Culture

Biomedical engineers at Duke University have used deep brain stimulation based on light to treat motor dysfunction in an animal model of Parkinson's disease. Succeeding where earlier attempts have failed, the method promises to provide new insights into why deep brain stimulation works and ways in which it can be improved on a patient-by-patient basis.

The results appear online on April 20 in The Journal of Neuroscience.

"If you think of the area of the brain being treated in deep brain stimulation as a plate of spaghetti, with the meatballs representing nerve cell bodies and the spaghetti representing nerve cell axons, there's a longstanding debate about whether the treatment is affecting the spaghetti, the meatballs or some combination of the two," said Warren Grill, the Edmund T. Pratt, Jr. School Distinguished Professor of Biomedical Engineering at Duke.

"But it's an impossible question to answer using traditional methods because electrical deep brain stimulation affects them both as well as the peppers, onions and everything else in the dish. Our new light-based method, however, is capable of targeting just a single ingredient, so we can now begin teasing out the individual effects of activating different neural elements."

In Grill's metaphor, the meatballs are the neurons that make up the subthalamic nucleus, a small component of the basal ganglia control system that is believed to perform action selection. While its exact function remains unknown, research suggests that it holds muscular responses in check. The spaghetti in the bowl represents long nerve fibers called the hyperdirect pathway that extend into the region from neurons in the cerebral cortex, the thin outer layer of neurons responsible for most of the brain's information processing. And the peppers, onions and other ingredients are the various types of support cells found throughout the brain.

As Grill suggests, teasing out the role all of these various types of cells plays in mediating the effects of deep brain stimulation is nearly impossible using traditional methods. Individual types of cells cannot be singled out by electrical stimulation, and the electric pulses blind researchers' sensors for a crucial millisecond directly after firing.

In 2006, a team of researchers attempted to use optogenetics to skirt these issues. Optogenetics is a method of genetically modifying specific cells to express light-sensitive ion channels, allowing researchers to control their activity with flashes of light. The researchers embedded these light-sensitive ion channels into the subthalamic nucleus "meatballs" in rats and flashed pulses of light at the same rate used in deep brain stimulation. The treatment, however, failed to alleviate any of the rats' physical symptoms, leading the researchers to conclude that stimulating the subthalamic nucleus on its own is an inadequate treatment approach.

But the study never sat quite right in Grill's mind.

"Neurons being stimulated with optogenetics don't generally respond very quickly, and it seemed to me that the researchers were flashing their lights faster than the neurons could keep up with," said Grill. "The data bore this out, as the neurons appeared to be responding randomly rather than in sync with the flashes. And previous research that we conducted showed that random patterns of deep brain stimulation are not effective at relieving symptoms."

It took more than a decade for Grill to be able to test his theory, but two recent developments allowed him to follow his hunch. Researchers developed a faster form of optogenetics called Chronos that could keep up with the speeds traditionally used in deep brain stimulation. And Chunxiu Yu, a research scientist with expertise in optogenetics, joined Grill's laboratory. Also contributing to the work in Grill's laboratory were Isaac Cassar, a biomedical engineering doctoral student, and Jaydeep Sambangi, a biomedical engineering undergraduate.

In the new paper, Yu embedded the Chronos optogenetics machinery into the subthalamic nucleus neurons of rats that have been given Parkinson's disease-like conditions in one-half of their brains. This model helps researchers determine when a treatment is successful because the resulting physical movement symptoms only occur on one side of the rat's body. They then delivered deep brain stimulation using light flashes at the standard 130 flashes per second.

As Grill first suspected nearly 15 years ago, the technique worked, and the rats' physical symptoms were substantially alleviated.

According to Grill, their result has several important implications. One is that researchers need to consider the kinetic properties of how rapidly optogenetic approaches can act when designing their experiments and pay close attention to performance in their studies. Another insight was the way that other neurons outside of the subthalamic nucleus responded to the treatment. While there was not a large difference in their average activity levels, there was a dramatic shift in the pattern in which those neurons fired, which offers clues as to how deep brain stimulation works.

But perhaps the most important result is simply that the technique worked at all. Besides offering a much clearer look at neural activity by removing electrical artifacts, the ability to deliver deep brain stimulation to precise subsets of neurons should allow researchers to begin probing exactly which parts of the brain need to be stimulated and how therapies might be tailored to treat different motor control symptoms on a case-by-case basis.

As their next experiment in this line of research, Grill and his colleagues plan to recreate this same study but in the hyperdirect pathway -- the spaghetti instead of the meatballs -- to see what its individual contribution to relieving symptoms might be.

"This is very important because somewhere in that big bowl of spaghetti are some elements that are responsible for treating symptoms and some elements that generate side effects," said Grill. "And if we can figure out which is which, we can design electrode stimulation geometries and patterns to target the elements that suppress symptoms while leaving the others alone."

In the most detailed study to date of epidemic spread, an international team of researchers has modeled measles dynamics based on over 40 years of data collected in England and Wales. The models--which span the prevaccination period, introduction of measles vaccination, and local elimination by vaccination in the 1990s--reveal that, before the introduction of a vaccine, measles could persist in both large population centers and by spread among sets of smaller towns. The study also provides critical data on the importance of spatial modeling for the long-term control of global epidemics and could help inform the long-term public health response to the current COVID-19 pandemic.

A paper describing the study appears April 27, 2020 in the journal Nature Ecology & Evolution.

"During the last 20 years there have been tremendous inroads towards eradicating measles--one of the major killers of children globally--as annual deaths have been driven down from more than a million to less than 200,000," said Ottar N. Bjørnstad, Distinguished Professor of Entomology and Biology at Penn State and one of the leaders of the research team. "However, previous efforts to eradicate smallpox and polio highlight the complexity of moving from local control to global eradication. Our study provides critical data on how long-term control efforts will need both general and detailed spatial models to finally stop this deadly disease."

Prior to the introduction of a vaccine, the number of measles cases in England and Wales would undergo, periodic--often biennial--epidemics. This pattern, driven by herd immunity, is common among a number of diseases and in other locales. The researchers sought to locate the reservoirs where the virus persists in the dips between epidemics, which are the sources for reintroduction of the virus into the general populace in the next major epidemic. This persistence question is central to understanding the dynamics of measles and other viral diseases and for coordinating public health interventions.

The research team combined spatial modeling with the detailed historical data of measles cases in England and Wales to address these questions. The uniquely detailed dataset includes weekly measles reports from almost a thousand locations across England and Wales beginning in 1944 and continuing until the disease was all but locally eliminated by vaccination in the 1990s.

"Previous work stressed the importance of large centers as sources of infection," said Bryan T. Grenfell, the Kathryn Briger and Sarah Fenton Professor of Ecology and Evolutionary Biology and of Public Affairs at Princeton University and another leader of the research team. "However, our new modeling shows that local spread among smaller towns can also contribute to persistence of the virus."

The researchers' new model quantifies the relative influence of different sources of infection, including major cities, spread among smaller towns, and unidentifiable outside sources. Following the introduction of vaccination, the source of reintroduction shifted from a combination of large centers and local spread to mainly unidentifiable sources, possibly outside of England and Wales.

"Having access to this unique dataset allowed us to test these news models of measles dynamics with unprecedented rigor," said Max S. Y. Lau, assistant professor in the Rollins School of Public Health at Emory University and first author of the paper. "Going forward, we can apply what we learn from this test case to understand disease spread beyond measles."

"Measles has always been the 'model organism' of epidemic dynamics--like C. elegans or the fruitfly are for evolution--and, along with influenza, a paradigm for understanding herd immunity," said Grenfell. "So, as COVID-19 approaches endemicity, these new models can help us understand and prepare for modeling its spatial spread, as well as understand the impact that the eventual development of a vaccine might have on its dynamics."

Beyond the COVID-19 pandemic, the models also could help scientists understand how diseases survive and spread at a time when a portion of the public is opposed to vaccines, said co-author C. Jessica E. Metcalf, assistant professor of ecology and evolutionary biology and public affairs. "Understanding the drivers of persistence is also of growing importance in a context of growing vaccine hesitancy, which further complicates dynamics and amplifies the challenges of control," she said.

The researchers added that wide perspective should be taken when applying the results to other diseases.

"Our model and previous experience highlights the complexity of globally eradicating a virus," said Bjørnstad. "Smallpox was eradicated by 1977 through a massive global effort of mass-vaccination of all children, followed by targeted efforts in regional hotspots and finally local quarantining and ring vaccination to squash the scourge. Polio, in contrast, while also targeted through vaccination for more than 50 years keeps escaping 'the final blow' as it successfully shifts and diffuses across regional pockets of susceptible individuals to evade eradication."

A new study finds that earlier high school start times can have significant adverse consequences for students, including increased rates of tardiness and absenteeism.

"The American Academy of Pediatrics recommends that high schools begin class after 8:30 a.m., but we know that most schools start much earlier," says Melinda Morrill, an associate professor of economics at North Carolina State University and corresponding author of a paper on the work. "We were able to look at five high schools that moved start times from 8:05 a.m. to 7:25 a.m. in order to examine the effect that the change had on students."

The researchers looked at data on seven cohorts of students, with graduation years ranging from 2013 to 2019. Specifically, researchers looked at data from the freshman, sophomore and junior years of each cohort. The change in start times was implemented in the 2012-13 school year. As an additional control group, the researchers also looked at data from 14 other high schools in the same school district that had already adopted a 7:25 a.m. start time.

"There's a growing body of research that suggests earlier start times can hurt test scores," Morrill says. "We looked at that, but the numbers weren't statistically significant one way or the other."

"However, the move to the earlier start times caused a small increase in the number of students who did not advance to 12th grade on time," says John Westall, a Ph.D. candidate at NC State and co-author of the paper. "Specifically, the move from 8:05 to 7:25 was associated with students being 8% more likely not to advance to 12th grade on schedule."

"We also wanted to look beyond testing to see if there were effects on other measures of academic engagement," Morrill says. "And we found a significant increase in both absences and tardiness."

"The change to an earlier start time led to an increase of about one additional absence per year and just over three additional tardy arrivals per year for students," Westall says. "So students were definitely missing more school."

"Looking at all 19 of the schools, we found that historically, the five schools that started at 8:05 had significantly lower rates of absenteeism and tardiness than the 14 schools that started at 7:25," Morrill says. "But once those five schools moved their start time to 7:25, those advantages disappeared.

"The take-home message here is that we need to look at more than just test scores if we want to understand all of the ways that early start times can affect high school students," Morrill says. "We know that school districts have to consider a wide range of issues, such as transportation logistics, student safety, extracurricular activities and school finances. But the more we look, the more the findings suggest that there are significant consequences of early start times for students."

University of Texas at Dallas researchers have developed a promising method for remotely stimulating activity in deep brain regions, advancing understanding of how molecules act in the brain and paving the way for better cancer treatments and therapies for other diseases.

The approach is based on the powerful combination of gold nanoparticles and lasers, which also plays a critical role in another UT Dallas research project aimed at developing a rapid diagnostic test for influenza and, possibly, the COVID-19 virus.

Gold for Neuromodulation

Light is an important tool to modulate biological systems, but absorption and scattering in biological tissues significantly limit its penetration. The system developed by researchers in the Erik Jonsson School of Engineering and Computer Science and the School of Behavioral and Brain Sciences packages molecules inside microscopic gold-coated capsules, or nanovesicles, that can be very sensitive to near-infrared light.

The system could solve challenges in treating diseases, such as ensuring that medication is delivered to difficult-to-reach tumors in deep brain regions while reducing damage to healthy tissue. Using that example, the nanovesicles and their cargo are injected into the brain tissue. External near-infrared lasers that penetrate the tissue cause the capsules to open and release the drug. The researchers describe the approach and results of tests in an animal model in an article published online in the chemistry journal Angewandte Chemie.

"Our system converts light to a mechanical wave that shakes the vesicle open," said Dr. Zhenpeng Qin, assistant professor of mechanical engineering at UT Dallas and corresponding author of the study.

Other researchers have used near-infrared light to trigger drug-carrying nanoparticles, such as phospholipid liposomes, which release their cargo when heated by the laser, but Qin's approach with gold-coated nanovesicles uses about 40 times less laser energy.

In tests in animal models, Qin and his colleagues found that the near-infrared light penetrated 4 millimeters in the brain, which was enough to reach most targeted brain regions. Qin said he anticipates the laser penetrates far enough to reach targets deep in the rodent brain that will help answer important questions in neuromodulation.

"We want to improve the tests' sensitivity so that doctors can make the judgment call right in front of the patient, to be able to say either you have it or you don't have it."

While the nanovesicle system must undergo more development and testing before it could be used in clinical care, Qin said the approach eventually could be applied to neurological disorders or other cancers. Dr. Hejian Xiong, research associate in Qin's lab and co-author of the journal article, received a new postdoctoral fellowship from the Phospholipid Research Center in Germany to study the use of gold-coated nanovesicles and ultra-short near-infrared lasers to target and relieve pain in patients after surgery. The project aims to provide an adjustable pain management system that could reduce the need for opioids.

Infectious Disease Testing

In a separate research project, Qin recently received a $293,000 grant from the Congressionally Directed Medical Research Programs to develop a rapid, accurate and less expensive test for infectious diseases, including influenza, that could be conducted in doctors' offices. The testing principle could also be applied to diagnose COVID-19.

While many doctors conduct rapid flu tests on site, the tests can miss influenza in 30% to 50% of cases, according to the Centers for Disease Control and Prevention. Samples must be sent to a lab for an accurate diagnosis, which can take days.

"We want to improve the tests' sensitivity so that doctors can make the judgment call right in front of the patient, to be able to say either you have it or you don't have it," Qin said.

In the testing method, gold nanoparticles are attached to antibody molecules that can recognize and bind with protein molecules found on the surfaces of viruses. Researchers apply short laser pulses to activate the nanoparticles to generate nanoscale bubbles, or nanobubbles. The accumulation of the nanobubbles signals the presence of a virus.

"By using optics to detect and count the nanobubbles, we can sensitively and quickly detect the presence of specific respiratory viruses," Qin said.

One of the advantages of the approach is that it would not require extensive sample preparation, Qin said. The method could help doctors diagnose viruses much faster and reduce health care costs by eliminating the need for expensive lab visits. The approach could be used to detect a single virus or multiple viruses.

Ultimately, researchers envision the test being broadly used in hospitals and clinics that do not have labs; however, the diagnostic method will need to be tested further before it can be made widely available.

Qin's group is not working with the live coronavirus, only with viral genes, proteins and antibodies. Qin has previously obtained such patient samples for his research on respiratory syncytial virus and influenza.

Researchers at Karolinska Institutet in Sweden and the University of North Carolina in the USA have mapped out the cell types behind various brain disorders. The findings are published in Nature Genetics and offer a roadmap for the development of new therapies to target neurological and psychiatric disorders. One interesting finding was that cells from the gut's nervous system are involved in Parkinson's disease, indicating that the disease may start there.

The nervous system is composed of hundreds of different cell types with very different functions. It is vital to understand which cell types are affected in each disorder so as to understand the causes of the disorders and, ultimately, develop new treatments.

Researchers have now combined mice gene expression studies with human genetics to systematically map cell types underlying various brain disorders, including Parkinson's disease, a neurodegenerative disorder with cognitive and motor symptoms resulting from the loss of dopamine-producing cells in a specific region of the brain.

"As expected, we found that dopaminergic neurons were associated with Parkinson's disease. More surprisingly, we found that enteric neurons also seem to play an important role in the disorder, supporting the hypothesis that Parkinson's disease starts in the gut," says one of the study's main authors Patrick Sullivan, Professor at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet and Yeargan Distinguished Professor at the University of North Carolina.

When the researchers analysed differences in brain tissue from healthy individuals and people with Parkinson's disease at different stages of the disease, they made another unexpected discovery. A type of support cell in the brain called oligodendrocytes were found to be affected early on, suggesting that they play a key role in the early stages of the disease.

"The fact that the animal studies pointed us to oligodendrocytes and that we were then able to show that these cells were also affected in patients suggests that the results may have clinical implications," says Jens Hjerling-Leffler, research group leader at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet and the other main author of the study.

The oligodendrocytes appear to be affected even before the loss of dopaminergic neurons.

"This makes them an attractive target for therapeutic interventions in Parkinson's disease," says Julien Bryois, researcher at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet and one of the first authors of the study.

The study was financed by the Swedish Research Council, StratNeuro, the Wellcome Trust, the Swedish Brain Foundation, the Swiss National Science Foundation, the US National Institute of Mental Health, and the Psychiatric Genomics Consortium.

Patrick Sullivan reports that he is currently a member of the pharmaceutical company Lundbeck's advisory committee and that he has received grants from them. For the past three years he has been a member of Pfizer's scientific advisory board and received fees from Element Genomics and Roche. Co-author Cynthia Bulik has received grants from Shire and is a member of their scientific advisory board. She is also an author and recipient of royalties from both Pearson and Walker.

Mylagic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling and complex illness. Affected persons often cannot pursue ordinary activities -- physical or mental -- because of an incapacitating loss of energy and other symptoms, and may find themselves confined to bed or house-bound for years.

Anyone can develop ME/CFS, though it most commonly afflicts people between the ages of 40 and 60; women more often than men. In nearly every case, ME/CFS begins after a sequence of severe environmental exposures, injuries or infections. Until relatively recently, the utter mystery and complexity of ME/CFS persuaded some that it was not a "real" condition. In 2015, the National Academy of Medicine declared ME/CFS to be a serious, chronic, complex and systemic disease.

In a new study, to be published in the May 1, 2020 print edition of https://www.immunohorizons.org/content/4/4/201ImmunoHorizons, a team of researchers at University of California San Diego School of Medicine and three German universities describe an underlying biological basis for ME/CFS, one that illustrates how efforts by the body to boost immune system protections can come at physiological cost elsewhere.

"These findings are important because they show for the first time that there is an antiviral activity in the serum of patients with ME/CFS that is tightly associated with an activity that fragments the mitochondrial network and decreases cellular energy (ATP) production," said Robert Naviaux, MD, PhD, professor of medicine, pediatrics and pathology at UC San Diego School of Medicine.

Naviaux is co-senior author of the study with Bhupesh K. Prusty, PhD, a scientist in the Department of Microbiology and Institute for Virology and Immunobiology at Julius Maximilians University in Würzburg, Germany.

"This provides an explanation for the common observation that ME/CFS patients often report a sharp decrease in the number of colds and other viral infections they experience after they developed the disease. Our work also helps us understand the long-known, but poorly understood link of ME/CFS to past infections with Human Herpes Virus-6 (HHV-6) or HHV-7," said Naviaux.

More than 90 percent of people are exposed to HHV-6 by three years of age. The virus DNA can insert itself into a chromosome and remain latent in just a few cells for years, silently being copied each time the cell divides. For most people, this causes no problem.

"However, we found that exposure to new metabolic or environmental chemical stresses caused cells with an integrated copy of HHV-6 to secrete an activity that warned neighboring cells of the threat," said Naviaux. "The secreted activity not only protected neighboring and distant cells from new RNA and DNA virus infections, but also fragmented the mitochondrial network and lowered their intracellular ATP reserve capacity. Cells without an integrated copy of HHV-6 did not secrete the antiviral activity.

"Our results show that cellular bioenergetic fatigue and cellular defense are two sides to the same coin in ME/CFS. When energy is used for cellular defense, it is not available for normal cell functions like growth, repair, neuroendocrine and autonomic nervous system functions."

The findings further illuminate a concept called cell danger response theory, which Naviaux and colleagues have been investigating for years. CDR theory posits that chronic disease is the consequence of the natural healing cycle becoming blocked by disruptions at the metabolic and cellular levels. In this case, persons with ME/CFS obtained protections against certain kinds of infections, but at a cost of fragmenting mitochondrial function. Persistence of fragmented mitochondria and the associated abnormalities in cell signaling block normal healing and recovery, and can lead to a lifetime of illness.

Mitochondria are organelles in cells that break down nutrients to create a fuel called adenosine triphosphate (ATP), the primary energy carrier in all living organisms. ATP provides the energy used to drive many cellular processes, including muscle contractions, nerve impulses and chemical synthesis.

"This paper will be a paradigm shift in our understanding of potential infectious causes behind ME/CFS. Human herpesvirus 6 and HHV-7 have long been thought to play a role in this disease, but there was hardly any causative mechanism known before," said senior co-author Prusty.

"For the first time, we show that even a few HHV-6 infected or reactivated cells can drive a powerful metabolic and mitochondrial remodeling response that can push even the non-virus containing cells towards a hypometabolic (abnormally low metabolic) state. Hypometabolic cells are resistant to other viral infections and to many environmental stresses, but this comes at the cost of severe symptoms and suffering for patients with ME/CFS."

Free open source hardware and 3D printing could help to alleviate the burden of Covid-19 on global health systems, according to scientists at the University of Sussex.

Free and open source hardware (FOSH) follows an ethos where blueprints for a tool are made freely available so that anyone can study, learn, modify, customize and commercialize them.

In a study published by PLoS Biology, Professor Tom Baden and Andre Chagas at the University of Sussex have suggested that this could be a viable option to provide our health services with the tools and equipment they so desperately need.

The study provides an overview of the blueprints which are currently available for free online and which could be used to help in the fight against coronavirus, focusing on personal protective equipment, ventilators and test kits.

Although some of the designs still need to be tested, many others have already received suitable verification, having been published in peer reviewed papers. The authors therefore believe that FOSH should be seriously considered as a method of quickly providing equipment where it's needed.

Tom Baden, Professor of Neuroscience, said: "Now is the time that Open Hardware could really shine and it's so important that we get on board quickly.

"Previous studies and experiences have shown that free and open source hardware is a brilliant option in disaster situations. Designs can be shared globally, it has typically lower implementation costs than mass manufacturing and it can be easily adapted to meet local resources.

"But the real power - and the way this could really help to tackle Covid-19 - is that once a tool has been designed and tested, anyone can build it. This bypasses the traditional manufacturing and distribution routes and means that it can become a community driven endeavour where anyone with the capacity to do so can help to produce much-needed equipment and supplies for the healthcare services.

"Anyone with the necessary knowhow, tools and time can build on this knowledge to meaningfully support their community. At a time when global health systems are facing immense pressure and becoming increasingly overburdened, we need a response not just from frontline workers such as medical staff and scientists, but from skilled members of the public who have the time, facilities and knowledge to meaningfully contribute."

The paper describes existing FOSH designs from simple tools like DIY facemasks to 3D printed valves which can regulate airflow in ventilator tubes. Others are far more complex including state-of-the-art scientific instruments for diagnosis, such as an automated pipetting robot, plate readers and a range of other medical tools and supplies.

Some blueprints are already being used to provide support to the NHS. A company in Portslade which produce face visors have recently removed their patent and license and asked for support from anyone with a 3D printer in order to produce more to meet demand and provide protection to NHS staff.

But for those unverified designs, testing and approval can be a lengthy process.

Andre Chagas said: "One thing governments could do right now, is to figure out a process in which we can legitimately fast track the testing and certification of tools which are in short supply."

"For instance, in Spain a group is already testing their ventilator designs with support from the government. While each country will have different rules and certifications to meet, this is a crucial moment for us to get together and figure out a single set of certification so that implementation can move faster."

Prof. Tom Baden added: "If governments can support this through financial support to ramp up production of the best tools, that would be incredibly useful right now.

"But asides from financial support, we also need support from those who actually know about the use of these tools, rather than just their design. To make this equipment properly and safely, we don't just need tech-savvy people building it. We need people in the healthcare sector who know how these tools should work and can actually test them. These people should contact ongoing products to see if they can help."

A team at the University of Sussex team recently finished creating 100 face shields which are to be tested within the NHS. Once the design is approved the University will launch a full-scale production operation, hoping to produce 1000 face shields a day by early May.

Antibiotics save lives -- but using them also helps antibiotic-resistant strains evolve and spread. Each year, antibiotic-resistant bacteria infect some 2.8 million people in the United States, killing more than 35,000, according to the Centers for Disease Control and Prevention. Infections by multidrug-resistant -- or MDR -- bacteria, which are resistant to two or more antibiotics, are particularly difficult to treat.

Scientists at the University of Washington and the University of Idaho have discovered just how readily MDR bacteria can emerge. In a paper published April 6 in Nature Ecology & Evolution, the researchers report that, for a bacterial pathogen already resistant to an antibiotic, prolonged exposure to that antibiotic not only boosted its ability to retain its resistance gene, but also made the pathogen more readily pick up and maintain resistance to a second antibiotic and become a MDR strain.

The team's experiments indicate that prolonged exposure to one type of antibiotic essentially "primed" the bacteria. This priming effect made it more likely that the bacteria would acquire resistance to additional antibiotics, even in the absence of further antibiotic exposure, and helped the strain hold on to those antibiotic-resistance traits for generations.

"Exposure to antibiotics appears to select indirectly for more stable antibiotic resistance systems," said Benjamin Kerr, a UW professor of biology and co-senior author on the paper. "A more stable system in a strain will increase the chances that it will acquire resistance to multiple antibiotics."

Their findings also show how antibiotic exposure affects the evolutionary dynamics within bacteria.

"This could help explain not only the rise of multidrug resistance in bacteria, but also how antibiotic resistance persists and spreads in the environment -- in health care settings, in soil from agricultural runoff -- even long after the antibiotic exposure has ended," said co-senior author Eva Top, a professor of biology at the University of Idaho.

The researchers tested a common mechanism for the spread of antibiotic resistance: plasmids. These are circular strands of DNA that can contain many types of genes, including genes for antibiotic resistance. Bacteria easily share plasmids, even across species.

Yet plasmids have their downsides, and past research has shown that bacteria readily shed them.

"Even though they can carry beneficial genes, plasmids can also interfere with many types of processes inside a bacterial cell, such as metabolism or DNA replication," said lead author Hannah Jordt, a UW research scientist in biology. "So, scientists have generally thought of plasmids as costly and burdensome to the host cell."

The UW-University of Idaho team worked with E. coli cells containing a tetracycline-resistance plasmid and Klebsiella pneumoniae cells containing a chloramphenicol-resistance plasmid. Both hosts, which had not been grown in the presence of antibiotics before, showed no great loyalty to their plasmids. After nine days in an antibiotic-free environment, the fraction of Klebsiella still harboring a plasmid dropped to less than 50%. For E. coli, less than 20% kept their plasmid.

When the researchers exposed the strains to antibiotics, growing each for 400 generations in their respective antibiotic, the strains showed greater affinity for their plasmids even after the antibiotic threat was lifted. After nine days in an antibiotic-free growth medium, more than half of E. coli and Klebsiella cells held on to their respective plasmid.

"Of course, the cells needed their plasmids to help them survive the antibiotic exposure. But even after we took away that selective pressure, both strains retained their plasmids at significantly higher levels than they had before the antibiotic exposure," said Jordt.

In addition, other experiments showed that antibiotic exposure increased the occurrence of MDR Klebsiella. Even without exposure to antibiotics, Klebsiella pneumoniae can acquire multiple plasmids. For example, when the researchers grew antibiotic-naive Klebsiella and E. coli plasmid-bearing strains together, a small fraction of Klebsiella became MDR by retaining their chloramphenicol-resistance plasmid and acquiring tetracycline-resistance plasmids from E. coli. But when the researchers repeated the experiment using antibiotic-exposed bacteria, they found roughly 1,000 times more MDR Klebsiella.

Prior prolonged exposure to just one antibiotic -- chloramphenicol -- had increased the likelihood that chloramphenicol-resistant Klebsiella would acquire the tetracycline-resistance plasmid from E. coli in an antibiotic-free environment. In addition, the team's experiments also showed that, when MDR cells were grown later in an antibiotic-free environment, chloramphenicol-exposed Klebsiella more readily held on to both resistance plasmids.

Evolution can explain both the persistence of the antibiotic-resistance plasmids and the increase of MDR in Klebsiella, the researchers say: Exposing the strains to their respective antibiotic selected for mutations in their genomes to minimize the clash between plasmid and host, making it less costly to keep that plasmid as well as others.

"We believe that by stabilizing one plasmid, these mutations make them more likely to stabilize additionally acquired plasmids," said Kerr.

Additional experiments may identify the specific mutations that helped E. coli and Klebsiella keep their plasmids, and why Klebsiella was more able to develop into a MDR strain than E. coli. Even though antibiotic exposure creates selective pressure to keep plasmids and acquire new ones, there is still widespread variation in how different species keep, share and receive plasmids.

"There are many, many details to be worked out in the future," said Top. "But what we see here is that even short-term exposure to just one antibiotic accelerates the development of multidrug resistance, which should give us pause as we use these drugs in health care, agriculture and other settings."

April 27, 2020 (Huntsville, Ala.) - Scientists at the HudsonAlpha Institute for Biotechnology, the University of California, San Francisco (UCSF), and the University of Alabama at Birmingham (UAB), have identified a new risk factor for multiple neurodegenerative diseases.

"Finding evidence for a risk factor that contributes to multiple neurodegenerative diseases is exciting," said Richard M. Myers, PhD, HudsonAlpha president and science director. "We already know that these diseases share some pathologies. This work shows that the underlying causes of those pathologies may also be shared."

In the study, which was published April 23 in the American Journal of Human Genetics, researchers sequenced and analyzed whole genomes of more than 1,100 people. They found that rare variation in the gene TET2 nearly doubled the risk of developing diseases like Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD).

"The project wouldn't have been possible without extensive collaboration between institutions," said first author Nicholas Cochran, PhD, a senior scientist in the Myers Lab. "You end up being able to find things that you can't find working alone."

Jennifer Yokoyama, PhD, an assistant professor of neurology at UCSF, worked with Cochran on technical details and also was the point person for sample collection. The majority of the samples used for the project were collected over decades at the UCSF Memory and Aging Center and then sequenced and analyzed at HudsonAlpha.

Once the research team had the sequence results, they analyzed the genomes of 493 people with either AD, ALS, or FTD and 671 healthy people. Many of the patients had early-onset versions of neurodegenerative disease, which suggests that it is more likely that there would be a genetic component of their illness. During genome analysis, the researchers looked at both coding and non-coding regions of the genome for DNA sequence variants, a strategy that allowed them to be more confident that any possible genes they pulled out were the real deal.

"We didn't go in with any suspicions about what we might [get], so we're excited that we did find a new genetic association here," Cochran said. TET2 is especially exciting because it encodes a protein that catalyzes DNA demethylation. Previous work has shown that changes in DNA methylation happen during aging, so the authors hypothesize that mutations in the gene could lead to a faulty TET2 protein that disrupts how the brain ages and contributes to the development of neurodegenerative diseases.

"Sometimes we get a hit, and it's hard to understand what it might be doing, but TET2 already has established roles in the brain. So this finding really made sense," Cochran explained.

After the team identified TET2, they looked at previously generated genetic data from more than 32,000 healthy people and people with neurodegenerative diseases. This data confirmed that variants in TET2, in both protein-coding and non-coding regions, were more likely to be present in the genomes of people with AD, ALS, or FTD than in people without these diseases. Next steps will focus on how changes in TET2 levels or function could contribute to aging and neurodegenerative disease.

While the human world is reeling from one pandemic, there are several ongoing epidemics that affect crops and put global food production at risk. Oranges, olives, and bananas are already under threat in many areas due to diseases that affect plants' circulatory systems and that cannot be treated by applying pesticides.

A new method developed by engineers at MIT may offer a starting point for delivering life-saving treatments to plants ravaged by such diseases.

These diseases are difficult to detect early and to treat, given the lack of precision tools to access plant vasculature to treat pathogens and to sample biomarkers. The MIT team decided to take some of the principles involved in precision medicine for humans and adapt them to develop plant-specific biomaterials and drug-delivery devices.

The method uses an array of microneedles made of a silk-based biomaterial to deliver nutrients, drugs, or other molecules to specific parts of the plant. The findings are described in the journal Advanced Science, in a paper by MIT professors Benedetto Marelli and Jing-Ke-Weng, graduate student Yunteng Cao, postdoc Eugene Lim at MIT, and postdoc Menglong Xu at the Whitehead Institute for Biomedical Research.

The microneedles, which the researchers call phytoinjectors, can be made in a variety of sizes and shapes, and can deliver material specifically to a plant's roots, stems, or leaves, or into its xylem (the vascular tissue involved in water transportation from roots to canopy) or phloem (the vascular tissue that circulates metabolites throughout the plant). In lab tests, the team used tomato and tobacco plants, but the system could be adapted to almost any crop, they say. The microneedles can not only deliver targeted payloads of molecules into the plant, but they can also be used to take samples from the plants for lab analysis.

The work started in response to a request from the U.S. Department of Agriculture for ideas on how to address the citrus greening crisis, which is threatening the collapse of a $9 billion industry, Marelli says. The disease is spread by an insect called the Asian citrus psyllid that carries a bacterium into the plant. There is as yet no cure for it, and millions of acres of U.S. orchards have already been devastated. In response, Marelli's lab swung into gear to develop the novel microneedle technology, led by Cao as his thesis project.

The disease infects the phloem of the whole plant, including roots, which are very difficult to reach with any conventional treatment, Marelli explains. Most pesticides are simply sprayed or painted onto a plant's leaves or stems, and little if any penetrates to the root system. Such treatments may appear to work for a short while, but then the bacteria bounce back and do their damage. What is needed is something that can target the phloem circulating through a plant's tissues, which could carry an antibacterial compound down into the roots. That's just what some version of the new microneedles could potentially accomplish, he says.

"We wanted to solve the technical problem of how you can have a precise access to the plant vasculature," Cao adds. This would allow researchers to inject pesticides, for example, that would be transported between the root system and the leaves. Present approaches use "needles that are very large and very invasive, and that results in damaging the plant," he says. To find a substitute, they built on previous work that had produced microneedles using silk-based material for injecting human vaccines.

"We found that adaptations of a material designed for drug delivery in humans to plants was not straightforward, due to differences not only in tissue vasculature, but also in fluid composition," Lim says. The microneedles designed for human use were intended to biodegrade naturally in the body's moisture, but plants have far less available water, so the material didn't dissolve and was not useful for delivering the pesticide or other macromolecules into the phloem. The researchers had to design a new material, but they decided to stick with silk as its basis. That's because of silk's strength, its inertness in plants (preventing undesirable side effects), and the fact that it degrades into tiny particles that don't risk clogging the plant's internal vasculature systems.

They used biotechnology tools to increase silk's hydrophilicity (making it attract water), while keeping the material strong enough to penetrate the plant's epidermis and degradable enough to then get out of the way.

Sure enough, they tested the material on their lab tomato and tobacco plants, and were able to observe injected materials, in this case fluorescent molecules, moving all they way through the plant, from roots to leaves.

"We think this is a new tool that can be used by plant biologists and bioengineers to better understand transport phenomena in plants," Cao says. In addition, it can be used "to deliver payloads into plants, and this can solve several problems. For example, you can think about delivering micronutrients, or you can think about delivering genes, to change the gene expression of the plant or to basically engineer a plant."

"Now, the interests of the lab for the phytoinjectors have expanded beyond antibiotic delivery to genetic engineering and point-of-care diagnostics," Lim adds.

For example, in their experiments with tobacco plants, they were able to inject an organism called Agrobacterium to alter the plant's DNA - a typical bioengineering tool, but delivered in a new and precise way.

So far, this is a lab technique using precision equipment, so in its present form it would not be useful for agricultural-scale applications, but the hope is that it can be used, for example, to bioengineer disease-resistant varieties of important crop plants. The team has also done tests using a modified toy dart gun mounted to a small drone, which was able to fire microneedles into plants in the field. Ultimately, such a process might be automated using autonomous vehicles, Marelli says, for agricultural-scale use.

Meanwhile, the team continues to work on adapting the system to the varied needs and conditions of different kinds of plants and their tissues. "There's a lot of variation among them, really," Marelli says, so you need to think about having devices that are plant-specific. For the future, our research interests will go beyond antibiotic delivery to genetic engineering and point-of-care diagnostics based on metabolite sampling."

New research by academics at the University of Bristol has found evidence that prolonged treatment of synthetic corticosteroid drugs increases adrenal gland inflammation in response to bacterial infection, an effect that in the long-term can damage adrenal function.

Synthetic corticosteroid drugs are widely prescribed to treat many inflammatory and autoimmune diseases but taking a high dose over a long period of time can cause adverse side effects. Patients undergoing prolonged corticosteroid treatment can also develop adrenal insufficiency, which in rare occasions can lead to adrenal gland failure.

Previous studies have concentrated on studying the long-term effects of corticosteroid treatment on the hypothalamus and pituitary but have not looked at the direct effects that these steroids may have on the adrenal gland.

In this study, published in Brain, Behavior, and Immunity, the research team tested the hypothesis that synthetic corticosteroids cause long-term changes in the adrenal gland steroidogenic pathways that are responsible for adrenal suppression.

The research found that the rhythms of glucocorticoid secretions are disrupted following prolonged treatment with synthetic corticosteroid drugs, and that the adrenal steroidogenic pathway is directly affected. Importantly, these changes persist long after discontinuation of the treatment.

The study also showed a pro-inflammatory effect of synthetic glucocorticoids treatment in the adrenal gland. This is an important finding with high clinical relevance as intra-adrenal activation of the immune system can affect adrenal functionality by interfering with the steroidogenic pathway, damaging adrenal endothelial microvascular cells, and by inducing apoptosis and reducing cell viability.

Dr Francesca Spiga, Honorary Research Fellow in the Bristol Medical School: Translational Health Sciences (THS) and corresponding author, said: "Our study provides valuable insights on the regulation of the adrenal steroidogenic pathway that are important starting points for future studies on adrenal gland physiology.

"Importantly, our research builds on our knowledge of the mechanisms through which corticosteroid drugs induce adrenal insufficiency, by showing simultaneous effects within multiple pathways involved in steroidogenesis, including circadian clock genes and inflammation pathways.

"A more detailed understanding of the effects of synthetic glucocorticoids on glucocorticoid hormone's dynamics and on adrenal steroidogenic activity and the identification of mechanisms regulating these effects, will help develop better treatments that will improve patient care."

Future studies should address whether adrenal insufficiency, and its effects, can be prevented by using synthetic corticosteroid drugs that more closely resemble endogenous glucocorticoids in term of effectiveness and plasma half-life.

Endogenous glucocorticoids (cortisol in humans, corticosterone in rodents) regulate many physiological functions, including metabolism, cardiovascular tone, reproduction, mood and cognition, and the immune system. Clinical therapy with high doses of synthetic corticosteroids results in adrenal insufficiency, characterised by adrenal atrophy and decreased basal and stress-induced cortisol secretion, that may persist for several years after therapy withdrawal. One of the pathological consequences of adrenal insufficiency is the potential development of an adrenal crisis resulting from decreased cortisol secretion in response to inflammatory stressors such as infections, injuries and major surgery.

The study was funded by a Medical Research Council programme grant.

Berkeley -- Government-enforced social isolation may help relatively affluent populations limit the spread of COVID-19, but these measures can be devasting for the nearly 1 billion people around the globe currently dwelling in urban slums, where physical space is scarce, and many rely on daily wage labor for survival.

To help the urban poor weather the COVID-19 pandemic, governments should instead prioritize providing basic needs, including fresh water, sanitation and a moratorium on evictions, and support existing community leadership in delivering health care and emergency preparedness, argues a new report published April 24 in the Journal of Urban Health.

The report, authored by a team of public health experts and epidemiologists working in collaboration with community leaders and non-governmental organizations (NGOs) from urban slums around the world, provides eight urgent recommendations for reducing the impact of COVID-19 on people living in poverty.

These recommendations are crucial not just for people living in urban slums in the global south, but for other vulnerable populations, such as migrant farm workers and those living in refugee camps and homeless encampments and on Native American reservations in the United States, the authors say. Evidence now suggests that the coronavirus is disproportionately affecting black Americans in some U.S. cities, possibly due to similar structural factors, such as the inability to take time off of work.

"The political and economic shocks and instability that are happening now and are likely to follow from this epidemic will likely kill more and lead to more disability in this population than the coronavirus itself," said Jason Corburn, a professor of public health and of city and regional planning at the University of California, Berkeley, and lead author of the paper. "We felt we needed a strategy that recognized the unique needs of the urban poor at the front."

Close living conditions and lack of basic sanitation make urban slum dwellers particularly vulnerable to contracting and spreading the coronavirus, said study co-author Lee Riley, a professor of epidemiology and infectious diseases at UC Berkeley. Many also have pre-existing medical conditions and lack access to health care, putting them at high risk of dying or developing serious complications if they do get sick with the virus.

Simply staying home is rarely an option for them, as it often means giving up work and even basic necessities like food, water and sanitation. In some countries, like Kenya and South Africa, people even face government violence for not obeying curfews and other restrictions.

"Shelter-in-place is a luxury of the wealthy," Riley said. "In many slums, people need to walk a long distance to collect water to use at home. Most people living in slums also have no choice but to participate in the informal economy, which will disappear under lockdowns."

Topping the list of recommendations is a call for governments to partner with existing community leadership and NGOs to form emergency planning committees that can consider the unique social, economic and cultural needs of the community in charting the appropriate response, rather than relying on top-down directives.

Similarly, as many communities lack easy access to health care, community and informal health workers should be deployed to monitor individuals for early symptoms and educate them about how to avoid transmitting the disease. Plans should be also be enacted for emergency transport into and out of settlements, which often lack adequate transportation infrastructure.

"The worst thing you can do in an emergency, particularly in an infectious disease outbreak, is to give everybody the same advice, because it doesn't recognize that not everybody starts in the same position," Corburn said. "Community health workers are uniquely positioned to know the preexisting conditions and the constraints that a group faces."

Finally, governments should ensure that people in slums have their basic needs for shelter and food met by enacting a moratorium on evictions and by providing payments for lost work, fresh water and food, and solid waste removal.

"COVID-19 became a pandemic because of the global spread of the virus by those people who can afford to travel on airplanes and cruise ships," Riley said. "As we are now seeing, inevitably, the disease has ended up in vulnerable communities of the world."

"We want to be bold in calling for actions that don't just tinker around the edges," Corburn added. "It's not just about getting people some more care or better care. We're really calling for a more holistic approach to public health."

Following an earlier study that validated the loss of smell and taste as indicators of SARS-CoV-2 infection, researchers at UC San Diego Health report in newly published findings that olfactory impairment suggests the resulting COVID-19 disease is more likely to be mild to moderate, a potential early indicator that could help health care providers determine which patients may require hospitalization.

The findings were published online April 24, 2020 in the journal International Forum of Allergy & Rhinology.

"One of the immediate challenges for health care providers is to determine how to best treat persons infected by the novel coronavirus," said first author Carol Yan, MD, a rhinologist and head and neck surgeon at UC San Diego Health. "If they display no or mild symptoms, can they return home to self-quarantine or will they likely require hospitalization? These are crucial questions for hospitals trying to efficiently and effectively allocate finite medical resources."

Yan's latest study, conducted with colleagues Farhoud Faraji, MD, PhD; Benjamin T. Ostrander, MD, and Adam S. DeConde, MD, all physicians in the Department of Surgery at UC San Diego Health, and Divya P. Prajapati, a student in the UC San Diego School of Medicine, suggests loss of smell may be predictive of a milder clinical course of COVID-19.

"Normosmia or the normal sense of smell is an independent predictor of admission in COVID-19 cases," said Yan. "In previous research, we found that loss of olfactory function is a common early symptom, following fever and fatigue.

"What's notable in the new findings is that it appears that loss of smell may be a predictor that a SARS-CoV-2 infection will not be as severe, and less likely to require hospitalization. If an infected person loses that sense, it seems more likely they will experience milder symptoms, barring other underlying risk factors."

Those risk factors previously reported by other studies, include age (older persons are more at-risk for severe illness) and underlying medical conditions, such as chronic lung disease, serious heart conditions, diabetes and obesity.

The researchers' latest study was a retrospective analysis between March 3 and April 8 of this year and included 169 patients who tested positive for COVID-19 at UC San Diego Health. Olfactory and gustatory data were obtained for 128 of the 169 patients; 26 of whom required hospitalization.

Patients who were hospitalized for COVID-19 treatment were significantly less likely to report anosmia or loss of smell (26.9 percent compared to 66.7 percent for COVID-19-infected persons treated as outpatients). Similar percentages were found for loss of taste, known as dysgeusia.

"Patients who reported loss of smell were 10 times less likely to be admitted for COVID-19 compared to those without loss of smell," said senior author DeConde, also a rhinologist and head and neck surgeon. "Moreover, anosmia was not associated with any other measures typically related to the decision to admit, suggesting that it's truly an independent factor and may serve as a marker for milder manifestations of Covid-19."

The researchers said that the findings possibly hint at some of the pathophysiological characteristics of the infection. "The site and dosage of the initial viral burden, along with the effectiveness of the host immune response, are all potentially important variables in determining the spread of the virus within a person and, ultimately, the clinical course of the infection," said DeConde.

In other words, if the SARS-CoV-2 virus initially concentrates in the nose and upper airway, where it impacts olfactory function, that may result in an infection that is less severe and sudden in onset, decreasing the risk of overwhelming the host immune response, respiratory failure and hospitalization.

"This is a hypothesis, but it's also similar to the concept underlying live vaccinations," DeConde said. "At low dosage and at a distant site of inoculation, the host can generate an immune response without severe infection."

Loss of smell, he said, might also indicate a robust immune response which has been localized to the nasal passages, limiting effects elsewhere in the body.

The researchers noted their study was limited in scope and by its nature: relying upon self-reporting of anosmia and a greater chance of recall bias among patients once they had been diagnosed with COVID-19, and that patients with more severe respiratory disease requiring hospitalization may not be as likely to recognize or recall the loss of smell.

Additional, more expansive studies are needed for validation, they said, but that the findings have important immediate practical applications for health care systems and patients.

Even as people are now being forced to social distance to avoid contracting coronavirus -- a situation considered stressful for many -- some people avoid social situations even under everyday circumstances. Social avoidance is a hallmark of a variety of psychiatric illnesses, including depression and anxiety disorders as well as autism.

Effective treatments for these symptoms remain elusive, with most therapies working for only a fraction of people that suffer from these illnesses. University of California, Davis, researchers studied the role of oxytocin, a neurotransmitter produced in the hypothalamus, which is known to play an important role in social behavior across species. By analyzing the behavior of mice receiving different treatments, they gained insight into whether oxytocin may be a good target for future pharmacological therapies that could alleviate social withdrawal in mental illness.

Curiously, oxytocin sometimes reduces social anxiety-related behaviors, but other times increases social anxiety, researchers said. In this study, researchers focused on identifying brain pathways that mediate the anxiety-reducing effects of oxytocin. To do this, researchers tested the effects of different pharmaceutical compounds that either activated or blocked the activity of oxytocin in the nucleus accumbens, a part of the brain known to control motivation.

"Unlike SSRIs (selective serotonin reuptake inhibitors, a class of anti-depressants), which take at least four weeks to show positive effects, pharmacological compounds changing oxytocin activity show rapid-acting effects on behavior," said Alexia Williams, a doctoral student who is the lead author of the study. "This makes oxytocin an exciting neurotransmitter to study. Our goal was to understand more about oxytocin's potential anxiety reducing properties."

The study was published last month in the journal Neuropsychopharmacology and highlighted by a commentary.

Researchers found that after California mice experienced negative social interactions, they had less expression of the oxytocin receptor gene. Typically, these negative interactions also create a state of social anxiety, with mice avoiding other mice. In this study, researchers show that when oxytocin activity was blocked, mice showed social avoidance, even though they had not experienced negative social interactions. When studying mice that had experienced negative social interactions, researchers found that increasing oxytocin activity reduced social avoidance behaviors. Although these mice had been exposed to stress, the pharmacological treatment led to normal social behaviors as if they had not been exposed to stress. Mice, Williams explained, are a social species and normally prefer to interact with other mice.

"This contributes to a clearer picture of how the neural circuits that affect social behaviors are affected by stress. Changes in neural circuits may be leading to some behaviors that have proved difficult to treat for many people struggling with mental disorders," she said.

Findings from basic science studies such as this one may guide the development of pharmacotherapies to effectively treat individuals suffering from anxiety disorders, the researchers said.

"We hope that by elucidating the role of oxytocin in anxiety-like behaviors on a molecular level, that we may begin to understand it's realistic potential as a novel therapeutic" said Williams.

New Rochelle, NY, April 27, 2020--In a new study among males depicted on Instagram, the majority of posts showed men with low body fat, while only a small fraction depicted men with high body fat. Sixty-two percent of posts showed men with low body fat and 41% showed high muscularity, whereas only 6% showed men with high body fat and 17% showed low muscularity. Men with both low body fat and high muscularity (35%) represented the largest group with a specific body type, according to the study published in Cyberpsychology, Behavior, and Social Networking, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Cyberpsychology, Behavior, and Social Networking website through May 27, 2020.

"Male Body Image Portrayals on Instagram" was coauthored by Thomas Gültzow, Francine Schneider, and Ciska Hoving, Maastricht University, Netherlands, and Jeanine Guidry, Virginia Commonwealth University, Richmond, VA. The researchers reported that exercise was the most frequently shown behavior. Furthermore, the number of likes and comments was significantly related to body composition, and the number of responses increased with decreasing levels of body fat and increasing levels of body muscularity.

"Based on Albert Bandura's Social Cognitive Theory, body image pictures on Instagram may, through positive modeling, help to counteract the obesity epidemic, with the portrayals leading men to lead more healthy lifestyles. On the negative side, the skewed images may lead to male body dissatisfaction, depression and eating disorders. We can use this knowledge to educate our patients about the false sense of reality often portrayed on social media," says Editor-in-Chief Brenda K. Wiederhold, PhD, MBA, BCB, BCN, Interactive Media Institute, San Diego, California and Virtual Reality Medical Institute, Brussels, Belgium.