Food Research: Could a drug engineered from bananas fight many deadly viruses? ♦ 'Everything in moderation' diet advice may lead to poor metabolic health

High-fat diet may cause changes in brain that lead to anxiety, depression A new study in mice reveals that increased body weight and high blood sugar as a result of consuming a high-fat diet may cause anxiety and depressive symptoms and measurable changes in the brain.

Could a drug engineered from bananas fight many deadly viruses? A banana a day may not keep the doctor away, but a substance originally found in bananas and carefully edited by scientists could someday fight off a wide range of viruses, new research suggests. And the process used to create the virus-fighting form may help scientists develop even more drugs, by harnessing the 'sugar code' that our cells use to communicate. That code gets hijacked by viruses and other invaders.

Some commercial coffees contain high levels of mycotoxins An analysis of 100 coffees sold in Spain has confirmed the presence of mycotoxins -- toxic metabolites produced by fungi. In addition, five of the samples that were tested were found to contain ochratoxin A, the only legislated mycotoxin, in amounts that exceeded maximum permitted levels. While the authors point out that these results are not alarming, they do recommend assessing the risk that exposure to mycotoxins from coffee poses to the general public.

'Everything in moderation' diet advice may lead to poor metabolic health in US adults Diet diversity, as defined by less similarity among the foods people eat, may be linked to lower diet quality and worse metabolic health, according to researchers.

Brain Research: New model to study HIV latency in brain cells ♦ Emotional brains 'physically different' from rational ones ♦ New imaging technique could make brain tumor removal safer

Brain injury patterns linked to post-concussion depression, anxiety Post-concussion psychiatric disorders like depression, anxiety and irritability can be extremely disabling for those among the nearly 3.8 million people in the United States who suffer concussions every year. Now, a new MRI study has found distinct injury patterns in the brains of people with concussion-related depression and anxiety

Emotional brains 'physically different' from rational ones Researchers have found physical differences in the brains of people who respond emotionally to others' feelings, compared to those who respond more rationally.

New model to study HIV latency in brain cells Over 35 million people worldwide are currently infected by HIV. Antiviral therapies can keep the virus from multiplying. However, no drug can cure infection so far, because various cell types continue to carry the virus in a latent, i.e. quiescent, state. Scientists have now established a model for latent HIV infection of brain cells. The researchers used this model to identify various compounds that affect latency of the virus in the brain.

Brain receptor found to significantly affect cocaine addiction By manipulating the activity of Activin receptors in the brain, researchers report that they were able to increase or decrease cocaine-taking and relapse behavior in animal models. The study focused on receptors in regions of the brain involved in pleasure and reward.

New imaging technique could make brain tumor removal safer, more effective, study suggests Brain surgery is famously difficult for good reason: When removing a tumor, for example, neurosurgeons walk a tightrope as they try to take out as much of the cancer as possible while keeping crucial brain tissue intact — and visually distinguishing the two is often impossible. Now researchers report they have developed an imaging technology that could provide surgeons with a color-coded map of a patient’s brain showing which areas are and are not cancer.

Children Health Toddler temperament influenced by gut bacteria ♦ Melanoma rates dramatically increasing in children ♦ Migraine surgery for teens ♦ Helping youth cope with anxiety, depression, and suicidal thoughts

Toddler temperament could be influenced by different types of gut bacteria The microbiome of a toddler's gut may influence their behavior, a new study suggests. Scientists found correlations between temperament and the presence of specific types of intestinal bacteria in both girls and boys. The researchers aren't looking for a way to help parents modify the 'terrible twos,' but for clues about how - and where - chronic illnesses like obesity, asthma, allergies and bowel diseases start

Melanoma rates dramatically increasing in children and young adults The incidence of melanoma, a deadly form of skin cancer, has increased by more than 250% among children, adolescents and young adults since 1973,

Migraine surgery for teens: Good results in initial experience As in adults, migraine surgery is effective for selected adolescent patients with severe migraine headaches that don't respond to standard treatments.

Helping youth cope with anxiety, depression, and suicidal thoughts A program is helping strengthen the mental health of public school students. The EMPATHY program, created and implemented in 2013, shows after just three months of use in schools, the program significantly decreased anxiety, depression and suicidal thoughts among the student population.

FDA Scientists Study Pediatric Brain Function

Study participants repeatedly press a lever on a large machine to make nickels slide out of a tube and drop into a cup. The coins pile up, but this activity in the Food and Drug Administration’s National Center for Toxicological Research (NCTR) laboratory at nearby Arkansas Children’s Hospital (ACH) isn’t a game of luck. It is a game that helps researchers compare important brain functions in children and animals—specifically their memory, attention, motivation, and time perception. The results provide the agency with important insights for the evaluation of the effects of pediatric drugs on psychological processes.

NCTR investigators have been studying brain function using this approach since 1988. They recruit human participants from ACH in Little Rock. The animal counterparts—monkeys—that play nearly identical games as the children are housed, cared for and tested at NCTR some 35 miles away.

So why are they doing this research? It is standard practice for the safety and effectiveness of new drugs to be tested in animals before these drugs are studied in humans. Unfortunately, it is sometimes difficult to predict how a new drug might affect brain function in humans based on the data obtained in animals. That’s because the types of tests given to assess brain function in animals often are different from the types of tests given to humans. By having animals and humans take exactly the same tests, researchers hope to be able to better predict the effects of drugs in humans using data obtained from animals.

It is hoped that the findings from these studies will help FDA, health care providers and parents make better informed decisions about medications for children—and to know more about how these medications might affect children’s brain function.

How the Testing Works

“We recruit a lot of our children from the general pediatric clinic. It’s a very broad sample and very diverse in terms of ethnicity, race, gender and age,” says John Chelonis, Ph.D., an NCTR research psychologist. Like all research involving human subjects, this study is subject to the many regulations designed to protect people of all ages who participate in clinical studies. “With human research,” Chelonis adds, “there are a lot of safeguards. If children decide they don’t want to play at any time, they can stop.”

The investigators have tested about 3,000 children since the lab opened. They see an average of eight to nine children per week, and the kids are always accompanied by consenting guardians.

Other NCTR staff train monkeys to participate in the research. The animals work for banana-flavored food pellets. “But they have to practice until they finally understand the rules of the games,” says Merle Paule, Ph.D., director of the Division of Neurotoxicology at NCTR. Some primates have been playing these games for almost 10 years. Once they learn the rules, which often takes months of trial and error performance, they can perform some games with accuracies of 95 percent or more.

“One of the important things about these games or tests is that they’re nonverbal,” says Paule. He explains that young kids don’t have language skills yet, and monkeys have none, and it’s the nonverbal nature of these tests, as opposed to traditional psychological tests, that makes more direct comparisons between the two groups possible.

Researchers study children who have attention deficit hyperactivity disorder (ADHD) and depression, and those who do not. “We try not to interfere with these kids’ treatment,” says Chelonis. “For instance, a lot of kids might be on their ADHD medication only during school days, and they’re off it on the weekends. So when we wanted to test the children when they were off their medication, we would typically schedule their sessions for the weekends when they were off of their medication.”

Researchers assess whether children’s responses vary in the presence or absence of medication and analyze the results based on gender and age. One of the tests that involves repeatedly pushing a lever on the behavior panel measures motivation. Children sit in front of the panel, which is positioned against a wall. They’re told to press one of the levers to get nickels. The first press releases one nickel. Children must press the lever 11 times for the second nickel (10 more than for the first nickel), 21 times for the third nickel, 31 times for the fourth nickel and so on, until the 10-minute game ends. The number of nickels earned depends on the strength of their motivation—how many times they press the lever.

Another game tests timing ability. For this, kids must hold one of the response levers down for at least 10 seconds, but not more than 14 seconds, to receive a nickel. It sounds simple. “But it’s a hard game,” says Chelonis. “It’s the cadence with which you count that gets you the nickel.” For this test, animals and kids tend to hold the lever down just long enough to meet the 10-second requirement. The timing ability of children with ADHD improves while on their medication. When children with ADHD are off their ADHD medication, they make more responses that are either too short or too long in duration compared to when they are on their ADHD medication.

What Researchers Hope to Accomplish

These FDA investigators are seeking to further validate their NCTR Operant Test Battery (OTB), the instrument they use to assess complex brain function in both children and monkeys.

They want to show:

• How OTB task performance relates to IQ and other clinical tests that measure mental function in humans;
• How OTB task performance relates to behavioral conditions such as ADHD, anxiety, and depression;
• Whether OTB task performance is affected by drugs used to treat behavioral conditions such as ADHD; and
• How children’s OTB performance compares to that obtained using animal models.

NCTR researchers have published many of their findings in a variety of scientific journals, including Experimental and Clinical Psychopharmacology, Behavioral Processes and Neurotoxicology and Teratology.

The value of animal models to predict clinical outcomes is important to FDA, Paule says. As researchers gain a better understanding of how animal OTB performance compares to human OTB performance, they’ll be able to develop better ways of using animal models to understand human behavior and better predict drug effects on human brain function. This eventually could help parents and medical professionals make more informed decisions about medication use and to understand the positive and negative effects that drugs may have on behavior.

FDA researchers are also studying the potential toxicity of general anesthetics and sedatives in children. Animal models suggest that a single episode of general anesthesia during critical stages of brain growth can cause lifelong deficits in brain function. The scientific community currently does not have enough human data to know whether this is a problem in the clinic, but it is suspected that prolonged or repeated exposures in children also could have cognitive consequences.

“Biology is basically the same across different species,” adds Paule, reflecting on NCTR’s comparative research. “Animals can do many things that we can do if we give them the right opportunity, and they can also show us a lot about drug effects if we can figure out how to look.”

FDA Scientists Study Pediatric Brain Function

Study participants repeatedly press a lever on a large machine to make nickels slide out of a tube and drop into a cup. The coins pile up, but this activity in the Food and Drug Administration’s National Center for Toxicological Research (NCTR) laboratory at nearby Arkansas Children’s Hospital (ACH) isn’t a game of luck. It is a game that helps researchers compare important brain functions in children and animals—specifically their memory, attention, motivation, and time perception. The results provide the agency with important insights for the evaluation of the effects of pediatric drugs on psychological processes.

NCTR investigators have been studying brain function using this approach since 1988. They recruit human participants from ACH in Little Rock. The animal counterparts—monkeys—that play nearly identical games as the children are housed, cared for and tested at NCTR some 35 miles away.

So why are they doing this research? It is standard practice for the safety and effectiveness of new drugs to be tested in animals before these drugs are studied in humans. Unfortunately, it is sometimes difficult to predict how a new drug might affect brain function in humans based on the data obtained in animals. That’s because the types of tests given to assess brain function in animals often are different from the types of tests given to humans. By having animals and humans take exactly the same tests, researchers hope to be able to better predict the effects of drugs in humans using data obtained from animals.

It is hoped that the findings from these studies will help FDA, health care providers and parents make better informed decisions about medications for children—and to know more about how these medications might affect children’s brain function.

How the Testing Works

“We recruit a lot of our children from the general pediatric clinic. It’s a very broad sample and very diverse in terms of ethnicity, race, gender and age,” says John Chelonis, Ph.D., an NCTR research psychologist. Like all research involving human subjects, this study is subject to the many regulations designed to protect people of all ages who participate in clinical studies. “With human research,” Chelonis adds, “there are a lot of safeguards. If children decide they don’t want to play at any time, they can stop.”

The investigators have tested about 3,000 children since the lab opened. They see an average of eight to nine children per week, and the kids are always accompanied by consenting guardians.

Other NCTR staff train monkeys to participate in the research. The animals work for banana-flavored food pellets. “But they have to practice until they finally understand the rules of the games,” says Merle Paule, Ph.D., director of the Division of Neurotoxicology at NCTR. Some primates have been playing these games for almost 10 years. Once they learn the rules, which often takes months of trial and error performance, they can perform some games with accuracies of 95 percent or more.

“One of the important things about these games or tests is that they’re nonverbal,” says Paule. He explains that young kids don’t have language skills yet, and monkeys have none, and it’s the nonverbal nature of these tests, as opposed to traditional psychological tests, that makes more direct comparisons between the two groups possible.

Researchers study children who have attention deficit hyperactivity disorder (ADHD) and depression, and those who do not. “We try not to interfere with these kids’ treatment,” says Chelonis. “For instance, a lot of kids might be on their ADHD medication only during school days, and they’re off it on the weekends. So when we wanted to test the children when they were off their medication, we would typically schedule their sessions for the weekends when they were off of their medication.”

Researchers assess whether children’s responses vary in the presence or absence of medication and analyze the results based on gender and age. One of the tests that involves repeatedly pushing a lever on the behavior panel measures motivation. Children sit in front of the panel, which is positioned against a wall. They’re told to press one of the levers to get nickels. The first press releases one nickel. Children must press the lever 11 times for the second nickel (10 more than for the first nickel), 21 times for the third nickel, 31 times for the fourth nickel and so on, until the 10-minute game ends. The number of nickels earned depends on the strength of their motivation—how many times they press the lever.

Another game tests timing ability. For this, kids must hold one of the response levers down for at least 10 seconds, but not more than 14 seconds, to receive a nickel. It sounds simple. “But it’s a hard game,” says Chelonis. “It’s the cadence with which you count that gets you the nickel.” For this test, animals and kids tend to hold the lever down just long enough to meet the 10-second requirement. The timing ability of children with ADHD improves while on their medication. When children with ADHD are off their ADHD medication, they make more responses that are either too short or too long in duration compared to when they are on their ADHD medication.

What Researchers Hope to Accomplish

These FDA investigators are seeking to further validate their NCTR Operant Test Battery (OTB), the instrument they use to assess complex brain function in both children and monkeys.

They want to show:

• How OTB task performance relates to IQ and other clinical tests that measure mental function in humans;
• How OTB task performance relates to behavioral conditions such as ADHD, anxiety, and depression;
• Whether OTB task performance is affected by drugs used to treat behavioral conditions such as ADHD; and
• How children’s OTB performance compares to that obtained using animal models.

NCTR researchers have published many of their findings in a variety of scientific journals, including Experimental and Clinical Psychopharmacology, Behavioral Processes and Neurotoxicology and Teratology.

The value of animal models to predict clinical outcomes is important to FDA, Paule says. As researchers gain a better understanding of how animal OTB performance compares to human OTB performance, they’ll be able to develop better ways of using animal models to understand human behavior and better predict drug effects on human brain function. This eventually could help parents and medical professionals make more informed decisions about medication use and to understand the positive and negative effects that drugs may have on behavior.

FDA researchers are also studying the potential toxicity of general anesthetics and sedatives in children. Animal models suggest that a single episode of general anesthesia during critical stages of brain growth can cause lifelong deficits in brain function. The scientific community currently does not have enough human data to know whether this is a problem in the clinic, but it is suspected that prolonged or repeated exposures in children also could have cognitive consequences.

“Biology is basically the same across different species,” adds Paule, reflecting on NCTR’s comparative research. “Animals can do many things that we can do if we give them the right opportunity, and they can also show us a lot about drug effects if we can figure out how to look.”