Heterogeneity analysis of Metastasis Associated in Colon Cancer 1 (MACC1) for survival prognosis of colorectal cancer patients: a retrospective cohort study.

BACKGROUND Metastasis of colorectal cancer (CRC) is directly linked to patient survival. We previously identified the novel gene Metastasis Associated in Colon Cancer 1 (MACC1) in CRC and demonstrated its importance as metastasis inducer and prognostic biomarker. Here, we investigate the geographic expression pattern of MACC1 in colorectal adenocarcinoma and tumor buds in correlation with clinicopathological and molecular features for improvement of survival prognosis. METHODS We performed geographic MACC1 expression analysis in tumor center, invasive front and tumor buds on whole tissue sections of 187 well-characterized CRCs by immunohistochemistry. MACC1 expression in each geographic zone was analyzed with Mismatch repair (MMR)-status, BRAF/KRAS-mutations and CpG-island methylation. RESULTS MACC1 was significantly overexpressed in tumor tissue as compared to normal mucosa (p < 0.001). Within colorectal adenocarcinomas, a significant increase of MACC1 from tumor center to front (p = 0.0012) was detected. MACC1 was highly overexpressed in 55% tumor budding cells. Independent of geographic location, MACC1 predicted advanced pT and pN-stages, high grade tumor budding, venous and lymphatic invasion (p < 0.05). High MACC1 expression at the invasive front was decisive for prediction of metastasis (p = 0.0223) and poor survival (p = 0.0217). The geographic pattern of MACC1 did not correlate with MMR-status, BRAF/KRAS-mutations or CpG-island methylation. CONCLUSION MACC1 is differentially expressed in CRC. At the invasive front, MACC1 expression predicts best aggressive clinicopathological features, tumor budding, metastasis formation and poor survival outcome.

Cell-to-cell communication--periodontal regeneration.

BACKGROUND Although regenerative treatment options are available, periodontal regeneration is still regarded as insufficient and unpredictable. AIM This review article provides scientific background information on the animated 3D film Cell-to-Cell Communication - Periodontal Regeneration. RESULTS Periodontal regeneration is understood as a recapitulation of embryonic mechanisms. Therefore, a thorough understanding of cellular and molecular mechanisms regulating normal tooth root development is imperative to improve existing and develop new periodontal regenerative therapies. However, compared to tooth crown and earlier stages of tooth development, much less is known about the development of the tooth root. The formation of root cementum is considered the critical element in periodontal regeneration. Therefore, much research in recent years has focused on the origin and differentiation of cementoblasts. Evidence is accumulating that the Hertwig's epithelial root sheath (HERS) has a pivotal role in root formation and cementogenesis. Traditionally, ectomesenchymal cells in the dental follicle were thought to differentiate into cementoblasts. According to an alternative theory, however, cementoblasts originate from the HERS. What happens when the periodontal attachment system is traumatically compromised? Minor mechanical insults to the periodontium may spontaneously heal, and the tissues can structurally and functionally be restored. But what happens to the periodontium in case of periodontitis, an infectious disease, after periodontal treatment? A non-regenerative treatment of periodontitis normally results in periodontal repair (i.e., the formation of a long junctional epithelium) rather than regeneration. Thus, a regenerative treatment is indicated to restore the original architecture and function of the periodontium. Guided tissue regeneration or enamel matrix proteins are such regenerative therapies, but further improvement is required. As remnants of HERS persist as epithelial cell rests of Malassez in the periodontal ligament, these epithelial cells are regarded as a stem cell niche that can give rise to new cementoblasts. Enamel matrix proteins and members of the transforming growth factor beta (TGF-ß) superfamily have been implicated in cementoblast differentiation. CONCLUSION A better knowledge of cell-to-cell communication leading to cementoblast differentiation may be used to develop improved regenerative therapies to reconstitute periodontal tissues that were lost due to periodontitis.

Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients

PURPOSE Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. METHODS AND MATERIALS Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. RESULTS The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). CONCLUSIONS The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this situation.

Assessment of the Hong Kong Liver Cancer Staging System in Europe.

BACKGROUND & AIMS European and American guidelines have endorsed the Barcelona Clinic Liver Cancer (BCLC) staging system. The aim of this study was to assess the performance of the recently developed Hong Kong Liver Cancer (HKLC) classification as a staging system for hepatocellular carcinoma (HCC) in Europe. METHODS We used a pooled set of 1693 HCC patients combining three prospective European cohorts. Discrimination ability between the nine substages and five stages of the HKLC classification system was assessed. To evaluate the predictive power of the HKLC and BCLC staging systems on overall survival, Nagelkerke pseudo R2, Bayesian Information Criterion and Harrell's concordance index were calculated. The number of patients who would benefit from a curative therapy was assessed for both staging system. RESULTS The HKLC classification in nine substages shows suboptimal discrimination between the staging groups. The classification in five stages shows better discrimination between groups. However, the BCLC classification performs better than the HKLC classification in the ability to predict OS. The HKLC treatment algorithm tags significantly more patients to curative therapy than the BCLC. CONCLUSIONS The BCLC staging system performs better for European patients than the HKLC staging system in predicting OS. Twice more patients are eligible for a curative therapy with the HKLC algorithm, whether this translates in survival benefit remains to be investigated. This article is protected by copyright. All rights reserved.

An ultrasensitive NanoLuc-based luminescence system for monitoring Plasmodium berghei throughout its life cycle

BACKGROUND: Bioluminescence imaging is widely used for cell-based assays and animal imaging studies, both in biomedical research and drug development. Its main advantages include its high-throughput applicability, affordability, high sensitivity, operational simplicity, and quantitative outputs. In malaria research, bioluminescence has been used for drug discovery in vivo and in vitro, exploring host-pathogen interactions, and studying multiple aspects of Plasmodium biology. While the number of fluorescent proteins available for imaging has undergone a great expansion over the last two decades, enabling simultaneous visualization of multiple molecular and cellular events, expansion of available luciferases has lagged behind. The most widely used bioluminescent probe in malaria research is the Photinus pyralis firefly luciferase, followed by the more recently introduced Click-beetle and Renilla luciferases. Ultra-sensitive imaging of Plasmodium at low parasite densities has not been previously achieved. With the purpose of overcoming these challenges, a Plasmodium berghei line expressing the novel ultra-bright luciferase enzyme NanoLuc, called PbNLuc has been generated, and is presented in this work. RESULTS: NanoLuc shows at least 150 times brighter signal than firefly luciferase in vitro, allowing single parasite detection in mosquito, liver, and sexual and asexual blood stages. As a proof-of-concept, the PbNLuc parasites were used to image parasite development in the mosquito, liver and blood stages of infection, and to specifically explore parasite liver stage egress, and pre-patency period in vivo. CONCLUSIONS: PbNLuc is a suitable parasite line for sensitive imaging of the entire Plasmodium life cycle. Its sensitivity makes it a promising line to be used as a reference for drug candidate testing, as well as the characterization of mutant parasites to explore the function of parasite proteins, host-parasite interactions, and the better understanding of Plasmodium biology. Since the substrate requirements of NanoLuc are different from those of firefly luciferase, dual bioluminescence imaging for the simultaneous characterization of two lines, or two separate biological processes, is possible, as demonstrated in this work.

Glioma-specific alternative RNA splicing: A role for polypyrimidine tract binding protein-1

Alternative RNA splicing plays an integral role in cell fate determination and function, especially in the cells of the brain. Errors in RNA processing contribute to diseases such as cancer, where it leads to the production of oncogenic proteins or the loss of tumor suppressors. In silica mining suggests that hundreds of splice isoforms are misexpressed in the glial cell-derived glioma. However, there is little experimental evidence of the prevalence and contribution of these changes and whether they contribute to the formation and progression of this devastating malignancy. To determine the frequency of these aberrant events, global profiling of alternative RNA splice patterns in glioma and nontumor brain was conducted using an exon array. Most splicing changes were less than 5-fold in magnitude and 14 cassette exon events were validated, including 7 previously published events. To determine the possible causes of missplicing, the differential expression levels of splicing factors in these two tissues were also analyzed. Six RNA splicing factors had greater than 2-fold changes in expression. The highest differentially expressed factor was polypyrimidine tract binding protein-1 (PTB). Evaluation by immunohistochemistry determined that this factor was elevated in both early and late stages of glioma. Glial cell-specific PTB expression in the adult brain led me to examine the role of PTB in gliomagenesis. Downregulation of PTB slowed glioma cell proliferation and migration and enhanced cell adhesion to fibronectin and vitronectin. To determine whether PTB was affecting these processes through splicing, genome-wide exon expression levels were correlated with PTB levels. Surprisingly, previously reported PTB target transcripts were insensitive to changes in PTB levels in both patient samples and PTB-depleted glioma cells. Only one validated glioma-specific splice target, RTN4/Nogo, had a significant PTB-mediated splicing change. Downregulation of PTB enhanced inclusion of its alternative exon 3, which encodes an auxiliary domain within a neurite inhibitor protein. Overexpression of this splice isoform in glioma cells slowed proliferation in a manner similar to that observed in PTB knockdown cells. In summary, aberrant expression of splicing factors such as PTB in glioma may elicit changes in splicing patterns that enhance tumorigenesis. ^

The feasibility of self-report advance directives among elderly patients with cognitive impairment

The central objective of this dissertation was to determine the feasibility of self-completed advance directives (AD) in older persons suffering from mild and moderate stages of dementia. This was accomplished by identifying differences in ability to complete AD among elderly subjects with increasing degrees of dementia and cognitive incompetence. Secondary objectives were to describe and compare advance directives completed by elders and identified proxy decision makers. Secondary objectives were accomplished by measuring the agreement between advance directives completed by proxy and elder, and comparing that agreement across groups defined by the elder's cognitive status. This cross-sectional study employed a structured interview to elicit AD, followed by a similar interview with a proxy decision maker identified by the elder. A stratified sampling scheme recruited elders with normal cognition, mild, and moderate forms of dementia using the Mini Mental-State Exam (MMSE). The Hopkins Competency Assessment Test (HCAT) was used for evaluation of competency to make medical decisions. Analysis was conducted on "between group" (non-demented $\leftrightarrow$ mild dementia $\leftrightarrow$ moderate dementia, and competent $\leftrightarrow$ incompetent) and "within group" (elder $\leftrightarrow$ family member) variation.^ The 118 elderly subjects interviewed were generally male, Caucasian, and of low socioeconomic status. Mean age was 77. Overall, elders preferred a "trial of therapy" regarding AD rather than to "always receive the therapy". No intervention was refused outright more often than it was accepted. A test-retest of elders' AD revealed stable responses. Eleven logic checks measured appropriateness of AD responses independent of preference. No difference was found in logic error rates between elders grouped by MMSE or HCAT. Agreement between proxy and elder responses showed significant dissimilarity, indicating that proxies were not making the same medical decisions as the elders.^ Conclusions based on these data are: (1) Self reporting AD is feasible among elders showing signs of cognitive impairment and they should be given all opportunities to complete advance directives, (2) variation in preferences for advance directives in cognitively impaired elders should not be assumed to be the effects of their impairment alone, (3) proxies do not appear to forego life-prolonging interventions in the face of increasing impairment in their ward, however, their advance directives choices are frequently not those of the elder they represent. ^

Variación estructural y hábitat de poblaciones de Gymnocalycium schickendantzii (Cactaceae) en Mendoza, Argentina : efecto de las plantas nurses

Este trabajo informa sobre aspectos ecológicos de la estructura y hábitat de poblaciones de Gymnocalycium schickendantzii (F. A. C. Weber) Britton & Rose var., un cactus endémico de Argentina. En Mendoza vive en los desiertos áridos del centro-este en matorrales de Larrea cuneifolia más Zuccagnia punctata. Las variaciones de densidad de poblaciones de este cactus, a nivel de muestra, dependen de la facilitación y protección ofrecida por las plantas nurses. El recuento de los individuos desarrollados bajo los arbustos determinó: una alta proporción de la población dentro de estados juveniles (67,3%) y maduros (21,8%), la poca cantidad de plántulas (9,9%) y la casi ausencia de plantas adultas (1,0%). La incorporación del cactus está condicionada a la altura y cobertura de las plantas nurses que regulan los valores de temperaturas y fertilidad bajo sus copas. En este sentido Larrea cuneifolia, Tricomaria usillo y Zuccagnia punctata son las nurses más aceptadas. Se encontró que las variaciones de los porcentajes de densidad de cactus vivos fueron altamente significativas. Esta población está amenazada potencialmente por actividades humanas: explotación petrolera, ganadera, etc. Los resultados, que muestran la variación natural del establecimiento de la población de Gymnocalycium, podrían ser de utilidad para su manejo y conservación.

La estética de lo bello y la exaltación de la cultura popular

Alegato en favor del concepto clásico de belleza y en contra de la concepción postmodernista de que todo puede ser arte y todos artistas. Se trata de rescatar la concepción de estética contenida en las obras de la Escuela de Frankfurt, especialmente de Theodor W. Adorno y Herbert Marcuse: el arte como lealtad a la promesa de felicidad. Se rescata la función crítica y anticipativa del gran arte y se pone en cuestión el carácter presumiblemente progresista y democrático del arte contemporáneo. Las élites actuales, legitimadas democráticamente, comparten las mismas inclinaciones estéticas de las masas, pero ejerciendo una función manipulativa en la configuración de la vida cotidiana.

Comparación a campo de distintos cultivares de olivo (Olea europaea L.) como hospedadores de Siphoninus phillyreae (Haliday)

La mosca blanca del fresno, Siphoninus phillyreae (Haliday) , es una especie polífaga invasiva que causa graves daños en sus hospedadores, entre ellos el olivo (Olea europaea L.). El uso del hospedador por parte de S. phillyreae fue observado en tres cultivares de olivo (Arauco, Arbequina y Aloreña) en el norte de la provincia de La Rioja (Argentina) durante 2007 y 2008. De cada cultivar se muestrearon seis plantas infestadas y de cada planta se tomaron ocho hojas. De cada hoja se registró la abundancia de adultos y estados inmaduros de la mosca blanca que fueron comparadas entre los cultivares mediante modelos lineales generales y mixtos. Los resultados obtenidos mostraron diferencias significativas entre las densidades de adultos y ninfas de S. phillyreae en los distintos cultivares de olivo analizados. Dichos resultados indican que este insecto realiza un uso diferente de los cultivares de olivo, siendo Arauco y Arbequina las variedades hospedadoras más utilizadas en la zona de estudio.

Detección de Ralstonia solanacearum en Solanum tuberosum L. en el Estado de Sonora, México

Ralstonia solanacearum (Rs) produce la enfermedad cuarentenaria denominada marchitez bacteriana en papa. México es un país importador de semilla de Estados Unidos de América y Canadá, aspecto significante para provocar una eventual introducción de esta enfermedad en áreas con amplias extensiones de papa. Sonora es una región importante en relación con la producción de este cultivo. Por lo anteriormente expuesto, se realizó la presente investigación, teniendo como objetivos: a) la producción de antisuero para la bacteria Rs; b) diagnosticar Rs en tubérculos de importación que se utilizan para siembra, y en tubérculos de procedencia mexicana para consumo humano, que son utilizados como semilla; c) la detección de la bacteria durante el desarrollo vegetativo de lotes de papa en Sonora, México. Se analizó tubérculo semilla de importación, de consumo humano, plantas de papa, hojas y tubérculos de producción; los métodos de detección utilizados fueron medios de cultivos específicos, ELISA, antisuero producido y pruebas de patogenicidad. Los resultados mostraron positiva la presencia de Rs en tubérculos de consumo; en tubérculos de importación y en etapas vegetativas fue negativa. Cada prueba de detección por separado no debe ser utilizada como método único; la presencia de Rs representa un riesgo de eventual manifestación de la enfermedad, por lo que es necesario que las áreas productoras realicen actividades de control preventivo fitosanitario.

Distribution of ostracoda in the lower Cretaceous succession of ODP Hole 80-549 (Figure 3)

Site 549 recovered a Lower Cretaceous succession which has been shown to include parts of the Barremian and Albian stages. Forty-four species of Ostracoda are illustrated and their stratigraphic distribution used to recognise three major facies units. An high diversity inner shelf facies earlier in the Barremian gives way to a low diversity, outer shelf facies, higher in the succession. The early Albian appears to indicate a return to an inner shelf fauna. The faunas recovered have been compared to similar faunas elsewhere in N. W. Europe.

La organización territorial del movimiento de trabajadores desocupados Aníbal Verón del barrio Malvinas de la ciudad de La Plata

Este trabajo sintetiza los resultados de un estudio de campo realizado en la Organización Territorial del Movimiento de Trabajadores Desocupados Aníbal Verón del Barrio Malvinas de la ciudad de La Plata, entre el mes de Marzo del año 2003 (momento en el cual la Organización Territorial comienza sus actividades en el barrio y se incorpora, paulatinamente, al Movimiento de Trabajadores Desocupados Aníbal Verón) y los primeros meses del año 2005, cuando esta Organización conforma, junto a otras, el Frente Popular Darío Santillán. Los principales temas aquí desarrollados están relacionados, en principio, con la novedosa forma de participación político-comunitaria que insertó esta Organización Territorial en un barrio como Malvinas donde predominaban, desde hacía más de veinte años, formas de participación político-comunitarias de tipo clientelar. Otro de los temas aquí abordados está relacionado con los vínculos existentes entre la Organización Territorial y el Movimiento Regional. En esta trama vincular, se observó un desfasaje entre los criterios y acuerdos propuestos por el movimiento y las prácticas político-comunitarias llevadas adelante por la organización y los vecinos del barrio. Por último, en esta investigación también son centrales los distintos tipos de actores que interpretaban al movimiento de diferente manera. Aquí se observaron diversas formas de actuar, participar y comprometerse. En aquel momento, esto me llevó a proponer el armado de una tipología de participación de la que se desprende que la participación de los integrantes de la Organización Territorial del MTD Aníbal Verón del Barrio Malvinas, entre el año 2003 y 2005 era directa, inestable y complementaria. Lo que hacía que se fuera modificando con el propio devenir de la organización en movimiento. Es un trabajo más bien empírico y se nutrió por un lado, de datos obtenidos de entrevistas y observaciones realizadas para dos proyectos de extensión en los cuales participé y por otro, del trabajo de campo realizado entre el mes de Junio del año 2003 y Marzo del año 2005. El trabajo de campo constó de observaciones participantes y no participantes y, de entrevistas a los integrantes de la organización territorial. Entre el mes de octubre del año 2003 y el mes de enero del año 2004 realicé veinte entrevistas en profundidad. Para su realización se tomaron cuotas por sexo y edad hasta agotar información

Counselors' education in complex contexts with special reference to Latin America

This paper makes reference to the importance lying, at present, on the professional education of counselors. It goes through the history of the different pre-scientific and scientific stages of counseling, and it points out the main representatives in Latin America . It also shows the current state of the specialization, taking as an antecedent some in-depth, widely encompassing research carried out in the European Union in this area. Coincidences and differences are exposed here in terms of professional profiles, university degrees, institutional dependence, up-dating processes and modes of intervention. The current state of postgraduate studies at university is also touched upon, and the different proposals for further education in Latin America are analyzed as well as their dependence upon an undergraduate degree in Psychology, Educational Sciences or Psycho-pedagogy. Finally, this paper places counseling within the complexity and the need to provide all-encompassing and integrative answers which require a wide and deep enough education so as to answer all these issues and problems.

Registro de lectura : Dispositivo pedagógico que acompaña trayectorias formativas universitarias

El siguiente trabajo se enmarca en la línea de investigación sobre formación docente en Educación Física, desarrollada en el Centro Regional Universitario Bariloche de la Universidad Nacional del Comahue (CRUB-UNCo). Los proyectos que la integran, a partir del incremento sostenido del número de estudiantes que abandonan la carrera durante los dos primeros años, procuran interrogar las prácticas pedagógicas universitarias en ese campo, desentrañar sus modos particulares de producción y analizar su impacto en la constitución de los trayectos formativos de los y las estudiantes. En las indagaciones hallamos indicios de un trabajo docente sistemático para mejorar las condiciones de la enseñanza y del aprendizaje e identificamos dispositivos pedagógicos institucionales y áulicos a modo de andamiaje de las trayectorias estudiantiles y modos de recepción a los y las ingresantes. En esta oportunidad describimos y analizamos uno de estos dispositivos, denominado "registro de lectura", generado en la cátedra Pedagogía del 1º año del Profesorado en Educación Física del mencionado centro universitario. Dicho instrumento forma parte de una serie de prácticas pedagógicas deliberadamente planificadas en relación con el ingreso, la permanencia y el egreso del nivel superior, que pretende habilitar mejores escenarios para el desarrollo de los procesos educativos. El dispositivo, construido a modo de andamiaje de las prácticas lectoras de los y las estudiantes, pretende contribuir a la promoción de trayectorias formativas democráticas y procura dar lugar a nuevas explicaciones en tanto anclajes para la transformación y para la construcción de nuevos conocimientos así como lograr mejores intervenciones pedagógicas