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SUMMARY Despite the well-accepted view that chronic inflammation contributes to the pathogenesis of Duchenne muscular dystrophy (DMD), the function and regulation of eosinophils remain an unclear facet of type II innate immunity in dystrophic muscle. We report the observation that group 2 innate lymphoid cells (ILC2s) are present in skeletal muscle and are the principal regulators of muscle eosinophils during muscular dystrophy. Eosinophils were elevated in DMD patients and dystrophic mice along with interleukin (IL)-5, a major eosinophil survival factor that was predominantly expressed by muscle ILC2s. We also find that IL-33 was upregulated in dystrophic muscle and was predominantly produced by fibrogenic/adipogenic progenitors (FAPs). Exogenous IL-33 and IL-2 complex (IL-2c) expanded muscle ILC2s and eosinophils, decreased the cross-sectional area (CSA) of regenerating myofibers, and increased the expression of genes associated with muscle fibrosis. The deletion of ILC2s in dystrophic mice mitigated muscle eosinophilia and impaired the induction of IL-5 and fibrosis-associated genes. Our findings highlight a FAP/ILC2/eosinophil axis that promotes type II innate immunity, which influences the balance between regenerative and fibrotic responses during muscular dystrophy., In brief Immune cells that comprise type II innate immunity coalesce to regulate tissue repair and fibrosis. Kastenschmidt et al. report that ILC2s reside in skeletal muscle, are activated in muscular dystrophy, and promote muscle eosinophilia. Stromal progenitors expressed IL-33, which expanded ILC2s and promoted a transcriptional program associated with muscle fibrosis., Graphical Abstract

Chronic muscle inflammation contributes to the pathogenesis of Duchenne muscular dystrophy (DMD), a lethal muscle disorder attributed to dystrophin gene mutations. However, the function and regulation of eosinophilia, an unappreciated facet of type II innate immunity in dystrophic muscle, remain poorly understood. Here, we report the novel observation that group 2 innate lymphoid cells (ILC2s) are present in skeletal muscle and are the principal regulators of muscle eosinophilia during muscular dystrophy. Eosinophils were elevated in DMD patients and dystrophic mice, along with the major eosinophil survival factor, interleukin-5 (IL-5). ILC2s were present in healthy skeletal muscle, were activated and expanded in number during muscular dystrophy in mice, and were the sole source of IL-5. Muscle ILC2s were expanded by IL-33, which was upregulated in dystrophic muscle and was predominantly produced by fibro/adipogenic progenitor cells (FAPs). Exogenous IL-33 also promoted muscle eosinophilia, which was further augmented by combined treatment with IL-2 complex (IL-2c). The deletion of ILC2s in dystrophic mice prevented eosinophilia and mitigated the IL-33/IL-2c-mediated increase of muscle eosinophils and IL-5 expression. Our findings establish that interactions between FAPs and ILC2s regulate type II innate immunity in dystrophic muscle and promote muscle eosinophilia during muscular dystrophy.

We show that a necessary and sufficient condition for a smooth function on the tangent bundle of a manifold to be a Lagrangian density whose action can be minimized is, roughly speaking, that it be the sum of a constant, a nonnegative function vanishing on the support of the minimizers, and an exact form. We show that this exact form corresponds to the differential of a Lipschitz function on the manifold that is differentiable on the projection of the support of the minimizers, and its derivative there is Lipschitz. This function generalizes the notion of subsolution of the Hamilton-Jacobi equation that appears in weak KAM theory, and the Lipschitzity result allows for the recovery of Mather's celebrated 1991 result as a special case. We also show that our result is sharp with several examples. Finally, we apply the same type of reasoning to an example of a finite horizon Legendre problem in optimal control, and together with the Lipschitzity result we obtain the Hamilton-Jacobi-Bellman equation and the Maximum Principle. This version contains errata correcting an issue in the published version., 24 pages. Contains errata for the published version

La Ley Nacional de Salud Mental -en adelante LSM- resulta aplicable a los supuestos contemplados en el. Art. 34 inc. 1 del Código Penal Argentino -en adelante CP-. Dado el carácter posterior y especial de la referida ley respecto al CP, este debe interpretarse a la luz de aquella. Esto repercute en que las medidas del art. 34 inc. 1 del CP deben: - Ser entendidas como internaciones involuntarias de la LSM con finalidad exclusivamente terapéutica, por ende, debe adoptarse al riesgo cierto e inminente como criterio para determinarlas -ya no debe utilizarse el concepto de peligrosidad. - Ejecutarse, en principio, en hospitales generales -nunca en unidades penitenciarias. - Desarrollarse de la manera menos restrictiva de derechos posible y durar el menor tiempo posible según las necesidades terapéuticas del caso -en virtud del principio “opción menos restrictiva”. Limite temporal que además tiene por techo la proporcionalidad que debe guardar la internación/medida con la pena que se hubiera impuesto de no mediar declaración de inimputabilidad. El contraste de esos estándares con los datos que se han recabado de las personas con declaración de inimputabilidad en la provincia de Buenos Aires, evidencia una falta de concreción de los mismos que se ve reflejada en: - Alojamiento de personas con padecimientos mentales en unidades penitenciarias. - Supuestos donde se mantiene las internaciones: a) sin mediar criterio de internación en razón de problemáticas de tipo social, y/o b) por periodos de tiempo que resultan desproporcionados en relación a la pena que podría haberse impuesto de no haber mediado declaración de inimputabilidad., Facultad de Ciencias Jurídicas y Sociales

Introducción y Objetivos: Los defectos craneales que llegan a nuestro hospital generalmente son secundarios a trauma o bien a su tratamiento neuroquirúrgico. La craneoplastia no suele ser inmediata, sin embargo el síndrome de trepanación o el deseo del paciente por mejorar su apariencia, son mandatorios para poder realizar la reconstrucción. El material ideal para una craneoplastia debe ser biocompatible, fácil de fabricar y biomecánicamente estable. En nuestro Servicio llevamos a cabo la reconstrucción craneal con una prótesis de metil-metacrilato diseñada mediante estereolitografía, cubierta completamente por un injerto de fascia lata. En nuestra experiencia esta nos brinda resultados predecibles, seguros y satisfactorios para los pacientes. Material y Método: Presentamos nuestra experiencia inicial en el uso de esta técnica a través de un análisis retrospectivo sobre 32 pacientes operados por un equipo multidisciplinario entre enero de 1996 y junio de 2014 en el Hospital General de México Dr. Eduardo Liceaga. Resultados: No tuvimos complicaciones importantes relacionadas con infección, hematoma o seroma. Los resultados estéticos obtenidos fueron de aceptables a buenos. Conclusiones: En esta serie de pacientes usando la técnica descrita, recogimos una tasa de complicaciones muy baja y un excelente grado de satisfacción de los pacientes en el seguimiento a largo plazo.

In the context of the Eskin-Okounkov approach to the calculation of the volumes of the different strata of the moduli space of quadratic differentials, the important ingredients are the pillowcase weight probability distribution on the space of Young diagrams, and the asymptotic study of characters of permutations that near-involutions. In this paper we present various new results for these objects. Our results give light to unforeseen difficulties in the general solution to the problem, and they simplify some of the previous proofs., This paper elaborates on some of the results of the author's PhD thesis (arXiv:1209.4333). This is the published version, http://ejp.ejpecp.org/article/view/3626