216 research outputs found

    Treatment Target in Newly Diagnosed Systemic Lupus Erythematosus: The Association of Lupus Low Disease Activity State and Remission With Lower Accrual of Early Damage

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    Objectives: To compare the effect of achievement and maintenance of lupus low disease activity state (LLDAS) and clinical remission (CR) in preventing early damage accrual in patients with systemic lupus erythematosus (SLE). Methods: In a monocentric cohort of 116 newly diagnosed SLE patients, LLDAS and CR achievement at 6 months (T1) after treatment initiation and their maintenance over the next 12 months were assessed. Early damage was recorded after 18 months of follow-up (T2) using the SLICC/damage index. Uni- and multivariate analysis were performed to evaluate the association of LLDAS and CR with early damage. Results: LLDAS was significantly more attained than CR both at T1 (42.2% vs. 21.6% of patients, p<0.001) and T2 (46.6% vs. 31.9%, p=0.022). Overlap rate between persistent LLDAS and persistent CR was 41.7% (n=15). On multivariate analysis, achievement of CR (OR 0.07, 95%CI 0.01 to 0.59, p=0.015) and LLDAS (OR 0.25, 95%CI 0.06 to 0.99, p=0.049) at T1 were independently associated with lower accrual of early damage. Patients who achieved LLDAS (including CR) at T1 and steadily persisted in this condition until T2 developed significantly less damage compared to those who failed to maintain it during the T1-T2 interval (p=0.003), those who achieved it later than T1 (p<0.001) or those who had never been in this condition (p<0.001). Conclusions: Although CR is recommended as the primary treatment target in SLE, LLDAS represents a valid alternative in the early stage of SLE management. LLDAS and CR maintenance should be targeted to prevent damage

    Antiproliferative and antiviral activity of methanolic extracts from Sardinian Maltese Mushroom (Cynomorium coccineum L.)

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    Cynomorium coccineum is a non-photosynthetic plant that grows in Mediterranean countries and that is amply used in the traditional medicine. The aim of this study was to extend previous studies on the chemical and biological properties of C. coccineum, evaluating the potential antiviral and antiproliferative activity of the methanolic extract. The MTT assay was used for the in vitro cytotoxic studies against human cancer-derived cell lines, while both MTT and plaque reduction (PRT) methods were used to evaluate the potential inhibitory effect of the extract against a panel of mammal viruses. The results obtained showed no selective activity against any DNA and RNA virus but revealed an interesting antiproliferative activity against human leukaemia-derived cell lines

    Collective response to the media coverage of COVID-19 pandemic on Reddit and Wikipedia: mixed-methods analysis

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    Background: The exposure and consumption of information during epidemic outbreaks may alter risk perception, trigger behavioral changes, and ultimately affect the evolution of the disease. It is thus of the uttermost importance to map information dissemination by mainstream media outlets and public response. However, our understanding of this exposure-response dynamic during COVID-19 pandemic is still limited. Objective: The goal of this work is to provide a characterization of media coverage and online collective response to COVID-19 pandemic in four countries: Italy, United Kingdom, United States, and Canada. Methods: We collect a heterogeneous dataset including 227’768 online news articles and 13’448 YouTube videos published by mainstream media, 107’898 users posts and 3’829’309 comments on the social media platform Reddit, and 278’456’892 views to COVID-19 related Wikipedia pages. Results: Our results show that public attention, quantified as users activity on Reddit and active searches on Wikipedia pages, is mainly driven by media coverage and declines rapidly, while news exposure and COVID-19 incidence remain high. Furthermore, by using an unsupervised, dynamical topic modeling approach, we show that while the attention dedicated to different topics by media and online users are in good accordance, interesting deviations emerge in their temporal patterns. Conclusions: Overall, our findings offer an additional key to interpret public perception and response to the current global health emergency and raise questions about the effects of attention saturation on collective awareness, risk perception and thus on tendencies towards behavioural change

    Survivin and p53 expression in patients with Crohn's disease: an immunohistochemical study

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    Crohn’s disease (CD) is characterized by acute phases of patchy transmural inflammation, involving any part of the intestinal tract with intervening periods of remission. It has been well established that patients with Crohn’s disease are at increased risk of developing intestinal adenocarcinoma. The regulation of apoptotic cell death may have an important effect on the pathogenesis and progression of colon cancer. Disturbance of apoptosis is known to be very crucial in neoplastic progression and transformation. Mutations in the proapoptotic and tumor suppressor gene p53 are associated with neoplasia in ulcerative colitis, but little is understood of their significance in Crohn’s disease. Members of the inhibitor of the apoptosis protein (IAP) family including survivin are expressed in many tumors. It is known that well differentiated adenocarcinoma tend to express higher level of survivin than normal mucosa. Expression of survivin was observed in the cytoplasm of adenoma with dysplasia and colonrectal carcinoma cells. In order to explore the role of p53 and survivin as marker of neoplasia in CD patient, the aim of this study was to evaluate, by immunohistochemical analysis, the expression and distribution of p53 and survivin immunoreactive cells in a series of Crohn’s disease bioptic tissues with apparently normal adjacent tissues. The immunohistochemical study showed an increase in p53 and survivin expression. Our results suggest that p53 and survivin overexpression in CD patients may predispose the intestinal mucosa to dysplasia that may progress to a higher grade of neoplasia overtime

    Development and validation of a general approach to predict and quantify the synergism of anti-cancer drugs using experimental design and artificial neural networks

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    The combination of two or more drugs using multidrug mixtures is a trend in the treatment of cancer. retain-->The goal is to search for a synergistic effect and thereby reduce the required dose and inhibit the development of resistance. An advanced model-free approach for data exploration and analysis, based on artificial neural networks (ANN) and experimental design is proposed to predict and quantify the synergism of drugs. The proposed method non-linearly correlates the concentrations of drugs with the cytotoxicity of the mixture, providing the possibility of choosing the optimal drug combination that gives the maximum synergism. The use of ANN allows for the prediction of the cytotoxicity of each combination of drugs in the chosen concentration interval. The method was validated by preparing and experimentally testing the combinations with the predicted highest synergistic effect. In all cases, the data predicted by the network were experimentally confirmed. The method was applied to several binary mixtures of cisplatin and [Cu(1,10-orthophenanthroline)2(H2O)](ClO4)2, Cu(1,10-orthophenanthroline)(H2O)2(ClO4)2 or [Cu(1,10-orthophenanthroline)2(imidazolidine-2-thione)](ClO4)2. The cytotoxicity of the two drugs, alone and in combination, was determined against human acute T-lymphoblastic leukemia cells (CCRF-CEM). For all systems, a synergistic effect was found for selected combinations

    Correlation between NGF/TrkA and microvascular density in human pterygium

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    Pterygium is a surface ocular lesion that is associated with chronic UV exposure. The primary effect is a solar actinic elastosis within the stroma. All the other changes are secondary. Pterygium is characterized by proliferation, inflammatory infiltrates, fibrosis, angiogenesis and extracellular matrix breakdown. The aim of this study was to correlate microvascular density and nerve growth factor (NGF)⁄NGFreceptor transmembrane tyrosine kinase (TrkA) expression in endothelial cells in human pterygium. Specimens of human pterygium obtained from 30 patients who had undergone surgical excision and of 10 normal bulbar conjunctiva were investigated immunohistochemically by using anti-CD31, anti-NGF and anti-TrkA antibodies. Results showed that endothelial cells in human pterygium are immunoreactive to both NGF and its receptor TrkA, and that this immunoreactivity is correlated to microvascular density. The results of this study suggest that an autocrine loop between NGF and its receptor TrkA is activated in pterygium and that it is involved in the angiogenic response taking place in this pathological condition. These data are in accord with recent evidences, which have clearly established that NGF plays a role as an angiogenic factor in several pathological conditions. Understanding the mechanism of angiogenesis in pterygium provides a basis for a rational approach to the development of anti-angiogenic therapy in patients affected by this disease

    Carne de perra, de Fátima Sime: la persistencia de lo urgente

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    La intención de este artículo es demostrar, a partir del análisis de la novela Carne de perra, de la escritora chilena Fátima Sime, la legitimidad y persistencia de un imaginario social que se resiste a desaparecer de la trama simbólica del Chile de la postdictadura. Se trata de una disposición colectiva a revitalizar la memoria del país, para no permitir que el olvido se superponga a la necesidad de vivenciar definitivamente el duelo colectivo, hasta hoy suspendido en el tiempo. La novela aquí revisada procesa y elabora estéticamente las demandas de ese discurso social. Abstract Through an analysis of the novel Carne de perra by Chilean author Fátima Sime, this article aims to demonstrate the legitimate, enduring social construction that persists in the symbolic realm within post-dictatorship Chile. It addresses a shared determination to revive the collective memory to allow the as yet uncompleted collective mourning process to take place before fading into oblivion. The novel reviewed here esthetically processes and elaborates upon the claims of that social discourse

    Nuclear factor-kB expression is predictive of overall survival in patients with cutaneous melanoma

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    Nuclear factor (NF)-kappa B is one of the most important transcription factors that plays a crucial role in the regulation of a wide spectrum of genes involved in modulating the cell cycle, apoptosis, cell growth, angiogenesis, inflammation and the tissue invasiveness of highly malignant cells NF-kappa B activity has been found to be constitutively elevated in a number of human tumors from either a haematological or solid origin, such as melanomas In several studies, NF-kappa B activation was shown to be an adverse prognostic factor, and in melanoma it was proposed as an event that promotes tumor progression This study aimed to evaluate whether NF-kappa B activation in tumor tissues, assessed by the expression of the NF-kappa B p65 subunit, has an effect on the survival of melanoma patients The expression of NF-kappa B was immunohistochemically investigated, and the correlation with survival was analyzed Furthermore, the immunostaining for p53 and survivin was evaluated, and the relationship of these apoptotic and anti-apoptotic factors with NF-kappa B expression was analyzed Kaplan-Meier analysis showed that patients with low levels of NF-kappa B in the nuclei of tumor cells had a significantly longer survival compared to those with high levels Multivariate analysis confirmed the predictive value of nuclear NF-kappa B, showing that its expression maintains significance after the model was adjusted using chnicopathological factors The results demonstrate the correlation of NF-kappa B p65 nuclear staining with the disease-specific 5-year survival of melanoma patients and suggest that nuclear NF-kappa B p65 may be promising as an early independent prognostic factor in patients with primary cutaneous melanoma

    Social data mining and seasonal influenza forecasts: The FluOutlook platform

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    FluOutlook is an online platform where multiple data sources are integrated to initialize and train a portfolio of epidemic models for influenza forecast. During the 2014/15 season, the system has been used to provide real-time forecasts for 7 countries in North America and Europe
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