Controlling Pain After Surgery Doesn’t Have to Mean Opioids, Study Shows (Medicine)

Comparison of opioid-sparing approach with standard care shows no difference in patient satisfaction, but less pain among those counseled to use opioids only as backup.

As surgeons balance the need to control their patients’ post-surgery pain with the risk that a routine operation could become the gateway to long-term opioid use or addiction, a new study shows the power of an approach that takes a middle way.

In a new letter in JAMA Surgery, a team from Michigan Medicine at the University of Michigan reports on findings from a study of 620 patients who had surgery in hospitals across Michigan, had their painkiller use tracked, and took surveys within one to three months after their operations.

Half of the patients received pre-surgery counseling that emphasized non-opioid pain treatment as their first option. Some patients in this group received small, “just in case” prescriptions, but a third of them didn’t receive any opioid prescription at all after surgery.

The other patients received standard care – meaning they got the usual amount of opioids given after these operations. Not only did every patient in that group get an opioid prescription, those prescriptions tended to be larger than those in the other group. And most patients didn’t take them all – leaving extra pills that can pose a hazard to the patient or others in their household if taken inappropriately, or diverted to illicit use.

The patients in the two groups had the same operations – gallbladder removal, full or partial thyroid removal or hernia repair. But despite the difference in painkiller use, the patients in both groups were equally satisfied with their care and reported similar quality of life when contacted later. And those in the opioid-sparing group actually reported experiencing less pain overall.

First author Maia Anderson, M.D., a resident in the U-M Department of Surgery, says, “It’s so exciting to think about the potential for opioid sparing postoperative pathways to not only reduce the risk of opioids for our patients, but also to substantially decrease the risk of opioid diversion into our communities.”

Senior author and surgical resident Ryan Howard, M.D., adds, “We know that opioids pose serious risks to patients after surgery. We can protect patients from those risks by reducing or eliminating opioids after surgery. But that idea always raises the concern that patients will have uncontrolled pain and feel miserable. This study suggests that’s not the case – patients who get small opioid prescriptions, or even no prescription, are just as satisfied with their recovery after surgery.”

Anderson and Howard worked with the three U-M Medical School faculty who direct the Michigan Opioid Prescribing and Engagement Network — Chad Brummett, M.D., Jennifer Waljee, M.D., M.P.H., M.S. and Michael Englesbe, M.D. — and with Alex Hallway, B.S., a member of the program’s staff who coordinates the effort to right-size surgery-related opioid prescribing in Michigan. Michigan-OPEN has published evidence-based prescribing guidelines for many procedures, as well as materials to support opioid-sparing patient education.

The study used data from the Michigan Surgical Quality Consortium that is working to improve surgical care in 70 hospitals across Michigan. Anderson and Howard are fellows of the U-M Center for Healthcare Outcomes and Policy.

Reference: Maia Anderson, Alex Hallway, Chad Brummett, Jennifer Waljee, Michael Englesbe,  Ryan Howard et al., “Patient-Reported Outcomes After Opioid-Sparing Surgery Compared With Standard of Care”, JAMA Surg. Published online January 27, 2021. doi:10.1001/jamasurg.2020.5646

Provided by University of Michigan

Optical Scanner Design for Adaptive Driving Beam Systems Can Lead to Safer Night Driving (Engineering)

Scientists couple adaptive driving beam technology with an electronically controllable optical scanner, enabling better road safety for drivers and pedestrians.

Car accidents are responsible for approximately a million deaths each year globally. Among the many causes, driving at night, when vision is most limited, leads to accidents with higher mortality rates than accidents during the day. Therefore, improving visibility during night driving is critical for reducing the number of fatal car accidents.

An adaptive driving beam (ADB) can help to some extent. This advanced drive-assist technology for vehicle headlights can automatically adjust the driver’s visibility based on the car speed and traffic environment. ADB systems that exist commercially are a marked improvement over manually controlled headlights, but they suffer from limited controllability. Whereas spatial light modulators, like liquid crystal pixels or digital micromirrors, can alleviate this problem, they are often expensive to implement and lead to heat loss from unutilized light power.

In a recent study published in the Journal of Optical Microsystems, researchers from Japan have come up with an alternative to conventional ADB systems: a microelectromechanical systems (MEMS) optical scanner that relies on the piezoelectric effect of electrically induced mechanical vibrations. This design consists of a thin film of lead-zirconate-titanate oxide (or PZT), which induces mechanical vibrations in the scanner in synchronization with a laser diode. The optical scanner spatially steers the laser beam to form structured light on the phosphor plate, where it is converted into bright white light. The light intensity is, in turn, modulated by the ADB controller based on the traffic, steering wheel angle, and vehicle cruising speed. University of Tokyo researcher Hiroshi Toshiyoshi, one of the authors on the paper, explains, “What is unique about this setup is that the laser beam is converted into white light at high efficiency, which reduces heating of the ADB system.”

The researchers designed the optical scanner on a single chip consisting of a bonded silicon-on-insulator wafer with the PZT layer grown on it and laminated with metal to form piezoelectric actuators. They arranged the actuators as suspensions to allow for large-angle horizontal and vertical deflections of the scanner. This, in turn, enabled two-dimensional scanning of the headlight beam. Further, they designed the modes so that they don’t react to low-frequency noise, such as from other vehicles. Their ADB system also accounts for temperature variations. Finally, they mounted the module on a vehicle and evaluated its performance for actual driving.

The researchers found that the ADB with a MEMS scanner provided the driver with better visibility, especially when it comes to seeing pedestrians. It could also reduce the glare from oncoming vehicles and reconfigure the illumination area depending on the cruising speed of the vehicle.

While this technology certainly advances drive-assist technology, it also has other potential applications in light detection and range finding, as well as inter-vehicle optical communication links, which means that the system could find use in self-driving technology of intelligent traffic systems in the future, taking us another step toward risk-free driving.

Read the original Gold Open Access article: T. Asari et al., “Adaptive driving beam system with MEMS optical scanner for reconfigurable vehicle headlight,” J. Opt. Microsys. 1(1), 014501 (2021), doi: 10.1117/1.JOM.1.1.014501

Featured image: Headlights Infographic: ADB with MEMS 2D optical scanner, based on the piezoelectric effect. © SPIE

Reference: Tomotaka Asari, Mamoru Miyachi, Yutaro Oda, Takaaki Koyama, Hiroaki Kurosu, Makoto Sakurai, Masanao Tani, Yoshiaki Yasuda, Hiroshi Toshiyoshi, “Adaptive driving beam system with MEMS optical scanner for reconfigurable vehicle headlight”, J. of Optical Microsystems, 1(1), 014501 (2021).

Provided by SPIE

New Study Points to Better Diagnostics for Cancer (Medicine)

Method helps researchers identify more reliable cancer biomarkers than traditional methods.

 A new University of California, Irvine-led study finds a new method for identifying biomarkers may aid in early cancer diagnosis. The study focused on lung cancer, however the Cell Heterogeneity-Adjusted cLonal Methylation (CHALM) method has been tested on aging and Alzheimer’s diseases as well and is expected to be effective for studying other diseases.

“We found the CHALM method may be a valuable tool in helping researchers to identify more reliable differentially methylated genes from sequence-based methylation data,” said Wei Li, PhD, the Grace B. Bell chair and professor of bioinformatics in the Department of Biological Chemistry at the UCI School of Medicine. “For clinicians, this method may aid in cancer diagnosis by helping them identify more useful biomarkers, which are overlooked by the traditional method.”

Published in Nature Communications, the study, titled, “Cellular Heterogeneity–Adjusted cLonal Methylation (CHALM) improves prediction of gene expression,” illustrates the importance of considering cell heterogeneity when calculating the DNA methylation level from sequencing data.

“After applying our CHALM method to a lung cancer dataset, we were able to identify more reliable and biological functions-related differentially methylated genes. Applying our CHALM method may lead to better early cancer detection,” said Li.

Using traditional methods for identifying cancer biomarkers, researchers have consistently found the correlation between gene expression and promoter methylation to be weak, especially for low methylated genes. This new study found the CHALM method allowed for more reliable identification of methylated markers that cannot be detected by traditional methods.

This study was funded in part by the National Institutes of Health.

Featured image: Scatter plots show the correlation between differential expression and differential methylation calculated by the traditional and CHALM methods. © UCI School of Medicine

Reference: Xu, J., Shi, J., Cui, X. et al. Cellular Heterogeneity–Adjusted cLonal Methylation (CHALM) improves prediction of gene expression. Nat Commun 12, 400 (2021).

Provided by UCI School of Medicine

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Melatonin Produced in the Lungs Prevents Infection by Novel Coronavirus (Medicine)

Melatonin synthesized in the lungs acts as a barrier against SARS-CoV-2, preventing expression of genes that encode proteins in cells such as resident macrophages in the nose and pulmonary alveoli, and epithelial cells lining the alveoli, all of which are entry points for the virus. The hormone, therefore, prevents infection of these cells by the virus and inhibits the immune response so that the virus remains in the respiratory tract for a few days, eventually leaving to find another host.

The discovery by researchers at the University of São Paulo (USP), in Brazil, helps understand why some people are not infected or do not manifest symptoms of COVID-19 even when reliably diagnosed as carriers of the virus by RT-PCR. In addition, it offers the prospect of nasal administration of melatonin, in drops or as a spray, to prevent disease from developing in pre-symptomatic patients. 

Pre-clinical and clinical trials will be needed to prove the therapeutic efficacy of melatonin against the virus, the researchers stress in an article on the study published in the journal Melatonin Research

The study was supported by FAPESP.

“We showed that melatonin produced in the lung acts as a barrier against SARS-CoV-2, preventing the virus from entering the epithelium, activating the immune system and triggering the production of antibodies,” Regina Pekelmann Markus, a professor at USP’s Institute of Biosciences (IB) and principal investigator for the project, told Agência FAPESP.

“This action mechanism by pulmonary melatonin must also involve other respiratory viruses such as influenza,” she added.

Markus began researching melatonin in the 1990s. In a study involving rodents, she showed that the hormone, produced at night by the pineal gland in the brain to tell the organism daylight has gone and it should prepare for sleep, can be produced in other organs, such as the lungs.

In a study also involving rodents, published in early 2020 in the Journal of Pineal Research, Markus and collaborators showed that resident macrophages in the pulmonary airspace absorb (phagocytize) particles of pollution. This aggressive stimulus induced the production of melatonin and other molecules by the macrophages, engulfing the particulate matter in the air breathed in by the animals and stimulating mucous formation, coughing, and expectoration to expel the particles from the respiratory tract.

When they blocked melatonin synthesis by resident macrophages, the researchers observed that the particles entered the bloodstream and spread throughout the organism, even invading the brain.

Based on the finding that melatonin produced in the lungs altered the entry points for particulate matter from air pollution, Markus and collaborators decided to investigate whether the hormone performed the same function with regard to SARS-CoV-2. “If so, the virus wouldn’t be able to bind to the ACE-2 receptor on cells, enter the epithelium and infect the organism,” Markus said.

Analysis of gene expression

To test this hypothesis, the researchers analyzed 455 genes associated in the literature with COVID-19 comorbidities, interaction between SARS-CoV-2 and human proteins, and viral entry points. The genes had been identified in studies conducted, among others, by Helder Nakaya, a professor at USP’s School of Pharmaceutical Sciences (FCF) and a co-author of the study on lung melatonin. 

From this group of genes, they selected 212 genes involved in viral cell entry, intracellular traffic, mitochondrial activity, and transcription and post-translation processes, to create a physiological signature of COVID-19.

Using RNA sequencing data downloaded from a public database, they quantified the level of expression of the 212 COVID-19 signature genes in 288 samples from healthy human lungs.

They then correlated these gene expression levels with a gene index that estimated the capacity of the lungs to synthesize melatonin (MEL-Index), based on their analysis of the lungs in healthy rodents. They found that the lower the index the higher the level of expression of genes that encode proteins for resident macrophages and epithelial cells.

The index also correlated negatively with genes that modify proteins in cell receptor CD147, a viral entry point in macrophages and other immune cells, indicating that normal lung melatonin production may be a natural protector against the virus.

The results were corroborated by three statistical techniques: the Pearson test, which measures the degree of linear correlation between two variables; a gene set enrichment analysis; and a network analysis tool that maps the connections among the most expressed genes so as to compare the same set of genes in different states. The latter was developed by Marcos Buckeridge, a professor at IB-USP and also a co-author of the study.

“We found that when MEL-Index was high the entry points for the virus in the lungs were closed, and when it was low these ‘doors’ were open. When the doors are shut, the virus wanders around for a time in the pulmonary airspace and then tries to escape in search of another host,” Markus said.

Because lung melatonin inhibits transcription of these genes that encode proteins for viral entry point cells, application of melatonin directly into the lungs in the form of drops or spray could block the virus. More research is required to prove that this is indeed the case, however, the researchers note. 

Another idea could be to use MEL-Index, the pulmonary melatonin metric, as a prognostic biomarker to detect asymptomatic carriers of SARS-CoV-2.

The Melatonin Research article “Melatonin-Index as a biomarker for predicting the distribution of presymptomatic and asymptomatic SARS-CoV-2 carriers” (doi: 10.32794/mr11250090) by Pedro A. Fernandes, Gabriela S. Kinker, Bruno V. Navarro, Vinicius C. Jardim, Edson D. Ribeiro-Paz, Marlina O. Córdoba-Moreno, Débora Santos-Silva, Sandra M. Muxel, Andre Fujita, Helder I. Nakaya, Marcos S. Buckeridge and Regina P. Markus can be read at:

Featured image: The hormone acts as a barrier against SARS-CoV-2, blocking the expression of genes that encode proteins in cells serving as viral entry points, according to a study by researchers at the University of São Paulo (image: NIAD/NIH)

Provided by FAPESP

IU Cancer Center Researchers Discover How Breast Cancer Cells Hide From Immune Attack (Medicine)

Researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center have identified how breast cancer cells hide from immune cells to stay alive. The discovery could lead to better immunotherapy treatment for patients.

Xinna Zhang, PhD, and colleagues found that when breast cancer cells have an increased level of a protein called MAL2 on the cell surface, the cancer cells can evade immune attacks and continue to grow. The findings are published this month in The Journal of Clinical Investigation and featured on the journal’s cover.

“Like other cancer cells, breast cancer cells present tumor-specific antigens on the cell membrane, which immune cells recognize so they can kill the tumor cells,” Zhang said. “But our study found that MAL2 can reduce the level of these antigens, so these tumor cells are protected and can no longer be recognized as a threat by these immune cells.”

The lead author of the study, Zhang is a member of the IU Simon Comprehensive Cancer Center and assistant professor of medical and molecular genetics at IU School of Medicine.

Considered the future of cancer treatment, immunotherapy harnesses the body’s immune system to target and destroy cancer cells. Understanding how cancer cells avoid immune attacks could offer new ways to improve immunotherapy for patients, explained Xiongbin Lu, PhD, Vera Bradley Foundation Professor of Breast Cancer Innovation and cancer center researcher. 

“Current cancer immunotherapy has wonderful results in some patients, but more than 70% of breast cancer patients do not respond to cancer immunotherapy,” Lu said. “One of the biggest reasons is that tumors develop a mechanism to evade the immune attacks.”

The collaborative research team set out to answer key questions: How do breast cancer cells develop this immune evasion mechanism, and could targeting that action lead to improved immunotherapies?

Zhang and Lu, members of the Vera Bradley Foundation Center for Breast Cancer Research, turned to biomedical data researcher Chi Zhang, PhD, assistant professor of medical and molecular genetics at IU School of Medicine. Chi Zhang developed a computational method to analyze data sets from more than 1,000 breast cancer patients through The Cancer Genome Atlas. That analysis led researchers to MAL2; it showed that higher levels of MAL2 in breast cancer, and especially in triple-negative breast cancer (TNBC), was linked to poorer patient survival.

“Dr. Chi Zhang used his advanced computational tool to build a bridge that connects cancer genetics and cancer genomics with a clinical outcome,” Lu said. “We can analyze molecular features from thousands of breast tumor samples to identify potential targets for cancer immunotherapy. From that data, MAL2 was the top-ranked gene that we wanted to study.”

Xinna Zhang took that data to her lab to determine MAL2’s purpose in the cells, how it affects breast cancer cell growth and how it interacts with immune cells. Using breast cancer tissue samples from IU patients, cell models and animal models, she found that breast cancer cells express more MAL2 than normal cells. She also discovered that high levels of MAL2 significantly enhanced tumor growth, while inhibiting the protein can almost completely stop tumor growth.

In Lu’s lab, he used a three-dimensional, patient-derived model called an organoid to better understand how reducing MAL2 could improve patient outcomes.

“Tumor cells can evade immune attacks; with less MAL2, the cancer cells can be recognized and killed by the immune system,” Lu said. “MAL2 is a novel target. By identifying its function in cancer cells and cancer immunology, we now know its potential as a cancer immunology target.”

Researchers now are exploring ways these findings could be used to develop and improve breast cancer therapies.

Lu is co-leading a cancer immunotherapy program for triple negative breast cancer as part of the Indiana University Precision Health Initiative. Both Xinna Zhang and Chi Zhang are also involved in the initiative for developing novel breast cancer immunotherapy. The Precision Health Initiative, the first recipient of funding from the Indiana University Grand Challenges Program, is enhancing the prevention, treatment, and health outcomes of human diseases through a more precise analysis of genetic, developmental, behavioral and environmental factors that shape an individual’s health.

Additional authors are Bryan P. Schneider, MD, Yunlong Liu, PhD, and Sha Cao, PhD, of IU Simon Comprehensive Cancer Center; Yuanzhang Fang, PhD, Lifei Wang, Changlin Wan, Yifan Sun, Kevin Van der Jeught, PhD, Zhuolong Zhou, PhD, Tianhan Dong, Ka Man So, Tao Yu, PhD, Yujing Li, PhD, Haniyeh Eyvani, Austyn B. Colter, Edward Dong, George E. Sandusky, PhD, of IU School of Medicine; and Jin Wang, PhD, of Baylor College of Medicine.

This study was supported by the Vera Bradley Foundation for Breast Cancer Research, the American Cancer Society Institutional Research Grant, and the National Institutes of Health (R01CA203737 and R01CA206366).

Featured image: Xinna Zhang, PhD © IU

Reference: Yuanzhang Fang, … , Xiongbin Lu, Xinna Zhang, “MAL2 drives immune evasion in breast cancer by suppressing tumor antigen presentation”, J Clin Invest. 2021;131(1):e140837.

Provided by Indiana University School of Medicine

Precision Measurements of Intracluster Light Suggest Possible Link to Dark Matter (Astronomy)

A combination of observational data and sophisticated computer simulations have yielded advances in a field of astrophysics that has languished for half a century. The Dark Energy Survey, which is hosted by the U.S. Department of Energy’s Fermi National Accelerator Laboratory, has published a burst of new results on what’s called intracluster light, or ICL, a faint type of light found inside galaxy clusters.

The first burst of new, precision ICL measurements appeared in a paper published in The Astrophysical Journal in April 2019. Another appeared more recently in Monthly Notices of the Royal Astronomical Society. In a surprise finding of the latter, DES physicists discovered new evidence that ICL might provide a new way to measure a mysterious substance called dark matter.

The source of ICL appears to be rogue stars, those not gravitationally bound to any galaxy. The ICL has long been suspected of possibly being a significant component of clusters of galaxies, but its faintness makes it difficult to measure. No one knows how much there is or to what extent it has spread through galaxy clusters.

“Observationally we discovered that intracluster light is a pretty good radial tracer of dark matter. That means that where intracluster light is relatively bright, the dark matter is relatively dense,” said Fermilab scientist Yuanyuan Zhang, who led both studies. “Just measuring the ICL itself is pretty exciting. The dark matter part is a serendipitous discovery. It’s not what we expected.”

Although invisible, dark matter accounts for most matter in the universe. What dark matter consists of stands as one of the major mysteries of modern cosmology. Scientists know only that it differs greatly from the normal matter consisting of the protons, neutrons and electrons that dominate everyday life.

But ICL, not dark matter, was initially on the research team’s agenda. Most astrophysicists measure intracluster light at the center of a galaxy cluster, where it is brightest and most abundant.

“We went very far away from the centers of the galaxy clusters, where the light is really faint,” Zhang said. “And the farther away from the center we went, the more difficult the measurement became.”

Nevertheless, the DES collaborators managed to come away with the most radially extended measurement of ICL ever.

The team used weak gravitational lensing to compare the radial distribution of the ICL — how it changes over distance from the center of a cluster — to the radial distribution of the mass of a galaxy cluster. Weak lensing is a dark-matter-sensitive method of measuring the mass of a galaxy or cluster. It occurs when the gravity of a foreground star or cluster bends the light from a more distant galaxy, distorting its apparent shape.

It turned out observationally that ICL reflects the distribution of both the total visible mass of a galaxy cluster and, possibly, the distribution of the invisible dark matter.

“We did not expect to find such a tight connection between these radial distributions, but we did,” said scientist Hillysson Sampaio-Santos, the lead author of the new paper.

Comparing observations with simulations

To gain more insight, the team used a sophisticated computer simulation to study the relationship between ICL and dark matter. They found that the radial profiles between the two phenomena in the simulation didn’t agree with the observational data. In the simulation, “the ICL radial profile was not the best component to trace dark matter,” said Sampaio-Santos, who is with the National Observatory in Rio de Janeiro, Brazil.

Zhang noted that it’s too soon to tell exactly what caused the conflict between observation and simulation.

“If the simulation didn’t get it right, it could mean that the simulated intracluster light is produced at a slightly different time than in observations. The simulated stars didn’t have enough time to wander around and start to trace dark matter,” she said.

Sampaio-Santos noted that further ICL studies could yield insights into the dynamics occurring inside galaxy clusters, including interactions that gravitationally release some of their stars, allowing them to wander around.

“I’m planning to study the intracluster light and the effects of relaxation,” or spreading out, he said. For example, some clusters have merged together. These merged clusters should have different properties of ICL compared to clusters that are relaxed.

Enhancing signals in noisy data sets

The ICL that the team measured is about a hundred to a thousand times fainter than what DES scientists normally attempt. That means the team had to deal with a lot of noise and contamination in the signal.

The technical aspect of the feat was challenging, Zhang said, “but because we had quite a bit of data from the Dark Energy Survey, we were able to cancel out a lot of noise to do this kind of measurement. It’s statistical averaging.”

Astrophysicists typically make ICL measurements using a handful of galaxy clusters at a time.

“That’s a great way to get information about the individual systems,” Zhang said.

To get the bigger picture and to beat down the noise, the DES team statistically averaged about 300 galaxy clusters in the first study and more than 500 clusters in the second. All of them are a couple of billion light-years from Earth.

Teasing the signal from the noise of each cluster takes a lot of data, which is exactly what the DES has generated. In early 2019, DES completed its six-year mission of observing hundreds of millions of distant galaxies in the southern skies and publicly issued its second data release in mid-January.

The ICL measurements probe clusters that are up to 3.3 billion light-years from Earth. In future studies, Zhang would like to study the redshift evolution of ICL — how it changes with cosmic time.

“My dream is to go all the way to redshift one — 10 billion light-years,” Zhang said. “Studies say that’s when the ICL has just started to evolve.”

Going that far would enable scientists to see ICL building over time.

“But that’s really hard because it’s three times as far as the distance of our latest measurements, so everything is going to be extremely faint there,” she said.

Featured image: On the left is a simulated image in which intracluster light is visible as a diffuse haze between discrete peaks of brightness — the galaxies. In observations, as seen in the right, this intracluster light component is largely drowned in noise. Left image: Jesse Golden-Marx; simulation by The IllustrisTNG. Right image: Dark Energy Survey and Yuanyuan Zhang

The Dark Energy Survey is a collaboration of more than 300 scientists from 25 institutions in six countries. For more information about the survey, please visit the experiment’s website.

Funding for the DES Projects has been provided by the U.S. Department of Energy, the U.S. National Science Foundation, the Ministry of Science and Education of Spain, the Science and Technology Facilities Council of the United Kingdom, the Higher Education Funding Council for England, the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign, the Kavli Institute of Cosmological Physics at the University of Chicago, Funding Authority for Studies and Projects in Brazil, Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro, Brazilian National Council for Scientific and Technological Development and the Ministry of Science, Technology and Innovation, the German Research Foundation and the collaborating institutions in the Dark Energy Survey.

Fermilab is supported by the Office of Science of the U.S. Department of Energy. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit

Provided by Fermi Lab

Purported Phosphine on Venus More Likely to be Ordinary Sulfur Dioxide, New Study Shows (Planetary Science)

In September, a team led by astronomers in the United Kingdom announced that they had detected the chemical phosphine in the thick clouds of Venus. The team’s reported detection, based on observations by two Earth-based radio telescopes, surprised many Venus experts. Earth’s atmosphere contains small amounts of phosphine, which may be produced by life. Phosphine on Venus generated buzz that the planet, often succinctly touted as a “hellscape,” could somehow harbor life within its acidic clouds.

Since that initial claim, other science teams have cast doubt on the reliability of the phosphine detection. Now, a team led by researchers at the University of Washington has used a robust model of the conditions within the atmosphere of Venus to revisit and comprehensively reinterpret the radio telescope observations underlying the initial phosphine claim. As they report in a paper accepted to the Astrophysical Journal and posted Jan. 25 to the preprint site arXiv, the U.K.-led group likely wasn’t detecting phosphine at all.

“Instead of phosphine in the clouds of Venus, the data are consistent with an alternative hypothesis: They were detecting sulfur dioxide,” said co-author Victoria Meadows, a UW professor of astronomy. “Sulfur dioxide is the third-most-common chemical compound in Venus’ atmosphere, and it is not considered a sign of life.”

The team behind the new study also includes scientists at NASA’s Caltech-based Jet Propulsion Laboratory, the NASA Goddard Space Flight Center, the Georgia Institute of Technology, the NASA Ames Research Center and the University of California, Riverside.

The UW-led team shows that sulfur dioxide, at levels plausible for Venus, can not only explain the observations but is also more consistent with what astronomers know of the planet’s atmosphere and its punishing chemical environment, which includes clouds of sulfuric acid. In addition, the researchers show that the initial signal originated not in the planet’s cloud layer, but far above it, in an upper layer of Venus’ atmosphere where phosphine molecules would be destroyed within seconds. This lends more support to the hypothesis that sulfur dioxide produced the signal.

This image, which shows the night side of Venus glowing in thermal infrared, was captured by Japan’s Akatsuki spacecraft.JAXA/ISAS/DARTS/Damia Bouic

Both the purported phosphine signal and this new interpretation of the data center on radio astronomy. Every chemical compound absorbs unique wavelengths of the electromagnetic spectrum, which includes radio waves, X-rays and visible light. Astronomers use radio waves, light and other emissions from planets to learn about their chemical composition, among other properties.

In 2017 using the James Clerk Maxwell Telescope, or JCMT, the U.K.-led team discovered a feature in the radio emissions from Venus at 266.94 gigahertz. Both phosphine and sulfur dioxide absorb radio waves near that frequency. To differentiate between the two, in 2019 the same team obtained follow-up observations of Venus using the Atacama Large Millimeter/submillimeter Array, or ALMA. Their analysis of ALMA observations at frequencies where only sulfur dioxide absorbs led the team to conclude that sulfur dioxide levels in Venus were too low to account for the signal at 266.94 gigahertz, and that it must instead be coming from phosphine.

In this new study by the UW-led group, the researchers started by modeling conditions within Venus’ atmosphere, and using that as a basis to comprehensively interpret the features that were seen — and not seen — in the JCMT and ALMA datasets.

“This is what’s known as a radiative transfer model, and it incorporates data from several decades’ worth of observations of Venus from multiple sources, including observatories here on Earth and spacecraft missions like Venus Express,” said lead author Andrew Lincowski, a researcher with the UW Department of Astronomy.

The team used that model to simulate signals from phosphine and sulfur dioxide for different levels of Venus’ atmosphere, and how those signals would be picked up by the JCMT and ALMA in their 2017 and 2019 configurations. Based on the shape of the 266.94-gigahertz signal picked up by the JCMT, the absorption was not coming from Venus’ cloud layer, the team reports. Instead, most of the observed signal originated some 50 or more miles above the surface, in Venus’ mesosphere. At that altitude, harsh chemicals and ultraviolet radiation would shred phosphine molecules within seconds.

“Phosphine in the mesosphere is even more fragile than phosphine in Venus’ clouds,” said Meadows. “If the JCMT signal were from phosphine in the mesosphere, then to account for the strength of the signal and the compound’s sub-second lifetime at that altitude, phosphine would have to be delivered to the mesosphere at about 100 times the rate that oxygen is pumped into Earth’s atmosphere by photosynthesis.”

The researchers also discovered that the ALMA data likely significantly underestimated the amount of sulfur dioxide in Venus’ atmosphere, an observation that the U.K.-led team had used to assert that the bulk of the 266.94-gigahertz signal was from phosphine.

“The antenna configuration of ALMA at the time of the 2019 observations has an undesirable side effect: The signals from gases that can be found nearly everywhere in Venus’ atmosphere — like sulfur dioxide — give off weaker signals than gases distributed over a smaller scale,” said co-author Alex Akins, a researcher at the Jet Propulsion Laboratory.

This phenomenon, known as spectral line dilution, would not have affected the JCMT observations, leading to an underestimate of how much sulfur dioxide was being seen by JCMT.

“They inferred a low detection of sulfur dioxide because of that artificially weak signal from ALMA,” said Lincowski. “But our modeling suggests that the line-diluted ALMA data would have still been consistent with typical or even large amounts of Venus sulfur dioxide, which could fully explain the observed JCMT signal.”

“When this new discovery was announced, the reported low sulfur dioxide abundance was at odds with what we already know about Venus and its clouds,” said Meadows. “Our new work provides a complete framework that shows how typical amounts of sulfur dioxide in the Venus mesosphere can explain both the signal detections, and non-detections, in the JCMT and ALMA data, without the need for phosphine.”

With science teams around the world following up with fresh observations of Earth’s cloud-shrouded neighbor, this new study provides an alternative explanation to the claim that something geologically, chemically or biologically must be generating phosphine in the clouds. But though this signal appears to have a more straightforward explanation — with a toxic atmosphere, bone-crushing pressure and some of our solar system’s hottest temperatures outside of the sun — Venus remains a world of mysteries, with much left for us to explore.

Additional co-authors are David Crisp at the JPL, Edward Schwieterman at UC Riverside, Giada Arney and Shawn Domagal-Goldman at the Goddard Space Flight Center, UW researcher Michael WongPaul Steffes at Georgia Tech and Niki Parenteau at NASA Ames. The research was funded by the NASA Astrobiology Program and performed at the NExSS Virtual Planetary Laboratory.

Featured image: An image of Venus compiled using data from the Mariner 10 spacecraft in 1974. NASA/JPL-Caltech

Reference: Andrew P. Lincowski, Victoria S. Meadows, David Crisp, Alex B. Akins, Edward W. Schwieterman, Giada N. Arney, Michael L. Wong, Paul G. Steffes, M. Niki Parenteau, Shawn Domagal-Goldman, “Claimed detection of PH3 in the clouds of Venus is consistent with mesospheric SO2”, ArXiv, pp. 1-12, 2021.

Provided by University of Washington

Vaccine Delivered Via Skin Could Help in Fight Against Respiratory Diseases (Medicine)

MVA delivered by skin scarification provoked a potent immune response in mice, suggesting a new strategy for lung-targeted T cell vaccines for respiratory illnesses such as COVID-19.

Among infectious diseases that have caused pandemics and epidemics, smallpox stands out as a success story. Smallpox vaccination led to the disease’s eradication in the twentieth century. Until very recently, smallpox vaccine was delivered using a technique known as skin scarification (s.s.), in which the skin is repeatedly scratched with a needle before a solution of the vaccine is applied. Almost all other vaccines today are delivered via intramuscular injection, with a needle going directly into the muscle, or through subcutaneous injection to the layer of tissue beneath the skin. But Thomas Kupper, MD, chair of the Department of Dermatology, and colleagues, had reason to suspect that vaccines delivered by skin scarification may offer better protection against respiratory diseases. In a study published in Npj vaccines, Kupper and co-authors present results from preclinical studies suggesting skin scarification may help generate lung T cells and provide protection against infectious diseases, with implications for prevention of COVID-19.

“We have known for years that this technique was a good way to generate T cells that would home to the skin, but our study shows that skin scarification is also an effective way to generate T cells that home to the lungs,” said Kupper. “Vaccine development today is focused on selecting the best antigen(s) for T cells and B cells. But for a vaccine to work to its full potential, it also needs to direct T cells to where they are needed most. For respiratory pathogens, that means getting T cells to the lungs.”

Historically, smallpox vaccines used live vaccinia virus (VACV). More recently, the Food and Drug Administration has approved the use of modified vaccinia Ankara (MVA), a modern alternative that lacks about 10 percent of the parent genome and cannot replicate in human cells, thus avoiding the serious side effects seen with VACV. MVA, as a smallpox vaccine, is injected subcutaneously.

Kupper and colleagues set out to determine if the skin scarification route of immunization with MVA could provoke a more effective T cell response than other routes of immunization. The team inoculated mice using either skin scarification, intramuscular, subcutaneous, or intradermal injection. Skin scarification generated more T cells, produced greater numbers of lung-specific T cells and provided superior protection against lethal viral doses than the others.

“We used to think that lung-homing T cells could only be generated by direct lung infection, but here we find overlap between T cells appearing after lung infection and T cells generated through skin scarification,” said Kupper.

The authors note that their work is preclinical — until clinical trials are conducted in humans, it’s unknown if the phenomenon seen in the mouse model can be replicated in people. But the work has spurred the Kupper lab to explore the potential for using the MVA vector and skin scarification technique to develop more powerful — and, potentially universal — vaccines against other infectious illnesses such as influenza and coronaviruses.

“We have known for a while that you can program T cells to go where you want them to go in the body — if you want protective T cells in the lungs, this is one way to achieve that. It is a serendipitous finding, but it seems to work very well,” said Kupper.

This work was supported by the National Institutes of Health/NIAID (R01 AI127654) and the National Institutes of Health/NIAMS (R01 AR065807). Kupper and a co-author are inventors on a patent relevant to this study (US8691502B2). The patent is now owned by Pellis Therapeutics, a biotech company specializing in vaccines, in which Kupper and a co-author have equity.

Kupper has received funding from the NIAID to study MVA s.s. immunization with constructs encoding SARS CoV2 proteins, including Spike as well as other conserved T cell antigens (R01 AI127654).

Featured image: Delivery of MVA via s.s. generates T cells that are both quantitatively more abundant and qualitatively distinct from those generated from i.d., s.c., and i.m.

Reference: Pan, Y., Liu, L., Tian, T. et al. Epicutaneous immunization with modified vaccinia Ankara viral vectors generates superior T cell immunity against a respiratory viral challenge. npj Vaccines 6, 1 (2021).

Provided by Brigham and Women’s Hospital

Research Finds Blood Pressure Can be Controlled Without Drugs After Spinal Cord Injury (Medicine)

Dr. Richi Gill, MD, is back at work, able to enjoy time with his family in the evening and get a good night’s sleep, thanks to research. Three years ago, Gill broke his neck in a boogie board accident while on vacation with his young family. Getting mobile again with the use of a wheelchair is the first thing, Gill says, most people notice. However, for those with a spinal cord injury (SCI), what is happening inside the body also severely affects their quality of life.

“What many people don’t realize is that a spinal cord injury prevents some systems within the body from regulating automatically,” says the 41-year-old. “My blood pressure would drop drastically, leaving me fatigued, dizzy, and unable to focus. The condition can be life threatening, requiring medication for life.”

Dr. Aaron Phillips, PhD, at the University of Calgary’s Cumming School of Medicine (CSM) and Grégoire Courtine, PhD, at Swiss Federal Institute of Technology (EPFL) , co-led an international study which has shown that spinal cord stimulators can bridge the body’s autonomous regulation system, controlling blood pressure without medication. Findings are published in Nature.

For people with SCI, the discovery is life changing, “The spinal cord acts as a communication line allowing the brain to send signals to tell the body such as when and how to move, as well as how to control vital functions, including blood pressure,” says Phillips, co-principal investigator and assistant professor at the CSM. “This communication line is broken after a spinal cord injury. We created the first platform to understand the mechanisms underlying blood pressure instability after spinal cord injury, which allowed us to develop a new cutting-edge solution.”

Gill is the first study participant in a series of clinical trials planned for Calgary and Switzerland. “We are going to collaborate with a company called Onward to develop a neurostimulation system dedicated to the management of blood pressure in people with spinal cord injury,” says Courtine, co-principal investigator and professor at the EPFL.

In the study, targeted epidural electrical stimulation (EES) of the spinal cord was used to stabilize hemodynamics (blood flow throughout the body) allowing for vital organs to maintain an appropriate supply of blood. The researchers discovered the exact placement on the spine for their stimulator, and the circuitry of the sympathetic nervous system underlying blood pressure control. This new knowledge allowed for the development of a neuroprosthetic closed-loop communication system, to replace lost hemodynamic control.

“We are really excited that people with spinal cord injury are able to stop their blood pressure medication and get back to enjoying a full daily routine with improved blood flow to their brain and organs,” says Dr. Sean Dukelow, MD, PhD, clinician scientist at the CSM and author on the study. “People feel more alert, are able to be upright and in their wheelchair without losing consciousness, and over the long-term we think this will reduce the risk of heart disease and stroke.”

“It’s exciting to see the science help push things forward,” says Gill. “I’m excited that Calgary will be one of the sites for a clinical trial. Research made a positive effect on my life and I’m glad others will benefit, too.”

Gill continues to work as part of the Calgary Adult Bariatric Surgery Clinic and is now the Director of the Alberta Obesity Centre.

Reference: Squair, J.W., Gautier, M., Mahe, L. et al. Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury. Nature (2021).

Provided by University of Calgary