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Broncemia [651]

de System Administrator - sábado, 2 de agosto de 2014, 02:09
 

La arrogancia como estilo en la práctica de la medicina

Esa vieja y terrible enfermedad "Broncemia". Una magistral conferencia del Dr. Francisco Occihuzzi pronunciada en TED Córdoba. La arrogancia como estilo en la práctica de la medicina. Un patético modo de alejarse del dolor de la gente y del afecto de sus colegas.

Seguir leyendo en el sitio web http://kwfoundation.org

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Bugs as Drugs: Seeking the Microbial Secret to Health [1600]

de System Administrator - jueves, 3 de diciembre de 2015, 19:33
 

Bugs as Drugs: Seeking the Microbial Secret to Health

BY SHELLY FAN

Our body is, in essence, more ecosystem than organism.

The human body teems with trillions of microbes — bacteria, viruses and fungi — and at any moment, we may be carrying between one and three pounds of these micro-hitchhikers in colonies on our skin, groin, mouths, and sinuses. By far, however, the gut microbiome ecosystem — the largest and most complex — is the one that has both academic researchers and pharmaceutical companies hooked.

The reason? Our gut bugs may be the new frontier of a billion-dollar bioceutical industry.

 

Manipulating the microbiome for health is nothing new. The growing probiotics industry earns some $30 billionglobally each year selling supplements and foods and drinks like yogurt or kombucha. The health claims are: improved intestinal health, buzzing energy, weight loss and “all natural” mood enhancement.

“It’s unregulated, unsupported,” says Dr. Martin Blaser, a pioneer of human microbiome studies at NYU and advisor to Second Genome, a startup based in the Bay Area.

But that’s set to change. For years, the boom in over-the-counter probiotics was more hype than science; now, mounting evidence is beginning to link conditions ranging from the physical ­­— irritable bowel syndrome, Type 2 diabetes — to the mental — autism, Parkinson’s, depression ­— to the gut’s resident microbugs.

"The microbiome field has produced some of the most exciting science discoveries of the last five years, and its potential impact on human health is just too big to ignore," says Bernat Olle, chief operating officer atVedanta Biosciences, a Boston startup that looks to treat autoimmune and inflammatory diseases by modulating the microbiome.

Dr. Justin Sonnenburg, a microbiologist at Stanford University, agrees. “Undoubtedly, the microbiome is a little drug factory in our intestine,” he says.

One with many unresolved mysteries, and a hell of a lot to offer.

Beyond the vanguard

The tantalizing links between gut microbes and health have only recently begun to be accepted by mainstream science.

The main roadblock is proving causality. “It's very difficult to tell if microbial differences you see associated with diseases are causes or consequences,” Rob Knight, a microbiologist at the University of California, San Diego.

 

So far, the question’s been hard to answer. Most sophisticated, tightly controlled experiments were done in mice raised in completely sterile environments — hardly the best model, given that most humans are colonized at birth by resident microbes in our mothers’ vaginal canal.

Data in humans are far more limited and often correlational in nature. In varying degrees, our microbiome connects to a slew of metabolic diseases, such as obesity and diabetes. It also, crucially, acts as a communication channel between our immune and digestive systems.

The link to brain disorders is perhaps the most tantalizing. Children with autism, for example, often also suffer from gastrointestinal problems. As do patients with anxiety, depression, schizophrenic and neurodegenerative disorders, suggesting malfunctioning gut microbes. But is it just a connected fact, or is it a cause for their illness?

Without figuring out causal relationships, there’s little use in pursuing a drug. But bioceutical companies like Second Genome have a workaround. The goal is not to target every disease, says CEO Peter DiLaura, it’s to take aim at just a few.

In particular, ones with large unmet therapeutics need and evidence showing a large microbiome-driven causation, explains DiLaura. Obesity, Type 2 diabetes and Crohn’s disease all fit the bill, and Second Genome is tackling each with laser focus.

Chemical exploration

If successful, Second Genome could relieve millions of people of their chronic disease. The key to unlocking the gut-health secret, said DiLaura, is tapping into the ancient language that connects host with microbe.

“We’re code breakers,” says DiLaura. For eons, we have only focused on the host side of things; with advances in genomic profiling and big data, we can finally tap into the conversation within and surrounding the microbiome.

Preliminary results hint at complex answers. The composition of the gut microbiome — the balance between “good” and “bad” bacteria — can influence health by regulating inflammation in the body.

We can easily change the microbiome composition with diet and antibiotics, sometimes in less than a week,says Sonnenburg. This works well in our favor. His team is currently working on a molecule called sialic acid, which prevents harmful bacterial from taking over the gut after heavy antibiotic use.

Other companies are taking “bugs as drugs” quite literally.

OpenBiome, a company based in Cambridge, Mass, is providing frozen stool samples from healthy, pre-screened individuals to hospitals. There, the samples are put into the colons of people suffering from the deadly — and otherwise untreatable — gut infection Clostridium difficile, which kills 14,000 Americans each year.

Early results have been nothing short of remarkable so far: in a 2011 review of 317 patients, fecal transplants cleared up the infection in 92% of cases. To facilitate long-term maintenance treatment, the team is working on capsules that patients can take orally.

 

You might be thinking eww: after all, it’s hard not to give a crap about swallowing poop pills. Researchers agree. The next step is to try to isolate and culture healthful strains of bacteria that bear the brunt of the therapeutic work in fecal matter, and make them into probiotics to stop recurrent infections or prevent one from happening altogether. So far, the effects are there but moderate, and scientists are tweaking the probiotic composition to further optimize treatment.

Arguably, however, the most pragmatic approach is looking at gutbug bioactives — that is, proteins and metabolites secreted by the microbiome that impact health.

Second Genome is striding down this path. In close collaboration with academic advisors, the company is striving to find bioactives that are secreted by a healthy microbiome. So far, research is homing in on a class of chemicals called short-chain fatty acids. These molecules are constantly produced as gut microbes break down starchy foods, which — in ways yet uncovered — regulate our immune system, the integrity of our brain cells and an array of metabolic pathways.

Other molecules may combat the deadly effects of multiple sclerosis, a devastating degenerative brain disease currently without cure. Yet others may prove to be a new source of antibiotics, to amp up our rapidly dwindling antibiotic arsenal.

We’ve uncovered only the tip of the bioactive iceberg, and it’s a field ripe for discovery.

“People are eager to learn what exactly helpful bacteria are doing,” says Dr. Michael Fischbach, a microbiologist at the University of California, San Francisco, who uses machine learning to hunt down drug-making genes in the human microbiome.

“Nobody had anticipated that they have the capability to make so many different kinds of drugs,” says Fischbach. “We used to think that drugs were discovered by drug companies and prescribed by a physician and then they get to you.”

Forget that. The future of drug making may be right on — and inside — your body.

RELATED TOPICS: 

Link: http://singularityhub.com

 

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Bullying and Depression in Youths [1646]

de System Administrator - miércoles, 3 de febrero de 2016, 17:03
 

Bullying and Depression in Youths

By Karen Dineen Wagner, MD, PhD 

During an evaluation, a 10-year-old girl who was depressed said that classmates called her stupid and laughed at her all the time. Fortunately, the teachers stopped this verbal bullying. However, unbeknownst to the teachers, the students would text disparaging comments to the girl throughout the school day. She was reluctant to inform the teachers because she thought it would worsen the situation.

A 14-year-old girl in treatment for depression reported that she was being bullied in school. She said that girls in her classes constantly made negative comments about her appearance, dress, and behavior. They excluded her from social activities despite her desire to participate. She said that the girls were telling lies about her to boys in the class, which was damaging her reputation. What upset her the most was that an online site had been created in which students were encouraged to write all the reasons they hated her. She cried and said that she could not avoid the bullying even outside of school. She believed the only way to escape the bullying was to not exist anymore, and she confirmed that she was suicidal.

Cyberbullying

Cyberbullying, which allows bullying to extend beyond face-to-face contact into electronic media, has received considerable recent attention. Hamm and colleagues1 examined its effects via social media among children and adolescents. They included 36 studies of cyberbullying in their review. Most youths in these studies were middle and high school students, aged 12 to 18 years. The majority were female (55.8%).

Across these studies, 23% of the youths reported having been bullied online. The most common electronic social media platforms for bullying included message boards, social networking sites, blogs, Twitter, and Web pages. The most common types of cyberbullying were name-calling or insults, circulating pictures, and spreading gossip and rumors. Often relationship issues preceded the bullying. Girls were more likely to be cyberbullied than boys.

Adolescents who had been cyberbullied reported becoming more withdrawn, losing self-esteem, and feeling uneasy. There were adverse effects on relationships with family and friends. School grades worsened, there were more school absences, and behavior problems in school became common.

Depression was associated with cyberbullying. The adolescent’s level of depression increased significantly with exposure to cyberbullying. In some cases, cyberbullying was associated with self-harm behavior and suicidal ideation and attempts.

The most common strategies employed by the adolescents to deal with cyberbullying were to block the sender, ignore or avoid messaging, and protect personal information. Nearly 25% of the adolescents did not tell anyone about the cyberbullying. If they did tell someone, it was most likely to be a friend rather than an adult. Often adolescents perceived that nothing could be done to prevent the bullying, and if they told their parent about the bullying, they would lose access to the computer. The researchers suggest that increased awareness of the prevalence of cyberbullying and its adverse effects may lead to better prevention and management strategies.

The correlation between depression and bullying

In a recent study, Bowes and colleagues2 examined the association between being bullied by peers at age 13 and the occurrence of depression at 18 years. The study comprised 6719 adolescents from the Avon Longitudinal Study of Parents and Children cohort in the UK. About 10% (n = 683) of the participants reported frequent bullying at age 13. The proportion of youths with depression increased with the frequency of bullying: 14.8% of the youths who were frequently bullied met criteria for depression, whereas 7.1% of youths who were occasionally bullied and 5.5% of youths who were not bullied met criteria for depression.

More: http://www.psychiatrictimes.com

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Bullying: The Uncomfortable Truth About IT [882]

de System Administrator - viernes, 19 de septiembre de 2014, 15:34
 

Bullying: The Uncomfortable Truth About IT

Provided by  IDG CONNECT

Overview

IDG Connect has spoken to a range of bullying experts and conducted research to a self-selecting sample of 650 IT professionals. This report blends new statistics with detailed feedback from over 400 testimonials and aims to shed light on this misunderstood and overlooked topic.

Bullying is rife in schools. In fact, its legacy can leave such a lasting impact through people’s lives, it has become a recurring theme in popular films, songs and books. Bullying is also rampant in the workplace, although many individuals vehemently deny this is the case. This phenomenon is far more complicated than the childhood equivalent, but the results are equally devastating for victims and organisations alike. There is some evidence to suggest that things might be slightly worse in IT. Over the last few months IDG Connect has been investigating this in more detail. We have spoken to numerous industry professionals, consulted a panel of experts and conducted a self-selecting survey of 650 IT professionals to gather over 400 in-depth personal testimonials. The results show 75% of our respondents claim to have been bullied at work and 85% have seen it happen to others. These results in no way prove that things are worse in IT than elsewhere, but they do paint a pretty comprehensive picture of the problem. Above all though, these findings highlight the fact that however these issues are defined, they are endemic through the IT workplace: if nothing else, they need to be acknowledged and discussed. In the course of this short report, we look at what we have discovered and see if we can shed some light on this seemingly ongoing problem. We profile the bullies and the bullied and try to provide some context on why IT could be worse than other professions. This is an insidious problem, it is extremely difficult to pinpoint, yet it is everyone’s responsibility to understand what goes on – this is the only way it will ever be tackled.

 

Please read the attached whitepaper.

 

 

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Calibración diagnóstica [642]

de System Administrator - sábado, 2 de agosto de 2014, 01:37
 

Precisión diagnóstica y exceso de confianza en médicos

¿Qué es la calibración diagnóstica? (Error en medicina)

Este estudio sugiere que podría no haber buena asociación entre la precisión diagnóstica de los médicos y su confianza en esa precisión. Mejorar esta asociación y aumentar el empleo de recursos en los casos difíciles podría reducir los errores diagnósticos. 

Continuar leyendo en el sitio http://kwfoundation.org

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Can Amyloid Spread Between Brains? [1410]

de System Administrator - viernes, 11 de septiembre de 2015, 01:58
 

FLICKR, ALLAN AJIFO

Can Amyloid Spread Between Brains?

By Jef Akst

A study of deceased patients who received injections of cadaver-derived growth hormone hints at the possible transmissibility of Alzheimer’s disease. 

Examining the brains of recently deceased patients who more than 30 years ago received injections of growth hormone derived from the pituitary glands of cadavers, researchers have found evidence that Alzheimer’s disease (AD) may be transmissible via extracts contaminated with amyloid-β. While none of the patients exhibited signs of dementia before their deaths, most had moderate to severe accumulation of amyloid-β in their brains. The results are published today (September 9) in Nature.

“It’s the first in-human indication of potential transmission of amyloid-β pathology,” said Claudio Soto of the University of Texas Health Science Center in Houston who was not involved in the study.

The results are “extremely provocative,” said neurologist and neuroscientist Costantino Iadecola, director of the Feil Family Brain and Mind Research Institute at Weill Cornell Medical College who also was not involved in the study. “The implications . . . are really astounding. They range from the way we should behave in the operating room all the way to the basic mechanistic questions that are still unsolved in Alzheimer’s disease.”

Before a synthetic growth hormone was created in 1985, patients with growth deficiencies were often treated with growth hormone extracted from homogenized human pituitary glands collected from cadavers. Later, researchers discovered that this therapy increased patients’ risk of developing Creutzfeldt-Jakob disease (CJD), a neurodegenerative disorder caused by the misfolding of proteins called prions. Because the prion proteins themselves are infectious agents, contaminated batches of cadaver-derived growth hormone can spur CJD pathology in recipients’ brains.

To test the possibility that AD can be transmitted in a similar way—a controversial idea hinted at by animals studies conducted in the last few years—John Collinge of University College London’s Institute of Neurology and his colleagues examined the brains of eight deceased CJD patients who’d received cadaver-derived growth hormone treatments as children. “What we find, very much to our surprise, is that, of these eight patients, four of them had quite significant and quite severe deposition of Alzheimer’s amyloid protein in their brain,” Collinge said. Three more had less substantial AD-like pathology, he added; only one patient was completely free of amyloid-β.

While amyloid-β is not uncommon among the elderly, the patients examined in this study were only 36 to 51 years old when they died, and none had mutations that would predispose them to early-onset AD. “That age group you usually don’t see this pathology,” Collinge said. “We think the most likely explanation is that the growth-hormone preparations with which these people were treated as children, in addition to being contaminated with prion proteins, were also contaminated with amyloid-β seeds.”

“There is very strong evidence coming from transgenic mice experiments that these things can happen in experimental models,” Soto said, noting that his group and others have induced amyloid-β deposition in mice by injecting brain extracts from an AD patient. “The big question in the field was can this happen in humans. I think this is the first study where something like this may be happening in real life.”

Not everyone is convinced that the data point to the transmissibility of AD, however. While the interpretation is “tantalizing,” the results are far from definitive, said the University of Pennsylvania’s John Trojanowski. “This is such a small study with so many confounds that I am surprised it appears in Nature as it does not provide a clear and resounding answer on the question of human-to-human spread of pathological amyloid-β.”

The study’s small sample size is one concern. “You’re talking about a handful of patients; you don’t know what else was going on in those patients,” said Iadecola. And while it is atypical to see amyloid-β pathology in people this young, it is not unheard of, Trojanowski added.

Yale Medical School’s Laura Manuelidis, who was not involved in the research, agreed that the results should be interpreted with caution. “Since classic pre-senile AD . . . is often evident in people aged 50–60, the few cases reported here does not mean that AD is infectious,” she wrote in an email to The Scientist. “The warning that AD amyloid . . . is infectious is not warranted.”

One alternative explanation for the results is that the prion aggregates that cause CJD spurred the formation of amyloid-β plaques, a phenomenon called cross-seeding that has been shown in transgenic mice for aggregates of tau and α-synuclein. But when Collinge and his colleagues looked at the brains of patients who’d died of CJD but had not received cadaver-derived growth hormone treatments, they found no evidence of amyloid-β accumulation in similarly aged individuals. Moreover, the prion aggregates and amyloid-β accumulation occurred in different parts of the patients’ brains, Collinge noted.

Yet another possibility is that the development of CJD in these patients may have hindered the brain’s clearance mechanisms, so the organs were unable to remove amyloid-β plaques as they formed, Soto said. Still, he believes that this study does point to the possible transmissibility of Alzheimer’s pathology. “To me it’s the most likely interpretation of the results,” he said. “They make a good case that what they’re seeing is really some form of transmission from human to human.”

“There certainly is no evidence out there that this treatment can cause Alzheimer’s disease, per se, but I do think it’s convincing that the treatments induce amyloid-β deposition,” said Lary Walker, a neuroscientist at the Yerkes National Primate Research Center and Emory University in Atlanta, Georgia, who wrote an accompanying perspective in Nature but was not involved in the work. “Whether this was a precursor of the eventual development of Alzheimer’s, we just can’t know at this point.”

Z. Jaunmuktane et al., “Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy,” Nature, doi:10.1038/nature15369, 2015.

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Can games create an education fit for the future? [1081]

de System Administrator - sábado, 31 de enero de 2015, 20:47
 

Can games create an education fit for the future? 

Imagine a school where playing video games is encouraged during classes and may even replace exams. A new educational programme uses SimCity to test children on vital problem-solving skills.

Video games usually get in the way of homework. GlassLab, however, is a collaboration between educators and technologists. Uniting commercial game studios and educational groups the aim is to embrace gaming technology to transform the learning process and make it more relevant to the demands of the 21st Century. 

They could even one day replace traditional exams.

SimCityEDU: Pollution Challenge, which has just launched, is an educational version of the video game SimCity. Designed for teenagers, students play the role of a city mayor, managing a city with some pressing pollution problems.   

BBC Future spoke to Jessica Lindl, general manager of GlassLab, at the Silicon Valley-based gaming company, EA (Electronic Arts) about how games could prepare children for jobs

If you would like to comment on this or anything else you have seen on Future, head over to our Facebook page or message us on Twitter. 

Link: http://www.bbc.com

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CAN WE CURE VIOLENCE? [624]

de System Administrator - viernes, 1 de agosto de 2014, 23:00
 

CAN WE CURE VIOLENCE?

Written By: Steven Kotler

Violence is contagious, this we know. Time and again, researchers have found that exposure to aggression links directly to increases in violent behavior. This is why, for example, 30% of abused children grow up to be abusers themselves. It’s also why, as Gary Slutkin, a professor of epidemiology and public health at the University of Illinois, Chicago and the executive director of CURE Violence, recently told New Scientist: “[P]eople who have observed violence are 30 times more likely to commit it. Under certain conditions it can be up to 100 to 1,000 times more likely.”

Continue reading on the site: http://kwfoundation.org

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Cáncer y Emoción [990]

de System Administrator - jueves, 13 de noviembre de 2014, 12:36
 

Cáncer y Emoción: Una relación Particular

por María Clara Ruiz

¿Y a quien no le ha pasado? Cualquier día abrimos el periódico y encontramos un titular que dice algo así como: “científicos han descubierto la cura para el cáncer”. Dudo que alguien no se detenga un momento para mirar, al menos de reojo, si esta vez es verdad una de las noticias más anheladas en los tiempos actuales.

Pero, a pesar de los múltiples avances, siguen enfermando nuestros amigos, nuestros vecinos, nuestra familia, nosotros mismos. Incluso, siguen muriendo personas cercanas ante nuestros ojos incrédulos y ante nuestra helada impotencia.

Esta es una de esas entradas del blog que llevo meses aplazando. El motivo es claro. No me gusta parecer como que estoy por encima de todo mal con mi lenguaje psicológico, que puesto en el papel o en la pantalla del ordenador suena a pretensión de infalibilidad, con su aire de arrogancia. He sido testigo de estas actitudes por parte de no pocos médicos/as, psicólogos/as, trabajadores/as sociales, enfermeros/as que se han quedado momificados, ellos sí, en una especie de frialdad crónica que les impide rescatar, al menos, una pequeña porción de empatía y para quienes el “saber” se ha convertido en un arma o, como mínimo, en una gran muralla que los hace inaccesibles.

Ese es el “saber” que yo no he querido aprender. Me resulta más interesante conocer lo que pasa con la persona que vive un proceso de enfermedad como el cáncer. Me preocupa si tiene un contexto que le permite expresar sus vivencias, sus expectativas, sus miedos, sus esperanzas. Me pregunto si ese contexto, lo que llamamos “red de apoyo”, está preparado para vivir consciente y saludablemente los cambios que inevitablemente se producen. En fin, no me preocupan demasiado las estadísticas, el gasto económico que genera, las horas de trabajo que ocupa un enfermo, ni tampoco a donde se va el alma de quien muere. Sí me interesa lo que nos sucede aquí y ahora, frente a esta enfermedad que parece tener algo que decirnos, pero que no estamos siendo capaces de escuchar.

Y me preocupa, especialmente, la parte de razón que tuvo W. Reich y luego algunos otros especialistas en psicosomática, cuando hablan de una estrecha relación entre el mundo emocional y el desarrollo de una biopatía como la del cáncer. Esta idea ha disgustado a muchos, que prefieren pensar que esta enfermedad se limita a una transmisión genética, o que dejando de fumar 20 cigarrillos al día o yéndose a vivir al campo y comiendo sólo de la huerta ya está todo controlado. Parece que, aunque esto ayuda, la cosa no es tan simple.

Reich hablaba de la resignación caracterológica como una de las actitudes más peligrosas y de la rigidez caracteromuscular como un caldo de cultivo extraordinario para el cáncer y otras biopatías. Ya que no me extenderé aquí en su teoría, sugiero revisar su libro La Biopatía del Cáncer (Ver biblioteca), en el cual habla sobre los componentes emocionales y bioenergéticos que contribuyen a su formación, además de describir un tratamiento para pacientes con esta biopatía. Para introducirse en el tema de la rigidez caracteromuscular, sugiero leer en este mismo blog La Coraza Caracterial y Muscular y para reflexionar sobre la resignación, invito a leer La Resignación, una Peligrosa Comodidad. Para entrar en la experiencia del cáncer desde una visión más cercana, recomiendo el libro de mi amiga y colega Nuria Casas: La Festa dels Crancs

Por otra parte, el pensamiento de Reich ha sido bien y mal usado en este campo y en muchos otros. En relación con las enfermedades psicosomáticas y las biopatías, no es raro encontrar interpretaciones abusivas, ya sea para empeñarse en que psique y cuerpo no tienen nada que ver (es necesario pensar así para que sigan saliendo las cuentas: 2+2=4) o, al revés, para generar un cierto sentimiento de culpabilidad ansiosa -como si ya no fuera bastante con el diagnóstico-, por no haber sido capaz de evitarse un cáncer cuando se trataba de algo tan “fácil” como respirar bien, pensar positivo, tener fe o expresar las emociones correctamente.

No, no es tan fácil. Y nada asegura que por claras que tengamos las cosas, esto no va a sucedernos también. Veamos lo que dice Luis Chiozza, quien tuvo siempre el arte de traducir con tremenda sencillez lo que a otros nos resulta tan complicado:

Sólo una mínima proporción entre los cánceres, de un 5 a un 10%, se demuestran ligados a una predisposición genética que se trasmite a los hijos a través de los gametos. Cabe aclarar además que hay una enorme distancia entre una predisposición a una determinada enfermedad y el hecho de que esa enfermedad se desarrolle. Para decirlo en palabras más simples, que un automóvil tenga la llave de contacto puesta no determina que el motor arranque a menos que alguien se ocupe de hacerla girar en la dirección que corresponde. Dejaremos sin embargo abierta la cuestión de si puede influir en el desarrollo del cáncer ese aspecto de la personalidad que denominamos carácter, y más allá de que pueda decirse que el carácter (también como predisposición) se hereda, no cabe duda de que en el seno de una familia con un estilo de vida el carácter se “contagia” más allá de la herencia biológica”.

(Fuente: Chiozza, L., “Cáncer: ¿Por qué a mí, por qué ahora?”)

Chiozza, como Reich, va más allá en el análisis y habla de los agentes carcinógenos, es decir, de los factores que contribuyen a que se desarrolle un cáncer. Sí, por supuesto que hay algún porcentaje de transmisión genética, como ha explicado anteriormente, y también una influencia del tabaco, de elementos contaminantes y radioactivos o de una mala alimentación. Pero también habría que tomar en cuenta esos factores de riesgo que se ignoran tan fácilmente, como son el agotamiento y la depresión, los disgustos permanentes, el estrés y las formas de atravesar un duelo.

Y son fáciles de ignorar estos factores cuando se normalizan. Porque estar deprimido/a ya parece una condición casi natural. Estar cansado/a da incluso cierto estatus, así como tener problemas o estrés. Y evitar los duelos a toda costa se está convirtiendo en un mandato, porque “perder tiempo” sufriendo por una pérdida grande o pequeña, está muy poco aceptado últimamente.

Lo que no se va, ni con antidepresivos, ni con alcohol, ni con tabaco, ni con otras drogas, es esa sensación de “hay algo que me falta”. A pesar de tener aparentemente todo -cuando se tiene- cada vez más nos encontramos en esa situación de insatisfacción crónica.

Ahí es donde vuelve a cerrarse el círculo y nos encontramos de nuevo frente al rasgo de resignación caracterial, cuyas secuelas estamos viendo día tras día, ya sea en las empresas, en los colegios y universidades, en los hospitales o en las consultas de psicoterapia.

Creo que no está siendo útil la sensación de no poder hacer nada frente a nuestra salud. Que si tenemos un costipado, una hernia o un cáncer es, o por nuestra mala suerte o porque algo hemos hecho mal. Ninguna de las dos causas son justas ni reales. Y ninguna nos está avalando como agentes de nuestra propia salud.

Prevenir, hacernos conscientes, sentir y elaborar los duelos, gestionar el estrés, es decir, hacernos cargo de nuestra propia vida, no nos va a garantizar la existencia pero, al menos, nos va a permitir vivir el presente con salud y disfrutar de cada momento, hasta que lo que no depende de nosotros decida otros caminos.

María Clara Ruiz

Link: http://mariaclararuiz.com

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Cell Transfection and Molecular Delivery Technologies [904]

de System Administrator - miércoles, 1 de octubre de 2014, 16:35
 

Entry Requirements

Recent developments in cell transfection and molecular delivery technologies

By Nicholette Zeliadt

Cell biologists have a variety of tricks up their sleeves when it comes to loading up cells with exogenous molecules, such as plasmid DNA or small interfering RNA (siRNA). The most popular options include chemical transfection reagents that ferry molecules into the cells using lipids or polymers; devices that use electricity to make cell membranes transiently porous; and viral delivery systems.

Choosing a delivery method typically boils down to a combination of the cell type being targeted, the class of molecule being delivered, and the transfection efficiency needed to answer the particular research question. “The method that people gravitate to the most is the simplest method, which is chemical transfection,” says Josh Snow, technical services manager at Wisconsin-based Mirus Bio, which sells a variety of transfection products.

By and large, conventional chemical and physical approaches to transfection cover the needs of most researchers using easy-to-transfect and easy-to-grow cell lines. But they’re often toxic, and chemical methods can have low transfection efficiency with primary cells, stem cells, or other difficult-to-transfect cell types. Viral approaches tend to provide very high transfection efficiency in a wide variety of cell types, but are labor-intensive to develop and require special precautions for the personnel using them.

Fortunately, transfection companies have taken notice and have begun developing products that can more efficiently transfect sensitive and finicky cells. For instance, this past January, California-based Life Technologies released a lipid nanoparticle product called Lipofectamine 3000, which was designed to target “hard-to-transfect and primary cells,” says Xavier de Mollerat du Jeu, senior staff scientist at Life Technologies. Other companies, such as Mirus Bio, have developed transfection reagents optimized for specific hard-to-transfect cell types, such as skin cells, neural cells, breast cancer lines, or blood cell lines.

Still others are working on completely new approaches for delivering not only nucleic acids but also additional types of materials such as small molecules and proteins. Here, The Scientist brings you the lowdown on some of the newest transfection and molecular-delivery products and methods.

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Exo-Fect

System Biosciences
systembio.com

 

EXO-FECT: Isolated exosomes are transfected with nucleic acids of interest using the nonliposomal transfection reagent, Exo-Fect. Transfected exosomes are then added to cells, which internalize the vesicles along with their cargo.
See full infographic: JPG | PDF
THE SCIENTIST STAFF

Exo-Fect is a nonliposomal transfection reagent that initially delivers nucleic acids, including plasmid DNA, mRNA, microRNA, and siRNA, directly into isolated exosomes—naturally occurring extracellular vesicles that are shed from most cell types and are present in most bodily fluids. Exosomes are thought to function in intercellular communication; after they are released from cells, exosomes can fuse with distant cells or become internalized through endocytosis. Transfected exosomes can therefore serve as delivery vehicles for nucleic acids of interest. “You add the exosomes to cells, and they will deliver that cargo that you put in,” says Travis Antes, senior director of product development at System Biosciences.

To get started, users will first need to isolate exosomes, which can be accomplished by ultracentrifugation of cell-culture media or bodily fluids, or by using a commercial exosome-isolation kit available from multiple vendors including System Biosciences, Life Technologies, and others. Alternatively, researchers can purchase pre-isolated exosomes from System Biosciences. The transfection protocol is relatively straightforward: Mix isolated exosomes with the nucleic acid to be delivered and the Exo-Fect reagent, heat at 37 °C for 10 minutes, and then chill on ice for half an hour. Add a second reagent to precipitate the exosomes so that they can be separated from the transfection reagent and any untransfected nucleic acid. The entire procedure takes about 45 minutes to complete and requires roughly one million exosomes per transfection reaction, which should be sufficient for exosome-mediated delivery of molecules to cells in two wells of a six-well culture plate.

Benefits

  • Exosome-mediated delivery is nontoxic, Antes says. “Once we add the exosomes onto cells, there’s zero [cell] death.”
  • Can be used to deliver mixtures of different nucleic acid types
  • The Exo-Fect transfection kit comes with a fluorescently labeled nontargeting siRNA that can be used to monitor the effectiveness of a transfection and subsequent delivery into cells.

Challenges

  • Depending on the method used, exosome isolation can be time-consuming and labor-intensive.
  • The product was only released in April 2014, so it remains relatively untested by researchers.
  • The fetal bovine serum (FBS) that is typically added to cell culture media is chock-full of cow exosomes that can interfere with exosome-mediated delivery. The company recommends users grow their cells in media with exosome-depleted FBS.

Cost

Kit costs range from $195 for 10 transfection reactions to $350 for 20 reactions. Exosome isolation kits start at $288, and a 50 mL bottle of exosome-depleted FBS sells for $153. The company also provides pre-isolated exosomes from a variety of sources starting at about $350 for a vial containing roughly one million exosomes.

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CellSqueeze

SQZ Biotechnologies
sqzbiotech.com

 CELLSQUEEZE: The rectangular microfluidic chip contains a series of parallel channels, each with at least one narrow constriction designed to be smaller than the diameter of a cell. As the cells squeeze through the constrictions, pores form transiently in the plasma membrane, allowing extracellular molecules to enter the cytoplasm by diffusion. The cell membrane then reseals within minutes.

See full infographic: JPG | PDF

REDRAWN FROM "NARROW STRAIGHTS," THE SCIENTIST, JULY 2013

CellSqueeze is a microfluidic system released to the market in 2013 that can deliver a variety of materials, including siRNA, drugs, proteins, or nanoparticles, into virtually any cell type. (See “Narrow Straits,” The Scientist, July 2013.) The system uses a rectangular microfluidic chip containing a series of 75 parallel channels, each of which is 30 microns in diameter and contains at least one narrow constriction designed to be smaller than the diameter of a cell.

As the cells squeeze through the constrictions, transient pores form in the plasma membrane, allowing extracellular molecules to enter the cytoplasm by diffusion. The cell membrane then reseals within minutes. Disrupting the cell membrane in this way “doesn’t seem to have any long-term side effects on the cells,” says Armon Sharei, a postdoctoral fellow at Harvard Medical School who cofounded SQZ Biotechnologies withRobert Langer and Klavs Jensen of MIT. “So it looks like we just open up their membrane and they repair it after the stuff is in, and they don’t think anything of it,” adds Sharei.

The system has a pressure regulator that allows control of the speed with which the cells flow through the channels, and a pair of reservoirs that sit atop the chip and interface with its inlet and outlet holes. Users simply add their material to be transfected to a sample of cells in solution, deposit the mixture into the one of the interchangeable reservoirs, and apply pressure to begin pumping the sample through the device. Cells that have passed through the chip collect in the opposite reservoir, where they can be retrieved. It only takes about 5 seconds for a sample to flow through the system, Sharei says.

Benefits

  • Easy to use and very fast, says user Morgane Griesbeck of the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard who used the system to introduce a recombinant protein into a rare subset of human primary blood cells, “without stressing them too much, which is something very difficult,” she adds.
  • Simple process that works well with a variety of cell types, including established cell lines, primary immune cells, and embryonic stem cells
  • Can deliver a medley of materials simultaneously
  • The company offers 16 different chip designs in which the length, width, and number of constrictions per channel vary, so researchers can tweak a variety of parameters to try to get the delivery that they desire.
  • Can reliably deliver molecules up to 2 MDa in size. “Bigger things probably get in too, but that’s the biggest we’ve tested,” Sharei says.
  • Unlike conventional delivery strategies, the process doesn’t involve proprietary buffers or delivery vectors that might be toxic to cells.

Challenges

  • The system is not currently suitable for delivering DNA and mRNA. “We know the mRNA and DNA get inside cells, but once they’re inside, something prevents them from getting expressed,” Sharei says. “We think we know what that is, and initial tests show that we may be able to get around it.”
  • The reservoirs hold a maximum volume of 250 μL. Larger volumes can be processed in small batches sequentially.
  • Requires two to three training sessions to learn how to use
  • The holder that clamps the reservoirs onto the chip will need to be replaced periodically because it tends to loosen over time, causing leaks that can ruin experiments, Griesbeck says.

Cost

  • Chips sell for $50 apiece. A starter kit consisting of the pressure system plus two holder sets is available for $3,000. Onsite training will set new users back about $800 to $1,000. The system is commercially available only to “approved partners,” Sharei says. Prospective users will need to consult with the company’s scientific team before they can gain access to the technology.

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 Gold nanoparticle–mediated laser transfection (GNOME)

Leibniz University Hannover, Germany

GNOME: Cells are incubated with gold nanoparticles (top); once the particles have settled on the cells, the molecule to be transfected is added as gold particles adhere to the cell membrane (middle); and irradiation with very brief pulses of a weakly focused green laser beam causes tiny holes to form in the cell membrane, allowing the diffusion of extracellular molecules into the cytoplasm (bottom).
See full infographic: JPG | PDF 
REDRAWN FROM PLOS ONE, 8:E58604, 2013.

Laser-based transfection uses very short pulses of light to poke tiny holes in the cell membrane, allowing the diffusion of extracellular molecules into the cytoplasm. The strategy has been used by laser specialists to deliver different molecules into cells for at least a decade, but it is has traditionally been painstakingly slow and low-throughput because the laser must be precisely focused on a cell with submicron resolution, one cell at a time.

To speed up the process, Dag Heinemann, a postdoctoral fellow at the Laser Zentrum Hannover e.V. in Germany, and his colleagues first incubate their cells with gold nanoparticles that are roughly 200 nm in diameter. After about three hours, the particles settle onto the cells, and the researchers irradiate the sample with very brief pulses of a weakly focused green laser beam with a diameter of about 90 microns. The irradiation is performed in an automated device that the researchers developed in-house, complete with a microscope stage and software that automatically moves the culture plate around to quickly irradiate all or parts of the sample.

Upon absorbing the light, electrons in the gold particles oscillate rapidly and heat up. What happens next is not well understood, Heinemann says, but the end result is that the cells’ membranes become perforated. Using the technique, Heinemann’s team delivered siRNA and effectively knocked down a gene in a canine cancer cell line (PLoS One, 8:e58604, 2013). The team estimated that nearly 90 percent of the cells were transfected, and more than 80 percent of the cells remained viable after the treatment.

Benefits

  • Very gentle. “We can achieve very high cell viabilities, which are typically above 90 percent even with a sensitive cell type,” Heinemann says.
  • High-throughput. Heinemann says that an entire 96-well plate of cells can be processed in about 4–5 minutes.
  • Compatible with a variety of cell types and highly reproducible, “because the physical mechanism stays the same and the cell itself is not actively involved in the mechanism,” Heinemann says. Working in collaboration with researchers at the Hannover Medical School, Heinemann says he has successfully transfected several different cell lines as well as primary neurons, cardiomyocytes, and stem cells, which tend to be difficult to transfect using established methods.
  • In addition to delivering siRNA, Heinemann has also used the method to deliver proteins, small molecules, and synthetic oligonucleotides called morpholinos. 

Challenges

  • Doesn’t work very well with plasmid DNA or other relatively large molecules. “We think the plasmid is quite large for the type of openings we introduce with the particles,” Heinemann says.
  • The gold particles eventually enter the cells in the process and could potentially alter cell behavior. “But as much as we know, [the particles] are completely biologically inert and they do not affect the cell afterward,” Heinemann says.
  • It’s still in the experimental stage at this point. Heinemann says he’s currently developing a user-friendly prototype device that could be operated in a typical cell biology lab with a simple press of a button. He says he hopes to have the system ready within a year.

Cost
None available. But Heinemann expects that his device will be competitive with sophisticated electroporation systems, which typically retail for about $10,000 or more.


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