Doctors need better ways to figure out fevers in newborns

Two days after my first daughter was born, her pediatrician paid a house call to examine her newest patient. After packing up her gear, she told me something alarming: “For the next few months, a fever is an emergency.” If we measured a rectal temperature at or above 100.4° Fahrenheit, go to the hospital, she said. Call her on the way, but don’t wait.

I, of course, had no idea that a fever constituted an emergency. But our pediatrician explained that a fever in a very young infant can signal a fast-moving and dangerous bacterial infection. These infections are rare (and fortunately becoming even rarer thanks to newly created vaccines). But they’re serious, and newborns are particularly susceptible.

I’ve since heard from friends who have been through this emergency. Their newborns were poked, prodded and monitored by anxious doctors, in the hopes of quickly ruling out a serious bacterial infection. For infants younger than two months, it’s “enormously difficult to tell if an infant is seriously ill and requires antibiotics and/or hospitalization,” says Howard Bauchner, a pediatrician formerly at Boston University School of Medicine and now editor in chief of the Journal of the American Medical Association.

A new research approach, described in two JAMA papers published in August, may ultimately lead to better ways to find the cause of a fever.

These days, for most (but not all) very young infants, their arrival at a hospital will trigger a workup that includes a urine culture and a blood draw. Often doctors will perform a lumbar puncture, more commonly known as a spinal tap, to draw a sample of cerebrospinal fluid from the area around the spinal cord.

Doctors collect these fluids to look for bacteria. Blood, urine and cerebrospinal fluid are smeared onto culture dishes, and doctors wait and see if any bacteria grow. In the meantime, the feverish infant may be started on antibiotics, just in case. But this approach has its limitations. Bacterial cultivation can take several days. The antibiotics may not be necessary. And needless to say, it’s not easy to get those fluids, particularly from a newborn.

Some scientists believe that instead of looking for bacteria or viruses directly, we ought to be looking at how our body responds to them. Unfortunately, the symptoms of a bacterial and viral infection are frustratingly similar. “You get a fever. You feel sick,” says computational immunologist Purvesh Khatri of Stanford University. Sadly, there are no obvious telltale symptoms of one or the other, not even green snot. In very young infants, a fever might be the only sign that something is amiss.
But more subtle clues could betray the cause of the fever. When confronted with an infection, our immune systems ramp up in specific ways. Depending on whether we are fighting a viral or bacterial foe, different genes turn up their activity. “The immune system knows what’s going on,” Khatri says. That means that if we could identify the genes that reliably get ramped up by viruses and those that get ramped up by bacteria, then we could categorize the infection based on our genetic response.

That’s the approach used by two groups of researchers, whose study results both appear in the August 23/30 JAMA. One group found that in children younger than 2, two specific genes could help make the call on infection type. Using blood samples, the scientists found that one of the genes ramped up its activity in response to a viral infection, and the other responded to a bacterial infection.

The other study looked at immune responses in even younger children. In infants younger than 60 days, the activity of 66 genes measured in blood samples did a pretty good job of distinguishing between bacterial and viral infections. “These are really exciting preliminary results,” says Khatri, who has used a similar method for adults. “We need to do more work.”

Bauchner points out that in order to be useful, “the test would have to be very, very accurate in very young infants.” There’s very little room for error. “Only time will tell how good these tests will be,” he says. In an editorial that accompanied the two studies, he evoked the promise of these methods. If other experiments replicate and refine the results of these studies, he could envision a day in which the parents of a feverish newborn could do a test at home, call their doctor and together decide if the child needs more care.

That kind of test isn’t here yet, but scientists are working on it. The technology couldn’t come soon enough for doctors and parents desperate to figure out a fever.

Hawaiian crows ace tool-user test

A second kind of crow, native to Hawaii, joins the famous New Caledonian crows as proven natural tool-users.

Tested in big aviaries, Hawaiian crows (Corvus hawaiiensis) frequently picked up a little stick and deftly worked it around to nudge out hard-to-reach tidbits of meat that researchers had pushed into holes in a log, scientists report September 14 in Nature.

“A goosebump moment,” says study coauthor Christian Rutz of his first sight of Hawaiian crows tackling the test. Their nimble handling is “not some little fluke where a bird picks up a stick and pokes it in a hole,” he says. Anecdotes of such flukes abound, especially for crows. What’s rare are demonstrations that most able-bodied adults in a species show a capacity for tool use in chores important for life in the wild. Because Hawaiian crows are extinct in the wild, Rutz and his colleagues had the bittersweet ability to test literally all adult members of the species. Youngsters too developed tool skills on their own.

Rutz, of the University of St. Andrews in Scotland, has worked with New Caledonian crows, which routinely shape and wield food-snagging tools. These birds, like the Hawaiian crows, are native to remote tropical islands. So is the Galapagos woodpecker finch, one of the handful of other bird species proven expert in tool use. Remote islands may favor the evolution of such capacities, Rutz muses. There are no true woodpeckers to compete with birds for treats in crevices there. And few predators lurk to pounce on a bird distracted with its head practically in a hole.
GOOD STICKWORK A Hawaiian crow manipulates a twig in its beak to wiggle out a meaty tidbit hidden in a log. Crows dissatisfied with sticks that researchers set out for snagging food sometimes flew into the shrubbery and selected their own tools for the task.

Endurance training leaves no memory in muscles

Use it or lose it, triathletes.

Muscles don’t have long-term memory for exercises like running, biking and swimming, a new study suggests. The old adage that once you’ve been in shape, it’s easier to get fit again could be a myth, at least for endurance athletes, researchers in Sweden report September 22 in PLOS Genetics.

“We really challenged the statement that your muscles can remember previous training,” says Maléne Lindholm of the Karolinska Institute in Stockholm. But even if muscles forget endurance exercise, the researchers say, other parts of the body may remember, and that could make retraining easier for people who’ve been in shape before.
Endurance training is amazingly good for the body. Weak muscle contractions, sustained over a long period of time — as in during a bike ride — change proteins, mainly ones involved in metabolism. This translates into more energy-efficient muscle that can help stave off illnesses like diabetes, cardiovascular disease and some cancers. The question is, how long do those improvements last?

Previous work in mice has shown that muscles “remember” strength training (SN: 9/11/10, p. 15). But rather than making muscles more efficient, strength-training moves like squats and push-ups make muscles bigger and stronger. The muscles bulk up as they develop more nuclei. More nuclei lead to more production of proteins that build muscle fibers. Cells keep their extra nuclei even after regular exercise stops, to make protein easily once strength training restarts, says physiologist Kristian Gundersen at the University of Oslo in Norway. Since endurance training has a different effect on muscles, scientists weren’t sure if the cells would remember it or not.
To answer that question, Lindholm’s team ran volunteers through a 15-month endurance training experiment. In the first three months, 23 volunteers trained four times a week, kicking one leg 60 times per minute for 45 minutes. Volunteers rested their other leg. Lindholm’s team took muscle biopsies before and after the three-month period to see how gene activity changed with training. Specifically, the scientists looked for changes in the number of mRNAs (the blueprints for proteins) that each gene was making. Genes associated with energy production showed the greatest degree of change in activity with training.
At a follow-up, after participants had stopped training for nine months, scientists again biopsied muscle from the thighs of 12 volunteers, but didn’t find any major differences in patterns of gene activity between the previously trained legs and the untrained legs. “The training effects were presumed to have been lost,” says Lindholm. After another three-month bout of training, this time in both legs, the researchers saw no differences between the previously trained and untrained legs.
While this study didn’t find muscle memory for endurance — most existing evidence is anecdotal — it still might be easier for former athletes to get triathalon-ready, researchers say. The new result has “no bearing on the possible memory in other organ systems,” Gundersen says. The heart and cardiovascular system could remember and more easily regain previous fitness levels, for example, he says.

Even within muscle tissue, immune cells or stem cells could also have some memory not found in this study, says molecular exercise physiologist Monica Hubal of George Washington University in Washington, D.C. Lindholm adds that well-trained connections between nerves and muscles could also help lapsed athletes get in shape faster than people who have never exercised before. “They know how to exercise, how it’s supposed to feel,” Lindholm says. “Your brain knows exactly how to activate your muscles, you don’t forget how to do that.”

Primitive signs of emotions spotted in sugar-buzzed bumblebees

To human observers, bumblebees sipping nectar from flowers appear cheerful. It turns out that the insects may actually enjoy their work. A new study suggests that bees experience a “happy” buzz after receiving a sugary snack, although it’s probably not the same joy that humans experience chomping on a candy bar.

Scientists can’t ask bees or other animals how they feel. Instead, researchers must look for signs of positive or negative emotions in an animal’s decision making or behavior, says Clint Perry, a neuroethologist at Queen Mary University of London. In one such study, for example, scientists shook bees vigorously in a machine for 60 seconds — hard enough to annoy, but not hard enough to cause injury — and found that stressed bees made more pessimistic decisions while foraging for food.
The new study, published in the Sept. 30 Science, is the first to look for signs of positive bias in bee decision making, Perry says. His team trained 24 bees to navigate a small arena connected to a plastic tunnel. When the tunnel was marked with a blue “flower” (a placard), the bees learned that a tasty vial of sugar water awaited them at its end. When a green “flower” was present, there was no reward. Once the bees learned the difference, the scientists threw the bees a curveball: Rather than being blue or green, the “flower” had a confusing blue-green hue.

Faced with the ambiguous color, the bees appeared to dither, meandering around for roughly 100 seconds before deciding whether to enter the tunnel. Some didn’t enter at all. But when the scientists gave half the bees a treat — a drop of concentrated sugar water — that group spent just 50 seconds circling the entrance before deciding to check it out. Overall, the two groups flew roughly the same distances at the same speeds, suggesting that the group that had gotten a treat first had not simply experienced a boost in energy from the sugar, but were in a more positive, optimistic state, Perry says.

In a separate experiment, Perry and colleagues simulated a spider attack on the bees by engineering a tiny arm that darted out and immobilized them with a sponge. Sugar-free bees took about 50 seconds longer than treated bees to resume foraging after the harrowing encounter.

The researchers then applied a solution to the bees’ thoraxes that blocked the action of dopamine, one of several chemicals that transmit rewarding signals in the insect brain. With dopamine blocked, the effects of the sugar treat disappeared, further suggesting that a change in mood, and not just increased energy, was responsible for the bees’ behavior.

The results provide the first evidence for positive, emotion-like states in bees, says Ralph Adolphs, a neuroscientist at Caltech. Yet he suspects that the metabolic effects of sugar did influence the bees’ behavior.
Geraldine Wright, a neuroethologist at Newcastle University in England, shares that concern. “The data reported in the paper doesn’t quite convince me that eating sucrose didn’t change how they behaved, even though they say it didn’t affect flight time or speed of flight,” she says. “I would be very cautious in interpreting the responses of bees in this assay as a positive emotional state.”

Painted lady butterflies’ migration may take them across the Sahara

Butterflies look so delicate as they flitter from flower to flower. And yet, they are capable of migrating incredibly long distances. The monarch, for example, migrates between Canada and Mexico, covering distances of up to 4,800 kilometers, riding a combination of columns of rising air, called thermals, and air currents to travel around 80 to 160 kilometers per day.

No single monarch makes this entire journey, though. The round trip is done by a succession of as many as five generations of butterflies. But now scientists have found that there’s a species of butterfly that may rival the monarch’s migratory record — the painted lady (Vanessa cardui).

Painted ladies are found throughout much of the world, except for South America and Australia. They’ve been seen as far north as Svalbard, Norway, and nearly as far south as Antarctica. The butterflies are known to migrate, particularly between Europe and Africa, but their route has been largely unknown. Scientists had tracked the butterflies to northern Africa (the region known as the Maghreb), but there have been hints that they may fly across the Sahara. Two new studies back up this claim.

Gerard Talavera and Roger Vila of Harvard University visited four sub-Saharan nations — Benin, Chad, Ethiopia and Senegal — in 2014. They found butterflies moving south through Chad. There were dense aggregations of breeding butterflies in Benin and Ethiopia. And as the dry season approached in Senegal, the pair found butterflies old and worn, as if they had just finished a long, tortuous journey. Plus, the timing of these appearances coincided with the butterflies’ fall and winter disappearance from Europe.

“Taken together, the results of our fieldwork provide evidence suggesting that most European populations may undertake long-range migratory flights to tropical Africa, thus crossing the combined hazards of the Mediterranean Sea and the completely hostile Sahara,” the pair write September 21 in the Biological Journal of the Linnean Society.

If butterflies truly are making that flight, they could be traveling more than 4,000 kilometers in a single generation — a potential record for a migratory insect, the researchers note. And while this seems nearly impossible, it may not be. A previous study found that with favorable winds, painted butterflies could travel as fast as 45 kilometers per hour. At that speed, it would take them as little as four days to make it from Central Europe to Central Africa. Since an adult painted butterfly lives for around four weeks, such a journey is feasible, Talavera and Vila argue.

But this evidence is only circumstantial; it doesn’t prove that butterflies are truly making that journey. So while Tavalera and Vila were in sub-Saharan Africa, they collected hundreds of adult painted ladies and larvae. Some of these were used in a second study, published October 4 in Biology Letters and led by Constantí Stefanescu of the Natural History Museum of Granollers in Spain. In this study, the team analyzed the isotopes of hydrogen found in the adult butterflies’ wings.
The hydrogen in the water that falls as precipitation can come in different isotopes, or forms, that vary in the number of neutrons. The ratio of these isotopes varies geographically. And the ratio present wherever the butterflies lived as larvae correlates with that later found in the adults’ wings. So researchers can tell where the adults were born.

Stefanescu and his team analyzed butterflies collected in seven European and seven African countries and developed a rough map of where the adults were moving. Those in sub-Saharan Africa had indeed started in Europe. But those in the Maghreb came from both sub-Saharan Africa and Europe.

What explains all this movement? The butterflies are following a combination of prevailing winds and favorable conditions for breeding. As rains come and go, the butterflies breed and move on. And while crossing the Sahara may seem like quite a way to go just for some rainy days and lush vegetation, painted lady butterflies are hardly the only creatures willing to go that far, Stefanescu and his colleagues note. There are plenty of other insects that make such a journey — as well as billions of birds.