¿Por qué nos enferma el estrés?

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Desarrollar varias actividades a la vez puede generar estrés. | Efe

Ir siempre corriendo de un sitio a otro, vivir angustiados por llegar a final de mes, sufrir la enfermedad de un ser querido... Son situaciones que generan un estrés crónico y que cada vez más se reproducen en la sociedad actual. Son muchos los estudios que han relacionado este tipo de angustia con un mayor riesgo de sufrir una enfermedad cardiaca, autoinmune o una infección. Pero, ¿cuál es el proceso por el que el estrés merma la salud? Parece que la clave está en una alteración de la respuesta inflamatoria.
Se sabe que en una situación de estrés puntual, nuestro organismo responde generando una mayor producción de una hormona, el cortisol. Sin embargo, ¿ocurre lo mismo cuando se trata de una tensión prolongada? "La sencilla noción de que el estrés crónico actúe mediante el efecto directo de un aumento de cortisol en sangre es cada vez menos aceptada. Lo que más importa es cómo los tejidos responden al cortisol, más que los niveles de la hormona por sí mismos", señalan un grupo de investigadores de la Universidad Carnegie Mellon (Pittsburgh, EEUU) en su trabajo, publicado en la revista 'Proceeding of the National Academy of Sciences' (PNAS).
Estudios previos de estos autores habían demostrado que el estrés crónico está asociado con un aumento de la susceptibilidad a tener un resfriado entre aquellas personas que han estado expuestas a un virus respiratorio. Sin embargo, en ellas, los niveles de cortisol no jugaron un papel determinante, pero hasta ahora no se había evaluado cómo la hormona influye en la respuesta inflamatoria, en concreto sobre los receptores de los glucocorticoides, encargados de regular los genes implicados en la respuesta inmune (el sistema defensivo del cuerpo humano).

Más propensos al resfriado

En un primer estudio, estos investigadores expusieron a 276 adultos a un virus responsable del resfriado común y los vigilaron a lo largo de cinco días para detectar signos de infección y enfermedad. Lo que comprobaron fue que en aquellos que habían estado sometidos a un estrés crónico sus células inmunes eran incapaces de responder a las señales hormonales que normalmente regulan la inflamación y, por lo tanto, fueron más propensos a sufrir un resfriado.
En un segundo estudio, se valoró la capacidad de 79 participantes sanos para regular la respuesta inflamatoria. De nuevo se utilizó la exposición a un virus del resfriado y se vigiló la producción de citocinas proinflamatorias, sustancias involucradas en la estimulación de la producción y liberación de otros mediadores proinflamatorios. Quienes fueron menos capaces de regular la respuesta inflamatoria, como se valoró antes de estar en contacto con el virus, produjeron más citocinas que inducen la inflamación, una vez que estas personas estuvieron expuestas al patógeno.

Incapaz de regular la inflamación

"La inflamación está en parte regulada por la hormona del cortisol y cuando ésta no desarrolla bien su función, la inflamación queda fuera de control [...] La capacidad del sistema inmunológico de regular la inflamación predijo [en este estudio] quién desarrollará un resfriado, pero lo más importante es que ofrece una explicación a cómo el estrés promueve una enfermedad", explica Sheldon Cohen, profesor de Psicología de la Universidad Carnegie Mellon y principal investigador del estudio.
"En situaciones de estrés, las células del sistema inmune son incapaces de responder al control hormonal, y consecuentemente, producen niveles de inflamación que conducen a una enfermedad. Porque la inflamación juega un papel en muchas patologías como la cardiovascular, el asma y los trastornos autoinmunes. Este modelo sugiere por qué el estrés les impacta tanto", señala Cohen.

**Publicado en "EL MUNDO"

Cone snail venom controls pain

Hidden in the mud, the cone snail Conus purpurascens lies in wait for its victims. It attracts its prey, fish, with its proboscis, which can move like a worm, protruding from the mud. Once a fish approaches out of curiosity, the snail will rapidly shoot a harpoon at it, which consists of an evolutionarily modified tooth. The paralyzed victim then becomes an easy meal. It takes the venomous cone snail about two weeks to digest a fish. During this time, its venomous harpoon is also replaced. Prof. Dr. Diana Imhof from the Pharmaceutical Institute of the University of Bonn, who is the project's PI, explained, "We are interested in the cone snail's neurotoxins, called conotoxins." They can be effective in minute quantities, interrupt the transmission of signals in nerve paths in a highly selective manner, and are thus able to block the transmission of pain very well. Consequently, these toxins are of great interest for developing analgesics for chronically ill or terminal cancer patients for whom other medications can no longer be used. "The advantage of these conotoxins is that they do not cause dependency," Imhof, a pharmaceutical chemist, explained. "Since the peptide we studied decomposes rather quickly in the body, we do, however, need more stable forms that we can administer."
Scientists replicate the rare venom in vitro
The Bonn researchers worked with Prof. Dr. Stefan H. Heinemann from the Biophysics Department of the University of Jena, scientists from the Leibniz Institute for Age Research Jena and the Technical University of Darmstadt. "The µ-PIIIA conotoxin, which was of interest in this study, occurs only in extremely minute quantities in marine cone snails," said Dr. Alesia A. Tietze, the lead author, who received her doctoral degree on Prof. Imhof's team. However, the scientists were able to produce the specific venom chemically in vitro for use in additional analyses. Tietze added, "We succeeded in identifying the structure of different µ-PIIIA conotoxin variants and their different effects using nuclear magnetic resonance."
The venom in question is a substance whose different amino acids are strung together like pearls. "This string can form clusters in different ways, forming divers 3D structures," explained Prof. Imhof. Until now it had been thought that only one of these forms is biologically effective. "It was exactly this dogma that we were able to disprove," the Bonn scientist added. "We identified three active types of peptide folding with a similar effect -- there are probably even more." These variants do, however, differ slightly with regard to their biological efficacy, representing valuable starting structures for further development into analgesics.
Consequently, the scientists want to conduct additional studies in order to find out more these different fold variants of the µ-PIIIA conotoxin. But it will take years until patients may be able to profit from this. "We are still in the basic research stadium," said Prof. Imhof.

**Source: Universität Bonn

Nuevas dudas sobre el cribado de detección del cáncer de próstata

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• Un nuevo estudio ha vuelto a poner en entredicho la utilidad de la prueba PSA (tasa de antígeno prostático específico, que se mide con un análisis de sangre) empleada para detectar el cáncer de próstata. Y ya no se trata de dudar de su eficacia en el cribado en la población general, sino en el diagnóstico del tumor en los individuos de riesgo (más de 50 años, antecedentes familiares).

La Alta Autoridad en Salud francesa (HAS, un organismo público consultivo) considera que “no es demostrable” la eficacia de esta prueba. Por un lado, porque no está claro el peso de los distintos factores de riesgo que intervienen en la enfermedad. Por otro, por su lenta e irregular evolución,  su tardía aparición (a los 71 años de media) y el elevado porcentaje de neoplasias asintómáticas. En todos estos casos, la detección temprana no sería útil y las medidas terapéuticas aportarían más riesgos que beneficios.

La prueba arroja muchos
“falsos positivos”, lo que puede implicar “riesgos secundarios”

A ello se suma el elevado número de “falsos positivos” que arroja la prueba, lo que puede implicar “riesgos secundarios” derivados a la biopsia o al tratamiento, como impotencia, incontinencia urinaria o problemas psicológicos. Por ello, quienes se sometan a este analisis, deben hacerlo “con conocimiento de causa”, y sabiendo que “en ocasiones deriva en operaciones o irradiaciones inútiles, con duras consecuencias para la sexualidad y la continencia de hombres jóvenes y activos”.

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“Es una prueba muy controvertida”, admite Josep Maria Borràs, responsable de la Estrategia Nacional en Cáncer de Ministerio de Sanidad. Borràs apunta que en España no se recomienda el PSA como prueba de cribado debido a su falta de precisión, al contrario de las mamografías. No solo por falsos positivos, también puede resultado puede confundirse con una prostatitis, traumatismos o hiperplasia prostática benigna.
“El año pasado dos importantes ensayos clínicos arrojaron resultados contradictorios sobre su utilidad. Uno sugirió que el cribado no servía para mejorar el pronóstico de los pacientes; otro, sin embargo, si aportaba cierta mejora en el porcentaje de supervivencia”, explica Borràs. “Ambos coincidieron en el riesgo de sobrediagnóstico”.

Dos ensayos clínicos dieron resultados contradictorios sobre la utilidad del PSA

En todo caso, Borràs destaca su utilidad como prueba rápida de diagnóstico -"su problema y su ventaja es que es muy fácil de hacer"- y, especialmente, en la evaluación de la respuesta al tratamiento del tumor, ya que permite seguir su evolución de forma cómoda (con un simple análisis de sangre).
El cáncer de próstata es el más frecuente en hombres, por delante de las neoplasias en el pulmón y colon. Según datos de la Asociación Nacional de Urología, cada año se detectan más de 18.800 casos.
La HAS ya advirtió en 2010 que el test aplicado a la población general no era útil. Un año después, otro grupo de expertos también cuestionó este procedimiento de detección de la enfermedad. El United States Preventive Services Task Force desaconsejó en un documento que se hicieran estas pruebas a hombres sanos. En la línea del organismo estatal francés, planteaba el riesgo que suponía que un falso resultado positivo desembocara en tratamientos agresivos irreversibles.
La mayor organización estadounidense de pacientes de cáncer de próstata no se mostró de acuerdo con las recomendaciones de esta entidad con el argumento que la PSA es la mejor prueba existente hasta el momento.

**Publicado en "EL PAIS"

Scientists solving the mystery of human consciousness

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Turku PET Center

Awakening from anesthesia is often associated with an initial phase of delirious struggle before the full restoration of awareness and orientation to one's surroundings. Scientists now know why this may occur: primitive consciousness emerges first. Using brain imaging techniques in healthy volunteers, a team of scientists led by Adjunct Professor Harry Scheinin, M.D. from the University of Turku, Turku, Finland in collaboration with investigators from the University of California, Irvine, USA, have now imaged the process of returning consciousness after general anesthesia. The emergence of consciousness was found to be associated with activations of deep, primitive brain structures rather than the evolutionary younger neocortex. These results may represent an important step forward in the scientific explanation of human consciousness. The study was part of the Research Programme on Neuroscience by the Academy of Finland.
"We expected to see the outer bits of brain, the cerebral cortex (often thought to be the seat of higher human consciousness), would turn back on when consciousness was restored following anesthesia. Surprisingly, that is not what the images showed us. In fact, the central core structures of the more primitive brain structures including the thalamus and parts of the limbic system appeared to become functional first, suggesting that a foundational primitive conscious state must be restored before higher order conscious activity can occur" Scheinin said.
Twenty young healthy volunteers were put under anesthesia in a brain scanner using either dexmedetomidine or propofol anesthetic drugs. The subjects were then woken up while brain activity pictures were being taken. Dexmedetomidine is used as a sedative in the intensive care unit setting and propofol is widely used for induction and maintenance of general anesthesia. Dexmedetomidine-induced unconsciousness has a close resemblance to normal physiological sleep, as it can be reversed with mild physical stimulation or loud voices without requiring any change in the dosing of the drug. This unique property was critical to the study design, as it enabled the investigators to separate the brain activity changes associated with the changing level of consciousness from the drug-related effects on the brain. The state-related changes in brain activity were imaged with positron emission tomography (PET).
The emergence of consciousness, as assessed with a motor response to a spoken command, was associated with the activation of a core network involving subcortical and limbic regions that became functionally coupled with parts of frontal and inferior parietal cortices upon awakening from dexmedetomidine-induced unconsciousness. This network thus enabled the subjective awareness of the external world and the capacity to behaviorally express the contents of consciousness through voluntary responses. Interestingly, the same deep brain structures, i.e. the brain stem, thalamus, hypothalamus and the anterior cingulate cortex, were activated also upon emergence from propofol anesthesia, suggesting a common, drug-independent mechanism of arousal. For both drugs, activations seen upon regaining consciousness were thus mostly localized in deep, phylogenetically old brain structures rather than in the neocortex.
The researchers speculate that because current depth-of-anesthesia monitoring technology is based on cortical electroencephalography (EEG) measurement (i.e., measuring electrical signals on the surface of the scalp that arise from the brain's cortical surface), their results help to explain why these devices fail in differentiating the conscious and unconscious states and why patient awareness during general anesthesia may not always be detected. The results presented here also add to the current understanding of anesthesia mechanisms and form the foundation for developing more reliable depth-of-anesthesia technology.
The anesthetized brain provides new views into the emergence of consciousness. Anesthetic agents are clinically useful for their remarkable property of being able to manipulate the state of consciousness. When given a sufficient dose of an anesthetic, a person will lose the precious but mysterious capacity of being aware of one's own self and the surrounding world, and will sink into a state of oblivion. Conversely, when the dose is lightened or wears off, the brain almost magically recreates a subjective sense of being as experience and awareness returns. The ultimate nature of consciousness remains a mystery, but anesthesia offers a unique window for imaging internal brain activity when the subjective phenomenon of consciousness first vanishes and then re-emerges. This study was designed to give the clearest picture so far of the internal brain processes involved in this phenomenon.
The results may also have broader implications. The demonstration of which brain mechanisms are involved in the emergence of the conscious state is an important step forward in the scientific explanation of consciousness. Yet, much harder questions remain. How and why do these neural mechanisms create the subjective feeling of being, the awareness of self and environment -- the state of being conscious?

**Source: Suomen Akatemia (Academy of Finland)

Así podrían ser las gafas de realidad aumentada de Google.

El buscador acaba de publicar un vídeo conceptual de las gafas. No tienen cristales y aún no están a la venta pero Google empezará a probarlas en público.

Más información, en su página de Google+:
http://cort.as/1nqE

DNA sequencing consortium unveils patterns of mutations in autism

It has long been recognized that autism runs in families, suggesting a substantial genetic component to the disease. Yet few genes have so far been identified and the underlying genetic architecture of autism -- that is, how many genes contribute and to what extent they influence a person's chances of developing the disorder -- remains poorly understood. Now, a consortium led by researchers from the Broad Institute, Massachusetts General Hospital (MGH), and six other organizations has taken a step toward addressing these questions by searching for mutations in the fraction of the human genome that codes for proteins. The researchers sequenced this region, known as the "exome," in 175 autism patients and their unaffected parents, looking for single-letter DNA changes present only in the children. Their results, along with simultaneously published findings from two other research groups, suggest modest roles for hundreds of genes in the development of autism and pinpoint a few specific genes as genuine risk factors. The work is described in a paper that appears online April 4 in the journal Nature.
"Autism, like many heritable disorders, results from the action of many genes -- not simply a single gene as in cystic fibrosis or Huntington's disease," said senior author Mark Daly, chief of the Analytic and Translational Genetics Unit at MGH, a senior associate member of the Broad Institute and co-director of its Program in Medical and Population Genetics, and a member of the Broad Institute's Stanley Center for Psychiatric Research. "These genes hold key insights into the true biological causes of autism -- insights we have been unable to gain through other lines of research."
Autism is a common neurodevelopmental disorder characterized by impaired social, behavioral, and communication abilities. Compared to other complex diseases, which are caused by a complicated mix of genetic, environmental, and other factors, autism is highly heritable -- genetics accounts for roughly 80-90% of the risk of developing autism. Yet the majority of autism cases cannot be attributed to known inherited causes.
Researchers in the ARRA Autism Sequencing Collaborative (AASC) -- formed by researchers from the Broad Institute, MGH, Baylor College of Medicine, Mount Sinai School of Medicine, Vanderbilt University, University of Pennsylvania, Carnegie Mellon University, and University of Pittsburgh -- used massively parallel sequencing to help shed light on the genes that influence autism risk. Concordant findings from separate studies by two other groups, from Yale University and the University of Washington respectively, also appear in Nature.
The AASC team focused its attention on a particular set of mutations, specifically single-letter mutations that are not present in the parents' DNA but instead appeared spontaneously in the children -- so-called de novo point mutations. Although it is not yet clear exactly when these changes arise, such genetic variations tend to be rare but also more severe in their impact on gene function. With such extreme effects, they can serve as important signposts toward genes involved in autism.
"The idea is that these de novo mutations can help identify candidate genes much more precisely because a newly arisen point mutation is considered really strong evidence that the mutation -- and the gene it resides in -- is involved in autism," said first author Benjamin Neale, a research affiliate at the Broad Institute and an assistant in genetics at MGH.
The researchers found that less than half of the autism cases studied carried a potentially protein-altering de novo point mutation. While this was only slightly higher than the number expected based on the rate of mutation in the general population, these events are sufficiently rare that they could be used to uncover specific risk genes.
"These data suggest that there is a role for de novo point mutations in the coding region of the genome for autism, but they do not constitute a sufficient cause," said Neale. "That is to say, most de novo variants do not fully explain the disorder in an individual."
To learn more about these mutations and the genes in which they reside, the scientists looked for any meaningful connections among them. Such connections, among different proteins for example, might reveal important biological networks or pathways that underlie autism. By mining these data, Daly, Neale, and their colleagues found that the mutated genes are more connected to each other and to previously identified autism genes than expected. Specifically, the results suggest that some of the proteins encoded by these genes physically interact with each other.
As described in their paper, Daly and his colleagues pooled their data with those published in the other two Nature papers, revealing 18 candidate genes with multiple functional de novo point mutations. Considering the severity of the mutations, the collective results pointed to three genes as strong autism candidates: KATNAL2, a gene whose function is unknown; SCN2A, which encodes a brain protein that forms a channel for sodium ions; and CHD8, a gene that regulates gene transcription and modifies chromatin (the network of proteins that surrounds DNA).

**Source: Broad Institute of MIT and Harvard

La FAD pone en marcha el telefono 901 350 350 de orientación a las familias sobre la droga

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¿No sabe cómo abordar determinadas cuestiones con sus hijos? ¿Le preocupa que empiecen a coquetear con las drogas? ¿Cree que puede tener un problema de comunicación en su familia? ¿Necesita hablar con alguien?

El horario de atención es de lunes a domingo, festivos incluidos, de 9 a 21

Para todos los padres y madres que lo deseen, la FAD pone a su disposición la línea telefónica 901 350 350, un servicio de información y orientación sobre prevención e información de sustancias para familias que funciona todos los días del año de 9 a 21 horas. El servicio es absolutamente anónimo y confidencial.

Si lo que necesita es un asesoramiento más continuado, pautas específicas para su familia y seguimiento personalizado, la FAD también pone a su disposición el teléfono 900 22 22 29 que está atendido por un equipo de especialistas en prevención y orientación familiar que le ayudarán a encontrar las claves para manejar adecuadamente situaciones y problemas surgidos en sus relaciones familiares.

Por último, la FAD también ofrece el Servicio de Información y Orientación sobre Drogodependencias (teléfono 900 16 15 15) que brinda información sobre sustancias, conductas adictivas o recursos asistenciales a aquellas personas interesadas y, en especial, a quienes sufren de forma directa los problemas derivados del consumo de drogas.