Brain

CHICAGO -- A study in the March issue of The Journal of the American Dental Association from the Centers for Disease Control and Prevention found that antibiotics and opioids are frequently prescribed during emergency department visits for dental conditions, further emphasizing the need for continued efforts to combat both opioid abuse and overuse of antibiotics.

The authors found that more than 50 percent of patients who visited the emergency department for a dental-related condition filled a prescription for antibiotics and approximately 40 percent filled a prescription for opioids, based on data from 2012-2014. Further, the authors found that more than 30 percent of patients filled prescriptions for both an antibiotic and an opioid as a result of their visit.

"Given previous findings that dental-related diagnoses are a common and potentially avoidable reason for [emergency department] visits, the prescribing of antibiotics and opioids for these conditions becomes even more concerning," wrote the study authors.

In 2019, as part of its longstanding antibiotic stewardship efforts, the American Dental Association (ADA) released a new guideline indicating that, in most cases, antibiotics are not recommended for toothaches, which are a common dental-related reason to visit an emergency department. The guideline was developed by a multidisciplinary panel, including an emergency medicine physician nominated by the American College of Emergency Physicians.

The ADA has also held a longstanding commitment to raising awareness and taking action on the opioid public health crisis. Since 2011, the ADA has advocated to keep opioid pain relievers from harming dental patients and their families and worked to raise professional awareness on medication alternatives to opioids. A growing body of research supports ADA policy that dentists should consider prescribing non-steroidal anti-inflammatory drugs (NSAIDs) alone or in combination with acetaminophen over opioids as first-line therapy for acute pain management. In March 2018, the organization adopted policy that indicates a combination of ibuprofen and acetaminophen can be just as effective as opioids for acute pain.

Do a Google search for dark-field images, and you'll discover a beautifully detailed world of microscopic organisms set in bright contrast to their midnight-black backdrops. Dark-field microscopy can reveal intricate details of translucent cells and aquatic organisms, as well as faceted diamonds and other precious stones that would otherwise appear very faint or even invisible under a typical bright-field microscope.

Scientists generate dark-field images by fitting standard microscopes with often costly components to illumine the sample stage with a hollow, highly angled cone of light. When a translucent sample is placed under a dark-field microscope, the cone of light scatters off the sample's features to create an image of the sample on the microscope's camera, in bright contrast to the dark background.

Now, engineers at MIT have developed a small, mirrored chip that helps to produce dark-field images, without dedicated expensive components. The chip is slightly larger than a postage stamp and as thin as a credit card. When placed on a microscope's stage, the chip emits a hollow cone of light that can be used to generate detailed dark-field images of algae, bacteria, and similarly translucent tiny objects.

The new optical chip can be added to standard microscopes as an affordable, downsized alternative to conventional dark-field components. The chip may also be fitted into hand-held microscopes to produce images of microorganisms in the field.

"Imagine you're a marine biologist," says Cecile Chazot, a graduate student in MIT's Department of Materials Science and Engineering. "You normally have to bring a big bucket of water into the lab to analyze. If the sample is bad, you have to go back out to collect more samples. If you have a hand-held, dark-field microscope, you can check a drop in your bucket while you're out at sea, to see if you can go home or if you need a new bucket."

Chazot is the lead author of a paper detailing the team's new design, published in the journal Nature Photonics. Her co-authors are Sara Nagelberg, Igor Coropceanu, Kurt Broderick, Yunjo Kim, Moungi Bawendi, Peter So, and Mathias Kolle of MIT, along with Christopher Rowlands at Imperial College London and Maik Scherer of Papierfabrik Louisenthal GmbH in Germany.

Forever fluorescent

In an ongoing effort, members of Kolle's lab are designing materials and devices that exhibit long-lasting "structural colors" that do not rely on dyes or pigmentation. Instead, they employ nano- and microscale structures that reflect and scatter light much like tiny prisms or soap bubbles. They can therefore appear to change colors depending on how their structures are arranged or manipulated.

Structural color can be seen in the iridescent wings of beetles and butterflies, the feathers of birds, as well as fish scales and some flower petals. Inspired by examples of structural color in nature, Kolle has been investigating various ways to manipulate light from a microscopic, structural perspective.

As part of this effort, he and Chazot designed a small, three-layered chip that they originally intended to use as a miniature laser. The middle layer functions as the chip's light source, made from a polymer infused with quantum dots -- tiny nanoparticles that emit light when excited with fluorescent light. Chazot likens this layer to a glowstick bracelet, where the reaction of two chemicals creates the light; except here no chemical reaction is needed -- just a bit of blue light will make the quantum dots shine in bright orange and red colors.

"In glowsticks, eventually these chemicals stop emitting light," Chazot says. "But quantum dots are stable. If you were to make a bracelet with quantum dots, they would be fluorescent for a very long time."

Over this light-generating layer, the researchers placed a Bragg mirror -- a structure made from alternating nanoscale layers of transparent materials, with distinctly different refractive indices, meaning the degrees to which the layers reflect incoming light.

The Bragg mirror, Kolle says, acts as a sort of "gatekeeper" for the photons that are emitted by the quantum dots. The arrangement and thicknesses of the mirror's layers is such that it lets photons escape up and out of the chip, but only if the light arrives at the mirror at high angles. Light arriving at lower angles is bounced back down into the chip.

The researchers added a third feature below the light-generating layer to recycle the photons initially rejected by the Bragg mirror. This third layer is molded out of solid, transparent epoxy coated with a reflective gold film and resembles a miniature egg crate, pocked with small wells, each measuring about 4 microns in diameter.

Chazot lined this surface with a thin layer of highly reflective gold -- an optical arrangement that acts to catch any light that reflects back down from the Bragg mirror, and ping-pong that light back up, likely at a new angle that the mirror would let through. The design for this third layer was inspired by the microscopic scale structure in the wings of the Papilio butterfly.

"The butterfly's wing scales feature really intriguing egg crate-like structures with a Bragg mirror lining, which gives them their iridescent color," Chazot says.

An optical shift

The researchers originally designed the chip as an array of miniature laser sources, thinking that its three layers could work together to create tailored laser emission patterns.

"The initial project was to build an assembly of individually switchable coupled microscale lasing cavities," says Kolle, associate professor of mechanical engineering at MIT. "But when Cecile made the first surfaces we realized that they had a very interesting emission profile, even without the lasing."

When Chazot had looked at the chip under a microscope, she noticed something curious: The chip emitted photons only at high angles forming a hollow cone of light. Turns out, the Bragg mirror had just the right layer thicknesses to only let photons pass through when they came at the mirror with a certain (high) angle.

"Once we saw this hollow cone of light, we wondered: 'Could this device be useful for something?'" Chazot says. "And the answer was: Yes!"

As it turns out, they had incorporated the capabilities of multiple expensive, bulky dark-field microscope components into a single small chip.

Chazot and her colleagues used well-established theoretical optical concepts to model the chip's optical properties to optimize its performance for this newly found task. They fabricated multiple chips, each producing a hollow cone of light with a tailored angular profile.

"Regardless of the microscope you're using, among all these tiny little chips, one will work with your objective," Chazot says.

To test the chips, the team collected samples of seawater as well as nonpathogenic strains of the bacteria E. coli, and placed each sample on a chip that they set on the platform of a standard bright-field microscope. With this simple setup, they were able to produce clear and detailed dark-field images of individual bacterial cells, as well as microorganisms in seawater, which were close to invisible under bright-field illumination.

Kolle says that in the near future these dark-field illumination chips could be mass-produced and tailored for even simple, high school-grade microscopes, to enable imaging of low-contrast, translucent biological samples. In combination with other work in Kolle's lab, the chips may also be incorporated into miniaturized dark-field imaging devices for point-of-care diagnostics and bioanalytical applications.

"If we can outsource some of the light management to a surface that you can slap as the sample substrate onto a microscope, it makes dark-field imaging an intriguingly accessible option in a whole lot of imaging scenarios," Kolle says.

CLEMSON, South Carolina -- In the quest to develop more effective treatments for parasitic diseases like African sleeping sickness, Chagas disease and Leishmaniasis, scientists look for weaknesses in the organisms' molecular machinery. These weaknesses can then be targeted with drug therapies designed to kill the parasites.

While they've made significant strides in recent years, scientists are still trying to unravel how the parasites' complex molecular systems work.

A team of Clemson University College of Science researchers recently contributed to that understanding by discovering the function of a specific protein in the three related parasites -- Trypanosama brucei, Trypanosoma cruzi and Leishmania -- which afflict millions worldwide with diseases that are sometimes fatal.

According to genetics and biochemistry associate professor Meredith Morris, the parasites share some of  the same molecular makeup as humans, so drugs that can kill the parasites often do harm or have adverse side effects to the human hosts.

"We are always looking for ways that the parasites differ from us," Morris said. "One of the main differences is that the parasites have a specialized cellular compartment or organelle that is absolutely essential to their survival."

Morris and her team reported their results in mSphere on Feb. 19, 2020. The title of their paper is "Trypanosoma brucei Pex13.2 is an accessory peroxin that functions in the import of PTS2 proteins and localizes to subdomains of the glycosome."

That parasite-specific organelle is called the glycosome, which plays a crucial role in cell processes, particularly energy metabolism. The glycosome organelle is surrounded by a single membrane, where several proteins reside. These proteins (Pex13.1, 13.2 and 14) import other proteins required for normal cell functioning.

In their study, Morris and her students used biochemical approaches to partially resolve the composition of those three glycosome proteins. In the process, they demonstrated that Pex13.2 is an integral glycosome membrane protein that interacts with Pex13.1 and Pex14, which was previously not known.

Utilizing the advanced microscopy technology in Clemson's Light Imaging Facility, they also obtained very high-resolution images, and found that Pex13.2 exhibits a unique localization pattern that may be critical to its function.

"No one knew what Pex13.2 was doing, but our study adds to that understanding," said Morris, a member of Clemson's Eukaryotic Pathogens Innovation Center (EPIC). "Now we know that it plays a role in import of proteins and the division of the organelles."

The team also silenced Pex13.2, which resulted in parasites with fewer, larger glycosomes. Without 13.2, the parasite couldn't import glycosome proteins, resulting in the parasite's death.

"Others have shown that when 13.2 is knocked out, the cell dies," said Morris, noting that by fully understanding the organelle's parts and functions, drug companies could someday design rational approaches to disrupting the system and killing the parasite.

COLUMBUS, Ohio - Researchers have known that kids who are at high risk of being mistreated at home - who live in poverty or have parents who use drugs or have mental health problems - are more likely to start smoking. Because abused and neglected children are often unsupervised, these teens have easy access to cigarettes and other substances that they use to deal with anxiety and other trauma-related symptoms.

A new study shows that physical abuse of children in high-risk homes, especially when they're toddlers or teens, dramatically increases the odds that their adolescent experimentation with cigarettes will lead to a heavy smoking habit.

Neglect of very young children in the same high-risk population was linked to a gradual increase in cigarette use among teens who smoked.

The study examined data on children who were at high risk for abuse and neglect - either because they had been referred to a child protective service or lived in conditions associated with the likelihood of maltreatment, or both.

"I wanted to look at different types of maltreatment and whether they have an impact on cigarette smoking," said lead author Susan Yoon, assistant professor of social work at The Ohio State University. "There's also the impact of timing - it's not just maltreatment, yes or no. When did it happen, and does that matter with regard to outcomes?"

The study is published online in the journal Substance Use and Misuse.

Yoon noted that substance abuse research doesn't often take cigarette smoking into consideration despite its significant damaging effects on health.

"Adolescent cigarette smoking is a really serious social problem and public health concern. Brain development is not complete until late adolescence or during young adulthood, and cigarette smoking is associated with damage in brain development," Yoon said. "We also know that those who start smoking cigarettes during adolescence are more likely to continue smoking into adulthood."

Yoon and colleagues used data from the Longitudinal Studies of Child Abuse and Neglect, a consortium of studies across different regions of the United States targeting children who were identified as maltreated or at risk for maltreatment. This study used data on 903 adolescents who were assessed at age 12, 16 and 18.

A breakdown of different types of abuse and neglect experienced by the sample population during three different time periods (early childhood, school age and adolescence) confirmed how vulnerable these kids were. Almost a quarter had been neglected during early childhood and their school-age years, and 19 percent reported school-age physical abuse. Almost half lived in poverty and 58 percent lived in households in which family members smoked cigarettes.

Yoon used their responses about smoking between the ages of 12 and 18 to identify three patterns of cigarette use: stable low/no use (61 percent of respondents), gradually increasing use (30 percent) and sharply increasing cigarette use (9 percent).

"It was almost shocking how the pattern of cigarette use over time went up so drastically in the sharply increasing use class," Yoon said. "They were pretty similar to the others at age 12 - almost 80 percent didn't smoke. At age 16, we saw that almost 60 percent had used cigarettes more than 20 days in the past year and by 18, every single kid in this group reported heavy use of cigarettes."

A statistical analysis showed that adolescents who experienced early childhood physical abuse were 2.3 times more likely to be in the sharply increasing cigarette use group compared with the stable no/low group. Physical abuse during adolescence had an even stronger effect - this type of mistreatment at that point in life was linked to 3.7 times higher odds for sharply increased cigarette use.

Adolescents who had been neglected during early childhood were 1.89 times more likely to be in the gradually increasing cigarette use group than in the stable no/low use group. Neglect can include a lack of appropriate supervision and failure to meet kids' needs - ranging from food and clothing to medical needs and education.

About 40 percent of these smokers had reported using cigarettes at age 16, and by age 18, more than 80 percent were smokers, and about 40 percent had smoked on more than 20 days in the previous year.

The analysis also measured the potential effects of sexual abuse and emotional abuse on cigarette use, but neither was a predictor of an increase in smoking.

"The different types of maltreatment predicted different patterns of cigarette use, but the timing mattered as well. It was early childhood and adolescence that appear to be really sensitive periods in which maltreatment influences these outcomes," Yoon said.

The results suggest efforts to prevent smoking by teens at risk of maltreatment - and especially children experiencing physical abuse and neglect - should start before age 12, she said.

"If we intervene too late, it's likely they've already started using cigarettes and are in the process of using more cigarettes," Yoon said. "We know from our studies that these kids experiencing physical abuse and neglect are at much higher risk of showing this poor pattern of cigarette use over time. We should be targeting this high-risk group for cigarette use prevention and intervention."

For decades, researchers have suggested a link between oral health and inflammatory diseases affecting the entire body -- in particular, heart attacks and strokes. Inflammation is intimately involved in the pathogenesis of atherosclerosis and is accurately measured by high sensitivity C-reactive protein (hs-CRP), a sensitive marker for future risks of heart attacks and strokes.

Researchers from Florida Atlantic University's Schmidt College of Medicine, Marshfield Clinic Research Institute, and the University of Wisconsin School of Medicine and Public Health, collaborated on a randomized trial titled, "Correlation between Oral Health and Systemic Inflammation" (COHESION), to further explore whether Plaque HD®, a plaque identifying toothpaste, reduces hs-CRP.

Results of the randomized pilot trial, published online ahead of print in the American Journal of Medicine, showed that Plaque HD® produced a statistically significant reduction in hs-CRP among those with elevations at baseline. Plaque HD® is the first toothpaste that identifies plaque so that it can be removed with directed brushing. In addition, the product's proprietary formulation contains unique combinations and concentrations of cleaning agents that weaken the core of the plaque structure to help the subject visualize and more effectively remove the plaque.

In this trial, all randomized subjects were given the same brushing protocol and received a 30-day supply of toothpaste containing either Plaque HD® or an identical non-plaque identifying placebo toothpaste. To assess hs-CRP, levels were measured by Quest Diagnostics using an enzyme linked immunosorbent assay.

"The current findings are similar to those from our previous pilot trial," said Charles H. Hennekens, M.D., Dr.P.H., senior author, first Sir Richard Doll Professor, and senior academic advisor in FAU's Schmidt College of Medicine. "Whether this plaque-identifying toothpaste decreases heart attacks or strokes requires a large-scale randomized trial of sufficient size and duration. These results provide a stronger rationale to conduct such trials. If positive, the results of these trials would have significant potential clinical and public health implications."

Based on these findings, Hennekens and colleagues at FAU and the University of Wisconsin School of Medicine and Public Health are drafting an investigator-initiated research grant proposal to the National Institutes of Health (NIH). Their proposed randomized trial will test whether Plaque HD® reduces progression of atherosclerosis in the coronary and carotid arteries, for which systemic inflammation is an important precursor.

A report from the United States Centers for Disease Control and Prevention found that 47.2 percent of American adults aged 30 years and older have some form of periodontal disease, a pathological inflammatory condition of the gums and tissues surrounding the teeth. Periodontal disease increases with age affecting more than 70 percent of adults 65 years and older. Prior research has suggested that periodontal disease may be connected to variety of other diseases, including heart disease and stroke and other inflammatory diseases such as rheumatoid arthritis. Inflammation throughout the body may be a crucial link between periodontal and other systemic diseases.

Further, two years ago, the prestigious New England Journal of Medicine ranked the original manuscript published in 1997 by Hennekens and colleagues on aspirin, inflammation and cardiovascular disease, as their most influential original report of the last 20 years. Those randomized data derived from the landmark Physician's Health Study, in which Hennekens was the founding principal investigator, and suggested that hs-CRP predicted future heart attacks and strokes.

BEER-SHEVA, ISRAEL...February 24, 2020 - While no one at work wants to be kept waiting, according to a new study by researchers from Ben-Gurion University of the Negev (BGU) and the University of British Columbia (UBC), reactions to waiting can be managed to reduce aggression that may result from the wait.

"We spend a part of our daily life waiting, and unfortunately, wait time can fuel aggressive tendencies," says Dr. Dorit Efrat-Treister, from the BGU Guilford Glazer Faculty of Business and Management. "Our study examines the relationship between wait time, perceived wait time, and aggressive tendencies from a construal level perspective."

Construal level refers to how abstract or concrete people perceive, comprehend and interpret the world around them.

Generally, abstract thinking leads to better outcomes, such as more creativity, wider vision and feeling more powerful. However, in the paper published in the Journal of Organizational Behavior (2020), Efrat-Treister, and UBC researchers Michael Daniels and Sandra Robinson demonstrate that abstract thinking can also lead to undesired outcomes in stressful situations, such as waiting.

"For example, if you are waiting for someone who is late to meet you, you are better off thinking in concrete terms, like assuming they got stuck in a traffic jam compared with abstract terms, like assuming they are disrespecting you," Efrat-Treister says. "When someone is late for a call, if you think abstractly, you may think they don't respect your time, or they don't think the call is important, and therefore you might become mad. But if you think they may have just misplaced your number or got another call first, you won't become so annoyed."

In the experiments, the researchers arranged a meeting of people in a lab and each were told their partner was late. Sitting in separate rooms, each waited for 30 seconds, five minutes or 10 minutes. Those that were prompted to think abstractly perceived the waiting time as longer, and reacted more aggressively than those that were led to think concretely.

Generation Y and Z participants had an especially difficult time in the experiment without their cell phone and started banging on the desks or fidgeting, and self-reported high levels of aggression after waiting for even short durations of time.

"We showed that the level of abstractness influences how long or short one perceives actual wait time. Therefore, we can influence the perception of the wait time and thus manage aggression," Efrat-Treister says.

It can be both costly and difficult for organizations to reduce wait time and can require additional resources that may not be available. As the study shows, managers can reduce the perception of wait time without adding resources by priming people to think more concretely and distracting them from the time that has passed.

"For example, medical offices might want to install video monitors with concrete information that distracts from long wait times," Efrat-Treister says. "The leader of a meeting can focus on getting started and on the agenda rather than focusing on why a partner is late. Any concrete focus that prevents abstract thinking about waiting can be helpful."

New research led by scientists from the University of Bristol has revealed new insights into how the microscopic algae that thrives along the edge of the Greenland Ice Sheet causes widespread darkening.

This darkening is critically important as darker ice absorbs more sunlight energy and melts faster, accelerating the overall melting of the ice, which is the single largest contributor to global sea level rises.

Extremophile microscopic algae, or so-called 'glacier algae', are able to live in the upper few centimetres of ice on the surfaces of glaciers and ice sheets and can form widespread blooms during the summer melt season.

Glacier algal blooms on the Greenland Ice Sheet are so extensive that their presence in the surface ice is thought responsible for widespread darkening along the western margin of the ice sheet known as the 'dark zone' that has appeared in satellite observations over the last two decades.

The link between ice sheet darkening and glacier algal blooms had already been supported by modelling and field observations, but it is still unknow exactly how or why the algae causes widespread darkening.

Using detailed field observations, sampling, experimentation and modelling, the Bristol-led team, as part of the NERC-funded Black and Bloom Project, have demonstrated how glacier algae regulate energy within their cells in order to balance their requirements for photosynthesis and growth with the extreme light and temperature environment of the Greenland Ice Sheet and how they are optimised to darken and melt the ice.

The study, published in the journal Proceedings of the National Academy of Sciences, reveals how glacier algae produce a unique phenolic 'sunscreen' pigment at 11-times the cellular content of chlorophyll-a (normally the most abundant pigment in green microalgae).

This phenolic pigment serves to capture and absorb most of the intense sunlight that the algae receive where they live on the surface of the ice sheet, protecting the algae's chloroplasts, which are located underneath vacuoles filled with this pigment, from excessive UV and visible radiation.

The energy that is absorbed by this sunscreen pigment is subsequently available to the cell as heat for melt generation - an incredibly clever mechanism for algae that lives in an icy world, where access to liquid water is a major limitation on growth and survival.

This pigmentation protects cells from excessive sunlight, but also harnesses the energy for melt generation proximal to the cell, providing access to liquid water and dissolved nutrients critical for life.

Unfortunately, this heavy production of pigment is also one of the reasons why the Greenland Ice Sheet darkens so significantly during summer melt seasons, when glacier algae reach bloom abundances (around 10,000 cells per millilitre of melt water) in surface ice, driving an approximate ten percent increase in surface melt.

The study's lead author, Dr Chris Williamson from the University of Bristol's Bristol Glaciology Centre and School of Geographical Sciences, said: "Permanently cold ecosystems make up more than 70 percent of the Earth's biosphere, though we know very little about the microorganisms that are able to thrive in these extreme environments.

"Our work has provided novel insight in the ecology and physiology of extremophile microalgae that live on the surfaces of glaciers and ice sheets, demonstrating how life is able to thrive within these extreme icy environments.

"This work has significant applied applications for studies of the mass balance (melt versus growth) of glacier and ice sheet systems, allowing the incorporation of such 'biological-albedo' effects into calculations of ice sheet surface reflectance (darkening) and melt."

After quantifying the full suite of pigments produced by glacier algae and modelling their growth on the surface of the Greenland Ice Sheet surface, the team's next step is to incorporate all of these 'biological effects' into larger models of Greenland ice sheet mass balance to predict their overall contribution to melt of the ice sheet and global sea level rise.

This next step necessitates a numerical modelling approach using large-scale regional climate models, given the size of the Greenland Ice Sheet. This work is currently underway as part of the Black and Bloom and Deep Purple projects.

DALLAS - Feb. 20, 2020 - Switching what the powerhouses of heart cells consume for energy could help the heart regenerate when cells die, a new study led by UT Southwestern researchers suggests. The finding, published in the Feb. 20, 2020, Nature Metabolism, could open whole new avenues for treating a variety of conditions in which heart muscle becomes damaged, including heart failure caused by viruses, toxins, high blood pressure, or heart attacks.

Current pharmaceutical treatments for heart failure - including ACE inhibitors and beta blockers - center on trying to stop a vicious cycle of heart muscle loss as strain further damages remaining heart muscle, causing more cells to die, explains UT Southwestern physician-researcher Hesham A. Sadek, M.D., Ph.D., the J. Fred Schoellkopf, Jr. Chair in Cardiology. There are no existing treatments for rebuilding heart muscle.

Nine years ago, Sadek and his colleagues discovered that mammalian hearts can regenerate if they're damaged in the first few days of life, spurred by the division of cardiomyocytes, the cells responsible for a heart's contractile force. However, this capacity is completely lost by 7 days old, an abrupt turning point in which division of these cells dramatically slows.

Subsequent research has shown that this change in regenerative capacity appears to stem, at least in part, from damaging free radicals generated by organelles known as mitochondria, which power cells. These free radicals damage cells' DNA, a phenomenon called DNA damage, which prompts them to stop dividing.

The shift in free radical production appears to be spurred by a change in what mitochondria in the cardiomyocytes consume for energy, Sadek explains. Although mitochondria rely on glucose in utero and at birth, they switch to fatty acids in the days after birth to utilize these energy-dense molecules in breast milk.

Sadek and his colleagues wondered whether forcing mitochondria to continue to consume glucose might stymie DNA damage and, in turn, extend the window for heart cell regeneration. To test this idea, the researchers tried two different experiments.

In the first, they followed mouse pups whose mothers were genetically altered to produce low-fat breastmilk and that fed on low-fat chow after they weaned. The researchers found that these rodents' hearts maintained regenerative capacity weeks later than normal, with their cardiomyocytes continuing to express genes associated with cell division for a significantly longer window than those fed a diet of regular breastmilk and chow. However, this effect didn't last into adulthood - their livers eventually made up the deficit by synthesizing the fats that their diets were missing, which significantly reduced their hearts' regenerative capacity.

In the second experiment, the researchers created genetically altered animals in which the researchers could delete an enzyme, known as pyruvate dehydrogenase kinase 4 (PDK4), necessary for the heart cells' mitochondria to digest fatty acids. When the researchers delivered a drug to turn off PDK4 production, the animals' cardiomyocytes switched to consuming glucose instead of fatty acids, even in adulthood. After researchers simulated a heart attack, these animals experienced improvement in heart function, which was accompanied by markers in gene expression that suggested their cardiomyocytes were still actively dividing.

Sadek notes that these findings provide proof of principle that it's possible to reopen the window for heart cell regeneration by manipulating what cardiomyocyte mitochondria consume for energy.

"Eventually," he says, "it may be possible to develop drugs that change what cardiomyocytes eat to make them divide again, reversing heart failure and representing a true cure."

Walking is one of our most natural, daily actions. Now, a new study led by a Tohoku University researcher suggests that walkers use step synchronization as a form of non-verbal social communication. The results lend credence to the effects of psychological traits on movement interaction between humans.

Published in PLOS ONE, the study results demonstrate how people's traits and first impression affect their nonverbal communication, i.e. synchronous walking.

In order to conduct the study, researchers divided participants into groups. In total, ten single-gender groups were formed - five female and five male. Group members took turns being paired up with other members, and they walked together along a quiet, barrier-free path. They wore voice recorders, and motion sensors disguised as GPS devices recorded their walking movements.

Researchers carried out the experiment under three conditions: a half silent walk half conversation condition where participants did not speak for half of the journey, yet conversed on  the way back; a silent walk condition where participants did not converse for the entirety of the journey; and lastly, a non-walking condition where participants did not walk and sat quietly filling in a questionnaire in a classroom.

Participants had no prior knowledge of each other, and were asked to rate their impression of their partners before and after each walk using the interpersonal judgment scale (IJS). Furthermore, researchers misled participants about the true nature of the study to prevent them from intentionally synchronizing their steps.

The results revealed an increase in the impression ratings for the two groups of participants who walked together, but not for the group of participants who simply spent time together. This suggests that walking side-by-side, even without verbal communication, is sufficient to alter the social relation between two strangers. Results also showed that conversations further enhanced impressions for participants who were allowed to talk. Ultimately, the experiment successfully dissociated the contribution of verbal communication from walking step synchronization, which was inseparable in previous studies.

The researchers also found that pairs with a better first impression had greater synchronization in their steps - particularly for female participants. In addition to social relation, personal traits are also important. Female pairs, compared to male pairs, exhibited higher walking synchrony in this experiment. There is also an age effect - older participants tend to synchronize with their partners more in walking. Participants with lower autistic tendencies synchronize better than pairs of higher autistic tendencies.

"It is very surprising for us to discover that a person's traits and our first impressions are reflected in the subtle action of walking. I think most people are not even aware that their steps are synchronized with other people as they walk," said Dr. Chia-huei Tseng, an associate professor at the Research Institute of Electrical Communication (RIEC) at Tohoku University. "It was previously known that a person's physical parameters such as height and weight affect how their movements interact with others. Now we know psychological traits also have an effect."

"There is a growing awareness of the validity of interpersonal interaction research in real-world scenarios, but daily natural environments are rich in their contextual information, making experiment control a challenge," said Dr. Miao Cheng, a post-doc researcher at NTT Communication Science Laboratories. "Our study is important because it is an approach to make the most use of an ecological paradigm while using scientific experimental method to control possible confounding variables to examine the function of implicit body synchrony."

LOS ANGELES, Feb. 21, 2020 - Skipping IV clot-busters and using mechanical clot removal alone for strokes may be just as good as the combination of both treatments, with less risk of brain bleeding, according to late breaking science presented today at the American Stroke Association's International Stroke Conference 2020. The conference, Feb. 19-21 in Los Angeles, is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

Using both therapies was previously reported to improve outcomes in acute stroke patients with large vessel occlusion. However, clot-busters could cause bleeding in the brain, and no studies have looked at mechanical clot removal alone without alteplase, the most commonly administered IV clot-busting medication, within 4.5 hours.

In a Japanese, multicenter, prospective, randomized trial, about 200 stroke patients (average age 74; 62% men) were assigned to either mechanical clot removal alone or the combination of IV clot-busters and mechanical clot removal. At 90 days, favorable outcomes, based on disability level, were similar: 59% for those who received clot removal alone and 57% for those who received the combination approach. There was no difference in death rates between the two groups. However, the rates of brain bleeding within 36 hours was significantly lower for the mechanical clot removal group than for the combination treatment group (34% vs. 50%, respectively).

"We feel that giving alteplase to dissolve clots is not necessary, and mechanical clot removal can be performed immediately," said Kentaro Suzuki, M.D., Ph.D., lecturer in the department of neurology at Nippon Medical School Hospital in Japan. "If we skip alteplase, we can perform mechanical thrombectomy with low risk of bleeding."

Suzuki noted that five ongoing trials including this study are investigating the optimal approach for stroke patients.

"Current recommendations from the American Heart Association/American Stroke Association recommend using intravenous therapy within the 4.5 hour-time window and then treating with mechanical clot removal, if appropriate," said Mitchell S. V. Elkind, M.D., M.S., FAHA, FAAN, president elect of the American Heart Association, past chair of the Advisory Committee of the American Stroke Association -- a division of the American Heart Association and professor of neurology and epidemiology at Columbia University New York and attending neurologist at Columbia University Medical Center of the New York-Presbyterian Hospital.

"The best strategy is usually to treat with [alteplase] . . . and then if the patient is eligible, the patient goes for endovascular therapy as well," Elkind said. "But [we] don't skip that initial step because sometimes the endovascular therapy gets delayed or doesn't occur for some reason or another."

CHICAGO (February 21, 2020): Colon cancer is more likely to be lethal in children and young adults than middle-aged adults. In a single-institution study, researchers at The University of Texas MD Anderson Cancer Center, Houston, Tex., found that differences in mortality rates persist regardless of whether pediatric, adolescent, and young adult patients (aged 24 and younger) were born with a predisposition for colon abnormalities or disease and for the first time conclude that young people are more likely to have metastases outside the colon, into the abdominal cavity, when they are diagnosed. Their findings put families, clinicians, and surgeons on alert to be sure abdominal complaints in young people are thoroughly and carefully evaluated when first reported, and aggressively treated if cancer is discovered. Study findings appears in an "article in press" on the Journal of the American College of Surgeons website in advance of print.

Colon cancer is rare in individuals under age 25. Prevalence of the disease in patients under age 20 is 0.2 percent. While the Surveillance, Epidemiology and End Results Program (SEER) estimates more than 145,000 new cases of colon cancer for 2019, only about 290 cases are expected in children and young adult people.1

The diagnosis of colon cancer in children, and young adults is often delayed. Most (70 percent) children and young adult patients in a 2019 survey by Colorectal Cancer Alliance were diagnosed with stage 3 or stage 4 disease. In contrast, older patients are more likely to be diagnosed with stage 1 or 2 disease.2

"Children with colon cancer can fall through the cracks. They may be seen by an oncologist who treats adults but who doesn't know how to treat children. Or they may be seen by a pediatrician who knows all about treating children but nothing about colon cancer," said Andrea Hayes-Jordan, MD, FACS, lead author of the paper, and Surgeon-in-Chief of the North Carolina Children's Hospital, University of North Carolina, Chapel Hill. She was a professor and section chief of pediatric surgery at MD Anderson at the time the study was conducted.

The result is no clear path for treating children with colon cancer, other than providing the same treatment as adults. Furthermore, study findings clearly show that these types of interventions are not effective. "Stage for stage, children fare 5 to 6 times worse with treatment. So a child with Stage 4 disease has a 6 times higher chance of dying than an adult with the same stage of cancer," Dr. Hayes-Jordan said.

For the study, researchers compared retrospective outcomes for 94 pediatric patients treated at MD Anderson between 1991 and 2017 with a prospectively maintained database of outcomes for adult patients who were treated for colon cancer. Three-year overall and relapse-free survival differed markedly: 90 percent and 78 percent for adults versus 42 percent and 32 percent for children. Except for patients with stage 1 disease, a stage-for-stage comparison showed much lower survival rates for children. Five-year overall survival at stage 2 was 90 percent for adults versus 64 percent for children, at stage 3, 85 percent for adults versus 58 percent for children, and at stage 4, 55 percent for adults and 16 percent for children.

Relapse-free survival by stage were: 85 percent for adults versus 55 percent for children with stage 2 disease, 73 percent for adults and 31percent for children with stage 3 cancer, and 27 percent for adults versus 5 percent for children with stage 4.

Although some congenital abnormalities have been associated with colon cancer in young people, 71 percent of the patients in this study had no predisposing syndrome. This study also is the first to show that peritoneal (inside the abdomen but outside of the colon) metastasis is significantly higher (p=0.00001) in pediatric patients, the authors report.

"Although some may think the study raises more questions than it answers, it at least illuminates the problem so we can start working on it," Dr. Hayes-Jordan said.

In fact, Dr. Hayes-Jordan will soon be co-leading a clinical trial that will gather tissue from adults and children with peritoneal disease and conduct genetic analyses to try to identify differences in tumors in children and investigate treatment alternatives that will benefit these patients.

Until more is known about pediatric colon cancer, Dr, Hayes-Jordan advises parents and clinicians to be vigilant. "Early symptoms, such as bloating, abdominal fullness, general abdominal discomfort need to be taken seriously. They need to be evaluated with computed tomography scans or other imaging technologies to identify the specific problem, and not dismissed as the stomach flu or a simple tummy ache after eating bad food," she said.

Dr. Hayes-Jordan also recommends a surgical procedure up front and surgical excision that removes as much of the tumor as possible.

"Children are not small adults. They should be treated with independent thought and careful evaluation," she concluded.

Resistance to antibiotics has been declared a global health emergency – and it’s not just humans who are impacted by this public health crisis. Antibiotics used in food-producing animals contribute to the development of bacteria that are resistant to treatment, impacting animal health and potentially human health.

A special issue of Animal Health Research Reviews turns the spotlight on the science underlying this growing crisis - looking at the evidence base for using antibiotics to prevent illness in beef and dairy cattle, swine, and broiler poultry.

The scientists who introduce the collection - from the University of Guelph in Canada and the Iowa State University - conclude that veterinarians and food-animal producers know far too little about prevention or control measures, including antibiotic efficacy and antibiotic alternatives that could help to support antibiotic stewardship among animals.

The collection of 14 articles in the special issue - written by experts in the field from the US, Canada and beyond - examine publicly available evidence related to control of diseases in livestock and poultry. The articles, which are available via open source, focus on management practices that are designed to keep animals healthy and therefore reduce the need to use antibiotics - as well as looking at the administration of antimicrobials to prevent or control disease.

Despite finding evidence that some of the interventions were effective, across the body of research scientists found inconsistency in outcomes among trials, and highlighted serious concerns related to the completeness of reporting and trial design and execution that have been hidden in veterinary medicine for years.

For some interventions, scientists found that the body of evidence of efficacy was compelling. For example, a study of existing clinical trials on the efficacy of teat sealants for dairy cows found that the products studied were likely to be effective for reducing mastitis. Similarly, several antibiotics were shown to be effective at controlling respiratory diseases among cattle.

However, other evidence was less compelling. For bovine respiratory disease in beef cattle, for example, scientists found no evidence that the current use of vaccines was effective. Similarly, for antibiotics and vaccines used to prevent bacterial respiratory disease in swine, the body of evidence was insufficient to determine whether or not these interventions were effective. For litter management in poultry and preventive antibiotics for the treatment of E coli, the body of evidence was also lacking.

The reviews conducted as part of the special issue of Animal Health Research Reviews highlighted that more and better research on these issues is urgently needed to help guide decision-making on the best use of antibiotics in future.

"As the threat of antimicrobial resistance grows, stewardship of these vital drugs is increasingly important in both human and animal health," the editors conclude. "Important facets of antimicrobial stewardship include using antibiotics judiciously as well as taking measures to minimize the need to use antimicrobials at all."

A new article by the Oxidative Stress and Cell Cycle research group at UPF identifies the main strategy of cells to deal with the accumulation of misfolded proteins. In the paper, published today in the journal Cell Reports, the Schizosaccharomyces pombe yeast model has been used to investigate the protein quality control process. The study was led by Elena Hidalgo, and postdoctoral researchers Margarita Cabrera and Susanna Boronat are its first authors.

Proteins are made up of chains of amino acids and during their formation they must fold to acquire an appropriate shape enabling them to perform their functions. However, when cells are subjected to stress or harm, such as high temperatures, some of the proteins may not fold properly. In this study, the researchers posed the question: what do cells do with misfolded proteins?

There are three ways to solve the problem. The first option is to try to fix the folding in order to regain function, but this can be tricky because if stress conditions continue, the proteins continue unfolding. A second way is to destroy proteins that have not properly folded by way of a machinery called proteasome. "But, in this study we reveal that the dominant route in yeast is a third option consisting of the formation of aggregates to protect misfolded proteins from degradation", Elena Hidalgo explains.

The dual role of chaperones

Chaperones are small biological machines whose function is to fold proteins to achieve their optimal performance form. They are usually involved in the folding process and their function is often to prevent aggregation. "However, under stress conditions due to high temperatures, we have identified chaperones that play a key role in enhancing the aggregation route", Margarita Cabrera explains. "They detect that protein folding is not the solution and thus will actively promote the aggregation route", she adds.

The chaperones in question work in pairs, one of them is responsible for recognizing the substrate that is misfolded --detecting regions that should be inside the protein and when not correctly folded remain exposed-- and transferring it to the other. "Therefore, we have determined that under stress, chaperones slightly change their role to promote aggregation", Susanna Boronat comments.

Although aggregates are usually associated with toxicity and adverse effects, for example in neurodegenerative diseases, in this case they are favourable. The main advantage of promoting aggregation in regard to degradation is that when the conditions return to optimal, the proteins can fold again and recover their function. Synthesizing proteins is a costly task for the cell because it requires resources and by keeping a reservoir it can save having to make them again. "As an example of stress conditions we use high temperatures, though for a very short time, to ensure that the damage is reversible", Susanna Boronat adds.

Schizosaccharomyces pombe, a model for understanding complex mechanisms

The team of researchers from the Department of Experimental and Health Sciences (DCEXS) at UPF has conducted this research on Schizosaccharomyces pombe yeast, an organism that has the advantage of simple, easily manipulated genetics, that allows handling many different conditions. Moreover, many of yeasts' basic molecular mechanisms can be extrapolated to other eukaryotic organisms. When dealing with as complex a process as protein stability it is always good to have a model that is very simple in order to lay the foundations.

In the words of Margarita Cabrera: "we would like to start a new line of research and study the formation of protein aggregates in other model organisms and during the ageing process".

The research team is made up of Margarita Cabrera, Susanna Boronat, Luis Marte, Montserrat Vega, José Ayté and Elena Hidalgo at UPF, and Pilar Pérez at the Institute of Functional Biology and Genomics (IBFG) of the CSIC and the University of Salamanca.

When carbonate rocks weather, karst landscapes are formed. The groundwater reserves in these layers of earth currently supply 10 to 20 percent of the world population with drinking water. So far, however, researchers have not been able to precisely determine the amount of water present in karst regions. The reason for this is that the computational models cannot adequately capture the special features of hydrological processes in karst regions without observational data. As a result, reliable information for sustainable water management is often lacking. To address this problem, a team led by Tunde Olarinoye, Vera Marx and Assistant Professor Dr. Andreas Hartmann from the University of Freiburg has developed the "World Karst Spring hydrographs database" (WoKaS). The group presented the database in the journal Nature Scientific Data.

Previous research on karst hydrology has concentrated on the local level and the respective catchment areas. Very few studies have taken into account how climate and land use changes affect karst water resources on a large scale. Scientists have not been able to draw on sufficient observational data for this. The new database contains more than 400 karst spring discharge data, which represents the highest number of observations of karst springs worldwide. For the study, the Freiburg researchers and more than 50 co-authors reviewed articles, reports and national hydrological databases and compiled the observations.

"Thanks to the database, researchers, hydrologists and people working in water management now have free access to a high-quality data set," explains Olarinoye. A large part of the data sets, available for download, is frequently updated. This makes the information suitable for various applications such as trend analyses, impact studies and model evaluations.

For his doctoral thesis, Olarinoye is analyzing large groundwater data sets from karst regions. The project is part of Hartmann's research project 'Global Assessment of Water Stress in Karst Regions in a Changing World" (GloW), which is funded by the Emmy Noether Programme of the German Research Foundation. The Karst Research Association and the Karst Commission of the International Association of Hydrogeologists supported the researchers in setting up the global database.

AMHERST, Mass. ¬- In a new paper, climate scientists at the University of Massachusetts Amherst and Woods Hole Oceanographic Institution propose that massive amounts of melting sea ice in the Arctic drained into the North Atlantic and disrupted climate-steering currents, thus playing an important role in causing past abrupt climate change after the last Ice Age, from about 8,000 to 13,000 years ago. Details of how they tested this idea for the first time are online now in Geology.

Raymond Bradley, director of UMass Amherst's Climate Systems Research Center, and lead author Alan Condron, research scientist at Woods Hole, explain that geologists have considered many theories about abrupt temperature plunges into "glacier-like" conditions since the last glaciers retreated, notably a very cold period about 12,900 years ago, known as the Younger Dryas. Meteorite impact and volcanic eruptions were proposed to explain these episodes, but evidence has been unconvincing, they add.

Now Condron and Bradley, with Ph.D student Anthony Joyce, say they have new evidence that periodic break-up of thick Arctic sea ice greatly affected climate. Melting of this ice led to freshwater flooding into the seas near Greenland, Norway and Iceland between 13,000 and 8,000 years ago, slowing the strength of the Atlantic Meridional Overturning Circulation (AMOC). They say their experiments show that there was enough cold, fresh water to disrupt ocean salt-temperature circulation patterns and triggr abrupt climate cooling such as the Younger Dryas.

Bradley explains, "Understanding the past helps us understand how the Arctic system works."

Condron says researchers once thought this cold period was triggered by the draining of Lake Agassiz, an enormous glacial lake at the edge of the massive ice sheet that once extended from the Arctic south into modern New York. "But although the lake was big by modern standards, it has been difficult in the climate modeling community to trigger a 1,000-year cold period with the water it contained, because the volume of water is not large enough to weaken the Atlantic circulation over a long period," he notes.

"However, the volumes of water we find stored as sea ice in the Arctic vastly exceed the volume of Lake Agassiz, making sea ice break-up a really good candidate for triggering the Younger Dryas cooling," he adds.

To establish that there was enough ice in the Arctic to disrupt the sea circulation pattern, the researchers used numerical climate model experiments to estimate past Arctic sea ice extent and thickness. They also examined diaries and journals of early 19th and 20th century Arctic expeditions to see if those explorers, whose explorations came at the end of a "Little Ice Age," encountered unusually thick sea ice.

Condron and Bradley cite the impressions of Vice-Admiral Sir George Nares, who led the 1875 British Arctic Expedition to the North Pole. He was so struck by the extensive, thick ice his expedition encountered that he introduced the term "palaeocrystic ice" to describe "floes... of gigantic thickness with a most uneven surface and covered with deep snow."

They note, "It seems from these, and other accounts kept by early Arctic explorers, that the Arctic Ocean was covered by ice considerably thicker than has been observed over the past 30-40 years. While recent climate warming in the Arctic has caused much of this old and thick ice to break up and melt, large pieces of it were also still being reported in the early 20th century." including floes used as scientific research stations by both the U.S. and Russia as late as the Cold War.

They say their numerical ocean/sea-ice model of the volume of freshwater stored as sea ice and changes in ice export at the end of the Ice Age show these were large enough to slow the AMOC and cool climate. Thick ice over the Arctic Ocean created "an enormous reservoir of freshwater, independent of terrestrial sourc¬es." As ice sheets retreated and sea level rose, changes in atmospheric circulation and land-based floods caused this ice to flow to the sea through Fram Strait east of Greenland, where it melted and freshened Nordic Seas enough to weaken Atlantic circulation.

As both the volume of ice stored in the Arctic Basin and the magnitude of these export events far exceed the volume of meltwater discharged from Lake Agassiz, they report, "our results show that ice from the Arctic Ocean itself may have played an important role in causing abrupt climate change in the past." This work was supported by the National Science Foundation and its Extreme Science and Engineering Discovery Environment. Also, numerical simulations were carried out using MITgcm.