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Calcinosis cutis (CC) is defined as the deposition of calcium salts on the skin and subcutaneous tissue. It is associated with different conditions, including some autoimmune diseases, and it can generate significant inflammation, pain, and functional impairment. Different therapies have been tried with limited results. Intralesional sodium thiosulfate seems a promising therapeutic option. We report a patient with diffuse systemic sclerosis who presented with two symmetrical plaques on both axillae, which caused pain and skin retraction. The clinical diagnosis was consistent with CC, which was confirmed by skin biopsy and ultrasound. The patient was treated with a 250 mg/ml solution of sodium thiosulfate injected into the plaques. Complete resolution was achieved after three monthly sessions. The only reported adverse effect was a transient burning sensation during the injections. Given its effectiveness and safety, we believe that intralesional sodium thiosulfate could become a valid first-line option for the treatment of CC.

Con este Trabajo de Fin de Máster, se pretende poner de manifiesto la importancia de la historia de las matemáticas en la didáctica, pudiendo introducir al alumnado la materia de manera más llevadera. Y es que conocer el origen de lo que se estudia es vital para replantearse su porqué. Es algo fundamental para trasladar el interés a los alumnos. Introducir contenidos de matemáticas comenzando por el origen es algo que promueve la curiosidad y despierta el interés del alumnado por dicho tema. Es por ello que, a lo largo del documento, se irán comentando los problemas más interesantes que han ido surgiendo a lo largo de la historia, así como el enfoque propio de cada civilización. Además, se ofrecerán curiosidades susceptibles de ser transmitidas en las aulas con el fin de despertar el debate, y con ello, la implicación de los alumnos., With this Master's Thesis, it is intended to highlight the importance of the history of mathematics in didactics, being able to introduce the subject to students in a more bearable way. To know the origin of what is studied is vital to rethink its why. It is essential to transfer interest to students. Introducing mathematics content starting with the origin is something that promotes curiosity and arouses the interest of students in said subject. That’s why, throughout the document, the most interesting problems that have arisen throughout history will be commented on, as well as the approach of each civilization. In addition, curiosities that can be told in the classrooms will be offered in order to spark debate, and with it, the involvement of students., Máster Universitario en Formación del Profesorado de ESO, Bachillerato, Formación Profesional y Enseñanza de Idiomas. Especialidad en Matemáticas (M088)

International audience; Abstract There is currently no approved treatment for primary Sjögren’s syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren’s syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials.

OBJECTIVE: Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. METHODS: Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. RESULTS: Four clusters were identified and validated. Three were pathologic, representing "inflammatory," "lymphoid," and "interferon" patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. CONCLUSION: Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases. ispartof: ARTHRITIS & RHEUMATOLOGY vol:73 issue:6 pages:1073-1085 ispartof: location:United States status: published

Funding for the preparation of this manuscript has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no 115,565, resources composed of the financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and the EFPIA companies' in kind contribution. MT is supported by a Spanish grant from Health Department, Junta de Andalucia (PI/0017/2016) and through the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806975. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. EC-M was funded by the Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness (FJCI_2014_20652). We thank Ralf Lesche for the production of RNASeq data and Marc Torres Ciuro for design support., Primary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population., Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Program (FP7/2007-2013) 115,565, EFPIA companies, Junta de Andalucia PI/0017/2016, Innovative Medicines Initiative 2 Joint Undertaking 806975 European Union's Horizon 2020 research and innovation programme, EFPIA, Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness FJCI_2014_20652

Calcinosis cutis (CC) is defined as the deposition of calcium salts on the skin and subcutaneous tissue. It is associated with different conditions, including some autoimmune diseases, and it can generate significant inflammation, pain, and functional impairment. Different therapies have been tried with limited results. Intralesional sodium thiosulfate seems a promising therapeutic option. We report a patient with diffuse systemic sclerosis who presented with two symmetrical plaques on both axillae, which caused pain and skin retraction. The clinical diagnosis was consistent with CC, which was confirmed by skin biopsy and ultrasound. The patient was treated with a 250 mg/ml solution of sodium thiosulfate injected into the plaques. Complete resolution was achieved after three monthly sessions. The only reported adverse effect was a transient burning sensation during the injections. Given its effectiveness and safety, we believe that intralesional sodium thiosulfate could become a valid first-line option for the treatment of CC.

Background Clinical heterogeneity, a hallmark of systemic autoimmune diseases (SADs) impedes early diagnosis and effective treatment, issues that may be addressed if patients could be grouped into a molecular defined stratification. Methods With the aim of reclassifying SADs independently of the clinical diagnoses, unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data of 918 patients with 7 SADs and 263 healthy controls was undertaken. An inception cohort prospectively followed for 6 and 14 months was studied to validate the results in early cases and analyze if cluster assignment was modified with time. Results Four clusters were identified Three aberrant clusters were ‘acute phase inflammatory’, ‘T cell immunity’, and ‘interferon’, each including all diagnoses, were defined by genetic, clinical, serological and cellular features. A fourth cluster showed no specific molecular pattern, to which 74% of healthy controls clustered with patients. The inception cohort showed that most patients were either assigned always to the same cluster or moved from the healthy-like cluster to a single aberrant cluster resembling the relapsing-remitting dynamic of these diseases, showing that single aberrant molecular signatures characterize each individual patient. Conclusions Patients with SADs share molecular signatures and can be therefore stratified into three disease clusters differentiating each patient into a specific molecular disease pathway. Such assignment is stable with time. These results have important implications for understanding disease progression and therapy design marking a paradigm shift in our view of SADs. Acknowledgment This work has been supported through a grant from the Innovative Medicines Initiative Joint Undertaking No. 115565 and in-kind and in-cash contributions from the EFPIA partners. G.B. is supported by the Instituto de Salud Carlos III (ISCIII, Spanish Health Ministry), through the Sara Borrell subprogram (CD18/00153). The authors would like to particularly express their gratitude to the patients, nurses and many others who helped directly or indirectly in the consecution of this study.

SUMMARYBackgroundClinical heterogeneity, a hallmark of systemic autoimmune diseases (SADs) impedes early diagnosis and effective treatment, issues that may be addressed if patients could be grouped into a molecular defined stratification.MethodsWith the aim of reclassifying SADs independently of the clinical diagnoses, unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data of 918 patients with 7 SADs and 263 healthy controls was undertaken. In addition, an inception cohort was prospectively followed for 6 and 14 months to validate the results and analyze if cluster assignment changed or not with time.ResultsFour clusters were identified. Three clusters were aberrant, representing ‘inflammatory’, ‘lymphoid’, and ‘interferon’ patterns each including all diagnoses and defined by genetic, clinical, serological and cellular features. A fourth cluster showed no specific molecular pattern and accumulated also healthy controls. An independent inception cohort showed that with time, the molecular clusters remain stable, showing that single aberrant molecular signatures characterize each individual patient.ConclusionsPatients with SADs can be jointly stratified into three stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of therapy non-responsiveness marking a paradigm shift in the view of SADs.

Objetivo: Evaluar los resultados de la biometría óptica utilizando IOLMaster 500, Lenstar LS 900 y Aladdin en ojos con catarata. Métodos: En 231 ojos de 152 pacientes con cataratas, se compararon retrospectivamente las medidas de 3 biómetros diferentes. Se realizaron comparaciones pareadas para la longitud axial (AL), la queratometría media (K media) y la profundidad de la cámara anterior (ACD). Resultados: En solo 197 de los 231 ojos (85,3%), fue posible obtener mediciones confiables de AL con los tres dispositivos. No fue posible determinar AL en 16 ojos (6,9%) con Lenstar LS 900; en 19 ojos (8,2%) con Aladdin; y en 20 ojos (8,6%) con IOLMaster 500 posiblemente relacionado con la severidad de la opacificación del cristalino (las córneas tenían buena transparencia en los ojos incluidos en el estudio). Hubo una diferencia estadísticamente significativa en AL entre IOLMaster 500 y los dos biómetros restantes (P = 0.03). Sin embargo, la cantidad de diferencia se consideró clínicamente no significativa (0,04 mm). La queratometría media (K media) se determinó en 203 ojos (87,9%) con los tres dispositivos. Las diferencias en la media de K estuvieron entre - 0,1 y 0,06 dioptrías (D), que no se consideraron ni estadísticamente (P> 0,05) ni clínicamente significativas. La profundidad de la cámara anterior (DCA) se determinó en 197 ojos (85,28%) con los tres biómetros. Las diferencias entre los tres dispositivos (0,03 a 0,13 mm) no fueron estadísticamente significativas y tampoco se consideraron clínicamente significativas. Conclusiones: No hubo diferencias clínicamente significativas entre estos 3 biómetros en AL, K medio y ACD. Especialización Purpose: To evaluate the results of optical biometry using the IOLMaster 500, Lenstar LS 900 and Aladdin in eyes with cataract. Methods: In 231 eyes of 152 patients with cataract,the measurements of 3 different biometers were retrospectively compared. Paired comparisons were performed for axial length (AL), mean keratometry (mean K) and anterior chamber depth (ACD). Results: In only 197 of the 231 eyes (85.3%), it was possible to obtain reliable measurements of AL with all the three devices. It was not possible to determine AL in 16 eyes (6.9%) with Lenstar LS 900; in 19 eyes (8.2%) with Aladdin; and in 20 eyes (8.6%) with IOLMaster 500 possibly related to the severity of lens opacification (the corneas had good transparency in the eyes included in the study). There was a statistically significant difference in AL between IOLMaster 500 and the remaining two biometers (P = 0.03). However, the amount of difference was considered clinically not significant (0.04 mm). The mean keratometry (mean K) was determined in 203 eyes (87.9%) with all the three devices. Differences in mean K were between - 0.1 and 0.06 Diopters (D), which were considered neither statistically (P > 0.05) nor clinically significant. The anterior chamber depth (ACD) was determined in 197 eyes (85.28%) with all the three biometers. The differences between the three devices (0.03 to 0.13 mm) were not statistically significant and considered also clinically not significant. Conclusions: There were no clinically significant differences between these 3 biometers in AL, mean K and ACD.

El tema de la Responsabilidad Social Empresarial ha ido ganando en importancia a nivel global. Uno de los aspectos principales considerados es el cuidado del medio ambiente. Esta investigación está referida a las prácticas que realizan las grandes empresas mineras específicamente en la gestión del agua. Muchas de las grandes empresas mineras presentan de manera pública una serie de prácticas relacionadas al uso y tratamiento del agua; sin embargo, esas prácticas corresponden en su mayoría al cumplimiento de obligaciones legales. En esta investigación desarrollaremos el significado de la Responsabilidad Social Ambiental Minera distinguiendo la responsabilidad jurídica de la responsabilidad social que tienen las grandes empresas dedicadas a ese rubro. La principal conclusión de este trabajo se referirá al hecho que es posible considerar a las grandes empresas mineras como socialmente responsables en materia ambiental, siempre que actúen mas allá de los parámetros establecidos por ley, buscando el bien común en mérito a la responsabilidad moral que tienen dentro de la sociedad. Tesis

La estratificación del riesgo cardiovascular en pacientes con artritis reumatoide no está bien establecida. Los índices utilizados habitualmente (SCORE) sólo identifican a una pequeña proporción de pacientes con riesgo cardiovascular alto-muy alto real. Son necesarias nuevas herramientas para una mejor determinación del riesgo cardiovascular individual en pacientes con artritis reumatoide, como son la Ultrasonografía (US) Carotídea y la Tomografía Computada Multidetector (TCMD). El propósito general es mejorar la detección de pacientes con artritis reumatoide y riesgo cardiovascular alto/muy alto. Para ello, se mide y compara la validez de las distintas herramientas disponibles en la práctica clínica para determinar el riesgo cardiovascular en pacientes con artritis reumatoide, en las diferentes categorías de riesgo cardiovascular, sobre todo los clasificados como de riesgo moderado y bajo mediante SCORE. Las herramientas que se han analizado son el índice SCORE y su modificación sugerida por EULAR(SCOREEULAR), la determinación de CC-GIM y la detección de placas de ateroma medidos por Ultrasonografía carotídea y la cuantificación de CACS mediante Tomografía Computada Multidetector (TCMD) coronaria.

Resumen: Objetivo General y Específicos: Determinar la sensibilidad y especificidad del patrón topográfico “Pinza de Cangrejo” para diferenciar los ojos con Degeneración Marginal Pelúcida (DMP) de los que tienen Queratocono. Material y Métodos: Se realizó un análisis retrospectivo de las topografías corneales incluidas dentro de los registros del equipo Orbscan II tomadas en el Centro Oftalmológico Virgilio Galvis tomadas desde el 15 de Febrero de 2009 hasta el 31 de Julio de 2015 para identificar ojos con patrón topográfico en “Pinza de Cangrejo”. En todos los casos, se analizaron los mapas de curvatura sagitales (queratométricos) y paquimétricos. Se incluyeron todos los ojos con patrón en pinza de cangrejo en el mapa sagital (o queratométrico) y además su ojo contralateral (sin importar si tuviese o no el patrón). Especialización Summary: General and Specific Objective: To determine the sensitivity and specificity of the “Crab Claw” topographic pattern to differentiate eyes with Pellucid Marginal Degeneration (MPD) from those with Keratoconus. Material and methods: A retrospective analysis of the corneal topographies included within the records of the Orbscan II team taken at the Virgilio Galvis Ophthalmology Center was carried out from February 15, 2009 to July 31, 2015 to identify eyes with a topographic pattern in "Pinza de Crab". In all cases, sagittal (keratometric) and pachymetric curvature maps were analyzed. All eyes with a crab claw pattern were included in the sagittal (or keratometric) map, as well as their contralateral eye (regardless of whether it had the pattern or not).