Doença de Behçet - Infliximab no Tratamento das Manifestações Mucocutâneas

A Doença de Behçet (DB) é uma doença inflamatória multisistémica, crónica e recidivante, cujo diagnóstico é essencialmente clínico. Em estudos recentes, os antagonistas do factor de necrose tumoral a têm mostrado bons resultados no tratamento das manifestações mucocutâneas da DB. Os autores descrevem três casos de DB com envolvimento mucocutâneo grave tratados com infliximab. Caso Clínico 1: Doente do sexo feminino de 16 anos de idade, com aftose bipolar grave com 8 anos de evolução. Verificou-se uma rápida resposta clínica à terapêutica biológica, com remissão parcial e total das úlceras à 2ª e 6ª semana de tratamento, respectivamente Caso Clínico 2: Doente do sexo feminino de 56 anos de idade com paniculite nodular crónica dos membros inferiores, artralgias e ulcerações orogenitais recorrentes. Após 6 semanas de terapêutica com infliximab, verificou-se uma remissão clínica completa. Caso Clínico 3: Doente do sexo feminino de 50 anos de idade, com ulcerações orofaríngeas recorrentes com 15 anos de evolução. Observou-se uma boa resposta clínica à terapêutica biológica, que foi interrompida à 22ª semana por abcessos dentários recorrentes. Na nossa experiência, o infliximab é uma alternativa terapêutica eficaz a considerar na presença de manifestações mucocutâneas resistentes aos tratamentos convencionais

Regulatory Cells, Cytokine Pattern and Clinical Risk Factors for Asthma in Infants and Young Children with Recurrent Wheeze

Several risk factors for asthma have been identified in infants and young children with recurrent wheeze. However, published literature has reported contradictory findings regarding the underlying immunological mechanisms. OBJECTIVES: This study was designed to assess and compare the immunological status during the first 2 years in steroid-naive young children with >or= three episodes of physician-confirmed wheeze (n=50), with and without clinical risk factors for developing subsequent asthma (i.e. parental asthma or a personal history of eczema and/or two of the following: wheezing without colds, a personal history of allergic rhinitis and peripheral blood eosinophilia >4%), with age-matched healthy controls (n=30). METHODS: Peripheral blood CD4(+)CD25(+) and CD4(+)CD25(high) T cells and their cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), GITR and Foxp3 expression were analysed by flow cytometry. Cytokine (IFN-gamma, TGF-beta and IL-10), CTLA-4 and Foxp3 mRNA expression were evaluated (real-time PCR) after peripheral blood mononuclear cell stimulation with phorbol 12-myristate 13-acetate (PMA) (24 h) and house dust mite (HDM) extracts (7th day). RESULTS: Flow cytometry results showed a significant reduction in the absolute number of CD4(+)CD25(high) and the absolute and percentage numbers of CD4(+)CD25(+)CTLA-4(+) in wheezy children compared with healthy controls. Wheezy children at a high risk of developing asthma had a significantly lower absolute number of CD4(+)CD25(+) (P=0.01) and CD4(+)CD25(high) (P=0.04), compared with those at a low risk. After PMA stimulation, CTLA-4 (P=0.03) and Foxp3 (P=0.02) expression was diminished in wheezy children compared with the healthy children. After HDM stimulation, CTLA-4 (P=0.03) and IFN-gamma (P=0.04) expression was diminished in wheezy children compared with healthy children. High-risk children had lower expression of IFN-gamma (P=0.03) compared with low-risk and healthy children and lower expression of CTLA-4 (P=0.01) compared with healthy children. CONCLUSIONS: Although our findings suggest that some immunological parameters are impaired in children with recurrent wheeze, particularly with a high risk for asthma, further studies are needed in order to assess their potential as surrogate predictor factors for asthma in early life

Training in Risk Management and Patient Safety

A Gestão do Risco define-se como a cultura, processos e estruturas que sustentam a gestão efetiva de potenciais oportunidades e efeitos adversos, implicando a definição e a utilização de vários instrumentos que permitem a identificação e a avaliação dos riscos (gestão de risco proactiva) e a deteção e análise de incidentes (gestão de risco reativa). A premência de disponibilizar formação sobre Gestão do Risco e Segurança do Doente a todos os profissionais do Centro Hospitalar de Lisboa Central (CHLC), criou a necessidade de encontrar múltiplas estratégias que permitam alcançar este objetivo. Desta forma a Equipa de Gestão do Risco do CHCL estabeleceu um programa de formação sobre este tema de forma a dar resposta às necessidades de formação neste âmbito em todas as áreas profissionais. Este programa de formação é realizado nos moldes tradicionais de ensino/aprendizagem com obrigatoriedade presencial, constando-se a necessidade de promover outras estratégias de formação modernas que atinjam o máximo de profissionais possível. Uma destas estratégias passa pelo planeamento e organização de formação e-learning nesta área com a finalidade de potencializar um modelo de ensino/aprendizagem não presencial

Informed Switching Strongly Decreases the Prevalence of Antibiotic Resistance in Hospital Wards

Antibiotic resistant nosocomial infections are an important cause of mortality and morbidity in hospitals. Antibiotic cycling has been proposed to contain this spread by a coordinated use of different antibiotics. Theoretical work, however, suggests that often the random deployment of drugs (“mixing”) might be the better strategy. We use an epidemiological model for a single hospital ward in order to assess the performance of cycling strategies which take into account the frequency of antibiotic resistance in the hospital ward. We assume that information on resistance frequencies stems from microbiological tests, which are performed in order to optimize individual therapy. Thus the strategy proposed here represents an optimization at population-level, which comes as a free byproduct of optimizing treatment at the individual level. We find that in most cases such an informed switching strategy outperforms both periodic cycling and mixing, despite the fact that information on the frequency of resistance is derived only from a small sub-population of patients. Furthermore we show that the success of this strategy is essentially a stochastic phenomenon taking advantage of the small population sizes in hospital wards. We find that the performance of an informed switching strategy can be improved substantially if information on resistance tests is integrated over a period of one to two weeks. Finally we argue that our findings are robust against a (moderate) preexistence of doubly resistant strains and against transmission via environmental reservoirs. Overall, our results suggest that switching between different antibiotics might be a valuable strategy in small patient populations, if the switching strategies take the frequencies of resistance alleles into account

Characterisation of Innate Fungal Recognition in the Lung

The innate recognition of fungi by leukocytes is mediated by pattern recognition receptors (PRR), such as Dectin-1, and is thought to occur at the cell surface triggering intracellular signalling cascades which lead to the induction of protective host responses. In the lung, this recognition is aided by surfactant which also serves to maintain the balance between inflammation and pulmonary function, although the underlying mechanisms are unknown. Here we have explored pulmonary innate recognition of a variety of fungal particles, including zymosan, Candida albicans and Aspergillus fumigatus, and demonstrate that opsonisation with surfactant components can limit inflammation by reducing host-cell fungal interactions. However, we found that this opsonisation does not contribute directly to innate fungal recognition and that this process is mediated through non-opsonic PRRs, including Dectin-1. Moreover, we found that pulmonary inflammatory responses to resting Aspergillus conidia were initiated by these PRRs in acidified phagolysosomes, following the uptake of fungal particles by leukocytes. Our data therefore provides crucial new insights into the mechanisms by which surfactant can maintain pulmonary function in the face of microbial challenge, and defines the phagolysosome as a novel intracellular compartment involved in the innate sensing of extracellular pathogens in the lung

The fourth wave of Portuguese emigration: Austerity policies, European peripheries and postcolonial continuities

Little is known about emigration in European countries. Migratory pressure and the recent refugee crisis have helped keep academic attention over the last few decades focused on immigration, asylum and integration in Europe. However, these dynamics promoting entries into European countries coexist with other fair-ly significant dynamics promoting departures from these countries. The sovereign debt crisis coupled with austerity policies that asymmetrically affected Europe’s peripheral countries have increased emigration in various European countries. Our book aims to counter the invisibility of emigration from European countries in the literature by examining the particularities of the Portuguese case. In methodological terms, the book compiles the work of authors from different academic backgrounds who have conducted empirical research using a wide vari-ety of extensive and intensive methods. It is argued that when analysing recent Portuguese emigration it is important to examine in further detail: i) the impact of the 2008 economic and financial crisis and the austerity policies that followed in its wake; ii) south-north emigration in Europe; iii) north-south emigration outside Europe and post-colonial continuities; iv) the importance of reassessing the exist-ing model of Southern European migration; v) highly skilled and less skilled mi-gration; and finally, vi) emigrants’ and their descendants’ identities.info:eu-repo/semantics/publishedVersio

Active and poised promoter states drive folding of the extended HoxB locus in mouse embryonic stem cells

Gene expression states influence the three-dimensional conformation of the genome through poorly understood mechanisms. Here, we investigate the conformation of the murine HoxB locus, a gene-dense genomic region containing closely spaced genes with distinct activation states in mouse embryonic stem (ES) cells. To predict possible folding scenarios, we performed computer simulations of polymer models informed with different chromatin occupancy features, which define promoter activation states or CTCF binding sites. Single cell imaging of the locus folding was performed to test model predictions. While CTCF occupancy alone fails to predict the in vivo folding at genomic length scale of 10 kb, we found that homotypic interactions between active and Polycomb-repressed promoters co-occurring in the same DNA fibre fully explain the HoxB folding patterns imaged in single cells. We identify state-dependent promoter interactions as major drivers of chromatin folding in gene-dense regions