Culture

New Haven, Conn. -- A drug once used to treat high blood pressure can help alcoholics with withdrawal symptoms reduce or eliminate their drinking, Yale University researchers report Nov. 19 in the American Journal of Psychiatry.

In a double-blind study, researchers gave the drug prazosin or a placebo to 100 people entering outpatient treatment after being diagnosed with alcohol use disorder. All of the patients had experienced varying degrees of withdrawal symptoms prior to entering treatment.

According to the researchers, subjects with more severe symptoms -- including shakes, heightened cravings and anxiety, and difficulty sleeping -- who received prazosin significantly reduced the number of heavy drinking episodes and days they drank compared to those who received a placebo. The drug had little effect on those with few or no withdrawal symptoms.

"There has been no treatment readily available for people who experience severe withdrawal symptoms and these are the people at highest risk of relapse and are most likely to end up in hospital emergency rooms," said corresponding author Rajita Sinha, the Foundations Fund Professor of Psychiatry, a professor of neuroscience, and director of the Yale Stress Center.

Prazosin was originally developed to treat high blood pressure and is still used to treat prostate problems in men, among other conditions. Previous studies conducted at Yale have shown that the drug works on stress centers in the brain and helps to improve working memory and curb anxiety and craving.

Sinha's lab has shown that stress centers of the brain are severely disrupted early in recovery, especially for those with withdrawal symptoms and high cravings, but that the disruption decreases the longer the person maintains sobriety. Prazosin could help bridge that gap by moderating cravings and withdrawal symptoms earlier in recovery and increasing the chances that patients refrain from drinking, she said.

One drawback is that in its current form prazosin needs to be administered three times daily to be effective, Sinha noted.

Montréal and Québec City, November 19, 2020 - Using the Advanced Laser Light Source (ALLS) facility, the research team of Professor François Légaré of the Institut national de la recherche scientifique (INRS) has pushed back the boundaries of high-energy pulse propagation in a nonlinear medium through the observation of high-energy multidimensional solitary states (MDSS). This breakthrough allows the direct generation of extremely short and intense, laser pulses that are highly-stable in time and space. The results of this work were published in Nature Photonics.

Common laser systems restrict operation to a single transverse mode, which puts an upper limit on laser technology. So far, higher dimensions have been considered detrimental since they are prone to high instability and collapse. This makes the scientific impact of this work remarkable. The observed self-sustained multidimensional wave-packets are driven by picosecond, near-infrared pump pulses in a gas-filled hollow-core fiber, which will be of significant interest to many scientists around the globe.

These MDSS also have a huge technological impact.

INRS researchers were able to generate high-energy and spatiotemporally engineered coherent light fields. This discovery could lead to breakthroughs in laser science for a wide range of applications. The research involves enormous theoretical advances, highly complex numerical simulations and systematic experimental studies. It was performed in the ALLS facility at INRS, a world-class research facility focusing on developing new types of lasers with revolutionary applications.

"Light at high energy levels behaves differently from what we thought," says Reza Safaei, PhD student at INRS, "We were able to design the system working in an overdriven, chaotic regime where dramatic nonlinear enhancement happens by itself. Interactions between multidimensional states actually cause the light in the laser pulses to self-organize toward highly-stable multidimensional states. This is a huge surprise, since these solitary states come out of highly unstable chaos, like hearing a note coming out of a drum!"

"The immediate technological impact of this work is the generation of few-cycle pulses from picosecond Yb driver lasers using a simple, robust, and efficient approach that provides a new laser technology for strong-field physics," said Guangyu Fan, PhD student at INRS.

"It is especially useful for scaling tabletop extreme-ultraviolet (XUV) and soft X-ray sources up to higher photon energies due to the longer central wavelength of the output beam," said Professor François Légaré. "As we look to the future, lasers and amplifiers that can elegantly work in multidimensional states may have significantly higher power than devices based on a single mode, with significant controllable nonlinear enhancement. This possibility extends beyond ultrafast laser technology to all of laser science, since dimensionality and spatial/spatiotemporal nonlinearities represent key limitations for high-power lasers of all kinds."

The team believes this idea could push forward laser technology, which has pretty much been locked in one mode for more than 20 years. This will enable the development of very compact, high-power laser systems with a wide variety of industrial applications, including micromachining and material processing. In addition, this innovative laser technology is now used to develop very compact tabletop, ultrashort X-ray sources with potential applications for tracking ultrafast phenomena such as chemical reactions and magnetization dynamics, as well as for high-spatial-resolution biomedical imaging in the water window spectral range. INRS has also protected the intellectual property related to this potentially revolutionary laser method.

In a new publication from Cardiovascular Innovations and Applications; DOI https://doi.org/10.15212/CVIA.2019.0590, Liu Yue, Qin Zhu-Yun, Yang Xin, Tang Rong and Gao Ling-Yun from the The First Affiliated Hospital of Chongqing Medical University, Chongqing, China consider the use of a social media platform (WeChat) to provide faster treatment and improve prognoses for a group of patients with acute ST-segment Elevation Myocardial Infarction.

The authors explored the effect of establishing a WeChat platform for a chest pain center as a medium to increase the treatment speed and improve the prognosis of patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).

The application of a WeChat platform significantly shortened the door-to-balloon time of patients receiving PPCI and increased the standard door-to-balloon time achievement rate for patients with STEMI. In addition, the platform is also conducive to integrating medical resources and sharing medical information. The establishment of the platform increased the treatment speed and improved the prognosis of patients with STEMI.

EAU CLAIRE, Wis. -- Before the COVID-19 pandemic, information about the dangers of vaping was emerging. To investigate the potentially serious health and respiratory implications of vaping, Mayo Clinic researchers wanted to better understand the factors influencing vaping in the community. They were ready to launch a survey of young adults in rural and urban areas when COVID-19 shifted the focus of this survey.

In a recent article in SAGE Open Medicine, the team of investigators report on vaping among adults ages 18-25 during the pandemic and their use of other common substances, such as alcohol, marijuana and tobacco. Inserting a timely additional survey question allowed the team to better understand the effects of compounding daily stresses with a public health crisis.

"As COVID-19 came on the scene, it was primarily thought to have severe respiratory implications," says Pravesh Sharma, M.D., a psychiatrist at Mayo Clinic Health System in Eau Claire, and the study's lead author. "Since we were about to launch a study examining the factors associated with vaping use, which can lead to lung injury, it made sense to revise our questionnaire slightly to address the broader question of the use of vaping and other common substances during a respiratory disease pandemic."

"We found shifts in substance use across the board," says Dr. Sharma. "Most concerning was a significant increase in alcohol use."

About the research

Dr. Sharma and his team developed a survey for patients who were seen for any reason in any outpatient setting at any Mayo Clinic location across the Midwest. The survey was emailed in April to 6,119 adults, ages 18-25 as of Jan. 24, who had been seen in the 4.2 months prior to the survey being sent. The survey came on the heels of state and local governments announcing stay-at-home orders and social distancing guidelines in March due to COVID-19.

The team's planned survey collected information on vaping attitudes and behaviors, as well as the types of vaping products used, including nicotine, marijuana extracts and oils, and other substances. The survey also asked respondents if any of their use had increased or decreased since the COVID-19 pandemic began.

"Substance use is highest in the young adult age group, so we wanted to target this population," says Dr. Sharma. "We would like to understand why they vape and what their attitudes were regarding the potentially harmful nature of vaping."

Of 1,018 respondents, more than half, or 542, reported vaping, or using marijuana, tobacco or alcohol, during the COVID-19 pandemic. Of the respondents, 269 self-reported having an anxiety disorder and 253 reported having depression. Of note, the authors write that study limitations are a reliance on self-reporting of these behaviors and disorders, as well as a 16.6% response rate.

Given that COVID-19 emerged as a primarily respiratory illness and vaping had been increasingly connected to lung damage, the team expected to see a reduction in vaping and smoking. The paper reports that 34.3%, or 186 people, reported a change in their use patterns due to COVID-19:

Nearly 70% increased alcohol consumption.

Vaping decreased in 44% of people, while 27.9% of people increased use.

Tobacco product use decreased in 47.3% of people, while 24.1% of people increased use.

Of the 140 people who described a change in marijuana use, 39.2% increased use and 36% decreased use.

Using a previously validated scale, the researchers also measured loneliness among the participants, and collected self-reported depression and anxiety information.

"We did see some reduction in inhaled substances, which could mean that young adults were reacting to the news coverage of COVID-19's respiratory effects," says Dr. Sharma.

"However, we saw that the more lonely, depressed or anxious these young people felt, the more likely they were to change their usage," he says. "They may be trying to cope with social and emotional strain by adding or replacing one substance with another, especially if their access to other support is limited."

"In this time of COVID-19, when we are focused on symptoms of infectious diseases, we need to remain vigilant about changes individuals experience with substance use," says Jon Ebbert, M.D., an internal medicine physician at Mayo Clinic in Rochester, Minn., and a study co-author.

"During the time of this pandemic, screening for substance use, loneliness, anxiety and depression is crucial," states Dr. Sharma. "Just asking, 'How are you holding up during this difficult time' goes a long way."

Drs. Sharma and Ebbert agree it is important for people to be aware of the effect of the pandemic on their well-being.

"As loneliness, anxiety and depression can potentially fuel increases in alcohol consumption during these times of social distancing, introspection with ourselves and observation of our social supports are critical for identifying and addressing substance use issues early," says Dr. Ebbert.

Dr. Sharma suggests checking in regularly with friends and family, inquiring about their well-being, and maintaining a connection. "Social distancing should not mean social isolation," he says.

He and fellow authors also highlight nontraditional socialization opportunities as essential during the continuing COVID-19 pandemic, especially for people with poor emotional health and loneliness.

In a new publication from Cardiovascular Innovations and Applications; DOI https://doi.org/10.15212/CVIA.2019.1262, Wen-Yuan Ding, Jia-Min Li, Fei Zheng, Li-Li Wang, Xin-Yi Wei and Guo-Hua Li from Shandong Provincial Qianfoshan Hospital, Ji'nan, China, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji'nan, China and Shandong First Medical University, Tai'an, China consider the challenges of treating acute myocardial infarction due to variant angina.

Coronary spasm plays an important part not only in the pathogenesis of variant angina (VA) but also in ischemic disease generally, including resting and effort angina, acute myocardial infarction (AMI), and sudden death. In approximately one in ten patients with AMI, angiography does not reveal any obstructive coronary artery disease. VA is characterized by chest pain that is not related to exercise and is frequently accompanied by transient ST segment elevation on ECG. The patient is symptom-free with normal ECG findings during the symptom-free periods. Although the underlying mechanism is not well understood, it appears to involve a combination of endothelial damage and vasoactive mediators.

In this case study, a 58-year-old man with myocardial infarction secondary to coronary artery vasospasm experienced recurrent chest pain and had a noncritical lesion as revealed by a normal coronary angiogram. The patient was treated with diltiazem. Diltiazem is a non-dihydropyridine CCB. CCBs seem to be the first-line therapy for VA. Nitrates were also found to be efficient therapy. Clinical trials have revealed that patients who received diltiazem have better outcomes than patients treated with other medical therapy. Diltiazem inhibits mainly L-type calcium channels. Diltiazem can reduce arterial wall injury caused by calcium overload, inhibit smooth muscle proliferation and arterial matrix protein synthesis, increase vascular compliance, inhibit lipid peroxidation, and protect endothelial cells.

This case provides information about the treatment with diltiazem of patients with AMI secondary to VA. VA can be life-threatening. Since the patient positively responded to the therapy, he was followed up without further intervention and did not have an additional episode of VA during a 3-month period of follow-up.

What The Study Did: Researchers report two cases of ophthalmic clinical examination findings in patients who underwent prolonged prone positioning in the intensive care unit during the COVID-19 pandemic.

Authors: Howard D. Pomeranz, M.D., Ph.D., of Northwell Health in Great Neck, New York, is the corresponding author.

 To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaophthalmol.2020.4988)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

November 19, 2020, New York - Water is a ubiquitous liquid with many highly unique properties. The way it responds to changes in pressure and temperature can be completely different from other liquids that we know, and these properties are essential to many practical applications and particularly to life as we know it. What causes these anomalies has long been a source of scientific inspiration with various theoretical explanations, but now an international team of researchers, which includes Nicolas Giovambattista, a professor at The Graduate Center, CUNY and chair for the Department of Physics at Brooklyn College, has proved that water can exist in two different liquid states -- a finding that can explain many of water's anomalous properties. Their research appears in a paper published in the November 20 issue of the journal Science. The possibility that water could exist in two different liquid states was proposed approximately 30 years ago, based on results obtained from computer simulations," Giovambattista said. "This counterintuitive hypothesis has been one of the most important questions in the chemistry and physics of water, and a controversial scenario since its beginnings. This is because experiments that can access the two liquid states in water have been very challenging due to the apparently unavoidable ice formation at the conditions where the two liquids should exist."

The usual "liquid" state of water that we are all familiar with corresponds to liquid water at normal temperatures (approximately 25 centigrade). However, the paper shows that water at low temperatures (approximately -63 centigrade) exists in two different liquid states, a low-density liquid at low pressures and a high-density liquid at high pressures. These two liquids have noticeably different properties and differ by 20% in density. The results imply that at appropriate conditions, water should exist as two immiscible liquids separated by a thin interface similar to the coexistence of oil and water.

Because water is one of the most important substances on Earth -- the solvent of life as we know it -- its phase behavior plays a fundamental role in different fields, including biochemistry, climate, cryopreservation, cryobiology, material science, and in many industrial processes where water acts as a solvent, product, reactant, or impurity. It follows that unusual characteristics in the phase behavior of water, such as the presence of two liquid states, can affect numerous scientific and engineering applications.

"It remains an open question how the presence of two liquids may affect the behavior of aqueous solutions in general, and in particular, how the two liquids may affect biomolecules in aqueous environments," Giovambattista said. "This motivates further studies in the search for potential applications."

Giovambattista is a member of the Physics and Chemistry Ph.D. programs at The Graduate Center of The City University of New York (CUNY).

The international team, led by Anders Nilsson, professor of chemical physics at Stockholm University, used complex experiments and computer simulations to prove this theory. The experiments, described as "science-fiction-like" by Giovambattista, were performed by colleagues at Stockholm University in Sweden, POSTECH University in Korea, PAL-XFEL in Korea, and SLAC national accelerator laboratory in California. The computer simulations were performed by Giovambattista and Peter H. Poole, professor at St. Francis Xavier University in Canada. The computer simulations played an important role in the interpretation of the experiments since these experiments are extremely complex and some observables are not accessible during the experiments.

Researchers from Edith Cowan University (ECU) in Western Australia have found a simple way to analyse the effectiveness of exercise training that could one day be conducted easily at a local gym or physio.

Using vertical jumps as a test activity, the researchers could predict detailed information regarding technique and muscle activation patterns just through a relatively simple analysis of forces produced against the ground during the jump.

Professor Tony Blazevich from ECU's School of Medical and Health Sciences said the new concept could transform injury diagnosis and treatment.

"Most human movements, whether high-speed sporting skills or daily activities in and around the home or workplace, are incredibly complex," Professor Blazevich said.

"Determining your technique and how your nervous system controls your muscles during those tasks requires a lot of complex data collection. This means your local doctor, physio, or gym or sports coach can't easily do it.

"We aimed to develop a simple method to describe how you move using a technique that you can use in the home or gym to assess whether your training, or rehabilitation from an injury, illness or disease, is on track."

By looking at the forces produced on the ground while someone is jumping as high as possible the researchers were able to then accurately describe the person's jump technique, determine how the muscles were controlled to perform the jump, and compare to others who use different strategies.

This information was checked against recorded movement technique and muscle activation patterns during the jumps.

The researchers also found a relatively easy way to more accurately and rapidly get the information that sports scientists need from vertical jump tests, which are commonly used in elite athletes.

Professor Blazevich said that the successful trial would now be tested on a range of human movements.

"We need to determine whether we can now use the same strategy to test other complex movements such as walking, stair climbing, running," he said.

"We are also examining the potential for using the accelerometer on a mobile phone to capture the data and then estimate the forces from that."

The use of yank-time signal as an alternative to identify kinematic events and define phases in human countermovement jumping can be read on the Royal Society Open Science website.

Fragrances - promising mystery, intrigue and forbidden thrills - are blended by master perfumers, their recipes kept secret. In a new study on the sense of smell, Weizmann Institute of Science researchers have managed to strip much of the mystery from even complex blends of odorants, not by uncovering their secret ingredients, but by recording and mapping how they are perceived. The scientists can now predict how any complex odorant will smell from its molecular structure alone. This study may not only revolutionize the closed world of perfumery, but eventually lead to the ability to digitize and reproduce smells on command. The proposed framework for odors, created by neurobiologists, computer scientists, and a master-perfumer, and funded by a European initiative for Future Emerging Technologies (FET-OPEN), was published in Nature.

"The challenge of plotting smells in an organized and logical manner was first proposed by Alexander Graham Bell over 100 years ago," says Prof. Noam Sobel of the Institute's Neurobiology Department. Bell threw down the gauntlet: "We have very many different kinds of smells, all the way from the odor of violets and roses up to asafoetida. But until you can measure their likenesses and differences you can have no science of odor." This challenge had remained unresolved until now.

This century-old challenge indeed highlighted the difficulty in fitting odors into a logical system: There are millions of odor receptors in our noses, consisting hundreds of different subtypes, each shaped to detect particular molecular features. Our brains potentially perceive millions of smells in which these single molecules are mixed and blended at varying intensities. Thus, mapping this information has been a challenge. But Sobel and his colleagues, led by graduate student Aharon Ravia and Dr. Kobi Snitz, found there is an underlying order to odors. They reached this conclusion by adopting Bell's concept - namely to describe not the smells themselves, but rather the relationships between smells as they are perceived.

In a series of experiments, the team presented volunteer participants with pairs of smells and asked them to rate these smells on how similar the two seemed to one another, ranking the pairs on a similarity scale ranging from "identical" to "extremely different." In the initial experiment, the team created 14 aromatic blends, each made of about 10 molecular components, and presented them two at a time to nearly 200 volunteers, so that by the end of the experiment each volunteer had evaluated 95 pairs.

To translate the resulting database of thousands of reported perceptual similarity ratings into a useful layout, the team refined a physicochemical measure they had previously developed. In this calculation, each odorant is represented by a single vector that combines 21 physical measures (polarity, molecular weight, etc.). To compare two odorants, each represented by a vector, the angle between the vectors is taken to reflect the perceptual similarity between them. A pair of odorants with a low angle distance between them are predicted similar, those with high angle distance between them are predicted different.

To test this model, the team first applied it to data collected by others, primarily a large study in odor discrimination by Bushdid and colleagues from the lab of Prof. Leslie Vosshall at the Rockefeller Institute in New York. The Weizmann team found that their model and measurements accurately predicted the Bushdid results: Odorants with low angle distance between them were hard to discriminate; odors with high angle distance between them were easy to discriminate. Encouraged by the model accurately predicting data collected by others, the team continued to test for themselves.

The team concocted new scents and invited a fresh group of volunteers to smell them, again using their method to predict how this set of participants would rate the pairs - at first 14 new blends and then, in the next experiment, 100 blends. The model performed exceptionally well. In fact, the results were in the same ballpark as those for color perception - sensory information that is grounded in well-defined parameters. This was especially surprising considering each individual likely has a unique complement of smell receptor subtypes, which can vary by as much as 30% across individuals.

Because the "smell map," or "metric" predicts the similarity of any two odorants, it can also be used to predict how an odorant will ultimately smell. For example, any novel odorant that is within 0.05 radians or less from banana will smell exactly like banana. As the novel odorant gains distance from banana, it will smell banana-ish, and beyond a certain distance, it will stop resembling banana.

The team is now developing a web-based tool. This set of tools not only predicts how a novel odorant will smell, but can also synthesize odorants by design. For example, one can take any perfume with a known set of ingredients, and using the map and metric, generate a new perfume with no components in common with the original perfume, but with exactly the same smell. Such creations in color vision, namely non-overlapping spectral compositions that generate the same perceived color, are called color metamers, and here the team generated olfactory metamers.

The study's findings are a significant step toward realizing a vision of Prof. David Harel of the Computer and Applied Mathematics Department, who also serves as Vice President of the Israel Academy of Sciences and Humanities and who was a co-author of the study: Enabling computers to digitize and reproduce smells. In addition, of course, to being able to add realistic flower or sea aromas to your vacation pictures on social media, giving computers the ability to interpret odors in the way that humans do could have an impact on environmental monitoring and the biomedical and food industries, to name a few. Still, master perfumer Christophe Laudamiel, who is also a co-author of the study, remarks that he is not concerned for his profession just yet.

Sobel concludes: "100 years ago, Alexander Graham Bell posed a challenge. We have now answered it: The distance between rose and violet is 0.202 radians (they are remotely similar), the distance between violet and asafoetida is 0.5 radians (they are very different), and the difference between rose and asafoetida is 0.565 radians (they are even more different). We have converted odor percepts into numbers, and this should indeed advance the science of odor."

Forensic science experts at Flinders University are refining an innovative counter-terrorism technique that checks for environmental DNA in the dust on clothing, baggage, shoes or even a passport.

The Flinders-led research, led by postdoctoral research associate Dr Jennifer Young, will developed a system to trace the source of dust on suspect articles to match a soil profile of a specific area or overseas country.

"This could help provide evidence of where a person of interest might have travelled based on the environmental DNA signature from dust on their belongings," says Dr Young, from the College of Science and Engineering at Flinders University.

"This microscopic environmental trace evidence, based on soil geochemical, bacterial and fungal analysis would complement and enhance current forensic intelligence tools," she says in new research in Forensic Science International: Genetics.

The project has received a State Government Defence Innovation Partnership (DIP) grant of almost $150,000 to develop the intelligence and forensic potential of dust traces for counter-terrorism and national security, working with the Australian Federal Police and university partners (University of Adelaide and University of Canberra) to match the DNA extraction and amplification technique to Australian soil profiles from Geosciences Australia.

Professor Linacre, chair in Forensic DNA Technology at Flinders, says environmental samples serve as ideal forms of contact trace evidence as detection at a scene can establish a link between a suspect, location and victim.

"Environment samples extracted via the 'massively parallel sequencing' technology provide biological signatures from complex DNA mixtures and trace amounts of low biomass samples," he says.

The project is among more than $1 million in funding announced in the fourth round of the Defence Innovation Partnership's Collaborative Research Fund.

InFoDust: The intelligence and forensic potential of dust traces for counter-terrorism and national security, led by Dr Young, will put the new technique on trial with soil reference data from across Australia provided by partner Geoscience Australia.

This project will utilise a series of soils with contrasting properties to understand the relationship between soil biogeochemical signals and the derived dust signal under controlled conditions, before introducing environmental variables through an 'in-situ' experiment.

According to the current state of knowledge, there are no cases that have shown evidence of humans being infected with the novel coronavirus via the consumption of contaminated food. Nor has any reliable evidence being presented to date concerning transmission of the virus via contact with contaminated objects or contaminated surfaces - such as packaging - which would have led to subsequent infections in humans. Imported refrigerated or frozen food and its packaging that has been produced under unhygienic conditions in regions affected by SARS-CoV-2 could contain the virus. Accordingly, the basic rules for day-to-day hygiene and for the preparation of food should always be followed.

The BfR is not aware of any reports of SARS-CoV-2 infections resulting from the consumption of meat or contact with contaminated meat products. According to the current state of knowledge, farm animals used for the production of meat cannot become infected with SARS-CoV-2 and are therefore unable to transmit the virus to humans via this pathway. Contamination of meat and meat products or its packaging with coronavirus could occur during the slaughtering, butchering, processing and packaging processes, however.

According to the reports in the Chinese media, traces of SARS-CoV-2 were found on the packaging of pork knuckles imported from Germany and on a door knob in a cold store. It is unclear whether the detected traces of virus are derived from an infectious virus or whether the virus had already been inactivated by storage or transportation. Nor do the reports state whether the traces of the virus were already present on the imported product or had been transferred to the packaging and door knob by the infected worker.

Generally, coronaviruses can potentially be transferred from an infected person to meat products if hygiene rules are not followed, for example, by sneezing or coughing onto these products, or through contaminated hands. The same applies to surface contaminations (on packaging, for example). However, the hygiene rules and safety precautions that are commonly observed during the slaughtering, processing and packaging of meat minimise the risk of contamination with pathogens, which also applies for SARS-CoV-2. Coronaviruses cannot multiply in or on food; they require a living animal or human host to do this. Transmis-sion of the virus to another person via a contact infection appears possible only if this person touches a contaminated item of food or packaging and then transfers the virus to the mucous membranes of their nose or eyes with the hands. According to the current state of knowledge, the oral/alimentary route of transmission through the consumption of meat is not relevant for the current SARS-CoV-2 pandemic.

To protect yourself from viral infection, always observe the general rules for everyday hy-giene: ensure that you wash your hands regularly and avoid touching your face with your hands - especially while preparing food. Furthermore, meat and poultry in general should be heated sufficiently and evenly before consumption, until the meat juice trickling out is clear and the meat is a whitish (poultry), greyish-pink (pork) or greyish-brown (beef) colour. More information on hygiene when handling food can be found here:

https://www.bfr.bund.de/cm/364/protection-against-foodborne-infections.pdf

We all react to stress in different ways. A sudden loud noise or flash of light can elicit different degrees of response from people, which indicates that some of us are more susceptible to the impact of stress than others.

Any event that causes stress is called a "stressor". Our bodies are equipped to handle acute exposure to stressors, but chronic exposure can result in mental disorders, e.g. anxiety and depression and even physical changes, e.g. cardiovascular alterations as seen in hypertension or stroke-disorders.

There has been significant effort to find a way to identify people who would be vulnerable to develop stress-related disorders. The problem is that most of that research has relied on self-reporting and subjective clinical rankings, or exposing subjects to non-naturalistic environments. Employing wearables and other sensing technologies have made some headway in the elderly and at-risk individuals, but given how different our lifestyles are, it has been hard to find objective markers of psychogenic disease.

Approaching the problem with VR

Now, behavioral scientists led by Carmen Sandi at EPFL's School of Life Sciences have developed a virtual-reality (VR) method that measures a person's susceptibility to psychogenic stressors. Building from previous animal studies, the new approach captures high-density locomotion information from a person while they explore two virtual environments in order to predict heart-rate variability when exposed to threatening or highly stressful situations.

Heart rate variability is emerging in the field as a strong indicator of vulnerability to physiological stress, and for developing psychopathologies and cardiovascular disorders.

VR stress scenarios

In the study, 135 participants were immersed in three different VR scenarios. In the first scenario they explored an empty virtual room, starting from a small red step, facing on of the walls. The virtual room itself had the same dimensions as the real one that the participants were in so that if they touched a virtual wall, they would actually feel it. After 90 seconds of exploration, the participants were told to return to the small red step they'd started from. The VR room would fade to black and then the second scenario would begin.

In the second scenario, the participants found themselves on an elevated virtual alley several meters above the ground of a virtual city. They were then asked to explore the alley for 90 seconds, and then to return to the red step. Once on it, the step began to descend faster and faster it reached the ground level. Another fade, and then came the final scenario.

In the third scenario, the participants were "placed" in a completely dark room. Armed with nothing but a virtual flashlight, they were told to explore a darkened maze corridor, in which four human-like figures were placed in corner areas, while three sudden bursts of white noise came through the participant's headphones every twenty seconds.

Developing a predictive model

The researchers measured the heart rates of the participants as they went through each VR scenario, collecting a large body of heart-rate variation data under controlled experimental conditions. Joao Rodrigues, a postdoc at EPFL and the study's first author, then analyzed the locomotor data from the first two scenarios using machine-learning methods, and developed a model that can predict a person's stress response - changes in heart rate variability - in the third threatening scenario.

The team then tested the model and found that its predictions can work on different groups of participants. They also confirmed that the model can predict stress vulnerability to a different stressful challenge in which participants were put through a final VR test, where they had to quickly perform arithmetic exercises, and see their score compared to others'. The idea here was to add a timed and social aspect to stress. In addition, when they gave wrong answers, parts of the virtual floor broke down while a distressing noise played.

Finally, the researchers also confirmed that their model outperforms other stress-prediction tools, such as anxiety questionnaires. Carmen Sandi says: "The advantage of our study, is that we have developed a model in which capturing behavioral parameters of how people explore two novel virtual environments is enough to predict how their heart rate variability would change if they were exposed to highly stressful situations; hence, eliminating the need of testing them in those highly stressful conditions."

Measuring stress vulnerability in the future

The research offers a standardized tool for measuring vulnerability to stressors based on objective markers, and paves the way for the further development of such methods.

"Our study shows the impressive power of behavioral data to reveal individuals' physiological vulnerability. It is remarkable how high-density locomotor parameters during VR exploration can help identify persons at risk of developing a myriad of pathologies -cardiovascular, mental disorders, etc - if exposed to high stress levels. We expect that our study will help the application of early interventions for those individuals at risk."

Researchers have identified a new druggable target for heart failure in neonates and infants, a condition for which there has been no specific treatment. Approximately 60 percent of children born with congenital heart abnormalities will develop overt heart failure within the first year of life. The progression of heart failure in these infants is often rapid, with a high frequency of fatalities. Stimulation of this target significantly increased the cardiac contractility of newborns and infants in mice with few side effects such as tachycardia, arrhythmias, and increased myocardial oxygen consumption, which are common problems with many cardiotonic drugs.

Unlike chronic heart failure in adults, evidence is lacking for the appropriate treatment of pediatric heart failure. The main reason for this is the great variety of pathogeneses and pathophysiologies of heart failure in children, making large-scale clinical trials difficult. Therefore, pediatric heart failure patients are currently being treated with adult medications without compelling evidence of their safety and effectiveness in children. The research group led by Professor Mitsuhiko Yamada of Shinshu University hopes to develop the world's first small molecule therapeutics for pediatric heat failure that can be easily used also by outpatients through collaborations with pharmaceutical companies.

The research group began this study in a bottom-up but not an outcome-oriented manner, which would be the most standard and effective way of translational science. Professor Yamada was interested in the molecular mechanism underlying the regulation of cardiac L-type Ca2+ channels (LTCC) by intracellular signaling pathways. In 2010, Professor Yamada came across a paper written by Prof. William A. Catterall's group describing that casein kinase can phosphorylate the main subunit of cardiac LTCC (Fuller, M.D. et al. (2010) Sci Signal: ra70). They started efforts to seek for the physiological significance of this phenomenon and fortunately found that it mediates the positive inotropic effect of angiotensin II only found in the neonatal period (Kashihara T. et al. (2017) J. Physiol. (Lond.) 595: 4207-4225). With this information, the research group changed their style and decided to serve a long-lasting unmet medical need, therapeutics specific for pediatric heart failure, by utilizing this pathway.

Children, especially those before weaning are not "miniture adults". They are in a so-called 'critical period' of life and thus, vulnerable but at the same time, formidably robust. Therefore, it may be sometimes more appropriate to develop drugs for children not only by extrapolating scientific and medical knowledge regarding adults to infants and children but by scrutinizing druggable targets underlying their robustness. Professor Yamada states that it was difficult "To gain lines of evidence against todays' scientific and medical dogma that angiotensin II and its type 1 receptors are a common cause of almost all cardiovascular and renal diseases."

The renin-angiotensin-aldosterone system was discovered more than a hundred years ago. Its importance in the mammalian perinatal period had been established by the end of the 20th century but had been almost completely forgotten mainly because of the great success of inhibitors of this system in adult medicine. The research group at Shinshu University School of Medicine and Institute of Biomedical Sciences fortunately succeed in digging up this valuable "fossil" in basic research work.

Professor Yamada sends a message on behalf of the group regarding their findings to "clinical practitioners to let us develop and dispatch novel therapeutics specific for pediatric heart failure together to all children worldwide. There is a Japanese word "onko-chishin" that means to study the past to learn new things. Nowadays, science is progressing at an astonishing speed. But it may be advisable that we sometimes stop and look back on the past. If you found something very old but shining in the darkness, it might be the very essence of nature."

A UC Davis Health pediatric team presented a powerful case series of three teenagers who had unexplained breathing problems during the COVID-19 pandemic. The series highlighted the similarities between e-cigarette, or vaping, product use-associated lung injury (EVALI) and COVID-19 symptoms and manifestations.

"EVALI and COVID-19 share many symptoms but have very different treatment plans," said Kiran Nandalike, associate professor of pediatrics and lead author on the study. "For this reason, providers caring for pediatric patients with unexplained respiratory failure should consider EVALI and ask for relevant smoking/vaping history."

Teenagers facing COVID-19 and EVALI

As of February 2020, over 2758 EVALI hospitalized cases and 64 deaths have been reported in the U.S. More than half of those hospitalized were younger than 25 years old.

According to Nandalike, most adolescents who vape using recreational marijuana get the substance from friends, family members or unlicensed dealers. The unregulated access to these products is linked to continued outbreaks in this underage population. E-cigarette products obtained through these informal channels may contain vitamin E acetate, an additive strongly connected to lung injury.

Recent studies indicate that COVID-19-related practices may increase vaping among teenagers. Isolation from the school environment, loneliness, stress of the current pandemic, and lack of social support could increase the potential for substance use. This risk is especially true for young people with preexisting mental health conditions.

EVALI and COVID-19 common symptoms

There are many similarities between EVALI and COVID-19 symptoms, laboratory results and radiologic findings. Common symptoms include fever, cough, nausea, abdominal pain and diarrhea. Both conditions also show bilateral ground glass opacities in chest imaging.

With the COVID-19 pandemic, it is easy to miss EVALI diagnosis. The patients in the case series showed up with fever, nausea and cough. They had fast heart rate, rapid breathing and low oxygen levels in their blood. Their laboratory results pointed to inflammation commonly seen in COVID-19, with higher white blood cells (WBC) count and elevated inflammation. Their chest imaging revealed non-specific ground glass opacities. While everything indicated COVID-19 infection, their SARS-CoV-2 testing returned negative.

The providers probed the teenagers and their parents for any history of vaping in the last 90 days. When the patients shared information about recent vaping, the providers could diagnose EVALI and treat them successfully with corticosteroids.

Daphne Darmawan, pediatric resident at UC Davis Health and first author of the study, is looking at the clinical course and long-term health impacts of teenagers with EVALI. She is working on developing protocols to help with the early identification and treatment of these cases. Starting steroids early for patients with EVALI can be lifesaving and may minimize the duration of hospital stay.

"To help reduce risk of EVALI recurrence, providers would recommend vaping cessation counseling to patients and close outpatient monitoring," Nandalike said.

The antiviral drug remdesivir is not suggested for patients admitted to hospital with covid-19, regardless of how severely ill they are, because there is currently no evidence that it improves survival or the need for ventilation, say a WHO Guideline Development Group (GDG) panel of international experts in The BMJ today.

The recommendation is part of a living guideline, developed by the World Health Organization with the methodological support of MAGIC Evidence Ecosystem Foundation, to provide trustworthy guidance on the management of covid-19 and help doctors make better decisions with their patients.

Living guidelines are useful in fast moving research areas like covid-19 because they allow researchers to update previously vetted and peer reviewed evidence summaries as new information becomes available.

Remdesivir has received worldwide attention as a potentially effective treatment for severe covid-19 and is increasingly used to treat patients in hospital. But its role in clinical practice has remained uncertain.

Today's recommendation is based on a new evidence review comparing the effects of several drug treatments for covid-19. It includes data from four international randomised trials involving over 7,000 patients hospitalised for covid-19.

After thoroughly reviewing this evidence, the WHO GDG expert panel, which includes experts from around the world including four patients who have had covid-19, concluded that remdesivir has no meaningful effect on mortality or on other important outcomes for patients, such as the need for mechanical ventilation or time to clinical improvement.

The panel acknowledged that the certainty of evidence is low and said the evidence did not prove that remdesivir has no benefit; rather, there is no evidence based on currently available data that it does improve important patient outcomes.

But given the remaining possibility of important harm, as well as the relatively high cost and resource implications associated with remdesivir (it must be given intravenously), they judged this to be an appropriate recommendation.

They also support continued enrolment into trials evaluating remdesivir, especially to provide higher certainty of evidence for specific groups of patients.

In a linked feature article, US journalist Jeremy Hsu asks what now for remdesivir, given that it is unlikely to be the lifesaving drug for the masses that many have hoped for?

The full story of remdesivir will not be known until manufacturer Gilead releases the full clinical study reports, writes Hsu, but much will depend on whether future studies are designed to test remdesivir's potential effectiveness.

In the meantime, he says alternative treatments, such as the well known, cheap, and widely available corticosteroid dexamethasone, that has been proved to reduce mortality among severely ill covid-19 patients, are now impacting discussions about remdesivir's cost-effectiveness.