[Knowledge, attitude and reservations of medical students about organ transplantation: results of a survey during the first year of study]

AIM: Establish a list of first year medical students' attitudes, doubts, and knowledge in the fields of organ transplantation and donation. METHOD: Anonymized questionnaire handed out to students during class lectures. RESULTS: 183 questionnaires were distributed and 117 returned (participation: 64%). The average age of the students was 21.6 +/- 2.7 years (range 18 to 38 years); the sample included 71 women (60.7%) and 48 men (39.3%). Only 2 students (2%) were not interested in the subject of organ donation. The students knew very little of the legal aspects of organ donation and 1/4 of them thought there was even a Federal law regarding organ transplantation. When asked if they knew whether a law existed in the Canton of Berne, 44% replied yes, but only 24 (20%) knew that this is contradictory. There was no gender difference in the answers to these question. From 57 students (48%) 246 individual comments on doubts and concerns were analyzed. In this respect, the students mainly questioned whether the donor was truly dead when donation took place (n = 48), if illegal transplantation could be eliminated (n = 44) and if transplantation was truly necessary (n = 43). Some also mentioned religious/ethical doubts (n = 42). In regard to organ donation by a living individual, 27 students were concerned about the health of this donor. 20 students had doubts regarding the pressure possibly applied by family members and friends and as many voiced doubts in regard to premature diagnosis of brain death of potential donors. Only 2 students were concerned about the post-mortem presentation. 45 students (48%) indicated discomfort with the donation of certain organs. They ranked the kidney as the first organ to donate, followed by the pancreas, heart, cornea, intestine, lung and liver. CONCLUSION: The interest in organ donation and transplantation is already strong in fist year medical students in the pre-clinical stage. However, differences from lay public are not readably detectable at this stage of medical training. Adequate information could influence future physicians in their mediatory role.

Enhancement of titanium implants via bioengineered periodontal tissues

Osseointegration of titanium dental implants into the jaw bone, which is required for maintenance of the implant in the jaw, results in ankylosis. Dental implants are therefore very unlike natural teeth, which exhibit significant movement in response to mechanical forces. The ability to generate periodontal ligament (PDL) tissues onto dental implants would better mimic the functional characteristics of natural teeth, and would likely improve implant duration and function. OBJECTIVES: The objective of this study was to investigate the feasibility of bioengineering PDL tissues onto titanium implant surfaces. METHODS: Bilateral maxillary first and second molars of 8-week old rats were extracted and used to generate single cell suspensions of PDL tissues, which were expanded in culture. Immunohistochemistry and RT-PCR were used to identify putative PDL progenitor/stem cell populations and characterize stem cell properties, including self-renewal, multipotency and stem cell maker expression. Cultured rPDL cells were harvested at third passage, seeded onto Matrigel-coated titanium implants (1.75 mm x 1 mm), and placed into healed M1/M2 extraction sites. Non-cell seeded Matrigel-coated titanium implants served as negative controls. Implants were harvested after 8, 12, or 18 weeks. RESULTS: Cultured rPDL cells expressed the mesenchymal stem-cell marker STRO-1. Under defined culture conditions, PDL cells differentiated into adipogenic, neurogenic and osteogenic lineages. While control implants were largely surrounded by alveolar bone, experimental samples exhibited fibrous PDL-like tissues, and perhaps cementum, on the surface of experimental implants. CONCLUSIONS: PDL contains stem cells that can generate cementum/PDL-like tissue in vivo. Transplantation of these cells might hold promise as a therapeutic approach for the bioengineering of PDL tissues onto titanium implant. Further refinement of this method will likely result in improved dental implant strategies for use of autologous PDL tissue regeneration in humans. This research was supported by CIMIT, and NIH/NIDCR grant DE016132 (PCY), and TEACRS (YL).

Regulation of mitochondrial function by hypoxia and inflammation in sepsis: A putative role for hypoxia inducible factor

Sepsis-related organ failure is the leading cause of mortality in European intensive care units (ICU). Although the inflammatory cascade of mediators in response to infection is well known, the relationships between regional inflammation, microvascular heterogeneity, hypoxia and hypoxia-inducible gene expression, and finally, organ dysfunction, are unknown. Growing evidence suggests that not only low oxygen supply to the tissues secondary to macrovascular and microvascular alterations, but also altered cellular oxygen utilization is involved in the development of multiorgan dysfunction [1]–[3]. Microbial products and innate and adaptive dysregulated immune response to infection directly affect parenchymal cells of organs and may contribute to multiorgan dysfunction.

Immunotoxic effects of environmental toxicants in fish - how to assess them?

Numerous environmental chemicals, both long-known toxicants such as persistent organic pollutants as well as emerging contaminants such as pharmaceuticals, are known to modulate immune parameters of wildlife species, what can have adverse consequences for the fitness of individuals including their capability to resist pathogen infections. Despite frequent field observations of impaired immunocompetence and increased disease incidence in contaminant-exposed wildlife populations, the potential relevance of immunotoxic effects for the ecological impact of chemicals is rarely considered in ecotoxicological risk assessment. A limiting factor in the assessment of immunotoxic effects might be the complexity of the immune system what makes it difficult (1) to select appropriate exposure and effect parameters out of the many immune parameters which could be measured, and (2) to evaluate the significance of the selected parameters for the overall fitness and immunocompetence of the organism. Here, we present - on the example of teleost fishes - a brief discussion of how to assess chemical impact on the immune system using parameters at different levels of complexity and integration: immune mediators, humoral immune effectors, cellular immune defenses, macroscopical and microscopical responses of lymphoid tissues and organs, and host resistance to pathogens. Importantly, adverse effects of chemicals on immunocompetence may be detectable only after immune system activation, e.g., after pathogen challenge, but not in the resting immune system of non-infected fish. Current limitations to further development and implementation of immunotoxicity assays and parameters in ecotoxicological risk assessment are not primarily due to technological constraints, but are related from insufficient knowledge of (1) possible modes of action in the immune system, (2) the importance of intra- and inter-species immune system variability for the response against chemical stressors, and (3) deficits in conceptual and mechanistic assessment of combination effects of chemicals and pathogens.

Plakoglobin as a regulator of desmocollin gene expression.

Desmosomes are cell adhesion junctions required for the normal development and maintenance of mammalian tissues and organs such as the skin, skin appendages, and the heart. The goal of this study was to investigate how desmocollins (DSCs), transmembrane components of desmosomes, are regulated at the transcriptional level. We hypothesized that differential expression of the Dsc2 and Dsc3 genes is a prerequisite for normal development of skin appendages. We demonstrate that plakoglobin (Pg) in conjunction with lymphoid enhancer-binding factor 1 (Lef-1) differentially regulates the proximal promoters of these two genes. Specifically, we found that Lef-1 acts as a switch activating Dsc2 and repressing Dsc3 in the presence of Pg. Interestingly, we also determined that NF-κB pathway components, the downstream effectors of the ectodysplasin-A (EDA)/ ectodysplasin-A receptor (EDAR)/NF-κB signaling cascade, can activate Dsc2 expression. We hypothesize that Lef-1 and EDA/EDAR/NF-κB signaling contribute to a shift in Dsc isoform expression from Dsc3 to Dsc2 in placode keratinocytes. It is tempting to speculate that this shift is required for the invasive growth of placode keratinocytes into the dermis, a crucial step in skin appendage formation.

DUAL ENERGY COMPUTED TOMOGRAPHY FOR PROTON THERAPY TREATMENT PLANNING

Proton radiation therapy is gaining popularity because of the unique characteristics of its dose distribution, e.g., high dose-gradient at the distal end of the percentage-depth-dose curve (known as the Bragg peak). The high dose-gradient offers the possibility of delivering high dose to the target while still sparing critical organs distal to the target. However, the high dose-gradient is a double-edged sword: a small shift of the highly conformal high-dose area can cause the target to be substantially under-dosed or the critical organs to be substantially over-dosed. Because of that, large margins are required in treatment planning to ensure adequate dose coverage of the target, which prevents us from realizing the full potential of proton beams. Therefore, it is critical to reduce uncertainties in the proton radiation therapy. One major uncertainty in a proton treatment is the range uncertainty related to the estimation of proton stopping power ratio (SPR) distribution inside a patient. The SPR distribution inside a patient is required to account for tissue heterogeneities when calculating dose distribution inside the patient. In current clinical practice, the SPR distribution inside a patient is estimated from the patient’s treatment planning computed tomography (CT) images based on the CT number-to-SPR calibration curve. The SPR derived from a single CT number carries large uncertainties in the presence of human tissue composition variations, which is the major drawback of the current SPR estimation method. We propose to solve this problem by using dual energy CT (DECT) and hypothesize that the range uncertainty can be reduced by a factor of two from currently used value of 3.5%. A MATLAB program was developed to calculate the electron density ratio (EDR) and effective atomic number (EAN) from two CT measurements of the same object. An empirical relationship was discovered between mean excitation energies and EANs existing in human body tissues. With the MATLAB program and the empirical relationship, a DECT-based method was successfully developed to derive SPRs for human body tissues (the DECT method). The DECT method is more robust against the uncertainties in human tissues compositions than the current single-CT-based method, because the DECT method incorporated both density and elemental composition information in the SPR estimation. Furthermore, we studied practical limitations of the DECT method. We found that the accuracy of the DECT method using conventional kV-kV x-ray pair is susceptible to CT number variations, which compromises the theoretical advantage of the DECT method. Our solution to this problem is to use a different x-ray pair for the DECT. The accuracy of the DECT method using different combinations of x-ray energies, i.e., the kV-kV, kV-MV and MV-MV pair, was compared using the measured imaging uncertainties for each case. The kV-MV DECT was found to be the most robust against CT number variations. In addition, we studied how uncertainties propagate through the DECT calculation, and found general principles of selecting x-ray pairs for the DECT method to minimize its sensitivity to CT number variations. The uncertainties in SPRs estimated using the kV-MV DECT were analyzed further and compared to those using the stoichiometric method. The uncertainties in SPR estimation can be divided into five categories according to their origins: the inherent uncertainty, the DECT modeling uncertainty, the CT imaging uncertainty, the uncertainty in the mean excitation energy, and SPR variation with proton energy. Additionally, human body tissues were divided into three tissue groups – low density (lung) tissues, soft tissues and bone tissues. The uncertainties were estimated separately because their uncertainties were different under each condition. An estimate of the composite range uncertainty (2s) was determined for three tumor sites – prostate, lung, and head-and-neck, by combining the uncertainty estimates of all three tissue groups, weighted by their proportions along typical beam path for each treatment site. In conclusion, the DECT method holds theoretical advantages in estimating SPRs for human tissues over the current single-CT-based method. Using existing imaging techniques, the kV-MV DECT approach was capable of reducing the range uncertainty from the currently used value of 3.5% to 1.9%-2.3%, but it is short to reach our original goal of reducing the range uncertainty by a factor of two. The dominant source of uncertainties in the kV-MV DECT was the uncertainties in CT imaging, especially in MV CT imaging. Further reduction in beam hardening effect, the impact of scatter, out-of-field object etc. would reduce the Hounsfeld Unit variations in CT imaging. The kV-MV DECT still has the potential to reduce the range uncertainty further.

Temperature dependence of postmortem MR quantification for soft tissue discrimination.

OBJECTIVES To investigate and correct the temperature dependence of postmortem MR quantification used for soft tissue characterization and differentiation in thoraco-abdominal organs. MATERIAL AND METHODS Thirty-five postmortem short axis cardiac 3-T MR examinations were quantified using a quantification sequence. Liver, spleen, left ventricular myocardium, pectoralis muscle and subcutaneous fat were analysed in cardiac short axis images to obtain mean T1, T2 and PD tissue values. The core body temperature was measured using a rectally inserted thermometer. The tissue-specific quantitative values were related to the body core temperature. Equations to correct for temperature differences were generated. RESULTS In a 3D plot comprising the combined data of T1, T2 and PD, different organs/tissues could be well differentiated from each other. The quantitative values were influenced by the temperature. T1 in particular exhibited strong temperature dependence. The correction of quantitative values to a temperature of 37 °C resulted in better tissue discrimination. CONCLUSION Postmortem MR quantification is feasible for soft tissue discrimination and characterization of thoraco-abdominal organs. This provides a base for computer-aided diagnosis and detection of tissue lesions. The temperature dependence of the T1 values challenges postmortem MR quantification. Equations to correct for the temperature dependence are provided. KEY POINTS • Postmortem MR quantification is feasible for soft tissue discrimination and characterization • Temperature dependence of the T1 values challenges the MR quantification approach • The results provide the basis for computer-aided postmortem MRI diagnosis • Diagnostic criteria may also be applied for living patients.

Invited review: Growth-promoting effects of colostrum in calves based on interaction with intestinal cell surface receptors and receptor-like transporters

The postnatal development and maturation of the gastrointestinal (GI) tract of neonatal calves is crucial for their survival. Major morphological and functional changes in the calf's GI tract initiated by colostrum bioactive substances promote the establishment of intestinal digestion and absorption of food. It is generally accepted that colostrum intake provokes the maturation of organs and systems in young calves, illustrating the significance of the cow-to-calf connection at birth. These postnatal adaptive changes of the GI tissues in neonatal calves are especially induced by the action of bioactive substances such as insulin-like growth factors, hormones, or cholesterol carriers abundantly present in colostrum. These substances interact with specific cell-surface receptors or receptor-like transporters expressed in the GI wall of neonatal calves to elicit their biological effects. Therefore, the abundance and activity of cell surface receptors and receptor-like transporters binding colostral bioactive substances are a key aspect determining the effects of the cow-to-calf connection at birth. The present review compiles the information describing the effects of colostrum feeding on selected serum metabolic and endocrine traits in neonatal calves. In this context, the current paper discusses specifically the consequences of colostrum feeding on the GI expression and activity of cell-receptors and receptor-like transporters binding growth hormone, insulin-like growth factors, insulin, or cholesterol acceptors in neonatal calves.

Coordination of murine limb muscle, skeleton and connective tissue development by Lmx1b

The underlying genetic defects of a congenital disease Nail-Patella Syndrome are loss-of-function mutations in the LMX1B gene. Lmx1b encodes a LIM-homeodomain transcription factor that is expressed specifically in the dorsal limb bud mesenchyme. Gain- and loss-of-function experiments suggest that Lmx1b is both necessary and sufficient to specify dorsal limb patterning. However, how Lmx1b coordinates patterning of the dorsal tissues in the limb, including muscle, skeleton and connective tissues, remains unknown. One possibility is that each tissue specifies its own pattern cell-autonomously, i.e., Lmx1b is expressed in tissues in which it functions and different tissues do not communicate with each other. Another possibility is that tissues that express Lmx1b interact with adjacent tissues and provide patterning information thereby directing the development of tissues non-cell-autonomously. Previous results showed that Lmx1b is expressed in limb connective tissue and skeleton, but is not expressed in muscle tissue. Moreover, muscles and muscle connective tissue are closely associated during development. Therefore, we hypothesize that Lmx1b controls limb muscle dorsal-ventral (DV) patterning through muscle connective tissue, but regulates skeleton and tendon/ligament development cell-autonomously. ^ To test this hypothesis, we first examined when and where the limb dorsal-ventral asymmetry is established during development. Subsequently, conditional knockout and overexpression experiments were performed to delete or activate Lmx1b in different tissues within the limb. Our results show that deletion of Lmx1b from whole limb mesenchyme results in all dorsal tissues, including muscle, tendon/ligament and skeleton, transforming into ventral structures. Skeleton-specific knockout of Lmx1b led to the dorsal duplication of distal sesamoid and metacarpal bones, but did not affect the pattern formation of other tissues, suggesting that Lmx1b controls skeleton development cell-autonomously. In addition, this skeleton-specific pattern alteration only occurs in distal limb tissues, not proximal limb tissues, indicating different regulatory mechanisms operate along the limb proximal-distal axis. Moreover, skeleton-specific ectopic expression of Lmx1b reveals a complementary skeletal-specific dorsalized phenotype. This result supports a cell-autonomous role for Lmx1b in dorsal-ventral skeletal patterning. This study enriched our understanding of limb development, and the insights from this research may also be applicable for the development of other organs. ^

(Table 1) Concentration of organohalogenated compounds in clean and contaminated hair of polar bears (Ursus maritimus) from East Greenland

In this pilot study, we report on levels of persistent organohalogenated contaminants (OHCs) in hair of polar bears (Ursus maritimus) from East Greenland sampled between 1999 and 2001. To our knowledge, this is the first study on the validation of polar bear hair as a non-invasive matrix representative of concentrations and profiles in internal organs and blood plasma. Because of low sample weights (13-140 mg), only major bioaccumulative OHCs were detected above the limit of quantification: five polychlorinated biphenyl (PCB) congeners (CB 99, 138, 153, 170 and 180), one polybrominated diphenyl ether (PBDE) congener (BDE 47), oxychlordane, trans-nonachlor and ß-hexachlorocyclohexane. The PCB profile in hair was similar to that of internal tissues (i.e. adipose, liver, brain and blood), with CB 153 and 180 as the major congeners in all matrices. A gender difference was found for concentrations in hair relative to concentrations in internal tissues. Females (n = 6) were found to display negative correlations, while males (n = 5) showed positive correlations, although p-values were not found significant. These negative correlations in females may reflect seasonal OHC mobilisation from periphery adipose tissue due to, for example, lactation and fasting. The lack of significance in most correlations may be due to small sample sizes and seasonal variability of concentrations in soft tissues. Further research with larger sample weights and sizes is therefore necessary to draw more definitive conclusions on the usefulness of hair for biomonitoring OHCs in polar bears and other fur mammals.

Palynofacies analysis of sediments in the eastern Equatorial Atlantic

Analyses of the palynofacies and sporomorph thermal alteration indices (TAI) of sediments from Ocean Drilling Program (ODP) Sites 959 to 962 in the Cote d'Ivoire-Ghana Transform Margin, West Africa were undertaken to (1) determine the source and depositional conditions of the organic matter in the sediments, (2) refine a paleobathymetric curve derived from other data for Site 959, which drilled the most continuous sedimentary sequence from Pleistocene to Albian and (3) interpret the paleothermal history of the area. Twelve types of dispersed organic matter were identified: amorphous organic matter (AOM), marine palynomorphs, algae, resins, black debris, yellow-brown fragments, black-brown fragments, cuticles, plant tissue, wood, sporomorphs and fungi, The relative abundances of these organic matter components at each site were analyzed using cluster analysis, resulting in the identification of seven palynofacies assemblages at Site 959, five each at sites 960 and 961, and four at Site 962. Amorphous organic matter (which is chiefly marine derived), black debris and wood have played the most significant role in defining palynofacies assemblages. The palynofacies assemblages show some correlation with lithologic units, sediment sources and depositional environments. Previous palynofacies studies in passive margins have demonstrated that changes in the ratio of AOM to terrestrial organic matter are related primarily to proximal-distal positions of depositional environments relative to the shoreline. However, this assumption does not always hold true for a transform margin where tectonic factors play an important role in the organic matter distribution, at least in the early stages of evolution. Lithofacies, CCD paleodepths for the North Atlantic, trace fossil association, benthic foraminifera and palynofacies data were the criteria used for reconstructing a paleobathymetric curve for Site 959. A cyclicity in the organic matter distribution of the Upper Miocene to Lower Pliocene pelagic sediments could be related to fluctuations in productivity of biosiliceous and calcareous organisms, and sedimentation rates. A drastic increase in the amount of AOM and a decrease in black debris and wood in the carbonate and clastic rocks (Lithologic Unit IV) overlying the tectonized Albian sediments (Lithologic Unit V) at Sites 959 and 960 coincide with the presence of an unconformity. Qualitative color analysis of palynomorphs was undertaken for all sites, although the main focus was on Site 959 where detailed organic geochemical data were available. At Site 959, TAI values indicate an immature stage of organic maturation (<2) down to the black claystones of Lithologic Unit III at about 918.47 mbsf. Below this, samples show an increase with depth to a moderately mature stage (>2 except for the claystone samples between 1012.52 and 1036.5 mbsf, and one limestone sample at 1043.4 mbsf), reaching peak levels of 2.58 to 3.0 in the tectonized Albian sediments below the unconformity. These TAI values show a positive correlation with the Tma x values derived from Rock-Eval pyrolysis data. The highest values recorded in the basal tectonized units at all the sites (Sites 960-962 have mean values between 2.25 and 3.13) may be related to high heat flow during the intracontinental to syntransform basin stage in the region.

Rem : a los dos lados del espejo = (Rem at both sides of the mirror)

Cuando se trata de Rem Koolhaas, su espejo no refleja una sola imagen sino múltiples, es un prisma poliédrico. Su espejo nos devuelve el Rem mediático, el intelectual, el conceptualizador, el constructor, el analista, el periodista, el actor... En el caso de esta investigación, fijamos el punto de mira en el Rem COMUNICADOR. “Rem a los dos lados del espejo” se enmarca en una investigación sobre los medios de comunicación de arquitectura, su reflejo en la producción arquitectónica y viceversa. Se trata de llegar a discernir si comunicación y producción arquitectónica colisionan y confluyen en el caso de grandes comunicadores como Rem Koolhaas, si el mensaje y el medio transmisor adquieren las mismas cualidades. Centrándose en la figura de Rem Koolhaas, la tesis aborda la evolución de su faceta comunicativa y las transformaciones sucesivas en el campo de la comunicación arquitectónica, en paralelo a su evolución conceptual a lo largo de su trayectoria. La investigación, por tanto, no se centra tanto en su componente teórica o en la práctica arquitectónica de OMA, sino en la exposición de su producción al mundo, especialmente a través de sus ensayos y libros. “Delirious New York” y “SMLXL” son un reflejo del momento conceptual en que se inscriben, y contienen mucha información sobre los referentes gráficos que irremediablemente han influido en su composición. Especialmente, la aparición de “SMLXL” supuso un revulsivo para el mundo de la comunicación arquitectónica, porque puso el foco sobre la importancia de dejar atrás un discurso narrativo linea y unifocal, para afrontar la comunicación barajando múltiples variables, y aproximaciones, en un proceso similar al desarrollo de un proyecto de arquitectura. Presenta un diseño muy novedoso y una edición extremadamente cuidada, que atiende a parámetros mucho más ambiciosos que los meramente narrativos. Profundiza en la necesidad de una temática global, planteando cuál es la aproximación más apropiada para cada uno de los proyectos que describe, transmitiendo al lector una percepción más allá de lo estrictamente visual, más próximo a lo sensorial. Además, su enorme repercusión a nivel internacional y el gran interés que despertó (no solamente entre los arquitectos, sino también entre diseñadores gráficos, publicistas, personas provenientes de todo tipo de tendencias artísticas y público en general), provocó la globalización del fenómeno de las publicaciones arquitectónicas y puso de manifiesto la importancia de la comunicación como una disciplina en sí misma, dentro de la producción arquitectónica en la era actual. A pesar de la importancia de “SMLXL” a todos los niveles, la presente tesis plantea que, donde realmente se culmina esa experiencia comunicativa, es en “Content”, al incluir nuevos parámetros relacionados con la fusión conceptual de continente y contenido. Es en esta publicación donde el objeto de la comunicación y la expresión de la misma se convierten en un único elemento, que se rige por leyes similares. En este caso, la ley fundamental es la aplicación hasta sus máximas consecuencias de la “cultura de la congestión”, tanto en el mensaje como en el medio, generando lo que hemos convenido en denominar “comunicación congestiva”. Esta concepción deviene en que necesariamente se materialice como un producto efímero, desechable, casi virtual, porque responde a las condiciones de un momento muy concreto y específico y fuera de ese contexto pierde su significación.. La “cultura de la congestión” empieza a surgir en los planteamientos de Koolhaas en la Architectural Association School of Architecture de Londres, bajo la tutela de Elia Zenghelis. Posteriormente se desarrolla en su manifiesto retroactivo sobre Manhattan, “Delirious New York”, donde declara la guerra abierta al urbanismo del movimiento moderno y afirma que la ciudad realmente contemporánea es aquella que es fruto de un desarrollo no planificado, hiperdensa y posible gracias a los avances tecnológicos de su era. Finalmente comienza a materializarse en la Diploma Unit 9 de la AA, donde entra como profesor en 1975, dejando una huella indeleble en las generaciones posteriores de arquitectos que pasaron dicha unidad. Rem Koolhaas es ante todo un intelectual y por ello, todo el constructo teórico sobre la metrópolis comienza a reflejarse en su obra a través de OMA desde el comienzo de su producción. Podemos decir a grandes rasgos que su carrera está marcada por dos hitos históricos fundamentales que determinan tres etapas diferenciadas en su producción. En sus primeros años de profesión, Koolhaas sigue fascinado por la metrópolis urbana y la aplicación del método paranoico crítico a su producción arquitectónica. Es un arquitecto profundamente surrealista. Entiende este método como una estrategia de conocimiento y aproximación al mundo que le rodea: “dejar salir el inconsciente pero sostenerlo con las muletas de la racionalidad”. Pero lo que en realidad le interesa es su aplicación a la gran escala, el “Bigness”, y por ello, participa en proyectos muy ambiciosos de los que surgen conceptos que, más allá de resultar premiados o no, han dejado una huella ideológica en el devenir de la arquitectura. Entre estos proyectos, cabe destacar su propuesta para el Parque de la Villette o la Très Grande Bibliotèque de París. Sus proyectos de esta época destilan una gran carga conceptual, que devienen en unos interiores sorprendentes pero una apariencia exterior sobria o incluso podríamos decir "povera", por el uso de materiales efímeros, poco habituales en la macro-arquitectura hasta ese momento. Súbitamente, en 1997, explotó el denominado “Efecto Bilbao”, de la mano de Frank Gehry (1). El Museo Guggenheim de Bilbao, con su espectacularidad, sus formas pregnantes e imposibles, impacta al mundo. Nace la era de la “Arquitectura del Espectáculo”; la transformación de la ciudad a través de ICONOS que actúen como nodos de atracción y concentración en torno a los cuales supuestamente se revitaliza la actividad económica, cultural y sociopolítica de la ciudad, como si a través de un único gesto se pudieran regenerar todos los tejidos internos de la urbe. Rem Koolhaas comprende rápidamente que la aproximación a la ciudad ha cambiado y, sobre todo, el mercado. En el mundo de la globalización, la única manera de llegar a materializar el “Bigness”, es encerrando sus ejercicios intelectuales en formas pregnantes, bellas, icónicas, espectaculares. Koolhaas encuentra su marca personal en la estética “Stealth”, proveniente de los aviones de combate facetados para evitar los radares, elaborados en los años 80. De esta época surgen proyectos como la Casa da Música de Oporto o la Biblioteca de Seattle; ambos edificios son iconos facetados, de belleza pregnante, que dejan una huella indeleble en la ciudad y provocan, al igual que el Guggenheim, un cierto efecto de recuperación y revitalización en el entorno en que se asientan, al menos de manera temporal. En cualquier caso, Koolhaas nunca abandona los ejercicios meramente teóricos, pero segrega su actividad en dos: OMA produce aquello que tiene vocación de ser construido y se rige por los parámetros del mercado global y AMO, la otra cara del espejo de Rem, aplica el pensamiento arquitectónico a campos no explorados, sin la dependencia de agentes externos, pudiendo permitirse ser un laboratorio puramente experimental. En este escenario, llega el 11 de septiembre de 2001 y el ataque a las Torres Gemelas de Nueva York tiene efectos devastadores a todos los niveles, significando, en un período de tiempo sorprendentemente corto, un cambio en el orden mundial. Rem Koolhaas da entonces un giro de 180 grados, dirige su mirada hacia China, donde entiende que sus aportaciones tienen un beneficio social más directo que en occidente. (2) Para presentar al mundo su nuevo cambio de rumbo y la creación del “Think Tank” AMO, plantea una gran exposición en la NeueGallerie de Berlín bajo el título de “Content”, experiencia paralela a la edición del libro con el mismo título, que inicialmente nace como “catálogo de la exposición, pero que internamente siempre se concibió como el documento más trascendente en el estudio desde “SMLXL”. Sin embargo, en muchos aspectos se trata de su opuesto: una publicación con formato revista, de tapa blanda, con paginado muy fino, formato de "folleto de supermercado" y contenido hiperdenso. Es un experimento efímero, fugaz, ligero, barato, de “usar y tirar”. De hecho, está fuera de stock, ya no se edita. Probablemente Rem Koolhaas desaprobaría que se hiciera una investigación que pusiera el foco sobre el mismo, porque diez años después de su publicación seguramente opine que su vigencia ha caducado. Sin embargo, muestra con una claridad meridiana el estado conceptual y vital de OMA en el momento de su publicación y representa, además un verdadero hito en la comunicación arquitectónica, un punto de no retorno, el máximo exponente de lo que hemos denominado “comunicación congestiva”. La presente tesis plantea que “Content” contiene la esencia de la mayor aportación de Rem Koolhaas al mundo de la arquitectura: la transformación profunda y definitiva de la comunicación arquitectónica mediante la convergencia del estado conceptual y la transmisión del mismo. Su legado arquitectónico y conceptual ha marcado a todas las generaciones posteriores de manera indeleble. Sus ensayos, sus teorías, sus proyectos y sus edificaciones ya pertenecen a la historia de la arquitectura, sin ninguna duda. Pero es su revisión del concepto de la comunicación en arquitectura lo que ha tenido y tendrá un reflejo inmediato en las generaciones futuras, no solamente en la comunicación sino en su arquitectura, a través de un intercambio biyectivo. El planteamiento a futuro sería determinar qué sucede tras “Content”, tras la hiperdensidad máxima, tras la cultura de la congestión visual; qué es lo que propone Koolhaas y qué se va a plantear también en el mundo de la comunicación arquitectónica. Para ello, estudiaremos en profundidad sus últimos proyectos relacionados con la comunicación, como su propuesta para la Biennale de Arquitectura de Venecia de 2014, su intensa investigación sobre el “Metabolismo” en “Project Japan: Metabolism Talks...”, o la dirección de sus últimos planteamientos territoriales. En los últimos tiempos Rem Koolhaas habla de “Preservación”, de “Sobriedad”, de “Esencialismo”, de “Performance”... El autor intelectual de la cultura de la congestión habla ahora de la “low density”...como no podía ser de otra manera en la otra cara del espejo. En definitiva, el color blanco como suma de todos los colores, todas las longitudes de onda del espectro visible recibidas al tiempo. ABSTRACT When talking about Rem Koolhaas, the mirror does not only reflect one but numerous images: it is nothing but a polyhedral prism. His mirror gives us the image of Rem the media celebrity, the intellectual, the conceptualizer, the builder, the analyst, the journalist, the actor... This research sets the spotlight on Rem the COMMUNICATOR. "Rem on both sides of the mirror" belongs to a research on architectural media, its influence on the architectural production and vice versa. It is aimed at getting to discern whether communication and architectural production collide and converge in the case of great communicators such as Rem Koolhaas, and whether the message and transmission media acquire the same features. Focusing on the figure of Rem Koolhaas, this thesis addresses the evolution of his communicative facet and the successive transformations in the field of architectural communication, parallel to the conceptual evolution he underwent throughout his career. Therefore, this research is not so much focused on his theoretical component or on the OMA’s architectural practice, but on the exhibition of his production to the world, especially through his essays and books. "Delirious New York" and "SMLXL" hold up a mirror to the conceptual moment they are part of, and contain a great deal of information about the graphic references that have inevitably influenced his work. Specially, the launch of "SMLXL" was a salutary shock for the architectural communication world, since it set the spotlight on the importance of leaving a linear and unifocal narrative behind in order to face communication considering multiple variables and approaches, based on a process similar to the development of an architectural project. It offers a very innovative design and an extremely careful editing, which deals with parameters much more ambitious than those merely narrative. It explores the need for a global subject and suggests the most appropriate approach for each of the projects described, giving the reader a closer insight to the sensory that goes beyond what’s strictly visual. In addition, its huge international impact and the great interest shown, not only by architects but also by graphic designers, publishers, people from all kinds of artistic trends and the general public, led to the globalisation of the architectural publications phenomenon and brought the importance of communication as a discipline in itself, within the architectural production in the age at hand, to light. Despite the importance of "SMLXL" at all levels, this thesis suggests that the communication experience really culminates in "Content", for it includes new conceptual parameters associated with the container-content conceptual fusion. It is in this book where the purpose of communication and the expression of such become a single element, ruled by similar laws. In this particular case, the fundamental law is to implement the "culture of congestion" to its extreme consequences in both the message and the media, leading to what we have agreed to refer to as "congestive communication”. This concept leads to its inevitable materialisation into an ephemeral, disposable, almost virtual product, because it meets the conditions of a very concrete and specific time, and outside that context it loses its significance. The "culture of congestion" emerged in Koolhaas’ approaches under the guidance of Elia Zenghelis, in the Architectural Association School of Architecture of London. Subsequently, his retroactive manifesto on Manhattan, "Delirious New York" developed it, waging an all-out war against the modern movement urbanism and maintaining that the really contemporary cities are those hyperdense ones that rise as a result of an unplanned development and thanks to the typical technological advances of their time. Finally it began to materialise in the Diploma Unit 9 of the AA, in which he started lecturing in 1975, leaving an indelible mark on subsequent generations of architects who passed that unit. First and foremost, Rem Koolhaas is an intellectual and, therefore, all the theoretical construct in the metropolis began to be reflected in his work through OMA since the beginnings of his production. Broadly speaking, we can say that his career is influenced by two essential historic events, which determine three different stages in his production. In the early years of his career, Koolhaas was still fascinated by the urban metropolis and the implementation of the paranoiac-critical method to his architectural production. He was then a deeply surreal architect. He understood this method as a knowledge strategy and an approach to the world around him: "let the subconscious out but hold it with the crutches of reasonableness”. However, he was actually interested in its implementation on a broad scale, the "Bigness", and therefore, he took part in ambitious projects that led to the accrual of concepts that, beyond being rewarded, left an ideological impression on the evolution of architecture. These projects included his proposal for the Parc de la Villette or the Très Grande Bibliotèque in Paris. The projects he carried out during this period showed a great conceptual background, which evolved into surprising interiors but a sober, or even "povera", exterior appearance, thanks to the use of ephemeral materials that were atypical in the macro-architecture field until that moment. Suddenly, in 1997, the so-called "Bilbao effect" boomed thanks to Frank Gehry (1). The Guggenheim Museum of Bilbao amazed the world with its spectacular nature and its pregnant and impossible shapes. It was the beginning of the era of “The architecture of spectacle”: the transformation of the city through ICONS that would act as nodes of attraction and gathering, around which the economic, cultural and socio-political activity of the city was supposed to be revitalized, as if through a single gesture all internal tissues of the city could be rebuilt. Rem Koolhaas quickly realized that the approach to the city, and especially to the global market, had changed. In the world of globalisation, the only way to get to materialise such "Bigness" was by keeping his intellectual exercises in pregnant, beautiful, iconic and spectacular shapes. Koolhaas found his personal brand in the Stealth aesthetic, resulting from the eighties American combat aircrafts whose shape was faceted in order to avoid radars. Projects such as the Casa da Música in Porto or the Seattle Library date from this period; both buildings are faceted icons of pregnant beauty that left an indelible mark on the city and caused, like the Guggenheim, some degree of recovery and revitalization on the environment in which they were based, at least temporarily. In any case, Koolhaas never gave the merely theoretical exercises up, but he segregated his work in two: OMA produced what was destined to be built and ruled by the parameters of the global market and AMO, Rem’s other side of the mirror, applied the architectural thought in unexplored fields, notwithstanding external agents and being able to work as a purely experimental laboratory. In light of this backdrop, September 11th 2001 came and the attacks on the Twin Towers in New York had devastating effects at all levels, leading to a change in the world order, in a surprisingly short period of time. Rem Koolhaas made a 180° turn directing his vision towards China, where he believed his contributions would have a more direct social benefit than in the Western world. (2) In order to introduce his new course of direction and the creation of the AMO "Think Tank", he planned a major exhibition in the Neue Nationalgalerie of Berlin under the title "Content", in parallel with edition of the book with the same title, which was at first the "exhibition catalog” but, deep down, was always conceived as the most important document of the Office since "SMLXL". However, in many ways it was just the opposite: a publication characterised by its magazine format, soft cover, very fine paging, "supermarket brochure" form and hyperdense content. It was an ephemeral, brief, light, cheap and "disposable" experiment. In fact, it is currently out of stock and out of print. Rem Koolhaas would probably disapprove of a research that sets the spotlight on him, for he would probably say that his validity has expired given that it has been ten years since its publication. However, it shows OMA’s conceptual and vital status at the time of its publication with crystalline clarity and it is also a true milestone in architectural communication. A point of no return. The epitome of the so-called "congestive communication ". This thesis suggests that "Content" contains the essence of Rem Koolhaas’ greatest contribution to the world of architecture: the deep and definitive transformation of architectural communication through the convergence of the conceptual state and the transmission thereof. His architectural and conceptual legacy has left an indelible mark on all subsequent generations. There is no doubt his essays, theories, projects and buildings already belong to the history of architecture. But it is his review on the concept of communication in architecture that has had and shall have an immediate influence on future generations, not only in their communication but also in their architecture, through a bijective exchange. Future approaches should try to determine what happens after "Content", after the maximum hyperdensity, after the visual culture of congestion; what shall Koolhaas suggest as well as what shall happen in the world of architectural communication. To this end, we shall study his latest communication-related projects, such as the design of the Venetian Architecture Biennale in 2014, his intensive research on the "Metabolism" in "Project Japan: Metabolism Talks ...", or the course of his latest territorial approaches in depth. Most recently, Rem Koolhaas has talked about "Preservation", "Sobriety" of "Essentialism", "Performance", etc. The mastermind of the culture of congestion now speaks of the "low density"... as it could not be otherwise, on the other side of the mirror. Summarizing, the white color as the sum of all colors; all wavelengths of the visible spectrum received at the same time.

House-organs: da teoria à prática

Este projeto tem como objetivo realizar uma análise da forma com que vem sendo realizada, na prática, a Comunicação Interna no Brasil por meio de house-organs. Para tanto, utiliza-se de duas fontes principais de consulta: a bibliografia publicada sobre o tema e os vencedores do Prêmio Aberje dos últimos 7 (sete) anos. Com isso, pretende-se verificar, de um lado, o que autores e especialistas sugerem e indicam como ideal para execução da Comunicação Interna através de house-organs; de outro, analisa-se, com base nessa teoria, o que vem sendo feito na prática. A escolha dos vencedores do prêmio Aberje categoria House-organ para Comunicação Interna, tem como objetivo apenas apresentar um critério lógico para a seleção das mídias analisadas, uma vez que se trata de um prêmio concedido pelo principal órgão de representação da Comunicação Empresarial do Brasil. O foco deste estudo é exclusivamente o conteúdo dos veículos e neste se encaixam itens como o fluxo do discurso organizacional (ascendente, descendente etc.), mensagens, o tipo de linguagem utilizada etc. Não se focarão, dessa maneira, aspectos de diagramação e estética.(AU)

House-organs: da teoria à prática

Este projeto tem como objetivo realizar uma análise da forma com que vem sendo realizada, na prática, a Comunicação Interna no Brasil por meio de house-organs. Para tanto, utiliza-se de duas fontes principais de consulta: a bibliografia publicada sobre o tema e os vencedores do Prêmio Aberje dos últimos 7 (sete) anos. Com isso, pretende-se verificar, de um lado, o que autores e especialistas sugerem e indicam como ideal para execução da Comunicação Interna através de house-organs; de outro, analisa-se, com base nessa teoria, o que vem sendo feito na prática. A escolha dos vencedores do prêmio Aberje categoria House-organ para Comunicação Interna, tem como objetivo apenas apresentar um critério lógico para a seleção das mídias analisadas, uma vez que se trata de um prêmio concedido pelo principal órgão de representação da Comunicação Empresarial do Brasil. O foco deste estudo é exclusivamente o conteúdo dos veículos e neste se encaixam itens como o fluxo do discurso organizacional (ascendente, descendente etc.), mensagens, o tipo de linguagem utilizada etc. Não se focarão, dessa maneira, aspectos de diagramação e estética.(AU)

Tissue factor gene expression in the adipose tissues of obese mice

Altered expression of proteins of the fibrinolytic and coagulation cascades in obesity may contribute to the cardiovascular risk associated with this condition. We previously reported that plasminogen activator inhibitor 1 (PAI-1) is dramatically up-regulated in the plasma and adipose tissues of genetically obese mice. This change may disturb normal hemostatic balance and create a severe hypofibrinolytic state. Here we show that tissue factor (TF) gene expression also is significantly elevated in the epididymal and subcutaneous fat pads from ob/ob mice compared with their lean counterparts, and that its level of expression in obese mice increases with age and the degree of obesity. Cell fractionation and in situ hybridization analysis of adipose tissues indicate that TF mRNA is increased in adipocytes and in unidentified stromal vascular cells. Transforming growth factor β (TGF-β) is known to be elevated in the adipose tissue of obese mice, and administration of TGF-β increased TF mRNA expression in adipocytes in vivo and in vitro. These observations raise the possibility that TF and TGF-β may contribute to the increased cardiovascular disease that accompanies obesity and related non-insulin-dependent diabetes mellitus, and that the adipocyte plays a key role in this process. The recent demonstration that TF also influences angiogenesis, cell adhesion, and signaling suggests that its exact role in adipose tissue physiology/pathology, may be complex.