Culture

The number of obstetrician-gynecologists who are able to prescribe a lifesaving opioid addiction medicine called buprenorphine to their patients is woefully small, comprising less than two percent of the 31,000-plus doctors studied across the country, according to new analysis. This is especially concerning as the proportion of those expecting to give birth who are using prescription opioids has increased exponentially in the last several decades. The researchers' findings were published today in JAMA Network Open.

"There is room for OB-GYNs to curb the opioid epidemic by filling gaps we see in treatment of pregnant patients," said the study's lead author, Max Jordan Nguemeni Tiako, MS, a medical student at Yale University who worked on this research as a fellow at the Perelman School of Medicine of the University of Pennsylvania. "Many of those who are getting substance use care are also not getting any reproductive care at all, so there's also a potential bridge opportunity here, too."

Tiako joined with several researchers, including the study's senior author, Zachary Meisel, MD, director for the Center for Emergency Care Research and Policy, and Sindhu Srinivas, MD, vice chair of quality and safety for Obstetrics and Gynecology, to examine how many United States OB-GYNs have their X-waiver, a certification that allows them to prescribe opioid treatment medications like buprenorphine. A "partial-agonist," buprenorphine soothes the brain's cravings for opioids by partially activating opiate receptors, and binding to them tightly (more than most other opioids), decreasing the risk of fatal overdoses. On top of that, buprenorphine has been approved by the Food and Drug Administration (FDA) for use in those who are pregnant.

This is important, because numbers are showing significant increases in opioid use among those who are expecting to give birth. In the 20 years between 1992 and 2020, the rate of pregnant patients receiving substance use treatment for opioids went from 1 percent to 19, and fatal overdoses are becoming a leading cause of postpartum deaths. Additionally, from 2000 to 2014, the number of children born with an opioid withdrawal-like condition called neonatal abstinence syndrome (NAS) spiked, increasing from 1.2 per 1,000 to 8 per 1,000.

However, X-waivers aren't extremely common among doctors overall, not just among obstetrician-gynecologists. Obtaining an X-waiver requires training, which takes eight hours for physicians and 24 hours for nurse-practitioners and physician assistants. This could be taxing for physicians whose schedules are often totally full with their responsibilities to patients. Stigma - seeping in from society's attitudes toward substance use and even from some health care workers themselves - is likely also playing a role, Tiako said.

In an attempt to gauge how many obstetrician-gynecologists across the United States can prescribe life-saving opioid agonists - and where they are - the researchers compiled county- and state-level data on doctors who accept Medicaid. The data was pulled from September 2019.

A total of 31,311 doctors were identified. Of them, only 560 had their X-waiver, 1.8 percent.

"We didn't come in with great expectations because X-waiver rates aren't extremely high nationwide even in specialties where efforts have been made to improve them, such as Emergency Medicine," said Meisel. "But the numbers we saw are exceedingly low for the need that we know exists."

When dividing the numbers by area - divided into urban, suburban, and rural settings - differences were noted. OB-GYN doctors in suburban counties were 85 percent more likely to have their X-waiver than those in urban areas. Doctors in rural areas were more than twice as likely to have their X-waiver, but those figures were not found to be statistically significant and could be misleading.

"There are, overall, very few OBGYNs in entirely rural areas, in which case the need for buprenorphine is being primarily met by nurse practitioners and physician assistants," said Tiako. "We did not capture their numbers in this study, but we believe that the level of care through buprenorphine there is also likely not to be high."

Additionally, the study showed that OB-GYN doctors in areas where the rates of infants born with neonatal abstinence syndrome were highest, doctors were five times as likely to have their X-waiver compared to those in the areas with the lowest rates of the syndrome.

"We saw that the need isn't being matched anywhere, but it seems possible that the severity of the opioid epidemic might be driving greater rates in areas that need it," Tiako said. "That said, these results matched some prior studies that showed buprenorphine was more accessible to people living in suburban settings, who are mostly white, commercially ensured patients. When buprenorphine was rolled out, the pharmaceutical campaign targeted private practice physicians who likely had more time to do the X-waiver training. If you work in a FQHC (federally qualified health center), time is a much rarer commodity and it's less likely that you can commit to that."

Moving forward, Tiako said he and his fellow researchers have distributed a survey to reproductive health providers as well as substance use disorder providers to gauge their attitudes and practices toward patients with substance use disorders, and toward pregnant patients, respectively. He's looking forward to analyzing the responses.

"We're trying to identify the gap so that it can be closed," Tiako explained. "That could help us improve care all around, from substance use to reproductive care."

An international study led by researchers from the Faculty of Pharmacy at the Complutense University of Madrid has identified a series of biosynthetic genes involved in the production of usnic acid in lichen, a compound showing antiviral, antioxidant, neuroprotective, antibacterial and anticancer activity.

Not all lichens --composite organisms resulting from the symbiosis of fungi and green algae or cyanobacteria-- produce this compound, and this study, published in Genome Biology and Evolution, has revealed why there is a loss of specific biosynthetic genes in non-producing species.

"Identifying the genes involved in the biosynthesis of these compounds is essential for future studies that require their isolation and mass production; similarly, the genomic approach adopted in this study has helped us identify new biosynthetic genes (PKS) of as yet unknown compounds that may be of pharmacological interest", explained David Pizarro, the first author of the study and a researcher in the Department of Pharmacology, Pharmacognosy and Botany at the UCM.

To carry out this study, researchers sequenced the genomes of 40 lichen species that produce and do not produce usnic acid.

"The genomes were assembled, annotated and compared using bioinformatics tools and computational biology, and we also analysed the diversity of lichen compounds using chromatography", Pizarro added.

New family with unknown function

This study also identified and described a new family of biosynthetic genes (PKS) with an unknown function that may be specific to lichens.

"We identified numerous clusters of biosynthetic genes of unknown function, some of which are homologous to other genes involved in the biosynthesis of antibiotics and tox-ins, thus opening a novel avenue of research into new molecules in the pharmaceutical industry", reported Pradeep Divakar, another researcher in the Department of Pharma-cology, Pharmacognosy and Botany.

Lichens are of great ecological importance. They have been widely used as bio-indicators of air pollution and other factors because of their high sensitivity to environmental changes, they form the basis of the food chain in specialised ecosystems and they are also an important nest-building resource for birds due to the antibacterial and antifungal activity of their secondary compounds.

"Another important function of lichens relates to soil formation, since they can prevent soil erosion and help maintain moisture, facilitating the establishment of vascular plants", concluded Pizarro.

Depression is a mental disorder that affects more than 264 million people of all ages worldwide. Understanding its mechanisms is vital for the development of effective therapeutic strategies. Scientists from the Institut Pasteur, Inserm and the CNRS recently conducted a study showing that an imbalance in the gut bacterial community can cause a reduction in some metabolites, resulting in depressive-like behaviors. These findings, which show that a healthy gut microbiota contributes to normal brain function, were published in Nature Communications on December 11, 2020.

The bacterial population in the gut, known as the gut microbiota, is the largest reservoir of bacteria in the body. Research has increasingly shown that the host and the gut microbiota are an excellent example of systems with mutually beneficial interactions. Recent observations also revealed a link between mood disorders and damage to the gut microbiota. This was demonstrated by a consortium of scientists from the Institut Pasteur, the CNRS and Inserm, who identified a correlation between the gut microbiota and the efficacy of fluoxetine, a molecule frequently used as an antidepressant. But some of the mechanisms governing depression, the leading cause of disability worldwide, remained unknown.

Using animal models, scientists recently discovered that a change to the gut microbiota brought about by chronic stress can lead to depressive-like behaviors, in particular by causing a reduction in lipid metabolites (small molecules resulting from metabolism) in the blood and the brain.

These lipid metabolites, known as endogenous cannabinoids (or endocannabinoids), coordinate a communication system in the body which is significantly hindered by the reduction in metabolites.
Gut microbiota plays a role in brain function and mood regulation

Endocannabinoids bind to receptors that are also the main target of THC, the most widely known active component of cannabis. The scientists discovered that an absence of endocannabinoids in the hippocampus, a key brain region involved in the formation of memories and emotions, resulted in depressive-like behaviors.

The scientists obtained these results by studying the microbiotas of healthy animals and animals with mood disorders. As Pierre-Marie Lledo, Head of the Perception and Memory Unit at the Institut Pasteur (CNRS/Institut Pasteur) and joint last author of the study, explains: "Surprisingly, simply transferring the microbiota from an animal with mood disorders to an animal in good health was enough to bring about biochemical changes and confer depressive-like behaviors in the latter."

The scientists identified some bacterial species that are significantly reduced in animals with mood disorders. They then demonstrated that an oral treatment with the same bacteria restored normal levels of lipid derivatives, thereby alleviating the depressive-like behaviors. These bacteria could therefore serve as an antidepressant. Such treatments are known as "psychobiotics".

"This discovery shows the role played by the gut microbiota in normal brain function," continues Gérard Eberl, Head of the Microenvironment and Immunity Unit (Institut Pasteur/Inserm) and joint last author of the study. If there is an imbalance in the gut bacterial community, some lipids that are vital for brain function disappear, encouraging the emergence of depressive-like behaviors. In this particular case, the use of specific bacteria could be a promising method for restoring a healthy microbiota and treating mood disorders more effectively.

Researchers at Drexel University's College of Engineering have reported that fabric coated with a conductive, two-dimensional material called MXene, is highly effective at blocking electromagnetic waves and potentially harmful radiation. The discovery is a key development for efforts to weave technological capabilities into clothing and accessories.

Materials that block electromagnetic waves had a commercial moment a handful of years ago when fears that high-tech thieves could scan or copy credit cards, passports or hack into laptops and contactless car keys had people putting them in special wallets, bags and protected pockets. While reporting suggests these fears were overblown, the demand for this sort of textile is likely to grow as more manufacturers incorporate sensing and communication technologies into fabrics.

They could also be deployed in national defense organizations to shield devices from tracing and hacking and to protect people from strong microwave radiation - the kind that might have been used against American and Canadian diplomats according to recent reports.

"Wearable devices will need shielding from the electromagnetic interference (EMI) regularly produced by mobile devices, and that shielding should be integrated as part of the garment," said Yury Gogotsi, PhD, Distinguished University and Bach professor at Drexel, who led research recently published in the materials science journal CARBON. "We have known for some time that MXene has the ability to block electromagnetic interference better than other materials, but this discovery shows that it can effectively adhere to fabrics and maintain its unique shielding capabilities."

The interference comes from residual electromagnetic fields produced by electronics devices. Users notice it as a buzz, a slowing or temporary stall in a device's function. It's a momentary inconvenience, but these moments are becoming more frequent with expanded use of mobile devices and connected technology - including wearables.

Improving the design of these devices, according to Gogotsi, entails using a shielding material to contain electromagnetic field generated by the device, as well as protecting it from interference produced by other devices. Gogotsi's team, which first produced and studied the conductive two-dimensional MXene materials nearly a decade ago, has been testing MXene coatings for this role, with promising results.

"MXenes are well-suited for use as shielding because they can be stably produced as a spray coating, an ink or a paint, so they can be applied to textiles without adding much weight or taking up more room," Gogotsi said. "We have also discovered that MXene shielding can absorb and reflect electromagnetic waves, so it not protects the wearable devices and electronic gadgets, but also protect people from strong electromagnetic field."

The researchers' most recent finding shows that dip-coating regular cotton or linen fabric in a MXene solution will turn it into an equally formidable shielding material - blocking EMI at greater than 99.9% effectiveness.

MXene flakes suspended in solution naturally adhere to the fibers in conventional cotton and linen fabrics because of their electric charge. This produces a thorough and durable coating, without the need for the pre- or post-treatment processes to produce most commercial conductive yarns and fabrics.

As part of the study, the MXene-coated fabrics were tested after being stored under normal conditions for two years and they showed only a slight drop in shielding efficiency - roughly 10%.

"This work provides a much-improved alternative to current EMI shielding textiles," said Simge Uzun, a doctoral student in Gogotsi's research group, who conducted this research as a part of her PhD program. "Not only do MXene-coated fabrics exceed the performance of commercial metal-coated fabrics, but they can be sustainably produced by coating form aqueous solution without extra processing or chemical additives."

Sebastian Lobentanzer of Goethe University, Frankfurt, has been studying small RNA dynamics in various contexts using bioinformatic methods. Recently, small RNAs have become more and more interesting for researchers, primarily because of their extensive regulatory functions. To examine these functions in stroke, Lobentanzer joined Katarzyna Winek of Hebrew University, Jerusalem, to study microRNAs and tRNA fragments in blood samples from ischemic stroke patients collected at Charité, Berlin. "tRNA fragments, which until now were only thought to be debris of the amino acid-transporting tRNAs, have recently been shown to possess biological functions; naturally, we were very interested in that," explains the pharmacologist.

The project was initiated and led by Hermona Soreq (Hebrew University, Jerusalem, Israel) and Andreas Meisel (Charité, Berlin), who jointly study the contributions of small RNA regulators of cholinergic signaling in blood cells of stroke patients, funded by the Einstein Foundation. Katarzyna Winek from The Edmond and Lily Safra Center of Brain Science at The Hebrew University collaborated with Sebastian Lobentanzer at the Institute for Pharmacology and Clinical Pharmacy (AK Jochen Klein) at Goethe University Frankfurt, Germany.

This collaborative effort was able to show, for the first time, the involvement of monocytic tRNA fragments in the poststroke immune response. "Simply put, there may be a 'changing of the guards,' in which tRNA fragments replace microRNAs in monocytes," explains Lobentanzer. "Bioinformatic network analyses show that these two small RNA species have vastly different functional roles in the immune response, and thus may work in synergy in the regulation of homeostasis." In the long run, the researchers want to find therapeutics to modify these processes. Indeed, if the immune status of each patient after a stroke could be individually determined, many complications could be avoided.

Bacteria are always hungry, according to Thomas Wood, Biotechnology Endowed Chair and professor of chemical engineering in the Penn State College of Engineering. If you gave a single bacterium all the food it wanted, it would obtain the mass of the Earth in about two days.

To survive periods of starvation, bacteria must slow down their activity, or "go to sleep," according to Wood. Toxin-antitoxin (TA) systems, or small genetic elements found in the chromosomes of bacteria, allow bacteria to either speed up growth -- using antitoxins -- or slow down growth -- using toxins -- in order to thrive in periods where food is either plentiful or scarce.

Wood and his colleagues detail their discovery of a TA system that they named the HEPN/MNT system -- higher?eukaryotes and prokaryotes nucleotide-binding and minimal nucleotidyltransferase -- in Nucleic Acids Research.

"If you eat three meals a day, bacteria in your stomach starve between each of the meals," Wood said. "If bacteria did not have toxins to slow their metabolism and save their resources, they would run out of energy and die during each starvation period."

In the HEPN/MNT system, the MNT antitoxin "bites" the HEPN toxin to inactivate and block it. More specifically, adenosine triphosphate?(ATP) is transferred near the active site of the toxin protein, inhibiting the toxin.

"The easiest way for a bacterial cell to turn off a toxin is to bear-hug and hold on to it," Wood said. "We found in this specific system that the antitoxin acts as an enzyme to inactivate the toxin."

The HEPN/MNT system is the most abundant system found in prokaryotes, or one-cell organisms like bacteria, according to Wood.

Wood's latest discovery is the third type of TA system he has helped to discover and name. In 2008, with follow-up studies published in 2016, Wood discovered a new type of antitoxin that functions to oxidize?the toxin sulfur. Wood named the system "TomB" after Tom, his nickname.

In 2012, Wood published on a TA system known as GhoST, the first known TA system in which the antitoxin functions as an enzyme. In the system, the antitoxin GhoS consumes the genetic material, or mRNA, to remove the toxin, GhoT, from a bacterial cell. Otherwise, the toxin GhoT punches a hole in the cell membrane and puts the cell to sleep, giving it a ghost-like appearance.

"All antitoxins inactivate toxins and prevent them from slowing cell growth," Wood said. "The difference lies in how each antitoxin interacts with the?toxin."

TA systems are important both to conserve healthy bacteria and to fight off viruses.

"We have a love-hate relationship with bacteria, but we need them, especially in our digestive systems," he said.

Wood discovered in 1996 that TA systems slow down bacteria growth when a virus attacks in order to prevent the virus from killing the cell.

"TA systems prevent viruses from propagating to a hundred neighbors and taking control of a bacterial population," Wood said. "A virus has no way to kill a bacterium if it is asleep."

A muscle fiber consists of just one cell, but many nuclei. A team at the MDC led by Professor Carmen Birchmeier has now shown just how varied these nuclei are. The study, which has been published in Nature Communications, can help us better understand muscle diseases such as Duchenne muscular dystrophy.

Usually, each cell has exactly one nucleus. But the cells of our skeletal muscles are different: These long, fibrous cells have a comparatively large cytoplasm that contains hundreds of nuclei. But up to now, we have known very little about the extent to which the nuclei of a single muscle fiber differ from each other in terms of their gene activity, and what effect this has on the function of the muscle.

A team led by Professor Carmen Birchmeier, head of the research group on Developmental Biology / Signal Transduction at the Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC), has now unlocked some of the secrets contained in these muscle cell nuclei. As the researchers report in the journal Nature Communications, the team investigated the gene expression of cell nuclei using a still quite novel technique called single-nucleus RNA sequencing - and in the process, they came across an unexpectedly high variety of genetic activity.

Muscle fibers resemble entire tissues

"Due to the heterogeneity of its nuclei, a single muscle cell can act almost like a tissue, which consists of a variety of very different cell types," explains Dr. Minchul Kim, a postdoctoral researcher in Birchmeier's team and one of the two lead authors of the study. "This enables the cell to fulfill its numerous tasks, like communicating with neurons or producing certain muscle proteins."

Kim undertook the majority of the experimental work in the study, and his data was also evaluated at the MDC. The bioinformatics analyses were performed by Dr. Altuna Akalin, head of the Bioinformatics and Omics Data Science Platform at the MDC's Berlin Institute of Medical Systems Biology (BIMSB), and Dr. Vedran Franke, a postdoctoral fellow in Akalin's team and the study's co-lead author. "It was only thanks to the constant dialogue between the experiment-based and theory-based teams that we were we able to arrive at our results, which offer important insight for research into muscle diseases," emphasizes Birchmeier. "New techniques in molecular biology such as single cell sequencing create large amounts of data. It is essential that computational labs are part of the process early on as analysis is as important as data generation," adds Akalin.

Injured muscles contain activated growth-promoting genes

The researchers began by studying the gene expression of several thousand nuclei from ordinary muscle fibers of mice, as well as nuclei from muscle fibers that were regenerating after an injury. The team genetically labeled the nuclei and isolated them from the cells. "We wanted to find out whether a difference in gene activity could be observed between the resting and the growing muscle," says Birchmeier.

And they did indeed find such differences. For example, the researchers observed that the regenerating muscle contained more active genes responsible for triggering muscle growth. "What really astonished us, however, was the fact that, in both muscle fiber types, we found a huge variety of different types of nuclei, each with different patterns of gene activity," explains Birchmeier.

Stumbling across unknown nuclei types

Before the study, it was already known that different genes are active in nuclei located in the vicinity of a site of neuronal innervation than in the other nuclei. "However, we have now discovered many new types of specialized nuclei, all of which have very specific gene expression patterns," says Kim. Some of these nuclei are located in clusters close to other cells adjacent to the muscle fiber: for example, cells of the tendon or perimysium - a connective tissue sheath that surrounds a bundle of muscle fibers.

"Other specialized nuclei seem to control local metabolism or protein synthesis and are distributed throughout the muscle fiber," Kim explains. However, it is not yet clear what exactly the active genes in the nuclei do: "We have come across hundreds of genes in previously unknown small groups of nuclei in the muscle fiber that appear to be activated," reports Birchmeier.

Muscle dystrophy seemingly causes many nuclei types to be lost

In a next step, the team studied the muscle fiber nuclei of mice with Duchenne muscular dystrophy. This disease is the most common form of hereditary muscular dystrophy (muscle wasting) in humans. It is caused by a mutation on the X chromosome, which is why it mainly affects boys. Patients with this disease lack the protein dystrophin, which stabilizes the muscle fibers. This results in the cells gradually dying off.

"In this mouse model, we observed the loss of many types of cell nuclei in the muscle fibers," reports Birchmeier. Other types were no longer organized into clusters, as the team had previously observed, but scattered throughout the cell. "I couldn't believe this when I first saw it," she recounts. "I asked my team to repeat the single-nucleus sequencing immediately before we investigated the finding any further." But the results remained the same.

The mouse nuclei resemble those of human patients

"We also found some disease-specific nuclear subtypes," reports Birchmeier. Some of these are nuclei that only transcribe genes to a small extent and are in the process of dying off. Others are nuclei that contain genes that actively repair damaged myofibers. "Interestingly, we also observed this increase in gene activity in muscle biopsies of patients with muscle diseases provided by Professor Simone Spuler's Myology Lab at the MDC," says Birchmeier. "It seems this is how the muscle tries to counteract the disease-related damage."

"With our study, we are presenting a powerful method for investigating pathological mechanisms in the muscle and for testing the success of new therapeutic approaches," concludes Birchmeier. As muscular malfunction is also observed in a variety of other diseases, such as diabetes and age- or cancer-related muscle atrophy, the approach can be used to better research these changes too. "We are already planning further studies with other disease models," Kim confirms.

Once the COVID-19 pandemic is over, a lot of things will go back to normal. We'll stop wearing masks. We'll crowd into restaurants. We'll walk whatever direction we want to down grocery store aisles. But some changes that the pandemic spurred might be here to stay. Among them: the expansion of telepsychiatry.

"This will be part of the new normal," said James Berry, a clinician with the West Virginia University School of Medicine. "The genie is now out of the bottle, and it isn't going back in."

After West Virginia's stay-at-home order took effect in March, Berry was part of the team that transitioned outpatient behavioral-health visits to telepsychiatry at WVU's Chestnut Ridge Center. These visits included group therapy sessions for people with opioid use disorder.

"Behavioral health issues are very treatable and manageable problems," said Berry, who chairs the Department of Behavioral Medicine and Psychiatry and directs addiction services at CRC. "Whatever we can do to create access for people who need help is something that we need to prioritize. People don't have to suffer."

In a new letter published in the Journal of Addiction Medicine, Berry and his colleagues explain how large-scale deployment of telepsychiatry is possible for both individual- and group-based visits.

His team of School of Medicine researchers and WVU Medicine clinicians includes Erin Winstanley, Laura Lander, Wanhong Zheng, Kari-Beth Law and Ashley Six-Workman.

Before the stay-at-home order, virtual care and therapy was offered for rural clinics only; however, during the week that the stay-at-home order began, CRC moved 75% of its on-site therapy sessions to Zoom. Soon after, 98% of the sessions had gone virtual.

Prior to the pandemic, the department was conducting pioneering telepsychiatry services to rural areas across West Virginia through funding from the Health Resources and Services Administration, as overseen by Law. With this experience, Law was able to lead the transition at CRC to virtual care.

Bad internet connections don't preclude good emotional connections

Even though West Virginia has the fourth-lowest rate of household broadband access in the nation, only 10% to 15% of the patients in CRC's virtual therapy sessions had connectivity problems--a percentage that was lower than Berry expected.

"Over time, people became very creative in making the connectivity work," he said. "For instance, several patients didn't have broadband access in their home, but many had access to a smartphone. It's just that not everybody had service. People used public Wi-Fi options in restaurant parking lots to conduct their visits. While this does not mean that access to quality broadband services is not a priority, it does speak to people's resilience and need for access.

Looking at a screen--instead of directly into someone's face in the same room--didn't make patients more reticent to participate in therapy sessions. If anything, the opposite was true.

"I don't know if it's because they were in the comfort of their own home or because they didn't feel like all eyes were on them, but one of the things I noticed early on is that people seemed more comfortable sharing details than they would have been in person," Berry said.

The best laid plans

Even before the pandemic, CRC had been planning to expand its telepsychiatry options. They just didn't expect to do it so quickly.

"Our five- to 10-year plan was to allow access for much of our care into the virtual world, but there were many barriers," Berry said.

One of those barriers was patients' and clinicians' unfamiliarity with telepsychiatry. Another was some insurers' unwillingness to pay for virtual therapy--or therapy in a patient's home--even when they would cover comparable in-person therapy.

Regulations and legislation have hindered the adoption of telepsychiatry, too. "As a physician, for instance, you're licensed to practice in a particular state," Berry said. "I'm licensed to practice medicine in West Virginia. Pre-pandemic, that meant that in order to treat somebody who was in a state that doesn't participate in the Interstate Medical Licensure Compact--for example, Ohio--I would have to have an Ohio license, or there would have to be an arrangement made between our two states that would allow me to do that. You can imagine the difficulty that would have presented when it comes to treating patients across state lines."

But the pandemic swept many of those obstacles away. "Now we're seeing patients from all over the country," Berry said.

Coming together while staying apart

Wherever they live, many of the patients that Berry and his colleagues are seeing may need more emotional support than usual right now. The feelings of isolation that can accompany staying at home--and seeing friends and family less frequently--can trigger new mental health problems and worsen old ones.

Social distancing has been linked to declines in mental health outcomes, increases in substance use and upticks in crises such as suicidal ideation.

For these reasons, telepsychiatry can be crucial during the pandemic.

Berry said, "When we saw the pandemic coming in early March, I said, 'Listen, everybody. We are already facing a behavioral health epidemic, an overdose epidemic and a suicide epidemic. Now we've got this COVID viral epidemic. Once people are isolated and don't have their personal connections anymore, we are going to be facing a huge increase in the number of people who are experiencing severe psychological distress and disorders. We need to be prepared for this.'"

If Berry could go back to the early days of those preparations--knowing what he knows now--he would give himself one piece of advice: be patient.

"Early on, it was really easy to get frustrated when you're talking to somebody and their connection is going in and out," he said. "But it's just a growing pain. Take a step back. If somebody connects at all, that's a victory."

Combining neuroscience and robotic research has gained impressive results in the rehabilitation of paraplegic patients. A research team led by Prof. Gordon Cheng from the Technical University of Munich (TUM) was able to show that exoskeleton training not only helped patients to walk, but also stimulated their healing process. With these findings in mind, Prof. Cheng wants to take the fusion of robotics and neuroscience to the next level.

Prof. Cheng, by training a paraplegic patient with the exoskeleton within your sensational study under the "Walk Again" project (LINK!), you found that patients regained a certain degree of control over the movement of their legs. Back then, this came as a complete surprise to you ...

... and it somehow still is. Even though we had this breakthrough four years ago, this was only the beginning. To my regret, none of these patients is walking around freely and unaided yet. We have only touched the tip of the iceberg. To develop better medical devices, we need to dig deeper in understanding how the brain works and how to translate this into robotics.

In your paper published in Science Robotics this month, you and your colleague Prof. Nicolelis, a leading expert in neuroscience and in particular in the area of the human-machine interface, argue that some key challenges in the fusion of neuroscience and robotics need to be overcome in order to take the next steps. One of them is to "close the loop between the brain and the machine" - what do you mean by that?

The idea behind this is that the coupling between the brain and the machine should work in a way where the brain thinks of the machine as an extension of the body. Let's take driving as an example. While driving a car, you don't think about your moves, do you? But we still don't know how this really works. My theory is that the brain somehow adapts to the car as if it is a part of the body. With this general idea in mind, it would be great to have an exoskeleton that would be embraced by the brain in the same way.

How could this be achieved in practice?

The exoskeleton that we were using for our research so far is actually just a big chunk of metal and thus rather cumbersome for the wearer. I want to develop a "soft" exoskeleton - something that you can just wear like a piece of clothing that can both sense the user's movement intentions and provide instantaneous feedback. Integrating this with recent advances in brain-machine interfaces that allow real-time measurement of brain responses enables the seamless adaptation of such exoskeletons to the needs of individual users. Given the recent technological advances and better understanding of how to decode the user's momentary brain activity, the time is ripe for their integration into more human-centered or, better ? brain-centered ? solutions.

What other pieces are still missing? You talked about providing a "more realistic functional model" for both disciplines.

We have to facilitate the transfer through new developments, for example robots that are closer to human behaviour and the construction of the human body and thus lower the threshold for the use of robots in neuroscience. This is why we need more realistic functional models, which means that robots should be able to mimic human characteristics. Let's take the example of a humanoid robot actuated with artificial muscles. This natural construction mimicking muscles instead of the traditional motorized actuation would provide neuroscientists with a more realistic model for their studies. We think of this as a win-win situation to facilitate better cooperation between neuroscience and robotics in the future.

You are not alone in the mission of overcoming these challenges. In your Elite Graduate Program in Neuroengineering, the first and only one of its kind in Germany combining experimental and theoretical neuroscience with in-depth training in engineering, you are bringing together the best students in the field.

As described above, combining the two disciplines of robotics and neuroscience is a tough exercise, and therefore one of the main reasons why I created this master's program in Munich. To me, it is important to teach the students to think more broadly and across disciplines, to find previously unimagined solutions. This is why lecturers from various fields, for example hospitals or the sports department, are teaching our students. We need to create a new community and a new culture in the field of engineering. From my standpoint, education is the key factor.

A team of McGill University researchers has found that young adults who perceived higher levels of social support reported fewer mental health problems.

In a study published today in JAMA Network Open, the team led by Marie-Claude Geoffroy, Assistant Professor in the Department of Educational and Counseling Psychology at McGill, reassessed the impact of the presence and awareness of social support, such as family and friends, as a safeguard against mental health problems, including depression, anxiety, suicidal ideation and suicide attempts. Their results indicate that young adults who perceived higher levels of social support - the feeling that there is someone who they can depend on for help should they need it - at the age of 19, showed lower levels of depression and anxiety symptoms one year later.

"Our study shows that even in cases where people previously experienced mental health problems, social support was beneficial for mental health later on," says Prof. Geoffroy, who holds the Canada Research Chair in Youth Suicide Prevention. "We discovered potential benefits of promoting and leveraging social support as a means to protect the mental health of young adults, even in individuals who experienced mental health problems at an earlier developmental stage in life. That social support is not only beneficial for depression, but for other salient mental health outcomes as well."

The power of perception

The team used data from the Quebec Longitudinal Study on Child Development, collected by the Institut de la statistique du Québec from over 1,000 participants of a representative birth cohort of individuals born in the province of Quebec. Following participants since their birth in 1997 and 1998, the researchers looked at their levels of perceived social support at the onset of adulthood.

The researchers found that people who experienced greater levels of social support experienced 47% less severe depression and 22% less anxiety than those with less social support. The team also found that those who reported higher levels of perceived social support were at a 40% decreased risk of experiencing suicidal ideation and attempts.

"Our study was conducted before the current COVID-19 pandemic, so we do not know whether our results will apply in the current context," adds Sara Scardera, a master's student in McGill's School/Applied Child Psychology program under the supervision of Prof. Geoffroy and co-author of the study. "However, in a 'normal' context, youth who perceived that they had someone to rely on reported better mental health outcomes. We believe that is beneficial to offer help to those in need, and to make sure your friends know that they can count on you."

The data collection is ongoing, therefore new mental health data will be available when participants turn 23 years old over the course of the 2021 winter season. The researchers will verify whether the same patterns of association have been present during the COVID-19 pandemic.

Future lines of research will examine whether certain types of social support - for example, parents vs. friends - is more beneficial to the mental health of young adults.

"The biohybrid retina is a cell therapy for the reconstruction of the damaged retina by implanting healthy cells in the patient's eye," says Fivos Panetsos, director of the Neuro-computation and Neuro-robotics Group of the UCM and member of the Institute of Health Research of the Hospital Clínico San Carlos de Madrid (IdISSC).

The cells of the artificial retina adhere to very thin silk fibroin biofilms - a biomaterial 100% biocompatible with human tissue - and covered by a gel which protects them during eye surgery and allows them to survive during the time they need to get integrated with thesurrounding tissue after transplantation.

"The transplanted retina also contains mesenchymal cells that function as producers of neuroprotective and neuroreparative molecules and facilitate functional integration between implanted and patient cells", adds UCM's researcher and director of the study, published in the Journal of Neural Engineering .

One more step in a problem with more than 196 million affected

To build this artificial retina, researchers have developed silk fibroin films with mechanical characteristics similar to Bruch's membrane - the layer of cells that supports the neural retina. Then, they have biofunctionalized them so that retinal cells could adhere, and on them they have grown epithelial and neural cells. Finally, they have carried out an in vitro study of the structural and functional characteristics of the biohybrid.

Age-Related Macular Degeneration (AMD) is a neurodegenerative disease that causes a progressive loss of central vision and even blindness in its most advanced stage. Triggered by heterogeneous, complex and still poorly understood mechanisms, it is the leading cause of irreversible vision loss in people over 65 years of age and affects more than 196 million people worldwide.

AMD is an incurable disease, and current treatments can only alleviate symptoms and slow down the progression of the disease. "This research is an important step towards solving the problem of blindness faced by AMD patients", concludes Panetsos.

Once the COVID-19 pandemic is over, a lot of things will go back to normal. We’ll stop wearing masks. We’ll crowd into restaurants. We’ll walk whatever direction we want to down grocery store aisles. But some changes that the pandemic spurred might be here to stay. Among them: the expansion of telepsychiatry.

“This will be part of the new normal,” said James Berry, a clinician with the West Virginia University School of Medicine. “The genie is now out of the bottle, and it isn’t going back in.”

After West Virginia’s stay-at-home order took effect in March, Berry was part of the team that transitioned outpatient behavioral-health visits to telepsychiatry at WVU’s Chestnut Ridge Center. These visits included group therapy sessions for people with opioid use disorder.

“Behavioral health issues are very treatable and manageable problems,” said Berry, who chairs the Department of Behavioral Medicine and Psychiatry and directs addiction services at CRC. “Whatever we can do to create access for people who need help is something that we need to prioritize. People don’t have to suffer.”

In a new letter published in the Journal of Addiction Medicine, Berry and his colleagues explain how large-scale deployment of telepsychiatry is possible for both individual- and group-based visits.

His team of School of Medicine researchers and WVU Medicine clinicians includes Erin Winstanley, Laura Lander, Wanhong Zheng, Kari-Beth Law and Ashley Six-Workman.

Before the stay-at-home order, virtual care and therapy was offered for rural clinics only; however, during the week that the stay-at-home order began, CRC moved 75% of its on-site therapy sessions to Zoom. Soon after, 98% of the sessions had gone virtual.

Prior to the pandemic, the department was conducting pioneering telepsychiatry services to rural areas across West Virginia through funding from the Health Resources and Services Administration, as overseen by Law. With this experience, Law was able to lead the transition at CRC to virtual care.

Bad internet connections don’t preclude good emotional connections

Even though West Virginia has the fourth-lowest rate of household broadband access in the nation, only 10% to 15% of the patients in CRC’s virtual therapy sessions had connectivity problems—a percentage that was lower than Berry expected.

“Over time, people became very creative in making the connectivity work,” he said. “For instance, several patients didn’t have broadband access in their home, but many had access to a smartphone. It’s just that not everybody had service. People used public Wi-Fi options in restaurant parking lots to conduct their visits. While this does not mean that access to quality broadband services is not a priority, it does speak to people’s resilience and need for access.

Looking at a screen—instead of directly into someone’s face in the same room—didn’t make patients more reticent to participate in therapy sessions. If anything, the opposite was true.

“I don’t know if it’s because they were in the comfort of their own home or because they didn’t feel like all eyes were on them, but one of the things I noticed early on is that people seemed more comfortable sharing details than they would have been in person,” Berry said.

The best laid plans

Even before the pandemic, CRC had been planning to expand its telepsychiatry options. They just didn’t expect to do it so quickly.

“Our five- to 10-year plan was to allow access for much of our care into the virtual world, but there were many barriers,” Berry said.

One of those barriers was patients’ and clinicians’ unfamiliarity with telepsychiatry. Another was some insurers’ unwillingness to pay for virtual therapy—or therapy in a patient’s home—even when they would cover comparable in-person therapy.

Regulations and legislation have hindered the adoption of telepsychiatry, too. “As a physician, for instance, you’re licensed to practice in a particular state,” Berry said. “I’m licensed to practice medicine in West Virginia. Pre-pandemic, that meant that in order to treat somebody who was in a state that doesn’t participate in the Interstate Medical Licensure Compact—for example, Ohio—I would have to have an Ohio license, or there would have to be an arrangement made between our two states that would allow me to do that. You can imagine the difficulty that would have presented when it comes to treating patients across state lines.”

But the pandemic swept many of those obstacles away. “Now we’re seeing patients from all over the country,” Berry said.

Coming together while staying apart

Wherever they live, many of the patients that Berry and his colleagues are seeing may need more emotional support than usual right now. The feelings of isolation that can accompany staying at home—and seeing friends and family less frequently—can trigger new mental health problems and worsen old ones.

Social distancing has been linked to declines in mental health outcomes, increases in substance use and upticks in crises such as suicidal ideation.

For these reasons, telepsychiatry can be crucial during the pandemic.

Berry said, “When we saw the pandemic coming in early March, I said, ‘Listen, everybody. We are already facing a behavioral health epidemic, an overdose epidemic and a suicide epidemic. Now we’ve got this COVID viral epidemic. Once people are isolated and don’t have their personal connections anymore, we are going to be facing a huge increase in the number of people who are experiencing severe psychological distress and disorders. We need to be prepared for this.’”

If Berry could go back to the early days of those preparations—knowing what he knows now—he would give himself one piece of advice: be patient.

“Early on, it was really easy to get frustrated when you’re talking to somebody and their connection is going in and out,” he said. “But it’s just a growing pain. Take a step back. If somebody connects at all, that’s a victory.”

URBANA, Ill. - Scientists are getting closer to finding the genes for maleness in waterhemp and Palmer amaranth, two of the most troublesome agricultural weeds in the U.S.

Finding the genes could enable new "genetic control" methods for the weeds, which, in many places, no longer respond to herbicides.

"If we knew which genes control maleness and we could make those genes proliferate within the population, every plant in the field would be a male after a few generations, and theoretically, the population would crash," says Pat Tranel, professor and associate head in the Department of Crop Sciences at the University of Illinois and lead author on a study in New Phytologist.

Tranel and his colleagues had previously identified molecular markers associated with the male genomic region. After sequencing male genomes for both species, the researchers were able to use those markers to zero in on the male-specific region. Now, they are within 120 to 150 genes of finding their target.

"We're confident most of those 120 or so genes are probably doing nothing. It's just stuff that's accumulated in that region of the genome," Tranel says. "If I had to guess, I'd say maybe 10 of them are actually doing something relevant."

Narrowing down the genes related to gender in these weeds could have practical value for control, but the study also sheds light on the phenomenon of dioecy - male and female sexual organs on separate individuals - more generally. The vast majority of animals are dioecious, but it's rare in plants. More than 90% of flowering plants have both sexual organs on the same individual, and often within the same flower.

Waterhemp and Palmer amaranth, however, are dioecious.

Dioecy means it's impossible for a plant to self-pollinate; instead, female gametes must be fertilized by male pollen from another plant. That's a good thing for ensuring genetic diversity in a population. And it's likely what has made waterhemp and Palmer amaranth so successful at evading the detrimental effects of multiple herbicides.

"To date, waterhemp and Palmer amaranth have evolved resistance to herbicides spanning seven and eight modes of action, respectively. Dioecious reproduction results in all these resistance traits being mixed and matched within individuals. This mixing has allowed populations of both species to combine multiple herbicide resistances, leaving producers with few effective herbicide choices," Tranel says.

Understanding the rare phenomenon of dioecy in plants can help scientists piece together how traits are inherited from each parent, and to understand how the phenomenon evolves.

Unlike in animals, in which dioecy is thought to have evolved just once, scientists believe dioecy in plants has evolved numerous times. And, according to Tranel's study, it appears to have evolved independently in waterhemp and Palmer amaranth, two very closely related species.

"I'm not ready to say we absolutely know they evolved separately, but all the information we found supports that idea. Only two of the 120-150 genes were similar to each other across the two species," Tranel says.

One of those shared genes, Florigen, helps plants respond to day length by initiating flowering. Tranel doesn't know yet whether it determines the gender of flowers, but he's intrigued that it showed up in the male-specific Y region for both species.

"We don't know for sure, but maybe it's involved with males flowering earlier than females. That could be advantageous to males because then they'd be shedding pollen when the first females become receptive. So if, in fact, Palmer and waterhemp really did evolve dioecy separately, but both acquired this Florigen gene for a fitness advantage, that would be a cool example of parallel evolution."

Tranel hopes to narrow down the male-specific Y region in both species even further to isolate the genes that determine maleness. There's no guarantee a genetic control solution will be developed once those genes are identified - Tranel would likely need to attract industry partners for that - but having such a tool is not as far off as it once was.

Already possessing more salamander species than any other state in the country with 63, North Carolina has just added one more to make it 64. The aptly named Carolina Sandhills Salamander (Eurycea arenicola) is found in association with springs, seepages and small blackwater streams of the Sandhills region of North Carolina.

The Carolina Sandhills Salamander was previously lumped in as an unusual population of the Southern Two-lined Salamander (Eurycea cirrigera), but researchers at the North Carolina Museum of Natural Sciences applied next generation sequencing technology to show that the new species differs genetically (in both the mitochondrial and nuclear genome) from other species of two-lined salamanders (Eurycea bislineata complex). These results, published in Herpetologica today, back up more conspicuous evidence, as the Carolina Sandhills Salamander also differs in coloration, size and natural history from other members of the complex.

It's a discovery 50 years in the making. The first specimen was collected and identified in October 1969 and brought to the attention of the NC Museum's Alvin Braswell, then the assistant curator for lower invertebrates and now only recently retired. At first, Braswell thought that this original specimen was just a weird individual of Eurycea cirrigera, but then in the mid-1970s he started finding more "weird individuals" and thought, "Whoa, maybe there's something to this." As it turned out, the original specimen had been misidentified. Among other things, Eurycea arenicola is smaller on average in size, and mature individuals have a pronounced reddish color. "It's a real neat critter," notes co-author Braswell.

The fact that its range is restricted to the Sandhills is also unique. The Sandhills, according to Braswell, is an area that comprises the "best of what's left in North Carolina" of the once extensive Longleaf Pine ecosystem, which stretched from southeast Virginia all the way south to Florida. So much of that ecosystem, roughly 95 percent, has been altered or lost through development and conversion to other land use practices, but the NC Sandhills includes extensive Game Lands and Fort Bragg, protecting some very important habitat. The name itself reflects the species' tie to the Sandhills, as arenicola means "dweller of a sandy place" in Latin.

In the 1980s, Braswell began the process of describing the new species but never completed it. Braswell, burdened with administrative duties, ultimately turned it over to Bryan Stuart, who joined the NC Museum as research curator of herpetology in 2008, imploring him to "take it and run with it." Finally, in 2013 Stuart received a National Science Foundation Research Opportunity Award (ROA) that enabled detailed genetic research using a new, next generation sequencer. "With that machine, we were able to sequence a sufficiently large number of genes to test the distinct species status of the Carolina Sandhills Salamander," says Stuart, lead author on the paper.

Carolina Sandhills Salamander specimens were located and collected in Harnett, Hoke, Montgomery, Moore, Richmond, Robeson and Scotland counties. "Almost every known specimen of the new species is housed in our collection, with just a handful of individuals at a few other museums," notes Jeff Beane, collections manager for herpetology at the NC Museum and a co-author on the paper. "No records are yet known from South Carolina, but we have a record in North Carolina that is only two miles from the state line, so it gets close."

Despite being unnamed until this paper came out, the small geographic range of the Carolina Sandhills Salamander has prompted it to be listed on the W3 Watch List by the North Carolina Natural Heritage Program - meaning it is a "species that is poorly known and perhaps needs listing in upcoming years."

"This research also shows that there are other undescribed species in this complex that await description, even some that occur in North Carolina," Stuart adds. "So, there is definitely more to do with two-lined salamanders in the state."

Aleksei Smirnov, Assistant Professor, HSE University Faculty of Economic Sciences, and Egor Starkov, Assistant Professor, University of Copenhagen, have constructed a mathematical model that explains why it is advantageous for sellers not to delete negative reviews of their products. A study detailing this conclusion has been accepted for publication in The American Economic Journal: Microeconomics.

Empirical studies have indicated that consumers are more likely to buy a product with a rating slightly below a perfect one rather than a perfect one. Using game theory, the researchers analysed how negative reviews affect sales.

The researchers' model, which they presented in their paper 'Bad News Turned Good: Reversal under Censorship', involves two sets of participants: sellers, who know the true quality of the products they are selling and can selectively publish reviews about it, and buyers, who do not know a product's quality and can be categorized as either 'naïve' or 'rational'. Rational buyers use all available information to determine the quality of a product, while naïve buyers tend to take product reviews at face value and do not make any further inference.

'If there were only naïve consumers in the market, sellers would leave only perfect reviews, because the naïve consumers believe what they read and there is no reason to disenchant them with negative reviews,' Aleksei Smirnov explains.

However, in reality there are both naïve and rational consumers in the market, and the situation is as follows. Good reviews are perceived positively by everyone. Bad reviews are bad for the naïve consumers, but for the rational consumers these reviews actually increase their confidence in the quality of a product. Why? Because, the authors say, every bad review weakens sales among naïve consumers. Therefore, only a seller of a high quality product will be confident enough to publish it--they can be certain that in the future their product will garner positive feedback, and sales among rational consumers will compensate for any losses among naïve consumers.

Thus, bad reviews become a positive signal to rational consumers, and, by attracting more rational consumers, sellers boost sales.

Examples where a seller is not only not shy about negative feedback but, on the contrary, flaunts it, can be found literally on the street. For example, roadside advertising billboards for digitec, the largest electronics retailer in Switzerland, feature poor customer reviews of their products. The authors of the study do not have data on how this advertising campaign has affected digitec's profits, but given that the billboards have been around for years, it can be assumed that this marketing move has been quite successful.