Culture

DALLAS, April 13, 2020 -- Type 2 diabetes (T2D) affects treatment options for patients who have both coronary artery disease (CAD) and T2D, according to a new American Heart Association Scientific Statement, published today in the Association's flagship journal Circulation. The scientific statement provides an overview of the latest advances for treating people who have both CAD and T2D and details the complexities of care for these conditions together.

"Recent scientific studies have shown that people with T2D may need more aggressive or different medical and surgical treatments compared to people with CAD who do not have T2D," said Suzanne V. Arnold, M.D., M.H.A., chair of the writing group for the scientific statement, associate professor of medicine at the University of Missouri Kansas City, and a cardiologist at Saint Luke's Mid America Heart Institute, also in Kansas City, Missouri.

When a person has T2D, their body is not able to efficiently use the insulin it makes to keep glucose (blood sugar) at a healthy level, and people with T2D often have overweight or obesity, high blood pressure and high cholesterol, which further increases the risk of cardiovascular disease. For many years, reducing glucose to healthy levels was considered the most important goal of therapy for T2D.

"What we've learned in the past decade is how you control glucose levels has a huge influence on cardiovascular risk. Lowering blood sugars to a certain level is not sufficient. There are now more options for controlling glucose in people with T2D, and each patient should be evaluated for their personal risk of cardiovascular disease, stroke and kidney disease. This combined health information as well as the patient's age should be used to determine the appropriate therapies to lower glucose," said Arnold.

Metformin is the most frequently recommended medication for initial treatment to lower glucose in people diagnosed with T2D. Metformin sometimes leads to mild weight loss, is at least neutral in terms of cardiovascular effects, is inexpensive and has a long use and safety history. However, the statement notes that the latest research indicates several newer classes of medications may both lower glucose and reduce the risk of cardiovascular diseases.

Sodium-glucose co-transporter inhibitors (SGLT2 inhibitors), which are oral medications, were the first class to show clear benefits on cardiovascular outcomes. In a recent study of people with T2D and a diagnosis of heart disease, researchers found that patients taking SGLT2 inhibitors were significantly less likely to die of cardiovascular disease. They had a reduced risk of heart failure, less progression of chronic kidney disease and also lost weight.

Glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) are a class of injectable medications that lower blood glucose and can also cause a reduction in weight. Recent study results about their efficacy in reducing cardiovascular diseases have been mixed. However, a few GLP-1 receptor agonists have been shown to reduce the risk of major cardiovascular events caused by cholesterol build-up in the arteries, such as heart attacks and strokes.

For older adults, relaxing glycemic control slightly might be beneficial because it may reduce the risk of hypoglycemia - when glucose levels become too low. "Hypoglycemia is incredibly hard on the heart and should be avoided particularly in older patients. We must ensure that we are weighing all of the options in consideration of the whole patient, keeping in mind that what may be appropriate for a 60-70 year old patient is likely not the same as for an 85-year old," said Arnold. With some medications, such as metformin, SGLT2 inhibitors and GLP-1 receptor agonists, the risk of hypoglycemia may be reduced.

Preventing blood from forming clots is also an important goal of CAD treatment. "Aspirin, which is a blood thinner, may be appropriate for many people with CAD, but may not work as effectively in people with T2D and CAD. Therefore, newer, stronger antiplatelet medications (a form of blood thinner) should be considered. Since all antiplatelet medications increase the risk of bleeding, it is important to balance the risk for each patient of increased bleeding versus the benefit of reducing the tendency of the blood to clot," said Arnold.

Type 2 diabetes may also influence what type of interventional procedure is best to use to re-open an artery to increase blood flow in indicated patients. Studies have found a greater reduction in the 5-year risk of death, heart attack or recurrent angina/chest pain when patients with T2D and CAD undergo coronary artery bypass graft (CABG) surgery to widen a narrowed blood vessel instead of treating the narrowing with angioplasty and stenting. In contrast, the advantage of bypass over stenting is not as dramatic in people without T2D.

Additionally, unhealthy cholesterol levels, such as high LDL (bad cholesterol), low HDL (good cholesterol) and high triglycerides (blood fat), which are major risk factors for CAD, are common among people with T2D. In many patients, even if LDL levels are not exceptionally high, people with T2D often have a type of LDL particle that is more likely to increase the risk of atherosclerosis, the slow narrowing of the arteries that underlies heart disease.

The vast majority of patients with T2D have hypertension. Blood pressure control is critically important in the management of CAD in patients with T2D.

"More aggressive steps may be needed to improve the cholesterol levels in people with T2D. Statins, the cornerstone of cholesterol-lowering therapy, may slightly increase blood sugar levels, however, the overall cardiovascular risk reduction they provide is far more beneficial. Blood sugar changes are not a reason to avoid prescribing statins for people with type 2 diabetes," said Arnold.

Some patients with CAD and T2D may also benefit from lowering cholesterol with additional classes of medications, such as oral cholesterol absorption inhibitors or newer injectable medications, which have been shown to be beneficial in people with diabetes.

"While treatment with medication is very important in the treatment of people who have both T2D and CAD, no pill is a substitute for a healthy lifestyle. No matter what new medicines there are, a heart-healthy diet, achieving and maintaining a healthy weight, regular physical activity and treating sleep disorders remain the major cornerstones of treatment for T2D and cardiovascular disease," said Arnold.

Mathematical modeling can take what information is reported about the coronavirus, including the clearly underreported numbers of cases, factor in knowns like the density and age distribution of the population in an area, and compute a more realistic picture of the virus' infection rate, numbers that will enable better prevention and preparation, modelers say.

"Actual pandemic preparedness depends on true cases in the population whether or not they have been identified," says Dr. Arni S.R. Srinivasa Rao, director of the Laboratory for Theory and Mathematical Modeling in the Division of Infectious Diseases at the Medical College of Georgia at Augusta University. "With better numbers we can better assess how long the virus will persist and how bad it will get. Without these numbers, how can health care systems and workers prepare for what is needed?"

Better numbers also are critical to better protecting the population and overall pandemic preparedness, Rao and his colleague Dr. Steven G. Krantz, professor of mathematics at Washington University in St. Louis, Missouri write in the journal Infection Control and Hospital Epidemiology.

"We wanted to provide info on the real magnitude of the problem, not just the tip of the iceberg," corresponding author Rao says.

They used their mathematical model, which takes COVID-19 numbers from sources like the World Health Organization, then used factors like an area's population density, proportion of population living in urban areas where people tend to live in closer proximity, and populations in three age groups -- ages zero to 14, 15 to 64 and 65+ -- to grow more accurate numbers. Because this virus is so infectious, they also considered "transmission probability," Rao says.

They also looked at the number of new cases daily above 10 and up to the first reported peak, and the date ranges for those peaks as an indicator of the trend in reported case numbers. Emerging information about how long the virus survives on a variety of surfaces and in the air will further refine their model, Rao says. The cutoff date for this study was March 9.

They found, for example, that Italy -- where images of jammed intensive care units were one of the clearest indicators of the virus' impact in this geographically small but fifth mostly densely populated European country with a high urbanization score -- did a comparatively good job of reporting early on, with 1 case reported for every four cases that Rao and Krantz projected. That means about 30,223 cases were not reported, according to their model, and Rao noted that Italy had not reached its peak by their March 9 study deadline.

With such a small percentage of people actually being tested in all countries, particularly at that time, South Korea also was reporting 1 case for about every four likely cases. In Spain -- where drive-thru funerals have been reported as occurring every 15 minutes, with nearly 20,000 deaths and a peak in cases March 19, when they reported a 27% increase in active cases -- the country was reporting 1 case for about every 53 likely actual cases, based on the mathematical model. That translates to about 87,405 cases and people not reported. The two modelers saw some of the higher numbers they projected actually playing out within a week of their study's conclusion in several of these European countries, Rao says.

In China, with its huge population numbers at more than 1.4 billion and widely perceived inconsistencies in data reporting, they projected two ranges for the number reported compared to the actual number of cases: 1 in 149 and 1 in 1,104, which translates to anywhere from 12 million to 89 million cases not reported.

A rate could not be calculated March 9 for the United States, where the virus appears to have shown up later, and reported case numbers were just reaching 500, a baseline for projections by mathematical modelers. Rao suspects that the actual number at that date in the U.S. was probably more like 90,000 cases.

A quick follow-up assessment of U.S. numbers by Rao on April 6 using their model indicated more than 561,000 cases with 367,000 actually reported and 8,910 deaths at that date. That calculates to a reporting rate of 2 out of every 3 actual cases in the U.S., reflecting the improvement in tracing positive cases, he says.

Among those 194,000 not yet reported, he projects that includes 3,298 children age 14 and younger, 147,441 ages 15-64 and 43,262 age 65+. That also means that in the U.S., at least 194,000 people at that April 6th moment likely don't know they were positive, more clear evidence of the need for social distancing and other preventive measures currently underway, Rao says.

The modelers visualized the disparities between reported cases and what they projected with a Meyer wavelet, which as the name implies goes up, peaks, and then recedes like a wave. In this case the higher the wave, the higher the underreporting, and lowering the wave means improved reporting, Rao says, of the consistent oscillations generated.

If reported numbers were more precise, mathematical models wouldn't be needed, Rao says, noting that underreporting is a problem for many conditions, not just COVID-19, including common, noninfectious problems like heart disease. "A model tells us something which has not been directly observed," he says. "It's a biological experiment done on computers rather than in a lab."

Rao notes the accuracy of reported cases likely has improved since March 9 with the slowly increased availability of testing, and that the earlier the testing, the earlier the actual peaking of infections.

In the meantime, he encourages everyone to continue to use steps like social isolation and self-quarantine to protect themselves and others by helping fight continued spread of the virulent virus.

"Social distancing is a must, must, must," Rao says.

As of March 9, there were 109,000 cases and 3,800 deaths reported worldwide, the majority from China as well as Italy, South Korea, Iran, France, Germany and Spain. As of the first full week in April -- about a month after their study deadline --nearly 1.4 million cases with more than 81,000 deaths were reported worldwide. More recent figures include the U.S. having more than 362,000 cases and about 11,000 deaths, Spain with more than 135,000 cases and more than 13,000 deaths, and Italy, Germany, France, China, Iran, the United Kingdom, Turkey and Switzerland falling next in line.

In a related research letter in the journal Current Science, they reported about 1 in 4 COVID-19 cases were detected in the month of March in India, that social distancing and other prevention/treatment policies should continue until new cases are not seen there and that spread from urban to more rural populations should be controlled.

WATERLOO, Ontario, April 13, 2020--A new peer-reviewed paper from five prominent ocular scientists will help eye care practitioners (ECPs) instruct and reassure contact lens wearers during the global COVID-19 / coronavirus pandemic. Published in Contact Lens & Anterior Eye, "The COVID-19 Pandemic: Important Considerations for Contact Lens Practitioners" delves into multiple aspects of eye health amidst the global health crisis, with a specific emphasis on the safe use of contact lenses.

The paper and related ECP and patient resources can be accessed from COVIDEyeFacts.org.

"Our findings indicate that contact lenses remain a perfectly acceptable form of vision correction during the coronavirus pandemic, as long as people observe good hand hygiene and follow appropriate wear-and-care directions," said Dr. Lyndon Jones, director of the Centre for Ocular Research & Education (CORE) at the University of Waterloo and the paper's lead author. "Unfortunately, we have seen a number of erroneous reports regarding contact lenses and spectacles in recent days. Our goal is to make sure that science-backed truths are understood and shared, helping eye care practitioners provide accurate, timely counsel to patients."

Based on the paper, CORE has developed five facts (also available as a downloadable infographic) for ECPs to share with anyone who relies on contact lenses or glasses / spectacles:

1. People Can Keep Wearing Contact Lenses. There is currently no scientific evidence that contact lens wearers have an increased risk of contracting COVID-19 compared with glasses / spectacles wearers. Patients should consult their eye care practitioners with questions.

2. Good Hygiene Habits are Critical. Thorough handwashing and drying are essential, as well as properly wearing and caring for contact lenses, ensuring good contact lens case hygiene, and regularly cleaning glasses / spectacles with soap and water. These habits will help wearers stay healthy and out of their doctor's office or hospital, thereby minimizing impacts on the wider healthcare system.

3. Regular Eyeglasses / Spectacles Do Not Provide Protection. No scientific evidence supports rumors that everyday eyeglasses / spectacles offer protection against COVID-19.

4. Keep Unwashed Hands Away from the Face. Whether people wear contact lenses, glasses / spectacles or require no vision correction at all, individuals should avoid touching their nose, mouth and eyes with unwashed hands, consistent with World Health Organization (WHO) and U.S. Centers for Disease Control and Prevention (CDC) recommendations.

5. If You Are Sick, Temporarily Stop Wearing Contact Lenses. Contact lens wearers who are ill should temporarily revert to wearing eyeglasses / spectacles. They can resume use with fresh, new contact lenses and lens cases once they return to full health and have spoken with their eye care practitioner.

On April 8, the CDC issued updated guidance on contact lens wear during the COVID-19 pandemic, further supporting key findings from the Contact Lens & Anterior Eye paper. The CDC additionally points out that personal eyeglasses and contact lenses do not qualify as personal protective equipment (PPE).

The Contact Lens & Anterior Eye paper also reviews why management of adverse events should be retained within optometric systems, offers guidance on sleeping in contact lenses, considers wearing modalities and lens materials, and offers areas for further study.

Unraveling interactions between metal ions and peptides in the body may eventually lead to improved treatments for diabetes, Alzheimer's and other diseases. Understanding these interactions is the focus of research, co-led by KAUST, that is revealing how metals, such as copper, can affect the formation of harmful clumps of misfolded peptide clusters called fibrils, which underpin many diseases.

Errant peptides are linked to neurological conditions such as Alzheimer's, as well as to blood sugar control disease diabetes. Blood sugar levels are normally controlled via peptide hormones released by specialist cells called β-cells. As well as insulin, healthy β-cells also release amylin, a peptide hormone that helps to reduce spikes in blood sugar level after eating by slowing stomach emptying. But amylin is prone to forming misfolded clumps, especially in the presence of copper ions, that damage β-cells and contribute to type II diabetes.

However, metal ions can also counteract peptide aggregation in some circumstances, says KAUST researcher, Mariusz Jaremko, who led the work in collaboration with researchers from the University of Wroclaw in Poland. To study the process in more detail, the team is examining the interaction between copper(II) ions and amylin and its molecular analogs. "Such knowledge would give us insights into the molecular mechanisms of type II diabetes, enabling us to design new strategies and therapies against this disease," Jaremko says.

In their latest work, the team studied the influence of copper ions on the aggregation of two analogs of human amylin: an amylin-mimicking drug called pramlintide and amylin from rats. "We found that differences in the structures of pramlintide and rat amylin mean that copper ions impede the aggregation of pramlintide, but not rat amylin," says Mawadda Alghrably, a Ph.D. student in Jaremko's team.

The researchers investigated the process using multiple techniques, including nuclear magnetic resonance (in collaboration with Abdul-Hamid Emwas from KAUST CoreLabs), and a "thioflavin T" fluorescence assay of protein aggregation. They found that although both amylin analogs bind copper, pramlintide could bind it in two different ways due to an extra copper-binding histidine amino acid that is present in pramlintide but not rat amylin. Copper-ion binding to this histidine probably explained why copper reduced pramlintide aggregation but not rat amylin aggregation, the researchers concluded.

The team is continuing to decipher the molecular basis of amylin aggregation, Alghrably says. "Understanding how these molecules behave, could ultimately help to facilitate the design of new efficient drugs and therapies for type II diabetes," she says.

In a new study, published in the journal Nature, Michigan State University scientists show how plant genes select which microbes get to live inside their leaves in order to stay healthy.

This is the first study to show a causal relationship between plant health and assembly of the microbial community in the phyllosphere -- the total above-ground portions of plants. The work suggests that organisms, from plants to animals, may share a similar strategy to control their microbiomes.

Microbiome studies are a hot topic in human health science. When scientists mention that human 'gut bacteria' should be well balanced, they refer to the gut microbiome, the genetic material of all the microbes living in human digestive systems.

"The field of large-scale plant microbiome study is only about a decade old," said Sheng Yang He, lead co-author of the study, a member of the MSU-DOE Plant Research Laboratory and a Howard Hughes Medical Institute Investigator. "We want to know if plants need a properly assembled phyllosphere microbiome.

Plant genes: Gatekeepers of microbes:

"In nature, plants are bombarded by zillions of microbes," said He, a University Distinguished Professor who holds joint appointments in the Department of Plant Biology and the Department of Microbiology and Molecular Genetics in the MSU College of Natural Science. "If everything is allowed to grow in the plants, it would probably be a mess. We want to know if the numbers and types of microbes matter, if there is a perfect composition of microbes. If so, do plants have a genetic system to host and nurture the right microbiome?"

It seems plants do. The newly discovered mechanism involves two genetic networks. One involves the plant immune system and the other controls hydration levels inside leaves. Both networks work together to select which microbes survive inside of plant leaves.

"When we remove both networks from a plant, the microbiome composition inside the leaves changes," He said. "The numbers and mix of bacteria types are abnormal, and our team sees symptoms of tissue damage in plants."

"The symptoms are conceptually like those associated with inflammatory bowel disease in humans," he said. "This is probably because the genes involved are ancient, in evolutionary terms. These genes are found in most plants, while some even have similarities to those involved in animal immunity. "

According to the scientists in the He lab, this may be the first time dysbiosis-associated sickness is formally described in the plant kingdom. The fact it seems conceptually similar to human health suggests a fundamental process in life.

Developing new tech to determine causality:

The reason it is difficult to find causality in microbiome studies is because it is practically impossible to cut through the noise of zillions of microbes.

The He lab has worked around this problem by developing a germ-free growth chamber they call the gnotobiotic system - an environment for rearing organisms in which all the microorganisms are either known or excluded.

"Very few people have grown a sterile plant in sterile, organic-rich material," He said. "Our system uses a peat-based soil-like substrate, basically greenhouse potting soil. We use heat and pressure to kill all the germs in the soil, and the plants can grow under this germ-free condition."

Researchers can then introduce microbes in a controlled fashion, into this environment.

"You can add one, two, or even a community of bacteria," He said. "In our study, we extracted a community of bacteria from dysbiotic, or sick, plants and introduced them to our healthy plants, and vice-versa. We found that both the microbiome composition and the plant genetic systems are required for plant health."

For example, a plant with defective genetics could not take advantage of a microbiome transplanted from a healthy plant. The microbiome slowly reverted to the state that caused sickness.

On the other end, a healthy plant exposed to a sick plant's microbiome also suffered. Although it had the genetic tools to select the right microbes, microbe availability was limited and abnormal. The plant couldn't fix the situation.

Microbe levels and composition matter:

It turns out that increased microbiome diversity correlates with plant health. Somehow, plant genes are gatekeepers that encourage this diversity.

The sick plants in the study had 100 times more microbes in a leaf, compared to a healthy plant. But the population was less diverse. To figure out why, the scientists did thousands of one-on-one bacteria face-offs to tease out which strains were aggressive.

In the sick plants, proteobacteria strains - many of which are harmful to plants - jumped from two-thirds the composition of a healthy microbiome to 96% in the abnormal population. Fermicutes strains, many which may be helpful to plants, went down in numbers.

"Perhaps, when the population of microbiome is abnormally higher in that sick plant, the microbes are physically too close to each other," He said. "Suddenly, they fight over resources, and the aggressive - in this case harmful - ones unfortunately win. Healthy plants seem to prevent this takeover from happening."

The big picture: Supporting plant health

The study is yet another example of how diversity is important to support healthy living systems. Each type of microbe might impart different benefits to plants, such as increased immunity, stress tolerance or nutrient absorption.

Scientists such as He want to be able to manipulate the plant genetic system to reconfigure the plant microbiome. Plants could become more efficient at selecting their microbial partners and experience improved plant health, resilience, and productivity.

"Our field is still young," He said. "Microbiome research tends to focus on human gut bacteria. But many more bacteria live on plant leaves, the lungs of our planet. It would be wonderful to understand how microbes impact the health of the phyllosphere in natural ecosystems and crop fields."

Molecules in tarantula venom could be used as an alternative to opioid pain killers for people seeking chronic pain relief.

University of Queensland researchers have designed a novel tarantula venom mini-protein that can potentially relieve severe pain without addiction.

Dr Christina Schroeder from UQ's Institute for Molecular Bioscience said the current opioid crisis around the world meant urgent alternatives to morphine and morphine-like drugs, such as fentanyl and oxycodone, were desperately needed.

"Although opioids are effective in producing pain relief, they come with unwanted side-effects like nausea, constipation and the risk of addiction, placing a huge burden on society," Dr Schroeder said.

"Our study found that a mini-protein in tarantula venom from the Chinese bird spider, known as Huwentoxin-IV, binds to pain receptors in the body.

"By using a three-pronged approach in our drug design that incorporates the mini-protein, its receptor and the surrounding membrane from the spider venom, we've altered this mini-protein resulting in greater potency and specificity for specific pain receptors.

"This ensures that just the right amount of the mini-protein attaches itself to the receptor and the cell membrane surrounding the pain receptors."

Dr Schroeder said the mini-protein had been tested in mouse models and shown to work effectively.

"Our findings could potentially lead to an alternative method of treating pain without the side-effects and reduce many individuals' reliance on opioids for pain relief," she said.

Scientists at the Severinov Laboratory in Skoltech and their colleagues from Russia and the US have uncovered a new mechanism of bacterial self-defense against microcin C, a potent antibiotic weapon in the microscopic world that can sometimes turn on its master.

Microcin C is a peptide-nucleotide antibiotic produced by some strains of Escherichia coli. It is essentially a Trojan horse: its peptide part helps it get into a cell, where the cell's own internal machinery turns it into what's called "processed McC". This compound completely blocks protein biosynthesis by interfering with its crucial component, aspartyl-tRNA synthetase.

Unfortunately for the microcin C producer, some of the "Greeks" in this metaphor inevitably escape from the "horse" too early, while it is still inside the producing cell, which leads to self-intoxication. That is why the producing cell has to get creative in developing defenses against its own weapon; one of these defenses is an enzyme that acetylates processed McC, rendering it useless.

Skoltech PhD student Eldar Yagmurov and his colleagues have found another way cells can protect themselves -- histidine-triad (HIT) superfamily hydrolases (that is, enzymes that break a larger molecule into smaller ones using water).

"HIT hydrolases have long been suspected to be involved in the mechanisms of self-defense against microcin C. One particular enzyme in this family is known to break the bond between phosphorus and nitrogen that connects the two parts in a complex very similar to McC -- so we figured there might be some other member of the superfamily that can work against microcin C," says Yagmurov.

The researchers used bioinformatics to predict a cluster in the genome of Hyalangium minutum, a Gram-negative bacterium, that encodes the production of its McC-like compounds and a particular HIT superfamily phosphoramidase that they suspected might provide self-immunity to these antibiotics. Experiments showed that this was indeed true: the enzyme apparently destroys the bond between the "transport" and "warhead" parts of processed McC, deactivating the latter.

"By studying the naturally existing means of antibiotic resistance, especially for a promising antimicrobial agent such as McC, we can try to be one step ahead of the bacteria and modify the antibiotic in a way that would help it evade these natural defenses", Yagmurov adds.

According to the paper, other bacteria may have their own analogues of the H. minutum HIT enzyme, each protecting against a specific McC-like compound that they use to survive in the tough bacterial world. This also implies a plethora of yet-unidentified McC-like compounds, some of which may have the potential to become practically used antibiotics of the future.

LOS ANGELES (April 11, 2020) -- In a small group of patients hospitalized with severe complications of COVID-19 and treated with the experimental antiviral drug remdesivir, clinical improvement was observed in 68% of patients treated, according to an analysis co-authored by Jonathan Grein, MD, director of Hospital Epidemiology at Cedars-Sinai.

The experimental therapy was given to patients through a "compassionate use" program that allows providers access to treatments not yet approved by the Food and Drug Administration when a patient has a life-threatening condition and no other options are available.

The analysis, published online today by The New England Journal of Medicine, evaluated data from 53 patients in the U.S, Europe, Canada and Japan who received at least one dose of remdesivir by March 7. The effort was led by Gilead Sciences, the pharmaceutical company that makes the experimental drug.

The study shows:

68% of patients treated with remdesivir demonstrated an improvement in the level of oxygen support they needed over a median follow-up of 18 days from the first dose of the drug.

Of the 34 patients who had been intubated and required support from mechanical ventilators (breathing machines), 57% had their breathing tubes taken out.

47% of all patients were discharged from the hospital following treatment with remdesivir

"Currently there is no proven treatment for COVID-19. We cannot draw definitive conclusions from these data, but the observations from this group of hospitalized patients who received remdesivir are hopeful," said Grein, who also leads the Special Pathogens Response Team at Cedars-Sinai. "We look forward to the results of controlled clinical trials to potentially validate these findings."

Cedars-Sinai is continuing to explore remdesivir as a therapeutic option for patients as part of a large international randomized controlled study sponsored by the NIH.

Compassionate use programs are less stringent than a randomized controlled study, which compares patients who are receiving the experimental treatment to patients receiving the standard treatment. However, during the COVID-19 pandemic, compassionate use data can help scientists understand potential risks and can offer a glimpse into whether an experimental treatment might or might not be viable.

"It's critical that the medical community finds a safe and effective treatment for COVID-19 that's supported by solid data," Grein said. "I'm very proud that Cedars-Sinai is contributing to the global effort to find that solution."

What The Study Did: This case series describes clinical characteristics of patients who died of coronavirus disease 2019 (COVID-19) in China.

Authors: Haibo Qiu, M.D., Ph.D., of Zhongda Hospital, Southeast University in Jiangsu, China, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.5619)

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

What The Article Says: An essay discusses the challenges associated with caring for patients with cancer during the COVID-19 epidemic in Italy.

Authors: Filippo Pietrantonio, M.D., and Marina Chiara Garassino, M.D., of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, are the authors.

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

(doi:10.1001/jamaoncol.2020.1426)

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

What The Study Did: This study investigates the neurologic symptoms of patients with coronavirus disease 2019 (COVID-19) in Wuhan, China.

Authors: Bo Hu, M.D., Ph.D., and Yanan Li, M.D., Ph.D., of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, are the corresponding authors.

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

(doi:10.1001/jamaneurol.2020.1127)

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

What The Viewpoint Says: The article emphasizes the importance of mitigating the mental health consequences of social distancing in the COVID-19 era.

Authors: Sandro Galea, M.D., of the Boston University School of Public Health, is the corresponding author.

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

(doi:10.1001/jamainternmed.2020.1562)

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

What The Viewpoint Says: Reasons why U.S. suicide rates may rise in tandem with the coronavirus disease 2019 (COVID-19) pandemic are explained in this article that also describes opportunities to expand research and care.

Authors: Mark A. Reger, Ph.D., of the VA Puget Sound Health Care System, and  Seattle, Washington; and the University of Washington in Seattle, is the corresponding author.

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

(doi:10.1001/jamapsychiatry.2020.1060)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

What The Viewpoint Says: This article offers lessons from Hubei, China, on potential methods to focus on mental health during the coronavirus disease 2019 (COVID-19) pandemic.

Authors: Yu-Tao Xiang, M.D., Ph.D., of the University of Macau in the Macao Special Administrative Region, China, is the corresponding author.

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

(doi:10.1001/jamapsychiatry.2020.1057)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

While everybody agrees that our blue planet is rich in water, this observation is at odd, first, with the exploration of other rocky planets, genuinely lacking surface water, and second, with the idea of a giant impact between the proto-Earth and a planetary embryo the size of Mars that created the Moon. Such a catastrophic event should have vaporized any pre-existing water, leaving behind a dry Earth. After the giant impact catastrophe, we have thus two options to explain the presence of water on Earth : either water was brought back later, after the catastrophe, notably by icy or water-rich asteroids; or the giant impact was not big enough to vaporize all the water on Earth.

Because of the importance of water to sustain life, the question of the origin of water on Earth is primordial. A major challenge in investigating this question is that Earth has lost all the traces of its formation since it is an active planet.

A team of numerical modelers and geochemists led by Cédric Gillmann - Université libre de Bruxelles, ULB, funded by the EoS project ET-HoME - has decided to look far beyond Earth - up to Venus - to investigate the origin of terrestrial water.

While Earth and Venus could be considered as twin sisters, their respective geological and climatic evolutions diverged dramatically in the past, leading to Venus' present-day 92 bar atmosphere heated by an infernal greenhouse up to 470°C, opposed to the mild conditions and only 1 bar pressure at the surface of Earth.

However, Venus' volcanic activity and outgassing are reduced compared to Earth, because it has no plate tectonics, but has a stagnant lid instead. Even better, such a convection mode implies very little recycling of volatile species into the mantle.

As such, despite being an inferno, the evolution of the atmosphere of Venus is much easier to understand and model over geological times. In addition, because of their proximity, the Earth and Venus should have received the same type of material during their history. All these aspects combine to make Venus a perfect place to study the primitive evolution of terrestrial planets.

Using numerical simulations of impacts of different types of asteroids containing various amount of water, the team has discovered that water-rich asteroids colliding with Venus and releasing their water as vapor cannot explain the composition of Venus atmosphere as we measure it today. It means that the asteroidal material that came to Venus, and thus to Earth, after the giant impact must have been dry, therefore preventing the replenishment of the Earth in water.

Because water can obviously be found on our planet today, it means that the water we are now enjoying on Earth has been there since its formation, likely buried deep in the Earth so it could survive the giant impact.

This idea has very deep implications in terms of habitability of ancient Earth, Venus and Mars, as it suggests that planets likely formed with their near-full budget in water, and slowly lost it with time. Because Mars is much smaller, it likely lost all its water while life developed on Earth. For Venus, those results shine a complementary light on recent work advocating that water oceans existed at the surface of the planet, and help constrain the maximum amount of water that can be expected on Venus. They will also help prepare the next generation of space missions to Venus.