Monday, February 05, 2024

 

Losing sleep over killings of unarmed Black individuals by police


Penn Medicine research found statistically significant decreases in sleep duration among Black adults after exposure to deaths of unarmed Black individuals during police encounters.

Peer-Reviewed Publication

UNIVERSITY OF PENNSYLVANIA SCHOOL OF MEDICINE





PHILADELPHIA – Black adults across the United States suffer from sleep problems following exposure to news about unarmed Black individuals killed by police during police encounters, according to new findings published today in JAMA Internal Medicine from researchers at the University of Pennsylvania Perelman School of Medicine. The issue, researchers said, may compound the risk factors that poor sleep already poses for many chronic and mental health conditions, from depression to post traumatic stress disorder.

Researchers conducted two separate analyses examining changes in sleep duration in the U.S. non-Hispanic Black population before and after exposure to such deaths of unarmed Black individuals, using data on adult respondents in U.S. Behavioral Risk Factor Surveillance Survey (BRFSS) and the American Time Use Survey (ATUS) and data on officer-involved killings from the Mapping Police Violence database, a nationally representative sample of 100,000 Black adults. “Exposure” was defined by the survey respondent’s county or state of residence, capturing the myriad ways in which these events become known to the public, such as viewing media coverage or participating in community discussions on the topic. The researchers also examined the impacts of incidents of officer-involved killings of unarmed Black individuals covered widely in national media, examining sleep durations for respondents living anywhere in the U.S. surveyed before and after such incidents.  

Worsening sleep duration primarily showed as increases in short sleep (fewer than seven hours a night) and very short sleep (fewer than six hours a night). The findings were specific to exposure to deaths of unarmed Black individuals during interactions with law enforcement, and no adverse impacts on sleep health were found for white respondents. In the BRFSS, 45.9 percent of Black respondents reported short sleep versus 32.6 percent of white respondents; the corresponding figures for very short sleep were 18.4 percent versus 10.4 percent.

“These findings show that poor sleep health is another unfortunate byproduct of exposure to these tragic occurrences,” said the study’s lead author, Atheendar S. Venkataramani, MD, PhD, an associate professor of Medical Ethics and Health Policy. “Exposure of Black Americans to police violence—which disproportionately effects Black individuals—adversely impacts sleep health of these individuals, a critical keystone that further impacts our mental, physical, and emotional well-being.”

The findings build on previously published work on the impact of structural racism—exposure to neighborhood violence, occupational stratification and shift work, and individual experiences of discrimination—on sleep health.

The researchers also noted that exposure to both lethal and nonlethal police encounters have been linked to poor health outcomes. Researchers suggested that poor sleep could be interrelated with these other health outcomes in several ways. For instance, awareness of the deaths of other Black individuals may diminish expectations about future well-being and longevity, induce hypervigilance, and increased stress including post-traumatic stress disorder (PTSD), many of which have been associated with poor sleep.

In addition, researchers noted “spillover” consequences of exposure to these killings through prominent news media coverage, suggesting that trauma response efforts may need to be deployed well-beyond the communities in which the events occur.

The study was supported by the National Institutes of Health (1R01MD014023-01A1).

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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.

The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.

 

 

 

Making drug use less dangerous for users is the only way to tackle overdose epidemic


Book Announcement

TAYLOR & FRANCIS GROUP



With more than 100,000 drug overdose deaths in the United States in one year, communities need more than ‘just say no’ drug prevention education and abstinence-only addiction treatment to save lives, an expert has warned.

Statistics show that most people who complete conventional drug prevention education as youth eventually go on to use alcohol, nicotine, or illegal drugs.

Harm reduction expert Sheila P. Vakharia, PhD, MSW, explains: “The majority have experimented, others use socially, and some experience substance-related problems or addictions. And, regardless of their patterns of use, most have never been taught strategies for safer substance use, moderation, or how to respond in a drug-related emergency such as an overdose.”

The limits of abstinence-only treatment

While Vakharia agrees that formal addiction treatment is an important option for people, most will never walk into a treatment facility. It is estimated that 90% of people with addictions in any given year will not receive treatment, with reasons including cost and lack of nearby options.

So how does Vakharia suggest helping those left behind by both abstinence-based drug prevention education and addiction treatment?

In her new book, The Harm Reduction GapVakharia proposes viewing people unserved by the current approaches to substance use as being in a gap, a ‘harm reduction gap’, where their needs for education, support, and safety surrounding drug use are unaddressed. In this gap, people are at risk of infectious disease, overdose, and other preventable substance-related harms.

Vakharia argues that harm reduction strategies can be an essential safety net for people who use substances who are unserved by the current system of care, and that expanding access will save lives and make communities safer.

She explains: “Drug-related harms and risks are manageable when people receive the knowledge, skills, and tools to do so. But as long as we continue to tell people never to use drugs and leave them with no support when they use them, we will continue to have to lose lives to preventable illness and death.”

What is harm reduction?

Vakharia explains: “Harm reduction is an approach that recognizes that drug use or other risky behaviors are a part of many people’s everyday lives. Harm reductionists understand that although abstinence may be a safe strategy, it is not feasible, appealing, or practical for all people in all situations.”

Despite evidence of their success in saving lives, harm reduction programs are still criminalized in many parts of the US and worldwide, and are not easily available and accessible to the people who need them the most.

These services include sterile syringe exchange programs, overdose prevention centers where naloxone, the opioid overdose medication is available, and safe supply programs where people with substance use disorders can access pharmaceutical alternatives to reduce the risk of fatal overdose.

Beyond these, Vakharia argues that quality drug education for youth and training in emergency responses are also needed, as is Harm Reduction Therapy as an alternative to abstinence-only treatment, and harm reduction mutual aid support groups as alternatives to Alcoholics Anonymous.

Rather than replacing abstinence-only messaging, Vakharia argues that harm reduction alternatives should be viewed as a complementary or supplementary option to those for whom abstinence is not a goal.

“While abstinence is a laudable goal, we must acknowledge that the majority of people in our society use mood-altering substances,” she explains. “Instead of leaving them on their own to figure out how to stay safe, we can promote greater public health by providing people with the tools, education, and support to understand drug-related risks and reduce them.

“At present, our current continuum of care is ill-equipped to serve the complex and diverse needs of our communities. ‘Just say no’ drug prevention and abstinence-only treatment are only suitable for a small minority, whereas integrating a harm reduction approach to substance use will broaden our impact and meet community needs more effectively.”

 

Veterinary drug newly found in illicit opioid supply resistant to naloxone


Peer-Reviewed Publication

CANADIAN MEDICAL ASSOCIATION JOURNAL





An article published in CMAJ (Canadian Medical Association Journal) describes five things clinicians and harm reduction workers should know about xylazine, a veterinary medication adulterating the illicit opioid supplyhttps://www.cmaj.ca/lookup/doi/10.1503/cmaj.231603.

There is no antidote to the effects of xylazine, and the authors explain that xylazine contamination should be suspected when naloxone appears not to work effectively in people with opioid toxicity.

Highlights:

  1. Xylazine is not approved for use in humans and is increasingly found in illicit drug samples along with fentanyl. People using opioids may be unaware of its presence.
  2. The drug is reported to increase euphoria and can cause sedation, low blood pressure, and slower than normal heart rate. These symptoms can persist after treatment with naloxone.
  3. Treating opioid-induced breathing issues with naloxone and supporting the airway remain the priorities, even when xylazine contamination is suspected.
  4. Xylazine is associated with severe ulcerative wounds distinct from those normally seen with intravenous drug use.
  5. Chronic use of xylazine can result in withdrawal symptoms, and other medications may be needed to manage discomfort, irritability, and low blood pressure.

"Xylazine is not part of routine urine drug screens, and there are no approved treatments or reversal agents beyond supportive care," writes Dr. Peter Wu, an internist at University Health Network and the University of Toronto with Dr. Emily Austin of the Hospital for Sick Children (SickKids), Toronto, Ontario.

"Specialized addictions care remains critical to addressing the underlying substance use disorder."

 

Down to the core of poxviruses


ISTA researchers uncover the architecture of poxvirus cores


Peer-Reviewed Publication

INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA

Structure of the poxviral core protein A10 

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STRUCTURE OF THE POXVIRAL CORE PROTEIN A10. THE THREE SUBUNITS OF THE TRIMER (COLORED DIFFERENTLY) ARE REPRESENTED AS SIMULATED CRYO-EM SURFACES IN FRONT OF A RAW CRYO-EM MICROGRAPH. THE CRYO-EM SURFACE IS INCREASINGLY MORE VISIBLE WITH EACH SUBUNIT.

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CREDIT: © JESSE HANSEN




A recent re-emergence and outbreak of Mpox brought poxviruses back as a public health threat, underlining an important knowledge gap at their core. Now, a team of researchers from the Institute of Science and Technology Austria (ISTA) lifted the mysteries of poxviral core architecture by combining various cryo-electron microscopy techniques with molecular modeling. The findings, published in Nature Structural & Molecular Biology, could facilitate future research on therapeutics targeting the poxvirus core.

Variola virus, the most notorious poxvirus and one of the deadliest viruses to have afflicted humans, wreaked havoc by causing smallpox until it was eradicated in 1980. The eradication succeeded thanks to an extensive vaccination campaign using another poxvirus, the aptly named Vaccinia virus. The 2022-2023 re-emergence and outbreak of Mpox virus reminded us once more that viruses find ways to return to the forefront as public health threats. Importantly, this has highlighted the fundamental questions about poxviruses that have remained unanswered to this day.

One such fundamental question lies, quite literally, at the core of the matter: “We know that for poxviruses to be infective, their viral core must be properly formed. But what is this poxviral core made of, and how do its individual components come together and function?” asks ISTA Assistant Professor Florian Schur, the corresponding author of the study. Schur and his team now put their finger on the missing link: a protein called A10. Interestingly, A10 is common to all clinically relevant poxviruses. In addition, the researchers found that A10 acts as one of the main building blocks of the poxviral core. This knowledge could be instrumental for future research on therapeutics targeting the poxviral core.

“The most advanced cryo-EM techniques available today”
The viral core is one of the factors common to all infectious poxvirus forms. “Previous experiments in virology, biochemistry, and genetics suggested several core protein candidates for poxviruses, but there were no experimentally-derived structures available,” says ISTA PhD student Julia Datler, one of the co-first authors of the study. Thus, the team started by computationally predicting models of the main core protein candidates, using the now-famous AI-based molecular modeling tool AlphaFold. In parallel, Datler was setting the project’s biochemical and structural foundations by drawing on her background in virology and the Schur group’s main expertise: cryogenic electron microscopy, or cryo-EM for short. “We integrated many of the most advanced cryo-EM techniques available today with AlphaFold molecular modeling. This gave us, for the first time, a detailed overall view of the poxviral core–the ‘safe’ or ‘bioreactor’ inside the virus that encloses the viral genome and releases it in infected cells,” says Schur. “It was a bit of a gamble, but we eventually managed to find the right mix of techniques to examine this complex question,” says postdoc Jesse Hansen, the study’s co-first author whose expertise in various structural biology techniques and image processing methods was pivotal for the project.

A global 3D view of the poxvirus
The ISTA researchers examined “live” Vaccinia virus mature virions and purified poxviral cores under every possible angle–quite literally. “We combined the ‘classic’ single-particle cryo-EM, cryo-electron tomography, subtomogram averaging, and AlphaFold analysis to gain an overall view of the poxviral core,” says Datler. With cryo-electron tomography, researchers can reconstitute 3D volumes of a biological sample as large as an entire virus by acquiring images while gradually tilting the sample. “It’s like doing a CT scan of the virus,” says Hansen. “Cryo-electron tomography, our lab’s ‘specialty,’ allowed us to gain nanometer-level resolutions of the whole virus, its core, and interior,” says Schur. In addition, the researchers could fit the AlphaFold models into the observed shapes like a puzzle and identify molecules that make up the poxviral core. Among these, the core protein candidate A10 stood out as one of the major components. “We found that A10 defines key structural elements of the core of poxviruses,” says Datler. Schur adds, “These findings are a great resource to interpret bits of structural and virological data generated over the last decades.”

A rugged path to uncovering poxviral cores
The path to these findings was all but straightforward. “We needed to find our own way from the start,” says Datler. Leveraging her expertise in biochemistry, virology, and structural biology, Datler isolated, propagated, and purified samples of Vaccinia virus and established the protocols to purify the complete viral core, all while optimizing these samples for structural studies. “Structurally, it was extremely hard to study these virus cores. But luckily, our perseverance and optimism paid off,” says Hansen.

The ISTA researchers are convinced that their findings could provide a knowledge platform for future therapeutics that seek to target poxviral cores. “For example, one could think of drugs that prevent the core from assembling – or even disassembling and releasing the viral DNA during infection. Ultimately, fundamental virus research, as done here, allows us to be better prepared against possible future viral outbreaks,” concludes Schur.

Cryo-electron tomogram of an entire Vaccinia virus. Top view of the virus and core. The inner core wall is colored pink and the viral DNA is green.

Cryo-electron tomogram of an entire Vaccinia virus. Side view of the virus and core. The inner core wall is colored pink and the viral DNA is green.

CREDIT

© Julia Datler

All authors of this work are affiliated with the Institute of Science and Technology Austria (ISTA). The work is a collaboration between members of the Schur group (Julia Datler, Jesse M. Hansen, Andreas Thader, Lukas W. Bauer, Florian K. M. Schur), the Scientific Computing Unit (Alois Schlögl), and the Electron Microscopy Facility (Victor-Valentin Hodirnau).

 

Improving climate predictions by unlocking the secrets of soil microbes


Scientists are using the DNA from soil microbes to model how they function and use carbon, ultimately helping to advance the accuracy of climate models


Peer-Reviewed Publication

DOE/LAWRENCE BERKELEY NATIONAL LABORATORY

Feature image 

IMAGE: 

MICROBE MODELS LEVERAGE EXTENSIVE GENOMIC DATA TO POWER SOIL-CARBON SIMULATIONS.

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CREDIT: ILLUSTRATION BY VICTOR O. LESHYK




Climate models are essential to predicting and addressing climate change, but can fail to adequately represent soil microbes, a critical player in ecosystem soil carbon sequestration that affects the global carbon cycle. A team of scientists led by the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) has developed a new model that incorporates genetic information from microbes. This new model enables the scientists to better understand how certain soil microbes efficiently store carbon supplied by plant roots, and could inform agricultural strategies to preserve carbon in the soil in support of plant growth and climate change mitigation.

"Our research demonstrates the advantage of assembling the genetic information of microorganisms directly from soil. Previously, we only had information about a small number of microbes studied in the lab,” said Berkeley Lab Postdoctoral Researcher Gianna Marschmann, the paper’s lead author. “Having genome information allows us to create better models capable of predicting how various plant types, crops, or even specific cultivars can collaborate with soil microbes to better capture carbon. Simultaneously, this collaboration can enhance soil health."

This research is described in a new paper that was recently published in the journal Nature Microbiology. The corresponding authors are Eoin Brodie of Berkeley Lab, and Jennifer Pett-Ridge of Lawrence Livermore National Lab, who leads the “Microbes Persist” Soil Microbiome Scientific Focus Area project that is funded by the DOE Office of Science in support of this work. 

Seeing the Unseen: Microbial Impact on Soil Health and Carbon

Soil microbes help plants access soil nutrients and resist drought, disease, and pests. Their impacts on the carbon cycle are particularly important to represent in climate models because they affect the amount of carbon stored in soil or released into the atmosphere as carbon dioxide during the process of decomposition. By building their own bodies from that carbon, microbes can stabilize (or store) it in the soil, and influence how much, and for how long carbon remains stored belowground. The relevance of these functions to agriculture and climate are being observed like never before.

However, with just one gram of soil containing up to 10 billion microorganisms and thousands of different species, the vast majority of microbes have never been studied in the lab. Until recently, the data scientists had to inform these models came from only a tiny minority of lab-studied microbes, with many unrelated to those needing representation in climate models. 

“This is like building an ecosystem model for a desert based on information from plants that only grow in a tropical forest,” explained Brodie.

The World Beneath our Feet

To address this challenge, the team of scientists used genome information directly to build a model capable of being tailored to any ecosystem in need of study, from California’s grasslands to thawing permafrost in the Arctic. With the model using genomes to provide insights into how soil microbes function, the team applied this approach to study plant-microbiome interactions in a California rangeland. Rangelands are economically and ecologically important in California, making up more than 40% of the land area. 

Research focused on the microbes living around plant roots (called the rhizosphere). This is an important environment to study because, despite being only 1-2% of Earth’s soil volume, this root zone is estimated to hold up to 30-40% of Earth’s carbon stored in soils, with much of that carbon being released by roots as they grow.

To build the model, scientists simulated microbes growing in the root environment, using data from the University of California Hopland Research and Extension Center. Nevertheless, the approach is not limited to a particular ecosystem. Since certain genetic information corresponds to specific traits, just as in humans, the relationship between the genomes (what the model is based on) and the microbial traits is transferable to microbes and ecosystems all over the world. 

The team developed a new way to predict important traits of microbes affecting how quickly they use carbon and nutrients supplied by plant roots. Using the model, the researchers demonstrated that as plants grow and release carbon, distinct microbial growth strategies emerge because of the interaction between root chemistry and microbial traits. In particular, they found that microbes with a slower growth rate were favored by types of carbon released during later stages of plant development and were surprisingly efficient in using carbon – allowing them to store more of this key element in the soil.

The Root of the Matter

This new observation provides a basis for improving how root-microbe interactions are represented in models, and enhances the ability to predict how microbes impact changes to the global carbon cycle in climate models.

“This newfound knowledge has important implications for agriculture and soil health. With the models we are building, it is increasingly possible to leverage new understanding of how carbon cycles through soil. This in turn opens up possibilities to recommend strategies for preserving valuable carbon in the soil to support biodiversity and plant growth at scales feasible to measure the impact,” Marschmann said.

The research highlights the power of using modeling approaches based on genetic information to predict microbial traits that can help shed light on the soil microbiome and its impact on the environment. 

This work was supported by the U.S. Department of Energy (DOE), Office of Biological and Environmental Research.

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Lawrence Berkeley National Laboratory (Berkeley Lab) is committed to delivering solutions for humankind through research in clean energy, a healthy planet, and discovery science. Founded in 1931 on the belief that the biggest problems are best addressed by teams, Berkeley Lab and its scientists have been recognized with 16 Nobel Prizes. Researchers from around the world rely on the Lab’s world-class scientific facilities for their own pioneering research. Berkeley Lab is a multiprogram national laboratory managed by the University of California for the U.S. Department of Energy’s Office of Science.

DOE’s 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, please visit energy.gov/science.

Fencing young mussels for ecosystem restoration


Reports and Proceedings

ROYAL NETHERLANDS INSTITUTE FOR SEA RESEARCH

Setting up a large-scale field experiment in de Oosterschelde. 

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SETTING UP A LARGE-SCALE FIELD EXPERIMENT IN DE OOSTERSCHELDE. CREDITS: EDWIN PAREE

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CREDIT: EDWIN PAREE




The restoration of mussel beds in the Wadden Sea or the Delta is a lot more successful when young mussels are helped a little with low, protective fences on the bottom. That is shown by research conducted by marine biologist Jildou Schotanus at the Hogeschool Zeeland / University of Applied Sciences in Vlissingen and at the Royal Netherlands Institute for Sea Research in Yerseke. She defends her thesis Restoring mussel beds on highly dynamic mudflats at the University of Groningen on Monday February 5th.

Ecosystem engineers

Mussels are so-called ecosystem engineers. On large banks, mussels shape the environment to their liking. In this way, they facilitate other mussels to settle, meanwhile helping other animals and plants to find a safe place on the sea floor as well. Moreover, mussel beds retain silt and sand and dampen the energy of waves during storms. "For this reason, there are lots of initiatives to restore mussel beds," Schotanus knows. "But it is, usually, a daunting task!"

Rough conditions

One of the problems in restoring mussel beds is the type of mussel that is used, Schotanus explains. "In the past, adult mussels that were not used to dry conditions of intertidal mud flats were often used for this purpose. But if you suddenly try to get these mussels to settle on a mudflat that is exposed to air during low tide, where they also have to endure much more wave energy, they turn out to be unaccustomed to these conditions. Experiments we have done with very small mussels, the so-called mussel seed, show that these are still flexible enough to adapt to the rougher conditions on the tidal flats."

Headstart

In another experiment, Schotanus looked at how to give mussels the best headstart on the barren banks of the Oosterschelde (Eastern Scheldt). She experimented with breakwaters, with netting to keep hungry crabs away and with coir mats to help the shellfish adhere to the bottom. "All of these methods do work to some extent, but they are also very labor intensive," Schotanus says. “Relatively simple fencing that creates eddies in the currents, and can thus create lee for young mussels, seemed the most efficient in that sense."

Unaccustomed birds

One of the reasons for restoring mussel beds is to boost biodiversity. That is why Schotanus also used cameras to see how birds such as curlew and oystercatcher reacted to these strange structures on the tidal flats. “They appear to get used to them after a while," the researcher observed. "Gulls found the larger quantities of shellfish near the fences very quickly anyway. Oystercatchers needed some time and curlews also only discovered after some time, that there were also many small crabs near the fences, which is their favorite food."

Positive interactions

The most important lesson from her research, Schotanus thinks, is that in restoring mussel beds, you must take advantage of the positive interactions between the shellfish themselves. "Mussels simply find strength and safety in numbers. All our artificial tools have their drawbacks, so the simpler we can make it for the mussels, the better."

 

  

Intertidal mussel cultivation plot in the Oosterschelde. Credits: Edwin Paree