Infliximab microencapsulation: an innovative approach for intra-articular administration of biologics in the management of rheumatoid arthritis-in vitro evaluation

Microencapsulation of the therapeutical monoclonal antibody infliximab (INF) was investigated as an innovative approach to improve its stability and to achieve formulations with convenient features for intra-articular administration. Ultrasonic atomization (UA), a novel alternative to microencapsulate labile drugs, was compared with the conventional emulsion/evaporation method (Em/Ev) using biodegradable polymers, specifically Polyactive® 1000PEOT70PBT30 [poly(ethylene-oxide-terephthalate)/poly(butylene-terephthalate); PEOT-PBT] and its polymeric blends with poly-(D, L-lactide-co-glycolide) (PLGA) RG502 and RG503 (PEOT-PBT:PLGA; 65:35). Six different formulations of spherical core-shell microcapsules were successfully developed and characterized. The UA method achieved a significantly higher encapsulation efficiency (69.7-80.25%) than Em/Ev (17.3-23.0%). Mean particle size, strongly determined by the microencapsulation method and to a lesser extent by polymeric composition, ranged from 26.6 to 49.9 µm for UA and 1.5-2.1 µm for Em/Ev. All formulations demonstrated sustained INF release in vitro for up to 24 days, with release rates modulated by polymeric composition and microencapsulation technique. Both methods preserved INF biological activity, with microencapsulated INF showing higher efficacy than commercial formulations at comparable doses regarding bioactive tumor necrosis factor-alpha (TNF-α) neutralization according to WEHI-13VAR bioassay. Microparticles' biocompatibility and extensive internalization by THP-1-derived macrophages was demonstrated. Furthermore, high in vitro anti-inflammatory activity was achieved after treatment of THP-1 cells with INF-loaded microcapsules, significatively reducing in vitro production of TNF-α and interleucine-6 (Il-6)Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Iván Lamela-Gómez received funding from the “Axudas á etapa predoutoral da Xunta de Galicia, cofinanciadas polo programa operativo FSE Galicia 2014–2020” predoctoral grant program. Consellería de Cultura, Educación e ordenación universitaria, Xunta de Galicia, Spain. This research was partially funded by Consellería de Cultura, Educación e ordenación universitaria, Xunta de Galicia, Spain. Axudas para a consolidación e estructuración de unidades de investigación competitivas Modalidad A: Grupos de Referencia Competitiva (ED341C 2017/13). This research was also partially funded by the Fundação para a Ciência e a Tecnologia (FCT), Portugal (UID/DTP/04138/2019 and UIDB/04138/2020 to iMed.ULisboa), and principal investigator grants CEECIND/03143/2017 (L. M. Gonçalves)S

Comparação do nível da presença do rasgo bs entre motoristas de motocicletas infratores e não infratores às normas de trânsito

Objective: To establish the differences in the level of presence of the trait between two groups of motorcyclists in the municipality of Piedecuesta. Method: BS Zuckerman Scale to two groups of motorcyclists, one of offenders and other of non-offenders of traffic rules, was applied. Descriptive statistical analysis using Student t was performed. Results: Significant differences were found in the subscales of thrill seeking-adventure, disinhibition and boredom-impulsivity, which means that the offending riders have a higher score on the three subscales compared to non-offenders. However, in the total score, no significant differences were found. Conclusions: The components that make the difference between both groups relate to the need to seek emotions, disinhibition and impulsivity versus the other part of the BS, search of experiences. Overall, the results are similar to those presented by literature from other countries and contexts in terms of age and gender differences.Objetivo: Establecer las diferencias en el nivel de presencia del rasgo entre dos grupos de conductores de motocicletas en el Municipio de Piedecuesta. Método: Se aplicó la Escala BS de Zuckerman a dos grupos de conductores de motocicletas, uno infractor y otro no infractor de las normas de tránsito. Se realizó el análisis estadístico descriptivo mediante la T de Student. Resultados: Se encontraron diferencias significativas en las subescalas búsqueda de emociones-aventura, desinhibición y aburrimiento-impulsividad, lo que significa que los conductores infractores registran un puntaje más alto en estas tres subescalas frente a los no infractores; en cambio, en la puntuación total no se encontraron diferencias significativas. Conclusiones: Los componentes que hacen la diferencia entre los dos grupos estudiados se relacionan con la necesidad de buscar emociones, desinhibición e impulsividad versus el otro componente de la BS, búsqueda de experiencias. En general, los resultados obtenidos son similares a lo que presenta la literatura proveniente de otros países y contextos en cuanto a las diferencias por edad y género.Objetivo: Estabelecer as diferenças no nível de presença do rasgo entre dois grupos de motoristas de motocicletas no Município de Piedecuesta. Método: Aplicou-se a Escala BS de Zuckerman a dois grupos de motoristas de motocicletas, uno infrator e outro não infrator das normas de trânsito. Realizou-se a análise estatística descritivo mediante o T de Student. Resultados: Encontraram-se diferenças significativas nas subescalas busca de emoções-aventura, desinibição e aborrecimento-impulsividade, o que significa que os condutores infratores registram uma pontuação mais alta nestas três subescalas frente aos não infratores; em mudança, na pontuação total não se encontraram diferenças significativas. Conclusões: Os componentes que fazem a diferença entre os dois grupos estudados se relacionam com a necessidade de procurar emoções, desinibição e impulsividade contra o outro componente da BS, busca de experiências. Em general, os resultados obtidos são similares ao que apresenta a literatura proveniente de outros países e contextos quanto às diferenças por idade e gênero

Enfoque de la política fiscal en Venezuela en el período 2000-2016

The investigation analyzes the approach of the fiscal policy in Venezuela for the period 2000-2016, determining the effectiveness of the same in the management of the fiscal deficit, tax base and fiscal income, based on data published by the BCV (Central Bank of Venezuela). Venezuela) (2016) and ONAPRE (National Budget Office) (2016). The study is based on the theory of the LafferCurve (1986). The research is analytical with a documentary design. The results corroborate that the increase in the tax base increases the fiscal deficit, and decreases the fiscal income in real terms.La investigación analiza el enfoque de la política fiscal en Venezuela para el período 2000-2016, determinando la efectividad de la misma en cuanto al manejo del déficit fiscal, base impositiva e ingreso fiscal, con base a datos publicados por el BCV (Banco Central de Venezuela) (2016) y ONAPRE (Oficina Nacional de Presupuesto) (2016). El estudio se basa en la teoría de la Curva de Laffer(1986). La investigación es analítica con un diseñodocumental. Los resultados corroboran queel aumento de la base impositiva acrecienta el déficit fiscal, y disminuye el ingreso fiscal en términos reales

Intravitreal implants manufactured by supercritical foaming for treating retinal diseases

Chronic retinal diseases, such as age-related macular degeneration (AMD), are a major cause of global visual impairment. However, current treatment methods involving repetitive intravitreal injections pose financial and health burdens for patients. The development of controlled drug release systems, particularly for biological drugs, is still an unmet need in prolonging drug release within the vitreous chamber. To address this, green supercritical carbon dioxide (scCO2) foaming technology was employed to manufacture porous poly(lactic-co-glycolic acid) (PLGA)-based intravitreal implants loaded with dexamethasone. The desired implant dimensions were achieved through 3D printing of customised moulds. By varying the depressurisation rates during the foaming process, implants with different porosities and dexamethasone release rates were successfully obtained. These implants demonstrated controlled drug release for up to four months, surpassing the performance of previously developed implants. In view of the positive results obtained, a pilot study was conducted using the monoclonal antibody bevacizumab to explore the feasibility of this technology for preparing intraocular implants loaded with biologic drug molecules. Overall, this study presents a greener and more sustainable alternative to conventional implant manufacturing techniques, particularly suited for drugs that are susceptible to degradation under harsh conditions

Multi-channel Transformers for Multi-articulatory Sign Language Translation

Sign languages use multiple asynchronous information channels (articulators), not just the hands but also the face and body, which computational approaches often ignore. In this paper we tackle the multi-articulatory sign language translation task and propose a novel multi-channel transformer architecture. The proposed architecture allows both the inter and intra contextual relationships between different sign articulators to be modelled within the transformer network itself, while also maintaining channel specific information. We evaluate our approach on the RWTH-PHOENIX-Weather-2014T dataset and report competitive translation performance. Importantly, we overcome the reliance on gloss annotations which underpin other state-of-the-art approaches, thereby removing future need for expensive curated datasets

Aproximación a la estima de la biomasa y producción primaria neta aéreas en una estación de la Laurisilva tinerfeña

Se realiza una primera aproximación a la estima de algunos parámetros tróficos en una estación de laurisilva en Tenerife. Los resultados son congruentes con los estimados para bosques similares en otras partes del mundo. La biomasa aérea se estimó a través de la técnica del análisis dimensional, mientras que la evaluación de la Producción Primaria Neta (pPN) se basó en el seguimiento de la caída de hojarasca durante un aIIO mediante bandej as. Se discute la validez de esta última técnica para determinar la PPN de los ecosistemas maduros.A first approach to the assesment of some trophics parameters of a laurel forest station in Tenerife is given. The results are congruent with those to be expected for similar forests of the world. The aereal biomass was calculated through the technique of dimensional analysis, while the evaluation ofNet Primary Production (NPP) was based in the study of the litter fall, using litter bags, during one year. The validity ofthis last technique to evaluate the NPP of mature ecosystems is discussed

Evaluación física y clínica de sementales bovinos en dos municipios de la costa chica de Guerrero, México

Objective: To evaluate the reproductive physical characteristics and general health of stallions in two municipalities of Costa Chica of Guerrero, Mexico. Design/methodology/approach: The study was carried out in the municipalities of Ometepec and Cuajinicuilapa. Thirty bulls between 2 and 10 years of age were evaluated. In the physical reproductive and clinical examination were performed by direct observation, using ultrasound to evaluate attached reproductive glands and testicular parenchyma. Blood samples were taken to determine the blood profile. Descriptive statistics was used to present the results. Results: The 86% of the bulls had adequate legs and feet as well as preputial length. Scrotal circumference was according to the age and breed of the animals. Testicular defects were showed for 30% of the bulls, the most common was hypoplasia and unilateral tumors of testicular parenchyma and epididymis, as well as calcifications of the testicular parenchyma. The 93% of the bulls had normal accessory genital glands. Clinically 24% of the bulls with signs suggestive of anaplasmosis were found. The 76% of the bulls, apparently healthy, presented monocytosis, thrombocytopenia and anemia. Limitations on study/implications: the lack of knowledge of the producers about the need for a comprehensive evaluation of the bulls allows them to suffer from diseases without receiving any type of treatment, decreasing their reproductive efficiency. Findings/conclusions: Most of the bulls evaluated had the minimum physical characteristics required, although the presence of anemia and respiratory diseases may have an indirect negative impact on the reproductive efficiency of the bulls.Objetivo: Evaluar las características físicas reproductivas y la salud general de los sementales en dos municipios de Costa Chica de Guerrero, México. Diseño/metodología/aproximación: Se evaluaron reproductiva y clínicamente 30 sementales, de entre 2 y 10 años. El examen reproductivo, se realizó por observación directa, empleándose ecografía para evaluar glándulas reproductivas anexas y el parénquima testicular. La evaluación clínica se realizó por medio del examen físico y perfil hemático. Se empleó estadística descriptiva para la presentación de los resultados. Resultados: El 86% de los sementales tuvieron aplomos y largo prepucial adecuado, así como circunferencia escrotal acorde a la edad y raza de los animales. El 30% de los sementales presentaron defectos testiculares, siendo los más comunes, hipoplasia y tumores unilaterales de parénquima testicular y epidídimos, así como calcificaciones del parénquima testicular. El 93% de las glándulas anexas fueron normales. Clínicamente se encontró un 24% de los sementales con signos sugerentes a anaplasmosis. El 76% de los toros, aparentemente sanos, presentaron monocitosis, trombocitopenia y anemia. Limitaciones del estudio/implicaciones: El desconocimiento de los productores sobre la necesidad de una evaluación integral de los sementales permite que éstos padezcan enfermedades que no son tratadas, disminuyendo su eficiencia reproductiva. Hallazgos/conclusiones: La mayoría de los sementales evaluados tuvieron las características físicas mínimas requeridas, aunque la presencia de anemia y enfermedades respiratorias pueden tener incidencia negativa indirecta sobre la eficiencia reproductiva de los sementales