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.

O mal que se adivinha: polícia e menoridade no Rio de Janeiro (1910-1920). En: Avá, nº 16

O mal que se adivinha: polícia e menoridade no Rio de Janeiro ( 1 9 1 0 - 1 9 2 0 ) de Adriana de Resende Vianna es un estudio que se ubica en el campo de la antropología histórica . Aborda el proceso por el cual se construyó un personaje social - el ‘menor ’- a través de las prácticas cotidianas que la Policía del Distrito Federal de Río de Janeiro ejercía sobre un conjunto de individuos entre 1910 y 1920. Se trata de un escrito minucioso que intenta iluminar cómo al identificar individuos bajo el rótulo ‘menores’, atribuir varios significados al término e intervenir sobre el los se crea la existencia social de ese personaje, y al mismo tiempo se instituyen y legitiman los actores que realizan estas tareas.

El Gaucho Cubillos

El hombre de existencia real Juan Francisco Cubillos sembró un itinerario de hechos delictivos en Mendoza y sur de San Juan. Fuerzas policiales lo mataron en Los Paramillos de Uspallata, cuando contaba sólo 27 años. Inmediatamente el recuerdo popular de sus hazañas exaltó su figura con devoción religiosa. Con el tiempo se fue acrecentando su fama hasta adquirir la dimensión de leyenda o, tal vez, de mito con repercusiones que bien pudieran incidir en la identidad cultural de Mendoza. El teatro local reflejó las posibilidades estéticas del personaje en varias oportunidades, marcando un ciclo tardío de la gauchesca de sorprendente éxito tanto en lo autoral y espectacular como en la recepción.

Espacio, presencia, acontecimiento: configuración semántica de la existencia ficcional en un modelo teatral históricamente hegemónico

¿Qué implica para un personaje o para cualquier entidad habitante de un universo de ficción existir ficcionalmente? ¿Cuáles son los procedimientos que construyen esa existencia y cuáles sus consecuencias en el plano semántico? Mi contribución pretende responder esos interrogantes a partir de la demostración de la siguientes hipótesis: existe en el teatro un modelo tradicionalmente dominante de construcción de la existencia ficcional; los habitantes de un mundo ficcional adquieren su existencia, en ese modelo teatral hegemónico, mediante dos tipos de procedimientos semióticos: cualquier presencia inscripta en el espacio escénico y la autoridad legitimadora de existencia que tienen ciertos par-lamentos; la configuración semántica de la existencia ficcional no resulta sólo de los principios constructivos semióticos sino también de presuposiciones que pone en marcha el espectador a partir de sus hábitos interpretativos; la interacción entre procedimientos semióticos y operaciones activadas por el espectador genera, para esta clase de mundos ficcionales, una configuración semántica particular de la categoría de existencia.

Maluco. La novela de los descubridores: la desacralización de la figura del cronista

En Maluco, la novela de los descubridores de Napoleón Baccino Ponce de León, el serio asunto de contar la Historia queda a cargo de Juanillo Ponce, el bufón de la expedición, quien desde su singular visión del mundo focalizará su mirada, en tanto narrador testigo de los hechos, en la diégesis del descubrimiento del estrecho de Magallanes. La infausta expedición que hace posible tan importante evento geopolítico comprende los años 1519-1520. El texto propone un debate intertextual, en particular a partir de los registros anteriores, de la impugnación de los mismos efectuada por el personaje narrador y, también, desde los juegos que se formalizan para desprestigiar un supuesto discurso histórico hegemónico. El signo dominante de estas reescrituras es su formulación paródica. Se escribe no desde la centralidad y las certezas que otorga la razón, sino desde los bordes, para dar voz a aquellos que durante siglos no la tuvieron o fueron silenciados.

Iverna Codina en su novela

Con La luna ha muerto, Iverna Codina escritora chileno-argentina inicia un camino de búsqueda del sentido de su obra y de su responsabilidad social como novelista. Parte del axioma de que la literatura es expresión de la vida humana, una vida que siempre es lucha y agonía. En una estructura ramificada de trama y cotramas, los personajes - Claudio, Valentina, Ariel, Marcelo, Felipe y otros, todos artistas- se cuestionan permanentemente acerca de su destino personal, pero también sobre las distintas formas de encarar la literatura y el arte. En estos dilemas es evidente la influencia de La gaviota de Chejov. Las indagaciones existenciales de los personajes -diversas según la personalidad de cada uno- se manifiestan por medio de las peripecias narrativas, del diálogo entre personajes y de los símbolos de la luna y del ascenso al Aconcagua. Por su parte, la novelista, en su propia búsqueda,toma la decisión de ser una escritora comprometida con el ser humano sufriente, como su personaje Valentina.

La teatralidad: eje temático de la narrativa de Roberto Arlt y Leopoldo Marechal

A partir de la común afición de Roberto Arlt y Leopoldo Marechal por el género dramático, se analizan los elementos teatralizadores presentes en sus novelas, en orden a señalar la importancia que adquieren en la configuración total de la obra y también el diverso fundamento ideológico que en cada uno de los escritores es dable advertir. En efecto, así como ambos mantienen la convicción de que hay una escisión entre el ser y la apariencia, Marechal entiende que Dios es el Espectador de una vistosa comedia interpretada por los hombres. De ahí que Sujeto y Objeto de la representación se distingan nítidamente. En Arlt, por el contrario, la actuación reúne dentro de un mismo personaje al Actor y al Espectador, que así se debate alocadamente en un juego sin fin.