Chagas disease (ChD), a complex and persistent parasitosis caused by Trypanosoma cruzi , represents a natural model of chronic infection, in which some people exhibit cardiac or digestive complications that can result in death 20–40 years after the initial infection. Nonetheless, due to unknown mechanisms, some T. cruzi -infected individuals remain asymptomatic throughout their lives. Actually, no vaccine is available to prevent ChD, and treatments for chronic ChD patients are controversial. Chronically T. cruzi -infected individuals exhibit a deterioration of T cell function, an exhaustion state characterized by poor cytokine production and increased inhibitory receptor co-expression, suggesting that these changes are potentially related to ChD progression. Moreover, an effective anti-parasitic treatment appears to reverse this state and improve the T cell response. Taking into account these findings, the functionality state of T cells might provide a potential correlate of protection to detect individuals who will or will not develop the severe forms of ChD. Consequently, we investigated the T cell response, analyzed by flow cytometry with two multicolor immunofluorescence panels, to assess cytokines/cytotoxic molecules and the expression of inhibitory receptors, in a murine model of acute (10 and 30 days) and chronic (100 and 260 days) ChD, characterized by parasite persistence for up to 260 days post-infection and moderate inflammation of the colon and liver of T. cruzi -infected mice. Acute ChD induced a high antigen-specific multifunctional T cell response by producing IFN-γ, TNF-α, IL-2, granzyme B, and perforin; and a high frequency of T cells co-expressed 2B4, CD160, CTLA-4, and PD-1. In contrast, chronically infected mice with moderate inflammatory infiltrate in liver tissue exhibited monofunctional antigen-specific cells, high cytotoxic activity (granzyme B and perforin), and elevated levels of inhibitory receptors (predominantly CTLA-4 and PD-1) co-expressed on T cells. Taken together, these data support our previous results showing that similar to humans, the T. cruzi persistence in mice promotes the dysfunctionality of T cells, and these changes might correlate with ChD progression. Thus, these results constitute a model that will facilitate an in-depth search for immune markers and correlates of protection, as well as long-term studies of new immunotherapy strategies for ChD.
Objective: To analyse the geographical distribution of multiple sclerosis in Spain from 1975 to 1998. Methods: Age-adjusted mortality rates by province were obtained by the indirect method using the whole Spanish population as the reference. Then, standardised mortality ratios (SMRs) and their 95% confidence intervals were estimated. Results: For both men and women, provinces with SMRs higher than the mean tended to be in the northern third of Spain, whilst those with SMRs lower than the mean were mostly located in the southern half. A linear regression analysis showed a significant positive association between mortality and latitude. Conclusion: A north-south gradient in age-adjusted multiple sclerosis mortality exists in Spain.
Initiatives for teachers’ professional development should rely on the epistemology of practice, that is, be founded on the premise that reflective teachers construct professional knowledge and develop professional skills through practice and through planning, observing or analysing practice. Reflection about teaching action and reflection in teaching action triggers innovation, especially when teachers work together to create the necessary conditions to transform learning. This paper advocates in favour of collaborative action research and innovation as a methodology to promote change in classroom practices. To illustrate this proposal, it presents a case study in which a secondary English teacher from a school which hosts adolescents at risk opens her classrooms to a researcher and a group of pre-service teachers with the objective to reflect upon her own practices and to become an agent of change. Our corpus is made of natural audio-recorded data from the discussions emerging during focus-group sessions held to evaluate the ongoing innovation and interviews to participating secondary students and trainee teachers. The analysis of those interactions will first lead us to reflect upon the challenges of promoting change in the classrooms. Then it will allow us to understand the impact of the experience and argue in favour of a model of teacher education based on team work as a tool to acquire professional skills and guarantee students’ learning success.
In her short story collection Krik? Krak!, the Haitian American writer Edwidge Danticat realizes new formal strategies that integrate vernacular orality into her writings. She does so to construct evocative narrative soundscapes through which difficult memories can be processed. This article examines Danticat’s approach to otherness, migration, and displacement in an attempt to disentangle the function of language, sound, and memory in the development of authentic Caribbean identities and literatures. It aims to trace the workings of sound and mobility in the literary spaces Danticat creates to revisit colonial and patriarchal history and, in so doing, reroot and reroute cultural memories previously lost to violence and organized forgetting. In crossing and replicating the oceanic routes in which past and present intersect, Krik? Krak! opens critical sites of (d)enunciation that rework personal and collective memories of displacement by means of language and sound.
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