressing lysosomal enzymes act as natural protein delivery systems, improving the activity and the efficacy of the recombinant proteins and facilitating their access to organs neglected by conventional enzyme replacement therapies.

JTD Keywords: alpha?galactosidase a, alpha‐galactosidase a, drug delivery, enzyme replacement therapy, fabry disease, lysosomal storage disorders, n-sulfoglucosamine sulfohydrolase, n?sulfoglucosamine sulfohydrolase, n‐sulfoglucosamine sulfohydrolase, sanfilippo syndrome, Alpha-galactosidase a, Drug delivery, Enzyme replacement therapy, Fabry disease, Lysosomal storage disorders, N-sulfoglucosamine sulfohydrolase, Sanfilippo syndrome

Ruano, G., Díaz, A., Tononi, J., Torras, J., Puiggalí, J., Alemán, C., (2020). Biohydrogel from unsaturated polyesteramide: Synthesis, properties and utilization as electrolytic medium for electrochemical supercapacitors Polymer Testing 82, 106300

The utilization of hydrogels derived from biopolymers as solid electrolyte (SE) of electrochemical supercapacitors (ESCs) is a topic of increasing interest because of their promising applications in biomedicine (e.g. for energy storage in autonomous implantable devices). In this work an unsaturated polyesteramide that contains phenylalanine, butenediol and fumarate as building blocks has been photo-crosslinked to obtain a hydrogel (UPEA-h). The structure of UPEA-h, which is characterized by a network of open interconnected pores surrounded by regions with compact morphology, favors ion transport, while the biodegradability and biocompatibility conferred by the α-amino acid unit and the ester group are appropriated for its usage in the biomedical field. Voltammetric and galvanostatic assays have been conducted to evaluate the behavior of UPEA-h when used as SE in ESCs with poly(3,4-ethylenedioxythiophene) (PEDOT) electrodes. Hence, PEDOT/UPEA-h devices displayed supercapacitor response of up 179 F/g and capacitance retention higher than 90%. Moreover, the long-term stability, leakage-current, and self-discharging response of PEDOT/UPEA-h ESCs reflect the great potential of UPEA-h as ion-conductive electrolyte. Indeed, the performance of PEDOT/UPEA-h is higher than found in analogous devices constructed using other biohydrogels as SE (e.g. κ-carrageenan, poly-γ-glutamic acid and cellulose hydrogels).

JTD Keywords: Energy storage, Hydrogel electronics, Ion conductivity, Photo-crosslinking, Wearable electronics

Saborío, M. G., Svelic, P., Casanovas, J., Ruano, G., Pérez-Madrigal, M. M., Franco, L., Torras, J., Estrany, F., Alemán, C., (2019). Hydrogels for flexible and compressible free standing cellulose supercapacitors European Polymer Journal 118, 347-357

Cellulose-based supercapacitors display important advantages in comparison with devices fabricated with other materials, regarding environmental friendliness, flexibility, cost and versatility. Recent progress in the field has been mainly focused on the utilization of cellulose fibres as: structural mechanical reinforcement of electrodes; precursors of electrically active carbon-based materials; or primary electrolytes that act as reservoirs of secondary electrolytes. In this work, a flexible, lightweight, robust, portable and manageable all-carboxymethyl cellulose symmetric supercapacitor has been obtained by assembling two electrodes based on carboxymethyl cellulose hydrogels to a solid electrolytic medium formulated with the same material. Hydrogels, which were made by cross-linking carboxymethyl cellulose paste with citric acid in water, rendered not only effective solid electrolytic media by simply loading NaCl but also electroactive electrodes. For the latter, conducting polymer microparticles, which were loaded into the hydrogel network during the physical cross-linking step, were appropriately connected through the in situ anodic polymerization of a similar conducting polymer in aqueous medium, thus creating conduction paths. The performance of the assembled supercapacitors has been proved by cyclic voltammetry, galvanostatic charge-discharge and electrochemical impedance spectroscopy. This design opens a new window for the green and mass production of flexible cellulose-based supercapacitors.

JTD Keywords: Conducting polymer, Energy storage, Flexible electrodes, In situ polymerization, Wearable electronics

Enshaei, H., Molina, B. G., del Valle, L. J., Estrany, F., Arnan, C., Puiggalí, J., Saperas, N., Alemán, C., (2019). Scaffolds for sustained release of ambroxol hydrochloride, a pharmacological chaperone that increases the activity of misfolded β-glucocerebrosidase. Macromolecular Bioscience 19, (8), 1900130

Ambroxol is a pharmacological chaperone (PC) for Gaucher disease that increases lysosomal activity of misfolded β-glucocerebrosidase (GCase) while displaying a safe toxicological profile. In this work, different poly(ε-caprolactone) (PCL)-based systems are developed to regulate the sustained release of small polar drugs in physiological environments. For this purpose, ambroxol is selected as test case since the encapsulation and release of PCs using polymeric scaffolds have not been explored yet. More specifically, ambroxol is successfully loaded in electrospun PCL microfibers, which are subsequently coated with additional PCL layers using dip-coating or spin-coating. The time needed to achieve 80% release of loaded ambroxol increases from ≈15 min for uncoated fibrous scaffolds to 3 days and 1 week for dip-coated and spin-coated systems, respectively. Furthermore, it is proven that the released drug maintains its bioactivity, protecting GCase against induced thermal denaturation.

JTD Keywords: Electrospinning, Gaucher's disease, Lysosomal storage disorders, Misfolding diseases, Poly(ε-caprolactone), Polyester, Release regulation

Garde, A., Sörnmo, L., Laguna, P., Jané, R., Benito, S., Bayés-Genís, A., Giraldo, B. F., (2017). Assessment of respiratory flow cycle morphology in patients with chronic heart failure Medical and Biological Engineering and Computing , 55, (2), 245-255

Breathing pattern as periodic breathing (PB) in chronic heart failure (CHF) is associated with poor prognosis and high mortality risk. This work investigates the significance of a number of time domain parameters for characterizing respiratory flow cycle morphology in patients with CHF. Thus, our primary goal is to detect PB pattern and identify patients at higher risk. In addition, differences in respiratory flow cycle morphology between CHF patients (with and without PB) and healthy subjects are studied. Differences between these parameters are assessed by investigating the following three classification issues: CHF patients with PB versus with non-periodic breathing (nPB), CHF patients (both PB and nPB) versus healthy subjects, and nPB patients versus healthy subjects. Twenty-six CHF patients (8/18 with PB/nPB) and 35 healthy subjects are studied. The results show that the maximal expiratory flow interval is shorter and with lower dispersion in CHF patients than in healthy subjects. The flow slopes are much steeper in CHF patients, especially for PB. Both inspiration and expiration durations are reduced in CHF patients, mostly for PB. Using the classification and regression tree technique, the most discriminant parameters are selected. For signals shorter than 1 min, the time domain parameters produce better results than the spectral parameters, with accuracies for each classification of 82/78, 89/85, and 91/89 %, respectively. It is concluded that morphologic analysis in the time domain is useful, especially when short signals are analyzed.

JTD Keywords: Chronic heart failure, Ensemble average, Periodic and non-periodic breathing, Respiratory pattern

Giraldo, B. F., Chaparro, J. A., Caminal, P., Benito, S., (2013). Characterization of the respiratory pattern variability of patients with different pressure support levels Engineering in Medicine and Biology Society (EMBC) 35th Annual International Conference of the IEEE , IEEE (Osaka, Japan) , 3849-3852

One of the most challenging problems in intensive care is still the process of discontinuing mechanical ventilation, called weaning process. Both an unnecessary delay in the discontinuation process and a weaning trial that is undertaken too early are undesirable. In this study, we analyzed respiratory pattern variability using the respiratory volume signal of patients submitted to two different levels of pressure support ventilation (PSV), prior to withdrawal of the mechanical ventilation. In order to characterize the respiratory pattern, we analyzed the following time series: inspiratory time, expiratory time, breath duration, tidal volume, fractional inspiratory time, mean inspiratory flow and rapid shallow breathing. Several autoregressive modeling techniques were considered: autoregressive models (AR), autoregressive moving average models (ARMA), and autoregressive models with exogenous input (ARX). The following classification methods were used: logistic regression (LR), linear discriminant analysis (LDA) and support vector machines (SVM). 20 patients on weaning trials from mechanical ventilation were analyzed. The patients, submitted to two different levels of PSV, were classified as low PSV and high PSV. The variability of the respiratory patterns of these patients were analyzed. The most relevant parameters were extracted using the classifiers methods. The best results were obtained with the interquartile range and the final prediction errors of AR, ARMA and ARX models. An accuracy of 95% (93% sensitivity and 90% specificity) was obtained when the interquartile range of the expiratory time and the breath duration time series were used a LDA model. All classifiers showed a good compromise between sensitivity and specificity.

JTD Keywords: autoregressive moving average processes, feature extraction, medical signal processing, patient care, pneumodynamics, signal classification, support vector machines, time series, ARX, autoregressive modeling techniques, autoregressive models with exogenous input, autoregressive moving average model, breath duration time series, classification method, classifier method, discontinuing mechanical ventilation, expiratory time, feature extraction, final prediction errors, fractional inspiratory time, intensive care, interquartile range, linear discriminant analysis, logistic regression analysis, mean inspiratory flow, patient respiratory volume signal, pressure support level, pressure support ventilation, rapid shallow breathing, respiratory pattern variability characterization, support vector machines, tidal volume, weaning trial, Analytical models, Autoregressive processes, Biological system modeling, Estimation, Support vector machines, Time series analysis, Ventilation

Giraldo, B.F., Gaspar, B.W., Caminal, P., Benito, S., (2012). Analysis of roots in ARMA model for the classification of patients on weaning trials Engineering in Medicine and Biology Society (EMBC) 34th Annual International Conference of the IEEE , IEEE (San Diego, USA) , 698-701

One objective of mechanical ventilation is the recovery of spontaneous breathing as soon as possible. Remove the mechanical ventilation is sometimes more difficult that maintain it. This paper proposes the study of respiratory flow signal of patients on weaning trials process by autoregressive moving average model (ARMA), through the location of poles and zeros of the model. A total of 151 patients under extubation process (T-tube test) were analyzed: 91 patients with successful weaning (GS), 39 patients that failed to maintain spontaneous breathing and were reconnected (GF), and 21 patients extubated after the test but before 48 hours were reintubated (GR). The optimal model was obtained with order 8, and statistical significant differences were obtained considering the values of angles of the first four poles and the first zero. The best classification was obtained between GF and GR, with an accuracy of 75.3% on the mean value of the angle of the first pole.

JTD Keywords: Analytical models, Biological system modeling, Computational modeling, Estimation, Hospitals, Poles and zeros, Ventilation, Autoregressive moving average processes, Patient care, Patient monitoring, Pneumodynamics, Poles and zeros, Ventilation, ARMA model, T-tube test, Autoregressive moving average model, Extubation process, Mechanical ventilation, Optimal model, Patient classification, Respiratory flow signal, Roots, Spontaneous breathing, Weaning trials

Chaparro, J.A., Giraldo, B.F., Caminal, P., Benito, S., (2012). Performance of respiratory pattern parameters in classifiers for predict weaning process Engineering in Medicine and Biology Society (EMBC) 34th Annual International Conference of the IEEE , IEEE (San Diego, USA) , 4349-4352

Weaning trials process of patients in intensive care units is a complex clinical procedure. 153 patients under extubation process (T-tube test) were studied: 94 patients with successful trials (group S), 38 patients who failed to maintain spontaneous breathing and were reconnected (group F), and 21 patients with successful test but that had to be reintubated before 48 hours (group R). The respiratory pattern of each patient was characterized through the following time series: inspiratory time (TI), expiratory time (TE), breathing cycle duration (TTot), tidal volume (VT), inspiratory fraction (TI/TTot), half inspired flow (VT/TI), and rapid shallow index (f/VT), where f is respiratory rate. Using techniques as autoregressive models (AR), autoregressive moving average models (ARMA) and autoregressive models with exogenous input (ARX), the most relevant parameters of the respiratory pattern were obtained. We proposed the evaluation of these parameters using classifiers as logistic regression (LR), linear discriminant analysis (LDA), support vector machines (SVM) and classification and regression tree (CART) to discriminate between patients from groups S, F and R. An accuracy of 93% (98% sensitivity and 82% specificity) has been obtained using CART classification.

JTD Keywords: Accuracy, Indexes, Logistics, Regression tree analysis, Support vector machines, Time series analysis, Autoregressive moving average processes, Medical signal processing, Pattern classification, Pneumodynamics, Regression analysis, Sensitivity, Signal classification, Support vector machines, Time series, SVM, T-tube testing, Autoregressive models-with-exogenous input, Autoregressive moving average models, Breathing cycle duration, Classification-and-regression tree, Expiratory time, Extubation process, Half inspired flow, Inspiratory fraction, Inspiratory time, Intensive care units, Linear discriminant analysis, Logistic regression, Rapid shallow index, Respiratory pattern parameter performance, Sensitivity, Spontaneous breathing, Support vector machines, Tidal volume, Time 48 hr, Time series, Weaning process classifiers

Valente, T., Gella, A., Fernàndez-Busquets, X., Unzeta, M., Durany, N., (2010). Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer's disease and diabetes mellitus Neurobiology of Disease , 37, (1), 67-76

It has been extensively reported that diabetes mellitus (DM) patients have a higher risk of developing Alzheimer's disease (AD). but a mechanistic connection between both pathologies has not been provided so far Carbohydrate-derived advanced glycation endproducts (AGEs) have been implicated in the chronic complications of DM and have been reported to play an important role in the pathogenesis of AD. The earliest histopathological manifestation of AD is the apparition of extracellular aggregates of the amyloid beta peptide (A beta). To investigate possible correlations between AGEs and A beta aggregates with both pathologies. we have performed an immuhistochemical study in human post-mortem samples of AD, AD with diabetes (ADD). diabetic and nondemented controls ADD brains showed increased number of A beta dense plaques and receptor for AGEs (RACE)-positive and Tau-positive cells, higher AGEs levels and major microglial activation, compared to AD brain. Our results indicate that ADD patients present a significant increase of cell damage through a RAGE-dependent mechanism, suggesting that AGEs may promote the generation of an oxidative stress vicious cycle, which can explain the severe progression of patients with both pathologies.

JTD Keywords: Abeta, Alzheimer's disease, Rage, Ages, Diabetes, Immunohistochemistry, Advanced glycation endproducts, Beta-amyloid peptide, End-products, Oxidative stress, Advanced glycosylation, Synaptic dysfunction, Cross-linking

Perera, A., Pardo, A., Barrettino, D., Hierlermann, A., Marco, S., (2010). Evaluation of fish spoilage by means of a single metal oxide sensor under temperature modulation Sensors and Actuators B: Chemical 146, (2), 477-482

In this paper the feasibility of using metal oxide gas sensor technology for evaluating spoilage process for sea bream (Sparus aurata) is explored. It is shown that a single sensor under temperature modulation is able to find a correlation with the fish spoilage process. Results are obtained in real frigorific storage conditions: that is, at low measurement temperatures with variations of relative humidity.

JTD Keywords: Gas sensors, Electronic nose, Spoilage process, Temperature modulation, Bream sparus-aurata, Electronic nose, Freshness, Quality, Sardines, Storage

Tarzan-Lorente, M., Gutierrez-Galvez, A., Martinez, D., Marco, S., (2010). A biologically inspired associative memory for artificial olfaction Practica 2010 International Joint Conference on Neural Networks (IJCNN 2010) , IEEE, Piscataway, NJ, USA (Barcelona, Spain) , 6 pp.

In this paper, we propose a biologically inspired architecture for a Hopfield-like associative memory applied to artificial olfaction. The proposed algorithm captures the projection between two neural layers of the insect olfactory system (Antennal Lobe and Mushroom Body) with a kernel based projection. We have tested its classification performance as a function of the size of the training set and the time elapsed since training and compared it with that obtained with a Support Vector Machine.

JTD Keywords: Biocomputing, Chemioception, Content-addressable storage, Hopfield neural nets, Support vector machines

Fonollosa, J., Halford, B., Fonseca, L., Santander, J., Udina, S., Moreno, M., Hildenbrand, J., Wöllenstein, J., Marco, S., (2009). Ethylene optical spectrometer for apple ripening monitoring in controlled atmosphere store-houses Sensors and Actuators B: Chemical 136, (2), 546-554

In today's store-houses the ripening of fruit is controlled by managing the ethylene concentration in the ambient atmosphere. Precise and continuous ethylene monitoring is very advantageous since low ethylene concentrations are produced by the fruit itself and are indicative of its ripeness, and on other occasions, ethylene is externally added when ripeness or degreening of the product must be promoted. In this work, a multichannel mid-infrared spectrometer for ethylene measurement is built and characterized. The instrument contains additional channels to reject potential cross-interferences like ammonia and ethanol. Additionally, these channels are useful for monitoring a potential malfunction of the cooling system and possible fouling of the fruit, respectively. The complete spectrometer contains a silicon-based macroporous infrared (IR) emitter, a miniaturized long path cell (white cell), a four-channel detector module, low-noise analog amplification and filtering, and a microcontroller-based lock-in amplifier. The new inner architecture of the detector module features a fourfold thermopile array with narrow band optical filters attached by flip-chip technology, and a Fresnel lens array attached on the lid of the package. Laboratory tests show that the system is able to distinguish between ammonia and ethylene, featuring a detection limit of 30 ppm and 160 ppm (95% confidence) for ethylene and ammonia, respectively. Field tests show that the spectrometer is suitable as an ethylene alarm to detect fruit ripening and prevent fruit to decline into senescence. Simulation results show that system selectivity could be improved by setting ammonia channel to another absorption wavelength.

JTD Keywords: IR spectrometer, Ethylene, Fruit storage, Fresnel lens, White cell, Lock-in amplifier