33 research outputs found

    The Extracellular Vesicles of the Helminth Pathogen, Fasciola hepatica: Biogenesis Pathways and Cargo Molecules Involved in Parasite Pathogenesis

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    Extracellular vesicles (EVs) released by parasites have important roles in establishing and maintaining infection. Analysis of the soluble and vesicular secretions of adult Fasciola hepatica has established a definitive characterization of the total secretome of this zoonotic parasite. Fasciola secretes at least two subpopulations of EVs that differ according to size, cargo molecules and site of release from the parasite. The larger EVs are released from the specialized cells that line the parasite gastrodermus and contain the zymogen of the 37 kDa cathepsin L peptidase that performs a digestive function. The smaller exosome-like vesicle population originate from multivesicular bodies within the tegumental syncytium and carry many previously described immunomodulatory molecules that could be delivered into host cells. By integrating our proteomics data with recently available transcriptomic data sets we have detailed the pathways involved with EV biogenesis in F. hepatica and propose that the small exosome biogenesis occurs via ESCRT-dependent MVB formation in the tegumental syncytium before being shed from the apical plasma membrane. Furthermore, we found that the molecular "machinery" required for EV biogenesis is constitutively expressed across the intramammalian development stages of the parasite. By contrast, the cargo molecules packaged within the EVs are developmentally regulated, most likely to facilitate the parasites migration through host tissue and to counteract host immune attack

    An International Consensus Definition of the Wish to Hasten Death and Its Related Factors

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    Background: The desire for hastened death or wish to hasten death (WTHD) that is experienced by some patients with advanced illness is a complex phenomenon for which no widely accepted definition exists. This lack of a common conceptualization hinders understanding and cooperation between clinicians and researchers. The aim of this study was to develop an internationally agreed definition of the WTHD. Methods: Following an exhaustive literature review, a modified nominal group process and an international, modified Delphi process were carried out. The nominal group served to produce a preliminary definition that was then subjected to a Delphi process in which 24 experts from 19 institutions from Europe, Canada and the USA participated. Delphi responses and comments were analysed using a pre-established strategy. Findings: All 24 experts completed the three rounds of the Delphi process, and all the proposed statements achieved at least 79% agreement. Key concepts in the final definition include the WTHD as a reaction to suffering, the fact that such a wish is not always expressed spontaneously, and the need to distinguish the WTHD from the acceptance of impending death or from a wish to die naturally, although preferably soon. The proposed definition also makes reference to possible factors related to the WTHD. Conclusions: This international consensus definition of the WTHD should make it easier for clinicians and researchers to share their knowledge. This would foster an improved understanding of the phenomenon and help in developing strategies for early therapeutic intervention

    Programa E-Health ICOnnecta't: un ecosistema para fomentar el bienestar en cáncer a través de la propuesta europea ONCOMMUN

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    Introducción: A pesar de que los tratamientos psico-oncológicos han demostrado su efectividad en disminuir el malestar emocional y mejorar la calidad de vida de las personas con cáncer, aún existen numerosas barreras que limitan su acceso. La transformación a online de esta atención se plantea como una solución para aumentar la cobertura del servicio y mejorar su coste-utilidad. Objetivo: Crear un ecosistema digital de salud para reducir el impacto del cáncer, aumentando el bienestar y la calidad de vida del ciudadano con cáncer. Método: Programa dirigido a pacientes diagnosticadas de cáncer de mama en fase de supervivencia aguda. Es un programa de atención escalonada dividido en 4 niveles de intervención jerarquizados por complejidad: Nivel 1, cribado y monitorización psicosocial; Nivel 2, Campus: psicoeducación y educación sanitaria; Nivel 3, soporte psicosocial comunitario; y Nivel 4, tratamiento psicoterapéutico grupal. Resultados: En 2019, 259 mujeres fueron incluidas en el programa (39,91% de los nuevos casos de cáncer de mama en los centros participantes). Solo el 3,47% (n = 9) requirió atención clínica especializada (Nivel 4). Conclusión: El programa Iconnecta't adopta un modelo integrado de atención psicosocial en cáncer que se adecúa a las necesidades específicas de los supervivientes. Da solución a algunas de las barreras de la atención sanitaria tradicional, democratizando el acceso a los servicios mediante el uso de tecnologías de uso común en la mayoría de ciudadanos. En un futuro próximo se prevé la implementación progresiva a otras neoplasias, junto con un ensayo clínico controlado y aleatorizado que evaluará su eficacia

    Pla estratègic d’atenció pal·liativa especialitzada de Catalunya: bases del model de futur

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    Pla estratègic; Atenció pal·liativa; Atenció centrada en la personaPlan estratégico; Atención paliativa; Atención centrada en la personaStrategic plan; Palliative care; Person centered careAquest Pla estratègic aborda la planificació estratègica de l’atenció a les persones amb necessitats pal·liatives per part dels equips i dispositius de cures pal·liatives específics (a partir d’ara, atenció pal·liativa especialitzada), mentre que de forma conjunta amb la direcció estratègica d’atenció primària i comunitària serà necessari el replantejament de l’atenció al final de vida de forma transversal

    The Transcriptome Analysis of Strongyloides stercoralis L3i Larvae Reveals Targets for Intervention in a Neglected Disease

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    BackgroundStrongyloidiasis is one of the most neglected diseases distributed worldwide with endemic areas in developed countries, where chronic infections are life threatening. Despite its impact, very little is known about the molecular biology of the parasite involved and its interplay with its hosts. Next generation sequencing technologies now provide unique opportunities to rapidly address these questions.Principal FindingsHere we present the first transcriptome of the third larval stage of S. stercoralis using 454 sequencing coupled with semi-automated bioinformatic analyses. 253,266 raw sequence reads were assembled into 11,250 contiguous sequences, most of which were novel. 8037 putative proteins were characterized based on homology, gene ontology and/or biochemical pathways. Comparison of the transcriptome of S. strongyloides with those of other nematodes, including S. ratti, revealed similarities in transcription of molecules inferred to have key roles in parasite-host interactions. Enzymatic proteins, like kinases and proteases, were abundant. 1213 putative excretory/secretory proteins were compiled using a new pipeline which included non-classical secretory proteins. Potential drug targets were also identified.ConclusionsOverall, the present dataset should provide a solid foundation for future fundamental genomic, proteomic and metabolomic explorations of S. stercoralis, as well as a basis for applied outcomes, such as the development of novel methods of intervention against this neglected parasite

    Consens d’escales i eines per a la valoració multidimensional de les persones a Catalunya

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    Model d'atenció integral; Valoració multidimensional; DiagnòsticModelo de atención integral; Valoración multidimensional; DiagnósticoComprehensive care model; Multidimensional valuation; DiagnosisActualment no existeix a Catalunya un consens sobre quin hauria de ser el mínim comú denominador d’escales i eines d’elecció per a la valoració de les diferents dimensions de les persones grans amb multimorbiditat, fragilitat, cronicitat complexa o avançada. Aquest escenari fa evident la necessitat de disposar d’escales i eines consensuades i compartides que facilitin l’aproximació multidimensional a aquestes persones de forma objectiva i pragmàtica, amb l’objectiu d'ajudar els professionals en aquest procés d’individualització de l’atenció. És per aquest motiu que, impulsat per la Direcció General de Planificació i Recerca en Salut i per l’oficina eSalut, s’ha promogut i desenvolupat aquest consens i es vol assegurar que la proposta pugui ser suportada en l’entorn digital

    Cellular immune responses in Echinostoma caproni experimentally infected mice

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    The Echinostoma caproni–mice system is extensively used as an experimental model for the study of the factors involved in the establishment of chronic intestinal helminth infections. Although several parameters of the immunobiology of the host–parasite system have been studied in detail, the current knowledge of the cellular responses in these infections is still scarce. In the present paper, we analyze the kinetics of the circulating CD3⁺ and CD19⁺ cell populations and the different T-cell phenotype profiles in mice experimentally infected with E. caproni. Whereas the CD3⁺ populations remained stable during the complete experiment, a marked increase in CD19⁺ cells was observed from 4 weeks post-infection and beyond. Similarly, a marked increase in CD8⁺ cell populations was observed in the 2 week post-infection. Our results show that E. caproni infection in mice alters the peripheral lymphoid cell populations, which may be important to determine the course of the infection. In this sense, CD8⁺ cells can be essential in relation to their role as a source of IFN-γ

    Analysis of the tegument of Zygocotyle lunata (Trematoda: Paramphistomidae) adults by scanning electron microscopy

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    Paramphistomiasis is a parasitic disease caused by various species of the Paramphistomidae. These species mainly affect domestic and wild ruminants; the economic impact of these diseases is often underestimated. Traditionally, the identification of paramphistomes has been difficult and has been based on morphological aspects such as the body shape, the position of the esophagus and cecae, or the tegumental papillae. Despite the many investigations regarding the tegumental papillae for other paramphistomes, very few efforts have been made using Zygocotyle lunata, partly because many authors differ with respect to the importance of papillae in the classification of paramphistomids. Herein, we characterize by scanning electron microscopy new tegumental papillae not previously described on the tegument of 3-wk-old Z. lunata adults obtained from mice. Three morphologically different papillae (rosette, ciliated, and conical papillae) were observed and are described. Based on these results, we assert that the newly recognized morphological features should be used for species differentiation in the future in addition to the new molecular techniques
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