Analysis of SIGLEC1 as a surrogate marker for a type I interferon signature in autoimmune congenital heart block and primary Sjögren’s syndrome

Interferon-α (IFN-α), belonging to the family of type I interferons, is a cytokine involved in the pathogenesis of many autoimmune diseases, including systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS). As there are no standardised tests for the direct measurement of IFN-α, the expression of the myeloid cell surface receptor SIGLEC1 on CD14+ monocytes was examined as potential biomarker for a type I interferon signature. While several studies have analysed the SIGLEC1 expression in SLE patients, further research is required into other autoimmune diseases, including pSS and congenital heart block (CHB). It was therefore the aim of this study to analyse the expression of SIGLEC1 on CD14+ monocytes, and how it is influenced by certain immunomodulatory medication, in pSS patients and in females with a CHB pregnancy complication. It was found that patients with pSS had an increased expression of SIGLEC1 compared to healthy individuals, with levels comparable to those found in SLE patients. PSS patients with a systemic or extraglandular disease manifestation (n = 16) had a significantly higher expression of SIGLEC1 compared to patients where the disease was restricted to the glandular organs (n = 15; p = 0.0001, Mann-Whitney U test (MWU)). A total of 9 pregnant females were included in the study whose children developed CHB in utero, and were compared to 14 pregnant at-risk females with anti-Ro autoantibodies who bore unaffected children. We found a significantly higher expression of SIGLEC1 and significantly higher plasma concentrations of IFN-α in the affected group compared to the unaffected group (p = 0.0034 and p = 0.0135, respectively, MWU), while there was no significant difference for plasma concentrations of interferon-γ induced protein 10 (IP10; p = 0.14, MWU). The expression of SIGLEC1 was reduced in patients with SLE, pSS, and females with a CHB pregnancy complication upon introduction of glucocorticoids and hydroxychloroquine. In summary, this study highlights a potential clinical use of the biomarker SIGLEC1 as a biomarker indicative of a more severe disease manifestation in patients with pSS, for dose titration and monitoring treatment response to hydroxychloroquine and glucocorticoids, as well as to other medication still in development, and for risk evaluation in pregnant females with anti-Ro antibodies. Further studies are needed to fully understand the pathogenetic and clinical implications of an increased SIGLEC1 expression, reflecting an activated type I interferon system, for patients with autoimmune diseases.Das Zytokin Interferon-α (IFN-α) aus der Familie der Typ-I-Interferone ist am Pathomechanismus vieler Autoimmunerkrankungen beteiligt, wie z.B. dem systemischen Lupus Erythematodes (SLE) und dem primären Sjögren-Syndrom (pSS). Dennoch gibt es keine standardisierten Testverfahren zur direkten Messung von IFN-α, sodass die Expression des auf Myelozyten exprimierten Oberflächenmoleküls SIGLEC1 als potentieller Biomarker für eine Typ-I-Interferon-Signatur untersucht wurde. Während vorherige Studien die Expression von SIGLEC1 in Patienten mit SLE untersucht haben, besteht weiterhin Forschungsbedarf in anderen Autoimmunerkrankungen, wie beispielsweise dem pSS und dem kongenitalen Herzblock (CHB). Es war daher das Ziel dieser Studie, in Patienten mit pSS und Frauen mit einer CHB-Schwangerschaftskomplikation sowohl die Expression von SIGLEC1 auf CD14+-Monozyten, als auch deren Beeinflussung durch immunmodulierende Medikamente zu untersuchen. Die Studie ergab, dass Patienten mit pSS gegenüber gesunden Kontrollprobanden eine erhöhte Expression von SIGLEC1 aufwiesen, die vergleichbar war zu der Expression in Patienten mit SLE. PSS-Patienten mit einer systemischen bzw. extraglandulären Krankheitsmanifestation (n = 16) hatten eine signifikant höhere Expression als Patienten, bei denen das Krankheitsgeschehen auf das Drüsengewebe begrenzt war (n = 15; p = 0.0001, Mann-Whitney-U-Test (MWU)). Es wurden 9 schwangere Frauen in die Studie eingeschlossen, deren Kinder im Uterus einen Herzblock entwickelten und mit 14 schwangeren Frauen verglichen, die mit Anti-Ro-Antikörpern zwar ein Risikoprofil aufwiesen, jedoch gesunde Kinder gebaren. Hier fanden wir ebenfalls eine signifikant höhere SIGLEC1-Expression, wie auch signifikant höhere IFN-α-Konzentrationen bei den betroffenen Frauen (p = 0.0034 und p = 0.0135, MWU), während die Konzentrationen von Interferon-γ-induziertem Protein 10 (IP-10) sich zwischen den beiden Gruppen nicht signifikant unterschieden (p = 0.14, MWU). Die Expression von SIGLEC1 konnte bei Patienten mit SLE und pSS, sowie bei Frauen mit einer CHB-Schwangerschaftskomplikation durch Glukokortikoide und durch Hydroxychloroquin gesenkt werden. Zusammenfassend erweitert diese Studie den potentiellen klinischen Nutzen von SIGLEC1, sowohl als Biomarker, der auf einen schwereren Krankheitsverlauf bei Patienten mit pSS hindeuten kann, zur Dosisfindung und Therapiekontrolle einer Therapie mit Glukokortikoiden und Hydroxychloroquin, bzw. auch von Medikamenten, die sich derzeit noch in der Entwicklung befinden, sowie zur Risikoevaluation bei schwangeren Frauen mit anti-Ro-Antikörpern. Weitere Studien sind erforderlich, um die vollständige pathogenetische und klinische Bedeutung einer erhöhten SIGLEC1-Expression als Indikator eines aktivierten Typ-I-Interferonsystems für Patienten mit Autoimmunerkrankungen zu verstehen

An Inventory and Valuation of the Furniture, Fittings and Fixtures Contained in the Hotel Russell, St. Stephens Green Dublin: First Floor

A valuation of the fixture and fittings of the Russell Hotel, Dublin carried out on the 1st. of July, 1954. The valuation covered the ground floor, first, second and third floors and the basement. For convenience sake the valuation has been broken into 5 files covering each storey. This would appear to be the carbon copy of the original document

An Inventory and Valuation of the Furniture, Fittings and Fixtures Contained in the Hotel Russell, St. Stephens Green Dublin: Index and Ground Floor

A valuation of the fixture and fittings of the Russell Hotel, Dublin carried out on the 1st. of July, 1954. The valuation covered the ground floor, first, second and third floors and the basement. Fore convenience sake the valuation has been broken into 5 files covering each storey. This would appear to be the carbon copy of the original document

An Inventory and Valuation of the Furniture, Fittings and Fixtures Contained in the Hotel Russell, St. Stephens Green Dublin: Third Floor

A valuation of the fixture and fittings of the Russell Hotel, Dublin carried out on the 1st. of July, 1954. The valuation covered the ground floor, first, second and third floors and the basement. For convenience sake the valuation has been broken into 5 files covering each storey. This would appear to be the carbon copy of the original document

An Inventory and Valuation of the Furniture, Fittings and Fixtures Contained in the Hotel Russell, St. Stephens Green Dublin: Summary Sheet of Complete Valuation

A valuation of the fixture and fittings of the Russell Hotel, Dublin carried out on the 1st. of July, 1954. The valuation covered the ground floor, first, second and third floors and the basement. For convenience sake the valuation has been broken into 5 files covering each storey. This would appear to be the carbon copy of the original document

An Inventory and Valuation of the Furniture, Fittings and Fixtures Contained in the Hotel Russell, St. Stephens Green Dublin: Second Floor

A valuation of the fixture and fittings of the Russell Hotel, Dublin carried out on the 1st. of July, 1954. The valuation covered the ground floor, first, second and third floors and the basement. For convenience sake the valuation has been broken into 5 files covering each storey. This would appear to be the carbon copy of the original documen

Más que basura en el Relleno Sanitario Doña Juana

This article details the mismanagement of organic waste and other residues of different kinds that arrive at the Doña Juana Landfill. Bad procedures and bad decisions have been identified in the problem due to the area where it is located and the design of the landfill. The recognition of all types of waste that arrive at the sanitary landfill should be done, and based on the conflicts that have been generated inside and outside the landfill, a better solution should be sought, so that the environmental impact is as small as possible, and the quality of life of the families that live in the periphery should be improved.Este artículo detalla el mal manejo de los residuos orgánicos y otros residuos de diferente índole que llegan al Relleno Sanitario Doña Juana. Se han identificado en el problemas, malos procedimientos y malas decisiones debido a la zona donde está ubicado y al diseño del mismo. Debe realizarse el reconocimiento de toda la clase de desechos que llegan al relleno sanitario, y con base en los conflictos que se han generado dentro y fuera del relleno, se debe buscar una mejor solución, para que el impacto ambiental sea lo menor posible, y mejorar la calidad de vida de las familias que habitan en la periferia

Changes in primary afferent depolarization of sensory neurones during peripheral nerve regeneration in the cat

Journal ArticleI. Micro-electrode recordings were made from normal and regenerating sural nerve fibres in cats. Increases in the excitability of the central terminals of these fibres after conditioning stimulation of other sural nerve fibres were taken as evidence for primary afferent depolarization. 2. At all recovery times studied the excitability changes seen were significantly less than those seen in control animals. Two factors contributed to the changes in primary afferent depolarization. First, the proportion of fibres that showed no evidence of primary afferent depolarization increased significantly. This proportion became smaller as recovery progressed. Secondly, where primary afferent depolarization was present, the magnitudes of the effects were slightly but significantly decreased compared with control values. 3. Excitability changes of the central terminals of sural nerve fibres were also measured after conditioning stimulation of the ipsilateral, unlesioned accessory sural nerve. One month after sural nerve transection there was a significant increase in the proportion of fibres showing no evidence of excitability changes following accessory sural nerve conditioning stimulation compared with control animals. Thus, the loss of primary afferent depolarization of regeneracing sural nerve fibres was neither simply a consequence of desynchronization of the volley of impulses entering the spinal cord after conditioning stimulation of other regenerating sural fibres, nor due to fewer fibres being activated during conditioning stimulation of the lesioned nerves. 4. A possible explanation of these results is that after peripheral nerve crush or transection the central terminals of the damaged fibres retract or atrophy. Then as regeneration of the nerve proceeds, the central terminals of the fibres re-form

Actualización del Manual de Gestión del Riesgo Radiológico e Implementación de una Estrategia Educativa sobre Protección Radiológica para el Talento Humano y Usuarios del Área de Imágenes Diagnósticas de la Clínica Nuestra Señora de Torcoroma de Ocaña, Norte De Santander

Anexo 1. En un archivo llamado manuales del servicio de radiología se encuentran 4 documentos como lo son, el manual de protección radiológica, manual de vigilancia radiológica, manual de capacitación de protección radiológica, la implementación del folleto de protección radiológica y el video.El presente trabajo se hizo en la Clínica Nuestra Señora De Torcoroma del Municipio De Ocaña Norte De Santander. El objetivo fue actualizar el manual de gestión de riesgos radiológicos e implementar una estrategia educativa sobre protección radiológica. La metodología que se aplicó a dicho proyecto se dividió en cuatro fases; la primera fue un análisis diagnóstico, en la fase 2 se sistematizo la información obtenida en una técnica 5W1H, en la fase 3 se ejecutó los análisis de los documentos que compone el manual de gestión de riesgos radiológicos de acuerdo a las normativas vigentes y se socializaron los riesgos con las partes interesadas internas y externas. En la fase 4 se hizo una evaluación de los documentos y se generó una estructura de las recomendaciones realizadas. De los resultados se observó que no se cumplía con la normativa vigente y no existía relación entre lo planeado y lo ejecutado. Debido a esto en su totalidad se actualizo el manual de riegos y quedo titulado manual de protección radiología. Divido en dos partes: vigilancia radiológica y protección radiológica. En conclusión se deben mantener actualizados los manuales de riesgos de la clínica mencionada para mejorar la calidad del servicio hospitalario.This work was done at the Nuestra Señora De Torcoroma Clinic in the Municipality of Ocaña Norte De Santander. The objective was to update the radiological risk management manual and implement an educational strategy on radiation protection. The methodology applied to this project was divided into four phases; The first was a diagnostic analysis, in phase 2 the information obtained in a 5W1H technique was systematized, in phase 3 the analyzes of the documents that make up the radiological risk management manual were executed in accordance with current regulations and they were socialized risks with internal and external stakeholders. In phase 4, an evaluation of the documents was made and a structure of the recommendations made was generated. From the results, it was observed that current regulations were not complied with and that there was no relationship between what was planned and what was executed. Due to this, the risk manual was updated in its entirety and it was titled radiology protection manual. I divide into two parts: radiological surveillance and radiation protection. In conclusion, the risk manuals of the aforementioned clinic should be kept updated to improve the quality of the hospital service

Competencias pedagógicas del docente democrático en la educación básica

In Venezuela, the educational one of Basic Education in its pedagogical task has to be compromised with the construction of the democracy as life style. In such sense, this study had as objective to characterize the pedagogical competitions of the democratic educational one in the II stage of Basic Education. Within the framework of the methodology it responds to a mixed approach (qualitative - quantitative), with case study design. The direct Nonparticipant observation and a written registry of actions, pedagogical processes and scenes, developed pedagogical competitions broken ties with democratic values, to respond to a memoirist, superficial and fragmented learning devoid of democratic procedures based on the socio-cultural experience, also demonstrated a dominant attitude by the exaggerated use of the power, combined to the presence of injustices and inequalities in the learning process. In conclusion, it is necessary to reinforce in the educational one the pedagogical competitions indispensable for the promotion of democratic values as basic directions to fulfill its roll successfully and to act based on constructing the democracy, with a high sense of freedom, solidarity, justice and participation.En Venezuela, el docente de Educación Básica en su quehacer pedagógico ha de estar comprometido con la construcción de la democracia como estilo de vida. En tal sentido, este estudio tuvo como objetivo caracterizar las competencias pedagógicas del docente democrático en la II etapa de Educación Básica. En el marco de la metodología responde a un enfoque mixto (cualitativo–cuantitativo), con diseño de estudio de caso. La observación directa no participante y un registro escrito de acciones, procesos y escenarios pedagógicos, desvelaron competencias pedagógicas desvinculadas de valores democráticos, por responder a un aprendizaje memorístico, superficial y fragmentado carente de procedimientos democráticos basados en la experiencia sociocultural, igualmente se evidenció una actitud dominante por el exagerado uso del poder, aunado a la presencia de injusticias y desigualdades en el proceso de aprendizaje. En conclusión, es necesario reforzar en el docente las competencias pedagógicas indispensables para la promoción de valores democráticos como orientaciones básicas para cumplir con éxito su rol y actuar en función de construir la democracia, con un alto sentido de libertad, solidaridad, justicia y participación