Coming soon: Male contraceptive pill inches closer

Researchers are one step closer to developing a male contraceptive pill, a medical conference has heard. Early trials show the pill to be both safe and effective.

The study, led by Professor Stephanie Page of the University of Washington, included 100 men aged between 18 and 50. The men were split into groups of between 17-20 and given three different doses of pills known as dimethandrolone undecanoate, or DMAU. Out of each group, five subjects were given a placebo while another 12-15 were given daily doses of DMAU for 28 days. Some 83 men completed the study.

READ MORE: ‘One size does not fit all’: Chinese condoms are too small for Zimbabweans, says health minister

The highest dose, 400mg of DMAU, showed “marked suppression” of testosterone levels as well as two other hormones required for the production of sperm. The results were compared to longer-term studies and appeared consistent with effective male contraception.

@RTUKnews Teach kids how to get pregnant, UK doctors say

"DMAU is a major step forward in the development of a once-daily 'male pill,'" Page reportedly told the Endocrine Society’s 100th annual meeting in Chicago. "Many men say they would prefer a daily pill as a reversible contraceptive, rather than long-acting injections or topical gels, which are also in development."

Page also said that few participants in the study reported having symptoms consistent with testosterone deficiency, although all groups reported weight gain and decreases in healthy cholesterol. "These promising results are unprecedented in the development of a prototype male pill," Page said. "Longer term studies are currently underway to confirm that DMAU taken every day blocks sperm production."

@RT_com Condom-free male contraceptive successfully trialed on monkeys - next stop, human testing

Various male contraceptives have been trialed in the past. In February last year, a gel injection used to block the sperm-carrying tubes, known as vas deferens, was trialed on monkeys. The Vasalgel injection, made by the Parsemus Foundation, has gone forward for human trials.

Brain is less flexible than we thought when learning

Nobody really knows how the activity in your brain reorganizes as you learn new tasks, but new research reveals that the brain has various mechanisms and constraints by which it reorganizes its neural activity when learning over the course of a few hours. The new research finds that, when learning a new task, the brain is less flexible than previously thought.

The research, published today in Nature Neuroscience, examined the changes that take place in the brain when learning a new task. To truly see how neural activity changes during learning, we need to look bigger -- at populations of neurons, rather than one neuron at a time, which has been the standard approach to date.

The research team used a brain-computer interface (BCI), where subjects move a cursor on a computer screen by thought alone. As with learning to play a new sport, they found that subjects learned to control the cursor more accurately with practice. They then investigated how the activity in the brain changed during learning that enabled the improved performance. They found that, on a time scale of a few hours, the brain does not reconfigure its neural activity to maximize the speed and accuracy by which it moves the cursor.

"In this experimental paradigm, we're able to track all of the neurons that can lead to behavioral improvements and look at how they all change simultaneously," says Steve Chase, an associate professor of biomedical engineering at Carnegie Mellon and the Center for the Neural Basis of Cognition. "When we do that, what we see is a really constrained set of changes that happen, and it leads to this suboptimal improvement of performance. And so, that implies that there are limits that constrain how flexible your brain is, at least on these short time scales."

When we're learning a new task, we can't instantaneously learn it to proficiency, in part due to the way in which the neurons are wired up in the brain. Learning takes time, and there are mechanisms by which neurons can change the way they communicate with each other to enable learning -- some of which can be fast, and some of which can take longer. The team found that the brain operates under a more stringent set of constraints than originally thought, resulting in good learning on the short term, but nevertheless suboptimal performance in controlling the BCI cursor.

Imagine a tennis player whose friends have asked her to play squash. When she picks up the squash racket, it's lighter than the tennis racket she is used to, and it has a slightly different balance point. But since she's a good tennis player, this difference in rackets doesn't cause her to miss the ball completely. She adjusts quickly, but she hasn't immediately picked up the swing form of a squash player. To really become an expert, it will require a long period of training with the new equipment. However, her experienced squash-playing friends will quickly see that she is a tennis player, because until she's learned the proper technique, she'll be swinging the squash racket the same as she would a tennis racket.

"Just as it takes time to train a person to swing a squash racket like an expert, it takes time to train one's neurons to produce the ideal activity patterns," says Byron Yu, associate professor of biomedical engineering and electrical and computer engineering at Carnegie Mellon. "When faced with a new task, we're finding that the brain is constrained to take the neural activity patterns that it's capable of generating right now and use them as effectively as possible in this new task."

"When we learn, at first the brain tends to not produce new activity patterns, but to repurpose the activity patterns it already knows how to generate," says Aaron Batista, an associate professor in the Department of Bioengineering at the University of Pittsburgh. "Learning over the course of a few hours is suboptimal. When first learning something new, our brain doesn't seem to be able to change its activity in the best possible way to allow us to be proficient at new skills.."

Acquiring a skill is very difficult, and it takes a lot of time and a lot of practice. But when you're first starting to learn a new skill, your brain has to adjust quickly to the new task. The researchers found that the brain is constrained to take neural activity patterns it already knows and use them for the new task. By repurposing neuron patterns the brain is already capable of generating, the brain applies a "quick and dirty fix" to the new problem it's facing.

"None of us predicted this outcome," says Matthew Golub, a postdoctoral researcher in electrical and computer engineering at Carnegie Mellon. "Learning is far more limited on the scale of a few hours than any of us were expecting when we started this. We were all surprised that the brain wasn't able to choose the best strategy possible."

The research was done in collaboration with the Center for Neural Basis of Cognition, a cross-university research and educational program between Carnegie Mellon and the University of Pittsburgh that leverages each institution's strengths to investigate the cognitive and neural mechanisms that give rise to biological intelligence and behavior.

Air pollutants linked to abnormal fetal growth

The findings, published in the International Journal of Epidemiology, were based on data collected from more than 8,000 women in Lanzhou, China from 2010 to 2012.

The researchers said that, to their knowledge, it is the first study of its kind to be conducted in areas with very high .

"There is a lack of studies investigating the association between air and fetal overgrowth," said Yawei Zhang, M.D., associate professor at YSPH. "We analyzed data from Lanzhou Birth Cohort Study to investigate the hypothesis that exposure to high levels of PM10 during pregnancy increases the risk of abnormal fetal growth, including both undergrowth and overgrowth, to determine if and how expectant mothers could protect themselves from possible contributing pollutants."

In collaboration with researchers from the Gansu Provincial Maternity and Child Care Hospital, the Yale scientists collected the daily average concentration for PM10—a diverse class of air pollution with health implications—from the government monitoring stations in Lanzhou. Using ultrasound measures of four fetal growth parameters during pregnancy, the researchers examined the associations between PM10 exposure and risk of abnormal fetal growth.

The researchers consistently identified positive associations between higher levels of exposure to a mixture of pollutants from car fumes, industry emissions, or construction activities and fetal head circumference overgrowth, they said.

Pregnant women's home and work addresses were collected through in-person interviews, and researchers calculated daily PM10 concentrations by incorporating each participant's home and work addresses.

Zhang says the novel finding that high levels of PM10 are associated with risk of overgrowth should be confirmed by other studies in different populations, and that it is also important to identify the specific pollutants that are responsible for this association by investigating the components of PM10.

"Our results have important public health implications and call for future studies to explore the underlying mechanisms and postnatal consequences to the findings," says Zhang. "We are going to replicate the findings in another and will continue to identify individuals who are more susceptible to air pollution."

Women in the region may lower the risk of fetal overgrowth by choosing their inception time and reducing their outdoor activities during the days with high , said Zhang.

Pregnant women who came to the Gansu Provincial Maternity and Child Care Hospital for delivery in 2010-2012 and who were 18 years or older with gestation age of more than 20 weeks were eligible to participate in this study.

Is punishment as effective as we think?

Punishment might not be an effective means to get members of society to cooperate for the common good, according to a social dilemma experiment.

A game to study human behavior has shown punishment is an ineffective means for promoting cooperation among players. The result has implications for understanding how cooperation has evolved to have a formative role in human societies.

Human societies maintain their stability by forming cooperative partnerships. But, cooperation often comes at a cost. For example, a person taking time to raise the alarm in order to alert other members of a group to impending danger could be losing valuable time to save oneself. It is unclear why natural selection favors cooperativeness among individuals who are inherently selfish.

In theoretical studies, punishment is often seen as a means to coerce people into being more cooperative. To examine such theory, a team of international researchers led by Marko Jusup of Hokkaido University in Japan and Zhen Wang of Northwestern Polytechnical University in China has conducted a "social dilemma experiment." The team investigated if providing punishment as an option helps improve the overall level of cooperation in an unchanging network of individuals.

They used a version of the commonly employed "prisoner's dilemma" game. Two hundred and twenty-five students in China were organized into three trial groups and played 50 rounds each of the game.

In group one, every student played with two opponents which changed every round. The students could choose between "cooperate" or "defect," and points were given based on the combined choices made. If a student and the two opponents chose "defect," the student gained zero points. If they all chose "cooperate," the student gained four points. If only a student chose to defect while the other two chose to cooperate, the gain for the student was eight points.

The second group was similar to the first one in every aspect except that the people playing the game with each other remained the same for the duration of the 50 rounds, enabling them to learn each other's characteristics.

In the third group, players also remained the same. However, a new option, "punish," was introduced. Choosing punishment led to a small reduction in points for the punisher and a larger reduction of points for the punishees.

At the end of the game, overall points were counted and the students were given monetary compensation based on the number of points won.

The expectation is that, as individuals play more with the same opponents over several rounds, they see the benefit of cooperating in order to gain more points. Introducing punishment as an option is basically saying: if you don't cooperate with me, I'll punish you. In theory, it is expected that applying this option would lead to more cooperation.

The researchers found that players in the constantly changing groups cooperated much less (4%) than those in the static groups (38%), where they were able to establish which players were willing to cooperate and thus gain a larger average financial payoff for all involved.

Surprisingly, however, adding punishment as an option did not improve the level of cooperation (37%). The final financial payoffs in this trial group were also, on average, significantly less than those gained by players in the static group. Interestingly, less defection was seen in the punishment group when compared to the static group; some players replaced defection with punishment.

"While the implied message when punishing someone is 'I want you to be cooperative,' the immediate effect is more consistent with the message 'I want to hurt you,'" write the researchers in their study published in the journal Proceedings of the National Academy of Sciences.

Punishment seems to have an overall demoralizing effect, as individuals who get punished on multiple occasions may see a good chunk of their total payoff vanish in a short period of time, explain the researchers. This could lead players to lose interest in the game and play the remaining rounds with less of a rational strategy. The availability of punishment as an option also seems to reduce the incentive to choose cooperation over competition.

Why, then, is punishment so pervasive in human societies? "It could be that human brains are hardwired to derive pleasure from punishing competitors," says Jusup. "However, it is more likely that, in real life, a dominant side has the ability to punish without provoking retaliation," adds Wang.

Although the study provides valuable insights into how cooperation arises in human society, the team advises it would be unwise to extrapolate the implications of their study far beyond the experimental setting.

Could humans ever regenerate a heart? A new study suggests the answer is 'yes'

When Mark Martindale decided to trace the evolutionary origin of muscle cells, like the ones that form our hearts, he looked in an unlikely place: the genes of animals without hearts or muscles.

In a new study published in the journal Proceedings of the National Academy of Sciences, the University of Florida scientist and colleagues found genes known to form hearts cells in humans and other animals in the gut of a muscle-less and heartless sea anemone. But the sea anemone isn't just any sea creature. It has superpower-like abilities: Cut it into many pieces and each piece will regenerate into a new animal.

So why does the sea anemone regenerate while humans cannot? When analyzing the function of its "heart genes," study researchers discovered a difference in the way these genes interact with one another, which may help explain its ability to regenerate, said Martindale, a UF biology professor and director of the Whitney Lab for Marine Bioscience in St. Augustine.

The study's findings point to potential for tweaking communication between human genes and advancing our ability to treat heart conditions and stimulate regenerative healing, he said.

"Our study shows that if we learn more about the logic of how genes that give rise to heart cells talk to each other, muscle regeneration in humans might be possible," Martindale said.

These heart genes generate what engineers calls lockdown loops in vertebrates and flies, which means that once the genes are turned on, they tell each other to stay on in an animal's cells for its entire lifetime. In other words, animals with a lockdown on their genes cannot grow new heart parts or use those cells for other functions.

"This ensures that heart cells always stay heart cells and cannot become any other type of cell," Martindale said.

But in sea anemone embryos, the lockdown loops do not exist. This finding suggests a mechanism for why the gut cells expressing heart genes in sea anemones can turn into other kinds of cells, such as those needed to regenerate damaged body parts, Martindale said.

The study supports the idea that definitive muscle cells found in the majority of animals arose from a bifunctional gut tissue that had both absorptive and contractile properties. And while the gut tissue of a sea anemone might not look like a beating heart, it does undergo slow, rhythmic peristaltic waves of contraction, much like the human digestive system.

Study authors argue that the first animal muscle cells might have been very heart-like, Martindale said.

"The idea is these genes have been around a long time and preceded the twitchy muscles that cover our skeleton," Martindale said.

Continued research could one day allow scientists to coax muscles cells into regenerating different kinds of new cells, including more heart cells, Martindale said

Sleep loss affects your waistline

Sleep loss increases the risk of obesity through a combination of effects on energy metabolism. This research, presented at the European Congress of Endocrinology in Lisbon, will highlight how disrupted sleep patterns, a common feature of modern living, can predispose to weight gain, by affecting people’s appetite and responses to food and exercise.

In the 24/7 culture of the modern world, an increasing number of people report routine reduced quality of sleep and several studies have correlated sleep deprivation with weight gain. The underlying cause of increased obesity risk from sleep disruption is unclear but may relate to changes in appetite, metabolism, motivation, physical activity or a combination of factors.

Dr Christian Benedict from Uppsala University, Sweden and his group have conducted a number of human studies to investigate how sleep loss may affect energy metabolism. These human studies have measured and imaged behavioural, physiological and biochemical responses to food following acute sleep deprivation. The behavioural data reveal that metabolically healthy, sleep-deprived human subjects prefer larger food portions, seek more calories, exhibit signs of increased food-related impulsivity, experience more pleasure from food, and expend less energy.

The group’s physiological studies indicate that sleep loss shifts the hormonal balance from hormones that promote fullness (satiety), such as GLP-1, to those that promote hunger, such as ghrelin. Sleep restriction also increased levels of endocannabinoids, which is known to have appetite-promoting effects. Further work from Dr Benedict’s team shows that acute sleep loss alters the balance of gut bacteria, which has been widely implicated as key for maintaining a healthy metabolism. The same study also found reduced sensitivity to insulin after sleep loss.

Dr Christian Benedict remarks, “Since perturbed sleep is such a common feature of modern life, these studies show it is no surprise that metabolic disorders, such as obesity are also on the rise.”

Although Dr Benedict’s work has shed light on how short periods of sleep loss can affect energy metabolism, longer-term studies are needed to validate these findings. The group are now investigating longer-term effects and also whether extending sleep in habitual short sleepers can restore these alterations in appetite and energy metabolism.

Dr Christian Benedict says, “My studies suggest that sleep loss favours weight gain in humans. It may also be concluded that improving sleep could be a promising lifestyle intervention to reduce the risk of future weight gain.”

Painkillers might not work if you are sleep deprived, study suggests

New research uncovers unexpected links between sleep deprivation and pain sensitivity. The findings may have significant implications for pain management therapies.

A recent study from the National Institutes of Health (NIH) estimates that more than 25 million adults in the United States live with chronic pain, and almost 40 million adults have experienced severe pain in the past 3 months.

Any pain that lasts for longer than 12 weeks is considered to be chronic. Chronic pain can be a consequence of injury, an underlying illness, or it may have no known cause.

Many people resort to complementary medical practices such as yoga or meditation to ease the pain. New research, however, examines the link between sleep deprivation, pain sensitivity, and common painkillers, and finds surprising connections. In the future, these findings could help patients with chronic pain to better manage their discomfort.

The study was carried out by researchers at Boston Children's Hospital and Beth Israel Deaconess Medical Center (BIDMC), both in Boston, MA, and their findings were published in the journal Nature Medicine.

Studying the link between sleep deprivation and pain in mice

The team - co-led by brain physiologist Alban Latremoliere, Ph.D., and sleep physiologist Chloe Alexandre, Ph.D. - investigated the impact of acute and chronic sleep deprivation, as well as the resulting sleepiness, on sensitivity to painful and non-painful stimuli.

They also examined the effect of common painkillers such as ibuprofen and morphine, alongside the effect of wakefulness-promoting drugs such as caffeine and modafinil, on pain sensitivity.

At the beginning of the study, the team monitored the sleep cycles and sensory sensitivity of between six and 12 mice using small headsets that took electroencephalography and electromyography measurements. This provided the researchers with baseline data.

The researchers then found a way to deprive the mice of sleep in a manner that was not stressful: by entertaining them. To replicate what happens when humans stay up too late, they distracted the mice with toys and fun activities when they were supposed to be asleep.

They were careful to prevent the mice from sleeping without overstimulating them. The mice were kept awake for either 12 hours straight, or for 6 hours during 5 successive days. Throughout these periods of wakefulness, the researchers monitored sleepiness, stress levels, and tested for pain sensitivity.

Sensitivity to painful stimuli was measured by applying controlled amounts of heat, cold, or pressure to the mice. Additionally, the rodents were also exposed to capsaicin - the active compound in hot chili peppers.

The researchers measured how long it took the mice to move away from the painful stimuli, or how long before they started licking away the pain caused by the hot chili compound.

Sensitivity to non-painful stimuli was tested by startling the mice with a sudden, loud noise and observing their response, which was usually to jump.

Pain killers do not work, but caffeine does

The study revealed a strong connection between sleep deprivation and pain sensitivity.

"We found that 5 consecutive days of moderate sleep deprivation can significantly exacerbate pain sensitivity over time in otherwise healthy mice. The response was specific to pain, and was not due to a state of general hyperexcitability to any stimuli."

Chloe Alexandre, Ph.D.

Probably the most surprising finding was that common painkillers seemed to have no efficacy in alleviating pain induced by sleep deprivation.

Neither ibuprofen nor morphine could prevent or stop the effects of the hypersensitivity induced by sleep loss.

By contrast, wakefulness-promoting drugs successfully stopped the pain hypersensitivity caused by acute and chronic sleep deprivation.

However, modafinil and caffeine did not have pain-relieving properties in the mice that had slept normally.

The findings suggest that patients with chronic pain who use common painkillers may have to increase their dose if they are also sleep deprived, which may introduce side effects. Fatigue and sleep disorder often accompany chronic pain.

The researchers say that their findings may pave the way for a new type of painkiller.

"This represents a new kind of analgesic that had not been considered before, one that depends on the biological state of the animal. Such drugs could help disrupt the chronic pain cycle, in which pain disrupts sleep, which then promotes pain, which further disrupts sleep."

Clifford Woolf, study co-author

The researchers also recommend that patients with chronic pain complement their painkillers with sleep-inducing medications at night and drugs that keep them alert during the day, in an attempt to break the pain cycle.

Dr. Kiran Maski, sleep disorders specialist at BIDMC, also weighs in on the findings, saying, "Many patients with chronic pain suffer from poor sleep and daytime fatigue, and some pain medications themselves can contribute to these co-morbidities."

She adds, "This study suggests a novel approach to pain management that would be relatively easy to implement in clinical care. Clinical research is needed to understand what sleep duration is required and to test the efficacy of wake-promoting medications in chronic pain patients."

Learn how brain differences between men and women affect response to pain relief.


Testosterone explains why women more prone to asthma

An international research team has revealed for the first time that testosterone protects males against developing asthma, helping to explain why females are two times more likely to develop asthma than males after puberty.

The study showed that testosterone suppresses the production of a type of immune cell that triggers allergic asthma. The finding may lead to new, more targeted asthma treatments.

One in nine Australians (2.5 million people) and around one in 12 Americans (25 million) have asthma, an inflammatory airway condition. During an asthma attack, the airways swell and narrow, making it difficult to breathe. In adults asthma is two times more prevalent and more severe in women than men, despite more being more common in boys than girls before puberty.

In 2016, the city of Melbourne, Australia, experienced a 'thunderstorm asthma' event that was unprecedented internationally in its scale and severity of consequences, with almost 10,000 people visiting hospitals over a two-day period. Thunderstorm asthma refers to allergic asthma thought to be initiated by an allergy to grass pollen. Many people with no history of asthma experienced severe asthma attacks.

Dr Cyril Seillet and Professor Gabrielle Belz from Melbourne's Walter and Eliza Hall Institute, with Dr Jean-Charles Guéry and his team at the Physiopathology Center of Toulouse-Purpan, France, led the study, published today in the Journal of Experimental Medicine.

Dr Seillet said hormones were speculated to play a significant role in the incidence and severity of asthma in women. "There is a very interesting clinical observation that women are more affected and develop more severe asthma than men, and so we tried to understand why this was happening," Dr Seillet said.

"Our research shows that high levels of testosterone in males protect them against the development of allergic asthma. We identified that testosterone is a potent inhibitor of innate lymphoid cells, a newly-described immune cell that has been associated with the initiation of asthma."

The research team found that innate lymphoid cells -- or ILC2s -- 'sensed' testosterone and responded by halting production of the cells.

"Testosterone directly acts on ILC2s by inhibiting their proliferation," Dr Seillet said. "So in males, you have less ILC2s in the lungs and this directly correlates with the reduced severity of asthma."

ILC2s are found in the lungs, skin and other organs. These cells produce inflammatory proteins that can cause lung inflammation and damage in response to common triggers for allergic asthma, such as pollen, dust mites, cigarette smoke and pet hair.

Professor Belz said understanding the mechanism that drives the sex differences in allergic asthma could lead to new treatments for the disease.

"Current treatments for severe asthma, such as steroids, are very broad based and can have significant side effects," Professor Belz said.

"This discovery provides us with a potential new way of treating asthma, by targeting the cells that are directly contributing to the development of allergic asthma. While more research needs to be done, it does open up the possibility of mimicking this hormonal regulation of ILC2 populations as a way of treating or preventing asthma. Similar tactics for targeting hormonal pathways have successfully been used for treating other diseases, such as breast cancer."

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