Limited Activity Of Miltefosine In Murine Models Of Cryptococcal Meningoencephalitis And Disseminated Cryptococcosis

Miltefosine is an alkyl phosphocholine with good oral bioavailability and in vitro activity against Cryptococcus species that has gained interest as an additional agent for cryptococcal infections. Our objective was to further evaluate the in vivo efficacy of miltefosine in experimental in vivo models of cryptococcal meningoencephalitis and disseminated cryptococcosis. Mice were infected intracranially or intravenously with either C. neoformans USC1597 or H99. Miltefosine treatment (1.8 to 45 mg/kg of body weight orally once daily) began at either 1 h or 1 day postinoculation. Fluconazole (10 mg/kg orally twice daily) or amphotericin B deoxycholate (3 mg/kg intraperitoneally once daily) served as positive controls. In our standard models, miltefosine did not result in significant improvements in survival or reductions in fungal burden against either C. neoformans isolate. There was a trend toward improved survival with miltefosine at 7.2 mg/kg against disseminated cryptococcosis with the H99 strain but only at a low infecting inoculum. In contrast, both fluconazole and amphotericin B significantly improved survival in mice with cryptococcal meningoencephalitis and disseminated cryptococcosis due to USC1597. Amphotericin B also improved survival against both cryptococcal infections caused by H99. Combination therapy with miltefosine demonstrated neither synergy nor antagonism in both models. These results demonstrate limited efficacy of miltefosine and suggest caution with the potential use of this agent for the treatment of C. neoformans infections.Pharmac

Linearizing Control Based on Adaptive Observer for Anaerobic Continuous Sulphate Reducing Bioreactors with Unknown Kinetics

Anaerobic reactors are a typical example of processes that exhibit non-linear behavior and, also time varying parameters; hence their operation is known to be difficult to model and control. In contrast to modeling approaches, in practice linear controllers are widely employed for industrial processes because of their easy implementation and manipulation by plant operators; nevertheless linear approaches are not robust when the operating conditions change suddenly and/or strong disturbances are present. In order to introduce robust controllers to these processes, this paper addresses the tracking problem for the substrate (sulphate) control in a class of continuous bioreactors. An experimentally corroborated bioreactor model serves as benchmark problem for advanced non-linear analysis and control techniques; taking into account system non-linearities, stability and performance objectives over large operating regions. It is considered that, as it is common in practice, the rate of substrate consumption exhibits uncertainty. Results show that the proposed controller exhibits better dynamic performance than a classical Proportional-Integral control tuned using the methodology suggested by Internal Model Control

Efecto del procesamiento sobre las propiedades antioxidantes de dos tipos comerciales de cacahuete cultivados en México

The effect of roasting, frying, microwave heating, and germination on the antioxidant properties, total phenolics and flavonoids content of two types of peanuts (Valencia and Virginia) grown in Mexico was investigated. The thermal treatments affected the phenolic content and the antioxidant capacity of the two varieties of peanuts differently (by ABTS, DPPH, FRAP and iron chelating activity methods). Germination was the best method to increase the antioxidant activity (up to 157% increase in the Virginia variety) and the contents of compounds with nutraceutical potential in the peanuts (up to 59% increase in total phenolics in the Valencia variety and 700% increase in total flavonoids in the Virginia variety). Germinated peanuts could be used as raw material for the production of functional foods.Se investigó el efecto del tostado, fritura, tostado en microondas y la germinación, sobre las propiedades antioxidantes, el contenido de compuestos fenólicos totales y flavonoides de dos tipos de cacahuete cultivados en México. Los tratamientos térmicos afectaron de forma diferente al contenido de fenólicos y la capacidad antioxidante de las dos variedades de cacahuete (por los métodos de ABTS, DPPH, FRAP y actividad quelante de hierro). La germinación fue el mejor método para aumentar la actividad antioxidante (hasta en 157% en la variedad Virginia) y el contenido de compuestos con potencial nutracéutico de los cacahuates (hasta en 59% de aumento en los fenólicos totales de la variedad Valencia y 700% de aumento en los flavonoides totales de la variedad Virginia). Los cacahuetes germinados podrían usarse como materia prima para la producción de alimentos funcionales

Structural interaction between bone and implants due to arthroplasty of the first metatarsophalangeal joint

Background: Currently, the metatarsophalangeal joint replacement through a restorative arthroplasty, where implants are used, is a viable invasive surgical medical procedure in the treatment of severe cases of osteoarthritis in this joint, better known as hallux rigidus. However, few things are known about the postoperative complications that implants can cause on the joint, like Swanson and Tornier implants.Research in this field can provide a valuable information that would help the specialist surgeon in the decision-making during the selection of the more suitable joint implant in each patient, as well as the redesign of the devices, to make them more efficient, durable and biocompatible with the human body. Methods: The aim of this work is to perform a structural biomechanical analysis of a restorative arthroplasty of the first metatarsophalangeal joint, and to analyze the interaction between bone and medical grade silicone implants. For that, a simulation of a foot with Swanson and Tornier joint implants were performed to evaluate the stress/strain distribution during a critical stage (toe-off). Results and conclusions: Principal stresses obtained for the first metatarsal with both implants suggest that failure is induced in this bone because, values exceed (up to 136.84% for Swanson model) the tensile strength reported for phalange trabecular bone, which may be related to osteolysis. Stress and strain values obtained in this work suggest that arthroplasty surgery with Swanson implant is more likely to cause postoperative complications versus Tornier implant

Emotional cues enhance the attentional effects on spatial and temporal resolution

In the present study, we demonstrated that the emotional significance of a spatial cue enhances the effect of covert attention on spatial and temporal resolution (i.e., our ability to discriminate small spatial details and fast temporal flicker). Our results indicated that fearful face cues, as compared with neutral face cues, enhanced the attentional benefits in spatial resolution but also enhanced the attentional deficits in temporal resolution. Furthermore, we observed that the overall magnitudes of individuals’ attentional effects correlated strongly with the magnitude of the emotion × attention interaction effect. Combined, these findings provide strong support for the idea that emotion enhances the strength of a cue’s attentional response

Beyond attentional bias: A perceptual bias in a dot-probe task

Previous dot-probe studies indicate that threat-related face cues induce a bias in spatial attention. Independently of spatial attention, a recent psychophysical study suggests that a bilateral fearful face cue improves low spatial-frequency perception (LSF) and impairs high spatial-frequency perception (HSF). Here, we combine these separate lines of research within a single dot-probe paradigm. We found that a bilateral fearful face cue, compared with a bilateral neutral face cue, speeded up responses to LSF targets and slowed down responses to HSF targets. This finding is important, as it shows that emotional cues in dot-probe tasks not only bias where information is preferentially processed (i.e., an attentional bias in spatial location), but also bias what type of information is preferentially processed (i.e., a perceptual bias in spatial frequency)

Animal assisted interventions in neurorehabilitation: a review of the most recent literature

Introduction: While conventional wisdom has always affirmed the value of animals in promoting human health and well-being, only recently has their therapeutic role in medicine become a topic for dedicated research. Animal assisted interventions (AAI) can be classified as animal-assisted activities, animal-assisted therapy, and service animal programmes. Objective: The aim of this review is to analyse original papers addressing AAI and neurological diseases and published in the most influential medical journals between 2001 and 2012, and discuss their findings in the light of what may be of interest in the field of neurology. Discussion: We selected a total of 23 articles on neurorehabilitation in cerebral palsy, pervasive developmental disorders, multiple sclerosis, spinal cord injury, stroke, and mental disorders. The main therapeutic results were improvement on the Gross Motor Function Classification Scale and in upper limb dexterity (cerebral palsy); improvement in social functioning and interaction; reductions in stress, anxiety, and loneliness (pervasive developmental disorders and mental disorders); and decreased spasticity with improved balance (multiple sclerosis, spinal cord injury, stroke). Conclusion: These interventions, performed with highly specialised animals in very specific neurological populations, deliver an increasing body of scientific evidence suggesting that they are an effective complement to other existing therapies. In these diseases, further high-quality studies are warranted in order to define the most appropriate programmes for therapy. Resumen: Introducción: Aunque siempre se ha afirmado el valor de los animales en la promoción del bienestar y la salud del ser humano, solo recientemente su papel terapéutico en medicina se ha convertido en el foco de investigación especializada. Las intervenciones asistidas por animales pueden dividirse en actividades asistidas por animales, terapia asistida por animales y programas de animales de servicio. Objetivo: El objetivo de esta revisión es analizar las publicaciones realizadas entre 2001 y 2012 en las revistas médicas más importantes, relacionadas con el campo de la rehabilitación de las enfermedades neurológicas, y discutir estos hallazgos a la luz de lo que pueda ser de interés para la neurología. Discusión: Se seleccionaron un total de 23 artículos de intervenciones en el campo de la parálisis cerebral infantil, trastornos generalizados del desarrollo, esclerosis múltiple, lesión medular, accidente cerebrovascular y trastornos mentales. Los principales resultados terapéuticos fueron: mejoría en la Gross Motor Function y en el manejo del miembro superior (parálisis cerebral infantil); aumento de la socialización y el contacto con el medio ambiente, reducción del estrés y la ansiedad y sentimientos de soledad (trastornos generalizados del desarrollo y trastornos mentales); disminución de la espasticidad y mejoría del equilibrio (esclerosis múltiple, lesión medular, accidente cerebrovascular). Conclusiones: Estas intervenciones asistidas con un tipo de animales muy limitado utilizadas en grupos clínicos neurológicos muy específicos muestran cada vez más pruebas científicas, como método complementario a otras terapias ya existentes. En estas enfermedades, se necesitan más estudios de alta calidad metodológica que permitan definir los programas más apropiados para la aplicación terapéutica. Keywords: Animal assisted therapy, Service animals, Nervous system diseases, Palabras clave: Terapia asistida por animales, Animales de servicio, Enfermedades del sistema nervios