942 resultados para systemic scleroderma


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A woman stung by the box jellyfish Carybdea marsupialis (Cnidaria, Cubozoa) at a Spanish Mediterranean beach, showed systemic manifestations over several months (pain far from the inoculation point, arthralgia, paresthesia, hyperesthesia, increase of eosinophils and IgE) in addition to the skin condition.

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Purpose: To determine whether systemic fungal infection could cause activation of retinal microglia and therefore could be potentially harmful for patients with retinal degenerative diseases. Methods: Activation of retinal microglia was measured in a model of sublethal invasive candidiasis in C57BL/6J mice by (i) confocal immunofluorescence and (ii) flow cytometry analysis, using anti-CD11b, anti-Iba1, anti-MHCII and anti-CD45 antibodies. Results: Systemic fungal infection causes activation of retinal microglia, with phenotypic changes in morphology, surface markers expression, and microglial re-location in retinal layers. Conclusions: As an excessive or prolonged microglial activation may lead to chronic inflammation with severe pathological side effects, causing or worsening the course of retinal dystrophies, a systemic infection may represent a risk factor to be considered in patients with ocular neurodegenerative diseases, such as diabetic retinopathy, glaucoma, age-related macular degeneration or retinitis pigmentosa.

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This brief study makes some reflections on the systemic paradigm and the claim that Reality is a system advocated by some thinkers. We argue that the General Systems Theory is an abstract theory relating to formal reasons that correspond to real systems scientifically established, and its development can facilitate the task mentioned, which is characteristic of ordinary scientific work.

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Building on the concept of Granger causality in risk in Hong et al. (2009), and focusing on an international sample of large-capitalization banks, we test for predictability in comovements in the left tails of returns of individual banks and the global system. The main results show that large individual shocks (defined as balance-sheet contractions exceeding the 1% VaR level) are a strong predictor of subsequent shocks in the global system. This evidence is particularly strong for US banks with large desks of proprietary trading. Similarly, we document strong evidence of financial vulnerabilities (exposures) to systemic shocks in US subprime creditors.

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La sclérodermie (SSc) est une maladie rare affectant les personnes génétiquement prédisposées d’une réponse immunitaire défectueuse. Malgré les derniers avancements et développements dans le domaine, l’étiologie et la pathogénèse de la maladie demeurent peu comprises. Par ailleurs, il y a un ralentissement dans la compréhension de cette maladie à cause du manque de modèle animal représentatif de la SSc humaine. Malgré plusieurs lacunes, les souris traitées avec la bléomycine ou portant des modifications génétiques (TSK-1) sont très utilisées dans les études précliniques de la SSc mais elles ne présentent pas toutes les caractéristiques de cette maladie. Pour contribuer à la recherche sur la SSc, la stagiaire postdoctorale Dre Heena Mehta a développé dans le laboratoire du Dre Sarfati en collaboration avec le Dr Senécal, un modèle de souris expérimental induit par l’immunisation de cellules dendritiques (DCs) chargées de peptides de la protéine topoisomérase I (TOPOIA et TOPOIB). Dans le but de caractériser ce modèle murin et d’établir un profil immunitaire, j’ai concentré mes analyses principalement sur les caractéristiques de la SSc telles que la fibrose, l’inflammation, l’hyper-γ-globulinémie polyclonale, la vasculopathie ainsi que de l’expression de cytokines. Brièvement, l’immunisation de souris avec les DCs chargées avec la topoisomérase I (TOPOI) a induit l’inflammation pulmonaire et cutanée, en plus de la fibrose sous forme diffuse (dcSSc). Les souris présentaient également des symptômes de la vasculopathie ainsi que des taux élevés d’anticorps polyclonaux. Les résultats démontraient que les peptides TOPOIA étaient efficaces dans l’induction de la fibrose et de la réponse inflammatoire alors que les peptides TOPOIB étaient surtout impliqués dans la fibrose cutanée. En plus de nos résultats, les observations préliminaires sur le profil de cytokines tissulaires suggéraient que ce modèle pourrait remplacer ou complémenter les autres modèles animaux de SSc.

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This CEPS Policy Brief examines the provisions for bail-in in the European Union – that is, the principle whereby any public measure to recapitalise a bank with insufficient prudential capital must be preceded by a write-down or conversion into equity of creditors’ claims – in state aid policies and in the new resolution framework for failing banks, with two aims: i) to assess whether and how they are coordinated and ii) more importantly, whether they address satisfactorily the question of systemic stability that may arise when investors fear that creditors’ claims are likely to be bailed-in in a bank crisis. The issue is especially relevant in the present context, as the comprehensive assessment exercise underway for EU banks falling under the direct supervision of the European Central Bank may lead supervisors to require substantial capital injections simultaneously for many of the banks involved, possibly shaking investors’ confidence across EU banking markets. The authors conclude that the two sets of rules are, broadly speaking, mutually consistent and that they already contain sufficient safeguards to address systemic stability concerns. However, the balance of the elements underpinning the European Commission’s decisions in individual cases may not be clear to bank creditors and potential investors in financial markets. The impression of unneeded rigidity on this very sensitive issue has been heightened by official statements over-emphasising that each case will be assessed individually under competition rules, thus feeding the concern that the systemic dimension of the issue may have been underestimated. Therefore, further clarification by the Commission may be needed on how the various criteria will be applied during the ongoing transition to banking union – perhaps through a new communication completing the state aid framework for banks in view of the adoption of the new resolution rules.

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The European Commission decided to carry out a public consultation, which closed on 13 July, on the possible inclusion of investor-to-state dispute settlement (ISDS) provisions in the Transatlantic Trade and Investment Partnership (TTIP). This decision came in a context of polarised public debate around this procedural mechanism which enables investors to bring a case against a country that hosts their investments. Even though the main question is whether or not to include ISDS in TTIP, the Commission eyes the public consultation as a way to correct the inconsistencies of the mechanism by modernising it. However, the inclusion of ISDS in TTIP will not be a miracle cure because ISDS is a complex multilayered systemic challenge which requires a multilateral solution. In this Policy Brief, Romain Pardo explores which challenges are posed by ISDS and the extent at which TTIP’s contribution can tackle these challenges.

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Measures undertaken by the Belarusian government in the areas of the economy, internal affairs and foreign policy in recent months have proven increasingly ineffective. Despite the deteriorating macroeconomic situation, Minsk is not implementing the reforms necessary to combat the crisis and its activity is limited only to feigned actions and administrative regulations. As a result, the economic situation is worsening but the chances of obtaining external loans as support, for example from the International Monetary Fund (IMF), are decreasing. At the same time there is mounting fear among the regime of social unrest, therefore by raising salaries of the least well-off groups of citizens it is trying to compensate for the increased costs of living. On the other hand, the government is extending the scope of control over society and competences of enforcement bodies. Belarus’s room for manoeuvre in foreign policy has also been diminishing substantially. Despite the EU’s declared willingness to reach an agreement and its encouragement, Lukashenko is not ready to make concessions in the political sphere (e.g. to rehabilitate political prisoners), and this is hindering the normalisation of relations with the West. Minsk furthermore feels a mounting pressure from Moscow, making the Belarusian negotiating position ever weaker. The lack of freedom of manoeuvre in foreign policy, no possibility to maintain a costly economic model and the lack of support from the majority of society all prove that Alexander Lukashenko’s regime is in severe crisis. The system he established is no longer able to respond to current threats with adequate and effective strategies. This situation is challenging the regime’s stability and calls into question its viability in the longer term.

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The Russian economy grew rapidly between 2000 and 2007, but growth decelerated after the 2008-09 global financial crisis, and since mid-2014 Russia has moved into recession. A number of short-term factors have caused recession: lower oil prices, the conflict with Ukraine, European Union and United States sanctions against Russia and Russian counter-sanctions. However Russia's negative output trends have deeper structural and institutional roots. They can be tracked back about a decade to when previous market-reform policies started to be reversed in favour of dirigisme, leading to further deterioration of the business and investment climate. • Russia must address its short-term problems, but in the medium-to-long term it must deal with its fundamental structural and institutional disadvantages: oil and commodity dependence and an unfriendly business and investment climate underpinned by poor governance. Compared to many other commodity producers, Russia is better placed to diversify its economy, mostly due to its excellent human capital. Ruble depreciation makes this task easier

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The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.

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Besides its importance in cattle, Neospora caninum may also pose a high risk as abortifacient for small ruminants. We have recently demonstrated that the outcome of experimental infection of pregnant sheep with 10(6) Nc-Spain7 tachyzoites is strongly dependent on the time of gestation. In the current study, we assessed peripheral and local immune response in those animals. Serological analysis revealed earlier and higher IFN-γ and IgG responses in ewes infected at early (G1) and mid (G2) gestation, when abortion occurred. IL-4 was not detected in sera from any sheep. Inflammatory infiltrates in the placenta mainly consisted of CD8+ and, to a lesser extent, CD4+ T cells and macrophages (CD163+). The infiltrate was more intense in sheep infected at mid-gestation. In the foetal mesenchyme, mostly free tachyzoites were found in animals infected at G1, while those infected in G2 displayed predominantly particulate antigen, and parasitophorous vacuoles were detected in sheep infected at G3. A similar pattern of placental cytokine mRNA expression was found in all groups, displaying a strengthened upregulation of IFN-γ and IL-4 and milder increases of TNF-α and IL-10, reminiscent of a mixed Th1 and Th2 response. IL-12 and IL-6 were only slightly upregulated in G2, and TGF-β was downregulated in G1 and G2, suggestive of limited T regulatory (Treg) cell activity. No significant expression of TLR2 or TLR4 could be detected. In summary, this study confirms the pivotal role of systemic and local immune responses at different times of gestation during N. caninum infection in sheep.

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BACKGROUND Stiff skin syndrome and systemic or localized scleroderma are cutaneous disorders characterized by dermal fibrosis and present clinically with induration of the skin, with or without joint, internal organ or vascular involvement. OBJECTIVES To provide clinical, histological and preliminary genetic analysis of two West Highland white terrier siblings presenting with indurated skin resembling stiff skin syndrome in humans. ANIMALS Two client owned full sibling West Highland white terriers from two different litters. METHODS Clinical examination, histopathological examination and whole genome sequencing analysis of affected and unaffected West Highland white terriers. RESULTS Affected dogs exhibited markedly indurated skin that was attached firmly to the underlying tissue and incomplete closure of the mouth and eyes. No abnormalities were found by neurological or orthopaedic examination, radiographs of the head or whole body computed tomography. Histologically, the dermis and pannicular septa were thickened by a marked increase in coarse collagen fibres and a mild to moderate increase in collagen fibre diameter. The syndrome most likely follows an autosomal recessive mode of inheritance. The sequence analysis did not reveal any obvious causative variant in the investigated candidate genes ADAMTSL2 and FBN1. CONCLUSION AND CLINICAL IMPORTANCE The clinical phenotype and histopathological features of two West Highland white terrier siblings resembled stiff skin syndrome in humans. Unlike in humans, or previously described beagles with stiff skin, there was no restriction of joint mobility. Genetic analysis did not detect a candidate causative variant and warrants further research.