Severe pulmonary hypertension and circulatory failure associated with Congenital syphilis. Case report.

BACKGROUND: Congenital syphilis is a vertical infection caused by Treponema pallidum. Despite the implementation of preventive strategies during pregnancy, its incidence is increasing, and it constitutes an important public health problem. Most patients with congenital syphilis are asymptomatic; however, a small group may develop severe disease at birth with the need of advanced resuscitation in the delivery room, acute hypoxemic respiratory failure, and hemodynamic instability. Therefore, awareness is needed. METHODS AND RESULTS: This series describes the clinical course of two late preterm infants with congenital syphilis who developed acute hypoxemic respiratory failure, pulmonary hypertension, and circulatory collapse early after birth. Integrated hemodynamic evaluation with neonatologist-performed echocardiography (NPE) and therapeutic management is provided. CONCLUSIONS: A comprehensive hemodynamic evaluation including early and serial functional echocardiography in these patients is needed to address the underlying complex pathophysiology and to help to establish accurate treatment.

Reports on the sensitivity enhancement in interferometric based biosensors by biotin-streptavidin system.

Antibody biotinylation is a process of attaching biotin molecules to antibodies by chemically modifying specific functional groups on the antibodies without altering their antigen recognition specificity. Biotin, a small vitamin, forms a strong and specific interaction with the protein streptavidin, resulting in a stable biotin-streptavidin (biotin-STV) complex. This biotin-STV interaction is widely exploited in various biotechnological applications, including biosensors. Biosensors are analytical devices that employ biological recognition elements, such as antibodies, enzymes, or nucleic acids, to detect and quantify target analytes in a sample. Antibodies are commonly used as recognition elements in biosensors due to their high specificity and affinity. In this study, the antibody anti-Bovine Serum Albumin (αBSA) has been biotinylated at different antibody:biotin ratios, and the stability of this labeling over time has been investigated. Furthermore, the sensitivity of the biosensor for detecting the Bovine Serum Albumin (BSA) protein has been compared using the biotinylated antibody and the non-biotinylated form, showing a four-fold improvement in detection. This system was also compared with the Enzyme-Linked ImmunoSorbent Assay (ELISA) technique. The advantages of using biotinylated antibodies in biosensors include increased stability and reproducibility of the biorecognition layer, as well as flexibility in sensor design, as different biotinylated antibodies can be utilized for diverse target analytes without altering the sensor's architecture.

Developing an improved optical biosensing system based on gold nanoparticles acting as interferometric enhancers in Lactoferrin detection.

We report for the first time the whole development of a biosensing system based on the Interferometric Optical Detection Method (IODM) enriched with gold nanoparticles (AuNPs), acting as interferometric enhancers for improving the performance of immunoassays. For this purpose, the Lactoferrin sandwich immunoassay model was employed. We describe in detail the entire value chain from the AuNPs production, its functionalization, and characterization with anti-Lactoferrin (anti-LF), the biosensing response of these conjugates as well as their corresponding calculation of the kinetic constants, performance comparison of the readout interferometric signals versus Scanning Electron Microscopy (SEM) and the percentage of the sensing surface covered. Finally, a Lactoferrin sandwich immunoassay was carried out and correlated with Enzyme-Linked ImmunoSorbent Assay (ELISA), and the Limit of Detection and sensitivity figures were obtained. As a result, we demonstrate how the AuNPs act as interferometric amplifiers of the IODM for improving the biosensing response, opening the possibility of being applied in multiple biological detection applications.

Developing an Optical Interferometric Detection Method based biosensor for detecting specific SARS-CoV-2 immunoglobulins in Serum and Saliva, and their corresponding ELISA correlation.

The standard rapid approach for the diagnosis of coronavirus disease 2019 (COVID-19) is the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. The detection of specific anti-SARS-CoV-2 immunoglobulins is crucial for screening people who have been exposed to the virus, whether or not they presented symptoms. Recent publications report different methods for the detection of specific IgGs, IgMs, and IgAs against SARS-CoV-2; these methods mainly detect immunoglobulins in the serum using conventional techniques such as rapid lateral flow tests or enzyme-linked immunosorbent assay (ELISA). In this article, we report the production of recombinant SARS-CoV-2 spike protein and the development of a rapid, reliable, cost-effective test, capable of detecting immunoglobulins in serum and saliva samples. This method is based on interferometric optical detection. The results obtained using this method and those obtained using ELISA were compared. Owing to its low cost and simplicity, this test can be used periodically for the early detection, surveillance, detection of immunity, and control of the spread of COVID-19.

A new microfluidic method enabling the generation of multi-layered tissues-on-chips using skin cells as a proof of concept.

Microfluidic-based tissues-on-chips (TOCs) have thus far been restricted to modelling simple epithelia as a single cell layer, but likely due to technical difficulties, no TOCs have been reported to include both an epithelial and a stromal component despite the biological importance of the stroma for the structure and function of human tissues. We present, for the first time, a novel approach to generate 3D multilayer tissue models in microfluidic platforms. As a proof of concept, we modelled skin, including a dermal and an epidermal compartment. To accomplish this, we developed a parallel flow method enabling the deposition of bilayer tissue in the upper chamber, which was subsequently maintained under dynamic nutrient flow conditions through the lower chamber, mimicking the function of a blood vessel. We also designed and built an inexpensive, easy-to-implement, versatile, and robust vinyl-based device that overcomes some of the drawbacks present in PDMS-based chips. Preliminary tests indicate that this biochip will allow the development and maintenance of multilayer tissues, which opens the possibility of better modelling of the complex cell-cell and cell-matrix interactions that exist in and between the epithelium and mesenchyme, allowing for better-grounded tissue modelling and drug screening.

A new optical interferometric-based in vitro detection system for the specific IgE detection in serum of the main peach allergen.

Food allergens cause worldwide chronic diseases with a great impact on public health. Immunoglobulins E (IgEs) trigger allergic reactions by specifically binding the allergens to which the allergic patients are sensitized. In this scientific work we report for the first time a new optical interferometric in vitro system for the detection of specific IgEs (sIgEs) to the principal peach allergen (Pru p 3) in real serum samples. Interferometric Optical Detection Method (IODM) was employed for reading out the signal of Fabry-Perot based interferometers acting as biotransducers. Pru p 3 was immobilized as bioreceptor onto the sensing surface for detecting the target biomolecules, sIgEs to Pru p 3. Moreover, the demanding low concentration of IgE, compared to other analytes in real serum samples, made it necessary to use nanoparticles (NPs) for two reasons: to collect only the IgEs from the serum sample and to enhance the optical interferometric read-out signal. The methodology was validated in advance by scanning electron microscopy (SEM). Consequently, we report in this article a novel high-performance in vitro detection method to recognize sIgE to molecular allergens by means of silicon dioxide (SiO2) NPs. Finally, this scientific work provides the basis for the in vitro component resolved diagnosis (CRD) of sIgEs to molecular allergens.

Contact lenses as drug-delivery systems: a promising therapeutic tool. / Lentes de contacto para vehiculizar principios activos: una prometedora herramienta terapéutica.

The ocular administration of drugs using traditional pharmaceutical forms, including eye drops or ointments, results in low bioavailability, as well as requiring multiple administrations per day, with the consequent danger of therapeutic non-compliance. Although, through the use of pharmaceutical technology, attempts have been made to use various solutions in order to increase bioavailability in the most common pharmaceutical forms, it has not been entirely satisfactory. In this context, contact lenses are presented as drug delivery systems that largely remedy these two major problems and offer other additional advantages. Therefore, the use of contact lenses as drug carrying systems has been increasingly investigated in recent years, as they can increase the bioavailability of these drugs, leading to an increase in therapeutic efficacy and compliance. The main techniques used to achieve this goal are included in this review, including immersion in drug solutions, use of vitamin E barriers, molecular printing, colloidal systems, etc. The most interesting results, depending on the different eye pathologies, are presented. Although the use of contact lenses as a vehicle for the release of active ingredients is a relatively novel strategy, there are already many studies and trials that support it. In any case, further research needs to be carried out to finally reach an effective, safe, and stable product that can be marketed.

Efectividad de la Wii Fit Balance frente a otras intervenciones para la recuperación del equilibrio en pacientes postictus. Revisión sistemática y metaanálisis / Effectiveness of Wii Fit Balance board in comparison with other interventions for post-stroke balance rehabilitation. Systematic review and meta-analysis

Introducción: La realidad virtual es una herramienta terapéutica en auge dentro del campo de la neurorrehabilitación. Entre los sistemas de realidad virtual no inmersiva más empleados destaca la videoconsola Wii Fit Balance. Objetivo: Revisar la literatura científica publicada en los últimos años acerca de la efectividad de la herramienta Wii Fit Balance para el entrenamiento del equilibrio en pacientes que han sufrido un ictus en comparación con las terapias convencionales y analizar dicha información desde un punto de vista cuantitativo y cualitativo. Sujetos y métodos: Se ha llevado a cabo una búsqueda en las bases de datos PubMed, Lilacs, PEDro, Scopus, Web of Science y Cochrane Library. Los descriptores de búsqueda utilizados fueron «Wii Fit Balance», «Wii», «stroke», «ictus» y «balance». Se analiza la calidad metodológica de los estudios incluidos a través de la escala PEDro. Para las variables que fue posible, se llevó a cabo un metaanálisis. Resultados: Se seleccionaron 16 ensayos clínicos aleatorizados para la revisión sistemática, y seis de ellos se incluyeron en el metaanálisis. Dentro del análisis descriptivo se observó heterogeneidad de resultados. Esta misma situación se confirmó a través de los resultados del metaanálisis, ya que tanto para las variables de equilibrio estático como dinámico analizadas se observaron mejoras intragrupo, pero sin que existieran diferencias significativas entre grupos postintervención. Conclusiones: La plataforma de realidad virtual Wii Fit Balance es una herramienta terapéutica válida que ha demostrado ser al menos igual de efectiva que el entrenamiento convencional del equilibrio en pacientes postictus

Introduction: Virtual reality is a booming therapeutic tool within the eurorehabilitation field. Among the different non-inmersive virtual reality systems, the most outstanding is the platform, Wii Fit Balance. Aim: To review the scientific literature published in recent years about the effectiveness of Wii Fit Balance tool. The use of this platform for balance training in patients who have suffered a stroke compared to conventional therapies is going to be analyzed from a quantitative and qualitative point of view. Subjects and methods: A search of the databases has been carried out: PubMed, Lilacs, PEDro, Scopus, Web of Science and Cochrane Library. Descriptors employed were «Wii Fit Balance», «Wii», «stroke», «ictus» and «balance». Studies were analyzed methodologically by PEDro Scale. For those possible variables a meta-analysis was elaborated. Results: Sixteen randomized clinical trials were selected for the systematic review and six of them were included in the meta-analysis. Results for the descriptive analysis were heterogeneous. This situation is confirmed through the meta-analysis results, because the analyzed variables for static and dynamic balance show intra-group improvement and no significant differences between groups post-intervention. Conclusion: Wii Fit Balance, virtual reality platform, is an available therapeutic tool which has been shown at least as effective as conventional balance training in post-stroke patients

[Effectiveness of Wii Fit Balance board in comparison with other interventions for post-stroke balance rehabilitation. Systematic review and meta-analysis]. / Efectividad de la Wii Fit Balance frente a otras intervenciones para la recuperacion del equilibrio en pacientes postictus. Revision sistematica y metaanalisis.

INTRODUCTION: Virtual reality is a booming therapeutic tool within the neurorehabilitation field. Among the different non-inmersive virtual reality systems, the most outstanding is the platform, Wii Fit Balance. AIM: To review the scientific literature published in recent years about the effectiveness of Wii Fit Balance tool. The use of this platform for balance training in patients who have suffered a stroke compared to conventional therapies is going to be analyzed from a quantitative and qualitative point of view. SUBJECTS AND METHODS: A search of the databases has been carried out: PubMed, Lilacs, PEDro, Scopus, Web of Science and Cochrane Library. Descriptors employed were «Wii Fit Balance¼, «Wii¼, «stroke¼, «ictus¼ and «balance¼. Studies were analyzed methodologically by PEDro Scale. For those possible variables a meta-analysis was elaborated. RESULTS: Sixteen randomized clinical trials were selected for the systematic review and six of them were included in the meta-analysis. Results for the descriptive analysis were heterogeneous. This situation is confirmed through the meta-analysis results, because the analyzed variables for static and dynamic balance show intra-group improvement and no significant differences between groups post-intervention. CONCLUSION: Wii Fit Balance, virtual reality platform, is an available therapeutic tool which has been shown at least as effective as conventional balance training in post-stroke patients.

TITLE: Efectividad de la Wii Fit Balance frente a otras intervenciones para la recuperacion del equilibrio en pacientes postictus. Revision sistematica y metaanalisis.Introduccion. La realidad virtual es una herramienta terapeutica en auge dentro del campo de la neurorrehabilitacion. Entre los sistemas de realidad virtual no inmersiva mas empleados destaca la videoconsola Wii Fit Balance. Objetivo. Revisar la literatura cientifica publicada en los ultimos años acerca de la efectividad de la herramienta Wii Fit Balance para el entrenamiento del equilibrio en pacientes que han sufrido un ictus en comparacion con las terapias convencionales y analizar dicha informacion desde un punto de vista cuantitativo y cualitativo. Sujetos y metodos. Se ha llevado a cabo una busqueda en las bases de datos PubMed, Lilacs, PEDro, Scopus, Web of Science y Cochrane Library. Los descriptores de busqueda utilizados fueron «Wii Fit Balance¼, «Wii¼, «stroke¼, «ictus¼ y «balance¼. Se analiza la calidad metodologica de los estudios incluidos a traves de la escala PEDro. Para las variables que fue posible, se llevo a cabo un metaanalisis. Resultados. Se seleccionaron 16 ensayos clinicos aleatorizados para la revision sistematica, y seis de ellos se incluyeron en el metaanalisis. Dentro del analisis descriptivo se observo heterogeneidad de resultados. Esta misma situacion se confirmo a traves de los resultados del metaanalisis, ya que tanto para las variables de equilibrio estatico como dinamico analizadas se observaron mejoras intragrupo, pero sin que existieran diferencias significativas entre grupos postintervencion. Conclusiones. La plataforma de realidad virtual Wii Fit Balance es una herramienta terapeutica valida que ha demostrado ser al menos igual de efectiva que el entrenamiento convencional del equilibrio en pacientes postictus.

Seminal vesicle fluid increases the efficacy of intravaginal HSV-2 vaccination.

Once considered merely as a vehicle for spermatozoa, it is now clear that seminal plasma (SP) induces a variety of biological actions on the female reproductive tissues able to modulate the immune response against paternal antigens. To our knowledge, the influence of SP on the immune response against sexually transmitted pathogens has not been yet evaluated. We here analyzed whether the seminal vesicle fluid (SVF), which contributes almost 60% of the SP volume in mice, could modulate the immune response against herpes simplex virus type 2 (HSV-2). We found that SVF does not modify the course of primary infection, but markedly improved protection conferred by vaginal vaccination with inactivated HSV-2 against a lethal challenge. This protective effect was shown to be associated to a robust memory immune response mediated by CD4+ and CD8+ T cells in both the lymph nodes draining the vagina and the vaginal mucosa, the site of viral replication. In contrast with the widespread notion that SP acts as an immunosuppressive agent, our results suggest that SVF might improve the female immune response against sexually transmitted pathogens.

Role of Nanotechnology for Enzyme Replacement Therapy in Lysosomal Diseases. A Focus on Gaucher's Disease.

Lysosomal storage diseases (LSDs) comprise a group of rare inherited chronic syndromes that cause deficiency of specific native enzymes within the lysosomes. The macromolecular compounds that are usually catabolized by lysosomal enzymes are accumulated within these organelles, causing progressive damage to tissues, skeleton and organs and, in several cases, the central nervous system (CNS). The damage caused by substrate accumulation finally results in physical deterioration, functional impairment and potential death. Up to date, the most promising therapy for most LSDs is enzyme-replacement therapy (ERT), which provides patients with the corresponding active enzyme. However, these enzymes do not have enough stability in blood, the treatment must be therefore periodically administrated by i.v. infusion under medical supervision, and immunogenicity issues are frequent. In addition, affected areas within the CNS, where the blood-brain barrier (BBB) is a major obstacle, cannot be reached by the enzymes. Nanotechnology can provide useful carriers to successfully protect and preserve enzymes, and transport them through the BBB towards brain locations. Several strategies based on targeting specific receptors on the BBB have led to nanoparticles that successfully carry sensitive molecules to the brain. Then, the main LSDs are described and a thorough review of nanotechnology strategies for brain delivery studied up to date is presented.

Arrays of resonant nanopillars for biochemical sensing.

In this Letter, we demonstrate for the first time the experimental capability for the biochemical sensing of resonant nanopillars (RNPs) arrays. These arrays are fabricated over a glass substrate and are optically integrated from the backside of this substrate. The reflectivity profiles of the RNPs arrays are measured by infiltrating different ethanol fractions in water in order to evaluate the optical response for the different refractive indexes, which range from 1.330 to 1.342. A linear fit of the resonant modes shift is observed as a function of the bulk refractive index of the liquid infiltrated. For the type of transducer analyzed, a relative sensitivity of 10017 cm(-1)/Refractive Index Unit (RIU) is achieved, allowing us to reach a competitive Limit of Detection (LoD) in the order of 1×10(-5) RIU.

Sub-micrometric reflectometry for localized label-free biosensing.

In this work we present an optical technique for characterizing sub-micrometric areas based on reflectivity of the light as a function of angle of incidence for the two pure polarizations s and p, covering a range of angles of incidence from -71.80° to 71.80° with a resolution of 0.1°. Circular areas with a diameter in the order of 600 nm can be characterized, and the spectra for the two polarizations can be obtained with a single measurement. For biosensing purposes, we have fabricated several Bio Photonic Sensing Cells (BICELLs) consisting of interferometers of 1240 nm of SU-8 polymer over silicon. An indirect immunoassay is performed over these BICELLs and compared experimentally with FT-VIS-NIR spectrometry and theoretical calculations. The Limit of Detection (LoD) achieved is comparable with standard high resolution spectrometry, but with the capability of analyzing sub-micrometric domains for immunoassays reactions onto a sensing surface.

Efecto neuroprotector de los cannabinoides en las enfermedades neurodegenerativas / Neuroprotective Effect of Cannabinoids in Neurodegenerative Diseases

Objetivos. Se analiza la situación actual de las investigaciones relacionadas con las sustancias cannabinoides, así como su interacción con el organismo, clasificación, efectos terapéuticos y su uso en las enfermedades neurodegenerativas. Métodos. Se realiza una exhaustiva revisión bibliográfica relacionada con las sustancias cannabinoides y sus derivados sintéticos, haciendo especial hincapié en la forma de interactuar con el organismo y los efectos que provocan dichas interacciones. Concretamente, se estudiarán sus efectos neuroantiinflamatorio y analgésico lo que conlleva al efecto neuroprotector en enfermedades neurodegenerativas tales como Alzheimer, Parkinson, Huntington, esclerosis múltiple y esclerosis lateral amiotrófica. Resultados. Desde hace miles de años la planta Cannabis Sativa ha sido utilizada por muchas culturas con distintos fines, de ocio, textiles, analgésicos, pero no es hasta finales del siglo XX cuando se empieza a incentivar los estudios científicos relacionados con ésta. La planta posee una mezcla de unos 400 componentes, de los cuales 60 pertenecen al grupo de los cannabinoides siendo los principales el cannabinol, cannabidiol y tetrahidrocannabinol. Con el descubrimiento de las sustancias cannabinoides, sus derivados, los receptores que interactúan, se amplían las posibilidades terapéuticas teniendo un especial interés el efecto neuroprotector que estas sustancias contienen. Conclusiones. Se ha demostrado el gran potencial de los cannabinoides como sustancias terapéuticas más allá de su uso analgésico o antiemético, esto es, en enfermedades neurodegenerativas en las que pueden no solo disminuir los síntomas, sino frenar el proceso de la enfermedad. Otra posible aplicación puede ser en el campo oncológico, siendo particularmente intensa la actividad investigadora realizada en los últimos 15 años

Objectives. It is analysed the actual situation of the investigations related to cannabinoids substances, as well as their interaction with the organism, classification, therapeutics effects and their use in neurodegenerative diseases. Methods. This study is based on the review of multiples scientific articles directly related with the cannabinoides Substance and its synthetic derivates, with a special attention on the way the organism interacts and the effects the Substances cause in it. Specifically, the study will get deep into the neuroantiinflammatory and analgesic effects of these substances, related with the neuroprotector effect in neurodegenerative diseases such as Alzheimer, Parkinson, Multiple Sclerosis and Amyotrophic Lateral Sclerosis. Results. From thousands years, the Cannabis Sativa has been used by multiples cultures with different purposes such as joy, textile, analgesics etc. But is not till ends of the XX century when there are diverse scientific studies related with the Cannabis encouraged. The plant has 400 components, 60 of them belong to the cannabinoides group. The main ones are cannabinol, cannabidiol and tetrahidrocannabinol. With the discoverment of the cannabinoids substances, its derivates, and the receptors which interact with them, it is increased the therapeutic possibilities and remarking the neuroprotective effect which these substances contain. Conclusions. It has been demostraded the huge potential of the cannabinoids as therapeutic substances apart from its analgesic and antiemetic uses, that is, neurodegenaritve diseases in which they can not only decrease its symptons but stop disease process. Another possible application could be in the oncologic area, being particularly intense the investigation´s activity realised the last 15 years

In vitro and in vivo evaluation of Δ9-tetrahidrocannabinol/PLGA nanoparticles for cancer chemotherapy.

Nanoplatforms can optimize the efficacy and safety of chemotherapy, and thus cancer therapy. However, new approaches are encouraged in developing new nanomedicines against malignant cells. In this work, a reproducible methodology is described to prepare Δ(9)-tetrahidrocannabinol (Δ(9)-THC)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles against lung cancer. The nanoformulation is further improved by surface functionalization with the biodegradable polymers chitosan and poly(ethylene glycol) (PEG) in order to optimize the biological fate and antitumor effect. Mean nanoparticle size (≈ 290 nm) increased upon coating with PEG, CS, and PEG-CS up to ≈ 590 nm, ≈ 745 nm, and ≈ 790 nm, respectively. Surface electrical charge was controlled by the type of polymeric coating onto the PLGA particles. Drug entrapment efficiencies (≈ 95%) were not affected by any of the polymeric coatings. On the opposite, the characteristic sustained (biphasic) Δ(9)-THC release from the particles can be accelerated or slowed down when using PEG or chitosan, respectively. Blood compatibility studies demonstrated the adequate in vivo safety margin of all of the PLGA-based nanoformulations, while protein adsorption investigations postulated the protective role of PEGylation against opsonization and plasma clearance. Cell viability studies comparing the activity of the nanoformulations against human A-549 and murine LL2 lung adenocarcinoma cells, and human embryo lung fibroblastic MRC-5 cells revealed a statistically significant selective cytotoxic effect toward the lung cancer cell lines. In addition, cytotoxicity assays in A-549 cells demonstrated the more intense anticancer activity of Δ(9)-THC-loaded PEGylated PLGA nanoparticles. These promising results were confirmed by in vivo studies in LL2 lung tumor-bearing immunocompetent C57BL/6 mice.

Enhanced cellular uptake and biodistribution of a synthetic cannabinoid loaded in surface-modified poly(lactic-co-glycolic acid) nanoparticles.

This article aimed to produce, characterize and evaluate different surface-modified naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (CB13) loaded poly(lactic-co-glycolic acid) nanoparticles in order to improve their oral absorption and in vivo biodistribution. Plain and surface-modified PLGA nanoparticles were successfully prepared using a nanoprecipitation method. Chitosan, Eudragit RS, lecithin and vitamin E were used as surface modifying agents. The NPs were evaluated in terms of mean diameter and size distribution, zeta potential, morphology, drug loading, drug release profiles, mucoadhesive properties, in vitro cell viability and uptake and in vivo biodistribution. Mean particle size distributions in the range of 253-344 nm, spherical shape and controlled zeta potential values were observed depending on the additive employed. High values of entrapment efficiency were obtained for all the formulations. Lecithin and vitamin E modified particles showed higher release rates when compared to the rest of formulations. A clear improvement in ex vivo mucoadhesion properties was observed in the case of chitosan- and Eudragit RS-modified nanoparticles. Chitosan-poly(lactic-co-glycolic acid) nanoparticles showed the highest uptake values on Caco-2 cells. Biodistribution assays proved that most of the particles were accumulated in liver and spleen. An important goal has been achieved in this investigation: CB13, a highly lipophilic drug with low water solubility, can reach the interior of cells more efficiently when it is included in these surface-modified polymeric carriers.

Biocompatible gemcitabine-based nanomedicine engineered by Flow Focusing for efficient antitumor activity.

We investigated the incorporation of gemcitabine into a colloidal carrier based on the biodegradable and biocompatible poly(d,l-lactide-co-glycolide) (PLGA) to optimize its anticancer activity. Two synthesis techniques (double emulsion/solvent evaporation, and Flow Focusing) were compared in terms of particle geometry, electrophoretic properties (surface charge), gemcitabine vehiculization capabilities (drug loading and release), blood compatibility, and in vitro antitumor activity. To the best of our knowledge, the second formulation methodology (Flow Focusing) has never been applied to the synthesis of gemcitabine-loaded PLGA particles. With the aim of achieving the finest (nano)formulation, experimental parameters associated to these preparation procedures were analyzed. The electrokinetics of the particles suggested that the chemotherapy agent was incorporated into the polymeric matrix. Blood compatibility was demonstrated in vitro. Flow Focusing led to a more appropriate geometry, higher gemcitabine loading and a sustained release profile. In addition, the cytotoxicity of gemcitabine-loaded particles prepared by Flow Focusing was tested in MCF-7 human breast adenocarcinoma cells, showing significantly greater antitumor activity compared to the free drug and to the gemcitabine-loaded particles synthesized by double emulsion/solvent evaporation. Thus, it has been identified the more adequate formulation conditions in the engineering of gemcitabine-loaded PLGA nanoparticles for the effective treatment of tumours.

Functional PLGA NPs for oral drug delivery: recent strategies and developments.

This article presents the potential of PLGA nanoparticles for the oral administration of drugs. Different strategies are used to improve oral absorption of these nanoparticles. These strategies are based on modification of nanoparticle surface properties. They can be achieved either by coating the nanoparticle surface with stabilizing hydrophilic bioadhesive polymers or surfactants, or by incorporating biodegradable copolymers containing a hydrophilic moiety. Some substances such as chitosan, vitamin E, methacrylates, lectins, lecithins, bile salts and RGD molecules are employed for this purpose. Of especial interest are nanoparticles production methods and, in order to improve oral bioavailability, the mechanism of each additive.

Conductismo radical y práctica investigadora: ¿por qué es skinneriano el Análisis Experimental del Comportamiento? / No disponible

El presente trabajo se sitúa en la perspectiva de analizar los procesos implicados en el desarrollo de la actividad científica, más que en el estudio de las características formales de los productos científicos. Dicho abordaje se realiza desde la teoría skinneriana de la conducta (condicionamiento operante). Así, se estudian tres momentos de la actividad científica: a) la selección del dato científico como conducta verbal discriminativa, b) el establecimiento de relaciones entre variables entendido como detección de relaciones de contingencia entre eventos y, c) la derivación de nuevos conceptos como u n caso de conducta gobernada por reglas. Por otra parte, las características metodológicas implícitas en la práctica del Análisis Experimental de la Conducta (AEC) se confrontan con las ideas propuestas anteriormente. Finalmente, se concluye que dichas características del AEC son altamente consistentes con el análisis de la actividad científica como conducta operante, dándose cuenta del alto grado de coherencia alcanzado por los conductistas radicales respecto a, por un lado, los aspectos formales de su práctica investigadora (AEC) y, por otro, al contenido de sus productos teóricos (condicionamiento operante) (AU)

The core of this paper lies more within the perspective of analyzing the processes involved in the development of scientific activity, than in the study of formal characteristics of scientific outcomes. The aforementioned approach is carried out from the Skinnerian theory of behaviour (operant conditioning). Thus, three moments of scientific activity are examined: a) the selection of scientific datum as discriminative verbal behaviour, b) the establishment of relations between variables understood as the detection of contingency relations between events and, c) the derivation of new concepts as a case of rule-governed behaviour. Moreover, the methodological characteristics implicit in the practice of The Experimental Analysis of Behaviour (TEAB) are contrasted with the previously proposed ideas. Finally, the paper concludes that the aforementioned characteristics of the TEAB are highly consistent with the analysis of scientific activity as operant behaviour, indicating the high level of coherence reached by the radical behaviorists in relation to, on the one hand, the formal aspects of their investigative practice (TEAB) and, on the other hand, the contents of their theoretical productions (operant conditioning) (AU)

La Ley del Efecto y el origen de la conducta / No disponible

El Análisis Experimental de la Conducta (AEC) puede considerarse uno de los herederos naturales de la tradición iniciada por Thorndike en 1898. Aspectos recogidos en la Ley del Efecto, tales como la selección y el mantenimiento de la conducta, han sido ampliamente abordados por los analistas de la conducta, convirtiéndose en un campo tradicional y fundamental de estudio del AEC. Sin embargo, y por contraste, con frecuencia suele achacársele al AEC el escaso tratamiento -o incluso el rechazo y abandono- dedicado al problema del origen, la novedad y la variación conductual. En este trabajo se revisan algunas aproximaciones teóricas que, dentro del AEC, se han ocupado de esa parte supuestamente olvidada de la Ley del Efecto, así como los principios propuestos por dichas teorías para dar cuenta de la novedad y variación conductual. Tal revisión abarca desde los iniciales planteamientos de Thorndike y de Skinner acerca del origen de la conducta, hasta las nuevas aproximaciones seleccionistas referidas a la conducta novedosa y compleja (AU)

Experimental Analysis of Behavior (EAB) can be considered one of the natural inheritors of the tradition initiated by Thorndike in 1898. Aspects reflected in the Law of Effect, such as behaviour selection and maintenance, have been greatly taken into consideration by behaviour analysts, thus becoming a tradicional and fundamental field of study for EAB. However, and in contrast with this, EAB is frequently accused of rarely considering - or even rejecting and abandoning - the problems of the origin, novelty and variation in behaviour. In this anicle we review sorne theoretical approaches that, within EAB, have studied this supposedly abandoned aspect of the Law of Effect. Principies proposed by these theories in order to explain behavioural novelty and variation are also presented. The revision begins with Thorndike and Skinner's initial proposals about the origin of behaviour, moving on to to the most recent selection approaches refered to novel and complex behaviour (AU)