Culture

Symptom-triggered medication for neonatal opioid withdrawal yields shorter hospital stays

BOSTON - A study led by researchers at Boston Medical Center (BMC) found that symptom-triggered medication dosing for neonatal opioid withdrawal syndrome instead of infants receiving a fixed schedule of medication with a long taper reduced the length of their hospital stay. The findings, published in Hospital Pediatrics, indicate that following the novel symptom-triggered approach - developed at BMC - for administering medication could be a more effective intervention for these infants and could help reduce unnecessary medication exposure.

Neonatal Opioid Withdrawal Syndrome (NOWS) effects infants exposed to opioids in utero. With the increase in both unprescribed and prescribed opioids use in the U.S., which has not spared pregnant women, there has been a five-fold increase in the rate of NOWS over the past decade. Approximately 50 to 80 percent of opioid-exposed infants require medication to manage their symptoms of withdrawal, which usually appear two to three days after birth and can include irritability, trouble eating and sleeping, diarrhea, muscle rigidity, and difficulty soothing. Medications that are currently used to manage these symptoms include methadone, morphine, and buprenorphine. The average hospital stay for infants with NOWS who are treated with medication is 23 days and costs approximately $93,000.

During the postpartum hospitalization, all infants with NOWS are assessed based on their ability to eat, sleep and be consoled every four hours. At BMC, clinicians utilize non-pharmacologic care interventions, including parental presence at the bedside, breastfeeding, and rooming in, as first line treatment of NOWS, which studies have shown to reduce the need for medication and hospital length of stay, thus reducing costs. If an infant is having difficulties with these core functions after using the non-pharmacologic treatments, the health care team determines if medication is the appropriate next step.

In this study, for infants who required medication for NOWS, the researchers investigated two treatment approaches: between June 2016 and November 2017, the fixed schedule medication approach was used, in which methadone was dosed every eight hours with the traditional slow taper to treat NOWS. Between December 2017 and May 2018, the researchers implemented the symptom-triggered approach, which was developed by clinician researchers at BMC as a novel way to treat NOWS by focusing on treating symptoms and keeping the infants comfortable. This approach helps reduce the incidence of creating a dependence on the opioid medication, which can sometimes occur with the traditional fixed scheduled medication approach.

Infants who were treated using the symptom triggered approach had a median length of stay of 10.5 days, versus 17 days for the fixed schedule approach. The symptom triggered group had 5.6 fewer days of methadone treatment compared to the fixed-medication schedule group. In addition, the percentage of infants who were successfully treated using the symptom-triggered approach reached 100 percent by the end of the study period, and there were no adverse events resulting from this treatment approach.

"Our study showed that treating symptoms acutely with medication, and not having a fixed schedule with a long taper not only improves patient outcomes, but shortens their hospitalizations and decreases further exposure to opioid medications," said Elisha Wachman, MD, the study's corresponding author who is a neonatologist at BMC and an associate professor of pediatrics at Boston University School of Medicine. "This novel approach prioritizes the non-pharmacologic care approach for infants experiencing withdrawal symptoms and decreases the risk for unintended dependence that frequently occurs when infants are placed on prolonged methadone or morphine tapers."

Credit: 
Boston Medical Center

New antibiotics developed by Inserm and Université de Rennes 1

Not only are they effective against Gram-positive and negative multi-resistant bacteria, they also appear not to trigger resistance when used to treat infection in mice. Such are the promises of the two new antibiotics created by Prof. Brice Felden and his team at the Inserm and Université de Rennes 1 'Bacterial Regulatory RNAs and Medicine' joint laboratory (U1230), in conjunction with a team from the Rennes Institute of Chemical Sciences (ISCR). This French advance could bring both fresh impetus and new possibilities for fighting antibiotic resistance worldwide. Details on this research will be published July 9 in PLOS Biology.

Antibiotics have saved so many lives over the previous century of their use in humans that they are considered to be one of the major breakthroughs of contemporary medicine. Unfortunately, growing resistance is gradually rendering them ineffective, with the threat of catastrophic public health consequences should this trend continue much longer. The few new antibiotics being brought to market essentially consist of so-called me-too drugs - meaning that they are derived from existing classes of antibiotics.

Researchers from Inserm and Université de Rennes recently identified a new bacterial toxin which they transformed into potent antibiotics active against various bacteria responsible for human infections, whether Gram-positive or negative. "It all started with a fundamental discovery made in 2011", explains Brice Felden, Director of the Bacterial Regulatory RNAs and Medicine laboratory in Rennes. "We realized that a toxin produced by Staphylococcus aureus whose role is to facilitate infection is also capable of killing other bacteria present in our body. What we had identified was a molecule with dual toxic and antibiotic properties. We thought that if we could separate these activities, we would be able to create a new antibiotic non-toxic to the body. A challenge that we accepted!"

In conjunction with the team of ISCR chemist Michèle Baudy Floc'h, a new family of so-called peptidomimetics was synthesized. As their name suggests, these peptides are inspired by the existing natural bacterial peptides but have been shortened and modified. Out of the twenty molecules created, two proved effective against resistant Staphylococcus aureus and Pseudomonas aeruginosa in mouse models of severe sepsis or skin infection. In addition, no toxicity to the other cells and organs, whether in animals or human cells was observed. These new compounds are well tolerated at their active doses - and even beyond - and are devoid of the renal toxicity issues often encountered with this type of compound. "We tested them at doses 10 to 50 times higher than the effective dose without seeing toxicity" specifies Felden, adding that "the participation and imagination of the team and our chemist colleagues was needed to devise the most active molecules possible."

Little resistance observed under experimental conditions

Important to note was that the bacteria that the researchers had left in contact for several days in the animals with these antibiotics showed no signs of resistance. In order to go further, the researchers created conditions favorable to the development of resistance in vitro and in vivo - with nothing happening. However, caution is still required here given the short experimental time periods (up to 15 days).

The antibacterial activity of these peptidomimetics is partially due to the capacity of its non-natural amino acids to reinforce the association of these compounds with the membranes of the infectious bacteria. This strong binding leads to membrane permeability and the death of the bacteria. "We think these new molecules represent promising candidates for the development of new antibiotics that can provide alternative treatments to antimicrobial resistance." The next step involves launching phase I clinical trials in humans. The patent has been licensed and a start-up created.

Credit: 
INSERM (Institut national de la santé et de la recherche médicale)

Aphrodisiac pheromone discovered in fish semen

image: The image depicts a sexually spermiating mature male sea lamprey, characterized with a dorsal ridge, in a typical gravel patch where sea lampreys build nests and release pheromones that signal to ovulatory females the presence of spawning aggregations.

Image: 
Anne M. Scott

An aphrodisiac pheromone discovered in the semen of sea lampreys attracts ready-to-mate females, according to a study publishing July 9 in the open-access journal PLOS Biology by Anne M. Scott of Michigan State University, Zhe Zhang of Shanghai Ocean University, and colleagues.

In fish and other animals that use external fertilization, exposure to semen promotes spawning behaviors. However, no specific compounds in semen have been identified as aphrodisiac pheromones. In the new study, Richard Neubig, Weiming Li, and their colleagues sought to identify a pheromone from the milt (fish semen) of the sea lamprey (Petromyzon marinus) -- a jawless fish that spawns in aggregations where each spermiating male defends a nest, and ovulatory females move from nest to nest in order to mate. The researchers hypothesized that compounds in the milt may signal to ovulatory females the presence of spawning, spermiating males.

They found that an odorous compound called spermine, originally identified from human semen, is indeed a milt pheromone. At very low concentrations, spermine stimulated the lamprey olfactory system and attracted ovulatory females, but did not attract males or pre-ovulatory females. They identified the specific spermine-activated receptor in lamprey olfactory tissue, and a compound that blocks this receptor prevented the attraction of ovulatory females to spermine.

"We found the semen of sea lamprey contains spermine, a highly specific and potent pheromone, which attracts only ready-to-mate female sea lampreys," said Anne Scott. "This discovery implicates a new strategy that male animals use to recruit mates through the release of chemical cues in semen. Ovulatory females likely use spermine released along with sperm as a reliable signal for the presence of actively spawning males in the vicinity."

The results elucidate a mechanism whereby a pheromone in semen attracts ready-to-mate females and implicates a possible conservation of the olfactory detection of semen from jawless vertebrates to humans. According to the authors, their identification of milt pheromones may also have management implications for either the control or conservation of sea lamprey populations.

Credit: 
PLOS

University of Pittsburgh group brings computation and experimentation closer together

image: Frames from a 10 hour long time-lapse sequence with model prediction (red line) and explant spreading (dotted line). 'Good' models predict not only the extent of the movement but also the amount of mechanical strain as the tissue spreads. The images in the lower row report the error between predicted and actual strain (gradient blue) at the time-points above.

Image: 
MechMorpho Lab/University of Pittsburgh

PITTSBURGH (July 9, 2019) … A bioengineering group from the University of Pittsburgh Swanson School of Engineering is bringing the worlds of computational modeling and experimentation closer together by developing a methodology to help analyze the wealth
of imaging data provided by advancements in imaging tools and automated microscopes.

Their study focuses on embryonic tissue spreading, a process that is critical during wound healing and the progression of many diseases. The article, recently published in PLOS ONE (DOI: 10.1371/journal.pone.0218021),
shows how using approximate Bayesian computation (ABC) - a statistical inference method - can help derive useful quantitative information for experimental design.

The work was overseen by Lance Davidson, professor of bioengineering, who runs the MechMorpho Lab in the Swanson School of Engineering. The study was led
by Tracy Stepien, a Pitt mathematics graduate alumnus, and Holley Lynch, a former postdoctoral associate in the MechMorpho Lab.

Davidson’s group cultured tissue from the Xenopus embryo to uncover the mechanical properties behind embryonic morphogenesis - the biological process of an organism developing its shape. During the study, they discovered that small explants spread slower
than larger ones so they began creating modeling approaches to find out why.

They collected time-lapse image sequences over the course a few weeks, but the challenge when integrating modeling with experiments is determining the best set of parameters.

“As models get more complex and the experimental systems produce more data, it is difficult to determine if the chosen parameters are the optimal set,” said Stepien, a postdoctoral associate at the University of Arizona. “This is where Bayesian computation
is useful - for each dataset, you can run the model thousands of times to identify sets of parameters that best match the experiment itself.”

Once the group applied a Bayesian approach to their model, they found that there was no one unique parameter set. Instead, they identified distributions of ‘almost-best’ parameters and then used statistical methods to compare the different distributions.

From the statistical analysis, they predict tissue properties such as force production and adhesion are more likely to vary with initial tissue size than factors such as rates of cell division or shape change.

“Our work provides predictive methods that can help guide more general studies of morphogenesis to better understand how tissue spreading is regulated during development and potentially control spreading during wound healing and cancer,” said Lynch, who
is currently an assistant professor of physics at Stetson University.

According to the research group, these parameters may also prove to be useful for improving models of other experiments.

“Though this paper focused on one specific type of tissue movement, it is more broadly impactful in that it is trying to identify a new way forward for the scientific community,” said Davidson. “Over several years our model went from something simple
to something more rigorous and robust. A paper that originally focused on tissue spreading eventually evolved to demonstrate a framework that very closely integrates modeling and experiment.”

In the short-term, Davidson’s lab will follow-up on the predictions made in this paper and further investigate the biophysics of tissue spreading. In the long-term, the group would like to apply an equally robust statistical approach to other computational
models being developed in the lab.

“We really want to integrate our experimental approaches with computational models, as robust statistically as this approach offers,” said Davidson. “Using the power of computation in conjunction with advanced biomechanical experiments could really impact
our knowledge of disease development and treatment.”

Journal

PLoS ONE

DOI

10.1371/journal.pone.0218021

Credit: 
University of Pittsburgh

Growth failure in preterm infants tied to altered gut bacteria

Extremely premature infants who fail to grow as expected have delayed development of their microbiome, or communities of bacteria and other micro-organisms living in the gut, according to a new study published in Scientific Reports. Analysis of these infants' metabolism revealed that their bodies are responding as if they were fasting, despite caloric intake similar to extremely premature infants with appropriate growth. The study findings also suggest that the unique makeup of the microbiome in infants with growth failure might contribute to their inability to properly metabolize nutrients.

"Our identification of the distinct features within the microbiome and metabolism associated with growth failure might point to new ways to predict, prevent and treat this pervasive problem among preterm infants," says one of the senior authors Patrick Seed, MD, PhD, Associate Chief Research Officer of Basic Sciences at Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago, and Research Professor of Pediatrics, Microbiology and Immunology at Northwestern University Feinberg School of Medicine. "Currently we lack the means to identify infants at highest risk of growth failure. The microbiome might give us the insights we need to guide individualized interventions and measure response to therapy."

The human microbiome is estimated to consist of over a trillion bacteria in a single person, with 10 times the number of microbial cells to every human cell. Research has established that specific microbiome characteristics play causal roles in obesity, allergy, asthma, diabetes, autoimmune disease, depression and a variety of cancers. Studies have shown stark differences in the microbiome composition of preterm infants compared to full term infants. Recent studies also found that childhood malnutrition is associated with persistent immaturity of the gut microbiome.

"In our study, we investigated the relationships between intestinal microbiome, metabolism and growth in preterm infants," says Dr. Seed, who also is Division Head of Infectious Diseases at Lurie Children's. "The significant associations we found will need to be reproduced by more studies in the future. We are looking to determine if the specific signatures of microbiome and metabolism maturation we discovered apply broadly to infants with and without growth failure."

Growth failure in preterm infants is a risk factor for cognitive and motor impairment and may predispose these children to obesity, type 2 diabetes and heart disease later in life.

The study included 58 infants who were born at or before 27 weeks of pregnancy, weighing less than two pounds on average. Growth failure in these infants was defined as weight less that the third percentile on sex-specific growth charts at 40 weeks of postmenstrual age (birth gestational age plus chronological age). In the study, 36 infants had growth failure, while the rest had appropriate growth. These groups had consistent differences in the microbiome and metabolism regardless of complications of prematurity, such as sepsis (blood infection), necrotizing enterocolitis (intestinal inflammation), or intestinal perforation.

Infants with growth failure had disrupted maturation of the intestinal microbiome, characterized by low bacterial diversity, dominance of certain disease-causing bacteria (Staphylococcus and Enterobacteriaceae) and low proportions of harmless bacteria (such as Veillonella). They also displayed delayed metabolic development with features that suggest deficiencies in metabolism of glucose and other non-lipid fuels, leading to greater reliance on fatty acids. The infants with growth failure were in a persistent physiologic state that resembled fasting.

"Our analyses of the relationship between the microbiome of infants with growth failure and the byproducts of their metabolism suggest that the unique composition of bacterial communities living in their gut might play a role in this metabolic state with similarities to fasting," says Dr. Seed. "This might explain why simply increasing caloric supply for infants with growth failure often does not work. In order to develop effective treatments, we need to better understand how their inability to utilize nutrients for energy is influenced by delayed maturation of the microbiome and metabolism."

Credit: 
Ann & Robert H. Lurie Children's Hospital of Chicago

Tracing the roots: Mapping a vegetable family tree for better food

image: A team of multi-institution scientists led by the University of Missouri challenged prior theories of the origins of three vegetables -- canola, rutabaga and Siberian kale -- by mapping the genetic family tree of these leafy greens.

Image: 
University of Missouri

Human genetic testing has evolved over the recent decades, allowing people to find their ancestors and even determine specific percentages of their heritage. Much like the advances in human genetic testing recently popularized by commercial organizations have allowed people to gain a better understanding of their ancestry, scientists are now a step closer to determining a genetic family tree for vegetables by linking biology with computer science.

"Domestication of plants -- the process of adapting wild plants for human use -- happened a long time ago before we knew about genetics," said Makenzie Mabry, a doctoral student of biological sciences. "Initially in wild plants there is a big pool of genes, and domestication only uses a few of those genes. Therefore, we often miss out on other possible genes that may be better than the current ones. By identifying the ancestors of our domesticated plants, we can take the evolutionary jump and go back in time to determine the genes that weren't initially selected in domestication -- genes that could lead to more healthy or more nutritious plants or plants adapted to different climates -- and add those back into our current domesticated plants."

In the new study, a team of multi-institution scientists led by the University of Missouri challenged prior theories of the origins of three vegetables -- canola, rutabaga and Siberian kale -- by mapping the genetic family tree of these leafy greens.

The scientists ground up leaves from each plant, added a liquid chemical and placed the mixture in test tubes. Next, they analyzed the RNA and DNA in each plant with the help of computer science. In addition, they grew one of the plants, and independently verified the origin discovered in the test tubes.

"Using an analogy, some of our human genetic history comes from both our mom and dad, but other parts only come from our mom," said J. Chris Pires, a professor of biological sciences in the College of Arts and Science and investigator in the Christopher S. Bond Life Sciences Center. "Here we are trying to determine the parents of these plants, and we found that it's not the previously hypothesized mom nor dad, it's some yet to be identified species."

With a recent grant from National Geographic, the team of scientists hopes to continue collecting data throughout the world to broaden their knowledge of this family tree to confidently identify the relatives of the parental species.

"Many people focus solely on the history of animals and people," said Hong An, a postdoctoral fellow of biological sciences. "But it's equally, if not more important, to also know the history of our food."

Credit: 
University of Missouri-Columbia

How do older adults fare after hip fracture?

Hip fractures in older adults can be extremely serious, and often result in chronic illness, death, and increased health care costs. Experts estimate that some 18 to 33 percent of all older adults who have suffered hip fractures will die within a year, with even higher rates of death among people who have dementia or who live in a nursing home.

As many as 50 percent of older adults face difficulties following a hip fracture, and may be unable to bathe, feed, or dress themselves (called "activities of daily living," or ADLs). They may not be able to get around for months to even years after their fracture. This physical decline can lessen their quality of life, and some 20 percent of older adults go on to long-term care facilities after having a hip fracture.

Studies conducted on older adults who have had hip fractures suggest that the strongest indication that a person will experience a decline after a hip fracture is being disabled before the fracture occurs.

What's more, hip fractures affect not only the quality of life and health of the older adult, but also that of their caregivers--and can cause financial burdens when the individual requires more care.

Despite all this, the number of daily hours of care people need after a hip fracture has not been well studied. To learn more, researchers designed a study to better understand how older adults fare after suffering hip fractures. Their study was published in the Journal of the American Geriatrics Society.

The researchers used information from the National Surgical Quality Improvement Program (NSQIP), a program designed to measure and improve the quality of surgical care. Through NSQIP at Yale New Haven Health System, data were collected on all patients older than 65 who were having surgery to repair hip fractures during 2015.

The researchers focused on participants who developed new difficulties performing their daily activities, or who developed new or worsened problems getting around on their own. The researchers also looked at how many hours of increased daily care the participants received.

The study included a total of 368 patients who had surgery for hip fractures at Yale New Haven Hospital--including 184 patients who did not live in care facilities, and who were completely independent in their daily living activities before their hip fracture.

By three months after their hip fracture, 21 patients had died. By six months, five more patients had died.

Of the participants, 11 percent had dementia, 18 percent had depression, 19 percent had chronic kidney disease, and 21 percent had congestive heart failure.

The researchers said that their study showed that having cognitive impairment, including dementia and in-hospital delirium, can be a major predictor of functional problems and disability following hip fracture, even for older adults who were able to function well before having a hip fracture.

The researchers also noted that the proportion of people who had difficulty performing their daily tasks three months after surgery did not improve after six months.

However, the proportion of people who were disabled and unable to get around was greater at three months than at six months, showing that some older adults could recover following hip fractures, and some were able to climb stairs and walk two blocks.

The researchers said that their work showed that older adults who were independent before their hip fractures, but who had cognitive impairment or experienced in-hospital delirium, experienced poorer outcomes after their hip surgery. The researchers suggested that all older adults be screened for these conditions when they're admitted to the hospital for hip fracture treatment and be screened throughout their hospitalization.

Credit: 
American Geriatrics Society

Portland State study shows ways to reduce extreme heat in city neighborhoods

image: An interactive map of Portland showing temperature differences under two scenarios: a largely paved environment, which makes for hotter temperatures, and one in which cooling solutions, such as planting more vegetation and using reflective materials on roofs and pavement, are employed. Users can move the map's vertical bar left or right to see differences in specific neighborhoods under the two scenarios.

Image: 
Portland State University

Portland State study demonstrates how plants, trees and reflective materials can reduce extreme heat in city neighborhoods

Planting more vegetation, using reflective materials on hard surfaces and installing green roofs on buildings can help cool potentially deadly urban heat islands -- a phenomenon that exists in nearly all large cities -- a new study from Portland State University shows. Those solutions, however, present a growing challenge to developers and planners as neighborhoods become increasingly dense and single-family homes give way to apartment buildings.

Led by Urban Studies and Planning Professor Vivek Shandas and published in the May 21 edition of the journal Atmosphere, the study used computer modeling to show the temperature differences that can be made in a variety of property types - from tree-filled neighborhoods to heavily-paved industrial areas -- through planting trees and vegetation, installing green roofs and using materials on roofs and pavement that reflect heat.

The modeling showed that the biggest differences came from using reflective materials and planting trees. Shandas said green roofs provided localized cooling of the roofs themselves, especially when watered, but that they needed to be studied further before they could be considered as a broader solution for urban heat. He noted, however, that green roofs provide other environmental benefits such as retaining storm water, controlling pollution and providing a habitat for wildlife.

The study was done at the request of the City of Portland, and may be used by city officials as a guide in Portland's planning and development. The work also includes interactive maps showing every land parcel in the city, their pollution index levels, percent of vegetation canopy and more.

"One of the biggest takeaways from this work is that in the places we live, work and play, the construction materials, colors, amount of roadways and greenery - decisions that are largely left to city planners - have an effect on the varying temperatures we experience in Portland," Shandas said. "We have control over the design of our cityscapes. If summers are getting hotter, shouldn't we be considering how different built designs impact local temperatures?"

The phenomenon of higher temperatures in areas with a lot of buildings and pavement is known as the urban heat island effect. Previous studies by Shandas and others show that urban heat islands are associated with higher pollution and negative health conditions, especially for the elderly, young children and people with lower incomes.

While testing solutions that reduce urban heat, the study also showed the effects of doing the opposite. For example, it showed that paving over places that previously had a lot of tree canopy could raise the temperature as much as 25 degrees Fahrenheit on a summer day. Nearby neighborhoods would experience a spillover effect.

"Nature-based solutions such as the ones described in the study - when applied effectively and used in combination - can reduce temperatures of even the hottest places," Shandas said.

Credit: 
Portland State University

Highway medians are a source of food for wildlife, study shows

Vegetated highway medians are a proverbial buffet for small mammals, according to new research by University of Alberta biologists. Animals such as weasels, mink, and chipmunks use the roadside bands of vegetation as habitat to find food.

"We observed animals foraging for everything from other mammals, such as red squirrels looking for birds, to vegetation, like chipmunks with full cheek pouches," said April Martinig, PhD student in the Department of Biological Sciences and lead author on the study. "Weasels were the most likely species to forage in the vegetated median, followed by red squirrels, chipmunks, mice, voles, shrews, moles, and mink."

The researchers collected data over a three-year period using infrared cameras situated at six different locations along a four-lane highway with vegetated medians in Quebec. The results show many small mammals accessing the medians through wildlife passages, which are designed to help animals circumvent human-made barriers, such as roadways.

"I did not expect to see such a wide variety of foraging behaviour," explained Martinig, who is conducting her PhD studies under the supervision of Professor Stan Boutin. "I also did not expect to see animals using the wildlife passages specifically to forage since the prevailing assumption is that animals use wildlife passages to cross highways, not spend time in the habitat between highway lanes."

Food for thought

So, should we be maintaining a vegetated median between highway lanes as foraging habitat for animals?

"While my research doesn't say anything about the wider ecosystem--short of showing how flexible and adaptable animals can be--it does have practical implications," said Martinig. "Maintaining habitat between highway lanes such as with a vegetated median and not providing safe access to it with something like wildlife passages might attract animals to roads, where they are at an increased risk of collisions with vehicles."

Credit: 
University of Alberta

Life is tough but so are worms -- thanks to mom

image: By loading their eggs with more yolk protein, underfed worm moms make sure their offspring are better able to bounce back from starvation.

Image: 
Image courtesy of Jim Jordan, Duke University

DURHAM, N.C. -- Numerous studies show that the legacy of hardship can be passed from one generation to the next. The good news is that resilience can cross generations too.

That's the takeaway from a Duke University study of C. elegans worms and their offspring. The researchers found that offspring of mothers who ate fewer calories during pregnancy were better able to bounce back from starvation themselves. The researchers also showed how a mother worm transmits her hard-won coping abilities to the next generation: via changes in insulin signaling that are transferred via her eggs to her offspring, and which help them make a better recovery from famine.

The results were published July 4 in the journal Current Biology.

C. elegans is a harmless millimeter-long worm that lives in soils and rotting vegetation, where it feeds on bacteria and other microbes. "Life in the wild is feast or famine for the worm," said Duke associate professor of biology Ryan Baugh.

A team led by Baugh and Ph.D. student James Jordan examined what happened to two generations of worms when food is in limited supply. One group of worms received as much food as they liked. Worms in another group got a watered-down diet.

The offspring of both groups were then completely deprived of food for the first eight days of life before returning to normal eating, and assessed once they reached adulthood.

The researchers found that offspring that were starved in early life developed reproductive abnormalities later on, despite being well-fed for the rest of their growing up. But surprisingly, worms were more likely to avoid such health problems and develop normally as adults if their mothers had been underfed during pregnancy.

The researchers identified the hormones that underlie the mother's protective effect. Reducing a mother's food supply depresses insulin signaling, a biochemical pathway that regulates carbohydrate metabolism in both worms and vertebrates like us.

These changes affect the way she provisions her eggs. She packs them with higher concentrations of yolk protein so her larvae have something else to rely on when food is likely to be in short supply. The boost in egg yolk, in turn, alters insulin signaling in her offspring, which buffers them from early starvation's long-reaching consequences on fertility.

The researchers acknowledge that it's not always safe to assume the future will resemble the past. "The animals could get it wrong. The environment could change," Baugh said. But the food levels a mother experiences during pregnancy are a reasonably reliable indicator of the future for her offspring, he explained -- if the mother happens to be a worm.

"We're only talking 12 to 16 hours from when she lays eggs to when they actually hatch," Baugh said. The dwindling food supplies she experienced could be a harbinger of "the food supply collapsing and the population starving."

The worms essentially retain a physiological "memory" of their mother's experience that helps them anticipate and adapt to lean times to come, all without changing their DNA sequence, Baugh explained.

"It's neat because it's not the idea of heredity most of us were taught growing up," Baugh said. "It turns out there are a variety of hereditary mechanisms besides DNA."

Credit: 
Duke University

Sneaky mating may be in female damselfies' interest

image: On the left, Female 2 lands very close to female 1 to avoid harassment by the dominant male. On the right, the male misrecognizes the female 2 and harasses female 1. Thus, female 2 (carrying sneaker male sperm) avoids risking bodily harm by avoiding further mating in a heavily populated territory.

Image: 
Photo courtesy of Rassim Khelifa

During the mating season, male damselflies battle fiercely for control of prime territories containing resources - typically patches of floating leaves used for egg deposition in wetlands - that are key to attracting females. To the victors go the spoils: though a dominant male must then diligently guard his hard-won territory against interlopers, ownership of a territory gives him exclusive access to the females that congregate within his domain.

Some of his rivals, however, refuse to play by the rules.

Instead of expending energy squabbling over territorial rights, rival males simply perch on nearby vegetation and await opportunities to swoop in and steal females from a dominant males' territory. Although the reproductive benefits of engaging in this kind of "sneaky mating" behavior are readily apparent for the sneaker males, females in contrast would seem to have little to gain from mating with inferior, non-territorial males. Moreover, there should be strong evolutionary selection pressure against sneaker male phenotypes. How and why sneaky mating behaviors arise and persevere therefore remains something of a mystery.

A new analysis of the mating behavior of a rare African damselfly that is endangered according to the IUCN Red List of Threatened Species, published in the Ecological Society of America's journal Ecology, suggests, however, that sneaky male phenotypes may endure in a population because females do in fact derive reproductive benefits from sneaky mating under certain conditions.

In this study, Rassim Khelifa, a postdoctoral fellow at the University of British Columbia's Biodiversity Research Centre, conducts surveys of egg-laying females in an unusually large population of Calopteryx exul (Glittering Demoiselle) - a damselfly found only in Morocco, Algeria, and Tunisia - in 2010 and 2011. His results indicate that the frequency of sneak attempts in this species is density-dependent, and thus sneaker male success rates track with changes in population abundance. "Sneaking attempts are more likely to be observed when the population is large," explains Khelifa. "That is, high population density promotes sneaky behavior, and is mainly driven by the limited availability of oviposition [i.e. egg-laying] patches that attract females."

Male C. exul have genital structures that enable them to remove sperm from the female reproductive tract, and egg fertilization results from the final mating, an adaptation known as "last sperm precedence." The continued existence of sneaky mating behavior in these damselflies is thus dependent not only on the ability of sneaker males to mate with harem females, but also on post-mating female behavior, as sneaker male paternity will only be ensured if the female does not subsequently copulate with any other male.

But why would a female damselfly purposefully avoid mating with a dominant male after mating with a sneaker male? Mating in species with territorial mating systems involving last sperm precedence is often aggressive, and multiple copulations may cause serious injury to females, says Khelifa. "If a female was forced to copulate with a sneaky male, and that extra-copulation damages her reproductive tract, then she will tend to avoid recopulating with the territorial male," he explains. She avoids the extra mating to preserve her health. Because females can evade the attentions of a dominant male more easily when there are many other females in his territory, a sneaker male stands a better chance of being a females' last partner when population abundance is high.

Such complex sexual interactions and conflicts over access to dominant males, females, and egg-laying sites can lead to alternative mating strategies in which females appear to reduce their own reproductive fitness costs by contributing to the reproductive success of non-dominant males, even if indirectly. "Understanding the mechanisms responsible for the existence and maintenance of phenotypic variability in natural populations is a central question in evolutionary biology," according to Khelifa. "The results of this analysis suggest that the fitness of sneaker males might not be as low as we think, and that the success of sneaky strategies depends greatly on female behavior following copulation."

Once widespread throughout its three-country range, the Glittering Demoiselle now only lives in segmented, isolated populations. Its wetland habitat is disappearing due primarily to habitat loss, pollution, drought and streams that are drying up due to a changing climate. "Amazing natural history stories that might advance our evolutionary thinking are still hidden in species that have received little research attention," says Khelifa, but he warns that many such tales are being lost as populations - and entire species - dwindle and disappear worldwide. Indeed, the population of damselflies that was the focus of this study - and the largest congregation of C. exul ever recorded within its geographical range - has since vanished.

Credit: 
Ecological Society of America

Ancient molar points to interbreeding between Denisovans and Homo sapiens in Asia

image: The three-rooted lower molar anomaly in a recent Asian individual. Left: tooth sockets showing position of accessory root; right: three-rooted lower first molar tooth.

Image: 
Christine Lee

An analysis of a 160,000-year-old archaic human molar fossil discovered in China offers the first morphological evidence of interbreeding between archaic humans and Homo sapiens in Asia.

The study, which appears in the journal Proceedings of the National Academy of Sciences, centers on a three-rooted lower molar--a rare trait primarily found in modern Asians--that was previously thought to have evolved after H. sapiens dispersed from Africa.

The new research points to a different evolutionary path.

"The trait's presence in the fossil suggests both that it is older than previously understood and that some modern Asian groups obtained the trait through interbreeding with a sister group of Neanderthals, the Densiovans," explains Shara Bailey, a professor of anthropology at New York University and the paper's lead author.

In a previous study, published in Nature, Bailey and her colleagues concluded that the Denisovans occupied the Tibetan Plateau long before Homo sapiens arrived in the region.

That work, along with the new PNAS analysis, focused on a hominin lower mandible found on the Tibetan Plateau in Baishiya Karst Cave in Xiahe, China in 1980.

The PNAS study, which also included NYU anthropologist Susan Antón and Jean-Jacques Hublin, director of the Department of Human Evolution at the Max Planck Institute for Evolutionary Anthropology, centered on the molar, with the aim of understanding the relationship between archaic humans who occupied Asia more than 160,000 years ago and modern Asians.

"In Asia, there have long been claims for continuity between archaic and modern humans because of some shared traits," observes Bailey. "But many of those traits are primitive or are not unique to Asians. However, the three-rooted lower molar trait is unique to Asian groups. Its presence in a 160,000-year-old archaic human in Asia strongly suggests the trait was transferred to H. sapiens in the region through interbreeding with archaic humans in Asia."

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New York University

WHO mental health guidelines could better capture 'lived experience'

Mental health patients want mental health diagnostic descriptions to better reflect what it feels like to live with their conditions in the World Health Organisation's global manual of diagnoses - according to a new Lancet Psychiatry report.

The study, by UK and US researchers at Norfolk and Suffolk NHS Foundation Trust (NSFT), the University of East Anglia, and Columbia University, in collaboration with the WHO Department of Mental Health and Substance Abuse, is the first to report feedback from service users on such a major mental health diagnosis guideline.

The WHO's International Classification of Diseases (ICD) is used by 194 countries and is the most influential and widely used classification guide, with around 55,000 unique codes for injuries, diseases and causes of death.

Researchers looked at the latest revision (ICD-11), which will come into effect in 2022, and focused on its chapter on mental, behavioural and neurodevelopmental disorders.

Researchers asked patients with schizophrenia, bipolar disorder, depression, anxiety and personality disorders in the UK, US and India to compare the WHO descriptions of their diagnoses with their own experiences.

Lead researcher Dr Corinna Hackman, from UEA's Norwich Medical School and NSFT, said:
"The ICD is the most widely used system to diagnose people with mental health conditions globally. It is extremely influential in framing our understanding of mental illness, and the policy and provision of mental health services.

"Despite this, service users' perspectives have not been included in previous versions of the ICD.

"We wanted to gain feedback from service users internationally on how the WHO intends to classify mental health conditions, and in particular - whether their diagnostic descriptions resonate with the lived experiences of patients.

"We found that the WHO diagnosis descriptions didn't always resonate with people's lived mental health experiences. In particular, the descriptions focused on external symptoms, things that can be seen on the outside, rather than the internal, felt-experience.

"Our findings suggest that this may have potential unintended consequences for service users of feeling alienated and misunderstood.

"People with bipolar disorder for example thought that the WHO description only reflected negative aspects of the condition, and identified increased levels of creativity, associated with mania, as a positive aspect.

"People with schizophrenia said that the WHO diagnosis wording didn't cover things like difficulties relating to, and communicating with, other people including feelings of isolation and alienation from other people.

"In some cases the wording was confusing or objectionable - for example the use of the word 'retardation' for depression.

"This research offers a unique insight into the views of service users and it really represents an overdue watershed moment in mental health diagnosis," she added.

Participants also compared the WHO's classification wording with alternate lay translations created by the research team.

Research collaborator Dr Caitlin Notley, also from UEA's Norwich Medical School, said: "Participants reported that the lay summaries were much more clear, accessible and easier to understand - and consequently they felt that they resonated much better with their own lived experience.

"What we have shown is that patients would benefit from a version of the WHO disease classification system that is easier to understand and includes more information about the felt-experience.

"We hope that the changes we are recommending would also help clinicians better understand and empathise with the felt experience of service users."

The study was undertaken by NSFT, UEA and the London School of Hygiene and Tropical Medicine, in collaboration with Columbia University, NYC, a peer-led service in New Jersey and the All India Institute of Medical Sciences, New Delhi.

It is hoped that the findings will help inform further ICD-11 revisions.

The findings were translated into coproduced recommendations for the WHO, which has established a process of review and consideration of incorporation into revisions of the clinical descriptions and diagnostic guideline for ICD-11 Mental, Behavioural and Neurodevelopmental Disorders.

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University of East Anglia

Does genetic testing pose psychosocial risks?

For the last quarter century, researchers have been asking whether genetic information might have negative psychosocial effects. Anxiety, depression, disrupted relationships, and heightened stigmatization have all been posited as possible outcomes--but not consistently found. What accounts for the discrepancy?

A new special report published by The Hastings Center explores this question. It considers the ways in which the prediction of adverse consequences has not been borne out by empirical research--and also the limits of those data. Given that today's genomic information is more voluminous and complex than the results that were at issue in the older studies, it is not likely that simple answers will be forthcoming to the question of the psychosocial impacts of receiving genetic or genomic information. Rather, the answers will depend on factors that include the condition being tested for, the reason for the testing, the social context of the testing, and the psychology of the individual being tested.

"Just coming to better understanding why one-size-fits-all answers will not be forthcoming is itself progress," states the introduction to the report, written by its editors, Erik Parens, a senior research scholar at The Hastings Center, and Paul Appelbaum, the Elizabeth K. Dollard Professor of Psychiatry, Medicine and Law, and director of the Center for Law, Ethics and Psychiatry at Columbia University, who is a Hastings Center Fellow.

The special report, "Looking for the Psychosocial Impacts of Genetic Information," is the product of a conference of the same name held at Columbia University in February 2018 and cosponsored by Columbia's Center for Research on Ethical, Legal & Social Implications of Psychiatric, Neurologic & Behavioral Genetics and The Hastings Center.

The report is divided into three parts, each with three essays. The first part examines the historical and social context for current debates about research on the impacts of communication genetic information to patients.

The second part focuses on studies that are skeptical about the existence of large psychosocial harms. In one of the essays, "Assessing the Psychological Impact of Genetic Susceptibility Testing," Scott Roberts discusses the findings of a major study that found that people who learned that they had a variant of the ApoE4 gene that increases the risk for Alzheimer's disease did not show elevated signs of depression or anxiety. However, Roberts also recognizes that there's much that is not known about the psychosocial effects of ApoE4 testing, and cites evidence that people who learn of a positive result show worse performance on memory tests.

The third part is devoted to studies that support reasons for continued concern about harms from genetic testing. One of the essays, "Actions and Uncertainty: How Prenatally Diagnosed Variants of Uncertain Significance Become Actionable," recounts how women talk about their experiences learning genetic information about their fetus that is of unknown significance. For some women, this information caused anxiety both during pregnancy and after their children were born. In addition, many of the women perceived their children as vulnerable, even if they showed no signs of the condition being tested for. "Raised levels of uncertainty as a result of [variations of unknown significance] carry major implications for parenting behaviors, children's outcomes, and medical and school system overuse, outcomes seldom assessed in research about genetic technologies," write Allison Werner-Lin, Judith L. M. McCoyd, and Barbara A. Bernhardt.

"It is reassuring that, on average, the receipt of genomic information about single genes does not have large, negative psychosocial effects on those who choose to receive that information," write Parens and Appelbaum. "But it is surely not the case that, because we see few negative psychosocial impacts in people who chose testing for informational purposes, we should expect to see equally few negative impacts among all people." They conclude that "we have an extraordinary amount more to learn about the psychosocial implications of sharing genetic information."

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The Hastings Center

Scientists' warning to humanity: Microbiology and climate change

When it comes to climate change, ignoring the role of microorganisms could have dire consequences, according to a new statement issued by an international team of microbiologists.

"Microbiology needs to be considered if we're going to solve any of the massive problems related to climate change," said Lisa Stein, professor in the University of Alberta's Department of Biological Sciences and co-author on the paper. "These microorganisms both affect and are affected by climate change--meaning that they both produce and consume greenhouse gases. Their role in a changing climate is critical."

The statement, authored by an international team of 30 researchers from nine different countries, calls for the inclusion of microbes in climate change research, improving public awareness, and support for new, innovative technology. The work was coordinated by Rick Cavicchioli, microbiologist and professor at the University of New South Wales in Sydney, Australia.

Bringing bacteria into the battle

Stein is a leading expert in the field of biofuels. Her research focuses on using microorganisms such as bacteria to turn greenhouse gas emissions from oil and gas production into biofuels such as methanol and isoprene--effectively closing the loop on legacy energy technology.

"When we think about climate change, we think about cars, fossil fuels, and industry." explained Stein. "These things are relevant, certainly. But what we're not yet fully considering is how microorganisms are either facilitating increased global warming, or how we can harness microbes to control those greenhouse gases. My area of work focuses on how we, as humans, can change our behaviours to allow microbes to help us bring the planet to a more sustainable zone."

The first step? Making sure microbes are top of mind for both scientists and the wider public. "We need to improve literacy about this topic, to both address the climate change disaster that is upon us, right now, today, and to encourage future generations to feel more comfortable in their understanding of our microbial world," said Stein.

"We really believe this is our last chance. Doing nothing is unethical. If we don't, we are possibly looking at the end of our species within the next two generations. We can't just sit back."

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University of Alberta