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Chemical Added To Consumer Products Impairs Response To Antibiotic Treatment

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Grocery store aisles are stocked with products that promise to kill bacteria. People snap up those items to protect themselves from the germs that make them sick. However, new research from Washington University in St. Louis finds that a chemical that is supposed to kill bacteria is actually making them stronger and more capable of surviving antibiotic treatment.

The study, available online Feb. 19 in the journal Antimicrobial Agents & Chemotherapy, suggests that triclosan exposure may inadvertently drive bacteria into a state in which they are able to tolerate normally lethal concentrations of antibiotics — including those antibiotics that are commonly used to treat urinary tract infections (UTIs).

Triclosan is the active ingredient responsible for the “antibacterial” property marketed on many consumer products. It is added to toothpaste, mouthwash, cosmetics and even to clothing, baby toys and credit cards with the intention of reducing or preventing bacterial growth.

“In order to effectively kill bacterial cells, triclosan is added to products at high concentrations,” said Petra Levin, professor of biology in Arts & Sciences.

In 2017, the U.S. Food and Drug Administration cited both safety concerns and lack of efficacy when it recommended against adding triclosan to consumer soaps, but these guidelines have not discouraged companies from adding it to other products. What’s more, Levin said, “Triclosan is very stable. It lingers in the body and in the environment for a long time.”

The new study in mice uncovers the extent to which triclosan exposure limits the body’s ability to respond to antibiotic treatment for urinary tract infection. It also sheds new light on the cellular mechanism that allows triclosan to interfere with antibiotic treatment.

Escaping death

Some antibiotics kill bacterial cells, while others keep them from growing.

Levin and her colleagues were particularly interested in bactericidal antibiotics — those that can kill bacterial cells and are typically prescribed by doctors to treat bacterial infections. They wanted to know whether triclosan could protect bacteria from death in the presence of killing antibiotics.

Corey Westfall, postdoctoral scholar in the Levin lab, treated bacterial cells with bactericidal antibiotics and tracked their ability to survive over time. In one group, the bacteria were exposed to triclosan prior to being given the bactericidal antibiotic. In the other group, they were not.

“Triclosan increased the number of surviving bacterial cells substantially,” Levin said.

“Normally, one in a million cells survive antibiotics, and a functioning immune system can control them. But triclosan was shifting the number of cells. Instead of only one in a million bacteria surviving, one in 10 organisms survived after 20 hours. Now, the immune system is overwhelmed.”

Triclosan exposure allowed the bacteria to escape death by antibiotics. And the protective property was not limited to any single family of antibiotics. In fact, multiple antibiotics that are considered unique in how they kill cells were less effective at killing bacteria exposed to triclosan.

“Triclosan increased tolerance to a wide breadth of antibiotics,” Westfall said.

“Ciprofloxacin (also known as Cipro) was the most interesting one to us because it is a fluoroquinolone that interferes with DNA replication and is the most common antibiotic used to treat UTIs.”

Antibiotics can’t do their job with triclosan around

UTIs occur when bacteria, primarily Escherichia coli (E. coli), enter and infect the urinary tract. Antibiotics such as Cipro are commonly used to kill the bacteria and treat the infection.

UTIs are common; so is exposure to triclosan. A shocking percentage — about 75 percent — of adults in the United States have detectable levels of triclosan in their urine. About 10 percent of adults have levels high enough to prevent E. coli from growing. Could triclosan’s presence in the body interfere with treating UTIs?

Westfall and Levin worked with collaborators at Washington University School of Medicine in St. Louis to answer this question.

Ana Flores-Mireles, an assistant professor at the University of Notre Dame, worked on this study as a postdoctoral scholar in the lab of Scott Hultgren, the Helen L. Stoever Professor of Molecular Microbiology at the School of Medicine. With the help of Jeffrey Henderson, associate professor of medicine and molecular biology, she figured out that mice which drink triclosan-spiked water have urine triclosan levels similar to those reported in humans.

“This result meant we could actually test the impact that human urine levels of triclosan have during antibiotic treatment of UTIs in mice,” Levin said.

All of the mice with the infection received Cipro to treat the UTI. Only some of the mice drank triclosan-spiked water. After antibiotic treatment, mice with triclosan exposure had a large number of bacteria in their urine and stuck to the bladder; mice without exposure had significantly lower bacterial counts.

“The magnitude of the difference in bacterial load between the mice that drank triclosan-spiked water and those that didn’t is striking,” Levin said.

“If the difference in the number of bacteria between the groups was less than tenfold, it would be difficult to make a strong case that the triclosan was the culprit,” Levin added.

“We found 100 times more bacteria in the urine of triclosan-treated mice — that is a lot.”

This striking result has an equally striking message — antibiotics are less effective at treating UTIs when triclosan is around, at least in mice.

Levin and her colleagues found that triclosan works with a cell growth inhibitor, a small molecule nicknamed ppGpp, to render cells less sensitive to antibiotics.

During times of stress, ppGpp responds by shutting down the biosynthetic pathways that make the building blocks — DNA, RNA, protein and fat — that ultimately become new cells. This response helps divert resources away from growth and towards survival.

“There is a rule in medicine that you don’t give drugs that slow cell growth before drugs that kill cells,” Levin said.

Bactericidal antibiotics kill by targeting specific biosynthetic pathways. Ampicillin targets the enzymes that make the bacterial cell wall, for example, while Cipro targets DNA synthesis. When these pathways are shut down, bactericidal antibiotics have trouble doing their job.

If triclosan triggers ppGpp, biosynthesis is curtailed and bactericidal antibiotics would become ineffective at killing cells. Biosynthesis continues in bacteria lacking ppGpp, however, and these cells would be expected to die.

Levin and colleagues tested their hypothesis by engineering E. coli mutants unable to make ppGpp and compared them to E. coli able to make ppGpp. The absence of ppGpp in the mutant E. coli removed triclosan’s ability to protect the cells from bactericidal antibiotics.

While clinical studies would be required to definitely prove that triclosan is interfering with antibiotic treatments in humans, Levin said, “My hope is that this study will serve as a warning that will help us rethink the importance of antimicrobials in consumer products.”

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Face It. Our Faces Don’t Always Reveal Our True Emotions

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Actor James Franco looks sort of happy as he records a video diary in the movie “127 Hours.” It’s not until the camera zooms out, revealing his arm is crushed under a boulder, that it becomes clear his goofy smile belies his agony.

That’s because when it comes to reading a person’s state of mind, visual context — as in background and action — is just as important as facial expressions and body language, according to a new study from UC Berkeley.

The findings, to appear online this week in the journal Proceedings of the National Academy of Sciences, challenge decades of research positing that emotional intelligence and recognition are based largely on the ability to read micro-expressions signaling happiness, sadness, anger, fear, surprise, disgust, contempt and other positive and negative moods and sentiments.

Implications include the potential limitations of facial recognition software.

“Our study reveals that emotion recognition is, at its heart, an issue of context as much as it is about faces,” said study lead author Zhimin Chen, a doctoral student in psychology at UC Berkeley.

Researchers blurred the faces and bodies of actors in dozens of muted clips from Hollywood movies and home videos. Despite the characters’ virtual invisibility, hundreds of study participants were able to accurately read their emotions by examining the background and how they were interacting with their surroundings.

The “affective tracking” model that Chen created for the study allows researchers to track how people rate the moment-to-moment emotions of characters as they view videos.

Chen’s method is capable of collecting large quantities of data in a short time, and could eventually be used to gauge how people with disorders like autism and schizophrenia read emotions in real time and help with their diagnoses.

“Some people might have deficits in recognizing facial expressions, but can recognize emotion from the context,” Chen said.

“For others, it’s the opposite.”

Moreover, the findings, based on statistical analyses of the ratings collected, could inform the development of facial recognition technology.

“Right now, companies are developing machine learning algorithms for recognizing emotions, but they only train their models on cropped faces and those models can only read emotions from faces,” Chen said.

“Our research shows that faces don’t reveal true emotions very accurately and that identifying a person’s frame of mind should take into account context as well.”

For the study, Chen and study senior author David Whitney, a UC Berkeley vision scientist, tested the emotion recognition abilities of nearly 400 young adults. The visual stimuli they used were video clips from various Hollywood movies as well as documentaries and home videos that showed emotional responses in more natural settings.

In the first of three experiments, 33 study participants viewed interactions in movie clips between two characters, one of which was blurred, and rated the perceived emotions of the blurred character. The results showed that study participants inferred how the invisible character was feeling based not only on their interpersonal interactions, but also from what was happening in the background.Study participants went online to view and rate the video clips. A rating grid was superimposed over the video so that researchers could track each study participant’s cursor as it moved around the screen, processing visual information and rating moment-to-moment emotions.

Next, approximately 200 study participants viewed video clips showing interactions under three different conditions: one in which everything was visible, another in which the characters were blurred, and another in which the context was blurred. The results showed that context was as important as facial recognition for decoding emotions.

In the final experiment, 75 study participants viewed clips from documentaries and home videos so that researchers could compare emotion recognition in more naturalistic settings. Again, the context was as critical for inferring the emotions of the characters as were their facial expressions and gestures.

“Overall, the results suggest that context is not only sufficient to perceive emotion, but also necessary to perceive a person’s emotion,” said Whitney, a UC Berkeley psychology professor.

“Face it, the face is not enough to perceive emotion.”

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Working Long Hours Linked To Depression In Women

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Women who work more than 55 hours a week are at a higher risk of depression but this is not the case for men, according to a new UCL-led study with Queen Mary University of London.

The study of over 20,000 adults, published today in the BMJ’s Journal of Epidemiology & Community Health, found that after taking age, income, health and job characteristics into account, women who worked extra-long hours had 7.3% more depressive symptoms than women working a standard 35-40 week. Weekend working was linked to a higher risk of depression among both sexes.

Women who worked for all or most weekends had 4.6% more depressive symptoms on average compared to women working only weekdays. Men who worked all or most weekends had 3.4% more depressive symptoms than men working only weekdays.

“This is an observational study, so although we cannot establish the exact causes, we do know many women face the additional burden of doing a larger share of domestic labour than men, leading to extensive total work hours, added time pressures and overwhelming responsibilities,” explained Gill Weston (UCL Institute of Epidemiology and Health Care), PhD candidate and lead author of the study.

“Additionally women who work most weekends tend to be concentrated in low-paid service sector jobs, which have been linked to higher levels of depression.”

The study showed that men tended to work longer hours in paid work than women, and having children affected men’s and women’s work patterns in different ways: while mothers tended to work fewer hours than women without children, fathers tended to work more hours than men without children.

Two thirds of men worked weekends, compared with half of women. Those who worked all or most weekends were more likely to be in low skilled work and to be less satisfied with their job and their earnings than those who only worked Monday to Friday or some weekends.

Researchers analysed data from the Understanding Society, the UK Household Longitudinal Study (UKHLS). This has been tracking the health and wellbeing of a representative sample of 40,000 households across the UK since 2009.

Information about working hours, weekend working, working conditions and psychological distress was collected from 11,215 working men and 12,188 working women between 2010 and 2012. Depressive symptoms such as feeling worthless or incapable were measured using a self-completed general health questionnaire.

“Women in general are more likely to be depressed than men, and this was no different in the study,” Weston said.

“Independent of their working patterns, we also found that workers with the most depressive symptoms were older, on lower incomes, smokers, in physically demanding jobs, and who were dissatisfied at work.”

She added: “We hope our findings will encourage employers and policy-makers to think about how to reduce the burdens and increase support for women who work long or irregular hours — without restricting their ability to work when they wish to.

“More sympathetic working practices could bring benefits both for workers and for employers — of both sexes.”

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Brain Response To Mom’s Voice Differs In Kids With Autism

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For most children, the sound of their mother’s voice triggers brain activity patterns distinct from those triggered by an unfamiliar voice. But the unique brain response to mom’s voice is greatly diminished in children with autism, according to a new study from the Stanford University School of Medicine.

The diminished response was seen on fMRI brain scans in face-processing regions and learning and memory centers, as well as in brain networks that process rewards and prioritize different stimuli as important.

The findings were published Feb. 26 in eLife.

“Kids with autism often tune out from the voices around them, and we haven’t known why,” said the study’s lead author, Dan Abrams, PhD, clinical assistant professor of psychiatry and behavioral sciences at Stanford.

“It’s still an open question how this contributes to their overall difficulties with social communication.”

The results suggest that the brains of children with autism are not wired to easily tune into mom’s voice, Abrams said. The study also found that the degree of social communication impairment in individual children with autism was correlated with the degree of abnormality in their brain responses to their mother’s voice.

“This study is giving us a handle on circuits and vocal stimuli that we have to make more engaging for a child with autism,” said the study’s senior author, Vinod Menon, PhD, the Rachael L. and Walter F. Nichols, MD, Professor and professor of psychiatry and behavioral sciences.

“We now have a template for targeting specific neural circuits with cognitive therapies.”

An important social cue

Mom’s voice is an important social cue for most children. For instance, tiny babies recognize and are soothed by their mother’s voice, while young teenagers are more comforted by words of reassurance spoken by their mothers than the same words sent by their mothers via text message, prior research has shown. The response to mom’s voice has a distinct brain-activation signature in children without autism, a 2016 paper co-authored by Abrams and Menon demonstrated.

Autism is a developmental disorder that affects 1 in 59  children. It is characterized by social and communication difficulties, restricted interests and repetitive behaviors. The disorder exists on a spectrum, with some children more impaired than others.

Mom’s voice is the primal cue for social and language communication and learning.

The new study included 42 children ages 7 to 12. Half had autism, and the other half didn’t. The children had their brains scanned using functional magnetic resonance imaging while listening to three different recorded sounds: their mother’s voice; the voices of unfamiliar women; and nonvocal environmental sounds. In the voice recordings, the women said nonsense words to avoid activating language comprehension regions in the brain.

The researchers compared patterns of brain activation and brain network connectivity between the two groups of children. They also asked the children to identify whether each brief (956-millisecond) voice recording they heard came from their mother or an unfamiliar woman. Children without autism correctly identified their mothers’ voices 97.5 percent of the time; those with autism identified their mothers’ voices 87.8 percent of the time, a statistically significant difference.

The brain response to unfamiliar voices, when compared with the response to environmental sounds, was fairly similar in children with and without autism, although those with autism had less activity in one area of the auditory association cortex.

When comparing the brain response to mom’s voice versus unfamiliar voices, children without autism had many more brain areas activated: Mom’s voice preferentially lit up part of the hippocampus, a learning and memory region, as well as face-processing regions. Brain-connectivity patterns measured in a network that included auditory-processing regions, reward-processing regions and regions that determine the importance, or salience, of incoming information also distinguished children with autism from children without autism. The network impairments in individual children with autism were also linked to their individual level of social communication impairment.

‘Really striking relationship’

“There is this really striking relationship between the strength of activity and connectivity in reward and salience regions during voice processing and children’s social communication activity,” Abrams said.

This suggests that brain responses to mom’s voice are a key element for building social communication ability, he added.

The findings support the social motivation theory of autism, which suggests that social interaction is intrinsically less engaging for children with the disorder than those without it.

Many current autism therapies involve motivating children to engage in specific types of social interaction. It would be interesting to conduct future studies to see whether these therapies change the brain characteristics uncovered in this study, the researchers said.

“Mom’s voice is the primal cue for social and language communication and learning,” Menon said.

“There is an underlying biological difference in the brain circuitry in autism, and this is a precision-learning signal we can target.”

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