A more sensitive way of testing water for contamination relies on the phosphorescence of urobilin, a compound in mammal urine and feces.

Working with a team of collaborators, Vladislav Yakovlev, professor in the department of biomedical engineering at Texas A&M University, has developed the ultrasensitive detection method, which can detect molecules associated with human and animal fecal matter in water systems.

These extremely small indicators, he explains, have been traditionally difficult to detect but can signal greater levels of contamination, which can lead to illness and even death.

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It details the development of technology that Yakovlev characterizes as affordable, highly sensitive, easy to implement, and capable of delivering analysis of water samples in real time.

That combination of benefits, he says, gives the system a leg up on other detection technologies, making it ideal for use not only in the United States but also in developing countries, which often face water-quality issues.

At home and abroad, animal and human waste can contaminate both recreational and source waters, carrying with diseases such as polio, typhoid, and cholera. This form of contamination can even result in environmental crises, such as devastation to the aquatic population and red-tide blooms, Yakovlev notes.

These types of contamination events, Yakovlev explains, might be mitigated or even avoided if samples from water systems are more thoroughly analyzed so that they can provide a better picture of what is in the water.

In other words, finding trace amounts of contaminants such as fecal matter in water systems can help sound the alarm for a serious contamination event because these trace amounts likely originate from a larger source in the water system, he says.

However, detecting these trace amounts isn’t easy, especially in a timely manner, Yakovlev says. High costs, sample-size limitations, and lengthy analysis times, he notes, have prevented environmental researchers from employing highly sensitive techniques that can deliver real-time analysis—until now.

Urobilin in the water

The new approach detects urobilin, a byproduct excreted in the urine and feces of many mammals, including humans and livestock such as cows, horses, and pigs.

Urobilin molecules, Yakovlev notes, are small and diffuse quickly so they easily occupy large volumes, such as lakes and reservoirs, for example.

In addition, urobilin possesses another interesting property; it glows—or more accurately, it can be made to glow. When mixed with zinc ions, urobilin forms a phosphorescent compound, Yakovlev explains.

This means if urobilin is present in a water sample—and zinc ions have been added—the sample will give off a greenish glow when examined under an ultraviolet light, he says. There’s just one catch. In some samples with low concentrations of urobilin, the glow, or phosphorescent emission, can be weak, making it difficult to analyze the sample.

Capturing the glow

Researchers, Yakovlev says, must be able to thoroughly excite the sample (causing the reaction), observe the glow, and then measure it in order to perform an accurate analysis.

Towards that goal, Yakovlev and his team have developed technology that allows them to thoroughly excite extremely small amounts of urobilin in large samples of water and then efficiently collect the resulting phosphorescent emission, regardless of how weak that emission might be. It’s done with the help of a device researchers refer to as an “integrated cavity.”

The integrated cavity used by the team of researchers is essentially a hollow, cylindrical container manufactured in Yakovlev’s laboratory. A water sample is placed inside the cylinder where it interacts with zinc ions, and a laser light is beamed into the object and onto the sample through a small hole, Yakovlev explains.

The light excites the urobilin compound present in the sample, causing it to emit a glow. The only way for the light to exit the cylinder, he notes, is through the hole that it initially entered. Not only does this ensure that all the light that enters the cylinder is used to excite the entire sample, but it also enables researchers to efficiently collect the resulting phosphorescent emission so that it can be directed to a photo detector, such as a spectrometer, for analysis, Yakovlev says.

Employing the integrated cavity in their detection efforts, Yakovlev and his team have detected the presence of urobilin down to a nanomole per liter. The technology also provides actual concentration levels of the contaminant, and it does so more quickly than other methods, he notes.

Larger samples

“We can demonstrate detection of ultralow concentrations of urobilin in solution,” Yakovlev says. “This is a huge improvement in terms of sensitivity, and our technique has tremendous potential for analysis of global drinking water supplies, particularly in developing nations and following natural disasters, where sophisticated laboratory equipment may not be available.”

Another key element of the technology, which can be produced for a few hundred dollars, is its ability to analyze large samples, Yakovlev notes. Conventional methods are not capable of analyzing large samples. This is a problem, he adds, because it is unlikely that an accurate analysis of an overall water system can be derived from a small sample.

For example, researchers might collect a small sample that is free of the contaminant, but that doesn’t mean the entire water system is contaminant-free. A larger sample, he says, gives researchers a better predictive power about the water system contains.

“The bigger the sample, the better,” Yakovlev says. “And with our technology the sensitivity scales with the amount of water in our sample. Using one liter will increase sensitivity by a factor of 20, and an additional 10 liters result in another order of magnitude increase in sensitivity.

A ‘smoke detector’ for your faucet

As its stands, Yakovlev and his team are working to commercialize the technology for urobilin detection. Because it delivers nearly instantaneous results, it could serve as the basis for in-home detection systems that alert users if the water coming from their faucets is suddenly contaminated, he says. Think smoke detector for a water faucet.

Equally as important, he notes, the technology can be used for detection of other types of toxic compounds in both liquids and gases, lending itself to anti-terrorism applications, among other uses.

The National Science Foundation funds the research, which appears in the Proceedings of the National Academy of Sciences.

Source: Texas A&M University

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Researchers investigated how quickly 32 different kinds of animals urinate—and big or small, it’s remarkably the same.

Even though an elephant’s bladder is 3,600 times larger than a cat’s—just under five gallons vs. about one teaspoon—both animals relieve themselves in about 20 seconds.

In fact, all animals that weigh more than 6.6 pounds urinate in that same time span.

“It’s possible because larger animals have longer urethras,” says study leader David Hu, an assistant professor at Georgia Institute of Technology (Georgia Tech).

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“The weight of the fluid in the urethra is pushing the fluid out. And because the urethra is long, flow rate is increased.”

For example, an elephant’s urethra is just over a yard long. The pressure of fluid in it is the same at the bottom of a swimming pool three feet deep. An elephant urinates about 13 feet per second, or the same volume per second as five showerheads.

“If its urethra were shorter, the elephant would urinate for a longer time and be more susceptible to predators,” Hu explains.

The findings conflict with studies that indicate urinary flow is controlled by bladder pressure generated by muscular contraction. The study appears in the Proceedings of the National Academy of Sciences.

Hu and graduate student Patricia Yang noticed that gravity allows larger animals to empty their bladders in jets or sheets of urine. Gravity’s effect on small animals is minimal.

“They urinate in small drops because of high viscous and capillary forces. It’s like peeing in space,” says Yang, a PhD student in the George Woodruff School of Mechanical Engineering. “Mice and rats go in less than two seconds. Bats are done in a fraction of a second.”

Using gravity

The research team went to a zoo to watch 16 animals relieve themselves, then watched 28 YouTube videos. They saw cows, horses, dogs, and more.

The more they watched, the more they realized their findings could help engineers.

“It turns out that you don’t need external pressure to get rid of fluids quickly,” says Hu. “Nature has designed a way to use gravity instead of wasting the animal’s energy.”

Hu envisions systems for water tanks, backpacks, and fire hoses that can be built for more efficiency. As an example, he and his students have created a demonstration that empties a teacup, quart, and gallon of water in the same duration using varying lengths of connected tubes.

In a second experiment, the team fills three cups with the same amount of water, then watches them empty at differing rates. The longer the tube, the faster it empties.

“Nature has shown us that no matter how big the fire truck, water can still come out in the same time as a tiny truck,” Hu adds.

Source: Georgia Tech

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Simpler, automatic alerts in electronic health records can cut the number of urinary tract infections in patients with urinary catheters, report researchers.

The alerts help physicians decide whether their patients need urinary catheters in the first place and then alert them to reassess the need for catheters that have not been removed within a recommended time period.

Approximately 75 percent of urinary tract infections acquired in the hospital are associated with a urinary catheter—a tube inserted into the bladder through the urethra to drain urine.

According to the Centers for Disease Control and Prevention, 15 to 25 percent of hospitalized patients receive urinary catheters during their hospital stay. As many as 70 percent of urinary tract infections in these patients may be preventable using infection control measures such as removing no longer needed catheters resulting in up to 380,000 fewer infections and 9,000 fewer deaths each year.

15 percent more catheters removed

“Our study has two crucial, applicable findings,” says lead author Charles A. Baillie, an internal medicine specialist and fellow in the Center for Clinical Epidemiology and Biostatistics at Penn Medicine.

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“First, electronic alerts do result in fewer catheter-associated urinary tract infections. Second, the design of the alerts is very important. By making the alert quicker and easier to use, we saw a dramatic increase in the number of catheters removed in patients who no longer needed them.

“Fewer catheters means fewer infections, fewer days in the hospital, and even, fewer deaths. Not to mention the dollars saved by the health system in general.”

In the first phase of the study, two percent of urinary catheters were removed after an initial “off-the-shelf” electronic alert was triggered (the stock alert was part of the standard software package for the electronic health record).

Hoping to improve on this result in a second phase of the study, the researchers developed and used a simplified alert based on national guidelines for removing urinary catheters they had previously published with the CDC. Following introduction of the simplified alert, the proportion of catheter removals increased more than seven-fold to 15 percent.

The study also found that catheter associated urinary tract infections decreased from an initial rate of .84 per 1,000 patient days to .70 per 1,000 patient-days following implementation of the first alert and .50 per 1,000 patient days following implementation of the simplified alert.

Harder to put in, easier to take out

Among other improvements, the simplified alert required two mouse clicks to submit a remove-urinary-catheter order compared to seven mouse clicks required by the original alert.

The study was conducted among 222,475 inpatient admissions in the three hospitals of the University of Pennsylvania Health System between March 2009 and May 2012. In patients’ electronic health records, physicians were prompted to specify the reason (among ten options) for inserting a urinary catheter. On the basis of the reason selected, they were subsequently alerted to reassess the need for the catheter if it had not been removed within the recommended time period based on the reason chosen.

Women’s health units had the highest proportion of alerts that led to a remove-urinary-catheter order and critical care units saw the lowest proportion of alerts leading to a remove order.

The study appears in Infection Control and Hospital Epidemiology.

Source: University of Pennsylvania

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Tiny animals such as zooplankton make the world’s biggest migration—from feeding at the open ocean’s surface at night to hiding in sunless depths during the day.

Their daytime ammonia output—the equivalent of urination—has a surprisingly big role in marine chemistry, particularly in low-oxygen zones.

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A study on the finding appears online in the Proceedings of the National Academy of Sciences.

“I’m very fascinated by these massive migrations,” says lead author Daniele Bianchi, a postdoctoral researcher in the UW School of Oceanography. “To me, it’s exciting to think about the effects of animal behavior on a large scale in the ocean.”

One might not think that peeing into the vastness of the oceans could have an effect. But the animals—which include tiny zooplankton, crustaceans such as krill, and fish such as lanternfish up to a few inches long—compensate for their small size with huge abundance throughout the world’s oceans.

After a nighttime feast near the surface, these small creatures take a couple of hours to swim about 650 to 2,000 feet (200 to 600 meters) deep. Solid waste falls as pellets. The liquid waste is emitted more gradually.

Low-oxygen zones

In earlier work, Bianchi made the surprising finding that the animals spend most of their day in low-oxygen water. Marine bacteria consume oxygen as they decompose sinking dead material, creating low-oxygen zones a few hundred feet below the surface.

“The animals really seem to stop in low-oxygen regions, which is sort of puzzling,” Bianchi says. Some speculated these zones might protect them from larger predators.

The earlier study also showed that animals actually contribute to these low-oxygen zones by using the little remaining oxygen to breathe.

Marine chemistry

For the new study, authors mined data from underwater sonar surveys to calculate how many animals are migrating to which depths, and where. Next they gauged the combined effect of their daytime digestion.

Results show that in certain parts of the ocean, ammonia released from animals drives a big part of the oxygen-free conversion of ammonium and other molecules to nitrogen gas, a key chemical transition.

“We still think bacteria do most of the job, but the effect of animals is enough to alter the rates of these reactions and maybe help explain some of the measurements,” Bianchi says.

Inside low-oxygen zones, it’s still mysterious how bacteria turn so much nitrogen-based ammonia into tight pairs of nitrogen atoms, like those found in air, which cannot be used by plants or animals. The conversion is important because it determines how much nitrogen-based fertilizer remains to support life in the world’s oceans.

Researchers typically model low-oxygen zones using factors such as ocean currents, weather, and bacterial growth. The new paper, Bianchi says, shows that diving animals, though more difficult to model, also play a role in marine chemistry.

The ocean’s low-oxygen zones are projected to expand under climate change, as warmer waters hold less oxygen and decrease oxygen content below the surface. Understanding these zones is thus important for predicting what might happen to the oceans under climate change.

The Canadian Institute for Advanced Research, the Canadian Foundation for Innovation, and the US National Science Foundation funded the work. Coauthors are Andrew Babbin at Princeton University and Eric Galbraith at Canada’s McGill University.

Source: University of Washington

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If kidney cancer is diagnosed early—before it spreads—80 percent of patients survive. However, finding it early has been among the disease’s greatest challenges.

Now, researchers have developed a noninvasive method to screen for kidney cancer that involves measuring the presence of proteins in the urine.

The researchers found that the protein biomarkers were more than 95 percent accurate in identifying early-stage kidney cancers. In addition, there were no false positives caused by non-cancerous kidney disease.

“These biomarkers are very sensitive and specific to kidney cancer,” says senior author Evan D. Kharasch of Washington University School of Medicine.

Tough to diagnose early

Kidney cancer is the seventh most common cancer in men and the tenth most common in women, affecting about 65,000 people each year in the United States. About 14,000 patients die of the disease annually.

Like most cancers, kidney tumors are easier to treat when diagnosed early. But symptoms of the disease, such as blood in the urine and abdominal pain, often don’t develop until later, making early diagnosis difficult.

“The most common way that we find kidney cancer is as an incidental, fortuitous finding when someone has a CT or MRI scan,” says Kharasch, professor of anesthesiology. “It’s not affordable to use such scans as a screening method, so our goal has been to develop a urine test to identify kidney cancer early.”

When kidney cancer isn’t discovered until after it has spread, more than 80 percent of patients die within five years.

The team analyzed urine samples from 720 patients at Barnes-Jewish Hospital who were about to undergo abdominal CT scans for reasons unrelated to a suspicion of kidney cancer.

Results of the scans let the investigators determine whether or not patients had kidney cancer. As a comparison, they also analyzed samples from 80 healthy people and 19 patients previously diagnosed with kidney cancer.

Biomarker combo

The researchers measured levels of two proteins in the urine—aquaporin-1 (AQP1) and perlipin-2 (PLIN2). None of the healthy people had elevated levels of either protein, but patients with kidney cancer had elevated levels of both proteins.

In addition, three of the 720 patients who had abdominal CT scans also had elevated levels of both proteins. Two of those patients were diagnosed subsequently with kidney cancer, and the third patient died from other causes before a diagnosis could be made.

“Each protein, or biomarker, individually pointed to patients who were likely to have kidney cancer, but the two together were more sensitive and specific than either by itself,” says principal investigator Jeremiah J. Morrissey, professor of anesthesiology.

“When we put the two biomarkers together, we correctly identified the patients with kidney cancer and did not have any false positives.”

Even when patients had other types of non-cancerous kidney disease, levels of the two proteins in the urine were not elevated and did not suggest the presence of cancer.

“Patients with other kinds of cancer or other kidney diseases don’t have elevations in these biomarkers,” Kharasch says. “So in addition to being able to detect kidney cancer early, another advantage of using these biomarkers may be to show who doesn’t have the disease.”

Not all kidney masses found by CT scans turn out to be cancerous, he says. In fact, about 15 percent are not malignant.

“But a CT scan can only tell you whether there is a mass in the kidney, not whether it’s cancer,” Kharasch says. “Currently, the only way to know for sure is to have surgery, and unfortunately, 10 to 15 percent of kidneys removed surgically turn out not to be cancerous.”

Before it’s too late

Kharasch and Morrissey are working to develop an easy-to-use screening test for kidney cancer, much like mammograms, colonoscopies, or other tests designed to identify cancer at early, more treatable stages before patients have symptoms.

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“By and large, patients don’t know they have kidney cancer until they get symptoms, such a blood in the urine, a lump or pain in the side or the abdomen, swelling in the ankles, or extreme fatigue,” Morrissey says. “And by then, it’s often too late for a cure.

“Metastatic kidney cancer is extremely difficult to treat, and if the disease is discovered after patients have developed symptoms, they almost always have metastases. So we’re hoping to use the findings to quickly get a test developed that will identify patients at a time when their cancer can be more easily treated.”

Researchers from Siteman Cancer Center, the Mallinckrodt Institute of Radiology, and the Division of Urologic Surgery contributed to the study. The findings appear in JAMA Oncology.

Funding came from the Barnes-Jewish Hospital Cancer Frontier Fund and the department of anesthesiology at Washington University School of Medicine in St. Louis, with additional support from the Bear Cub Fund of Washington University, Barnes-Jewish Hospital Foundation, and Washington University Institute of Clinical and Translational Science, with additional funding from the National Cancer Institute of the National Institutes of Health.

Source: Washington University in St. Louis

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The acidity of urine—as well as the presence of small molecules related to diet—may influence how well bacteria can grow in the urinary tract, a new study shows.

The research may have implications for treating urinary tract infections, which are among the most common bacterial infections worldwide.

Urinary tract infections (UTIs) often are caused by a strain of bacteria called Escherichia coli (E. coli), and doctors long have relied on antibiotics to kill the microbes. But increasing bacterial resistance to these drugs is leading researchers to look for alternative treatment strategies.

“Many physicians can tell you that they see patients who are particularly susceptible to urinary tract infections,” says senior author Jeffrey P. Henderson, assistant professor of medicine at Washington University School of Medicine in St. Louis.

“We often don’t know why certain people seem to be prone to recurrent UTIs. For a long time, we had inexpensive antibiotics that worked really well for this. But over the last 10-15 years, we have seen a huge jump in bacterial infections that are resistant to many of these drugs.”

Pee pH

With this in mind, Henderson and his team, including first author Robin R. Shields-Cutler, a graduate student in Henderson’s lab, were interested in studying how the body naturally fights bacterial infections. They cultured E. coli in urine samples from healthy volunteers and noted major differences in how well individual urine samples could harness a key immune protein to limit bacterial growth.

“We could divide these urine samples into two groups based on whether they permitted or restricted bacterial growth,” Henderson says. “Then we asked, what is special about the urine samples that restricted growth?”

The urine samples that prevented bacterial growth supported more activity of this key protein, which the body makes naturally in response to infection, than the samples that permitted bacteria to grow easily.

The protein is called siderocalin, and past research has suggested that it helps the body fight infection by depriving bacteria of iron, a mineral necessary for bacterial growth. Their data led the researchers to ask if any characteristics of their healthy volunteers were associated with the effectiveness of siderocalin.

“Age and sex did not turn out to be major players,” Shields-Cutler says. “Of all the factors we measured, the only one that was really different between the two groups was pH—how acidic or basic the urine was.”

‘An incredibly complex medium’

Henderson says that conventional wisdom in medicine favors the idea that acidic urine is better for restricting bacterial growth. But their results were surprising because samples that were less acidic, closer to the neutral pH of pure water, showed higher activity of the protein siderocalin and were better at restricting bacterial growth than the more acidic samples.

Importantly, the researchers also showed that they could encourage or discourage bacterial growth in urine simply by adjusting the pH, a finding that could have implications for how patients with UTIs are treated.

“Physicians are very good at manipulating urinary pH,” says Henderson, who treats patients with UTIs. “If you take Tums, for example, it makes the urine less acidic. But pH is not the whole story here. Urine is a destination for much of the body’s waste in the form of small molecules. It’s an incredibly complex medium that is changed by diet, individual genetics, and many other factors.”

After analyzing thousands of compounds in the samples, the researchers determined that the presence of small metabolites called aromatics, which vary depending on a person’s diet, also contributed to variations in bacterial growth. Samples that restricted bacterial growth had more aromatic compounds, and urine that permitted bacterial growth had fewer.

Iron binders

Henderson and his colleagues suspect that at least some of these aromatics are good iron binders, helping deprive the bacteria of iron. And perhaps surprisingly, these molecules are not produced by human cells, but by a person’s gut microbes as they process food in the diet.

“Our study suggests that the body’s immune system harnesses dietary plant compounds to prevent bacterial growth,” Henderson says. “We identified a list of compounds of interest, and many of these are associated with specific dietary components and with gut microbes.”

Indeed, their results implicate cranberries among other possible dietary interventions. Shield-Cutler note that many studies already have investigated extracts or juices from cranberries as UTI treatments but the results of such investigations have not been consistent.

“Its possible that cranberries may be more effective when paired with a treatment to make the urine less acidic,” Henderson says. “And even then, maybe cranberries only work in people who have the right gut microbes.”

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The investigators also studied the bacteria’s strategies for resisting the body’s innate immunity. E.coli make a compound called enterobactin that binds strongly to iron, stealing it from the host. The new study showed that enterobactin is particularly good at binding iron in urine. So finding ways to block it may open up new opportunities for developing antimicrobial drugs that work very differently from traditional antibiotics.

The researchers say there are many future directions for this research, including working out more of the details governing whether the body or the bacteria will win the battle over iron, and exploring the specifics of the gut microbiomes of their healthy volunteers.

The study appears in the Journal of Biological Chemistry.

The National Institutes of Health (NIH), including the National Institute of Diabetes and Digestive and Kidney Diseases; the National Center for Advancing Translational Sciences; the Longer Life Foundation; United States Public Health Service; a Career Award for Medical Scientists from the Burroughs Wellcome Fund; a Monsanto Excellence Fund Graduate Fellowship; and the Barnes-Jewish Hospital Patient Safety & Quality Fellowship Program supported the work.

Source: Washington University in St. Louis

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About one in five wounded soldiers suffers from traumatic brain injury, and an estimated 52 percent of those injuries are blast-induced neurotrauma.

Some of those brain injuries are difficult to diagnose because people don’t always display obvious motor impairment or other neurological symptoms.

“Many times they don’t even realize they’ve been injured, and this is particularly alarming because these injuries have been linked to severe long-term psychiatric and degenerative neurological dysfunction,” says Riyi Shi, a professor in the basic medical sciences department and school of biomedical engineering at Purdue University.

“The underlying mechanisms of injury remain poorly understood, impeding development of diagnostic and treatment strategies.”

[IED blasts leave scars on brain]

The initial injury is caused by the shock wave from explosions. However, secondary damage can take place in the days and weeks that follow the initial injury—and this secondary damage might be treatable.

Scientists have developed a new strategy to establish a clinically relevant “animal model” that recreates typical human symptom profiles. The model can be used to study the effects and pinpoint mechanisms responsible for ongoing damage that occurs following the initial injury, Shi says.

The findings, published in the Journal of Neurosurgery, suggest that a simple urine test could be used to diagnose the injury—and damaging effects might be alleviated through drug therapy that reduces the concentration of a toxic compound produced by traumatized cells.

Long-term consequences

“Early detection and intervention could potentially mitigate or prevent delayed onset development of significant neurological dysfunction,” Shi says.

The research shows evidence of brain inflammation that may indicate ongoing damage, potentially leading to altered brain function and degenerative diseases.

“We detected structural and biochemical brain damage without obvious motor or cognitive deficits,” Shi says. “These findings highlight the difficulty and importance of early detection, indicating missed early diagnosis and subsequent lack of intervention could lead to serious long-term consequences.”

[Military sensors capture blast data]

A neurotoxin called acrolein is produced within the body after nerve cells are damaged and has been shown to lead to continued damage.  However, the concentration of acrolein could be reduced using the drug hydralazine, which has been approved by the US Food and Drug Administration for hypertension.

The drug was shown to be effective in reducing acrolein levels in previous research led by Shi, who is working to develop a low-dose version for that purpose in humans.

New findings indicate elevated levels of acrolein in brain tissue and in urine from research animals lacking neurological signs of damage. Acrolein concentrations were three times the normal level the first day of the experiment and remained elevated five days later.

Urine tests showing elevated acrolein might indicate trauma despite the lack of symptoms following mild blast injury. Treatment at this point could reduce the risk of developing chronic neurological diseases, Shi says.

The Indiana State Department of Health, National Institutes of Health, and an Indiana CTSI Collaboration in Biomedical Translational Research Pilot Program Grant provided support for the research.

Source: Purdue University

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Two chemical scents in the urine of female mice drive males wild. When scientists removed the chemicals from the pee, males lost interest in mating.

“Science has long recognized that urine, sweat, and other bodily fluids contain chemical communication signals called pheromones that can influence the biology or behavior of others,” says senior author Timothy E. Holy, associate professor of neurobiology and anatomy at Washington University in St. Louis.

“Most mammals use the information in these signals for social purposes, such as establishing territory or dominance, or in courtship and mating. In many cases, though, the specific chemical identities of the signals are unknown.”

The new study, published in the journal Cell, took advantage of the neurons in the noses of male mice to start narrowing down the compounds of interest. Using a new technique developed to identify pheromones in complex mixtures, researchers narrowed down a list of 1,600 potentially relevant chemicals in male and female mouse urine to a list of just 23. Among those 23 chemicals might be signals that convey information about sex, age, dominance, and other factors.

[Does dad’s ‘cologne’ make baby mice smarter?]

Researchers then focused on neurons that fired in response to all samples of female urine but no samples of male urine, hoping that these neurons would lead them to female sex pheromones. Only two of the 23 chemicals fit the pattern. Through collaboration with Michael L. Gross, professor of chemistry, the scientists discovered that both chemicals are waste products of steroid metabolism.

“Mice make hormones and steroids that regulate aspects of their physiology,” Holy says. “At some point, those hormones have to be cleared out and converted into waste products. So when an animal’s nose detects the waste products from another animal, it’s a bit like spying on the neighbors by going through their garbage. These chemicals send signals about what’s going on internally in another animal.”

The firing patterns of the male olfactory neurons in different strains of mice when exposed to various female urine samples implicated the two specific chemicals, providing the first evidence that they have a role in social communication by activating neurons in the nose.

“Male mice will spend a lot of time investigating female urine,” Holy says. “But they show very little interest in male urine—one sniff and they move on—and similarly little interest in the urine of female mice after their ovaries have been removed. So presumably there is some cue in normal female urine that attracts male interest.”

But beyond simply measuring the activity of neurons, the researchers analyzed male mouse behavior when exposed to the two chemicals.

[Bumblebee pheromones aren’t so simple after all]

“These two compounds alone are very good at mimicking the increased interest that males show to female mouse urine,” Holy says. “If you take one or both of these compounds and add them to male mouse urine—a stimulus male mice normally spend little time with—all of a sudden they become much more interested. It doesn’t explain the whole effect of female urine on male mice, but it explains a large fraction of the response. We think there’s still some component of the response to female urine that we’re not mimicking yet.”

Similarly, applying these chemicals to the bodies of female mice without ovaries substantially increased the number of times males attempted to mate with them. And conversely, the researchers showed that removing these two chemicals from female mouse urine substantially reduced male mating behavior.

The study is an important piece of the puzzle in understanding the neurobiology of mammals, Holy says.

“One of the nice things about this pheromone system is that it’s a relatively simple and compact neural circuit in a complicated animal. It doesn’t occupy a large percentage of the mouse’s brain and yet it does interesting things like sex recognition, decision making and learning. It’s great that we now have a new set of tools to manipulate neurons and see how they respond and what the downstream consequences are.”

The National Institutes of Health supported the work.

Source: Washington University in St. Louis

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Bearcats, also known as binturongs, smell just like buttered popcorn. For many zookeepers, the smell wafting from the binturong enclosure is so striking that they name their resident binturongs after the popular snack.

Solitary animals that rarely come face to face, binturongs use their roasty, popcorn-like aroma as a calling card to say “this is my turf” and find potential mates.

Previous studies searched for compounds in secretions from the scent glands under the binturong’s tail that could explain its signature scent, but nothing turned up.

[Male mice can’t resist 2 chemicals in female pee]

For a new paper, researchers analyzed urine samples collected during routine physical examinations of 33 binturongs at Carolina Tiger Rescue, a nonprofit wildlife sanctuary in Pittsboro, North Carolina.

Binturongs pee in a squatting position, soaking their feet and bushy tails in the process. They also drag their tails as they move about in the trees, leaving a scent trail on the branches and leaves behind them.

Using a technique called gas chromatography-mass spectrometry, the researchers identified 29 chemical compounds in the animals’ urine. The one compound that emanated from every sample was 2-acetyl-1-pyrroline, or 2-AP—the same compound that gives popcorn its tantalizing scent.

What’s more, 2-AP was among the few compounds that lingered and became more dominant over time, a fact the researchers discovered when a rush airmail shipment of frozen binturong urine was delayed on a hot tarmac en route to coauthor Thomas Goodwin of Hendrix College in Arkansas for analysis.

How do they do it?

Males secrete more 2-AP than females. “The fact that the compound was in every binturong we studied, and at relatively high concentrations, means it could be a signal that says, ‘A binturong was here,’ and whether it was male or female,” says Lydia Greene, a graduate student at Duke University and first author of the study that is published in the journal the Science of Nature.

The compound 2-AP normally forms in popcorn during the popping process, when heat kicks off reactions between sugars and amino acids in the corn kernels. The cooking produces a variety of new odor and flavor molecules in a chemical reaction called the Maillard reaction. The same compound is also responsible for the comforting aromas of toasted bread and cooked rice.

“If you were to make this compound, you would have to use temperatures above what most animals can achieve physiologically,” says Christine Drea, professor of evolutionary anthropology at Duke who led the study. “How does this animal make a cooking smell, but without cooking?”

[Smell can sweeten birds’ chances of mating]

It could be that binturong urine smells funny because of something they eat. The team searched for 2-AP in the binturongs’ kibble, the one cooked item in their diet, but they didn’t detect any.

A more likely explanation, is that 2-AP is produced when binturong urine comes in contact with bacteria and other microorganisms that live on the animal’s skin or fur or in its gut.

Bacteria make smelly compounds as they break down sweat in our armpits in much the same way, Drea says.

The time-release action of the microbes could help the binturongs’ urine smell-o-grams last long after the animals move on, an essential mode of communication for solitary animals that rarely encounter each other.

Tim Wallen of the Centers for Disease Control and Prevention and Anneke Moresco of the Cincinnati Zoo are coauthors of the study. Duke, Hendrix College, and the National Science Foundation funded the work.

Source: Duke University

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An experimental system could ease the burden urine tests put on clinics and primary care doctors. A smartphone camera on top of an easily assembled box captures video and accurately analyzes color changes in a standard paper dipstick.

The simple, color-changing paper tests can measure levels of glucose, blood, protein, and other chemicals, which in turn can indicate evidence of kidney disease, diabetes, urinary tract infections, and even signs of bladder cancer.

The simple test is powerful, but it isn’t perfect: It takes time, costs money, and often gives inconclusive results that require both patient and doctor to book another appointment. Patients with long-term conditions like chronic urinary tract infections must wait for results to confirm what both patient and doctor already know before getting antibiotics. Tracking patients’ progress with multiple urine tests a day is out of the question.

In the past, innovators have created a low-cost way to analyze the urinary dipstick in any setting, even at home.

Although the test seems simple, do-it-yourself systems can be error prone, says Audrey (Ellerbee) Bowden, assistant professor of electrical engineering at Stanford University.

“You think it’s easy—you just dip the stick in urine and look for the color change, but there are things that can go wrong,” she says. “Doctors don’t end up trusting those results as accurate.”

[Urine acidity may affect odds of UTI]

Writing in Lab on a Chip, Bowden and Gennifer Smith, a PhD student in electrical engineering, detail their new low-cost, portable device that would allow patients to get consistently accurate urine test results at home, easing the workload on primary care physicians.

Other do-it-yourself systems are emerging, but the Stanford engineers think their approach is inexpensive and reliable, in part because they base their system on the same tried and trusted dipstick used in medical offices.

Fool-proofing three ways

Invented to test blood sugar in 1956, the standard dipstick test is now a paper strip with 10 square pads. Dipped in a sample, each pad changes color to screen for the presence of a different disease-indicating chemical. After waiting the appropriate amount of time, a medical professional—or, increasingly, an automated system—compares the pad shades to a color reference chart for results.

Considering the dipstick as a given, Bowden and Smith designed a system to overcome three main potential errors in a home test: lighting, volume control, and timing.

As a color-based test, the dipstick needs consistent lighting conditions. The same color can look different depending on its background, so Smith and Bowden created a black box that covers the dipstick. Its flat, interlocking parts make it easy to mail, store, and assemble.

They also tackled volume control. “If you have too little or too much urine on the dipstick, you’ll get erroneous results,” Smith says.

[Urine test might detect brain injury from blasts]

To fix this, the engineers designed a multi-layered system to load urine onto the dipstick. A dropper squeezes urine into a hole in the first layer, filling up a channel in the second layer and ten square holes in the third layer. When the third layer is inserted into the black box, some clever engineering ensures that a uniform volume of urine is deposited on each of the ten pads on the dipstick at just the right time.

Finally, a smartphone is placed on top of the black box with the video camera focused on the dipstick inside the box. Custom software reads video from the smartphone and controls the timing and color analysis.

To perform the test a person would load the urine and then push the third layer into the box. When the third layer hits the back of the box, it signals the phone to begin the video recording at the precise moment when the urine is deposited on the pads.

Timing is critical to the analysis. Pads have readout times ranging from 30 seconds to 2 minutes. Once the two minutes are up, the person can transfer the recording to a software program on their computer. For each pad, it pulls out the frames from the correct time and reads out the results.

An app for that

In the future, the engineers would like to design an app that would do the analysis on the phone and then send results directly to the doctor.

Meanwhile, they are working with the Stanford Office of Technology Licensing to see whether and how the idea might be commercialized, either as a home test in developed nations or as a baseline medical instrument in areas that don’t have easy access to well-stocked clinics.

“It’s such a hassle to go into the doctor’s office for such a simple test,” says Smith. “This device can remove the burden in developed countries and in facilities where they don’t have the resources to do these tests.”

Funding for this research came from the National Institutes of Health, the Rose Hills Foundation Graduate Engineering Fellowship, the Electrical Engineering Department New Projects Graduate Fellowship, the Oswald G. Villard Jr. Engineering Fellowship, the Stanford Graduate Fellowship, and the National Science Foundation Graduate Research Fellowship.

Source: Shara Tonn for Stanford University

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In coral reefs where fishing occurs, nearly half of key nutrients are missing from the ecosystem. Why? Fewer large-bodied and predator fish are around to pee in the water.

When fish urinate, they release phosphorus into the water. This phosphorus, along with nitrogen excreted as ammonium through the gills of fish, is crucial to the survival and growth of coral reefs.

“If biomass is shrinking, there are fewer fish to pee.”

“Part of the reason coral reefs work is because animals play a big role in moving nutrients around,” says Jacob Allgeier, a postdoctoral researcher at the University of Washington’s School of Aquatic and Fishery Sciences, and lead author of the study in Nature Communications.

“Fish hold a large proportion, if not most of the nutrients in a coral reef in their tissue, and they’re also in charge of recycling them. If you take the big fish out, you’re removing all of those nutrients from the ecosystem.”

50 percent fewer nutrients

Coauthors Abel Valdivia at the Center for Biological Diversity in San Francisco and Courtney Cox at Smithsonian Marine Station at Fort Pierce, Florida, surveyed 143 fish species at 110 sites across 43 Caribbean coral reefs that varied in the amount of fishing pressure sustained—ranging from marine preserves that banned all fishing to heavily fished reefs where large predator fish are almost gone.

Tiny creatures ‘pee’ enough to shift ocean chemistry

The researchers found that reefs with more large, predator fish had healthy levels of nutrients, while reefs depleted of large fish had nearly 50 percent fewer nutrients, including phosphorous and nitrogen, essential to their survival.

“This study is useful to understand alternative ways fishing is affecting coral reef ecosystems,” Allgeier says.

Missing fish biomass

The researchers determined that, despite the substantial reduction in fish-mediated nutrients, fishing didn’t substantially reduce the number of fish species present. Instead, the large reductions in fish pee were driven by the reduction of large-bodied fish and predator fish such as grouper, snapper, or barracuda that occurs through selective fishing practices.

“Simply stated, fish biomass in coral reefs is being reduced by fishing pressure. If biomass is shrinking, there are fewer fish to pee,” Allgeier says.

Phosphorus in fish pee and nitrogen excreted through their gills are important nutrients for coral reefs to grow. In many reef communities, fish will take shelter in and around coral during the day—peeing out valuable nutrients—then forage for prey in and around the reef by night.

Big or small, animals take about 20 seconds to pee

A Science paper in the 1980s showed that coral reefs where fish were present grew at more than double the speed of reefs where fish were absent. It was that study, undertaken by now emeritus research professor Judith Meyer at the University of Georgia, that inspired Allgeier to figure out why fish help coral reefs grow.

Coral reefs are the very definition of a delicate ecosystem. They are highly productive in terms of the biodiversity they support, but there aren’t a lot of nutrients to spare. Reefs operate on what scientists call a “tight” nutrient cycle, meaning there must be an efficient transfer of nutrients for coral to grow. This cycle is largely controlled by fish, which hold nutrients in their tissue and then excrete them through their gills and urine.

Allgeier spent four years measuring the amount of nutrients in fish pee and fish tissue to eventually build a massive dataset that tracks fish size and nutrient output and the amount they store in their tissue.

As a graduate student, Allgeier’s kitchen on Abaco Island in the Bahamas became his lab, and he caught hundreds of live fish, put them in plastic bags for half an hour, then measured the nutrients in the water before and after. He found that nitrogen output varied consistently with body size among all fish, and that carnivorous fish would pee more phosphorus than smaller herbivores.

Now, with these data serving as the basis for their models, Allgeier and collaborators can estimate the total amount of nutrient output from fish by knowing the species and body size of fish in a coral reef community.

“It’s remarkable how robust the models are just from knowing fish size and species,” he adds.

Coral reefs continue to decline in the Caribbean and worldwide, but curbing fishing practices that target large predator fish could help reefs recover, Allgeier says.

The researchers expect this relationship between fish and coral exists in other reefs around the world. Allgeier is currently working with researchers at the University of California, Santa Barbara, to collect data next on fish pee in tropical Pacific Ocean reefs.

Craig Layman of North Carolina State University is the paper’s other coauthor. The Environmental Protection Agency and the National Science Foundation supported the work.

Source: University of Washington

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When women suffer from bladder incontinence, the urge to urinate can come on suddenly and sometimes uncontrollably, leading to leaks.

Patients looking for relief can initially opt for first- and second-line therapies such as drinking fewer liquids or caffeinated beverages, pelvic floor muscle training, and medication.

If those treatments don’t offer relief, more invasive options are available, including nerve stimulation called sacral neuromodulation (an implanted device sold as InterStim), or a bladder injection of botulinum toxin, sold as Botox.

Researchers conducted a head-to-head comparison of the two and discovered that Botox provides more daily relief for women—but also might be associated with more adverse events.

An injection of botulinum toxin in the bladder muscle works to address urgency urinary incontinence by relaxing the overactive bladder muscles that cause the condition. A sacral neuromodulation implant does the same thing by sending electrical pulses to nerves in the spine.

Demand for female urologists outpaces supply

“Urgency urinary incontinence is common, with 17 percent of women over age 45 and 25 percent of women over age 75 suffering from it,” says Cindy L. Amundsen, professor of obstetrics and gynecology at Duke University School of Medicine. “That’s why it’s important for both patients and health care providers to have information that can guide their choice between these two therapies.”

Published in the Journal of the American Medical Association, the study involved 381 women from nine US medical centers who recorded at least six urgency incontinent episodes over three consecutive days and had not improved with other treatments.

Participants were randomly assigned to either receive sacral neuromodulation or a 200-unit injection of botulinum toxin. After a trial period to test their responsiveness to the therapies, 364 women were enrolled and followed for six months after treatment.

Researchers analyzed the number of urgency incontinent episodes on monthly “bladder diaries.” Participants who received botulinum toxin saw their number of daily urgency incontinent episodes decrease by 3.9 on average versus 3.3 on average in the sacral neuromodulation group. The difference was statistically significant.

Toxin in Botox can travel through nerves

Botulinum toxin participants also reported a greater reduction in bothersome symptoms, higher satisfaction with treatment, and a greater likelihood of endorsing the treatment.

Additionally, among participants who completed at least four monthly diaries, a higher percentage of botulinum toxin participants saw at least a 75-percent reduction in or complete resolution of urgency incontinent symptoms. However, the Botox patients also had three times the rate of urinary tract infections. Some botulinum toxin participants also required intermittent self-catheterization, although at lower rates than reported in previous studies using this dose.

The most common adverse event for the sacral neuromodulation participants was removal or revision of the implant during the six months. This occurred at a low rate, similar to previous studies.

“This study is valuable because it is the first randomized trial comparing the efficacy of two FDA-approved, third-line therapies in a severely affected population,” Amundsen says. “The information should help guide care.”

While the study didn’t compare the cost of the two treatments, patients who receive botulinum toxin may require additional injections as part of continued treatment. Additionally, the study only takes Botox into account and no conclusions can be drawn for other botulinum toxin preparations that may be used to treat urgency incontinence.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women’s Health funded the work. One coauthor reported financial relationships with the commercial makers of both InterStim and Botox. Full disclosures are available in the study’s manuscript.

Source: Duke University

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A battery made with urea, commonly found in fertilizers and mammal urine, could provide a low-cost way of storing energy produced through solar power or other forms of renewable energy for consumption during off hours.

The battery is nonflammable and contains electrodes made from abundant aluminum and graphite. Its electrolyte’s main ingredient, urea, is already industrially produced by the ton for plant fertilizers.

“Who would have thought you could take graphite, aluminum, urea, and actually make a battery that can cycle for a pretty long time?”

“So essentially, what you have is a battery made with some of the cheapest and most abundant materials you can find on Earth. And it actually has good performance,” says Hongjie Dai, chemistry professor at Stanford University. “Who would have thought you could take graphite, aluminum, urea, and actually make a battery that can cycle for a pretty long time?”

In 2015, Dai’s lab was the first to make a rechargeable aluminum battery. This system charged in less than a minute and lasted thousands of charge-discharge cycles. The lab collaborated with Taiwan’s Industrial Technology Research Institute (ITRI) to power a motorbike with this older version, that had one major drawback: it involved an expensive electrolyte.

The newest version includes a urea-based electrolyte and is about 100 times cheaper than the 2015 model, with higher efficiency and a charging time of 45 minutes. It’s the first time urea has been used in a battery. The cost difference between the two batteries, Dai says, is “like night and day.” The findings appear in the Proceedings of the National Academy of Sciences.

Unlike energy derived from fossil fuels, solar energy can essentially be harnessed only when the sun is shining. A solar panel pumps energy into the electrical grid during daylight hours. If that energy isn’t consumed right away, it is lost as heat. As the demand for renewable technologies grows, so does the need for cheap, efficient batteries to store the energy for release at night. Today’s batteries, like lithium-ion or lead acid batteries, are costly and have limited lifespans.

Solar homes could get batteries from this glowing dye

The new battery could provide a solution to the grid’s storage problem, says doctoral candidate Michael Angell. “It’s cheap. It’s efficient. Grid storage is the main goal.”

Grid storage is also the most realistic goal, because of the battery’s low cost, high efficiency, and long cycle life, Angell says. One kind of efficiency, called Coulombic efficiency, is a measurement of how much charge exits the battery per unit of charge that it takes in during charging. The Coulombic efficiency for this battery is high—99.7 percent.

Though also efficient, lithium-ion batteries commonly found in small electronics and other devices can be flammable. By contrast, the urea battery is inflammable and therefore less risky.

“I would feel safe if my backup battery in my house is made of urea with little chance of causing fire,” Dai says.

How to store solar energy by heating up rust

To meet the demands of grid storage, a commercial battery will need to last at least ten years. By investigating the chemical processes inside the battery, Angell hopes to extend its lifetime. The outlook is promising. In the lab, these urea-based aluminum ion batteries can go through about 1,500 charge cycles with a 45-minute charging time.

“With this battery, the dream is for solar energy to be stored in every building and every home,” Dai says. “Maybe it will change everyday life. We don’t know.”

The battery’s patents have been licensed to AB Systems, founded by Dai. A commercial version is currently in development.

The US Department of Energy, the Global Networking Talent 3.0 Plan, the Ministry of Education of Taiwan, and the Taishan Scholar Project funded the work.

Source: Jackie Flynn for Stanford University

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The acidity of urine—as well as the presence of small molecules related to diet—may influence how well bacteria can grow in the urinary tract, a new study shows.

The research may have implications for treating urinary tract infections, which are among the most common bacterial infections worldwide.

Urinary tract infections (UTIs) often are caused by a strain of bacteria called Escherichia coli (E. coli), and doctors long have relied on antibiotics to kill the microbes. But increasing bacterial resistance to these drugs is leading researchers to look for alternative treatment strategies.

“Many physicians can tell you that they see patients who are particularly susceptible to urinary tract infections,” says senior author Jeffrey P. Henderson, assistant professor of medicine at Washington University School of Medicine in St. Louis.

“We often don’t know why certain people seem to be prone to recurrent UTIs. For a long time, we had inexpensive antibiotics that worked really well for this. But over the last 10-15 years, we have seen a huge jump in bacterial infections that are resistant to many of these drugs.”

Pee pH

With this in mind, Henderson and his team, including first author Robin R. Shields-Cutler, a graduate student in Henderson’s lab, were interested in studying how the body naturally fights bacterial infections. They cultured E. coli in urine samples from healthy volunteers and noted major differences in how well individual urine samples could harness a key immune protein to limit bacterial growth.

“We could divide these urine samples into two groups based on whether they permitted or restricted bacterial growth,” Henderson says. “Then we asked, what is special about the urine samples that restricted growth?”

The urine samples that prevented bacterial growth supported more activity of this key protein, which the body makes naturally in response to infection, than the samples that permitted bacteria to grow easily.

The protein is called siderocalin, and past research has suggested that it helps the body fight infection by depriving bacteria of iron, a mineral necessary for bacterial growth. Their data led the researchers to ask if any characteristics of their healthy volunteers were associated with the effectiveness of siderocalin.

“Age and sex did not turn out to be major players,” Shields-Cutler says. “Of all the factors we measured, the only one that was really different between the two groups was pH—how acidic or basic the urine was.”

‘An incredibly complex medium’

Henderson says that conventional wisdom in medicine favors the idea that acidic urine is better for restricting bacterial growth. But their results were surprising because samples that were less acidic, closer to the neutral pH of pure water, showed higher activity of the protein siderocalin and were better at restricting bacterial growth than the more acidic samples.

Importantly, the researchers also showed that they could encourage or discourage bacterial growth in urine simply by adjusting the pH, a finding that could have implications for how patients with UTIs are treated.

“Physicians are very good at manipulating urinary pH,” says Henderson, who treats patients with UTIs. “If you take Tums, for example, it makes the urine less acidic. But pH is not the whole story here. Urine is a destination for much of the body’s waste in the form of small molecules. It’s an incredibly complex medium that is changed by diet, individual genetics, and many other factors.”

After analyzing thousands of compounds in the samples, the researchers determined that the presence of small metabolites called aromatics, which vary depending on a person’s diet, also contributed to variations in bacterial growth. Samples that restricted bacterial growth had more aromatic compounds, and urine that permitted bacterial growth had fewer.

Iron binders

Henderson and his colleagues suspect that at least some of these aromatics are good iron binders, helping deprive the bacteria of iron. And perhaps surprisingly, these molecules are not produced by human cells, but by a person’s gut microbes as they process food in the diet.

“Our study suggests that the body’s immune system harnesses dietary plant compounds to prevent bacterial growth,” Henderson says. “We identified a list of compounds of interest, and many of these are associated with specific dietary components and with gut microbes.”

Indeed, their results implicate cranberries among other possible dietary interventions. Shield-Cutler note that many studies already have investigated extracts or juices from cranberries as UTI treatments but the results of such investigations have not been consistent.

“Its possible that cranberries may be more effective when paired with a treatment to make the urine less acidic,” Henderson says. “And even then, maybe cranberries only work in people who have the right gut microbes.”

[related]

The investigators also studied the bacteria’s strategies for resisting the body’s innate immunity. E.coli make a compound called enterobactin that binds strongly to iron, stealing it from the host. The new study showed that enterobactin is particularly good at binding iron in urine. So finding ways to block it may open up new opportunities for developing antimicrobial drugs that work very differently from traditional antibiotics.

The researchers say there are many future directions for this research, including working out more of the details governing whether the body or the bacteria will win the battle over iron, and exploring the specifics of the gut microbiomes of their healthy volunteers.

The study appears in the Journal of Biological Chemistry.

The National Institutes of Health (NIH), including the National Institute of Diabetes and Digestive and Kidney Diseases; the National Center for Advancing Translational Sciences; the Longer Life Foundation; United States Public Health Service; a Career Award for Medical Scientists from the Burroughs Wellcome Fund; a Monsanto Excellence Fund Graduate Fellowship; and the Barnes-Jewish Hospital Patient Safety & Quality Fellowship Program supported the work.

Source: Washington University in St. Louis

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About one in five wounded soldiers suffers from traumatic brain injury, and an estimated 52 percent of those injuries are blast-induced neurotrauma.

Some of those brain injuries are difficult to diagnose because people don’t always display obvious motor impairment or other neurological symptoms.

“Many times they don’t even realize they’ve been injured, and this is particularly alarming because these injuries have been linked to severe long-term psychiatric and degenerative neurological dysfunction,” says Riyi Shi, a professor in the basic medical sciences department and school of biomedical engineering at Purdue University.

“The underlying mechanisms of injury remain poorly understood, impeding development of diagnostic and treatment strategies.”

[IED blasts leave scars on brain]

The initial injury is caused by the shock wave from explosions. However, secondary damage can take place in the days and weeks that follow the initial injury—and this secondary damage might be treatable.

Scientists have developed a new strategy to establish a clinically relevant “animal model” that recreates typical human symptom profiles. The model can be used to study the effects and pinpoint mechanisms responsible for ongoing damage that occurs following the initial injury, Shi says.

The findings, published in the Journal of Neurosurgery, suggest that a simple urine test could be used to diagnose the injury—and damaging effects might be alleviated through drug therapy that reduces the concentration of a toxic compound produced by traumatized cells.

Long-term consequences

“Early detection and intervention could potentially mitigate or prevent delayed onset development of significant neurological dysfunction,” Shi says.

The research shows evidence of brain inflammation that may indicate ongoing damage, potentially leading to altered brain function and degenerative diseases.

“We detected structural and biochemical brain damage without obvious motor or cognitive deficits,” Shi says. “These findings highlight the difficulty and importance of early detection, indicating missed early diagnosis and subsequent lack of intervention could lead to serious long-term consequences.”

[Military sensors capture blast data]

A neurotoxin called acrolein is produced within the body after nerve cells are damaged and has been shown to lead to continued damage.  However, the concentration of acrolein could be reduced using the drug hydralazine, which has been approved by the US Food and Drug Administration for hypertension.

The drug was shown to be effective in reducing acrolein levels in previous research led by Shi, who is working to develop a low-dose version for that purpose in humans.

New findings indicate elevated levels of acrolein in brain tissue and in urine from research animals lacking neurological signs of damage. Acrolein concentrations were three times the normal level the first day of the experiment and remained elevated five days later.

Urine tests showing elevated acrolein might indicate trauma despite the lack of symptoms following mild blast injury. Treatment at this point could reduce the risk of developing chronic neurological diseases, Shi says.

The Indiana State Department of Health, National Institutes of Health, and an Indiana CTSI Collaboration in Biomedical Translational Research Pilot Program Grant provided support for the research.

Source: Purdue University

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Two chemical scents in the urine of female mice drive males wild. When scientists removed the chemicals from the pee, males lost interest in mating.

“Science has long recognized that urine, sweat, and other bodily fluids contain chemical communication signals called pheromones that can influence the biology or behavior of others,” says senior author Timothy E. Holy, associate professor of neurobiology and anatomy at Washington University in St. Louis.

“Most mammals use the information in these signals for social purposes, such as establishing territory or dominance, or in courtship and mating. In many cases, though, the specific chemical identities of the signals are unknown.”

The new study, published in the journal Cell, took advantage of the neurons in the noses of male mice to start narrowing down the compounds of interest. Using a new technique developed to identify pheromones in complex mixtures, researchers narrowed down a list of 1,600 potentially relevant chemicals in male and female mouse urine to a list of just 23. Among those 23 chemicals might be signals that convey information about sex, age, dominance, and other factors.

[Does dad’s ‘cologne’ make baby mice smarter?]

Researchers then focused on neurons that fired in response to all samples of female urine but no samples of male urine, hoping that these neurons would lead them to female sex pheromones. Only two of the 23 chemicals fit the pattern. Through collaboration with Michael L. Gross, professor of chemistry, the scientists discovered that both chemicals are waste products of steroid metabolism.

“Mice make hormones and steroids that regulate aspects of their physiology,” Holy says. “At some point, those hormones have to be cleared out and converted into waste products. So when an animal’s nose detects the waste products from another animal, it’s a bit like spying on the neighbors by going through their garbage. These chemicals send signals about what’s going on internally in another animal.”

The firing patterns of the male olfactory neurons in different strains of mice when exposed to various female urine samples implicated the two specific chemicals, providing the first evidence that they have a role in social communication by activating neurons in the nose.

“Male mice will spend a lot of time investigating female urine,” Holy says. “But they show very little interest in male urine—one sniff and they move on—and similarly little interest in the urine of female mice after their ovaries have been removed. So presumably there is some cue in normal female urine that attracts male interest.”

But beyond simply measuring the activity of neurons, the researchers analyzed male mouse behavior when exposed to the two chemicals.

[Bumblebee pheromones aren’t so simple after all]

“These two compounds alone are very good at mimicking the increased interest that males show to female mouse urine,” Holy says. “If you take one or both of these compounds and add them to male mouse urine—a stimulus male mice normally spend little time with—all of a sudden they become much more interested. It doesn’t explain the whole effect of female urine on male mice, but it explains a large fraction of the response. We think there’s still some component of the response to female urine that we’re not mimicking yet.”

Similarly, applying these chemicals to the bodies of female mice without ovaries substantially increased the number of times males attempted to mate with them. And conversely, the researchers showed that removing these two chemicals from female mouse urine substantially reduced male mating behavior.

The study is an important piece of the puzzle in understanding the neurobiology of mammals, Holy says.

“One of the nice things about this pheromone system is that it’s a relatively simple and compact neural circuit in a complicated animal. It doesn’t occupy a large percentage of the mouse’s brain and yet it does interesting things like sex recognition, decision making and learning. It’s great that we now have a new set of tools to manipulate neurons and see how they respond and what the downstream consequences are.”

The National Institutes of Health supported the work.

Source: Washington University in St. Louis

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Bearcats, also known as binturongs, smell just like buttered popcorn. For many zookeepers, the smell wafting from the binturong enclosure is so striking that they name their resident binturongs after the popular snack.

Solitary animals that rarely come face to face, binturongs use their roasty, popcorn-like aroma as a calling card to say “this is my turf” and find potential mates.

Previous studies searched for compounds in secretions from the scent glands under the binturong’s tail that could explain its signature scent, but nothing turned up.

[Male mice can’t resist 2 chemicals in female pee]

For a new paper, researchers analyzed urine samples collected during routine physical examinations of 33 binturongs at Carolina Tiger Rescue, a nonprofit wildlife sanctuary in Pittsboro, North Carolina.

Binturongs pee in a squatting position, soaking their feet and bushy tails in the process. They also drag their tails as they move about in the trees, leaving a scent trail on the branches and leaves behind them.

Using a technique called gas chromatography-mass spectrometry, the researchers identified 29 chemical compounds in the animals’ urine. The one compound that emanated from every sample was 2-acetyl-1-pyrroline, or 2-AP—the same compound that gives popcorn its tantalizing scent.

What’s more, 2-AP was among the few compounds that lingered and became more dominant over time, a fact the researchers discovered when a rush airmail shipment of frozen binturong urine was delayed on a hot tarmac en route to coauthor Thomas Goodwin of Hendrix College in Arkansas for analysis.

How do they do it?

Males secrete more 2-AP than females. “The fact that the compound was in every binturong we studied, and at relatively high concentrations, means it could be a signal that says, ‘A binturong was here,’ and whether it was male or female,” says Lydia Greene, a graduate student at Duke University and first author of the study that is published in the journal the Science of Nature.

The compound 2-AP normally forms in popcorn during the popping process, when heat kicks off reactions between sugars and amino acids in the corn kernels. The cooking produces a variety of new odor and flavor molecules in a chemical reaction called the Maillard reaction. The same compound is also responsible for the comforting aromas of toasted bread and cooked rice.

“If you were to make this compound, you would have to use temperatures above what most animals can achieve physiologically,” says Christine Drea, professor of evolutionary anthropology at Duke who led the study. “How does this animal make a cooking smell, but without cooking?”

[Smell can sweeten birds’ chances of mating]

It could be that binturong urine smells funny because of something they eat. The team searched for 2-AP in the binturongs’ kibble, the one cooked item in their diet, but they didn’t detect any.

A more likely explanation, is that 2-AP is produced when binturong urine comes in contact with bacteria and other microorganisms that live on the animal’s skin or fur or in its gut.

Bacteria make smelly compounds as they break down sweat in our armpits in much the same way, Drea says.

The time-release action of the microbes could help the binturongs’ urine smell-o-grams last long after the animals move on, an essential mode of communication for solitary animals that rarely encounter each other.

Tim Wallen of the Centers for Disease Control and Prevention and Anneke Moresco of the Cincinnati Zoo are coauthors of the study. Duke, Hendrix College, and the National Science Foundation funded the work.

Source: Duke University

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An experimental system could ease the burden urine tests put on clinics and primary care doctors. A smartphone camera on top of an easily assembled box captures video and accurately analyzes color changes in a standard paper dipstick.

The simple, color-changing paper tests can measure levels of glucose, blood, protein, and other chemicals, which in turn can indicate evidence of kidney disease, diabetes, urinary tract infections, and even signs of bladder cancer.

The simple test is powerful, but it isn’t perfect: It takes time, costs money, and often gives inconclusive results that require both patient and doctor to book another appointment. Patients with long-term conditions like chronic urinary tract infections must wait for results to confirm what both patient and doctor already know before getting antibiotics. Tracking patients’ progress with multiple urine tests a day is out of the question.

In the past, innovators have created a low-cost way to analyze the urinary dipstick in any setting, even at home.

Although the test seems simple, do-it-yourself systems can be error prone, says Audrey (Ellerbee) Bowden, assistant professor of electrical engineering at Stanford University.

“You think it’s easy—you just dip the stick in urine and look for the color change, but there are things that can go wrong,” she says. “Doctors don’t end up trusting those results as accurate.”

[Urine acidity may affect odds of UTI]

Writing in Lab on a Chip, Bowden and Gennifer Smith, a PhD student in electrical engineering, detail their new low-cost, portable device that would allow patients to get consistently accurate urine test results at home, easing the workload on primary care physicians.

Other do-it-yourself systems are emerging, but the Stanford engineers think their approach is inexpensive and reliable, in part because they base their system on the same tried and trusted dipstick used in medical offices.

Fool-proofing three ways

Invented to test blood sugar in 1956, the standard dipstick test is now a paper strip with 10 square pads. Dipped in a sample, each pad changes color to screen for the presence of a different disease-indicating chemical. After waiting the appropriate amount of time, a medical professional—or, increasingly, an automated system—compares the pad shades to a color reference chart for results.

Considering the dipstick as a given, Bowden and Smith designed a system to overcome three main potential errors in a home test: lighting, volume control, and timing.

As a color-based test, the dipstick needs consistent lighting conditions. The same color can look different depending on its background, so Smith and Bowden created a black box that covers the dipstick. Its flat, interlocking parts make it easy to mail, store, and assemble.

They also tackled volume control. “If you have too little or too much urine on the dipstick, you’ll get erroneous results,” Smith says.

[Urine test might detect brain injury from blasts]

To fix this, the engineers designed a multi-layered system to load urine onto the dipstick. A dropper squeezes urine into a hole in the first layer, filling up a channel in the second layer and ten square holes in the third layer. When the third layer is inserted into the black box, some clever engineering ensures that a uniform volume of urine is deposited on each of the ten pads on the dipstick at just the right time.

Finally, a smartphone is placed on top of the black box with the video camera focused on the dipstick inside the box. Custom software reads video from the smartphone and controls the timing and color analysis.

To perform the test a person would load the urine and then push the third layer into the box. When the third layer hits the back of the box, it signals the phone to begin the video recording at the precise moment when the urine is deposited on the pads.

Timing is critical to the analysis. Pads have readout times ranging from 30 seconds to 2 minutes. Once the two minutes are up, the person can transfer the recording to a software program on their computer. For each pad, it pulls out the frames from the correct time and reads out the results.

An app for that

In the future, the engineers would like to design an app that would do the analysis on the phone and then send results directly to the doctor.

Meanwhile, they are working with the Stanford Office of Technology Licensing to see whether and how the idea might be commercialized, either as a home test in developed nations or as a baseline medical instrument in areas that don’t have easy access to well-stocked clinics.

“It’s such a hassle to go into the doctor’s office for such a simple test,” says Smith. “This device can remove the burden in developed countries and in facilities where they don’t have the resources to do these tests.”

Funding for this research came from the National Institutes of Health, the Rose Hills Foundation Graduate Engineering Fellowship, the Electrical Engineering Department New Projects Graduate Fellowship, the Oswald G. Villard Jr. Engineering Fellowship, the Stanford Graduate Fellowship, and the National Science Foundation Graduate Research Fellowship.

Source: Shara Tonn for Stanford University

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In coral reefs where fishing occurs, nearly half of key nutrients are missing from the ecosystem. Why? Fewer large-bodied and predator fish are around to pee in the water.

When fish urinate, they release phosphorus into the water. This phosphorus, along with nitrogen excreted as ammonium through the gills of fish, is crucial to the survival and growth of coral reefs.

“If biomass is shrinking, there are fewer fish to pee.”

“Part of the reason coral reefs work is because animals play a big role in moving nutrients around,” says Jacob Allgeier, a postdoctoral researcher at the University of Washington’s School of Aquatic and Fishery Sciences, and lead author of the study in Nature Communications.

“Fish hold a large proportion, if not most of the nutrients in a coral reef in their tissue, and they’re also in charge of recycling them. If you take the big fish out, you’re removing all of those nutrients from the ecosystem.”

50 percent fewer nutrients

Coauthors Abel Valdivia at the Center for Biological Diversity in San Francisco and Courtney Cox at Smithsonian Marine Station at Fort Pierce, Florida, surveyed 143 fish species at 110 sites across 43 Caribbean coral reefs that varied in the amount of fishing pressure sustained—ranging from marine preserves that banned all fishing to heavily fished reefs where large predator fish are almost gone.

Tiny creatures ‘pee’ enough to shift ocean chemistry

The researchers found that reefs with more large, predator fish had healthy levels of nutrients, while reefs depleted of large fish had nearly 50 percent fewer nutrients, including phosphorous and nitrogen, essential to their survival.

“This study is useful to understand alternative ways fishing is affecting coral reef ecosystems,” Allgeier says.

Missing fish biomass

The researchers determined that, despite the substantial reduction in fish-mediated nutrients, fishing didn’t substantially reduce the number of fish species present. Instead, the large reductions in fish pee were driven by the reduction of large-bodied fish and predator fish such as grouper, snapper, or barracuda that occurs through selective fishing practices.

“Simply stated, fish biomass in coral reefs is being reduced by fishing pressure. If biomass is shrinking, there are fewer fish to pee,” Allgeier says.

Phosphorus in fish pee and nitrogen excreted through their gills are important nutrients for coral reefs to grow. In many reef communities, fish will take shelter in and around coral during the day—peeing out valuable nutrients—then forage for prey in and around the reef by night.

Big or small, animals take about 20 seconds to pee

A Science paper in the 1980s showed that coral reefs where fish were present grew at more than double the speed of reefs where fish were absent. It was that study, undertaken by now emeritus research professor Judith Meyer at the University of Georgia, that inspired Allgeier to figure out why fish help coral reefs grow.

Coral reefs are the very definition of a delicate ecosystem. They are highly productive in terms of the biodiversity they support, but there aren’t a lot of nutrients to spare. Reefs operate on what scientists call a “tight” nutrient cycle, meaning there must be an efficient transfer of nutrients for coral to grow. This cycle is largely controlled by fish, which hold nutrients in their tissue and then excrete them through their gills and urine.

Allgeier spent four years measuring the amount of nutrients in fish pee and fish tissue to eventually build a massive dataset that tracks fish size and nutrient output and the amount they store in their tissue.

As a graduate student, Allgeier’s kitchen on Abaco Island in the Bahamas became his lab, and he caught hundreds of live fish, put them in plastic bags for half an hour, then measured the nutrients in the water before and after. He found that nitrogen output varied consistently with body size among all fish, and that carnivorous fish would pee more phosphorus than smaller herbivores.

Now, with these data serving as the basis for their models, Allgeier and collaborators can estimate the total amount of nutrient output from fish by knowing the species and body size of fish in a coral reef community.

“It’s remarkable how robust the models are just from knowing fish size and species,” he adds.

Coral reefs continue to decline in the Caribbean and worldwide, but curbing fishing practices that target large predator fish could help reefs recover, Allgeier says.

The researchers expect this relationship between fish and coral exists in other reefs around the world. Allgeier is currently working with researchers at the University of California, Santa Barbara, to collect data next on fish pee in tropical Pacific Ocean reefs.

Craig Layman of North Carolina State University is the paper’s other coauthor. The Environmental Protection Agency and the National Science Foundation supported the work.

Source: University of Washington

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When women suffer from bladder incontinence, the urge to urinate can come on suddenly and sometimes uncontrollably, leading to leaks.

Patients looking for relief can initially opt for first- and second-line therapies such as drinking fewer liquids or caffeinated beverages, pelvic floor muscle training, and medication.

If those treatments don’t offer relief, more invasive options are available, including nerve stimulation called sacral neuromodulation (an implanted device sold as InterStim), or a bladder injection of botulinum toxin, sold as Botox.

Researchers conducted a head-to-head comparison of the two and discovered that Botox provides more daily relief for women—but also might be associated with more adverse events.

An injection of botulinum toxin in the bladder muscle works to address urgency urinary incontinence by relaxing the overactive bladder muscles that cause the condition. A sacral neuromodulation implant does the same thing by sending electrical pulses to nerves in the spine.

Demand for female urologists outpaces supply

“Urgency urinary incontinence is common, with 17 percent of women over age 45 and 25 percent of women over age 75 suffering from it,” says Cindy L. Amundsen, professor of obstetrics and gynecology at Duke University School of Medicine. “That’s why it’s important for both patients and health care providers to have information that can guide their choice between these two therapies.”

Published in the Journal of the American Medical Association, the study involved 381 women from nine US medical centers who recorded at least six urgency incontinent episodes over three consecutive days and had not improved with other treatments.

Participants were randomly assigned to either receive sacral neuromodulation or a 200-unit injection of botulinum toxin. After a trial period to test their responsiveness to the therapies, 364 women were enrolled and followed for six months after treatment.

Researchers analyzed the number of urgency incontinent episodes on monthly “bladder diaries.” Participants who received botulinum toxin saw their number of daily urgency incontinent episodes decrease by 3.9 on average versus 3.3 on average in the sacral neuromodulation group. The difference was statistically significant.

Toxin in Botox can travel through nerves

Botulinum toxin participants also reported a greater reduction in bothersome symptoms, higher satisfaction with treatment, and a greater likelihood of endorsing the treatment.

Additionally, among participants who completed at least four monthly diaries, a higher percentage of botulinum toxin participants saw at least a 75-percent reduction in or complete resolution of urgency incontinent symptoms. However, the Botox patients also had three times the rate of urinary tract infections. Some botulinum toxin participants also required intermittent self-catheterization, although at lower rates than reported in previous studies using this dose.

The most common adverse event for the sacral neuromodulation participants was removal or revision of the implant during the six months. This occurred at a low rate, similar to previous studies.

“This study is valuable because it is the first randomized trial comparing the efficacy of two FDA-approved, third-line therapies in a severely affected population,” Amundsen says. “The information should help guide care.”

While the study didn’t compare the cost of the two treatments, patients who receive botulinum toxin may require additional injections as part of continued treatment. Additionally, the study only takes Botox into account and no conclusions can be drawn for other botulinum toxin preparations that may be used to treat urgency incontinence.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women’s Health funded the work. One coauthor reported financial relationships with the commercial makers of both InterStim and Botox. Full disclosures are available in the study’s manuscript.

Source: Duke University

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