Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression.

BACKGROUND: It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis. METHODS: We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression. RESULTS: No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does.

Mechanisms of apoptosis in chronic lymphocytic leukemia (CLL)

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by the accumulation of terminally differentiated, mature B cells that do not progress beyond the G1 stage of cell cycle, suggesting that these cells possess intrinsic defects in apoptosis. Treatment relies heavily on chemotherapy (primarily nucleoside analogs and glucocorticoids) that may initially be effective in patients, but ultimately give rise to refractory, untreatable disease. The purpose of this study was to determine whether key components of the apoptotic machinery were intact in CLL lymphocytes, especially in patients refractory to therapy. ^ Activation of proteases has been shown to be at the core of the apoptotic pathway and this work demonstrates that protease activation is required for glucocorticoid and nucleoside analog-induced apoptosis in CLL cells. Inhibitors of serine proteases as well as caspase inhibitors blocked induced DNA fragmentation, and a peptide inhibitor of the nuclear scaffold (NS) protease completely suppressed both induced and spontaneous apoptosis. However, the NS protease inhibitor actually promoted several pro-apoptotic events, such as caspase activation, exposure of surface phosphatidylserine, and loss of mitochondrial membrane potential. These results suggested that the NS protease may interact with the apoptotic program in CLL cells at two separate points. ^ In order to further investigate the role of the NS protease in CLL, patient isolates were treated with proteasome inhibitors because of previous results suggesting that the ISIS protease might be a β subunit of the proteasome. Proteasome inhibitors induced massive DNA fragmentation in every patient tested, even in those resistant to the effects of glucocorticoid and nucleoside analogs in vitro. Several other features of apoptosis were also promoted by the proteasome inhibitor, including mitochondrial alterations such as release of cytochrome c and drops in mitochondrial membrane potential. Proteasome inhibitor-induced apoptosis was associated with inhibition of NFκB, a proteasome-regulated transcription factor that has been implicated in the suppression of apoptosis in a number of systems. The NS protease inhibitor also caused a decrease in active NFκB, suggesting that the proapoptotic effects of this agent might be due to depletion of NFκB. ^ Given these findings, the role of NFκB, in conferring survival in CLL was investigated. Glucocorticoid hormone treatment was shown to cause decreases in the activity of the transcription factor, while phorbol dibutyrate, which blocks glucocorticoid-induced DNA fragmentation, was capable of upregulating NFκB. Compellingly, introduction of an undegradable form of the constitutive NFκB inhibitor, IκB, caused DNA fragmentation in several patient isolates, some of which were resistant to glucocorticoid in vitro. Transcription of anti-apoptotic proteins by NFκB was postulated to be responsible for its effects on survival, but Bcl-2 levels did not fluctuate with glucocorticoid or proteasome inhibitor treatment. ^ The in vitro values generated from these studies were organized into a database containing numbers for over 250 patients. Correlation of relevant clinical parameters revealed that levels of spontaneous apoptosis in vitro differ significantly between Rai stages. Importantly, in vitro resistance to nucleoside analogs or glucocorticoids predicted resistance to chemotherapy in vivo, and inability to achieve remission. ^

Random Sampling with Interspike-Intervals of the Exponential Integrate and Fire Neuron: A Computational Interpretation of UP-States

Oscillations between high and low values of the membrane potential (UP and DOWN states respectively) are an ubiquitous feature of cortical neurons during slow wave sleep and anesthesia. Nevertheless, a surprisingly small number of quantitative studies have been conducted only that deal with this phenomenon’s implications for computation. Here we present a novel theory that explains on a detailed mathematical level the computational benefits of UP states. The theory is based on random sampling by means of interspike intervals (ISIs) of the exponential integrate and fire (EIF) model neuron, such that each spike is considered a sample, whose analog value corresponds to the spike’s preceding ISI. As we show, the EIF’s exponential sodium current, that kicks in when balancing a noisy membrane potential around values close to the firing threshold, leads to a particularly simple, approximative relationship between the neuron’s ISI distribution and input current. Approximation quality depends on the frequency spectrum of the current and is improved upon increasing the voltage baseline towards threshold. Thus, the conceptually simpler leaky integrate and fire neuron that is missing such an additional current boost performs consistently worse than the EIF and does not improve when voltage baseline is increased. For the EIF in contrast, the presented mechanism is particularly effective in the high-conductance regime, which is a hallmark feature of UP-states. Our theoretical results are confirmed by accompanying simulations, which were conducted for input currents of varying spectral composition. Moreover, we provide analytical estimations of the range of ISI distributions the EIF neuron can sample from at a given approximation level. Such samples may be considered by any algorithmic procedure that is based on random sampling, such as Markov Chain Monte Carlo or message-passing methods. Finally, we explain how spike-based random sampling relates to existing computational theories about UP states during slow wave sleep and present possible extensions of the model in the context of spike-frequency adaptation.

Clonality and Antimicrobial Susceptibility of Burkholderia cepacia complex Isolates Collected from Cystic Fibrosis Patients during 1998-2013 in Bern, Switzerland.

For the first time, we analyzed the clonality and susceptibility of Burkholderia cepacia complex isolates (n=55) collected during 1998-2013 from 44 Swiss cystic fibrosis (CF)-patients. B. cenocepacia (n=28) and B. multivorans (n=14) were mainly of sequence type (ST) 833 and ST874, respectively; B. contaminans isolates were of ST102. Overall, the following MIC50/90s (mg/l) were obtained: piperacillin/tazobactam (≤ 4/≥ 128), ticarcillin/clavulanate (≥ 256/≥256), ceftazidime (2/≥ 32), aztreonam (16/≥ 32), meropenem (2/8), tobramycin (8/≥ 16), minocycline (≤ 1/16), levofloxacin (≤ 0.5/≥ 16), and trimethoprim/sulfamethoxazole (≤ 0.5/4). This is the first survey providing information on the clonality of Bcc detected in Switzerland. Species identification and antimicrobial susceptibility tests should always be routinely performed to adapt more targeted therapies.

Rescatando del Leteo crítico a Juan Crisóstomo Lafinur

A menudo la diosa Crítica argentina se empecina en sumergir en el río del olvido a no pocas figuras literarias de nuestro país del siglo XIX. Se podrían ofrecer como excusas, en algunos casos, el despótico paso del tiempo (mientras más nos alejamos del presente más difícil es indagar sobre talo cual autor); en otros, la escasa información biográfica; o la condición paupérrima de ciertas ediciones; o el estado a veces inabarcable de hombresorquesta de estos individuos (son poetas, guerreros, filósofos, etc. y esto sin descuidar ninguno de sus oficios), y así seguiríamos enumerando hasta el hartazgo. Pero así como existe una tendencia a lograr una moderna historiografia argentina de la mano de estudiosos como Tulio Halperin Donghi, revisando los hechos a la luz de sus desencadenantes ideológicos, también se debería proponer un buceo histórico-literario para sacar a la luz varias perlas literarias, engarzadas en sus correspondientes ideologías. Este trabajo se propone ser la ayuda virgiliana que rescate del olvido a Juan Crisóstomo Lafinur, sobre todo su labor poética, ya que de la filosófica todos sabemos de su importante trascendencia. Para esta última sólo tenemos que recordar las palabras de Roberto F. Giusti: "La historia de la evolución mental argentina quedaría incompleta si en ella no hiciésemos un lugar a Lafinur".

Conflito, resistência e philía no Héracles furioso, de Eurípides

En la pieza Heracles Furioso, de Eurípides, el héroe se somete a la prueba definitiva: vencerse a sí mismo, aceptar seguir con vida después de cometer un error irremediable. La acción dramática tiene doble motivación, humana y divina. El conflicto humano requiere capacidad de resistencia de la familia y amigos de Heracles y la oposición de Lico es un elemento clave para la acción. En el enfrentamiento posterior entre Heracles y la diosa Hera, la victoria corresponde a la deidad, motivando a la catástrofe, pero se confirma la heroicidad de Heracles, que se resiste a la tentación de aniquilación tras el asesinato de sus niños. Su amigo, el rey Teseo, le proporciona el apoyo necesario para disuadirle de su propósito de aniquilamiento y fortalece al héroe decaído para la resistencia. La valoración de philia es un elemento importante en la constitución de la significación del texto de Eurípides

O Programa Esporte e Lazer da Cidade e o seu Processo Formativo para Egressos do Curso de Educação Física da Universidade Federal de Santa Maria

O Programa Esporte e Lazer da Cidade - Universidade Federal de Santa Maria (PELC/UFSM) tem por objetivo através de atividades de esporte e lazer, proporcionarem espaços para a prática de diferentes modalidades para a comunidade em geral. E para alunos egressos do curso de Educaçao Física que integram este Programa, observamos uma oportunidade de experiência e construçao de conhecimentos teóricos e práticos frente às dificuldades encontradas no decorrer do mesmo. O presente trabalho buscou identificar e compreender de que maneira a atuaçao no referido Programa repercute sobre percurso formativo dos egressos do Curso de Educaçao Física Licenciatura do Centro de Educaçao Física e Desportos (CEFD/UFSM). O estudo caracterizou- se como uma pesquisa qualitativa e de caráter exploratório e descritivo com análise documental. O instrumento aplicado aos participantes da pesquisa foi um questionário contendo nove questoes. Através dos dados obtidos realizamos uma discussao entre o percurso formativo dos egressos e suas experiências formativas, formaçao inicial do Curso de Licenciatura e as atividades extensionistas, sendo possível assim, constatar a relevância do Programa para construçao e consolidaçao de uma identidade profissional e pessoal, do ?ser Professor?, frente às experiências e conhecimentos adquiridos ao longo do percurso formativo

Proceso de creación de una lista de autoridades de nombres geográficos de Argentina

La diversidad de los nombres geográficos de Argentina, sumados a los casos de sinonimia, homonimia y variantes de la forma del nombre ?incluida la ortografía-hace necesario realizar el control de puntos de acceso para asegurar la coherencia del catálogo y, por ende, el acceso a la colección documental. Se propone entonces, una metodología para la confección de una Lista de nombres geográficos de Argentina que proporcione un punto de acceso controlado y sus referencias, de acuerdo a las Reglas angloamericanas de catalogación, 2ª edición, revisión de 2002, actualización de 2003 [AACR2]. Se presentan los ejemplos en una base de datos diseñada sobre el software CDS/ISIS 1.5 [build3] para Windows [versión completa: AR], UNESCO, 2003 [llamado comúnmente Winisis], con el formato de autoridades UNIMARC de IFLA [International Federation of Library Associations and Institutions], 2ª edición y actualización, siguiendo las Directrices para registros de autoridad y referencias [GARR], 2ª edición y las Directrices para los registros de autoridad y referencia de materia [GSARE]

Apontamentos sobre a representação de Afrodite em Baquílides

Este artículo se dedica al estudio de Afrodita en los poemas del poeta mélico tardo-arcaico Baquílides, específicamente en el Fr.20 B, el Ditirambo 17 y en el Epinicio 5. Se toma como base la rperesnetación de la diosa en la mélica griega arcaica, con excepción de Píndaro, a fin de observar semejanzas y diferencias en su diseño en el poeta de Ceos y en el modo en que el erotismo figura en el pequeño corpus considerado, principalmente en el tercer texto indicado