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http://www.eurekalert.org/pub_releases/2015-04/osu-ypr041315.php

Your pain reliever may also be diminishing your joy

Acetaminophen reduces both pain and pleasure, study finds

COLUMBUS, Ohio -- Researchers studying the commonly used pain reliever acetaminophen found it has a previously unknown side effect: It blunts positive emotions. In the study, participants who took acetaminophen reported less strong emotions when they saw both very pleasant and very disturbing photos, when compared to those who took placebos.

Acetaminophen, the main ingredient in the over-the-counter pain reliever Tylenol, has been in use for more than 70 years in the United States, but this is the first time that this side effect has been documented.

Previous research had shown that acetaminophen works not only on physical pain, but also on psychological pain. This study takes those results one step further by showing that it also reduces how much users actually feel positive emotions, said Geoffrey Durso, lead author of the study and a doctoral student in social psychology at The Ohio State University.

"This means that using Tylenol or similar products might have broader consequences than previously thought," Durso said. "Rather than just being a pain reliever, acetaminophen can be seen as an all-purpose emotion reliever."

Durso conducted the study with Andrew Luttrell, another graduate student in psychology at Ohio State, and Baldwin Way, an assistant professor of psychology and the Ohio State Wexner Medical Center's Institute for Behavioral Medicine Research. Their results appear online in the journal Psychological Science.

Way said people in the study who took the pain reliever didn't appear to know they were reacting differently. "Most people probably aren't aware of how their emotions may be impacted when they take acetaminophen," he said.

Acetaminophen is the most common drug ingredient in the United States, found in more than 600 medicines, according to the Consumer Healthcare Products Association, a trade group. Each week about 23 percent of American adults (about 52 million people) use a medicine containing acetaminophen, the CHPA reports.

There were two studies of college students. The first involved 82 participants, half of whom took an acute dose of 1000 milligrams of acetaminophen and half who took an identical-looking placebo. They then waited 60 minutes for the drug to take effect.

Participants then viewed 40 photographs selected from a database (International Affective Picture System) used by researchers around the world to elicit emotional responses. The photographs ranged from the extremely unpleasant (crying, malnourished children) to the neutral (a cow in a field) to the very pleasant (young children playing with cats).

After viewing each photo, participants were asked to rate how positive or negative the photo was on a scale of -5 (extremely negative) to +5 (extremely positive). They then viewed the same photos again and were asked to rate how much the photo made them feel an emotional reaction, from 0 (little or no emotion) to 10 (extreme amount of emotion).

Results in both studies showed that participants who took acetaminophen rated all the photographs less extremely than did those who took the placebo. In other words, positive photos were not seen as positively under the influence of acetaminophen and negative photos were not seen as negatively. The same was true of their emotional reactions.

"People who took acetaminophen didn't feel the same highs or lows as did the people who took placebos," Way said. For example, people who took the placebo rated their level of emotion relatively high (average score of 6.76) when they saw the most emotionally jarring photos of the malnourished child or the children with kittens. People taking acetaminophen didn't feel as much in either direction, reporting an average level of emotion of 5.85 when they saw the extreme photos. Neutral photos were rated similarly by all participants, regardless of whether they took the drug or not.

These findings seem dramatic, but one possibility is that acetaminophen changes how people judge magnitude. In other words, acetaminophen may blunt individuals' broader judgments of everything, not just things having emotional content, Durso said.

So the researchers did a second study in which they had 85 people view the same photos and make the same judgments of evaluation and emotional reactions as in the prior study. Additionally, participants in this second study also reported how much blue they saw in each photo.

Once again, individuals who took acetaminophen (compared to placebo) had evaluations and emotional reactions to both negative and positive photographs that were significantly blunted. However, judgments of blue color content were similar regardless of whether the participants took acetaminophen or not.

The results suggest that acetaminophen affects our emotional evaluations and not our magnitude judgments in general. At this point, the researchers don't know if other pain relievers such as ibuprofen and aspirin have the same effect, although they plan on studying that question, Durso said.

Acetaminophen, unlike many other pain relievers, is not a nonsteroidal anti-inflammatory drug, or NSAID. That means it not thought to control inflammation in the body. Whether that fact has any relevance to possible emotional effects of the drugs is still an open question, Durso said.

These results may also have an impact on psychological theory, Way said. An important question in psychological research is whether the same biochemical factors control how we react to both positive and negative events in our lives. A common theory is that certain factors control how we react to the bad things that happen in life -- for example, how devastated people feel when they go through a divorce.

But this study offers support to a relatively new theory that says that common factors may influence how sensitive we are to both the bad as well as the good things in life. That means the person who is more devastated by a divorce may thrive more than others when they get a promotion at work or have some other extremely positive event happen.

In this study, acetaminophen may have tapped into the sensitivity that makes some people react differently to both positive and negative life events.

"There is accumulating evidence that some people are more sensitive to big life events of all kinds, rather than just vulnerable to bad events," Durso said.



http://www.eurekalert.org/pub_releases/2015-04/nbi-nef041315.php

New evidence for how green tea and apples could protect health

Scientists from the Institute of Food Research have found evidence for a mechanism by which certain food compounds could help protect our health.

Dietary studies have shown that people who eat the largest amounts of fruit and vegetables have a reduced risk of developing chronic conditions, such as heart disease and cancer.

There could be several reasons for this. Some fruit and vegetables naturally contain high amounts of compounds called polyphenols, which could provide protective health benefits.

In this study, Dr Paul Kroon and his team at IFR have shown that polyphenols in green tea and apples block a signalling molecule called VEGF, which in the body can trigger atherosclerosis and is a target for some anti-cancer drugs.

In the body, VEGF is a main driver of blood vessel formation in these cell types via a process called angiogenesis.

Angiogenesis is crucial in cancer progression, as well as in the development of atherosclerotic plaques and plaque rupture which can cause heart attacks and stroke.

Using cells derived from human blood vessels, the researchers found that low concentrations of the polyphenols epigallocatechin gallate (EGCG) from green tea and procyanidin from apples stopped a crucial signalling function of VEGF.

Inhibition of VEGF signalling by dietary polyphenols has previously been implicated in other studies, but this study provides the first evidence that polyphenols can directly interact with VEGF to block its signals, at the levels you would see in the blood stream after eating polyphenol rich foods.

"If this effect happens in the body as well, it provides very strong evidence for a mechanism that links dietary polyphenols and beneficial health effects," said Dr Paul Kroon, Research Leader at IFR.

The polyphenols also activated another enzyme signalling system that generates nitric oxide in the blood, which helps widen the blood vessels and prevent damage. This was unexpected, as VEGF itself stimulates nitric oxide, and anti-cancer drugs that block VEGF also reduce nitric oxide, leading to an increased risk of hypertension in some users.



Reference: Potent inhibition of VEGFR-2 activation by tight binding of green tea epigallocatechin gallate and apple procyanidins to VEGF: Relevance to angiogenesis, Christina W. A. Moyle et al, Molecular Nutrition and Food Research, 59(3) 401-412 doi: 10.1002/mnfr.201400478

http://www.eurekalert.org/pub_releases/2015-04/ucl-his041315.php

Human immune system can control re-awakened HIV, suggesting cure is possible

May be possible to possible to cure HIV with a 'kick and kill' strategy

The human immune system can handle large bursts of HIV activity and so it should be possible to cure HIV with a 'kick and kill' strategy, finds new research led by UCL, the University of Oxford and the University of North Carolina at Chapel Hill.

The 'kick and kill' strategy aims to cure HIV by stimulating the immune system with a vaccine, then re-awakening dormant HIV hiding in white blood cells with a chemical 'kick' so that the boosted immune system can identify and kill them.

While this approach is promising in theory, it was previously unclear whether the human immune system would be able to control HIV following full-blown reactivation of the virus. The new research, published in Clinical Infectious Diseases, demonstrates that this is possible using a single patient case study.

"Our study shows that the immune system can be as powerful as the most potent combination drug cocktails," explains study co-author Dr Ravi Gupta (UCL Infection & Immunity). ". We're still a long way from being able to cure HIV patients, as we still need to develop and test effective vaccines, but this study takes us one step closer by showing us what type of immune responses an effective vaccine should induce."

The study looked at a single 59 year old man in London who was an 'elite controller', meaning that his immune system could control HIV for a long time without needing treatment. Elite controllers, who make up 0.3% of HIV patients, eventually require treatment to prevent progression to AIDS but they can go a lot longer without treatment because their immune systems are more active against HIV.

The patient in the study had both HIV and myeloma, a cancer of the bone marrow. The bone marrow produces white blood cells, including those that help to control HIV. To treat the patient's myeloma, his bone marrow was completely removed and replaced using his own stem cells. When the bone marrow was removed, the immune system was severely impaired, allowing the HIV to re-activate and replicate. This caused the level of virus in his bloodstream to rise from fewer than 50 copies per millilitre to approximately 28,000 copies per ml before immune function returned.

When the patient's immune function returned about two weeks after the transplant, the levels of HIV in his bloodstream rapidly fell. His immune system reduced HIV levels at a similar rate to the most powerful treatments available, bringing them back down to 50 copies per ml within six weeks.

"By measuring the strength of the immune system required to keep this virus under control in this rare individual, we have a better idea of the requirements for successful future treatment," says co-author Professor Deenan Pillay (UCL Infection & Immunity, and now also Director of the Africa Centre for Health and Population Studies, in South Africa). "We also managed to identify the specific immune cells that fought the infection. This is a single patient study, but nevertheless it is often the unusual patients who help us to understand the HIV disease process."

The patient was not given anti-HIV medication in this study due to concerns about side-effects affecting the myeloma treatment and low initial levels of HIV in his bloodstream. It is possible that an equally strong immune response in combination with powerful drugs could have cured the HIV completely, however this is far from certain.

"We need to be cautious in interpreting observations from a single subject," says Dr Nilu Goonetilleke, who began working on the study at the University of Oxford and is now at the University of North Carolina at Chapel Hill. "However, demonstration even from a single subject, that our immune system can rapidly control HIV-1 tells us a lot about the types of immune responses we should target and augment through vaccination."

Dr Gupta adds: "Drugs to stimulate reactivation of dormant HIV are still imperfect, and we do not know if they would be able to flush out all of the HIV from the body. Likewise, it remains to be seen whether a vaccine could enable a normal HIV patient's immune system to kill HIV with the full strength of an elite controller. Our study is a proof of principle and the results are promising, but it is unlikely to lead to a cure for at least a decade."



http://www.eurekalert.org/pub_releases/2015-04/thuo-scv041315.php

Study challenges view that sight-based brain sensory network organization is impaired with blindness

Is visual input essential to how the topographical map of the visual cortex develops in the human brain?

In new research published today, scientists at the Hebrew University of Jerusalem and in Germany and the USA show that the way in which the brain organizes its visual sense remains intact even in people who are blind from birth, and that at least the pattern of functional connectivity between the visual area and the topographical representation of space (up/down, left/right, etc.) can develop on its own without any actual visual experience.

The findings, reported in the prestigious peer-reviewed neuroscience journal Brain, dispel the nearly half-century belief that the visual cortex - the area of the brain concerned with the sense of sight - completely fails to develop properly in people who are blind at birth, suggesting it might not be completely correct.

"Though the 'blind brain' wiring may change greatly in the blind in its frontal language related parts, it still retains the most fundamental topographical and functional connectivity organizational principles of the visual cortex, known as 'retinotopic mapping' - the processing of two-dimensional visual images through the eye," said co-lead researcher Amir Amedi, associate professor of medical neurobiology at the Hebrew University's Edmond and Lily Safra Center for Brain Sciences and IMRIC, the Institute for Medical Research Israel-Canada.



This functional magnetic resonance imaging map shows a center periphery connectivity mass in the primary visual cortex (V1) of the congenitally blind brain. Ella Striem-Amit and Amir Amedi

Operating within the Hebrew University's Faculty of Medicine, IMRIC coordinates research within the departmental areas of medical neurobiology, molecular genetics and biology, immunology and cancer research.

The researchers found that the same "mapping" divisions-of-labor present in the normally sighted brain are also present in the brains of people born blind as reflected from their resting state connectivity patterns. This fundamental organization of the visual cortex was even found in people whose eyes did not develop normally, suggesting normal eye development may not be necessary for the establishment of large-scale functional connectivity network mapping in the most fundamental visual areas like V1, the primary visual cortex.

Contrary to conventional wisdom, the latest findings reported by Prof. Amir Amedi, Dr. Ella Striem-Amit and Smadar Ovadia-Caro suggest that some key features and properties of visual cortex organization do not require visual experience to progress. The study further adds that the brain's visual cortex does not lose all of its properties even when completely deprived of vision.

"Some of the brain's connectivity maps is hardwired, possibly dependent on genetically-driven processes that do not need any external sensory information for their activation, while other process might indeed need visual input to specialize," Amedi said. The visual brain resting-state connectivity networks separated to up vs. down, right vs. left, front vs. back are also present in the brain of those born blind, according the study. Videos and images for the media are available at http://www.brainvisionrehab.com/#!videosformedia/c1yju.

Previous research by neurophysiologists David Hubel and Torsten Wiesel, which earned them a Nobel Prize in 1981, suggested that sight restoration could not be attempted on people blind from birth. Therefore, they surmised, the blinded cortex could not enable the blind-from-birth to have sight.

According to Hebrew University's Amedi, this latest research, combined with other research conducted in the Amedi Lab for Multisensory Research, "means that it may be possible to successfully teach blind people to 'see with sounds and touch.'" Using tools of sensory substitution, it may be possible to aid people born blind (or late blind) in a variety of new ways in the future, including restoring high-order functional pattern recognition for objects, localization, shape and even numbers and text, as previously reported in the prestigious journal Nature Communications (Abboud et al., Nature Comm., 2015). Any blind person can download and train themselves on using such technologies for free via the following link: http://www.amedilab.com.

The research paper, "Functional connectivity of visual cortex in the blind follows retinotopic organization principles," appears in the peer-reviewed journal Brain (DOI: http://dx.doi.org/10.1093/brain/awv083; first published online 13 April 2015).

Research co-authors include Dr. Daniel Margulies (Humboldt University and Max Planck Institute for Human Cognitive and Brain Sciences, Germany); and Profs. Alfonso Caramazza (Harvard University and Università degli Studi di Trento, Polo di Rovereto, Italy) and Arno Villringer (Humboldt University and Max Planck Institute for Human Cognitive and Brain Sciences, Germany); Dr. Ella Striem-Amit, who recently earned her Ph.D. from Hebrew University and who is now pursuing a post-doctoral fellowship from Harvard University's Department of Psychology; and Smadar Ovadia-Caro, at the Mind and Brain Institute at Humboldt University.

The research or researchers were supported by a European Research Council grant and The James S. McDonnell Foundation scholar award (to Amir Amedi), The Edmond and Lily Safra Center for Brain Sciences (ELSC) Vision Center grant, and the German Excellence Initiative Grant to the Berlin School of Mind and Brain.

http://www.bbc.com/news/science-environment-32287609

Evidence of liquid water found on Mars

Nasa's Curiosity rover has found that water can exist as a liquid near the Martian surface.

By Paul Rincon Science editor, BBC News website

Mars should be too cold to support liquid water at the surface, but salts in the soil lower its freezing point - allowing briny films to form.

The results lend credence to a theory that dark streaks seen on features such as crater walls could be formed by flowing water.

The results are published in the journal Nature Geoscience.

Scientists think thin films of water form when salts in the soil, called perchlorates, absorb water vapour from the atmosphere.

The temperature of these liquid films is about -70C - too cold to support any of the microbial life forms that we know about.

Forming in the top 15cm of the Martian soil, the brines would also be exposed to high levels of cosmic radiation - another challenge to life.

But it's still possible that organisms could exist somewhere beneath the surface on Mars, where conditions are more favourable.



Evaporation cycle

The researchers drew together different lines of evidence collected over a Martian year, and from different instruments carried by the Curiosity rover.



Scientists see a daily water cycle maintained by the brines

The Rover Environmental Monitoring System (REMS) - essentially the vehicle's weather station - measured the relative humidity and temperature at the rover's landing site of Gale Crater.

Scientists were also able to estimate the subsurface water content using data from an instrument called Dynamic Albedo of Neutrons (DAN). These data were consistent with water in the soil being bound to perchlorates.

Finally, the Sample Analysis at Mars (SAM) instrument gave the researchers the content of water vapour in the atmosphere.

The results show conditions were right for the brines to form during winter nights at the Martian equator, where Curiosity landed. But the liquid evaporates during the Martian day when temperatures rise.

Javier Martin-Torres, a co-investigator on the Curiosity mission and lead scientist on REMS, told BBC News the detection was indirect but convincing:

"What we see are the conditions for the formation of brines on the surface. It's similar to when people were discovering the first exoplanets.

"They were not seeing the planets, but they were able to see the gravitational effects on the star.

"These perchlorate salts have a property called deliquescence. They take the water vapour from the atmosphere and absorb it to produce the brines."

He added: "We see a daily water cycle - which is very important. This cycle is maintained by the brine. On Earth we have an exchange between the atmosphere and the ground through rain. But we don't have this on Mars."

While one might think that liquid water would form at warmer temperatures, the formation of brines is the result of an interaction between temperature and atmospheric pressure. It happens that the sweet spot for formation of these liquid films is at colder temperatures.

The fact that the scientists see evidence for these brines at the Martian equator - where conditions are least favourable - means that they might be more persistent at higher latitudes, in areas where the humidity is higher and temperatures are lower. In these regions they might even be present all year round.

Dark streaks on slopes seen by orbiting spacecraft have long been thought to be the product of running water seeping from the Martian soil.

But this interpretation has been contested.

"It's speculation at this point... but these observations at least support or go in this direction," said Dr Martin-Torres.

http://www.eurekalert.org/pub_releases/2015-04/tjnj-bmd040915.php

Bone mineral density improved in frail elderly women treated with zoledronic acid

Single intravenous dose of zoledronic acid improved bone mineral density in a group of frail elderly women

A single intravenous dose of the osteoporosis drug zoledronic acid improved bone mineral density in a group of frail elderly women living in nursing homes and long-term-care facilities, according to an article published online by JAMA Internal Medicine.

Nearly 2 million frail elderly Americans live in long-term care facilities and many of them have osteoporosis and bone fracture rates higher than less impaired elderly individuals. A hip fracture can be dire, decreasing mobility, independence and often leading to death, according to background in the study.

Susan L. Greenspan, M.D., of the University of Pittsburgh, and coauthors conducted a clinical trial to determine the efficacy and safety of zoledronic acid to treat osteoporosis in frail elderly women living in long-term care facilities. Zoledronic acid was chosen because it can be given in a single intravenous dose and the effect can last for two years.

The two-year study included 181 women 65 or older with osteoporosis, including women with cognitive impairment, immobility and multiple coexisting illnesses, who were living in nursing homes and assisted-living facilities. Of the women, 89 were assigned to receive a single 5-mg dose of zoledronic acid and 92 were assigned to receive placebo, while all participants received daily vitamin D and calcium supplementation.

The authors measured hip and spine bone mineral density (BMD) at 12 and 24 months, as well as adverse events, which included falls.

The average total hip BMD increased more in the treatment group than in the placebo group both at 12 months (2.8 percent vs. -0.5 percent) and at 24 months (2.6 percent vs. -1.5 percent), according to the results. The average spine BMD also increased more in the treatment group than placebo group at 12 months (3 percent vs. 1.1 percent) and at 24 months (4.5 percent vs. 0.7 percent).

Overall, in the measure of adverse events, there were no significant differences in the number of deaths, fractures or cardiac disorders. The treatment and placebo groups' fracture rates were 20 percent (18 women) and 16 percent (15 women), respectively, and mortality rates were 16 percent (14 women) and 13 percent (12 women), respectively. There were no significant differences between groups in the number of single fallers but more participants in the treatment group has multiple falls (49 percent vs. 35 percent), although this difference did not remain significant after adjusting for baseline frailty, the results indicate.



"In summary, we found that a single infusion of zoledronic acid in frail, cognitively challenged, less mobile elderly women improved bone density and reduced bone turnover for two years. This suggests that even a very frail cohort may benefit. However, prior to changing practice, larger trials are needed to determine whether improvement in these surrogate measures will translate into fracture reduction for vulnerable elderly persons," the study concludes.

(JAMA Intern Med. Published online April 13, 2015. doi:10.1001/jamainternmed.2015.0747. Available pre-embargo to the media at http://media.jamanetwork.com.)

Editor's Note: Authors made conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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