Culture

Human white blood cells, known as leukocytes, swim using a newly described mechanism called molecular paddling, researchers report in the September 15th issue of Biophysical Journal. This microswimming mechanism could explain how both immune cells and cancer cells migrate in various fluid-filled niches in the body, for good or for harm.

"The capacity of living cells to move autonomously is fascinating and crucial for many biological functions, but mechanisms of cell migration remain partially understood," says co-senior study author Olivier Theodoly of Aix-Marseille University in France. "Our findings shed new light on the migration mechanisms of amoeboid cells, which is a crucial topic in immunology and cancer research."

Cells have evolved different strategies to migrate and explore their environment. For example, sperm cells, microalgae, and bacteria can swim through shape deformations or by using a whip-like appendage called a flagellum. By contrast, somatic mammalian cells are known to migrate by attaching to surfaces and crawling. It is widely accepted that leukocytes cannot migrate on 2D surfaces without adhering to them.

A prior study reported that certain human white blood cells called neutrophils could swim, but no mechanism was demonstrated. Another study showed that mouse leukocytes could be artificially provoked to swim. It is widely thought that cell swimming without a flagellum requires changes in cell shape, but the precise mechanisms underlying leukocyte migration have been debated.

In contrast to previous studies, Theodoly, co-senior study author Chaouqi Misbah of Grenoble Alpes University, and their collaborators provide experimental and computational evidence in the new study that human leukocytes can migrate on 2D surfaces without sticking to them and can swim using a mechanism that does not rely on changes in cell shape. "Looking at cell motion gives the illusion that cells deform their body like a swimmer," Misbah says. "Although leukocytes display highly dynamic shapes and seem to swim with a breast-stroke mode, our quantitative analysis suggests that these movements are inefficient to propel cells."

Instead, the cells paddle using transmembrane proteins, which span the cell membrane and protrude outside the cell. The researchers show that membrane treadmilling--rearward movement of the cell surface--propels leukocyte migration in solid or liquid environments, with and without adhesion.

However, the cell membrane does not move like a homogenous treadmill. Some transmembrane proteins are linked to actin microfilaments, which form part of the cytoskeleton and contract to allow cells to move. The actin cytoskeleton is widely accepted as the molecular engine propelling cell crawling. The new findings demonstrate that actin-bound transmembrane proteins paddle and propel the cell forward, whereas freely diffusing transmembrane proteins hinder swimming.

The researchers propose that continuous paddling is enabled by a combination of actin-driven external treadmilling and inner recycling of actin-bound transmembrane proteins through vesicular transport. Specifically, the paddling proteins at the rear of the cell are enclosed inside a vesicle that pinches off from the cell membrane and transported to the front of the cell. By contrast, the non-paddling transmembrane proteins are sorted out and do not undergo this process of internal recycling through vesicular transport.

"This recycling of the cell membrane is studied intensively by the community working on intracellular vesicular traffic, but its role in motility was hardly considered," Theodoly says. "These functions of protein sorting and trafficking seemed highly sophisticated for swimming. Our investigations, to our own surprise, bridge such distant domains as the physics of microswimmers and the biology of vesicular traffic."

The authors say that molecular paddling could allow immune cells to thoroughly explore all locations in the body as they migrate in liquid-filled niches such as swollen body parts, infected bladders, cerebrospinal fluid, or amniotic fluid. Moving forward, the researchers plan to investigate the functions of molecular paddling in various environments and assess whether other types of cells use this mode of migration.

Sacramento, CA-- In 2018, Lin Tian and her team at UC Davis Health developed dLight1, a single fluorescent protein-based biosensor. This family of highly specific sensors detects dopamine, a hormone released by neurons to send signals to other nerve cells. When combined with advanced microscopy, dLight1 provides high resolution, real-time imaging of the spatial and temporal release of dopamine in live animals.

Recently, Tian and her team succeeded in expanding the color spectrum of the dLight1 sensor. In an article published Sept. 7 in Nature Methods, they introduced two new spectral variants of dLight1: the yellow YdLight1 and the red RdLight1.

"The new sensors will help researchers to detect and monitor different information processing activities in the brain," said Lin Tian, associate professor of biochemistry and molecular medicine and the lead author on the study. "With the different colors, we will be able to see multiple neurochemical release and neural activities at the same time."

The RdLight1 permits the simultaneous assessment of dopamine, pre- or post-synaptic neuronal activity and the glutamate release in specific types of cells and neuronal projections in animals. Its increased light penetration and imaging depth provide enhanced dopamine signal quality. This allows researchers to optically dissect dopamine's release and model its effects on neural circuits.

As a neurotransmitter, dopamine plays an important role in movement, attention, learning and the brain's pleasure and reward system.

"These exciting new tools opened a new door to developing color-shifted neurochemical indicators. Together with other tools, they have great potential to unlock the mysteries of brain chemistry in health and disease," Tian said. "The knowledge we gain from these sensors will facilitate the development of safer next-generation therapies to neuropsychiatric disorders such as depression, anxiety, schizophrenia and addiction."

September 15, 2020 - Digital phenotyping approaches that collect and analyze Smartphone-user data on locations, activities, and even feelings - combined with machine learning to recognize patterns and make predictions from the data - have emerged as promising tools for monitoring patients with psychosis spectrum illnesses, according to a report in the September/October issue of Harvard Review of Psychiatry. The journal is published in the Lippincott portfolio by Wolters Kluwer.

John Tourous, MD, MBI, of Harvard Medical School and colleagues reviewed available evidence on digital phenotyping and machine learning to improve care for people living with schizophrenia, bipolar disorder, and related illnesses. "Digital phenotyping provides a much-needed bridge between patients' symptomatology and the behaviors that can be used to assess and monitor psychiatric disorders," the researchers write.

Digital Phenotyping in Schizophrenia and Bipolar Disorder - The Evidence So Far

"Digital phenotyping is the use of data from smartphones and wearables collected in situ for capturing a digital expression of human behaviors," according to the authors. Psychiatry researchers think that collecting and analyzing this kind of behavioral information might be useful in understanding how patients with severe mental illness are functioning in everyday life outside of the clinic or lab - in particular, to assess symptoms and predict clinical relapses.

Dr. Tourous and colleagues identified 51 studies of digital phenotyping in patients with schizophrenia or bipolar disorder. The review focused on studies using "passively" collected data - for example, accelerometer readings (step counters) and GPS signals. Other digital phenotyping approaches use "actively" collected data - for example, surveys to ask patients to report their mood.

The studies varied in terms of the digital phenotyping features used, data handling, analytical techniques, algorithms tested, and outcome measures reported. Nearly all studies included patients with bipolar disorder or schizophrenia. The studies included an average of 31 participants and monitored them for about four months.

Most studies used passive data collected by accelerometers and GPS; other measures included voice call and text message logs. The studies used a wide range of different apps, as well as different clinical tools/questionnaires for assessing patients' mental health status.

The studies presented higher variability in reporting of basic data such as smartphone model and operating system, patient age and race/ethnicity, and whether patients had received training in use of the technology. The authors make suggestions for a standardized reporting format that would improve the comparability of future studies.

Sixteen of the studies used machine learning-based approaches to analyze the passively collected data. As Dr. Tourous and coauthors note, the studies used various different algorithms, and for different purposes. The most commonly used algorithm type was "random forests," which work by combining many small, weak decisions to make a single strong prediction. For example, one study used passively tracked behavioral data to predict mental health scores in patients with schizophrenia.

Other studies used machine-learning approaches such as support vector machine/support vector regression or neural nets. These algorithms work in different ways to use behavioral data - where patients are going, whether they're returning calls, even their tone of voice - to assess patients' current mental health status, predict their risk of relapse, and so forth.

"Digital phenotyping provides a much-needed bridge between patients' symptomatology and the behaviors that can be used to assess and monitor psychotic disorders," Dr. Tourous and colleagues write. They call for larger studies with higher-quality data - along with "expanded efforts to apply machine learning to passive digital phenotyping data in early diagnosis and treatment of psychosis, including in clinical high risk and early-course psychosis patients."

A molecule known as ACE2 sits like a doorknob on the outer surfaces of the cells that line the lungs. Since January 2020, researchers have known that SARS-CoV-2, the novel coronavirus that causes COVID-19, primarily uses ACE2 to enter these cells and establish respiratory infections. Finding a way to lock out that interaction between virus and doorknob, as a means to treat the infection, has become the goal of many research studies.

University of California San Diego School of Medicine researchers have discovered that SARS-CoV-2 can't grab onto ACE2 without a carbohydrate called heparan sulfate, which is also found on lung cell surfaces and acts as a co-receptor for viral entry.

"ACE2 is only part of the story," said Jeffrey Esko, PhD, Distinguished Professor of Cellular and Molecular Medicine at UC San Diego School of Medicine and co-director of the Glycobiology Research and Training Center. "It isn't the whole picture."

Esko's study, published September 14, 2020 in Cell, introduces a potential new approach for preventing and treating COVID-19.

The team demonstrated two approaches that can reduce the ability of SARS-CoV-2 to infect human cells cultured in the lab by approximately 80 to 90 percent: 1) removing heparan sulfate with enzymes or 2) using heparin as bait to lure and bind the coronavirus away from human cells. Heparin, a form of heparan sulfate, is already a widely used medication to prevent and treat blood clots, suggesting that a Food and Drug Administration-approved drug might be repurposed to reduce virus infection.

Esko's team has long studied heparan sulfate and the role it plays in health and disease. He led this study with visiting scholar Thomas Mandel Clausen, PhD, and postdoctoral researcher Daniel Sandoval, PhD. While Esko's lab doesn't necessarily focus on viruses, Clausen had previously studied how the malaria parasite interacts with a related carbohydrate on human cells and Sandoval had been interested in viruses since he was an undergraduate student -- he still keeps up with the latest virology research for fun.

Late one Friday afternoon in March 2020, Clausen was tired and, he admits, putting off his experiments. Instead, he perused the latest research coming out about SARS-CoV-2. That's when he came across a preliminary study that suggested an interaction between the coronavirus's spike protein -- the "hand" the virus uses to grab the ACE2 doorknob -- and another carbohydrate related to heparan sulfate.

"I ran down to Daniel to tell him to look at the study -- and of course, he was already thinking the same thing," said Clausen, who is also an associate professor at University of Copenhagen in Denmark.

Within a week, the team was testing their theories in the lab. They discovered that the SARS-CoV-2 spike protein binds to heparin. The team also drilled down to uncover the exact part of the SARS-CoV-2 spike protein that interacts with heparin -- the receptor binding domain. When heparin is bound, the receptor binding domain opens up and increases binding to ACE2. The virus, they found, must bind both heparan sulfate on the cell surface and ACE2 in order to get inside human lung cells grown in a laboratory dish.

With this viral entry mechanism established, the researchers next set about trying to disrupt it. They found that enzymes that remove heparan sulfate from cell surfaces prevent SARS-CoV-2 from gaining entry into cells. Likewise, treatment with heparin also blocked infection. The heparin treatment worked as an anti-viral at doses currently given to patients, even when the researchers removed the anticoagulant region of the protein -- the part responsible for preventing blood clots.

The findings are still far from translating into a COVID-19 treatment for people, said Esko. Researchers will need to test heparin and heparan sulfate inhibitors in animal models of SARS-CoV-2 infection. In a related study, UC San Diego scientists are also exploring the role human microbiomes, including the bacteria that live in and on the body, play in altering heparan sulfate and thus influencing a person's susceptibility to COVID-19.

"This is one of the most exciting periods of my career -- all of the things we've learned about heparan sulfate and the resources we've developed over the years have come together with a variety of experts across multiple institutions who were quick to collaborate and share ideas," Esko said. "If there's a silver lining to this pandemic, I hope it's that the scientific community will continue to work rapidly together like this to address other problems."

Boulder, Colo., USA: When early humans began to travel out of Africa and spread into Eurasia over a hundred thousand years ago, a fertile region around the eastern Mediterranean Sea called the Levant served as a critical gateway between northern Africa and Eurasia. A new study, published in Geology, shows that the existence of that oasis depended almost entirely on something we almost never think about: dust.

Dr. Rivka Amit, at the Geological Survey of Israel, and her team initially set out with a simple question: why are some soils around the Mediterranean thin and why are some thick? Their investigation led them to discover not only that dust deposition played a critical role in forming thick soils in the Levant, but also that had the source of dust not changed 200,000 years ago, early humans might have had a much tougher time leaving Africa, and parts of the Fertile Crescent wouldn't have been so hospitable for civilization to take root.

Thick soils tend to form in areas with wet, humid climates, and thin soils form in arid environments with lower weathering rates. But in the Mediterranean, where much of the bedrock is dissolvable carbonate, the opposite is true: wetter northern regions have thin, unproductive soils, and more arid southeastern regions have thick, productive soils. Some scientists have attributed these patterns to differences in the rates of erosion, driven by human activity. But for Amit, who has been studying the area for years, a high erosion rate alone didn't make sense. She challenged the existing hypotheses, reasoning that another factor--dust input--likely plays a critical role when weathering rates are too slow to form soils from bedrock.

To assess the influence of dust on Mediterranean soils, Amit and her team needed to trace the dust back to its original source. They collected dust samples from soils in the region, as well as nearby and far-flung dust sources, and compared the samples' grain size distribution. The team identified a key difference between areas with thin and thick soils: thin soils comprised only the finest grain sizes sourced from distant deserts like the Sahara, whereas the thicker, more productive soils had coarser dust called loess, sourced from the nearby Negev desert and its massive dune fields. The thick soils in the eastern Mediterranean formed 200,000 years ago when glaciers covered large swaths of land, grinding up bedrock and creating an abundance of fine-grained sediments. "The whole planet was a lot dustier," Amit said, which allowed extensive dune fields like those in the Negev to build up, creating new sources of dust and ultimately, thicker soils in places like the Levant.

Amit, then, had her answer: regions with thin soils simply hadn't received enough loess to form thick, agriculturally productive soils, whereas the southeastern Mediterranean had. "Erosion here is less important," she said. "What's important is whether you get an influx of coarse [dust] fractions. [Without that], you get thin, unproductive soils."

Amit didn't stop there. She now knew that the thickest soils had received a large flux of coarse dust, leading to the area's designation as the "land of milk and honey" for its agricultural productivity. Her next question was, had it always been like this?

She was surprised at what they found. Looking below the loess in the soil profile, they found a dearth of fine-grained sediments. "What was [deposited] before the loess were very thin soils," she said. "It was a big surprise... The landscape was totally different, so I'm not sure that people would [have chosen] this area to live in because it was a harsh environment and [an] almost bare landscape, without much soil." Without the changing winds and formation of the Negev dune field, then, the fertile area that served as a passage for early humans may have been too difficult to pass through and survive.

In the modern Mediterranean, the soils aren't accumulating any more. "The dust source is cut off," Amit explained, since the glaciers retreated in the Holocene, "now we're only reworking the old loess." Even if there were a dust source, it would take tens of thousands of years to rebuild a soil there. That leaves these mountainous soils in a fragile state, and people living there must balance conservation and agricultural use. Employing responsible agricultural practices in the region, as terracing has been used for thousands of years, is critical for soil preservation if agriculture is to continue.

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

1. Active surveillance and routine on-site testing could prevent spread of COVID-19 in homeless shelters

Passive sentinel surveillance for COVID-19 in homeless shelters and other congregate living situations may only detect symptomatic cases while missing milder ones. Active testing is needed to identify cases and potentially prevent outbreaks and further viral spread. Findings from a community-based surveillance study are published in Annals of Internal Medicine.

Researchers from University of Washington School of Medicine conducted COVID-19 case counts across several adult and family homeless shelters in King County, Washington between January and April 2020 to demonstrate how active surveillance and surge testing could identify asymptomatic or mild cases. Routine surveillance involved self-selected participation at staffed kiosks in shelters during standardized days and times. Surge testing was initiated on 30 March 2020 (and continued through 24 April) in collaboration with Public Health--Seattle & King County's Communicable Disease Epidemiology Team to conduct contact tracing at 6 shelters where cases of COVID-19 were previously detected. During these 1-day events, the researchers offered testing to all residents and staff. Among 1434 encounters, 29 cases of SARS-CoV-2 infection were detected across 5 shelters. Most of those cases were detected during surge testing events rather than routine surveillance, and of those, most were asymptomatic at the time of sample collection. Eighty-six percent of persons with positive test results slept in a communal space rather than in a private or shared room.

According to the authors, their findings provide key insights into detection strategies for SARS-CoV-2 in a vulnerable, hard-to-reach population. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-3799.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. To reach the lead author, Helen Y. Chu, MD, MPH, please contact Leila Gray at leilag@uw.edu.

2. Researchers discuss research needs for developing guidelines in the era of COVID-19

The sudden emergence and scale of the COVID-19 pandemic have led to substantial pressure and heightened expectations for accelerated systematic reviews and rapid guidelines. Researchers, systematic reviewers, and guideline developers have been tasked with resolving uncertainty in much shorter time frames, in an emerging field, and with types of evidence that they may not have used previously. The evidence base for COVID-19 is characterized by many studies and systematic reviews that are poorly designed and conducted, presenting numerous complications for guideline developers. In addition to presenting the challenges, authors from the Guidelines International Network, Pitlochry, Scotland, and Joanna Briggs Institute, University of Adelaide, Adelaide, Australia discuss several solutions for those developing guidelines and recommendations related to COVID-19. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-4907.

The COVID-NMA Project

In an accompanying article, authors from the Université de Paris, Centre of Research Epidemiology and Statistics (CRESS), Inserm, Cochrane France and international colleagues describe a large collaborative project called the COVID-NMA project. Researchers proposed and implemented an "evidence ecosystem" for COVID-19-related studies that minimizes multiple low-quality reviews and helps connect evidence generation, synthesis, and decision making. The ecosystem consists of living mapping of all trials and a comprehensive living synthesis of all available trial evidence evaluating the effect of interventions for the prevention or treatment of COVID-19. There is a master protocol and subprotocols dedicated to specific questions, which are discussed and agreed on by a steering committee. A search to identify eligible RCTs is performed daily. As soon any trial with results is identified, data are collected, risk of bias fully assessed and forest plots of appropriately pooled data produced. All data are made available on a website (https://covid-nma.com). This ecosystem, called the COVID-NMA Project, is intended to change and improve primary research, evidence synthesis and the guideline development process. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-5261.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. To reach the lead author for the COVID-NMA Project, Isabelle Boutron, MD, PhD, contact her directly at isabelle.boutron@aphp.fr.

A new study, co-led by University of Cincinnati researchers, describes the development of a refining process that scientists deem a superior method to help produce better dietary omega-3 health and dietary supplements containing fish oil.

Fish oil is widely known to be an excellent dietary source of omega-3 polyunsaturated fatty acids (PUFAs) having positive effects on human health including heart and eye health, inflammation and bone density.

The novel process uses a new tool called a vortex fluidic device (VFD) developed by research collaborators at Flinders University of Australia. The process is successful in lifting the quality of active ingredients of the PUFAs in fish oil, says Harshita Kumari, the study's co-author and associate professor of pharmaceutical sciences at UC's James L. Winkle College of Pharmacy.

The study now appears in Nature Papers Journals Science of Food.

Researchers applied the VFD-mediated encapsulated fish oil to enrich the omega-3 fatty acid content of apple juice.

"This novel process enriches the omega-3 fatty acid content of apple juice remarkably without changing its taste," says Kumari, adding that two common consumer complaints regarding fish oil supplements is the taste and odor. Liquid omega-3 oils can also break down over time when exposed to oxygen which leads to degradation.

Compared to regular homogenization processing, Kumari says the device can raise PUFA levels and purity by lowering oxidation and dramatically improving shelf life. Natural bioactive molecules, also used in processing, reveal that the fish oil medium can absorb flavonoids and other health supplements.

Roughly 1 in 10 patients diagnosed with COVID-19 needed to return to the hospital within a week of discharge from an emergency department visit, according to data from the first three months of the COVID-19 outbreak in the Philadelphia region--March, April and May 2020. Researchers in the Perelman School of Medicine at the University of Pennsylvania also found that factors like lower pulse oximetry levels and fever were some of the most telling symptoms that resulted in return trips that resulted in admission. This information, published in Academic Emergency Medicine, could prove invaluable to clinicians working to fight a disease.

"We hope this study helps emergency clinicians have more informed conversations with patients suspected to have COVID-19," said the study's lead author Austin Kilaru, MD, an Emergency Medicine physician at Penn Medicine. "It can be difficult to make this diagnosis and send patients home without knowing if they will get sick in the coming days. This study gives clinicians a few signposts to know how often and when patients may need to return, and what risk factors to pay attention to."

The study looked at 1,419 patients who went to an emergency department (ED) between March 1 and May 28, 2020, were discharged, and tested positive for COVID-19 in the seven days surrounding that visit. Data showed that 4.7 percent of the patients returned to the hospital and were admitted within just three days for their initial ED visit, and an additional 3.9 percent were hospitalized within a week. In total, that meant that 8.6 percent of patients were coming back to the hospital after their first ED visit due to COVID-19.

"We were surprised with the overall rate that patients return and need admission, which is twice that of other illnesses," Kilaru explained. "The concern is not that emergency physicians are making wrong decisions, but rather that COVID can be unpredictable and turn severe rather quickly."

A population that the study showed was particularly vulnerable were patients over 60 years old. Compared to patients in the 18 to 39 years of age range, those over 60 were more than five times as likely to require hospitalization after being discharged from their initial emergency department visit. Those in the 40 to 59 age range were found to be three times as likely to require hospitalization than the younger group.

When it came to individual symptoms, the study showed that patients of any age with low pulse oximetry readings were about four times as likely to require hospitalization upon return as compared to those with higher readings, while patients with fevers were more than three times as likely as compared to those without.

"If the patient had other factors such as an abnormal chest x-ray, the likelihood of needing to come back to be hospitalized goes up even more," said the study's senior author, M. Kit Delgado, MD, an assistant professor of Emergency Medicine and Epidemiology.

The study collected demographic data for patients, which showed no signs of differences along racial or gender lines.

"This further contributes to the evidence that the known racial disparities in COVID mortality are not related to differences in care and outcomes among patients once treated in the same hospital system. Rather, the disparities are structural related to the higher rates of infection and access to care in low-income communities, which are disproportionately Black and Hispanic."

With the hope that their findings can better inform doctors on who is most appropriate for home recovery, the researchers called out remote monitoring as a useful tool for looking after COVID-19 patients.

An example of this is Penn Medicine's COVID Watch system, a text-message-based system that sends daily check-ups on known COVID-19 patients recuperating at home to make sure their symptoms aren't worsening. To date, more than 5,500 patients have been enrolled in the system, which is the subject of a new Patient-Centered Outcomes Research Institute (PCORI) study for which Delgado, Kilaru amd the other researchers on this study are also serving as investigators.

"We are eagerly awaiting the result of this study, which focuses specifically on pulse oximetry," Delgado said.

Other authors on the completed hospital readmission study included Kathleen Lee, MD; Christopher K. Snider; Zachary F. Meisel, MD; David A. Asch, MD; and Nandita Mitra, PhD; all of Penn.

Final report card on Aichi Biodiversity Targets, set in 2010: 6 of world's 20 goals "partially achieved" by 2020 deadline.

Towards a landmark new global post-2020 biodiversity framework: GBO-5 synthesizes scientific basis for urgent action.

Bright spots include: extinctions prevented by conservation, more land and oceans protected, fish stocks bounce back in well-managed fisheries.

15 September 2020 - Despite encouraging progress in several areas, the natural world is suffering badly and getting worse. Eight transformative changes are, therefore, urgently needed to ensure human wellbeing and save the planet, the UN warns in a major report. 

The report comes as the COVID-19 pandemic challenges people to rethink their relationship with nature, and to consider the profound consequences to their own wellbeing and survival that can result from continued biodiversity loss and the degradation of ecosystems.

The Global Biodiversity Outlook 5 (GBO-5), published by the UN Convention on Biological Diversity (CBD), offers an authoritative overview of the state of nature. It is a final report card on progress against the 20 global biodiversity targets agreed in 2010 with a 2020 deadline, and offers lessons learned and best practices for getting on track.

"This flagship report underlines that 'humanity stands at a crossroads with regard to the legacy we wish to leave to future generations,'" said CBD Executive Secretary, Elizabeth Maruma Mrema.

"Many good things are happening around the world and these should be celebrated and encouraged. Nevertheless, the rate of biodiversity loss is unprecedented in human history and pressures are intensifying.  Earth's living systems as a whole are being compromised.  And the more humanity exploits nature in unsustainable ways and undermines its contributions to people, the more we undermine our own well-being, security and prosperity."

"As nature degrades," Ms. Mrema continued, "new opportunities emerge for the spread to humans and animals of devastating diseases like this year's coronavirus. The window of time available is short, but the pandemic has also demonstrated that transformative changes are possible when they must be made."

"The decisions and level of action we take now will have profound consequences -- for good or ill -- for all species, including ours."

With respect to the Aichi Biodiversity Targets, set in 2010, the analysis based on the 6th set of national reports to the CBD and the latest scientific findings shows that seven of 60 "elements" -- success criteria -- within the 20 targets have been achieved and 38 show progress. In the case of 13 elements, no progress was made, or a move away from the target was indicated, and for two elements the level of progress is unknown. The report concludes that, overall, of the 20 targets, six of them (9, 11, 16, 17, 19 and 20) were partially achieved by the 2020 deadline.

By partially met, GBO5 refers to targets where at least one distinct element has been met. For example, the elements of Target 11 regarding the proportions of lands and seas protected was met, but the elements related to the quality of protected areas were not. Similarly, for Target 19, biodiversity knowledge has improved but it has not been widely shared or applied. For Target 20, official development assistance doubled but resources did not increase from all sources.

The national reports to the CBD (available via http://bit.ly/GBO5Public) offer evidence that the types of transitions needed moving forward are beginning; that virtually all countries are taking steps to protect biodiversity. GBO5 cites several exemplary national actions and programmes, in the absence of which conditions would certainly be worse (extinctions would be higher for example). In addition, for example, deforestation rates continue to fall, eradication of invasive alien species from islands is increasing, awareness of biodiversity appears to be increasing.

"The actions that have been taken need to be significantly scaled up, move from being project driven and become more systemic and broadened," says Ms. Mrema. "Also, the gaps in national ambition and action need to be filled. The information in part III of GBO-5 is about doing this and provides examples of the types of actions that needed going forward."

The report calls for a shift away from "business as usual" across a range of human activities. It outlines eight transitions that recognize the value of biodiversity, the need to restore the ecosystems on which all human activity depends, and the urgency of reducing the negative impacts of such activity:

The land and forests transition: conserving intact ecosystems, restoring ecosystems, combatting and reversing degradation, and employing landscape level spatial planning to avoid, reduce and mitigate land-use change.

The sustainable agriculture transition: redesigning agricultural systems through agroecological and other innovative approaches to enhance productivity while minimizing negative impacts on biodiversity.

The sustainable food systems transition: enabling sustainable and healthy diets with a greater emphasis on a diversity of foods, mostly plant-based, and more moderate consumption of meat and fish, as well as dramatic cuts in the waste involved in food supply and consumption.

The sustainable fisheries and oceans transition: protecting and restoring marine and coastal ecosystems, rebuilding fisheries and managing aquaculture and other uses of the oceans to ensure sustainability, and to enhance food security and livelihoods.

The cities and infrastructure transition: deploying "green infrastructure" and making space for nature within built landscapes to improve the health and quality of life for citizens and to reduce the environmental footprint of cities and infrastructure.

The sustainable freshwater transition: an integrated approach guaranteeing the water flows required by nature and people, improving water quality, protecting critical habitats, controlling invasive species and safeguarding connectivity to allow the recovery of freshwater systems from mountains to coasts.

The sustainable climate action transition: employing nature-based solutions, alongside a rapid phase-out of fossil fuel use, to reduce the scale and impacts of climate change, while providing positive benefits for biodiversity and other sustainable development goals. 

The biodiversity-inclusive One Health transition: managing ecosystems, including agricultural and urban ecosystems, as well as the use of wildlife, through an integrated approach, to promote healthy ecosystems and healthy people.

As nations negotiate a new pact to guide global biodiversity efforts in the 2020s, GBO5 synthesizes abundant evidence of biodiversity's global decline, based on an extensive range of sources, including:

6th National Reports to the CBD from Convention's member Parties

Four previous GBO reports (2001, 2006, 2010, 2015)

Assessments by the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES), including the landmark Global Assessment (2019) and regional assessments (2018)
Recent research and indicators updated since the IPBES Global Assessment

Reports from other international bodies, including: Food and Agriculture Organization (FAO), the Intergovernmental Panel on Climate Change (IPCC), the Organization for Economic Cooperation and Development (OECD), and others

Plant Conservation Report (Global Strategy for Plant Conservation targets, 2011-2020)

Two Local Biodiversity Outlooks* (presenting the perspectives and experiences of indigenous peoples and local communities on the current biodiversity crisis, and their contributions to the implementation of the Strategic Plan for Biodiversity 2011-2020). The second edition of the Local Biodiversity Outlooks will be launched at a separate event on the 16th September 2020 (details below).

GBO-5 underlines the urgent need to act to slow and end further loss, and highlights examples of proven measures available to help achieve the world's agreed vision: "Living in harmony with nature" by 2050.

WWF's Living Planet Report, released on 10 Sept, documenting the precipitous fall in monitored populations of mammals, birds, amphibians, reptiles and fish between 1970 and 2016, further underlines the urgency to act.

GBO-5 reports financing for biodiversity (public, private, domestic and international), was up in some countries, roughly constant in others for the past decade, and resources available for biodiversity through international flows and official development assistance roughly doubled.  In all, an estimated annual $78-91 billion is available, but "estimates of biodiversity finance needs are conservatively estimated in the hundreds of billions of dollars."

"Moreover, these resources are swamped by support for activities harmful to biodiversity," the report says. "These include $500 billion in fossil fuel and other subsidies that potentially cause environmental harm, $100 billion of which relate to agriculture."

GBO-5 highlights that action on biodiversity is essential to address climate change, long- term food security and health. The time for action on all these issues is now - the global community must seize the opportunity to build back better from the COVID-19 pandemic in order to reduce the risk of future pandemics.

GBO-5 also underlines the importance of biodiversity for achieving the high-level, agreed Sustainable Development Goals established in 2015, and the 2016 Paris Agreement and, at the UN's Nature Summit on 30 September, GBO-5's findings will be taken up by heads of State and Government.

GBO-5 will also have an important impact on CBD's ongoing process to create a set of new global biodiversity targets for 2021-2030, as part of a post-2020 framework for the Convention.

That framework, now under negotiation, will be considered at CBD's 15th meeting of the Conference of Parties (COP-15), Kunming, China - postponed as a result of the coronavirus pandemic from October 2020 to 2021.

Comments

"As we emerge from the immediate impacts of the pandemic, we have an unprecedented opportunity to 'build back better', incorporating the transitions outlined in this Outlook and embodied in an ambitious plan to put the world on track to achieve the 2050 Vision for Biodiversity. Part of this new agenda must be to tackle the twin global challenges of climate change and biodiversity loss in a more coordinated manner, understanding both that climate change threatens to undermine all other efforts to conserve biodiversity; and that nature itself offers some of the most effective solutions to avoid the worst impacts of a warming planet."
- António Guterres, Secretary-General, UN

"Now, we must accelerate and scale-up collaboration for nature-positive outcomes - conserving, restoring and using biodiversity fairly and sustainably. If we do not, biodiversity will continue to buckle under the weight of land- and sea-use change, overexploitation, climate change, pollution and invasive alien species. This will further damage human health, economies and societies - with particularly detrimental effects on indigenous peoples and local communities. We know what needs to be done, what works and how we can achieve good results. If we build on what has already been achieved, and place biodiversity at the heart of all our policies and decisions - including in COVID-19 recovery packages - we can ensure a better future for our societies and the planet.
- Inger Andersen, Executive Director, UNEP

"We need global, swift and transformative action to halt the decline of our planet's biological diversity and the loss of wild species of fauna and flora across ecosystems. The fifth edition of the Global Biodiversity Outlook can arm decision-makers with the facts and knowledge needed to move towards meeting these urgent challenges."
- Ivonne Higuero, Secretary-General, CITES

"Our dependence on nature is more evident today than ever. The GBO-5 is a call for action to reverse biodiversity loss and ensure our health, wellbeing and prosperity. The report highlights the rapid global decline of wetlands that affects water availability, as well as the 40% of the planet's species which live in these ecosystems.  Contracting Parties to the Convention on Wetlands are committed to wetland conservation and wise use as a key element of the post-2020 biodiversity framework."
- Martha Rojas Urrego, Secretary General, Convention on Wetlands

"The 5th Global Biodiversity Outlook, launched just before the first UN Biodiversity Summit, paints a stark message - that we are continuing to lose biodiversity, our essential planetary safety net. We are not on track to meet most of Aichi Biodiversity Targets, and we know that the loss of nature poses grave consequences for us all. However, there are reasons for hope. The report shows that we are on track to have at least 17% of terrestrial protected areas and 10% marine protected areas by the end of 2020 - a remarkable accomplishment from where we were a decade ago. This tells us we can do more, and we must do more, in the coming decade of action."
- Achim Steiner,  Administrator, UNDP

As the Chair of IPBES, I welcome the 5th edition of the Global Biodiversity Outlook. IPBES is proud to have contributed to GBO-5, in particular through our Global Assessment of Biodiversity and Ecosystem Services. GBO-5 includes, among several new sources of evidence, an interesting analysis of the 6 th national reports provided by countries on the state of their biodiversity. Sadly, GBO-5 confirms that none of the 20 Aichi Targets have been fully achieved. GBO-5 calls for transformative change in eight areas and IPBES is currently preparing two directly relevant reports: one on transformative change, and the other on ways to simultaneously achieve the SDGs related to water, food, health, energy, climate and biodiversity. Together I believe that they will form a strong body of knowledge to further inform the work of the CBD in the post-2020 era. It is my great hope that all of the evidence, expertise and options now available to Parties at CBD COP 15 will finally raise the level of awareness about the severe and ongoing reduction of biodiversity and raise both the level of ambition and the resources needed to address this tragedy.
- Ana María Hernández, Chair, Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES)

"The Global Biodiversity Outlook report underscores that global efforts have failed to address the growing global biodiversity crisis or achieve agreed targets. Urgent action and real commitment are needed to reverse the trends of biodiversity loss and the threat of extinction of as many as one million species, including migratory species of wild animals."
- Amy Fraenkel, Executive Secretary, Convention on Migratory Species (CMS)

"We cannot afford to ignore the findings of this major report. Despite some progress, the loss of nature continues unabated, highlighting not only a failure of our moral duty to preserve Earth’s diversity of life, but also the undermining of the very natural systems that support human health and the global economy. Importantly, the report also tells us that halting and reversing biodiversity loss is entirely possible, by protecting more of the remaining natural spaces, curbing wildlife overexploitation and, crucially, reforming the way we produce and consume food. "World leaders must take decisive action now - not later - to set nature on the path to recovery this decade and secure a nature-positive economy. They will have an important opportunity to raise ambition at the UN Summit on Biodiversity later this month ahead of the UN biodiversity negotiations next year.”

- Marco Lambertini, Director General, WWF International

“It is very important to see a global report highlighting the limited progress made in recent years towards the global biodiversity targets pointing to the need to step up our efforts [collectively and holistically] to conserve and sustainably use biodiversity. The report confirms the findings of various other reports, including FAO’s 2019 report on The State of the World's Biodiversity for Food and Agriculture. As the adoption of its Strategy on Mainstreaming Biodiversity across Agricultural Sectors shows, we are more committed than ever to work for fair, healthy and sustainable agri-food systems.”

- Qu Dongyu, Director-General, FAO

“The news of our slow progress in achieving the 20 Aichi biodiversity targets set for 2020 should give us pause, coming as it does during the worst global pandemic in nearly 100 years. Reckless land use change is now not only leading to the loss of biological diversity; it is enabling the emergence of new infectious diseases in which alien viruses spread from the wild to humans. The Global Land Outlook 5 is clear about where to focus our attention to live in harmony with nature. But we have one shot – a decade – to make swift progress and with impact. The choices of our action or inaction are as stark as they are clear. Let us choose actions for a greener future where ecosystems thrive.”

- Ibrahim Thiaw, Executive Secretary, UN Convention to Combat Desertification

GBO 5: By the Numbers

33% Proportion of people in the most biodiverse countries with high awareness of both the values of biodiversity and the steps required for its conservation and sustainable use.

91 Number of countries applying global standards for integrating environment into national accounting -- roughly double the number from 2006

$500 billion Value of government subsidies that potentially cause environmental harm,

1.7 Number of "Earths" needed to regenerate the biological resources used by humanity from 2011 to 2016

33% Reduction in global deforestation rates comparing the last five years with rates in the decade to 2010.

66% Proportion of marine fish stocks in 2017 fished within biologically sustainable levels, down from 71% in 2010, with great variation among regions, and among stocks.

163 million Number of farms (29% of all worldwide) practicing sustainable intensification, on

453 million hectares of agricultural land (9% of the worldwide total.

260,000 tonnes Weight of the estimated 5.25 trillion plastic particles in the world's oceans

~200 Eradications of invasive mammals on island since 2010, benefitting an estimated 236 native terrestrial species, including 100 highly-threatened bird, mammal and reptile species such as the island fox and Seychelles magpie-robin

60%+ Proportion of world's coral reefs under threat, especially due to overfishing and destructive fishing

43% Area of key biodiversity areas covered by protected areas -- up from 29% in 2000.

28-48 Estimated number of bird and mammal species prevented from going extinct thanks to conservation actions since 1993, when the CBD came into force, including 11 - 25 species since 2010.

1,940 Number of local domesticated animal breeds) considered to be at risk of extinction, out of 7,155, with risk status unknown for another 4,668 breeds

164: Number of countries that explicitly recognize women's rights to own, use, make decisions and use land as collateral on equal terms with men

27 million Hectares of land under restoration activities - only 2% of the estimated potential

12 Number of Parties to the Nagoya Protocol on Access and Benefits Sharing, 87 of them having ABS measures in place and competent national authorities established

69 Number of countries with National Biodiversity Strategies and Action Plans (NBSAP) adopted as whole-of-government policy instruments

40 Number of Parties that involved indigenous and local communities in the preparation of their NBSAP

1.4 billion Number of species occurence records freely accessible through the Global Biodiversity Information Facility (GBIF), a seven-fold increase over the decade

$9.3 billion: Total value of annual international public biodiversity finance for biodiversity -- double the levels of the previous decade -- of which $3.9 billion has biodiversity as a principle focus

More: https://bit.ly/2EW2jmt

FLAGSTAFF, Ariz. -- Sept. 15, 2020 -- Initial findings reported by the Arizona COVID-19 Genomics Union (ACGU) suggest that following Arizona's first reported case of COVID-19 in late January, the state experienced no cases that went undetected and was COVID-free until at least 11 distinct incursions occurred between mid-February and early April.

The published results appear in the scientific journal mBio.

Faculty at the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, Northern Arizona University (NAU), University of Arizona (UArizona) and Arizona State University (ASU) launched the ACGU in April with the express purpose of tracking the causative agent of COVID-19, SARS-CoV-2: how it evolves and how it spreads into, within and out of Arizona.

The ACGU sequenced the SARS-CoV-2 genomes in as many virus-positive patient samples in Arizona as possible, and working with Arizona's public health officials, applied the results toward statewide efforts to test and track patients, as well as provide guidance for Arizona public policy makers.

Quick action by ASU and Maricopa County public health officials, ACGU scientists agree, likely kept the first identified COVID-19 patient in Arizona -- a student who had just returned from Hubei, the Chinese province where the disease originated -- from igniting an outbreak, and prevented Arizona from becoming an early epicenter for the contagion.

"This is a great example of how a rapid and thorough public health response can be successful in preventing the spread of this disease," said ACGU Director Dr. Paul Keim, Regents' Professor of Biological Sciences and Cowden Endowed Chair in Microbiology at NAU and Executive Director of NAU's Pathogen and Microbiome Institute.

"Similar steps could be taken when shaping future efforts to reopen businesses and schools, even though the virus continues to circulate and people remain susceptible," added Keim, who is also a Distinguished Professor and Co-Director of TGen's Pathogen and Microbiome Division.

Dr. Michael Worobey, an ACGU co-founder and the head of University of Arizona's Department of Ecology and Evolutionary Biology, agrees.

"It's a combination of the patient doing the right things to isolate himself and be aware that he possibly had this disease, and public health officials doing all the right things. Stopping an incursion of COVID-19 was a victory for the state of Arizona," Dr. Worobey said.

This bought Arizona valuable time for preparedness efforts. The first reported case of "community" transmission occurred in Arizona in early March descended from the Washington state outbreak that was discovered in February. More than 80% of the SARS-CoV-2 genome sequences from Arizona COVID-19 cases descended from at least 11 separate lineages that were initially circulating widely in Europe, and by travel have since dominated the outbreak throughout the U.S. None of the observed transmission clusters are epidemiologically linked to the original travel-related case in the Arizona, suggesting successful early isolation and quarantine.

The ACGU uses state-of-the-art sequencers, custom computational analysis workflows, and supercomputers to determine the sequence of the virus's RNA genome, which is just under 30,000 bases long. In contrast, there are nearly 3 billion bases in the human genome, which determine traits as simple as eye and hair color, and as complex as an individual's propensity for cancer and other disease.

TGen has so far sequenced SARS-CoV-2 genomes from nearly 3,000 COVID-19 positive samples for the ACGU, and additional sequencing was performed at ASU and UArizona, from among the more than 200,000 positive cases in Arizona, making it one of the most robust such efforts in the nation. ACGU receives Arizona samples collected by state, county, tribal and private healthcare systems.

ACGU scientists take advantage of small changes or mutations in the virus' genome, which naturally occur over time as the virus reproduces, to track the spread of the virus. By comparing mutations observed in Arizona to those present in strains circulating across the globe, they can determine when and from where the virus has been introduced to Arizona.

Using molecular clock analyses, researchers found that the majority of Arizona sequences are represented by two lineages -- and several sub-lineages -- most of which were likely introduced through domestic travel, but with some evidence for international importation.

"Through the ACGU, we are harnessing expertise in virology, genomics, evolution and bioinformatics from throughout Arizona in order to rapidly distill these genomic data into actionable insights that can complement the state's public health response," Dr. Keim said. "These results demonstrate the power of public health contact tracing and self-isolation following a positive test for stemming the tide of infections moving forward."

Dr. David Engelthaler, Director of TGen North in Flagstaff, which includes the institute's infectious disease branch, said the initial ACGU findings show how each community, each state is writing its own story for what is happing in the COVID-19 pandemic.

"We need to understand all of those plot lines that have led to where we are now," said Dr. Engelthaler, another of the co-founders of the ACGU. "Once this disease was detected in Arizona on Jan. 26, public health immediately jumped in to make sure that all contacts were identified, samples were collected and the patient was watched very closely for the next couple of weeks to make sure there were not any more cases."

In the coming months, he said, it will be necessary to track COVID-19 outbreaks and build epidemiological walls around each case, especially for those most at risk: persons older than 65, those in long-term care facilities, prisons, and those with pre-existing health problems.

"When you don't have eyes on this, when you don't have contact tracing, then it can really easily move from person-to-person," Dr. Engelthaler said. "It's really useful for public policy makers to be making locally-informed decisions."

Dr. Efrem Lim, a virologist who leads the ASU team, said the SARS-CoV-2 genome sequence data can give health care providers and public policy makers an edge in fighting the pandemic.

"Tracking the transmission of the virus and its mutations ensures that therapeutics and vaccines being developed are on the right course," said Dr. Lim, an assistant professor at ASU's Biodesign Institute. "We now have a handle on what the SARS-CoV-2 virus in our communities looks like at the sequence level."

DALLAS, September 15, 2020 -- Patients with psoriasis treated with biologic therapy, which are protein-based infusions to suppress inflammation, had a significant reduction in high-risk plaque in heart arteries, over one-year, according to new research published today in Circulation: Cardiovascular Imaging, an American Heart Association journal.

Chronic inflammation in people with psoriasis is associated with a higher risk of developing coronary artery disease. Biologic therapy medications are proteins that are given by injection or infusion and suppress the inflammation process by blocking the action of cytokines, which are proteins that promote systemic inflammation.

Previous research has shown a clear link between psoriasis and the development of high-risk coronary plaque. This study provides characterization of a lipid-rich necrotic core, a dangerous type of coronary plaque made up of dead cells and cell debris that is prone to rupture. Ruptured plaque can lead to a heart attack or stroke.

"Having inflamed plaque that is prone to rupture increases the risk of heart attack five-fold within ten years," said Nehal N. Mehta, M.D., M.S.C.E., FAHA, study senior author, a Lasker Senior Investigator and chief of the Lab of Inflammation and Cardiometabolic Diseases at the National Heart, Lung, and Blood Institute at the National Institutes of Health in Bethesda, Maryland.

"This is the first time an imaging study in humans has shown what one year of ongoing, untreated inflammation can do to arteries of the heart and that we can reverse this damage. Untreated inflammation is dangerous. You are just waiting for a heart attack or stroke to happen," Mehta said.

The analysis involved 209 middle-aged patients (ages 37-62) with psoriasis who participated in the Psoriasis Atherosclerosis Cardiometabolic Initiative at the National Institutes of Health, an ongoing observational study. Of these participants, 124 received biologic therapy, and 85 were in the control group, treated only with topical creams and light therapy.

To measure the effects of biologic therapy on arteries of the heart, the researchers performed cardiac computed tomography (CT) scans on all study participants before they started therapy and one year later. The CT results between the two groups were then compared.

At the start of the study, participants with psoriasis had low cardiovascular risk by conventional cardiovascular risk scores, and severe psoriasis was associated with higher body mass index (BMI), high-sensitivity C-reactive protein (a measure of systemic inflammation) and higher levels of coronary artery plaque.

After one year of treatment, patients who received biologic therapy were compared to the control group. Researchers found:

Biologic therapy was associated with an 8% reduction in coronary plaque. In contrast, those in the control group experienced slightly increased coronary plaque progression.

Even after adjusting for cardiovascular risk factors and psoriasis severity, patients treated with biologic therapy had reduced coronary plaque.

"There is approximately 6-8% reduction in coronary plaque following therapy with statins. Similarly, our treatment with biologic therapy reduced coronary plaque by the same amount after one year. These findings suggest that biologic therapy to treat psoriasis may be just as beneficial as statin therapy on heart arteries," Mehta said.

This study has implications for people with psoriasis and possibly for people with other chronic inflammatory conditions such as HIV, lupus and rheumatoid arthritis, who also have increased risk of heart disease.

"We have never before been able to show healing of an inflamed plaque like this in humans. Biologic therapy reduces systemic inflammation and immune activation, and it has a favorable impact on improving overall vascular health," Mehta said. "Imagine if we can treat both psoriasis and coronary heart disease with one therapy - that is the question to be asked in future studies."

The study's findings should be interpreted with caution because it was limited by a short follow-up period and a relatively small number of patients. Larger, randomized controlled studies are needed to better understand how changes in coronary plaque may lead to a reduction in heart attacks and strokes in people with psoriasis.

DALLAS, Sept. 15, 2020 -- Health care professionals should become more familiar with medications that cause irregular heart rhythms called arrhythmias, according to "Drug- Induced Arrhythmias," a new scientific statement from the American Heart Association, published today in the Association's flagship journal Circulation.

"Many commonly used medications can cause irregular heartbeats as a side effect," said James E. Tisdale, Pharm.D., FAHA, professor of pharmacy practice at the College of Pharmacy at Purdue University, adjunct professor at the School of Medicine at Indiana University and chair of the writing committee for the American Heart Association's scientific statement. "While the risk is relatively low, it is important for health care professionals to consider that their patient's arrhythmia could be caused or worsened by a medication."

During an arrhythmia, the heart can beat too fast, too slowly or with an irregular rhythm. Arrhythmias can be caused by genetics or numerous conditions, including coronary artery disease, thyroid problems or electrolyte imbalances. This statement reviewed medications that can cause or exacerbate arrhythmias, risk factors for these side effects and prevention, monitoring and treatment options for people who are at risk for or develop arrhythmias.

While the statement was written for health care professionals, patients should know to continue to take their medications as directed and talk with their health care professional about any concerns with their medicines and any risk factors for a medication-induced arrhythmia.

There are several different types of drug-induced arrhythmias. Some medications can cause slower heart rates, and others can cause rapid heart rhythms from the upper chambers (atria) or lower chambers (ventricles) of the heart. When a heart beats too fast, the condition is called tachycardia. When a heart beats too slowly, the condition is called bradycardia. Often there are no symptoms, but some people feel their heart "racing" or "fluttering" or have trouble breathing, faint or become dizzy. If an arrhythmia is left untreated, the heart may not be able to pump enough blood to the body, which can damage the heart, the brain or other organs, and possibly cause the person to faint. Some arrhythmias are life-threatening and require immediate treatment.

Heart rhythm side effects during the COVID-19 pandemic

During the COVID-19 pandemic, chloroquine, hydroxychloroquine and azithromycin have been used to manage the novel coronavirus disease, noted the writing group. These medications can cause heart rhythm disturbances, and there have been some clinical trials to assess their effectiveness to treat COVID-19, including one National Institutes of Health trial that was halted in June. In June and July, the U.S. Food and Drug Administration revoked emergency use and issued a warning against the use of hydroxychloroquine or chloroquine for the treatment of COVID-19 outside of a clinical trial or hospital.

Heart rhythm disorders have been reported as a side effect of hydroxychloroquine alone and in combination with azithromycin among patients with COVID-19. Other medications proposed for managing COVID-19 such as lopinavir/ritonavir also have the potential to interfere with the heart's normal rhythm. Guidance from the American Heart Association for managing arrhythmia risk associated with these medications in patients with COVID-19 was issued earlier this year: Considerations for Drug Interactions on QTc in Exploratory COVID-19 Treatment.

Who's at risk?

People with a history of heart attack, heart disease or previous heart surgery are more likely to develop an irregular heartbeat after exposure to certain medications. Other risk factors for medication-induced arrhythmias include older age, deficiencies of potassium or magnesium, and excessive drinking. Some patients who experience drug-induced arrhythmia may have a genetic predisposition. The most common test used to diagnose an arrhythmia is an electrocardiogram (ECG).

Prevention and monitoring

Taking medications as directed and maintaining normal electrolyte levels, kidney and liver function can help reduce risk. Other strategies for prevention include using the lowest effective dose of arrhythmia-inducing medications, minimizing or avoiding the use of stimulants and avoiding excessive alcohol intake (women: 1 or fewer drinks per day; men: 2 or fewer drinks per day). Understanding and avoiding medication interactions can also help minimize risk.

For certain high-risk medications, patients may need to be hospitalized using a heart monitor while starting the medication. For patients at increased risk of a drug-induced arrhythmia, regular ECG monitoring may also be performed.

Treatment

Treatment usually includes discontinuing the medicine that is causing the arrhythmia, and may also include antiarrhythmic medicines, or placement of a device that can correct an irregular heartbeat. "Medications are extremely important and beneficial for treating a large variety of diseases and chronic health conditions, and patients should not change or stop taking any of their medicines without talking with their health care professional," said Tisdale.

Tisdale added, "Much remains unknown about the underlying mechanisms of arrhythmias associated with specific medications,and further research is needed to better understand risk factors and treatment options. We hope raising awareness will result in clinicians being attentive to risk factors, and avoiding, where possible, medications that can cause or worsen arrhythmias in patients who are at higher risk."

NEW YORK, Sept. 15, 2020 - The last several years have brought mounting evidence that the molecules inside our cells can self-organize into liquid droplets that merge and separate like oil in water in order to facilitate various cellular activities. Now, a team of biologists at the Advanced Science Research Center at The Graduate Center, CUNY (CUNY ASRC) have identified unique roles for the amino acids arginine and lysine in contributing to liquid phase properties and their regulation. Their findings are available today online in Nature Communications.

Known as liquid-liquid phase separation, the process allows some molecules within a cell to cloister themselves into membraneless organelles in order to carry out certain duties without interruption from other molecules. The mechanism can also allow molecules to create multiphase droplets that resemble, say, a drop of honey inside a drop of oil surrounded by water in order to carry out sophisticated jobs.

"This is a really exciting new research area because it uncovers a core biological function that, when gone awry, may be at the root of disease, particularly neurodegeneration as in ALS or Alzheimer's," said principal investigator and Graduate Center, CUNY Biochemistry Professor Shana Elbaum-Garfinkle, whose lab at the CUNY ASRC Structural Biology Initiative conducted the study. "With an understanding of how individual amino acids contribute to phase behavior, we can begin to investigate what's going wrong in liquid phase separation that may interfere with normal biological function and potentially design therapies that can modulate the process."

Researchers have suspected for a while that arginine and lysine -- two of the 20 amino acids that make up all proteins -- were responsible for regulating liquid phase separation, but they weren't certain how each contributed to phase behavior and to creating the differing viscosities that cloister molecules into separate communities.

"Arginine and lysine are very similar amino acids in terms of both being positively charged, but they differ in terms of binding capability. We were really curious to understand what effect this difference would have on the material properties, such as viscosity or fluidity, of the droplets they form," said Rachel Fisher, the paper's first author and a postdoc in Elbaum-Garfinkle's lab. "We also wanted to know how these differences manifest themselves when the arginine and lysine systems are combined. Will the droplets coexist? When we saw they did, we then wanted to understand how we could modulate this multi-phase behavior."

To answer their questions, Elbaum-Garfinkle's team used a technique called microrheology -- whereby tiny tracers are used to probe material structures -- to track and investigate the properties of arginine and lysine droplets. They found that arginine-rich droplets were over 100 times more viscous than lysine-rich droplets, comparable to the difference between a thick syrup or ketchup and oil. The viscosity differences are significant enough that if lysine and arginine polymers are combined, they don't mix. Instead, they create multi-phase droplets that sit within one another like Dutch nesting dolls. Additionally, arginine has such strong binding properties that under some conditions it can compete with lysine and replace or dissolve lysine droplets. The researchers further identified ways to tune the balance between competition and coexistence of the two phases. The results present a novel mechanism for designing, controlling or intervening in molecular liquid phases.

Scientists have long believed that ocean viruses always quickly kill algae, but Rutgers-led research shows they live in harmony with algae and viruses provide a "coup de grace" only when blooms of algae are already stressed and dying.

The study, published in the journal Nature Communications, will likely change how scientists view viral infections of algae, also known as phytoplankton - especially the impact of viruses on ecosystem processes like algal bloom formation (and decline) and the cycling of carbon and other chemicals on Earth.

"It's only when the infected algal cells become stressed, such as when they run out of nutrients, that the viruses turn deadly," said lead author Benjamin Knowles, a former post-doctoral researcher in the Department of Marine and Coastal Sciences in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick who is now at UCLA. He was also a post-doctoral fellow at Rutgers' Institute of Earth, Ocean, and Atmospheric Sciences. "We feel that this entirely new model of infection is widespread in the oceans and stands to fundamentally alter how we view host-virus interactions and the impact of viruses on ecosystems and biogeochemical cycling since it goes against the long-accepted classic model of viruses always being lethal and killing cells."

Biogeochemical cycling refers to essential nutrients like carbon, oxygen, nitrogen, phosphorus, calcium, iron and water circulating through organisms and the environment. The coccolithophore algae Emiliania huxleyi was the focus of the study as a model for other algae-virus systems and is a central driver of this process.

The scientists studied virus-algae interactions in the lab and in controlled, mini-blooms in coastal waters of Norway. They focused on viral infection of a form of algae that is responsible for generating much of the oxygen and carbon cycling on Earth. A group of ocean viruses called coccolithoviruses routinely infect and kill E. huxleyi over 1,000 square miles, which is viewable from space via Earth-observing satellites.

The viruses eventually rupture algal cells, contributing to the global food web by making energy and organic matter available to other organisms. But infected cells don't die right away, the scientists discovered. Instead, infected cells multiply and bloom across dozens of miles of ocean waters and die in a coordinated manner. These dynamics have been routinely observed in previous studies but couldn't be explained by the rate at which algal hosts and viruses encounter each other in nature.

"The algae and viruses have a quasi-symbiotic type of relationship, allowing both algal cells and viruses to replicate happily for a while," said senior author Kay D. Bidle, a professor and microbial oceanographer in the Department of Marine and Coastal Sciences at Rutgers-New Brunswick and the Institute of Earth, Ocean, and Atmospheric Sciences. "We feel that these newly discovered dynamics also apply to other virus-algal interactions across the oceans and are fundamental to how infection works. By combining experimental, theoretical and environmental approaches, our work presents a template to diagnose this type of infection in other systems."

The algae-virus dynamics have important implications for the outcome of infections and the flow of carbon and may lead to scenarios where carbon dioxide is sequestered, or stored, in the deep ocean rather than retained in the upper ocean, Bidle said. Further research is needed to fully understand the extent of these dynamics and their impacts on ecosystems and the cycling of carbon in the oceans.

Scientists at Sanford Burnham Prebys Medical Discovery Institute, Fondazione Santa Lucia IRCCS, and Università Cattolica del Sacro Cuore in Rome have shown that pharmacological (drug) correction of the content of extracellular vesicles released within dystrophic muscles can restore their ability to regenerate muscle and prevent muscle scarring (fibrosis). The study, published in EMBO Reports, reveals a promising new therapeutic approach for Duchenne muscular dystrophy (DMD), an incurable muscle-wasting condition, and has far-reaching implications for the field of regenerative medicine.

"Our study shows that extracellular vesicles are bioactive mediators that can transfer the benefits of medicine--in this case, HDAC inhibitors (HDACi)--to treat DMD," says Pier Lorenzo Puri, M.D., professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys and co-corresponding author of the study. "We discovered the promise of this treatment almost 20 years ago and did all of the preclinical work, which led to a current clinical trial for boys with DMD. However, the therapeutic potential of HDACi has been so far limited by its systemic adverse effects."

In the current clinical trial, boys with DMD are treated with HDACi at suboptimal doses due to the risk of adverse side effects. The scientists are hopeful that extracellular vesicles might provide a cell-free, non-immunogenic, transplantable tool for local delivery of bioactive particles that transfer HDACi to dystrophic muscles, thereby overcoming the undesirable secondary effects caused by chronic use at high doses.

"We believe this novel approach of using pharmacologically corrected extracellular vesicles may be used to safely deliver drugs such as HDACi directly to dystrophic muscles to obtain the beneficial action that would otherwise only be achieved at higher, toxic doses," says Puri.

Extracellular vesicles are bioactive particles, meaning they have an effect in the body. They have recently attracted significant attention from the biomedical community because of their therapeutic potential. These particles contain information in the form of DNA, RNA or proteins and are exchanged from one cell to another. Alterations in the content of these particles leads to faulty communication between cells in dystrophic muscles and changes their behavior. In this study, the scientists discovered that these content alterations can be corrected to restore the physiological communication between the cells of dystrophic muscles.

Communication breakdown

Prior research from Puri's team showed that as DMD progresses, special muscle-healing cells called fibro-adipogenic progenitors (FAPs) become corrupted and start to promote muscle wasting and fibrosis. The team suspected that altered communication between FAPs and muscle stem cells--perhaps via extracellular vesicles--might be part of the problem.

To answer this question, Martina Sandonà, Ph.D., first author of the study, and her colleagues conducted a series of experiments using muscle biopsies from boys with DMD who are enrolled in the clinical trial testing experimental HDACi treatment as well as a mouse model of DMD. The scientists were able to show that as DMD progresses, cellular communication via extracellular vesicles is progressively altered over time, which impairs the regeneration potential of DMD muscles. Importantly, the researchers demonstrated that correcting the content of the extracellular vesicles with an HDAC inhibitor activates muscle stem cells and promotes regeneration while reducing fibrosis and inflammation.

"Our findings can likely be extended to other conditions and diseases, as pharmacologically 'lifted' extracellular vesicles could be exploited as a general therapeutic tool in regenerative medicine," says Valentina Saccone, Ph.D., group leader at Fondazione Santa Lucia IRCCS, tenured assistant professor at Università Cattolica del Sacro Cuore and co-corresponding author of the study. "These particles might also be used as an adjuvant approach for other treatments, such as gene or cell therapies."

A ray of hope

Treatment advances can't come soon enough for people with DMD and their loved ones. The genetic condition is caused by a lack of dystrophin, a protein that strengthens muscles, and causes progressive muscle degeneration. DMD primarily affects boys, with symptoms often appearing between the ages of 3 and 5. With recent medical advances, children with DMD now often survive beyond their teenage years into their early 30s, but effective treatments are still needed.

"For children and adults living with DMD and their families, research provides a ray of hope for a better future," says Filippo Buccella, founder of Parent Project Italy, which has provided continual support to Puri's team for the last 20 years. "This study uncovers a promising new therapeutic approach for DMD and brings us one step closer to treatments that may help children maintain muscle strength for as long as possible and live long, fulfilling lives."

"The more options we have to treat DMD, the better, as it's likely that drugs with different mechanisms of action could be more effective in combination," says Sharon Hesterlee, Ph.D., executive vice president and chief research officer of the Muscular Dystrophy Association. "Dr. Puri's work represents a unique approach that could prove complementary."