Unraveling the Mechanisms of Cutaneous Graft-Versus-Host Disease

The skin is the most common target organ affected by graft-versus-host disease (GVHD), with severity and response to therapy representing important predictors of patient survival. Although many of the initiating events in GVHD pathogenesis have been defined, less is known about why treatment resistance occurs or why there is often a permanent failure to restore tissue homeostasis. Emerging data suggest that the unique immune microenvironment in the skin is responsible for defining location- and context-specific mechanisms of injury that are distinct from those involved in other target organs. In this review, we address recent advances in our understanding of GVHD biology in the skin and outline the new research themes that will ultimately enable design of precision therapies

Progression of retinopathy and alteration of the blood-retinal barrier in patients with type 2 diabetes: a 7-year prospective follow-up study

BACKGROUND: The study was carried out to evaluate the correlation between blood-retinal barrier (BRB) permeability and the progression of diabetic retinopathy (DR), defined by development of "need for photocoagulation", over a 7-year period by means of vitreous fluorometry (VF). METHODS: Forty type 2 diabetic patients with minimal or no retinopathy, aged 40-65 years (mean 53.9 + 7.3 years), were followed up prospectively for 7 years. Investigations including standard ophthalmological examination, fundus photography, fluorescein angiography and VF were performed at entry and 1, 4, 5 and 7 years later. Only one eye per patient was included in the study. Need for photocoagulation was based on Early Treatment Diabetic Retinopathy Study protocols and decided by the attending ophthalmologist. RESULTS: After 7 years of follow-up a total of 22 of the 40 eyes had received photocoagulation. The eyes that needed photocoagulation were those that had higher VF values at the entry of the study and showed higher rates of deterioration (initial values 5.1 + 1.9 vs 2.8 + 1.5 x 10(-6) min-1, P < 0.001; annual increase in leakage for the first year, 1.5 + 0.8 vs 0.5 + 1.0 x 10(-6) min-1, P < 0.001,). The eyes that did not need photocoagulation during the 7 years of follow-up showed stable VF readings (-0.1 + 1.2 x 10(-6) min-1, difference between initial values and 7 years later). CONCLUSIONS: Abnormally high VF values and their rapid increase over time are good indicators of progression and worsening of the retinopathy in diabetes type 2

Aprendizajes de Estudiantes de Enfermería Involucrados en Proyectos de Investigación: Revisión Integrativa de la Literatura

To identify the learning outcomes and skills obtained of undergraduate nursing students involved in research projects. Methods: This was an integrative literature review, based on a research protocol in the CINAHL Complete databases; Cochrane Central Register of Controlled Trials; Cochrane Database of Systematic Reviews; Cochrane Methodology Register; MedicLatina; MEDLINE, Scopus and JBI, including primary and secondary studies, published between 2015 and 2020. Results: A total of five heterogeneous articles were included, which were categorized using Kirkpatrick’s (adapted) model. Seventeen learning outcomes acquired through participation in research projects were identified, from the learning of new knowledge and skills to the development of new attitudes and behaviors. Final considerations: The involvement of nursing students in research projects is important to their professional development. Future investment in research on this topic can help cement the potential of this type of student involvement.info:eu-repo/semantics/publishedVersio

Graft-versus-host disease reduces lymph node display of tissue-restricted self-antigens and promotes autoimmunity

Acute graft-versus-host disease (GVHD) is initially triggered by alloreactive T cells, which damage peripheral tissues and lymphoid organs. Subsequent transition to chronic GVHD involves the emergence of autoimmunity although the underlying mechanisms driving this process are unclear. Here, we tested the hypothesis that acute GVHD blocks peripheral tolerance of autoreactive T cells by impairing lymph node (LN) display of peripheral tissue-restricted antigens (PTA). At the initiation of GVHD, LN fibroblastic reticular cells (FRC) rapidly reduced expression of genes regulated by DEAF1, an Autoimmune Regulator-like transcription factor required for intra-nodal expression of PTA. Subsequently, GVHD led to the selective elimination of the FRC population, and blocked the repair pathways required for its regeneration. We used a transgenic mouse model to show that the loss of presentation of an intestinal PTA by FRC during GVHD resulted in the activation of auto-aggressive T cells and gut injury. Finally, we show that FRC normally expressed a unique PTA gene signature that was highly enriched for genes expressed in the target organs affected by chronic GVHD. In conclusion, acute GVHD damages and prevents repair of the FRC network, thus disabling an essential platform for purging auto-reactive T cells from the repertoire

The modified patient enablement instrument: a Portuguese cross-cultural adaptation, validity and reliability study

"Article number: 16087"Enabling patients with asthma to obtain the knowledge, confidence and skills they need in order to assume a major role in the management of their disease is cost effective. It should be an integral part of any plan for long-term control of asthma. The modified Patient Enablement Instrument (mPEI) is an easily administered questionnaire that was adapted in the United Kingdom to measure patient enablement in asthma, but its applicability in Portugal is not known. Validity and reliability of questionnaires should be tested before use in settings different from those of the original version. The purpose of this study was to test the applicability of the mPEI to Portuguese asthma patients after translation and cross-cultural adaptation, and to verify the structural validity, internal consistency and reproducibility of the instrument. The mPEI was translated to Portuguese and back translated to English. Its content validity was assessed by a debriefing interview with 10 asthma patients. The translated instrument was then administered to a random sample of 142 patients with persistent asthma. Structural validity and internal consistency were assessed. For reproducibility analysis, 86 patients completed the instrument again 7 days later. Item-scale correlations and exploratory factor analysis were used to assess structural validity. Cronbach's alpha was used to test internal consistency, and the intra-class correlation coefficient was used for the analysis of reproducibility. All items of the Portuguese version of the mPEI were found to be equivalent to the original English version. There were strong item-scale correlations that confirmed construct validity, with a one component structure and good internal consistency (Cronbach's alpha >0.8) as well as high test-retest reliability (ICC=0.85). The mPEI showed sound psychometric properties for the evaluation of enablement in patients with asthma making it a reliable instrument for use in research and clinical practice in Portugal. Further studies are needed to confirm its responsiveness.Financial support for this work was provided by FEDER funds through the Operational Programme Competitiveness Factors-COMPETE and National Funds through FCT-Foundation for Science and Technology under the project POCI-01-0145-FEDER-007038, and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).info:eu-repo/semantics/publishedVersio

Lusophone community in the digital age: the ambiguous place of scepticism and performance

(Excerto) "This article addresses the setting up of the political Community of the Portuguese Language Countries (Comunidade dos Países de Língua Portuguesa (CPLP)) and its present-day social and cultural dynamics. As the other articles in this Special Section from Martins, Salgado and Santos also demonstrate, media and communication systems are playing a role in the development of this loose aggregation and in the internal dynamics of the Portuguese language countries."(undefined)info:eu-repo/semantics/publishedVersio