Factors affecting clinical decision-making in inflammatory bowel disease and the role of point-of-care calprotectin

Objectives: Patient-reported symptoms correlate poorly with mucosal inflammation. Clinical decision-making may, therefore, not be based on objective evidence of disease activity. We conducted a study to determine factors associated with clinical decision-making in a secondary care inflammatory bowel disease (IBD) population, using a cross-sectional design. Methods: Decisions to request investigations or escalate medical therapy were recorded from outpatient clinic encounters in a cohort of 276 patients with ulcerative colitis (UC) or Crohn’s disease (CD). Disease activity was assessed using clinical indices, self-reported flare and faecal calprotectin ≥ 250 µg/g. Demographic, disease-related and psychological factors were assessed using validated questionnaires. Logistic regression was performed to determine the association between clinical decision-making and symptoms, mucosal inflammation and psychological comorbidity. Results: Self-reported flare was associated with requesting investigations in CD [odds ratio (OR) 5.57; 95% confidence interval (CI) 1.84-17.0] and UC (OR 10.8; 95% CI 1.8-64.3), but mucosal inflammation was not (OR 1.62; 95% CI 0.49-5.39; and OR 0.21; 95% CI 0.21-1.05, respectively). Self-reported flare (OR 7.96; 95% CI 1.84-34.4), but not mucosal inflammation (OR 1.67; 95% CI 0.46-6.13) in CD, and clinical disease activity (OR 10.36; 95% CI 2.47-43.5) and mucosal inflammation (OR 4.26; 95% CI 1.28-14.2) in UC were associated with escalation of medical therapy. Almost 60% of patients referred for investigation had no evidence of mucosal inflammation. Conclusions: Apart from escalation of medical therapy in UC, clinical decision-making was not associated with mucosal inflammation in IBD. The use of point-of-care calprotectin testing may aid clinical decision-making, improve resource allocation and reduce costs in IBD

Full genome sequence and sfRNA interferon antagonist activity of Zika virus from Recife, Brazil

Background: The outbreak of Zika virus (ZIKV) in the Americas has transformed a previously obscure mosquito-transmitted arbovirus of the Flaviviridae family into a major public health concern. Little is currently known about the evolution and biology of ZIKV and the factors that contribute to the associated pathogenesis. Determining genomic sequences of clinical viral isolates and characterization of elements within these are an important prerequisite to advance our understanding of viral replicative processes and virus-host interactions. Methodology/Principal findings: We obtained a ZIKV isolate from a patient who presented with classical ZIKV-associated symptoms, and used high throughput sequencing and other molecular biology approaches to determine its full genome sequence, including non-coding regions. Genome regions were characterized and compared to the sequences of other isolates where available. Furthermore, we identified a subgenomic flavivirus RNA (sfRNA) in ZIKV-infected cells that has antagonist activity against RIG-I induced type I interferon induction, with a lesser effect on MDA-5 mediated action. Conclusions/Significance: The full-length genome sequence including non-coding regions of a South American ZIKV isolate from a patient with classical symptoms will support efforts to develop genetic tools for this virus. Detection of sfRNA that counteracts interferon responses is likely to be important for further understanding of pathogenesis and virus-host interactions

Modular Composition of Gene Transcription Networks

Predicting the dynamic behavior of a large network from that of the composing modules is a central problem in systems and synthetic biology. Yet, this predictive ability is still largely missing because modules display context-dependent behavior. One cause of context-dependence is retroactivity, a phenomenon similar to loading that influences in non-trivial ways the dynamic performance of a module upon connection to other modules. Here, we establish an analysis framework for gene transcription networks that explicitly accounts for retroactivity. Specifically, a module's key properties are encoded by three retroactivity matrices: internal, scaling, and mixing retroactivity. All of them have a physical interpretation and can be computed from macroscopic parameters (dissociation constants and promoter concentrations) and from the modules' topology. The internal retroactivity quantifies the effect of intramodular connections on an isolated module's dynamics. The scaling and mixing retroactivity establish how intermodular connections change the dynamics of connected modules. Based on these matrices and on the dynamics of modules in isolation, we can accurately predict how loading will affect the behavior of an arbitrary interconnection of modules. We illustrate implications of internal, scaling, and mixing retroactivity on the performance of recurrent network motifs, including negative autoregulation, combinatorial regulation, two-gene clocks, the toggle switch, and the single-input motif. We further provide a quantitative metric that determines how robust the dynamic behavior of a module is to interconnection with other modules. This metric can be employed both to evaluate the extent of modularity of natural networks and to establish concrete design guidelines to minimize retroactivity between modules in synthetic systems.United States. Air Force Office of Scientific Research (FA9550-12-1-0129

Diphenyl diselenide protects neuronal cells against oxidative stress and mitochondrial dysfunction : involvement of the glutathione-dependent antioxidant system

Oxidative stress and mitochondrial dysfunction are critical events in neurodegenerative diseases; therefore, molecules that increase cellular antioxidant defenses represent a future pharmacologic strategy to counteract such conditions. The aim of this study was to investigate the potential protective effect of (PhSe)2 on mouse hippocampal cell line (HT22) exposed to tert-BuOOH (in vitro model of oxidative stress), as well as to elucidate potential mechanisms underlying this protection. Our results showed that tert-BuOOH caused time- and concentration- dependent cytotoxicity, which was preceded by increased oxidants production and mitochondrial dysfunction. (PhSe)2 pre-incubation significantly prevented these cytotoxic events and the observed protective effects were paralleled by the upregulation of the cellular glutathione-dependent antioxidant system: (PhSe)2 increased GSH levels (> 60%), GPx activity (6.9-fold) and the mRNA expression of antioxidant enzymes Gpx1 (3.9-fold) and Gclc (2.3-fold). Of note, the cytoprotective effect of (PhSe)2 was significantly decreased when cells were treated with mercaptosuccinic acid, an inhibitor of GPx, indicating the involvement of GPx modulation in the observed protective effect. In summary, the present findings bring out a new action mechanism concerning the antioxidant properties of (PhSe)2. The observed upregulation of the glutathione-dependent antioxidant system represents a future pharmacologic possibility that goes beyond the well-known thiol-peroxidase activity of this compound

Simple and lowecost transition metal-free borophosphate glass catalyst for aromatic alcohol oxidation by sodium hypochlorite

The oxidation of primary and secondary alcohols to their respective aldehydes/ketones is one of the most important reactions in fine chemistry due to the industrial application of these products. Based on this, a large number of new catalysts and oxidants have been tested using this reaction as a catalytic model, mainly looking for a process that ensures high aldehyde selectivity. In this paper, we have used moisture stable borophosphate glass doped with 10 mol% Al2O3 as a heterogeneous catalyst in the oxidation of sodium hypochlorite, an effective, greener, and low-cost oxidant, using acetonitrile as solvent under mild conditions. The glass catalyst mass and the particle size were evaluated, as were the reaction temperature and oxidant amount, to determine the ideal reaction conditions where the conversions achieved 87.0 mol% for 1-phenylethanol to acetophenone and 79.4 mol% for benzyl alcohol to benzaldehyde, with benzaldehyde selectivity above 95%. Although sodium hypochlorite is a strong oxidant, benzaldehyde was the main product of the oxidation of benzyl alcohol due to the formation of a biphasic organic-aqueous system that protects the aldehyde from oxidation and allows the reaction to occur without the use of a phase transfer catalyst (PTC). HPLC analysis of both phases showed that alcohols, aldehyde, and ketone were mostly present in the organic phase (concentrations above 98.7%). During the reaction, a small amount of alcohol is transferred to the aqueous phase, where the oxidation took place. Once formed, the products are transferred back to the organic phase. ICP-OES analysis indicates that borophosphate glass acts in the reaction by partially releasing phosphate-based groups, reducing the pH of hypochlorite to 9. In this sense, borophosphate glasses prove to be a simple and inexpensive alternative for the development of new catalysts

Uso de laserterapia de baixa potência no tratamento da inflamação gengival em paciente portadorde mucopolissacaridose tipo II: relato de caso clínico

Trabalho de Conclusão de Curso apresentado para obtenção do grau de Bacharel no Curso de Odontologia da Universidade do Extremo Sul Catarinense – UNESC.A terapia a laser tem sido amplamente reconhecida como um dos principais avanços tecnológicos na área da saúde e seu uso tem se expandido de forma significativa em diversas áreas, inclusive na odontologia. A laserterapia de baixa potência tem sido adotada como uma modalidade terapêutica para promover efeitos analgésicos, bioestimulação e antiinflamatórios. A eficácia dessa terapia em casos de inflamações gengivais pode ser explicada por seus efeitos biológicos, como o aumento do fluxo sanguíneo, a modulação da resposta imunológica e a redução da dor e do inchaço. A utilização dessa prática tecnológica tem sido adotada com sucesso em pacientes portadores de doenças sistêmicas, sendo essencial seguir protocolos e observar a resposta aos seus efeitos visando desta forma minimizar os efeitos inflamatórios, e proporcionando melhor qualidade de vida aos pacientes. Objetivo: Analisar a efetividade da laserterapia de baixa potência no tratamento de inflamação gengival em um paciente com síndrome de Hunter. Caso clínico: Paciente sindrômico apresentando inflamação e hiperplasia gengival, recebe tratamento com o uso do laser vermelho com energia de 1 Joule em sessões rotineiras de 15 em 15 dias. Conclusão: Após a análise deste estudo o uso de um tratamento com laserterapia de baixa potência mostra ser uma abordagem terapêutica eficaz para o tratamento de inflamação proporcionando um conforto e uma melhor qualidade de vida para o paciente

Extracellular superoxide dismutase is necessary to maintain renal blood flow during sepsis development

Background: Extracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasing superoxide levels and preventing peroxynitrite generation, which is important in maintaining renal blood flow and in preventing acute kidney injury. However, the profile of ECSOD expression after sepsis is not fully understood. Therefore, we intended to evaluate the content and gene expression of superoxide dismutase (SOD) isoforms in the renal artery and their relation to renal blood flow. Methods: Sepsis was induced in Wistar rats by caecal ligation and perforation. Several times after sepsis induction, renal blood flow (12, 24 and 48 h); the renal arterial content of SOD isoforms, nitrotyrosine, endothelial and inducible nitric oxide synthase (e-NOS and i-NOS), and phosphorylated vasodilator-stimulated phosphoprotein (pVASP); and SOD activity (3, 6 and 12 h) were measured. The influence of a SOD inhibitor was also evaluated. Results: An increase in ECSOD content was associated with decreased 3-nitrotyrosine levels. These events were associated with an increase in pVASP content and maintenance of renal blood flow. Moreover, previous treatment with a SOD inhibitor increased nitrotyrosine content and reduced renal blood flow. Conclusions: ECSOD appears to have a major role in decreasing peroxynitrite formation in the renal artery during the early stages of sepsis development, and its application can be important in renal blood flow control and maintenance during septic insult

PADRÕES GLOBAIS DE INGESTÃO DE MICROPLÁSTICOS POR PEIXES: UMA REVISÃO CIENCIOMÉTRICA

Abstract: Billions of tons of plastic released into the environment are mostly fragmented into smaller particles that reach rivers and oceans and can be toxic to aquatic organisms. This study aimed to review and quantify published data on the abundance of Microplastics (MPs) ingested by fish through a scientometric analysis. A search was conducted in the Web of Science database using keywords (microplastic, nanoplastic, plastic, fish) and Boolean operators (or), including studies from natural and controlled environments. This search resulted in the registration of 673 documents, with the majority of studies conducted in China (24.55%). The most influential countries in addressing scientific topics were England and the United States, showing that the high impact of research is not related to the high number of publications. Keywords: plastic particles, aquatic organisms, fibers, emerging pollutants, microplastics.        Resumen: Billones de toneladas de plástico liberadas en el ambiente, en su mayoría se fragmentan en partículas más pequeñas que llegan a ríos y océanos y pueden ser tóxicas para los organismos acuáticos. Este estudio tuvo como objetivo revisar y cuantificar datos publicados sobre la abundancia de microplásticos (MPs) ingeridos por peces mediante un análisis cientométrico. Se realizó una búsqueda en la base de datos de Web of Science utilizando palabras clave (microplástico, nanoplastico, plástico, pez) y operadores booleanos (o), incluyendo estudios de ambientes naturales y controlados. Esta búsqueda resultó en el registro de 673 documentos, siendo la mayoría de los estudios realizados en China (24,55%). Los países más influyentes en el abordaje de temas científicos fueron Inglaterra y Estados Unidos, mostrando que el alto impacto de la investigación no está relacionado con el alto número de publicaciones. Palabras clave: partículas plásticas, organismos acuáticos, fibras, contaminantes emergentes, microplásticos.Résumé: Les milliards de tonnes de plastique libérées dans l'environnement, principalement fragmentées en particules plus petites qui atteignent les rivières et les océans, peuvent être toxiques pour les organismes aquatiques. Cette étude visait à passer en revue et à quantifier les données publiées sur l'abondance de microplastiques (MP) ingérés par les poissons à travers une analyse scientométrique. Une recherche a été menée dans la base de données Web of Science en utilisant des mots-clés (microplastique, nanoplastique, plastique, poisson) et des opérateurs booléens (ou), y compris des études menées dans des environnements naturels et contrôlés. Cette recherche a abouti à l'enregistrement de 673 documents, la plupart des études ayant été menées en Chine (24,55 %). Les pays les plus influents dans l'approche des thèmes scientifiques étaient l'Angleterre et les États-Unis, montrant que l'impact élevé de la recherche n'est pas lié au nombre élevé de publications. Mots-clés: particules plastiques, organismes aquatiques, fibres, polluants émergents, microplastiques.Resumo: Os bilhões de toneladas de plástico liberados no ambiente, em sua maioria são fragmentados em partículas menores que chegam aos rios e oceanos e podem ser tóxicas para os organismos aquáticos. Este estudo teve como objetivo revisar e quantificar dados publicados sobre a abundância de Microplásticos (MPs) ingeridos por peixes por meio de análise cienciométrica. Foi realizada uma busca na base de dados Web of Science utilizando palavras-chave (microplástico, nanoplástico, plástico, peixe) e operadores booleanos (or), incluindo estudos de ambientes naturais e controlados. Essa busca resultou no registro de 673 documentos, dos quais a maior parte dos estudos foi realizada na China (24,55%). Os países mais influentes na abordagem de temas científicos foram Inglaterra e Estados Unidos, mostrando que o alto impacto das pesquisas não é referente ao alto número de publicações. Palavras-chave: partículas plásticas. organismos aquáticos. fibras. poluentes emergentes. microplástico

Full genome sequence and sfRNA interferon antagonist activity of Zika virus from Recife, Brazil

BACKGROUND: The outbreak of Zika virus (ZIKV) in the Americas has transformed a previously obscure mosquito-transmitted arbovirus of the Flaviviridae family into a major public health concern. Little is currently known about the evolution and biology of ZIKV and the factors that contribute to the associated pathogenesis. Determining genomic sequences of clinical viral isolates and characterization of elements within these are an important prerequisite to advance our understanding of viral replicative processes and virus-host interactions. METHODOLOGY/PRINCIPAL FINDINGS: We obtained a ZIKV isolate from a patient who presented with classical ZIKV-associated symptoms, and used high throughput sequencing and other molecular biology approaches to determine its full genome sequence, including non-coding regions. Genome regions were characterized and compared to the sequences of other isolates where available. Furthermore, we identified a subgenomic flavivirus RNA (sfRNA) in ZIKV-infected cells that has antagonist activity against RIG-I induced type I interferon induction, with a lesser effect on MDA-5 mediated action. CONCLUSIONS/SIGNIFICANCE: The full-length genome sequence including non-coding regions of a South American ZIKV isolate from a patient with classical symptoms will support efforts to develop genetic tools for this virus. Detection of sfRNA that counteracts interferon responses is likely to be important for further understanding of pathogenesis and virus-host interactions

The Dreyfus model of clinical problem-solving skills acquisition: a critical perspective

Context: The Dreyfus model describes how individuals progress through various levels in their acquisition of skills and subsumes ideas with regard to how individuals learn. Such a model is being accepted almost without debate from physicians to explain the ‘acquisition’ of clinical skills. Objectives: This paper reviews such a model, discusses several controversial points, clarifies what kind of knowledge the model is about, and examines its coherence in terms of problem-solving skills. Dreyfus’ main idea that intuition is a major aspect of expertise is also discussed in some detail. Relevant scientific evidence from cognitive science, psychology, and neuroscience is reviewed to accomplish these aims. Conclusions: Although the Dreyfus model may partially explain the ‘acquisition’ of some skills, it is debatable if it can explain the acquisition of clinical skills. The complex nature of clinical problem-solving skills and the rich interplay between the implicit and explicit forms of knowledge must be taken into consideration when we want to explain ‘acquisition’ of clinical skills. The idea that experts work from intuition, not from reason, should be evaluated carefully