Type I IFNs at the interface between cutaneous immunity and epidermal remodeling.

Type I IFNs are key cytokines in antiviral host defense. Preferentially expressed by plasmacytoid dendritic cells, type I IFNs are induced by viral infection and in common skin wounds. In this issue, Tohyama et al. identify a new link between type I IFNs and epidermal remodeling, by showing that type I IFNs specifically upregulate IL-22R expression on keratinocytes and, thereby, IL-22-mediated Stat3 phosphorylation in keratinocytes. The findings suggest that type I IFNs play dual roles in human skin: first, they induce immune activation with the induction of IL-22-producing T cells; second, they provide the interface between immune activation and epidermal remodeling by increasing keratinocyte responsiveness to IL-22.

Aspectes sanitaris dels arxius parroquials de Sant Feliu de Cabrera, Sant Genís de Vilassar, Sant Joan de Vilassar i de la Creu de Cabrils en els segles XVI, XVII i XVIII

L'autor exposa aquí el seu treball fruit de l'estudi dels arxius parroquials de dites localitats del Maresme. En concret, el seu estudi està fet sobre els llibres de Naixements, Òbits i Matrimonis. D'aquí n'extreu la informació de caràcter sanitari però també informació sobre la societat de l'època, la demografia i dades estadístiques.

Cost-utility analysis of a three-month exercise programme vs usual care following multidisciplinary rehabilitation for chronic low back pain.

OBJECTIVE: To assess the cost-utility of an exercise programme vs usual care after functional multidisciplinary rehabilitation in patients with chronic low back pain. DESIGN: Cost-utility analysis alongside a randomized controlled trial. SUBJECTS/PATIENTS: A total of 105 patients with chronic low back pain. METHODS: Chronic low back pain patients completing a 3-week functional multidisciplinary rehabilitation were randomized to either a 3-month exercise programme (n = 56) or usual care (n = 49). The exercise programme consisted of 24 training sessions during 12 weeks. At the end of functional multidisciplinary rehabilitation and at 1-year follow-up quality of life was measured with the SF-36 questionnaire, converted into utilities and transformed into quality--adjusted life years. Direct and indirect monthly costs were measured using cost diaries. The incremental cost-effectiveness ratio was calculated as the incremental cost of the exercise programme divided by the difference in quality-adjusted life years between both groups. RESULTS: Quality of life improved significantly at 1-year follow-up in both groups. Similarly, both groups significantly reduced total monthly costs over time. No significant difference was observed between groups. The incremental cost-effectiveness ratio was 79,270 euros. CONCLUSION: Adding an exercise programme after functional multidisciplinary rehabilitation compared with usual care does not offer significant long-term benefits in quality of life and direct and indirect costs.

A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes.

The Nrf2 transcription factor controls the expression of genes involved in the antioxidant defense system. Here, we identified Nrf2 as a novel regulator of desmosomes in the epidermis through the regulation of microRNAs. On Nrf2 activation, expression of miR-29a and miR-29b increases in cultured human keratinocytes and in mouse epidermis. Chromatin immunoprecipitation identified the Mir29ab1 and Mir29b2c genes as direct Nrf2 targets in keratinocytes. While binding of Nrf2 to the Mir29ab1 gene activates expression of miR-29a and -b, the Mir29b2c gene is silenced by DNA methylation. We identified desmocollin-2 (Dsc2) as a major target of Nrf2-induced miR-29s. This is functionally important, since Nrf2 activation in keratinocytes of transgenic mice causes structural alterations of epidermal desmosomes. Furthermore, the overexpression of miR-29a/b or knockdown of Dsc2 impairs the formation of hyper-adhesive desmosomes in keratinocytes, whereas Dsc2 overexpression has the opposite effect. These results demonstrate that a novel Nrf2-miR-29-Dsc2 axis controls desmosome function and cutaneous homeostasis.

Sensing of mammalian IL-17A regulates fungal adaptation and virulence.

Infections by opportunistic fungi have traditionally been viewed as the gross result of a pathogenic automatism, which makes a weakened host more vulnerable to microbial insults. However, fungal sensing of a host's immune environment might render this process more elaborate than previously appreciated. Here we show that interleukin (IL)-17A binds fungal cells, thus tackling both sides of the host-pathogen interaction in experimental settings of host colonization and/or chronic infection. Global transcriptional profiling reveals that IL-17A induces artificial nutrient starvation conditions in Candida albicans, resulting in a downregulation of the target of rapamycin signalling pathway and in an increase in autophagic responses and intracellular cAMP. The augmented adhesion and filamentous growth, also observed with Aspergillus fumigatus, eventually translates into enhanced biofilm formation and resistance to local antifungal defenses. This might exemplify a mechanism whereby fungi have evolved a means of sensing host immunity to ensure their own persistence in an immunologically dynamic environment.

Naturaleza humana y lenguaje en el pensamiento de Descartes

Frente a interpretaciones estandarizadas, el presente trabajo pretende poner de relieve elmomento de trascendencia del cogito, acudiendo al concepto de 'naturaleza' y a la noción de 'lenguaje'. Destácase la importancia del concepto de 'encarnación' como idea clave para la constitución del 'hombre verdadero', así como su dimensión intersubjetiva.

La inversión ontológica de la crítica en Spinoza

El presente trabajo pretende poner de relieve los rasgos esenciales que configuran la sistematización spinozista del racionalismo heredado de Descartes, analizando las diferencias abismales que separan la actitud subjetual y antropológica de la crítica cartesiana, defensora de la categoría de "individualidad", frente a la de "totalidad" preconizada por Spinoza. La tarea se lleva a cabo, concretamente, contraponiendo las nociones de "método","razón" e "ideas", tal como se entienden en uno y otro sistema.

Subjetividad humana y "error" en la filosofía cartesiana

El presente trabajo, continuando la línea investigadora acerca de las nociones derazón, conciencia y subjetividad en Descartes, tal como se ha defendido en otros artículos ya publicados, aporta un nuevo argumento a una línea de trabajo previamente iniciada, poniendo de relieve que el problema gnoseológico del error viene condicionado por la misma noción cartesiana de racionalidad, y que ésta dista mucho de lo que tradicionalmente se ha entendido como una racionalidad abstracta y formal, libre de los imperativos humanos. Por otro lado, y a la inversa, también se intenta mostrar como el hecho del error contribuye, cartesianamente hablando, a definir un modelo de racionalidad profundamentehumanizada. El artículo, tras una introducción, se propone analizar las relaciones entre los conceptos básicos de racionalidad, dogma, y naturaleza, lo que permitirá a continuación dejar constancia de la copertenencia entre racionalidad y error, para acabar viendo como la libertad humana es la vez, y para ambos, su fundamento último.