63 research outputs found
Use of intravenous immunoglobulin in patients with active vasculitis associated with concomitant infection
Nutritional profile of the Portuguese cabbage (Brassica oleracea L var. costata) and its relationship with the elemental soil analysis
The economic and financial crisis has increased the number of urban horticulture on lands close to present or past industrial areas. "Tronchuda" or the Portuguese cabbage (Brassica oleraceae L var. costata DC) was studied because of its importance in Portuguese diet. It belongs to a number of economically significant horticultural crops (Brassica species), which are also known to be nutritionally well-balanced vegetables. "Tronchuda" produced in urban horticultures from 4 regions of mainland Portugal was studied for its nutritional profile along with elemental soil analysis of each sampling site. This study revealed significant interactions between essential elements in soil and plant leaves - the edible part of the plant for human nutrition. In general, these organs contained poor concentrations of Fe and Si, while Mn is absent, regardless of the sampling sites. Conversely, Ca levels were abundant with values ranging between 3.3% and 3.9%. Soils from CAP showed a soil nutrient exhaustion of Fe, Mn and Mo, although the highest protein and sucrose contents in the leaves was observed in plants growing in those soils. Protein, lipids and carbohydrates concentrations differed according to sampling site, reflecting different production practices.publishersversionpublishe
Fat and Sugar—A Dangerous Duet. A Comparative Review on Metabolic Remodeling in Rodent Models of Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is a common disease in Western society and ranges from steatosis to steatohepatitis to end-stage liver disease such as cirrhosis and hepatocellular carcinoma. The molecular mechanisms that are involved in the progression of steatosis to more severe liver damage in patients are not fully understood. A deeper investigation of NAFLD pathogenesis is possible due to the many different animal models developed recently. In this review, we present a comparative overview of the most common dietary NAFLD rodent models with respect to their metabolic phenotype and morphological manifestation. Moreover, we describe similarities and controversies concerning the effect of NAFLD-inducing diets on mitochondria as well as mitochondria-derived oxidative stress in the progression of NAFLD
AVALIAÇÃO DE FRATURAS RADICULARES POR MEIO DE TOMOGRAFIA COMPUTADORIZADA DE FEIXE CÔNICO
The objective of this article is to critically review the current literature on the evaluation of root fractures using cone beam computed tomography. Electronic databases, such as PubMed, Scopus and Web of Science, were consulted to obtain published articles. In short, the assessment of root fractures using cone beam computed tomography (CBCT) represents an essential tool in contemporary dental practice. The diagnostic accuracy, detailed treatment planning and post-treatment follow-up provided by TCFC are fundamental to ensuring strategic and urgent results for patients. However, it is crucial to consider the limitations and challenges associated with the use of this technology, as well as to continue investing in research and development to further improve the diagnostic and therapeutic capacity in the evaluation of root fractures, always providing the best possible care to patients.O objetivo deste artigo é revisar criticamente a literatura atual sobre a avaliação de fraturas radiculares por meio da tomografia computadorizada de feixe cônico. Realizou-se uma extensa revisão da literatura para identificar estudos relevantes acerca da avaliação de fraturas radiculares por meio de tomografia computadorizada de feixe cônico. Bases de dados eletrônicas, como PubMed, Scopus e Web of Science, foram consultadas para obter artigos publicados. Em suma, a avaliação de fraturas radiculares por meio da tomografia computadorizada de feixe cônico (TCFC) representa uma ferramenta essencial na prática odontológica contemporânea. A precisão diagnóstica, o planejamento de tratamento detalhado e o acompanhamento pós-tratamento fornecido pela TCFC são fundamentais para garantir resultados eficazes e satisfatórios para os pacientes. No entanto, é crucial reconhecer as limitações e desafios associados à utilização dessa tecnologia, bem como continuar investindo em pesquisa e desenvolvimento para aprimorar ainda mais a capacidade diagnóstica e terapêutica na avaliação de fraturas radiculares, visando sempre proporcionar o melhor cuidado possível aos pacientes
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials
Aims:
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594).
Conclusions:
GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Gut microbiota activate Toll-like receptor 4 to trigger vascularization and BMP2 signalling in the murine small intestine
In den vergangenen Jahren wurde erforscht, wie die Darmflora auf die Physiologie des Wirtes wirkt. Mikroorganismen fördern die Erneuerung der Dünndarmmukosa und fördern die Ausprägung vaskulärer Netzwerke in den Villusstrukturen des Dünndarms. Trotz der enormen Fortschritte in der Erforschung der Interaktionen zwischen Darmflora und Wirt sind die durch die Darmflora induzierten Signalwege noch weitgehend unerforscht.
Durch den Einsatz keimfreier Maustechnologie erkundet diese Arbeit neue Signalwege. Die Expression der Adaptormoleküle MyD88, TRIF und TOLLIP des angeborenen Immunsystems wurden durch die Darmflora beeinflusst. Diese Adaptormoleküle sind wichtige Determinanten der Toll-like Rezeptor (TLR) mRNA Expression im Dünndarm. TLR5 Transkripte wurden nicht durch die Darmflora beeinflusst und TLR5 war für die Expression anderer TLR Rezeptoren nicht essentiell. TLR5 hatte jedoch eine entscheidende Rolle bei der Induktion der Bone Morphogenetischen Proteine 4 und 7 im Dünndarm.
Die kommensale Darmflora induziert die verstärkte Vaskularisierung der Dünndarmmukosa und verstärkt die Expression von BMP2. Mit einer Tlr4-defizienten Mauslinie konnte gezeigt werden, dass dieser Rezeptor besonders wichtig für die Vaskularisierung der Dünndarmmukosa ist. Die Hemmung von BMP Typ I Rezeptoren in vitro und in vivo zeigte jedoch keine veränderte Angiogenese, was auf andere Funktionen dieser Rezeptoren im Dünndarm hindeutet. Komponenten des Hedgehog Signalwegs waren im keimfreien Mausmodell vermindert exprimiert und die Regulation dieses Signalwegs wurde über TLR4 und TLR5 vermittelt. In vitro Versuche unterstützen eine wichtige aktivatorische Rolle des Hedgehog-Signalwegs bei der Angiogenese intestinaler Endothelzellen.Over the last years there is increasing evidence of the profound impact of gut microbiota in host physiology. Microbes promote renewal of the small intestinal mucosa and increase vascular networks in small intestinal villi. Despite rapid advances in exploring gut microbiota and host interactions, microbiota-induced signalling pathways remain elusive. By taking advantage of germ-free technology, this work reveals novel signalling pathways. Immune adaptors MyD88, TRIF and TOLLIP were affected by gut microbiota and are determinants of Toll-like receptor (TLR) mRNA expression in the small intestine. TLR5 transcripts were not changed by microbiota nor participated in TLR crosstalk but induced the expression of small intestinal Bone Morphogenetic Proteins BMP4 and BMP7, suggesting a novel pathway. Gut microbiota induces vascularization of the gut mucosa and upregulates small intestinal BMP2 levels. TLR4 was shown to be a pivotal pattern recognition receptor supporting mucosal angiogenesis in the small intestine. Inhibition of BMP type I receptors in in vitro and in vivo experiments did not show implications in angiogenesis, suggesting these receptors have other roles in the small intestine. Also, Hedgehog (Hh) signalling was found to be upregulated by gut microbiota and this seemed mediated by TLR4 and TLR5 immune signalling. In vitro experiments appoint for a crucial role of the Hh pathway in promoting angiogenesis of intestinal endothelial cells
Casas, fantasmas e margens : silêncio e memória traumática em Toni Morrison, Arnaldo Santos e Cornélio Penna
This work proposes a comparative reading of Toni Morrison s Beloved, Cornélio Penna s A menina morta, and Arnaldo Santo s A casa velha das margens, vis-a-vis the presentification of traumatic memory in the haunted houses represented in the these works. Through a reading of Kafka s short story The Burrow , we have sought to study space as both motivation and strategem for rescuing traumatic memory in the three novels under study. In this sense, the presence of the ghost is perceived not only as a structural element in the narratives being investigated, but as a character representing subalternity. The silence which pervades these fictional works has also been analysed both as a representation of the (im)possibility of speaking and as a form of representing the subaltern within the haunted houses from the perspective of the different ways in which, in its randomness, it deconstructs space, constructing, through language, Beloved, A menina morta and A casa velha das margens as representations of precarious and problematic identitiesCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorEste trabalho propõe uma leitura comparativa de Beloved, de Toni Morrison, A menina morta, de Cornélio Penna e A casa velha das margens, de Arnaldo Santos, tendo em vista a questão da presentificação da memória traumática no interior de casas assombradas. A partir de A construção, de Kafka, procurou-se estudar o espaço como motivador e artifício dos resgates de memória que se dão nas três obras citadas. Nesse sentido, foi investigada a presença do fantasma enquanto elemento estruturante da narrativa e enquanto personagem dos três romances, em uma perspectiva de subalternidade. Explorou-se, ainda, o silêncio enquanto (im)possibilidade de fala e de representação do subalterno dentro desses locais, e a forma como ele desconstrói em sua errância o espaço das casas, das construções, fazendo de Beloved, A casa velha das margens e A menina morta, enquanto linguagem, representações de identidade precárias e problemáticas
VOICES FROM THE SOUTH: DECOLONIAL AND POSTCOLONIAL CONVERSATIONS
Over the last ten years, although a certain amount of critical effort has gone into bringing the debates around Postcolonial and Decolonial Studies closer together, these two areas still remain on opposite or different sides of a debate that is often heated and irreconcilable. Particularly at the beginning of the current century, following the publication of Walter Mignolo's (2000) Local Histories/Global Designs, much of the postcolonial criticism found itself on a collision course with decolonial discourse. In the same way, the main authors of the Modernity/Coloniality/Decoloniality group became critics of Postcolonial Studies by formulating the bases of Decolonial thought under the concept of the "Decolonial Turn", which demands a disconnection and break with the Western structures of thought, under which Postcolonialism built its responses to the literature of the former colonialist empires. In this sense, this text intends to investigate the theoretical path that culminates in the break between Decolonial and Postcolonial studies, and our aim is to open up questions that can favor dialogue between the two theoretical fields and also open up possibilities for a South-South dialogue based on a new understanding of the new and old epistemologies
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