Health Meaning

A bill to accelerate the discovery and development of new medical treatments was approved by a large majority in the House of Representatives of the States STATES today. The law, called Act 21st century Cures, has changed slightly from the version that won the unanimous support of the Energy and Commerce Committee of the House in May. And although it continues to enjoy the support of hundreds of industry, research and patient organizations, some scientists and advocates wonder if the effort to accelerate cures for patients could inadvertently compromise their safety.

The bill provides new funding for the National Institutes of Health (NIH) through a temporary "innovation fund" which would give the agency an additional $ 8.75 billion over 5 years; 500 million $ per year would finance specific projects in the 27 NIH institutes, including research on biomarkers and precision medicine remaining money would be to support young scientists. high risk, high reward research ; the intramural research;. and other areas the fund lost more than $ 1 billion from its previous authorization of $ 10 billion as sponsors struggle to pay for it in the midst of severe budget restrictions But lawmakers. Republicans have failed to adopt an amendment that would have made the discretionary-fund subject to the annual process of budget appropriations and therefore budget caps rather than mandatory.

project legislation also would authorize $ 550 million for the Food and Drug administration (FDA) and give the agency a host of new responsibilities. These include a new priority review process for some antibiotics, a process of accelerated approval for medical devices, and the creation of new guidance documents to counsel drug developers.

Several provisions are intended to smooth the way for approval of a large -priority treatments. It could allow the FDA to approve certain medical devices based on case studies and medical reports rather than data from larger clinical trials. In another, the agency could approve the drug to treat infections, threatening rare on the basis of smaller clinical trials. This could make the process easier for drug manufacturers who are struggling to recruit enough patients. "I think it's pretty broad understanding that this is necessary," says Amanda Jezek, vice president of public policy at the Infectious Diseases Society of America in Washington, DC "This would open the way for studies that were all just not able to do before. "

But some are concerned about the practical consequences of the fastest approval." For us, there are certainly concerns about ... the misperception that you might be able to speed innovation by lowering standards of safety and efficiency, and we think it would be a terrible mistake, "said former FDA Commissioner Margaret Hamburg at the National Press Club event just prior to resign in April.

in a perspective published in the New England Journal of Medicine last month, drug epidemiologist Jerry Avorn and expert in public health policy Aaron Harvard University Kesselheim landscaped concerns more detailed. they say that new provisions for appliances could lower safety standards, and they suggest that the accelerated antibiotics could pose a risk for patients who do not fit the limited pool of profile of patients on which they were tested. They also criticized a provision that would increase Medicare reimbursements to hospitals that use newer and more expensive antibiotics for serious infections. This move is intended to create an incentive for more profit for developers, but some argue that it could increase the use of hospital drugs and encourage greater bacterial resistance

Some policymakers apparently share this concern. An amendment adopted with the bill directs the Centers for Disease Control and Prevention study whether this incentive could actually contribute to the problem of resistance. The updated version of the bill will now go to the Senate, which has not yet issued its own bill on biomedical innovation.

The libido enhancement drug flibanserin (Addyi trade name) took the stage last week after winning approval awaited from the US Food and Drug Administration (FDA ). Coverage of defenders and unbelievers has run the gamut advisory, caution, and critical likely to confuse undecided but-curious spectators. But exactly how Addyi battery until libido is still cloudy.

The drug has a long backstory. It was originally designed in 1995 by Franco Borsini pharmacologist and a team of researchers from Boehringer Ingelheim Italia in Milan as an antidepressant because of its ability to regulate chemical signaling molecules neurotransmitters-brain. In particular, the team suspects that the regulated drug three key neurotransmitters that can affect mood: serotonin, dopamine and norepinephrine. One clinical trial found that it did little to relieve depression, but a seem to have an effect on mood. It was not just the mood of researchers were expecting. These initial tests point to the greater role of clinicians flibanserin in sexual health, as female subjects had higher scores on the Arizona Sexual Experience Scale, a survey that asked participants to rate their satisfaction on a variety of sexual health topics, such as how often participants felt sexual desire and intensity of that desire was.

a separate group of researchers, also at Boehringer Ingelheim, completed their first clinical trials to explore flibanserin as libido enhancer in 08. They measured the levels of desire through a day- based assessment in which subjects recorded their levels of sexual desire on a daily basis. But the FDA concluded twice the resulting increases in libido are not statistically significant, and regulators are wary of potentially dangerous side effects such as dizziness, drowsiness, nausea and fainting.

So what became red green light from the FDA? For one: the test parameters. clinical investigator on the latest tests Addyi Sheryl Kingsberg explains that the evaluation of sexual desire in the brain are not a clear measure in particular. As the three clinical trials have increased in about 8 years, so have the techniques to determine the desire, says Kingsberg, a reproductive biology and psychology researcher at University Hospitals Case Medical Center in Cleveland, Ohio, and consultant to Sprout Pharmaceuticals, which bought flibanserin Boehringer Ingelheim in 2011, and was in turn bought last week by Valeant Pharmaceuticals. The results of the last test, in 2014, focused on three parameters: sexual function index (where women responded to questions about the sexual experience and levels of sexual desire rated on a scale from one to five in the 28 days), satisfied sexual events, and distress felt from low libido. Overall, women have about a more positive sexual experience per month, and about 10% more of the patients who took Addyi reported significant improvements, according to a survey of these three categories, compared to a placebo group. By these measures, the FDA approved Addyi as the first drug for igniting desire.

Although it has been dubbed the "female Viagra," the two drugs work very differently, Viagra is designed to improve performance while Addyi aims to balance the chemicals in the brain that correlate with desire. Yet, researchers have only a rough idea of ​​what drugs on the brain. Stephen Stahl, a psychologist at the University of California, San Diego, and Boehinger Ingelheim researchers wanted to clarify how it works on . chemical level in a 2011 document the Journal of sexual Medicine which examines previous studies its mechanisms, as they explain: Serotonin, which is thought to impede sexual interest, two types of receptors in the brain. 5-HT1A acts as brakes for the production of serotonin, 5-HT2A and speeds up production. Flibanserin works improving 5-HT1A (put on the brakes) and inhibition (stop acceleration) 5-HT2A . In between, serotonin production is strongly downregulated. Furthermore, downregulation of flibanserin serotonin decreases the firing of certain neurons thought to regulate the release of other neurotransmitters, namely dopamine and norepinephrine (both thought to improve sexual interest). The exact mechanism of these transient changes in neurotransmitter levels, however, is still largely unknown.

Stahl said that these same mechanisms likely to cause side effects that potential users-flibanserin concern effect on serotonin receptor called 5-HT1A probably causes dizziness and nausea, and its effects on the other, 5-HT2A, are probably related to drowsiness. Clinical trials have also shown that the combination of alcohol and flibanserin exacerbates these effects. Tests after the drug is on the market (scheduled for October) will look more closely at how alcohol actually interacts with the drug. For now, the FDA warned users against a black box warning.

A new analysis may provide some comfort to those who fear that studies US of dangerous pathogens multiply without control. Federal officials say that more than 8 years, they rejected two-thirds of proposals for some 0 studies that fall into a category of studies considered so risky to public health they need a special examination. But a spectator, although praising the results, said the definition of small studies should be expanded to include controversial flu experiments not now covered by the rules.

The report, published online Sept. 8 in the journal safety , sums up examinations by an office in the Centers for Disease Control and Prevention (CDC) in Atlanta. This office, the CDC Division of Select Agents and Toxins (DSAT), oversees the use and handling of certain viruses, bacteria and toxins that appear on a government list of "select agents" that could be used as weapons organic. In 05, in the wake of / 11 post-9 anthrax attacks, the federal government began requiring DSAT examine two types of select agent research.

One category consists in a selection agent resistant to drugs or chemicals. Researchers sometimes intentionally create this resistance to select clones of bacteria that carry a desired trait. (Those not bearing the desired trait are killed by the treatment, remove them from the study population.)

The second "limited experience" category implies adding a gene for a toxin of the selection agent to a microbe. This is often done in order to allow the bacteria to produce large amounts of a toxin, such as botulinum, for experimental purposes.

Both kinds of experiences involve risks, analysts say. If a resistant bug escapes the lab, for example, doctors may not be able to easily handle a person who becomes infected. And engineering of bacteria to produce toxins could be a first step towards the production of a stock of bioweapons.

From 06 to 2013, DSAT has received 618 applications for approval of limited experiences of 109 governments, universities and private organizations. DSAT found that most of the proposed experiments do not meet the definition example for limited purposes, because the toxin was not powerful or because other antibiotics can control the drug-resistant strain.

Of the 91 studies that did meet the definition, officials refused to approve 60 the reasons for rejection included with the laboratory equipment and inadequate biosecurity procedures, and no other medicine existed to treat a selection agent that would be designed to resist existing treatments.

All 61 of the studies involved rejected the inclusion of traits in drug-resistant bugs. In about half the cases, the agents were Burkholderia mallei or Brucella abortus bacteria, which can cause disease in livestock and humans.

Do the results mean scientists are being too cautious and ask DSAT for approval when they should not? DSAT director and co-author of the study Robbin Weyant said that prevention is better than cure. "It is a matter of due diligence," he said. "We encourage regulated entities that research activities involving any kind of selection or cloning component to go ahead and send their protocols for us. We try to be very fast and provide quick turnaround. "

the DSAT program is" a small bright spot "in the monitoring of the pathogens to the risk of the government, said the molecular biologist Richard Ebright of the Waksman Institute of Microbiology at Rutgers University Piscataway, New Jersey, who has long argued that regulation of these experiments is too lax. But Ebright would like to see federal officials to expand the definition of limited experiences so it covers a controversial type of experiment in which a high risk bird flu, the respiratory syndrome Middle East, or SARS virus are refined to make them more likely to spread and cause disease in the man. The government stopped financing these studies "gain of function" there is one year and is currently conducting a complex, long months of examination of their risks.

At present, however, it seems that most experiences pause would not require a DSAT examination. (But federal officials recently proposed the addition of the H5N1 avian influenza, the target of the break of funding, to the list of selected agents, regulated by the CDC.)

One reason for expand the definition of CDC, Ebright said, is that the select agent rules have the force of law and apply to all laboratories, even without federal funding. The downside, he said, is that the inter-agency high-level committee that advises on DSAT these experiences working behind closed doors

Weyant said it for a reason "The process is opaque." public disclosure "sensitive information" might "open the security risks to the institution that sent [the proposed experiments] for us," he said.

it should also be noted in the safety paper is that the number of entities or organizations registered with DSAT fell 15% between 06 and 2013, from 336 to 284 . Ebright suspect, 'the megaburst "biodefense funding after 9/11, more than initially focused on site laboratories" that could be housed, "and some have now moved to other research. But he says the modest decline does not allay concerns that the large number of labs that do work raises risk of biodefense a dangerous pathogen could escape into the environment

* Fixed: October 5, 24:05: An earlier version of this story badly told that the H5N1 bird flu virus is not listed as selected agents H5N1 viruses are currently on the list of selected agents regulated by the Ministry. of Agriculture of the United States. However, H5N1 viruses are not on the Department of Health and Human Services list of some agents that are regulated by the CDC.

Men, your semen know how heavy you are. A new study reveals that sperm carry chemical tags on their DNA as their owner is skinny or obese. The results suggest that men may be able to provide information on the availability of food in their environment down to their offspring, which could affect the chances of being overweight for their child.

The new data are preliminary but provocative, says Wolf Reik, who studies epigenetics the Babraham Institute in Cambridge, UK, but was not involved in this work. It is the first time anyone has identified changes in these chemical tags called-epigenetic changes in sperm of obese men, he said. But the small number of subjects, he notes, and these studies are always complicated by genetic differences between subjects. It is also notoriously difficult to show exactly how epigenetic changes in sperm or eggs affect the development.

The observations correspond with evidence from a number of studies that have shown that the body weight of parents has long-term effects on the offspring. Mothers who were pregnant during a famine in 1944 in the Netherlands, for example, were more likely to have children and grandchildren-prone to heart disease, diabetes and obesity. Female mice that are malnourished during pregnancy and give birth to puppies that are more likely to develop diabetes and their male offspring have epigenetic changes in sperm. The offspring of these men are also prone to diabetes. Male rats are overfed, when mated with healthy females also had descendants who were prone to developing diabetes. Connections sense of evolution, because it could be an advantage to report the next generation if food is abundant or scarce.

Romain Barres, who studies the genetics of metabolism at the University of Copenhagen, wanted to see if this was evidence of epigenetic changes in human sperm. He and his colleagues collected semen samples from 13 men who were "lean", with a median body mass index (BMI) of 23 and 10 men who were obese, with a median BMI of 32. (A man who is 180 cm and weighs 75 kg has a BMI of 23. Someone of the same height with a BMI of 32 weighs 104 kilograms-229 pounds.) They then examined various epigenetic markers in sperm.

The reasons of a type of molecule that influences epigenetic inheritance, called Small Non-coding RNA, differed between the two groups, such as methylation patterns in sperm DNA in both groups, reports the team today in the Cell Metabolism . Gene methylation, also called imprinting, to determine whether a gene is activated or deactivated. The researchers found more than 9,000 genes that were more or less likely to be methylated according to the subject was thin or obese. Most genes were linked to the development of the brain control of appetite and metabolism.

Changes in genes related to the development and functioning of the brain are particularly intriguing, said Barres. "Brain function is a very important variable in terms of obesity." He also noted that other studies have shown that obese men have a higher risk of having children with disorders of the spectrum of autism. the methylation differences between thin and obese groups were consistent with those found in a recent study of methylation changes in the sperm of fathers who had more than one child with an autism spectrum disorder.

to see if losing weight would affect sperm epigenetic markers, the researchers collected semen samples from six men who were about to undergo surgery for gastric bypass surgery. They then collected samples of a week after the surgery, and a year later. They found differences in DNA methylation genes in 1509 just a week after surgery, suggesting that epigenetic changes can occur quickly. "This means that it is very dynamic," said Barres. A year later, when the weight of men was stabilized, the team found changes in genes 3910. Approximately 40% of these genes were also found to be modified in the study comparing obese and thin men.

Gilean McVean, who studies statistical genetics at the University of Oxford University in the UK, said much stronger data is necessary to argue that nutritional signals are transmitted by epigenetics. obese men were lean and very probably different epigenetic patterns in all tissues throughout the body, he said, including semen. "What differences in sperm have functional consequences for children, "he wrote in an email," is an entirely different matter "

Fixed, December 3, 3:37 p.m.. history has been updated to correct the name of the journal publishing the document. It is Cell Metabolism not Molecular Cell .

A Science function this week described the ongoing concerted efforts to develop more aggressively many vaccines that are found sitting in freezers because of a lack of laboratory market. Below an expanded array of vaccines specialists survey mentioned in the function.

(Click on the picture to enlarge.)

Ticks that transmit Lyme disease, a debilitating disease caused by influenza like Borrelia bacteria spread quickly across the United States. A new study shows how quickly. Over the past 20 years the two species known to spread the disease to humans were so advanced in half of all US counties.

Lyme disease cases have tripled in the US over the past two decades, making the vector-borne disease most frequently reported in the northern hemisphere. The disease now affects about 300,000 Americans each year. If the early diagnosis of a rash usually appears around the site of the tick bite, Lyme can be treated effectively with antibiotics, but the long-term infections may produce more severe symptoms, including stiffness of joints, the inflammation of the brain, and nerve pain.

For a comprehensive map of where the two black-legged tick species ( Ixodes scapularis ) and the western black-legged tick ( I pacificus .) - lived, Rebecca Eisen and colleagues from the Centers for Disease Control and Prevention (CDC) in Fort Collins, Colorado, combined data from published articles with state monitoring data and ticks County dating back to 1996. they counted tick sighting reports in each of the 3110 continental US counties to determine if these counties have welcomed an established population or only a few individuals. Ticks were considered "established" when observations of at least six ticks or two of the three stages of life, have been reported in one year.

Their findings, published in the Journal of Medical Entomology , show that the black-legged tick has undergone a population explosion, doubling its range established in less than 2 decades. It is now reported in 45.7% of US counties, up from 30% in 1998. The black-legged ticks are found in 37 states across the eastern United States. Western tick rare black legs, limited to just six states showed modest increases of established populations, from 3.4% to 3.6% of the counties. Together, these two vectors of Lyme disease are now found in half of all US counties.

"Since the late 190s, the number of counties in the northeast of the United States who are considered at high risk of Lyme disease have increased over 320%," says Eisen. "The tick is now established in areas where he was not there 20 years ago," she added.

Perhaps the most worrying northeast of tic-dense is where Lyme disease is most common. Although the tick black-legged is found from Florida to Minnesota, 95% of confirmed cases come from only 14 states in the northeast and upper Midwest. "Although our map shows a wide distribution ... the risk of people getting the disease Lyme are not equal in the country, "says Eisen.

a study published in PLOS ONE last year could hold the answer. Isis Parasitologist Arsnoe of Michigan State University East Lansing and colleagues found that populations of black-legged ticks behave differently in the northern and southern United States. tick nymphs black-legged in the north are bolder and more active in the search for hosts a behavior known quests. Arsnoe and his team found that tick nymphs from Wisconsin and Rhode Island were 20 times more likely to get out of the leaf litter, putting them in the path of passing humans, the nymphs of Tennessee and Florida. "Behaviour Questing is a key factor that affects the risk of tick bites," says Arsnoe. "Ticks that remain buried in the leaves are not likely to have the opportunity to bite the man pass and unless they bite, they can not transmit the disease." Arsnoe is concerned that the ticks found in the north may also develop in the southern states, taking their quest behavior with them.

But despite the wide distribution of vectors, the chances of a tick to come into contact with humans are still relatively low. Avoid thick vegetation zones, using a strong repellent and bath after hiking are usually enough to avoid contact, CDC said. Eisen said the most important thing now is to carefully monitor the spread of the black-legged tick, so that people can learn about potential vectors of diseases in their area and take steps to protect

An experimental technique of assisted reproduction that could allow some families to avoid having children with certain types of diseases hereditary should be allowed to go ahead in the United States, provided it takes place slowly and carefully. This is the conclusion of a report released today from a panel organized by the US National Academies of Sciences, Engineering and Medicine (NAS), which assesses the ethical issues surrounding the controversial replacement therapy technique called mitochondrial DNA. (Part of the panel also summarizes the deliberations in a Policy Forum in Science .)

More controversially, however, the committee recommended that only modified male embryos should be used to attempt pregnancy, limit the possible risks for future generations. (Men can not pass along the mitochondrial DNA that is modified in the procedure.)

Mitochondria are organelles that provide energy to cells. They carry their own DNA, which encodes 37 genes, which is passed from mother to child through the mitochondria in the cytoplasm of the egg. (Sperm have mitochondria, but they are thought to deteriorate soon after fertilization.) Mutations in mitochondrial genes cause a series of problems, life-threatening some sweet and others. They tend to affect the tissues and organs that need a lot of energy, including the brain, eyes and muscles. Often the disease is progressive, and there are few available treatments.

Scientists have developed ways of transferring the genetic material of an egg with faulty mitochondria into a healthy egg, either before or just after fertilization. These techniques, known as replacement therapy for mitochondrial DNA (MRT), could theoretically allow women who are carriers of mitochondrial disease to have genetically related children. (Current options include adopting or using an egg donor.)

The embryo resulting from MRT door of three DNA: the current torque of nuclear DNA processing and mitochondrial DNA from the donor egg healthy. The prospect of these "embryos from three parents" and that any offspring pass their mitochondrial genes to their own children, made the controversial technique. So the US Food and Drug Administration (FDA) requested the review as part of its deliberations on whether to allow researchers to the United States to use the technique.

the potential benefits of MRT outweigh the problems, the NAS committee said, provided that work is progressing slowly. This means that women who are considered very likely to pass severe forms of mitochondrial disease should be candidates for early clinical trials.

In addition, to avoid the possibility that babies born by unforeseen problems MRT pass along to their own children, the Committee also recommended that only male embryos be used to start a pregnancy.

"This is the first time that this will happen in humans. We do not know how it will work," says Jeffrey Kahn, a bioethicist at the Berman Bioethics Institute at Johns Hopkins University in Baltimore , Maryland, who chaired the panel. "We thought it prudent to make sure it will not affect the individual for future generations and not born."

This restriction would add an additional burden couples interested in MRT, said Sarah Norcross, director of the state education Trust in London, an advocacy group that focuses on issues of infertility and surrounding genetic diseases. male embryos could not be healthy embryos that result from the already complicated process, she said, and in some cases it could mean that women would have to undergo collecting additional eggs procedures.

Kahn notes the recommendation is temporary, however. After early research shows that the technique can be safe, in addition to animal data are available on possible effects in future generations, regulators could consider loosening the restriction.

think long term

The Committee strongly recommends that all studies be designed so that the results of several studies may be combined to learn as much as possible on technical security. They also recommend that all children born by MRT be followed by researchers in the long term, so that the physical or even psychological effects could be better understood. This requires parental permission at first, but later require permission from the children themselves once they are old enough. This is a challenge, says Kahn. "You can not give consent for those who have not yet been designed."

The group also encourages the FDA to carefully consider how they can prevent other uses of technology. Some researchers have proposed using MRT to treat infertility related to age, for example, but that is not morally justified, the committee said.

This is a potential problem, said Marcy Darnovsky, executive director of the Center for Genetics and Society and advocacy group in Berkeley, California, who opposed the approval of MRT. "It is important to realize that if the FDA were to approve these techniques, it would have few mechanisms to prevent what would essentially" off-label uses, "says Darnovsky in a statement. "An American promoter of these techniques has already made clear publicly he would like to expand their use largely to fertility clinics. Their use could easily spiral out of control. "

After years of scientific and ethical debate, the UK passed a law last year that would allow fertility clinics here to provide technical, but in each case if and closely supervised by the human fertilization and embryology countries (HFEA), which regulates assisted reproduction and embryo research. No clinical has not received approval to use the technical there.

the United States has no equivalent to HFEA, but the FDA said that all those who want to use the technique must apply to the agency for approval because that MRT is a form of gene therapy. in 2014, he began a process to evaluate the scientific and ethical issues surrounding the technology. the NAS report will help the FDA decision form of regulations and guidelines for such applications.

But do not expect such experiments to proceed rapidly in the United States. Federal legislation passed in December limits the ability of the agency to grant permission to all mitochondrial replacement therapy efforts for the year 2016. Due to the legislation, a spokesman for the FDA noted in a email, "the agency does not receive or INDs [Investigational New Drug applications] examination to the research about humans using genetic modification of embryos to prevent transmission of mitochondrial disease during the 2016 financial year and research the human subject using these technologies can be conducted in compliance with the Federal Food, Drug and Cosmetic Act and FDA implementing regulations. "

* Update, February 4, 5:55 p.m.: This article has been updated to include comments from the FDA and the link to science political forum. "