Can e-cigarettes actually help smokers quit? - ] Medical devices usually come in flavors like "Spiked Nog," "Apple Jaxx," or "Aphrodite case," but proponents e-cigarettes introduced in 06, argued that the pen-shaped nicotine vaporizers could help cigarette smokers to quit the habit. Now, a review of the scientific literature published today, gives credibility to this claim, although the issue is far from settled.
Led by the UK Cochrane Centre, the review focused on testing two randomized, but has also examined data from 11 cohort studies that compared people who were already trying stop with and without e-cigarettes. Overall, the data "suggest that electronic cigarettes may be useful [for] stop smoking and reduce cigarette consumption," says lead author and specialist Hayden McRobbie behavior of the Wolfson Institute of Preventive Medicine in London.
After 1 year, trial participants who used the devices were more than twice as likely (4% against 9%) to quit successfully compared to those who used a placebo spray without nicotine. Another 36% of users e-cigarettes have been able to reduce the number of traditional cigarettes they smoked by 50% or more. But 28% of placebo users also reduced their cigarette consumption by at least 50%, suggesting that some can leave the e-cigarette can be derived from the simple fact of "smoke" it.
Because there are so few studies of how e-cigarettes work as a tool to leave the examination of confidence levels are low and estimates for efficacy may change. But still, McRobbie said he would recommend e-cigarettes to a friend or family member who was trying to stop smoking, and he thinks that health professionals should be more open to recommending the devices.
The Cochrane review looked for signs of severe adverse reactions to the therapy e-cigarette, but found none. This is certainly not to say that electronic cigarettes are completely harmless. "We do not yet know the long-term use of risk," said McRobbie. Previous analyzes of their vapors were found numerous toxic chemicals and heavy metals. These compounds are present in sufficiently large doses to cause long term health problems remains to be seen. But compared to the dangers of tobacco, "the effects on the real health are quite likely to be smaller because the e-cigarette vapor ... has fewer toxins in it," says Schick Suzaynn a biologist at the Centre research for the fight against smoking and education at the University of California, San Francisco.
of course, the safest thing to do is to avoid or otherwise-e-cigarettes altogether. But for those who are already addicted to nicotine, electronic cigarettes may be the lesser of two evils. "now, I want the debate can move on the best way that we can advise and support smokers who use these products to stop smoking completely as soon as possible, "said Ann McNeill, professor of tobacco dependence in national addiction Centre at King's College London, in an official statement. The Cochrane review called for further study, specifically comparing e-cigarettes with other methods of quitting, like the patch in terms of safety and efficiency. "We need more data to strengthen the evidence," said McRobbie.
Bad luck and cancer: A science reporter’s reflections on a controversial story -
We reporters or it, in any case, often fail to anticipate the gripping stories that readers and that will quickly disappear into oblivion. Given that, maybe I should not have been surprised that a story that I live out of the printing press in the lull between Christmas and New Year has generated more comments than any other, I ' wrote.
The piece, which appeared online with the title "the simple calculation which is why you can (or not) a cancer" (and in the section of the journal News with the title "bad luck Cancer . "), describes an article published in the edition of January 2 science as I and many other reporters explained, the study suggested that" bad luck "single mutations - RANDOM accumulate in stem cells healthy may account for about two thirds of cancers than the risk conferred by environmental and genetic factors combined. A message was that some cancers could not be avoided and detect early was key to fight .
the players wasted little time skewer the authors, mathematician Cristian Tomasetti and geneticist at Johns Hopkins University's Bert Vogelstein cancer in Baltimore, Maryland Their statistics were defective, some argued. they included many rare cancers and left several more common. Earlier today, the International Agency for Research on Cancer, the World Organization of cancer arm of health, put on a press release stating that unusual "strongly disagree" with the report. The agency said that "almost half of all cases of cancer worldwide can be avoided." He accused the authors push for early detection "if misinterpreted ... could have serious negative consequences both cancer research and perspectives of public health. "
Reporters, if anything, do less well." please journalists, get a clue before you write about science, "argued an angry column in the Guardian , co-written by an evolutionary biologist who goes by the Twitter handle and @GrrlScientist statistician Bob O'Hara at the biodiversity and climate research Centre in Frankfurt, Germany
given the fury I wondered :. was I wrong? Had the authors? Answering these seemingly simple questions have proven surprisingly difficult, exposing the challenges that come with scientific communication and the desire to scientific authors and journalists in order to streamline the story they are trying to say.
I started with my own story, working behind the science that spawned it. I wrote that the theory of random mutations in stem cells, "says two-thirds of all cancers." Immediately, I knew that I had written some of this sloppily, to put it generously: The study did not include all cancers. In fact, he did not include two of the most common, prostate and breast cancer, because the authors were not able to identify the size of the stem cell compartment or frequency of stem cell divisions in the tissues . Although my piece then recorded the number of cancers in the study, I pointed out the earlier omissions.
Encore, was "two-thirds" referring to the number of cases of the study include cancers, like me and other journalists had suggested or something else? Journalists like figures that shorten a study at a ball point. I immediately asked if this finding two thirds could be such a gem. Tomasetti had explained to me in a long interview that "if you go to the American Cancer Society website and check what causes cancer, you will find a list of things either inherited or environmental. We say two thirds is not one of them. "I ran the text of my" two-thirds "phrase by him before publication and he had no objection (there were other details).
Last week we talked again. Tomasetti had received over 0 emails. Parents of children who were cancer deaths were grateful that it could have happened entirely by chance, suggesting that there was nothing they could have done. biologists and statisticians disputed its findings or simply surprised that so many cancer could be random.
"We do not claim that two-thirds of cancer cases are due to bad luck," Tomasetti said softly. what the study argued, he explained, is that two-thirds of the variation in cancer rates in different tissues can be explained by random bad luck (a point made by others). what meant, I wondered? Tomasetti, chatting by phone, had me draw graphs to help me understand. At the end of the day, I'm still not sure I grasp the essence.
Tomasetti was friendly. "There are many scientists who need clarification" on the document, he said, with some statisticians. He was preparing a technical report with additional details, and Johns Hopkins had just put a press release explainer. "Honestly, I feel and what I say to the BBC, and you can definitely quote me on this-general, reporters who have interacted with made us a very honest and sincere effort to be as accurate as possible. "
it was only after several hours of interviews that I finally understood the figure of two thirds. Some fabrics are overwhelmed by the cancer more easily than others, and accumulating mutations in stem cells explained two-thirds of this variability, Tomasetti and Vogelstein had concluded. It was my "aha" moment, and it came too late, after my initial deadline.
I contacted some of the criticism. "I just read your article, and I do not think it falls into the wrong category (at worst, it bypasses the lip without dropping in)" wrote O'Hara, author of Guardian room, in an e-mail to confuse me further, because I had not goofed up? By phone, he explained that one of his quibbles was the word "luck" -present in the summary document, emphasized by the authors, and highlighted in almost every news story. He looked sexy, but O'Hara felt it was inaccurate, because virtually all cancers is a product of chance in a sense.
"It is too easy to blame the media," said David Spiegelhalter, a biostatistician at the University of Cambridge in the UK, who blogged about the story. ( "Your article is fine," he assured me.) In this case, he felt, "most of the coverage is very reasonable, most cases of cancer are due to chance."
However, mistakes were made along the way, which has not surprised. "this is very difficult things," said Spiegelhalter. "I feel for you. It's one of those things that is so superficially simple, yet superficial simplicity is not correct. "
The authors of the paper, many felt, also were guilty of trying too hard to develop a simple message. The document included a diagram visually arresting splitting cancers in green and blue categories. the green cancers were "mainly due" to mutations suggesting random-write the authors, they were less likely to be prevented by changes in behavior or diet. However, this category included cancer and melanoma of the esophagus, both of which are considered to have close links with environmental factors such as excessive alcohol consumption and exposure sun, respectively.
Melanoma sitting just a bit inside the green border, but still, it was green, which left many readers exercised. "They have ignored some of the basic lifestyle factors," said Graham Colditz, a specialist in cancer prevention at the University of Washington in St. Louis. "Obviously, they had good intentions," said Anne McTiernan, a physician and epidemiologist at the Fred Hutchinson Cancer Research Center in Seattle, Washington. But, she continued, the authors assume that a correlation exists between the number of divisions of stem cells and cancer risk was meant one behind the other, something their data could not prove. Tomasetti agreed that this is correct, but noted that "all the biology that we have on this subject supports" the idea that the accumulation of random mutations in healthy cells can trigger cancer. Some scientists have argued that the graphic carried a missive for the prevention, with huge risk differentials between cancer caused by environmental or genetic, such as lung cancer in smokers or head and neck related to human papillomavirus and cancer at the same site without obvious cause.
The shades were many. Although they quibble over the details, most would agree that random mutations play a real role in cancer - but for many other things. Despite the fury, this common ground is shared by the two authors of the paper and its critics. "This is a really fascinating pattern they observed, but it is a small message," said Timothy Rebbeck, a specialist in cancer prevention at the University of Pennsylvania. "It does not exclude the ability to prevent and treat cancer. It does not exclude our need to better understand the causes of cancer" bottom line of the paper was not simple, but the message was for me. The science is complex, and people care deeply about the biology of diseases that affect their families and themselves. Distillation history-with space constraints, with a clear desire to write that will hold readers' attention and help them understand-has risks for scientists and for journalists. They are the ones that I hope will never forget, even if I wrong now and again
Revised 2:53 p.m., 01.14.15 :. This story has been revised to remove references to unpublished letters to science.
In perhaps the most famous study of neglect in childhood, the researchers monitored the progress, or lack of celui- one, in children who lived as infants in dark orphanages in Romania and are now teenagers. A new analysis now shows that these children, who have a variety of behavioral and cognitive problems, have less white matter in their brains that make a comparable group of children in local families. affected brain regions include the nerve bundles that support the attention of the general cognition, and processing of emotion. The work suggests that sensory deprivation early in life can have dramatic anatomical effects on the brain and may help explain the long-term negative effects previously documented behavior. But there is some good news possibilities: A small group of children who had been abducted orphanages and moved to shelters to 2 years seemed to bounce back, at least in brain structure
"This is an exciting and important. study, "says Harvard Medical School psychiatric researcher Martin Teicher, who runs the Biopsychiatry research program development at McLean Hospital in Belmont, Massachusetts. The "crucial question" of whether children can recover from the setback of early adversity has not been answered before, he added.
The work is based on MRI and other measures taken in Romania by researchers at the Bucharest Early Intervention Project (BEIP). The group, led by neurologist Charles Nelson of Harvard Medical School, was moved to action by the collapse of Nicolae Ceausescu regime in Romania in 1989, which had shunted tens of thousands of unwanted children in orphanages run by the state. Nelson said that guards in orphanages worked factorylike team; children could see as much as 17 different guards in a week. Infants rarely enjoyed the interactions one-on-one, which are considered essential to normal development.
Orphanages have sharply reduced their consumption today. But there's more than a decade, when they were still in favor of BEIP leaders saw a need for humanitarian assistance; they also saw a rare opportunity to study the effects of child neglect. Drawing mainly on the research funding from the US government, BEIP offered a limited number of children a chance to get out of orphanages in foster care, providing desperately needed attention. BEIP also worked with Romanian officials to recruit orphans and local children in clinical studies.
BEIP initially enrolled 136 children in research. Only 69 participated in the MRI study published online today in JAMA Pediatrics . Of these, 23 have been established in the group randomly assigned to foster care, 26 from a group assigned to remain in orphanages, and 20 of the local community, as witnesses. The lead author Johanna Bick, a clinical psychologist at Children's Hospital Boston, and colleagues in the BEIP group used an MRI imaging technique called diffusion tensor to watch 48 microstructural white matter tracts in each child, comparing the results at 2 and 8 years of age.
The analysis revealed that children who remain in orphanages were still worse off with the less mature development in four key sets of white matter. The most affected routes included neural circuits involved in cognitive overall performance, emotion, maintaining attention and executive function and sensory processing. Further analysis suggests that the foster care group was more like the community group in brain development, but this conclusion seems to be less robust.
Other non-randomized studies have reported broad cognitive deficits or reduced white matter in adults and some children who have suffered neglect or abuse in the past. They stressed "the same areas we find ourselves affected by the negligence of early life. These results and those of BEIP converge, "claims Bick.
More importantly, Bick said, compared with the children taken by adoptive parents suggests that the loss of white matter may be reversible. What worked in Romania to improve the brain development of children moving in an environment breadwinner could work elsewhere as a remedy for child neglect. "This has very important implications," she said. He suggests that the damage that occurs in a family setting may reversible, too
In a prepared statement, a psychiatric researcher Andrea Danese of King's College London has welcomed the study but noted that more research is needed to determine how these changes in the white matter are related to changes in behavior.
Bick agrees on this point. "What I'm really interested in the investigation right now," she said, "is whether the improvements [seen in the foster children’s white matter profiles] effectively support improvements in the security superior capabilities" such as IQ, the attention and control of emotion. BEIP plans to collect new neurological data this year Romanian orphans as they turn 16.
White House fleshes out Obama’s $215 million plan for precision medicine -
revealed the White House today a price tag and other details Precision Medicine Initiative announced in the State of President Barack Obama of the Union address last week. As expected, most of the $ 215 million proposed to launch the multi-agency initiative in fiscal 2016, which begins in October, will support the construction of a cohort of 1 million US volunteers to genomics and other research biomedical. Another part of the money will fund efforts to understand the genomes of cancer cells. (Click here for a fact sheet from the White House on the map and here for a National Cancer Institute [NCI] fact sheet.)
Precision medicine, a term for tailoring treatments to the constitution genetics, microbiome of an individual, and other factors, is "a game changer" that "has the potential to revolutionize the way we approach health in this country and ultimately the world," said Jo Handelsman, deputy director for science in the White House office of science policy and technology, in a call with reporters yesterday to discuss the initiative. The $ 215 million will be new money added to the budgets of agencies, not funds redirected from existing programs, says the National Institutes of Health (NIH) Director Francis Collins.
Like Science Insider previously reported, the centerpiece of the initiative funded by $ 130 million in 2016, is a longitudinal research cohort consists of at least 1 million volunteers. Such studies large cohort of both healthy people and patients who represent the general population, often called biobanks already-established in countries such as the UK and Japan.
The cohort of US will be assembled by connecting the existing cohort studies. There are at least 0, from the Framingham Heart Study to basic genetic and medical data of patients at Kaiser Permanente in Northern California, which may be invited to join, Collins said. The initiative can also recruit new volunteers to "fill the gaps" and ensure diversity, Collins said.
In addition to developing information such as electronic medical-records and analyzing the genomes of existing patients, the study may have participants wear devices to monitor their health and activities, as Fitbits. And in a departure from traditional cohort, patients will be actively involved in the design of the study and control the use of their data, officials said. (These characteristics make it "more of a biobank," said Collins.) A blue ribbon panel will plan the study, advised by the working groups and a firm compound, ethicists, and others are already forming watching protect privacy, Handelsman said.
another $ 70 million will go to genomics NCI NIH cancer. NCI is wound a 9-year project called the cancer genome Atlas who cataloged the mutations that appear to stimulate the growth of cancer cells, and has several ongoing trials to treat patients based on changes in their tumor. This area is "cutting edge precision medicine," said Collins ; many patients, such as people with breast cancer already receive genetic or other molecular tests to determine the best medication.
The new funds will enable the organization to expand the testing of genetically tailored treatments, explore the biology of cancer, and together a "knowledge network on cancer" to share this information with researchers and oncologists treating patients.
The Food and Drug Administration (FDA) will receive $ 10 million to hire experts to help assess the tests based on sequencing of large portions of the patient's genome, and build disease mutation databases, such as that used to examine two new tests for the genes for cystic fibrosis, said the FDA commissioner Margaret Hamburg.
another $ 5 million will go to the Office of the National Coordinator for Health Information Technology to develop ways to share and preserve the confidentiality of patient data safely.
President Obama is expected to unveil details of initiatives at 11 am ET today at the White House before an audience of researchers, pharmaceutical company executives and others. Congress must approve ultimately spending on the initiative, which will be part of the 2016 budget request the White House is expected to unveil Monday.
Click here to see all of our coverage of the 2016 budget
* Updated January 30 2:55 p.m. a statement that was falsely attributed to Dr. Collins has been corrected.
'Positive' results for Ebola drug upsets plans for trials -
Even researchers whose trial of a potential drug for Ebola made headlines last week worked hard to minimize the glare efficiency, it showed. "It is a weak signal in a non-randomized trial," Yves Levy, director of the French Institute of Health and Medical Research (INSERM) in Paris said Science on the data, which has not published INSERM. Low or not, the ratio The New York Times that favipiravir, a drug against the Japanese flu had halved mortality in a group of patients Ebola in Guinea was a piece of good news that complicates prospects for testing over other Ebola drugs.
the Guinean government has already announced that he wants to favipiravir to more people, and if the results hold for further review, they could force a change in the design of further clinical trials move on front. Meanwhile, the decline in new cases investigators revamping or even cancellation of tests at a time when manufacturers have finally enough material to test some of the most promising experimental drugs. The balance sheet of the epidemic checked last week, Guinea, Liberia and Sierra Leone-three countries counted 124 confirmed cases most affected, against 99 cases the previous week. As Bruce Aylward said the World Health Organization (WHO) at a press conference on 5 February: "The virus has told us this week, loud and clear:" I will not go the way you me expected. "Still, the figures represent a sharp drop in the height of the epidemic in September when there were more than 700 cases reported in one week in West Africa.
Last week, the Wellcome Trust, a charitable organization in the UK which funds several Ebola trials, announced that the trial of Liberian brincidofovir, antiviral developed by Chimerix Durham, North Carolina, would be canceled because the company withdrew its support. "It was quite a surprise to us and a bit of a mystery," said Peter Horby, a researcher at the University of Oxford in the United Kingdom who led the study. Chimerix said he made the decision after discussions with the US Food and Drug Administration (FDA), noting that the trial was also to have patients of difficulty recruiting. Horby said his group was planning to open a second test site in Sierra Leone, where the numbers are much higher. Luciana Borio FDA said Chimerix also refused the request of the agency to make public its correspondence with the company. Chimerix said he focused on the completion of drug trials treat other infections :. cytomegalovirus and adenovirus
Although a trial is canceled, others are about to move forward. Horby said his group hopes to begin evaluating an RNA inhibitor called TKM-Ebola soon. the drug, manufactured by Tekmira Pharmaceuticals in Burnaby, Canada, has worked in monkeys, but has been in short supply.
The test is about to begin on the zmapp antibody cocktail. Seen by many researchers as the best shot to treat Ebola due to promise monkey studies, zmapp was used in nine patients last summer before the company behind it, Mapp Biopharmaceutical of San Diego, California, announced he had no more supplies. Now the company says it has enough doses to begin a clinical trial in Liberia this week. But there may be too few patients in this country for the experimental drug to prove its value, says Clifford Lane, director of clinical research at the US National Institute of Allergy and Infectious Diseases, which launched the study in Monrovia with the Liberian Ministry of Health and welfare.
So far, Guinea and Sierra Leone, where the Ebola virus is still infecting dozens of people a week, declined invitations to join the study. Their main stumbling block is the test design. Zmapp will be the first Ebola treatment that will be tested in a randomized controlled trial. "I think that the only way to know if these drugs are safe and effective," says Lane.
The governments of Guinea and Sierra Leone as well as Doctors Without Borders, which operates centers Ebola in these countries were for ethical reasons reluctant to participate in treatment trials using a randomized design, controlled. Jeremy Farrar, director of the Wellcome Trust, also opposes the randomized controlled trial design for Ebola drugs given the high mortality rate of the disease. "given the data we have animals and individual patients, I would not be comfortable to be random," he said.
Lane notes that the trial may not need many participants: If the drug is 100% effective and Ebola kills 50% of people infected, he said, as little as 30 people will need to receive zmapp to see if it works. And even if there are not enough patients to provide a clear answer on efficiency, Lane says that scientists could still get valuable information by looking at parameters such as blood levels of Ebola virus in those treated with the drug and the control arm.
study favipiravir in Guinea illustrates the complexity to discern clear answers without robust control and difficulties in communicating. Test data are reviewed every 20 patients by an independent supervisory board. On January 26, they evaluated data from 80 patients. Because they have detected a signal of efficacy, they asked the researchers to share information with regulators in Guinea and France, said Levy. INSERM researchers do not make public their data up to February 25, at the Conference on Retroviruses and Opportunistic Infections in Seattle, Washington. "It is important to have a scientific debate about what these results really mean," said Levy, noting that the organizers of the meeting stressed the data under embargo. A researcher who had seen the data and asked not to be identified said Science favipiravir that did not help all patients treated with it at two test sites in Guinea. In a subset of trial participants who had low levels of Ebola virus in the blood, however, the mortality rate was only 15%. Among similar patients who entered centers earlier and did not receive favipiravir, mortality was 30%. Marie-Paule Kieny, Assistant Director-General of WHO, said it was difficult to make sense of the data at this stage. "You can say it means nothing or you can say that it is promising. More research is needed to know what happened."
Meanwhile, the study in Guinea continues and has enrolled more than 100 patients. "The end result can still be different," says Levy. But preliminary data have already led the Guinean authorities to increase the number of sites where favipiravir be used.
Further tests may be more difficult organize and interpret if favipiravir is widely distributed. a study testing the use of convalescent serum began in Guinea this week. "if there is a decision now to use favipiravir everywhere, what happens with this trial ? »Request Kieny. The zmapp trial may also be affected. This trial is designed to compare zmapp with the standard of care. "If the level of care changes, as is the control used in the trial," said Lane. But he did not see any results, he said. "The only information that I have seen in this study are what was in the New York Times "
* Ebola files. Since the Ebola current epidemic, unprecedented in terms of number of people killed and the rapid geographic spread, science and science Translational Medicine made a collection of research articles and news on the viral disease available for researchers and the general public
* Correction February 13 11:05 :. This story refers to evil zmapp a trial, an Ebola antibody cocktail, as a placebo-controlled trial. as reports of history, zmapp will be tested in a trial which, for the first time, used a randomized control group. But the control group will receive a placebo. People in the control arm will receive the current standard of care, which comprises providing intravenous fluids, balancing electrolytes, maintaining the state of oxygen and blood pressure, and treating other infections if they occur.
Common ingredient in packaged food may trigger inflammatory disease -
The ingredients that give a stable smooth ice cream, chocolate bars and other packaged snacks can promote certain inflammatory diseases chronic. This is the claim of a new study, which finds increasing metabolic diseases and intestinal inflammation in mice fed two emulsifiers commonly used in processed foods. The authors are far from confirming the similar effects in humans, but they suggest that these ingredients cause damage by disrupting the barrier between the immune system and the microbiome-the collection of microbes that inhabit our bodies.
The finding, published online today in Nature is "credible and remarkable," says Karen Madsen, a microbiologist at the University of Alberta in Edmonton, Canada, who was not involved in the study. "It sends a clear message that the changes in our food supply are altering our microbiota and our health."
Gut microbes help us fight infection and resist to allergies, but there is one thing we do not want them to do. touch our intestinal mucosa "These trillion bugs have sort of got to be kept away from us," said Madsen. Normally, mucus layer separates the intestinal cells of the intestine bacteria. But if these bacteria reach the cells, they can stimulate the immune system and cause inflammation. This inflammation of the digestive tract out-of-control is the hallmark of the inflammatory bowel disease (IBD), which causes diarrhea, fatigue and abdominal pain. Chronic inflammation has also been associated with metabolic-a set of concomitant requirements syndrome, including obesity and high blood pressure, that increase the risk of heart disease and diabetes from one person.
Benoit Chassaing, a microbiologist at Georgia State University in Atlanta, wonders if such bacterial invasion could explain what he described as a "perfect correlation" between the increasing use of food additives in industrialized countries and the incidence of IBD. (The disease affects more than one million people in the United States and appears to be rising.) The work by other groups led Chassaing and his colleagues to focus on emulsifiers detergentlike-Coax compounds in a surface smooth, creamy mixture of the ingredients that might otherwise prefer to separate, as the milk fat and water in the ice cream. A 09 study found that carboxymethylcellulose emulsifier supply (CMC) in genetically engineered mice that were already predisposed to intestinal inflammation has led to excessive growth of bacteria in their small intestines and increased inflammation.
In the new work, researchers fed two common emulsifiers, CMC and polysorbate 80, both a strain of genetically susceptible mice and type mice wild-without genetic mutations that put them at increased risk of IBD or metabolic syndrome. Among the sensitive mouse, eat or drink emulsifiers for 12 weeks increased the risk of developing symptoms of colitis mouse model of intestinal inflammation seen in humans with IBD - 40 to 80% %. wild type mice do not develop colitis, but showed a low-grade inflammation in their intestines and several features of the metabolic syndrome: slight weight gain, increased body fat and food intake, and higher levels of blood sugar, which indicates poor regulation of glucose associated with diabetes.
How emulsifiers induce these changes is still uncertain, but the study offers some advice. microscopic imaging of the intestines has shown that the average distance between intestinal bacteria and intestinal cells was reduced by more than half; bacteria seemed to move toward the intestinal mucosa. And fed emulsifier mouse feces showed a greater number of bacteria known to digest and penetrate the mucus. The feces contain a microbiome also seemed more "pro-inflammatory", meaning more highly activated receptors bacteria that trigger inflammation but it is not yet clear that bacteria have that effect. The conclusion of Chassaing: Either emulsifiers damage the mucus layer directly, leaving vulnerable to bacteria, or change the composition of the microbiota, favoring mucus microbes penetrating
This is not at all surprising that these substances have a . effect on intestinal microbes, said Mia Phillipson, a physiologist at the University of Uppsala in Sweden, which studies the interactions of gut inflammation and mucus bacteria. All to be vegetarian to be born by Caesarean section may change the composition of our microbiome significantly, she notes. But relatively few studies to date have examined the effect of food additives on the microbiome in this level of detail. "I think we're just about to realize how important this is," she said. Regarding the implications in humans, Phillipson said it is too early to make general recommendations, but it suggests that people with IBD or a family history of the disease consider avoid these ingredients.
Chassaing, too, is careful not to throw these emulsifiers as the ultimate villain. "Of course, society has changed so dramatically in the last century ... and so many other factors were used in the foods that we can not really even know that the most important role we play." His group is preparing a more ambitious study comparing microbiomes of people who avoid completely emulsifiers for several weeks with those on a standard Western diet.
Why a powerful cancer drug only helps some patients -
A new type of drug that releases the immune system against tumors has been remarkably successful, but only for certain cancer patients. Researchers have found a genetic signature in lung tumors that seems to predict if this immunotherapy drug will work and who will benefit most.
Tumor cells can hide from the immune system by activating a receptor called PD-1 on the surface of immune cells called T cells Instead of attacking tumor cells, T cells leave alone. The new drug is an antibody that inhibits PD-1 blocking this "checkpoint" and release the T cells to remove tumor cells. In clinical trials, PD-1 blockers and other checkpoint inhibitors have prolonged the lives of patients with several types of cancer for years, much longer than conventional treatments. The US Food and Drug Administration has approved several of these drugs for melanoma and one of them, nivolumab, became the first to win approval for lung cancer last week. But the checkpoint inhibitors only work for some people inhibitors-PD-1 shrink tumors in about 20% to 30% of patients and lung cancer researchers are scrambling to figure out why.
One hypothesis is that the checkpoint inhibitors are more likely to work on tumors with more mutations. These mutations are not necessarily those that allow tumor cells to divide uncontrollably or spread to other locations; instead, they can simply encode abnormal proteins that do nothing to the cancer cell. But they can importance for immunotherapies because aberrant molecules may act as foreign-antigens molecules in the body that trigger an immune response. The more mutations in the tumor of a patient, most of these so-called neoantigens and therefore a stronger T cell response in patients taking a checkpoint inhibitor, the thinking goes.
Recent studies support this view. the melanoma patients with more mutations in their tumors neoantigen encoding, for example, were more likely to respond to a checkpoint inhibitor which blocks a protein called CTLA-4.
Now the same seems true for lung cancer. Timothy Chan of Memorial Sloan Kettering Cancer Center in New York, who led the melanoma study, and his colleagues sequenced the exome-protein-encoding DNA-tumors of 34 people with lung cancer non-small cell that had been treated with a PD-1 inhibitor called pembrolizumab. They found that patients were more likely to respond to the drug if the tumor was more the type of mutation which leads to a modified protein. For example, 13 of 18 (72%) patients with at least 178 mutations responded for 6 months or more, compared with one of 13 (8%) of those with fewer mutations. In addition, cancer patients 16 lung that had a distinctive pattern of mutations caused by smoking were more likely to respond that the alleged non-smokers, who had less, different mutations, the group of Chan reports online aujourd 'hui in Science .
the correlation between mutations and therapeutic response to drugs against cancer is "eye-popping" says cancer researcher Drew Pardoll Johns University School Hopkins of Medicine in Baltimore, Maryland, which does was not involved in the study but has worked with the group of Chan. "It is a very important result." Although the results do not necessarily mean that all non-smokers do not respond to PD-1 blockers, DNA sequencing of tumor biopsies could help oncologists decide which drug to give first, he and Chan say. and he suggests that these drugs may work on other smoking-related cancers, such as esophageal cancer and head and neck, Chan added.
the researchers are also studying the possibility of giving patients a personalized vaccine made from neoantigens in their tumor to enhance their response to a checkpoint inhibitor. "I think the potential is huge," said Roy Herbst, a cancer researcher lung at Yale University.
Mitochondria are the central energy production of our cells. Now a Massachusetts company believes that these microscopic cylinders are also essential to conceive a baby and several physician groups outside the United States are testing this hypothesis controversial in women with fertility problems. More than 10 women are pregnant via exclusive in vitro fertilization (IVF) method of the company, adding a bolus of mitochondria associated with a woman in his mature egg. Meanwhile, the Food and Drug Administration (FDA) has set up roadblocks in front of a fertility specialist and stem cell biologist who want to clinically test a different strategy IVF: swapping the mitochondria of a woman transferring chromosomes from its egg into an egg of another woman. The technique, called mitochondrial replacement therapy, was simply legalized in the UK to prevent rare genetic diseases. FDA says it needs more data before allowing the work to proceed. A central question for both in vitro fertilization techniques is whether defective mitochondria or aging actually lead to infertility, and whether the correction of this problem restores health to eggs.
Breast cancer drug may help men with prostate cancer -
PHILADELPHIA, Pennsylvania- A new type of drug against cancer originally intended for women with scarce hereditary forms of breast cancer and ovarian cancer can also help a wider band of patients, according to a small clinical study. The drug halted tumor growth in a third of men with a usually fatal form of advanced prostate cancer. Almost all those who responded had linked mutations in their tumors, indicating that the drug was a common cellular processes, researchers reported this week at the annual meeting of the American Association for Cancer Research (AACR).
The drug blocks an enzyme called poly (adenosine diphosphate [ADP] Ribose) polymerase (PARP), which helps cells repair a type of DNA damage. Oncologists are especially test PARP inhibitors in patients with ovarian and breast cancer born with mutations in BRCA1 and BRCA2 , two genes linked to the cancer most infamous. These mutations raise the risk of a woman breast and ovarian cancer, and the risk of a man's prostate cancer because they inactivate proteins that repair DNA damage that can lead additional stimulus cancer mutations. But the defects in the two genes also allow tumor cells vulnerable to PARP inhibitors, because the drugs interfere with DNA repair further tumor cells machines. This combination makes tumor cells unable to correct DNA damage and die, an idea known as synthetic lethality.
In December, the first PARP inhibitor, olaparib the AstraZeneca has received approval in the US and Europe for patients with ovarian cancer who had inherited a BRCA1 or BRCA2 mutation.
But some cancer patients who lack such mutations also saw their tumors shrink in the tests. A team led by Johann de Bono of the Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, both in London, suspected that these patients had inherited errors in other DNA repair genes or had acquired mutations in BRCA or other genes in a tumor as formed or increased. There are three years, a sequencing project revealed that such defects in DNA repair genes are frequent in tumors of advanced prostate.
To test their hypothesis, group and collaborators of Bono, whose funding was independent of AstraZeneca, the drug gave 50 men with metastatic castration-resistant prostate, which means that their tumors have stopped responding to drugs that block hormones that stimulate the growth of prostate cancer. Of the 49 men who remained in the trial, 33%, or 16 patients responded to the drug, according to three measures decreased levels of tumor cells in the patient's blood, lower levels prostate specific antigen blood biomarkers scans or imaging found that their tumors shrank. When the researchers sequenced the DNA of the tumor patients, they found their hunch was correct: Fourteen of 16 respondents had mutations in one or more of a repair genes dozen DNA in their tumors, and only two nonresponders had these mutations, reported Joaquin Mateo, a clinical fellow in the laboratory of Bono, at the meeting of the AACR. (While three speakers had inherited BRCA2 mutations, four apparently had new mutations in this gene.) Most of these patients responded to the drug for at least 6 months (four for more than 1 year) while those without these mutations usually have worsened within 3 months.
Although genetic testing of tumors are already used to determine whether certain drugs will work for several types of cancer, this is the first time researchers have found such a test for prostate cancer, group Bono said. Olaparib could offer a new option for these men: The trial shows "it's a good swat to this disease," said researcher on prostate cancer William Nelson of Johns Hopkins University in Baltimore, Maryland, during a press AACR conference, adding that the prospect of genetic tests to identify cancer patients with prostate that could benefit from olaparib "looks very promising."
the results also suggest that women of ovarian and breast cancer who do not have a BRCA inherited mutation could still meet PARP inhibitors, if they have DNA repair mutations in tumors group Bono said. Ursula Matulonis of the Dana-Farber cancer Institute in Boston, who presented the results at AACR olaparib a combined test with another drug for patients with breast cancer and ovarian cancer, said at the press conference that his team plans to explore this possibility by DNA testing of biopsies of patients.
Unless a new case is diagnosed in the coming hours, Liberia is expected to announce tomorrow that the country is officially free of Ebola. Cases have been down there since October, and May 9 mark 42 days since the last confirmed Ebola patient in the country was buried safely. The incubation period for Ebola is up to 21 days, and the World Health Organization requires a country to go twice this period without case before declaring the official end of an epidemic.
" May 9 is our day magic ," said the Liberian Minister of Commerce and Industry Axel Addy reporters earlier this week, according to Voice of America. The US Centers for Disease Control and Prevention has already adjusted its travel advice not recommending against non-essential travel. National Public Radio describes some of the challenges the country still faces , including survivorship care, keeping vigilant for reintroductions of Guinea or Sierra Leone, and training replacements for physicians and health workers who died in the epidemic.
* Ebola files: science and Science Translational Medicine made a collection research and articles on the Ebola virus and the current epidemic available for researchers and the general public.
Canadian registry to track thousands of pot smokers -
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Fifteen years after learning about the medical benefits of cannabis from patients in a clinic for sickle cell disease in Kingston, Mark Ware studied the drug on a large scale. A pain management researcher at McGill University Health Centre in Montreal, Canada, he directed the registry Cannabis Quebec, a new one-of-a-kind database that collects information about each prescribed marijuana patient the province over the next 10 years -an estimated 3,000 in all. By collecting data on symptoms, dosage, improvement, and side effects, registry, launched on 11 May and funded by a consortium of nonprofit grant from Canada for the cannabinoid research, aims to fill gaps in knowledge about the effectiveness and safety of medical marijuana treatment. Although more and more states and countries legalize pot for medical purposes, clinical trials of smoked cannabis are rare. "Decisions [about medical marijuana] are made at the ballot box rather than in laboratories," said Raul Gonzalez, a psychologist at Florida International University in Miami, who studies the cognitive effects of cannabis use in HIV patients / AIDS.
The recommended dose for the human papilloma virus (HPV) vaccine Cervarix may be exaggerated in some quarters, according to a new analysis. The vaccine, which prevents certain types of cervical cancer, has seen poor adoption, particularly in developing countries. There, the planned series of three injections is a financial and logistical burden for those without easy access to health care. But a new analysis of the two efficacy trials sponsored by the National Cancer Institute and the maker of Cervarix, GlaxoSmithKline, suggests that even one dose confers roughly the same protection against the virus after 4 years as two or three doses do. Women in the trial who missed two doses of Cervarix followed saw even a protection rate of 85.7% against HPV types 16 and 18, strains that account for 70% of cervical cancers and for which Cervarix has been designed. But three doses were more effective than one or two to prevent several types of HPV-31 carcinogens less common, 33 and 45. Two doses separated by at least 6 months apart appeared to have the same effect as three. In a commentary that ran today in the paper The Lancet , Julia Brotherton of the national immunization against HPV registry Australia to Melbourne-who was not involved in the work program that the finding "opens a great opportunity to expand the scope of protection ... to more people than we ever thought possible."
If you had a vaccine against the flu or fall last winter, you learned the hard way that the vaccine does has not worked as well as usual. Now researchers think they know why :. A mutation that allowed some influenza viruses to beat the vaccine
When we get a vaccine against the flu, our immune cells crank out antibodies that recognize and bind to a known viral protein as the hemagglutinin, which deactivates the virus. However, influenza viruses continually evolve new versions of hemagglutinin that the antibodies do not recognize. This means that the protection provided by the firing of a year generally does not next year, and manufacturers regularly to improve their formulations.
To determine the composition of the vaccine each year, scientists with the World Health Organization (WHO) study the virus strains that are on the loose, and then try to predict which ones will do people sick when the flu season hits. Although patients do not start to get the shots to fall, WHO must deliver its recommendations in February (or September for the southern hemisphere) to allow time for the preparation and delivery of vaccine. "It is very difficult to predict what [viral strains] will be circulated next season," said viral immunologist Scott Hensley of the Wistar Institute in Philadelphia, Pennsylvania. "It is a bit of a guessing game."
last year, WHO has missed the mark :. the vaccine only provides protection of 19%, against less than 60% in other years
Researchers know that some of the problems were. a vaccine against influenza contains a mixture of virus strains, and from 2014 to 2015 shots included a strain of H3N2 influenza virus first isolated in Texas in 2012. WHO scientists think the Texas strain would prevail during the winter, but instead of three other varieties H3N2 jumped. Although the researchers found several mutations of haemagglutinin modifying these H3N2 viruses renegades, they did not know which allowed the virus to evade the vaccine.
to find out, Hensley and his colleagues created a laboratory version of the Texas strain as a comparison standard. The team then developed several varieties of the virus, each of which performs one of the candidates mutations in the haemagglutinin. Next, the researchers mixed the virus in the blood of sheep and ferrets that had recovered from infection with the strain control Texas. This test is a common way to determine how closely the antibodies bind to the virus, an indicator of the amount of protection they offer against infection.
As expected Hensley and colleagues, antibodies in blood samples reacted strongly to the Texas virus control. But as the researchers conclude online today cell reports , the antibodies were a poor match for several viruses that harbored mutations. The transformation with the most powerful effect, known as the F159S name, switch the identity of a single amino acid on top of hemagglutinin.
The scientists saw a similar picture when they tested blood samples from people who had been immunized with the vaccine of 2014 to 2015. The antibodies in the blood switched on the standard virus Texas, but modified virus carrying the mutation F159S triggered a much smaller effect. "They were able to escape or avoid human antibody responses," said Hensley, suggesting that this mutation is largely responsible for the poor performance of last year's vaccine.
For the vaccine this year, the WHO recommended that manufacturers replace the Texas strain with a catch in 2013 in Switzerland. It contains several mutations the researchers tested as F159S. Hensley and colleagues found that sheep antibodies which had recovered from an episode with the Swiss strain reacted strongly to all with mutation of viruses, including those with the mutation F159S.
"This is a solid piece of work," says immunologist Alain Townsend of the University of Oxford in the UK. But this is not the last word on which mutations allowed the virus escape the vaccine, he said. "There are many more [research] can be done with multiple mutations."
In the meantime, the production of this year's vaccine containing the Swiss strain is already underway, and patients should be in line to receive their shots in a few months. Said Gillian Air, a virologist at the University of Oklahoma College of Medicine in Oklahoma City: "We hope the results of this year will be better."
Dozens human enzymes incorporate or use copper, taking advantage of the willingness of metal to give or accept electrons to catalyze chemical reactions bio keys. Tumors can however be particularly dependent on the metal. Copper, for example, promotes angiogenesis, the growth of blood vessels that can feed a growing tumor, and the exhaust can keep the cancer in check. Copper also binds an enzyme which allows tumor cells metastasize and is required for signaling by BRAF mutant, which causes half of melanomas and many other cancers. "Maybe what we'll find is that the particular types of cancer are more susceptible to particular processes copper-dependent," says pharmacologist Donita Brady of Duke University in Durham, North Carolina
One might think that the first vaccine candidate to protect against malaria as cause of jubilation. But instead, the data on the candidate, known as RTS, S or Mosquirix have dribbled over the past two years, he was greeted with considerable-scratching head and some consternation about whether and how use.
The problem is that the vaccine developed by pharmaceutical giant GlaxoSmithKline (GSK), in partnership with the PATH Malaria Vaccine Initiative, does not work very well. In a large phase III trial, it reduced malaria episodes by about one third among young children in sub-Saharan Africa. That's well below the 50% efficiency expected at the beginning of the trial, and a far cry from the 95% efficiency of the dream vaccine manufacturers, leaving scientists and policy makers asking: What is good enough
part of the answer came today, as the European medicines Agency (EMA) has approved the use of the vaccine in African children aged 6 weeks to 17 month. The movement is a key first step on the way potentially complicated the deployment of the vaccine in sub-Saharan Africa. According to the fastest scenario, however, the introduction will not begin until 2017.
"We are very pleased with the outcome, said Moncef Slaoui, GSK vaccine president who for 30 recent years has been working alongside Joe Cohen and others to develop the vaccine. "the health of children in Africa will be transformed," he predicted.
But ask a malaria expert on what to do with RTS, S and they will tell you "it's complicated" There is no doubt that the vaccine candidate is a great achievement. Nobody never developed a vaccine against a parasite, especially one as cunning as Plasmodium falciparum , the main cause of malaria in Africa. And malaria is a huge problem, claiming nearly 0,000 lives a year , mostly children in sub-Saharan Africa. new tools to reduce the number of victims of malaria are desperately needed.
at the same time, everyone, including scientists at GSK wants some something better from a vaccine. at the end of the multicellular RTS, S trial, which involved all 16,000 children in eight African countries, the vaccine reduced malaria cases by 39% in young children 5 to 17 months and 27% for infants 6 to 12 weeks. Because vaccine efficacy decreases with time, trial tested three doses delivered 1 month apart, followed by a booster 18 months later.
"positive scientific opinion," The EMA as it is clumsily called, essentially concludes that the benefits outweigh the risks of using the vaccine in two age groups. The opinion is not a recommendation for use or formal approval is for countries to decide, but it opens the way to the World Health Organization (WHO) to make an overall recommendation on whether and how to use the vaccine. WHO should issue this recommendation by the end of the year.
The EMA review is part of an arcane regulatory process known as Article 58. As a service to poor countries that might not have the scientific expertise, the Committee of agency of human medicines reviewed the evidence in this case scientific hundreds of thousands of pages-with the same rigor as it would be in the review of a drug to be marketed in the European Union.
Then, in his review, WHO will address issues such as the real world cost-effectiveness, feasibility and public health value of the vaccine compared with other interventions. The result could go many ways. For example, WHO might recommend the use of the vaccine in all African countries affected by malaria only in areas where transmission is high. It could only recommend its use in toddlers whose effectiveness was higher, or in infants as well.
A second WHO committee decide whether the vaccine meets international standards of quality and safety and efficiency.
As with the EMA, the WHO recommendations are not binding, but poor countries the resources usually follow. And donors like GAVI Alliance vaccine, will not pay for the vaccine in poor countries without this recommendation.
Ultimately, it is up to regulators in each country to decide whether to approve RTS, S. Assuming that the WHO recommends the use of the vaccine, it will be a "difficult decision "for countries with limited resources, says Mary Hamel, an epidemiologist with the US centers for disease control and prevention and one of the principal investigators. David Kaslow, vice president of product development for PATH, agrees. "It is a bit unusual since the vaccine was introduced in the context of other interventions that also have costs associated with them," he said.
If the vaccine is not moving forward, scientists and policy makers agree it should be used only as a complement to other tools in the fight against malaria, such as bed nets and antimalarial drugs, not as a replacement. vaccine funding should not divert more effective interventions and research resources, WHO said today in a statement.
the opinion of the EMA is sure to fuel a debate over whether is preferable to wait a near-perfect vaccine against malaria or do better with what you have. in a comment to the BBC, the head GAVI Seth Berkley and Mark Dybul, head of the global Fund to explore the dilemma. "Mosquirix is about 5 to 10 years ahead of all other vaccine candidates," they write, "and there is no guarantee any of them will be better. "
" With every vaccine, of course you hope for 100% protection, "said Slaoui, GSK and is already working on a second-generation vaccine. But he called the current vaccine protection "substantial". "If your child has three severe malaria a year instead of six, it will change their lives."
Each fall, millions of people roll up their sleeves for a vaccine against the flu, hoping to give their immune system a leg on influenza. But flu viruses are thousands of strains that mutate and evolve with the seasons, and the vaccine can not protect against all. Now, two groups of researchers have independently created vaccines that provide the basis for a long-sought shot that could protect against all types of flu.
"This is really cutting-edge technology," said Antonio Lanzavecchia, an immunologist at the Federal Technology Institute in Zurich Switzerland, which is affiliated to two studies. "There is still work to do, but this is a step forward and it is heading in the right direction. "
scientists are developing vaccines against influenza by predicting the most likely strains infecting a population. They use monitoring flu the year as well as field reports from the countries of the southern hemisphere to guess which strains are most likely to hit North America at the height of the flu season, December to March. But viral conjecture is a tricky business, and it is impossible to be 100%. This uncertainty makes the uneven protection, and that flu strains mutate during the season, vaccines are becoming less and less effective.
influenza vaccines stimulate the production of antibodies against pieces of dead virus. If the return of the virus, antibodies can recognize, attack and neutralize the threat. But because these vaccines are based on parts of the virus that evolve during a flu season, the protection is not guaranteed.
To solve this problem, two research teams independently focused on a protein called hemagglutinin, found on the surface of the H1N1 influenza virus. It has two main components: the head of the part of the virus that mutates and changes of the strain to strain and the rod, which is similar in most strains of influenza. The teams tried to remove the variable region of the head and hold the rod as a basis for vaccines. But hemagglutinin appears to be quite low. Once decapitated, the rod falls apart, and antibodies can not bind to it.
To anchor the stem headless, teams had different approaches. Researchers writing today Nature Medicine used a two-step method: They introduced a combination of mutations to stabilize the core of the hemagglutinin stem. Then they delimit a nanoparticle derived bacteria of the rod, which has reached the subunits of the protein as well as to hold it in the correct position. The other team, wrote today in Science applied a combination of mutations that realigned the subunits of the stem at the top. This was enough to sustain a functional structure for the vaccine.
When vaccinated mice teams, both groups saw a complete protection against the H5N1 virus, a deadly flu strain distantly related H1N1. In both studies, mice that did not receive the vaccine strains derived died, but the vaccinated mice all survived. In other experiments, anchoring the nanoparticle vaccine have shown partial protection in ferrets, while the other vaccine showed partial protection in monkeys. Two of six ferrets vaccinated became ill and died, compared to a death rate of 100% for unvaccinated ferrets. None of the monkeys died, but those who were vaccinated were significantly lower than their unvaccinated mates fevers.
"The [experimental] designs were different, but the end results were very similar and highly complementary," said Ian Wilson, co-author on the science paper and a structural biologist and computer at the Scripps research Institute in San Diego, Calif. "it is a promising first step, and it is very exciting to see this research to fruition." The authors of both studies say the next step is expanding the protection to other flu strains, namely H3 and H7.
a new study that supercharges influenza viruses used to make vaccines a moratorium questions the US government on such research. Yoshihiro Kawaoka, a virologist at the University of Wisconsin, Madison, who is at the center of a long-standing controversy about the research called "gain of function", conducted experiments that were completed before the moratorium began in October 2014. Kawaoka supports the work emphasizes that the ban, which includes both a "financing pause" and demand that investigators voluntarily suspend work related casts too broad and hinders the search for low-risk who may benefit from public health. in this study, Kawaoka's team showed how to streamline the production of vaccines against influenza, which could be critical during a pandemic and also help seasonal vaccine manufacturers. Basically, the flu virus used to make vaccines have a backbone of six genes that remain the same each year and support two surface proteins of genes that are constantly changing. Kawaoka and his colleagues designed a skeleton that produces higher yields of surface proteins in both cell culture systems and eggs of mammals. The US government is currently reviewing research and gain of function plans to keep the moratorium in place at least until spring 06.
Is an ancient virus responsible for some cases of Lou Gehrig’s disease? -
A virus that had long been spliced into the human genome may play a role in amyotrophic lateral sclerosis (ALS) the deadly muscular degenerative disease that paralyzed baseball great Lou Gehrig, and eventually took his life. This is the controversial conclusion of a new study, which found levels of human endogenous retrovirus K (HERV-K) higher in the brains of 11 people who died of the disease.
"This is certainly an interesting and provocative work," said Raymond Roos, a neurologist at the University of Chicago in Illinois who treats and studies of ALS, but has not participated in the conclusion . yet even scientists behind the work caution that more research is needed to confirm the link. "I'm very careful to say HERV-K does not cause the disease but can play a role in the pathophysiology," says study leader AVINDRA Nath, a neuroimmunologist the National Institute of neurological disorders and Stroke in Bethesda, Maryland. "The thing is damn in the chromosomes to start. It will be very difficult to prove causation."
There was another retrovirus, HIV, which led to the first Nath suspect a link between the virus and ALS. In 06, it was to help a patient to control his HIV infection with antiretroviral drugs when he noticed that the SLA of man has also improved. "It intrigued me, and I looked in the literature of ALS and saw that people had reported they could see reverse transcriptase in blood." reverse transcriptase, an enzyme that converts RNA to DNA is a hallmark of retroviruses, which use to insert copies of their genes into the chromosomes of their host.
No study had ever found a convincing retrovirus in patients with ALS. But the researchers only looked at viruses that came from outside the body. About 8% of the human genome consists of endogenous retroviruses "" such as HERV-K, which are likely the remains of old viruses. These retrovirus initially infected an egg cell or human sperm and entrenched themselves in the chromosomes, which allows them to spread from one generation to another. The finally deactivated DNA mutations retroviral incorporated.
In 2011, Nath and colleagues reported they had found increased levels of expression for HERV-K gene in the brains of autopsied people who died of ALS . Their new study, published online today in Science Translational Medicine , is based on previous work with analyzes of more brains and evidence supporting tube experiments and mouse test.
In about 10% of people with ALS, someone else in the family has the disease, suggesting that it comes from an aberrant gene inherited. Nath and colleagues focused instead on what is known as sporadic ALS: where people have no family history of the disease. Strengthen their 2011 study, the team found high levels of three different HERV-K genes in the brain autopsied ALS. Researchers are not isolate the virus itself, which notes Nath is logistically difficult because it would have to analyze the brains "fresh" soon after death.
Researchers have also shown in test tube experiments that the addition HERV-K genes to neuronal cultures led to a significant decrease of the cells. Using as the electroporation technique known to insert a HERV-K gene in the brains of embryonic mice, the researchers showed neuronal lesions similar. The researchers then developed mice that express HERV-K gene in all neurons. Again, the gene leads to neural mayhem, and the animals had similar muscle problems to what is observed in patients with ALS.
retrovirologists Some warn that the evidence remains thin that endogenous virus causes ALS. John Coffin who studies HERV-K at Tufts University in Boston, notes that high expression levels of genes of this retrovirus found in many conditions, including breast cancer, multiple sclerosis, schizophrenia, and melanoma, but none has been conclusively shown to be caused by it. "There are many documents like this," said Coffin. "The upregulation of the endogenous virus group is a very common finding."
Coffin said "group" because there are about 0 different HERV-K, and that's another concern that has labor laboratory Nath: the study does not show that all ALS patients have exactly the same version of the virus in their brains "I. am quite prepared to accept that there is toxicity, but I'm never quite sure what to do these kinds of experiences, "said Coffin. He notes that in the 1970s and 1980s, so many researchers wrongly asserted that exogenous human viruses-those who move between people or tumors commonly, humans and animals caused that they became known as "virus rumor." "There is a good amount of buzz around virology endogenous retroviruses responsible for the disease."
Even Nath stressed that he wants other labs to confirm the findings of his team. "I work with HIV for many years, and I am aware of the pitfalls, and that's why we wanted to ensure that we were very, very careful before we stuck our necks out," said Nath. "It took us 10 years to produce this document."
Nath is launching a clinical study to evaluate the impact of treatment of ALS patients who have high levels of HERV-K genes expressed in blood with a combination four antiretroviral drugs used to treat HIV infection. The Phase I study will mainly determine if treatment for 24 weeks can lower gene expression to undetectable levels HERV-K, but Nath also monitor the progression of the disease. Whether the anti-HIV drugs will even have an impact on HERV-K does not know. Drugs targeting reverse transcriptase and protease enzymes, both viruses depend, but there are differences between the HERV-K versions and HIV.
Coffin, who warns that antiretroviral toxicities have said the trial is madness. "The reason for this is non-existent," he said. Nath counters that there are about 40 cases described in the literature of ALS patients taking antiretrovirals, but it is difficult to make sense of these reports, about half of the claimed improvements. "No one has ever made a systematic study," he said.
Again, Nath allows increased expression of HERV-K genes in ALS patients may simply be the result of something else that causes real damage. "The reasons for skepticism are very valid," Nath said. "We could be wrong too."
India has the largest number of blind children in the world, many of which are born with cataracts. A simple surgery early in life can reverse this condition. But in India, poverty and lack of access to health care shall record most children with congenital cataracts to a life in the dark. Prakash project was launched in 04 to provide cataract surgery in older children and young adults who were considered beyond help because they passed a critical age when the vision develops in the brain. The project has so far provided nearly 500 children and young adults in the light, and in the process revealed some surprising insights into how the brain learns to see. Read the full story here.
a controversial fertility company called OvaScience is concerned about a persistent mystery in human biology, why eggs fail and palpable hope we can do something about it. The company offers a new treatment, called BOOST, depending on what he considers egg precursor cells found in a woman's ovaries. INCREASE, which costs up to $ 25,000, as well as thousands more in clinic fees and about $ 25,000 for the in vitro fertilization cycle (IVF) to accompany him, based on mitochondrial precursor cells putative egg to stimulate the success of IVF. Seventeen babies were born to date. The company, which has attracted hundreds of millions of dollars from investors, is ready to introduce a second treatment. But many scientists are skeptical that the egg precursor cells actually exist.
outbreaks A little-known virus called Zika caused in the Pacific ocean islands in recent years and arrived in South America this year. Scientists predict that spread throughout the Western Hemisphere, and perhaps in southern Europe as well, because Aedes mosquitoes that transmit the virus are so prevalent. Scientifically speaking, the Zika virus is still largely terra incognita. Its symptoms, including rash, fatigue, headache, muscle aches and swollen and painful joints, seem to be generally mild, but during an outbreak in French Polynesia, which began in 2013, some patients developed an affection severe neurological called Guillain-Barre syndrome. While primarily spread by mosquitoes, some evidence suggests sexual transmission is possible both
Since November 29, not a single new case of Ebola was reported in Guinea, Sierra Leone or Liberia. If no new cases pop up, the world will be able to declare January 14 as 2 years Ebola epidemic has ended at the end, after more than 28,0 cases and 11,300 deaths.
The victory also mean the end of an unprecedented era in the search for Ebola. The tragedy provided a unique opportunity: Never had the disease affected enough people to allow researchers to test drugs and Ebola vaccines in a real context. As the number of cases exploded in mid-2014, they initiated a broad research program that runs at breakneck speed.
But the harvest of this massive effort is thin.
The greatest success to date is a vaccine produced by Merck. A July 31 report to The Lancet documented remarkable effectiveness in a real-world test in Guinea. But all other results have yet to appear in the scientific literature. And careful consideration of the data so far supported by dozens of interviews with leaders of the study and other experts Ebola clearly shows that almost every other trial seems destined to end questionable results or total failure . The results of those who have completed are proving difficult to publish in high-level journals.
The reasons are varied and complex. Even under the best circumstances, clinical trials may not provide satisfactory results. In this case, many studies have begun too late, when the epidemic was already down, and ran out of patients. Others had ideas which from the beginning were unlikely to provide a clear answer. A pharmaceutical company abandoned a trial for reasons he never specified, and the fate of another trial remains obscure, even to the World Health Organization.
"thin harvest", explains where the Ebola clinical trials in Guinea, Sierra Leone and Liberia stand today and what they are most likely to yield
brincidofovir :. A test purposes without explanation
TKM-Ebola: Negative results prove difficult to publish
favipiravir: A large study fails to give solid answers
Interferon: A test that few believed in
zmapp: the front-runner is fading
the blood of survivors A trial whose fate is not known
plasma Cloudy results filtered blood
vaccines: The only real success story so far
for more science news and research coverage of the Ebola epidemic to visit our collection "files Ebola." For more coverage, see the January 1 issue of Science.
Next
brincidofovir
a trial ends without an explanation
Brinfidofovir.jpg
Change
Chimerix, brincidofovir the manufacturer, does not become a superhero defeated Ebola, that this comic in 2014 suggested.
BIDNESSETC
On January 30, Chimerix Durham, North Carolina, has pulled the plug on a clinical trial of its experimental drug brincidofovir patients Ebola. The drug, which mimics a DNA building block is active against many viruses in test tube experiments and in human studies to treat cytomegalovirus and adenovirus. But the Ebola test began on 1 January by researchers working with Médecins Sans Frontières (MSF) in a clinic Ebola in Monrovia, was canceled after only four registered patients.
The announcement surprised even the scientists running the trial. "The press knew before me," says Stephen Kennedy, a Liberian investigator on the study's principal investigator Peter Horby of Oxford University in the UK said the reasons Chimerix not be told;. In a statement press the company has simply noted that the number of new cases in Liberia had "decreased significantly."
Horby said he doubts the decision was related to how the drug made in the first four patients. Instead, he believes Chimerix decided he did not want to continue bringing to market brincidofovir Ebola after discussions with the US Food and Drug Administration (FDA) has raised questions about the interpretation of studies animals. As chief scientist of the FDA, Luciana Borio in Silver Spring, Maryland, says she can not comment. "We have asked the company to disclose the facts surrounding the case and we could not." (FDA does not oversee the trial of Liberia itself.)
"Someone should call Chimerix and ask them," said Marie-Paule Kieny of the World Health Organization in Geneva Switzerland, who coordinated the international research effort on the Ebola virus. Science did this, but a spokesman for the company declined to comment.
Whatever motivation, "it was frustrating," said Horby. "We have invested a huge amount of resources, time, effort, in very difficult circumstances, such as MSF. it must not have been arrested at least it was for a very good reason. "With so few patients enrolled, the study results are" uninterpretable "said Horby, which nevertheless still hopes to publish a paper on the subject
Contents | . Next
TKM-Ebola
negative results prove difficult to publish
TEKMIRA.jpg
Change
Tekmira announced the end of the first trial in the world real TKM-Ebola with this press release vaguely worded.
Tekmira PHARMACEUTICALS CORPORATION
at the peak of the Ebola outbreak in September 2014, the World health Organization (WHO) gathered experts in Geneva, Switzerland, to discuss the myriad potential treatments and help identify the most promising. The group has given priority to interventions that have proven successful in monkeys experimentally infected with Ebola and a drug called TKM-Ebola ended at the front of the pack. Made by Tekmira Pharmaceuticals Corporation of Vancouver, Canada, TKM-Ebola interferes with RNA of the Ebola virus.
But the company has had precious few doses, and a formal clinical trial was slow to start. Some researchers also frowned upon because the study was launched March 11 in Sierra Leone, has not had a randomized controlled design. But Peter Horby, a respected researcher from the University of Oxford in the UK, led the study, and the Wellcome Trust funded. Hopes ran high that it would at least give an indication of whether the encouraging results monkey would be supported in humans.
On June 19, however, Tekmira ended suddenly the study, without fully explaining why. Horby said after testing the drug on 14 patients, the study had reached a predefined "border futility." This means entering other patients was "unlikely to show that the drug was significantly beneficial," he said.
The absence of a clear advantage was "disappointing," Horby said, but he noted that it is not unusual for drugs to work in monkeys and humans fail. A problem may have been that animals were treated early in their illness; most Ebola patients seek care very late, he said.
next disappointment came when Horby The New England Journal of Medicine ( NEJM ) rejected a paper describing the results. He speculates that scientific publications are losing interest in Ebola, and the fact that this study lacked a randomized design and clear results have worked against her as well.
"Newspapers have published large amounts of anecdotal evidence on one or two cases and hundreds and hundreds of opinion and comment pieces, but we struggled to publish final data information but no trial, "said Horby. Although he understands that negative studies are less exciting," you have to balance this against the enormous difficulty of these tests and the almost complete absence of any data on the effects of treatment. "
WHO Assistant Director-General Marie Paule Kieny shares her frustration." it is problematic because it is very important that these results are in the open, "she said. A spokesman NEJM says she can not comment because the journal publication process is confidential. Horby said the document is currently being studied in another paper
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favipiravir
A large study fails to give solid answers
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favipiravir, an approved drug against influenza in Japan, allegedly helped patients, but Ebola if they had low levels of virus when treatment began.
The largest study on the treatment done in the favipiravir tested Ebola epidemic, drug against influenza. The trial ended after the listing of more than 0 people, and its results could soon appear in a scientific journal. But the study may not give a clear answer to the key question: he works
favipiravir that inhibits viral enzyme called RNA polymerase critical and is developed by Fujifilm in Japan, has shown activity Ebola virus in test tubes and in mice. At the beginning of the epidemic, there was a big advantage over other drug candidates: He was generous and had proven safe when administered to healthy volunteers in Phase trials. Researchers at the National Institute of France for Health and Medical Research (INSERM) began a collaboration with researchers in Guinea, French-speaking countries, to test favipiravir four Ebola treatment units.
In February, the INSERM researchers presented what they said were encouraging preliminary results based on the first 69 patients. The drug appeared to save the lives of people who came to clinics with low levels of Ebola, they said. French President Francois Hollande welcomed the results in a press release and invited leading research Ebola at the Elysee Palace in Paris. Since then, all patients Ebola in Guinea were offered favipiravir.
Many researchers were less impressed. INSERM team has not used a randomized controlled trial (RCT) design, but gave all eligible patients of the drug; their results were compared to a group of Ebola patients who fell ill before the start of the trial. The problem is that the mortality greatly depends on the quality of care Ebola, which varies considerably over time and from one to another treatment facility. This makes such comparisons difficult. The drug also worked only in people without treatment have a much better chance of surviving Ebola because when they first sought care, they had relatively low levels of virus in their blood.
An RCT would have been impossible, says researcher INSERM Denis Malvy; it was unacceptable for the local population, already distrustful of the government and foreign workers Ebola. He said building research collaborations was hard enough without the added stress of asking local employees to refuse treatment to a control group. "It is easy to criticize a study," he said. "We decided to look for a signal, not a formal proof of efficacy."
But now, nobody is sure favipiravir should be used in the next Ebola outbreak. That's the bottom line, says Luciana Borio of the US Food and Drug Administration, and it shows that uncontrolled studies can cause more harm than good. "The result was that the nebula data area we were so scared about," said Borio. "We left not knowing if the product help, hurt, or does nothing."
The study design was also one of the reasons why the New England Journal of Medicine (NEJM) rejected an article on the results, said Malvy; instead of the newspaper offered him a letter of 300 words to the publisher, he said was laughable. (A NEJM spokesman declined to comment.) The study is now under review at PLOS Medicine Malvy said
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Interferon
A trial that few believed in
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Interferon
A trial that no one believed in
When Ebola spiral out of control in the summer of 2014, immunologist Eleanor Fish of the University of Toronto in Canada thought it was something that could save lives. Because
CBC
When Ebola spiral out of control in the summer of 2014, immunologist Eleanor Fish, University of Toronto in Canada thought it had some thing that could save lives. Since no treatment was available, Fish said it was logical to try interferon, a group of biochemicals with antiviral activity she had long studied.
Many scientists Ebola disagreed.
Fish sent the World Health Organization (WHO) study showing that interferon-α, delivered by an adenovirus and combined with a cocktail of antibodies, has an efficacy in monkeys infected with Ebola virus. But other researchers noted that has not been shown only interferons do anything. A panel requested by WHO to prioritize drugs for testing interferons considered "problematic". Side effects such as fever and muscle aches, which are similar to Ebola symptoms-could create problems in the Ebola treatment centers, the group said. "Basically, all interferons do not work," Peter Jahrling, a researcher Ebola veteran at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, told a WHO meeting, summarizing the evidence animal therapies for Ebola. "I do not know why you want to do a clinical trial with them."
given the lack of alternatives at the time, Fish pushed forward with a test of the interferon-β, including in vitro studies suggested was the most effective way to counteract the replication of the Ebola virus, she said. she teamed with Guinean epidemiologist Mandy Kader Konde set up a clinical trial in the Ebola treatment center in Coyah, about 2 hours northeast of the capital, Conakry. But it was not until March 2015 to write the protocol and get the study approved by Guinean regulators. D by then, the number of Ebola cases had fallen sharply. Because interferons may make things worse if taken at the end of the infection, the trial enrolled patients within 6 days after onset of symptoms, which still has limited enrollment.
Ultimately, only nine patients participated in the study. All received interferon-β; having a placebo arm was unacceptable in Guinea, Fish said, that patient outcomes were compared with those of 21 untreated patients, matched for age, who were seen in the same center in the same period. Given the study design and small size, "I do not think there will be something out of this," said Marie-Paule Kieny WHO.
But fish disagrees. "Statistical analyzes indicate that [interferon] offered a therapeutic advantage," she wrote in an email to Science . "We have a number of measures that we evaluated that support this." Fish declined to elaborate, but said the data will soon be submitted for publication
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zmapp
A front- fane runner
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Augustin Ngafuan, a official of Liberia, a few bottles of promising antibody cocktail zmapp from New York to Monrovia in August 2014.
JOHN MOORE / GETTY IMAGES
zmapp, cocktail three artificial Ebola antibodies, has been the darling of the world of research and the media since missionary Kent Brantly and Nancy Writebol received treatment in the summer of 2014. CNN has described as a "secret serum that probably saved" their lives . CNN reporter Sanjay Gupta, a medical doctor said one source describes how Brantly had a "sudden deterioration" in Liberia and "thought he was going to die," but after receiving zmapp, "within 20 minutes to an hour" it was "a nearly complete reversal of symptoms. "However, from individual cases for statistical data that the drug really works in people was difficult.
zmapp worked brilliantly in monkey experiments, even save the animals in advanced stages of infection. When the antibody cocktail was administered to animals up to 5 days after infection with Ebola virus, each of them survived, scientists reported in Nature in August 2014. veteran Ebola researcher Thomas Geisbert of the University of Texas Medical Branch in Galveston called the result a "monumental achievement." But zmapp made by Mapp biopharmaceutical in San Diego, California, was so rare that by the mid-February 2015, only nine people had received and some were dead, adding that whatever its potential, there were limits.
it took until 27 February for a formal trial randomized controlled zmapp to start in Liberia, conducted by the US National Institute of allergy and infectious diseases (NIAID). But by then, the epidemic in Liberia was practically over. the team expanded the study Sierra Leone and hit a collaboration with french researchers working in Guinea to recruit patients there. (One patient in the US has also been included in the trial.)
But time was not on the side of the study. To date, the trial has enrolled about 70 patients, said lead researcher Clifford Lane NIAID in Bethesda, Maryland. Complicating the study is that patients also receive favipiravir Guinea, based on a French study inconclusive in this country that suggested he was an anti-Ebola effect. The team will zmapp a subset of country analysis to see if the effects of the two drugs can be untangled.
What the forerunner of the past will be shown to work remains the big question. The study safety data independently and the Supervisory Board (DSMB) that looks at the results once a month or more. "They have not yet stopped the trial, so we know he must at least do something," said Marie-Paule Kieny of the World Health Organization, which is still hopeful that zmapp become second story clinical success of the Ebola outbreak, after Merck
vaccine. But Lane's safer. "it is very difficult to read between the lines of a DSMB recommendation," he said. However, "I am hopeful that, although the data do not reach statistical significance, there could be at least a tendency to effectiveness of humans who support animal data."
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the blood of survivors
A trial whose fate is not known
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ZOOM DOSSO IMAGES / AFP / GETTY
whole blood of Ebola survivors has been given to people with the disease as an experimental treatment. This tarpaulin hung outside of Liberia treatment center when closing
The people who survive an infection like Ebola have a powerful weapon in their blood. Antibodies that conquered the invading microbe. In principle, a surviving blood infusion could be a lifeline for people newly infected. But an initial study in Sierra Leone test this concept remained unpublished and nobody seems to know what happened with the data.
The World Health Organization (WHO) has pushed for therapies studies based on blood early in the Ebola epidemic as the most promising drug candidates were rare, while the number of survivors was growing. These studies can be performed with either whole blood or its plasma, which has removed the cells; it is much more difficult technically because it requires so-called plasmapheresis machine to separate the plasma and cells.
Gevao Sahr, a hematologist at the University of Sierra Leone in Freetown and consultant to the Ministry of Health of the country and sanitation, decided to try the simplest option from the start. A study of whole blood transfusion began in the fall of 2014 in the hospital 34 military in Freetown. But at the same time, an international consensus has emerged that the use of plasma was the way forward, and collaborations have been set up to ship plasmapheresis machines and West Africa to test this strategy in Ebola three affected countries.
The whole blood study in Sierra Leone seems to have ended at the end of 2014; Gevao became the principal investigator for the plasma study of the country, in collaboration with the University of Liverpool in the UK and other partners.
But data from the whole blood study were published. Some press reports have suggested that he was successful, and Wiltshire Johnson Pharmacy Board of Sierra Leone to oversee clinical trials in the country, said Science 33 patients out of 44 who received transfusion survived. These are much higher survival rates than were reported at the time to untreated Ebola. But scientists warn that it is unclear how patients were selected for the trial, or if their care differed in other ways that made them more likely to survive.
Gevao did not respond to emails from Science . Scientists working on plasma studies say they do not know what happened with the whole study of blood. Neither is WHO. "I have not yet seen the results," said WHO Assistant Director-General Marie-Paule Kieny. "We have to chase it, we need to know what happened"
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Plasma
Cloudy results filtered blood
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Ebola survivors of such man in Monrovia plasma donation made to determine whether the it contains antibodies might help patients with Ebola.
DANIEL Berehulak / GETTY IMAGES
the blood of Ebola survivors contains antibodies that could help sick people with the disease, but blood is a precious commodity: donors can not be bled frequently, and the product must be used within a few months. .
