The Vitamin A Derivative All-Trans Retinoic Acid Repairs Amyloid-β-Induced Double-Strand Breaks in Neural Cells and in the Murine Neocortex.

The amyloid-β peptide or Aβ is the key player in the amyloid-cascade hypothesis of Alzheimer's disease. Aβ appears to trigger cell death but also production of double-strand breaks (DSBs) in aging and Alzheimer's disease. All-trans retinoic acid (RA), a derivative of vitamin A, was already known for its neuroprotective effects against the amyloid cascade. It diminishes, for instance, the production of Aβ peptides and their oligomerisation. In the present work we investigated the possible implication of RA receptor (RAR) in repair of Aβ-induced DSBs. We demonstrated that RA, as well as RAR agonist Am80, but not AGN 193109 antagonist, repair Aβ-induced DSBs in SH-SY5Y cells and an astrocytic cell line as well as in the murine cortical tissue of young and aged mice. The nonhomologous end joining pathway and the Ataxia Telangiectasia Mutated kinase were shown to be involved in RA-mediated DSBs repair in the SH-SY5Y cells. Our data suggest that RA, besides increasing cell viability in the cortex of young and even of aged mice, might also result in targeted DNA repair of genes important for cell or synaptic maintenance. This phenomenon would remain functional up to a point when Aβ increase and RA decrease probably lead to a pathological state.

Avaliação de parâmetros morfométricos calculados a partir do contorno de lesões de mama em ultrassonografias na distinção das categorias do sistema BI-RADS

OBJETIVO: Avaliar o desempenho de parâmetros morfométricos, calculados a partir do contorno de lesões de mama em ultrassonografias, na quantificação de suas características morfológicas e na distinção das categorias 2, 3, 4 e 5 do sistema de classificação ecográfica BI-RADS. MATERIAIS E MÉTODOS: A casuística é composta por 40 casos com registro ortogonal de pacientes submetidas à cirurgia. A partir das lesões segmentadas, foram calculados cinco parâmetros morfométricos para quantificar o contorno e a forma das lesões: razão de área, razão de superposição, valor residual normalizado, circularidade e razão entre largura e profundidade. A análise discriminante linear foi usada para selecionar os parâmetros mais significativos na distinção das características morfológicas das lesões, usando como figura de mérito a curva ROC. RESULTADOS: A razão de superposição foi capaz de diferenciar estatisticamente as lesões classificadas como BI-RADS 3 daquelas classificadas como BI-RADS 4 (a = 5%; p = 0,015), sendo, também, o parâmetro morfométrico que apresentou melhor desempenho na diferenciação entre lesões malignas e benignas. CONCLUSÃO: Este resultado indica que a análise morfométrica de lesões de mama em ultrassonografias tem potencial para auxiliar na distinção de pacientes que deveriam ser submetidas à biópsia, daquelas que poderiam manter controle por métodos de imagem.

Aesthetic breast augmentation with hyaluronic acid: imaging findings and implications for radiological assessment

New injectable fillers such as hyaluronic acid have recently been employed as a non-surgical alternative to implants such as silicone for aesthetic breast enhancement. Although their utilization is not yet widespread in Brazil, radiologists should be aware of the imaging findings in this context and of the implications of the presence of this filler for the radiological evaluation in the screening for breast cancer.

Consequences of lineage-specific gene loss on functional evolution of surviving paralogs: ALDH1A and retinoic acid signaling in vertebrate genomes

Genome duplications increase genetic diversity and may facilitate the evolution of gene subfunctions. Little attention, however, has focused on the evolutionary impact of lineage-specific gene loss. Here, we show that identifying lineage-specific gene loss after genome duplication is important for understanding the evolution of gene subfunctions in surviving paralogs and for improving functional connectivity among human and model organism genomes. We examine the general principles of gene loss following duplication, coupled with expression analysis of the retinaldehyde dehydrogenase Aldh1a gene family during retinoic acid signaling in eye development as a case study. Humans have three ALDH1A genes, but teleosts have just one or two. We used comparative genomics and conserved syntenies to identify loss of ohnologs (paralogs derived from genome duplication) and to clarify uncertain phylogenies. Analysis showed that Aldh1a1 and Aldh1a2 form a clade that is sister to Aldh1a3-related genes. Genome comparisons showed secondarily loss of aldh1a1 in teleosts, revealing that Aldh1a1 is not a tetrapod innovation and that aldh1a3 was recently lost in medaka, making it the first known vertebrate with a single aldh1a gene. Interestingly, results revealed asymmetric distribution of surviving ohnologs between co-orthologous teleost chromosome segments, suggesting that local genome architecture can influence ohnolog survival. We propose a model that reconstructs the chromosomal history of the Aldh1a family in the ancestral vertebrate genome, coupled with the evolution of gene functions in surviving Aldh1a ohnologs after R1, R2, and R3 genome duplications. Results provide evidence for early subfunctionalization and late subfunction-partitioning and suggest a mechanistic model based on altered regulation leading to heterochronic gene expression to explain the acquisition or modification of subfunctions by surviving ohnologs that preserve unaltered ancestral developmental programs in the face of gene loss.

Positive predictive values of Breast Imaging Reporting and Data System (BI-RADS®) categories 3, 4 and 5 in breast lesions submitted to percutaneous biopsy

Objective To evaluate the BI-RADS as a predictive factor of suspicion for malignancy in breast lesions by correlating radiological with histological results and calculating the positive predictive value for categories 3, 4 and 5 in a breast cancer reference center in the city of São Paulo. Materials and Methods Retrospective, analytical and cross-sectional study including 725 patients with mammographic and/or sonographic findings classified as BI-RADS categories 3, 4 and 5 who were referred to the authors' institution to undergo percutaneous biopsy. The tests results were reviewed and the positive predictive value was calculated by means of a specific mathematical equation. Results Positive predictive values found for categories 3, 4 and 5 were respectively the following: 0.74%, 33.08% and 92.95%, for cases submitted to ultrasound-guided biopsy, and 0.00%, 14.90% and 100% for cases submitted to stereotactic biopsy. Conclusion The present study demonstrated high suspicion for malignancy in lesions classified as category 5 and low risk for category 3. As regards category 4, the need for systematic biopsies was observed.

Biópsia percutânea de lesões ósseas guiada por tomografia computadorizada: taxas de definição diagnóstica e complicações

Objetivo: Determinar taxas de definição diagnóstica e complicações da biópsia percutânea guiada por tomografia computadorizada (TC) de lesões ósseas suspeitas de malignidade. Materiais e Métodos: Estudo retrospectivo que incluiu 186 casos de biópsia percutânea guiada por TC de lesões ósseas no período de janeiro de 2010 a dezembro de 2012. Todas as amostras foram obtidas usando agulhas de 8 a 10 gauge. Foram coletados dados demográficos, história de neoplasia maligna prévia, dados relacionados à lesão, ao procedimento e ao resultado histológico. Resultados: A maioria dos pacientes era do sexo feminino (57%) e a idade média foi 53,0 ± 16,4 anos. Em 139 casos (74,6%) a suspeita diagnóstica era metástase e os tumores primários mais comuns foram de mama (32,1%) e próstata (11,8%). Os ossos mais envolvidos foram coluna vertebral (36,0%), bacia (32,8%) e ossos longos (18,3%). Houve complicações em apenas três pacientes (1,6%), incluindo uma fratura, um caso de parestesia com comprometimento funcional e uma quebra da agulha necessitando remoção cirúrgica. Amostras de 183 lesões (98,4%) foram consideradas adequadas para diagnóstico. Resultados malignos foram mais frequentes nos pacientes com suspeita de lesão secundária e história de neoplasia maligna conhecida (p < 0,001) e nos procedimentos orientados pela PET/CT (p = 0,011). Conclusão: A biópsia percutânea guiada por TC é segura e eficaz no diagnóstico de lesões ósseas suspeitas.

Tumores primários da órbita incomuns diagnosticados por biópsia com agulha grossa guiada por tomografia computadorizada: relato de dois casos

Biópsia percutânea guiada por tomografia computadorizada é uma alternativa segura e eficaz para avaliação de lesões intraorbitárias selecionadas, em que o diagnóstico pré-operatório é importante para o planejamento terapêutico. Descrevemos dois casos de pacientes com tumores orbitários incomuns em que o diagnóstico foi obtido por biópsia com agulha grossa guiada por tomografia computadorizada, dando ênfase para os aspectos técnicos do procedimento.

The role of gadoxetic acid as a paramagnetic contrast medium in the characterization and detection of focal liver lesions: a review

Recent studies have demonstrated that the use of paramagnetic hepatobiliary contrast agents in the acquisition of magnetic resonance images remarkably improves the detection and differentiation of focal liver lesions, as compared with extracellular contrast agents. Paramagnetic hepatobiliary contrast agents initially show the perfusion of the lesions, as do extracellular agents, but delayed contrast-enhanced images can demonstrate contrast uptake by functional hepatocytes, providing further information for a better characterization of the lesions. Additionally, this intrinsic characteristic increases the accuracy in the detection of hepatocellular carcinomas and metastases, particularly the small-sized ones. Recently, a hepatobiliary contrast agent called gadolinium ethoxybenzyl dimeglumine, that is simply known as gadoxetic acid, was approved by the National Health Surveillance Agency for use in humans. The authors present a literature review and a practical approach of magnetic resonance imaging utilizing gadoxetic acid as contrast agent, based on patients' images acquired during their initial experiment.

Stabilization of the ionic form of weak acid cation exchange resins

Weak acid cation exchange (WAC) resins are used in the chromatographic separation of betaine from vinasse, a by-product of sugar industry. The ionic form of the resin determines the elution time of betaine. When a WAC-resin is in hydrogen form, the retention time of betaine is the longest and betaine elutes as the last component of vi-nasse from the chromatographic column. If the feed solution contains salts and its pH is not acidic enough to keep the resin undissociated, the ionic form of the hydrogen form resin starts to alter. Vinasse contains salts and its pH is around 5, it also contains weak acids. To keep the metal ion content (Na/H ratio) of the resin low enough to ensure successful separation of betaine, acid has to be added to either eluent (water) or vinasse. The aim of the present work was to examine by laboratory experiments which option requires less acid. Also the retention mechanism of betaine was investigated by measuring retention volumes of acetic acid and choline in different Na/H ratios of the resin. It was found that the resulting ionic form of the resin is the same regardless of whether the regeneration acid is added to the eluent or the feed solution (vinasse). Be-sides the salt concentration and the pH of vinasse, also the concentration of weak acids in the feed affects the resulting ionic form of the resin. The more buffering capacity vinasse has, the more acid is required to keep the ionic form of the resin desired. Vinasse was found to be quite strong buffer solution, which means relatively high amounts of acid are required to prevent the Na/H ratio from increasing too much. It is known that the retention volume of betaine decreases significantly, when the Na/H ratio increases. This is assumed to occur, because the amount of hydrogen bonds between the carboxylic groups of betaine and the resin decreases. Same behavior was not found with acetic acid. Choline has the same molecular structure as betaine, but instead of carboxylic group it has hydroxide group. The retention volume of choline increased as the Na/H ratio of the resin increased, because of the ion exchange reaction between choline cation and dissociated carboxylic group of the resin. Since the retention behavior of choline on the resin is opposite to the behavior of be-taine, the strong affinity of betaine towards hydrogen form WAC-resin has to be based on its carboxylic group. It is probable that the quaternary ammonium groups also affect the behavior of the carboxylic groups of betaine, causing them to form hydrogen bonds with the carboxylic groups of the resin.

Effect of diet composition and ration size on key enzyme activities of glycolysis-gluconeogenesis, pentose phosphate pathway and amino acid metabolism in liver of Sparus aurata

The effects of diet composition and ration size on the activities of key enzymes involved in intermediary metabolism were studied in the liver of gilthead sea bream (Sparus aurata). Highcarbohydrate, low-protein diets stimulated 6-phosphofructo 1-kinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40), glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (EC 1.1.1.44) enzyme activities, while they decreased alanine aminotransferase (EC 2.6.1.2) activity. A high degree of correlation was found between food ration size and the activity of the enzymes 6-phosphofructo 1-kinase, pyruvate kinase, glucose-6-phosphate dehydrogenase (positive correlations) and fructose-1,6-bisphosphatase (EC 3.1.3.11) (negative correlation). These correlations matched well with the high correlation also found between ration size and growth rate in starved fish refed for 22 d. Limited feeding (5 g/kg body weight) for 22 d decreased the activities of the key enzymes for glycolysis and lipogenesis, and alanine aminotransferase activity. The findings presented here indicate a high level of metabolic adaptation to both diet type and ration size. In particular, adaptation of enzyme activities to the consumption of a diet with a high carbohydrate level suggests that a carnivorous fish like Sparus aurata can tolerate partial replacement of protein by carbohydrate in the commercial diets supplied in culture. The relationship between enzyme activities, ration size and fish growth indicates that the enzymes quickly respond to dietary manipulations of cultured fish.

Effect of diet composition and ration size on key enzyme activities of glycolysis-gluconeogenesis, pentose phosphate pathway and amino acid metabolism in liver of Sparus aurata

The effects of diet composition and ration size on the activities of key enzymes involved in intermediary metabolism were studied in the liver of gilthead sea bream (Sparus aurata). Highcarbohydrate, low-protein diets stimulated 6-phosphofructo 1-kinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40), glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (EC 1.1.1.44) enzyme activities, while they decreased alanine aminotransferase (EC 2.6.1.2) activity. A high degree of correlation was found between food ration size and the activity of the enzymes 6-phosphofructo 1-kinase, pyruvate kinase, glucose-6-phosphate dehydrogenase (positive correlations) and fructose-1,6-bisphosphatase (EC 3.1.3.11) (negative correlation). These correlations matched well with the high correlation also found between ration size and growth rate in starved fish refed for 22 d. Limited feeding (5 g/kg body weight) for 22 d decreased the activities of the key enzymes for glycolysis and lipogenesis, and alanine aminotransferase activity. The findings presented here indicate a high level of metabolic adaptation to both diet type and ration size. In particular, adaptation of enzyme activities to the consumption of a diet with a high carbohydrate level suggests that a carnivorous fish like Sparus aurata can tolerate partial replacement of protein by carbohydrate in the commercial diets supplied in culture. The relationship between enzyme activities, ration size and fish growth indicates that the enzymes quickly respond to dietary manipulations of cultured fish.

Análisis de herramientas BI en el mercado actual

En este trabajo final de grado se pretende hacer una valoración objetiva de las herramientas disponibles en el mercado actual para la realización de proyectos de business intelligence.

Clasificación automática de textos y explotación BI

El presente proyecto tiene como objetivo desarrollar una tecnología que permita codificar grandes cantidades de texto de manera automática para posteriormente ser visualizada y analizada mediante una aplicación diseñada en Qlikview. El motor de la investigación e implementación de este proyecto se ha encontrado en la incipiente presencia de tecnologías informáticas en los procesos de codificación para ciencias políticas. De esta manera, el programa creado tiene como objetivo automatizar un proceso que se desarrolla comúnmente de manera manual y, por ende, las ventajas de introducir técnicas informáticas son notablemente valiosas. Estas automatizaciones permiten ahorrar tanto en tiempo de codificación, como en recursos económicos o humanos. Se ha elaborado una revisión teórica y metodológica que han servido como instrumentos de estudio y mejora, con el firme propósito de reducir al máximo el margen de error y ofrecer un instrumento de calidad con salida de mercado real. El método de clasificación utilizado ha sido Bayes, y se ha implementado utilizando Matlab. Los resultados de la clasificación han llegado a índices del 99.2%. En la visualización y análisis mediante Qlikview se pueden modificar los parámetros referentes a partido político, año, categoría o región, con lo que se permite analizar numerosos aspectos relacionados con la distribución de las palabras repartidas entre las diferentes categorías y en el tiempo.