Culture

Tiny particle, big payoff

image: Visually indistinguishable particles of Brome Mosaic Virus.

Image: 
Ayala Rao/UCR

UC Riverside scientists have solved a 20-year-old genetics puzzle that could result in ways to protect wheat, barley, and other crops from a devastating infection.

Ayala Rao, professor of plant pathology and microbiology, has been studying Brome Mosaic virus for decades. Unlike some viruses, the genetic material of this virus is divided into three particles that until now were impossible to tell apart.

"Without a more definitive picture of the differences between these particles, we couldn't fully understand how they work together to initiate an infection that destroys food crops," Rao said. "Our approach to this problem has brought an important part of this picture into very clear focus."

A paper describing the work Rao's team did to differentiate these particles was recently published in the Proceedings of the National Academy of Sciences.

Inside each of the particles is a strand of RNA, the genetic material that controls the production of proteins. The proteins perform different tasks, some of which cause stunted growth, lesions, and ultimately death of infected host plants.

Two decades ago, scientists used the average of all three particles to create a basic description of their structure. In order to differentiate them, Rao first needed to separate them, and get them into their most pure form.

Using a genetic engineering technique, Rao's team disabled the pathogenic aspects of the virus and infused the viral genes with a host plant.

"This bacterium inserts its genome into the plant's cells, similar to the way HIV inserts itself into human cells," Rao said. "We were then able to isolate the viral particles in the plants and determine their structure using electron microscopes and computer-based technology."

Now that one of the particles is fully mapped, it's clear the first two particles are more stable than the third.

"Once we alter the stability, we can manipulate how RNA gets released into the plants," Rao said. "We can make the third particle more stable, so it doesn't release RNA and the infection gets delayed."

This work was made possible by a grant from the University of California Multicampus Research Program and Initiatives. Professors Wiliam Gelbart and Hong Zhou of UCLA, as well as graduate students Antara Chakravarthy of UCR and Christian Beren of UCLA, made significant contributions to this project.

Moving forward, Rao is hoping to bring the other two viral particles into sharper focus with the expertise of scientists at UCLA and UC San Diego.

Brome Mosaic virus primarily affects grasses such as wheat and barley, and occasionally affects soybeans as well. According to Rao, it is nearly identical to Cucumber Mosaic virus, which infects cucumbers as well as tomatoes and other crops that are important to California agriculture.

Not only could this research lead to the protection of multiple kinds of crops, it could advance the understanding of any virus.

"It is much easier to work with plant viruses because they're easier and less expensive to grow and isolate," Rao said. "But what we learn about the principles of replication are applicable to human and animal viruses too."

Credit: 
University of California - Riverside

UHN-U of T-led study shows antiviral drug can speed up recovery of COVID-19 patient

image: Dr. Eleanor Fish working in her lab at University Health Network, Toronto.

Image: 
University Health Network

(Toronto - May 15, 2020) - An international team of researchers led by Dr. Eleanor Fish, emerita scientist at the Toronto General Hospital Research Institute, University Health Network, and professor in the University of Toronto's Department of Immunology, has shown for the first time that an antiviral drug can help speed up the recovery of COVID-19 patients.

According to the new study, published today in Frontiers in Immunology, treatment with interferon(IFN)- α2b may significantly accelerate virus clearance and reduce levels of inflammatory proteins in COVID-19 patients.

The research team found that treatment with this drug, which has been used clinically for many years, significantly reduced the duration of detectable virus in the upper respiratory tract, on average by about 7 days. It also reduced blood levels of interleukin(IL)-6 and C-reactive protein (CRP), two inflammatory proteins found in COVID-19 patients.

Dr. Fish says that the research team considered IFN-α therapy for COVID-19 after they demonstrated interferon provided therapeutic benefit during the SARS outbreak of 2002 and 2003.

"Rather than developing a virus-specific antiviral for each new virus outbreak, I would argue that we should consider interferons as the 'first responders' in terms of treatment," says Dr. Fish.

"Interferons have been approved for clinical use for many years, so the strategy would be to 'repurpose' them for severe acute virus infections."

Boosting a natural defense mechanism

Interferons are a group of signaling proteins released by the human body in response to all viruses. As Dr. Fish explains, they are a "first line of defense."

They target different stages of a virus's life cycle, inhibiting them from multiplying. They also boost an immune response by activating different immune cells to clear an infection. Some viruses, however, can block this natural defense mechanism.

"But it is possible to override this block. If a virus blocks interferon production, then treating with interferon can offset this."

Study details

The researchers conducted this exploratory study on a group of 77 patients with COVID-19 in Wuhan, China. These patients were admitted to Union Hospital, Tongii Medical College, between January 16 and February 20, 2020. They represented moderate cases of the disease as none of the patients required intensive care or prolonged oxygen supplementation or intubation.

Despite the study's limitations of a small, non-randomized group of patients, the work provides several important and novel insights into COVID-19 disease, notably that treatment with IFN-α2b can accelerate viral clearance from the upper respiratory tract and also reduce circulating levels of inflammatory factors that are associated with severe COVID-19.

Dr. Fish says a randomized clinical trial is a crucial next step. According to her, a clinical trial with a larger group of infected patients who are randomized to treatment or placebo would further this research.

In the meantime, the findings from this study are the first to suggest therapeutic efficacy of IFN-α2b as an available antiviral intervention for COVID-19, which may also benefit public health measures by shortening the duration of viral clearance and therefore slowing the tide of the pandemic.

Credit: 
University Health Network

Enhancement of bitter taste sensor reduces salt intake and improves cardiovascular dysfunction

image: Long-term high salt intake impairs TRPM5 activity on tongue epithelial cells.

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©Science China Press

High salt intake is a well-known risk factor of hypertension and cardiovascular diseases. Reducing salt intake can significantly lower blood pressure and ameliorate target organ damage caused by hypertension. However, in the past three decades, several strategies have failed to decrease daily salt intake to an optimal level. Therefore, it is important to identify alternative approaches for reducing excessive salt intake and antagonizing high salt-induced hypertension.

Salt taste perception is an important factor in determining salt intake at an individual level. Previous studies have shown that aversion induced by salt beyond the physiological concentration range is mediated by a bitter taste sensor-transient receptor potential channel M5 (TRPM5) in taste receptor cells. High salt stimuli might produce a bitter taste for a defensive response to reduce salt intake. Recently, Professor Zhiming Zhu's team from Army Medical University found that acute high-salt stimulation activated TRPM5-mediated bitter taste and increased aversion reaction. However, long-term high salt intake impairs the activity of the TRPM5 by inhibiting protein kinase C (PKC) activity and PKC-dependent threonine phosphorylation. "The TRPM5-mediated aversion response to high salt is weakened, which results in a progressive increase of high salt intake and increased blood pressure in mice fed with long-term high-salt-diet." Said Dr. Yuanting Cui, the first author of this work. These results were published in Hypertension recently.

On this basis, Professor Zhiming Zhu's team continued to explore how to restore TRPM5 function damage caused by long-term high salt intake. They found that long-term dietary intervention with bitter melon extract (BME) restored the TRPM5-mediated aversion to high salt stimuli in tongue epithelium, thus reduced excessive salt intake, and improved the cardiovascular damage in mice. Mechanistically, dietary BME inhibited high salt-induced RhoA/Rho kinase activation, leading to reduced phosphorylation levels of myosin light chain kinase and myosin phosphatase targeting subunit 1. Furthermore, cucurbitacin E (CuE), the major active compound in BME, also inhibited vasoconstriction by attenuating L-type Ca2+ channel-induced Ca2+ influx in vascular smooth muscle cells. "We found that BME and CuE increased TRPM5 expression and function in tongue epithelium. Therefore, the mice fed with high salt plus BME diet showed a lower salt intake, and improved the high salt-induced hypertension and cardiac hypertrophy compared with mice only fed with high-salt diet." said Dr. Hao Wu, the first author and Prof. Zhiming Zhu, the corresponding author of this work. These results were published in SCIENCE CHINA Life Sciences recently.

These encouraging results from Professor Zhu's team provide further suggestions for promoting the use of dietary factors to reduce salt consumption. Enhancing bitter taste function by dietary bitter melon might provide a promising approach for antagonizing excessive salt intake and preventing of high salt-induced cardiovascular dysfunction.

Credit: 
Science China Press

One in ten patients with major vascular event, infection, or cancer will be misdiagnosed

According to a new study published in De Gruyter's open access journal "Diagnosis", approximately one in 10 people (9.6%) in the United States with symptoms caused by major vascular events, infections, or cancers will be misdiagnosed.

The study's authors, led by David E. Newman-Toker from the Johns Hopkins University School of Medicine and CRICO Strategies, analyzed modern, U.S.-based studies and literature-based estimates to calculate rates of diagnostic error and related harms.

Based on the analysis, the authors provide estimates of diagnostic error and serious misdiagnosis-related harm rates (i.e., misdiagnoses that result in permanent disability or death) for each of the five most frequently misdiagnosed major vascular events, infections, and cancers. In total, these 15 diseases represent roughly half of all diagnostic error-related permanent disabilities or deaths in the U.S. health system and suggest a focal area for quality improvement efforts.

Of the people with the most-commonly misdiagnosed major vascular events, infections, and cancers, roughly half (53.9%) suffer a permanent disability or die because of the error.

According to the study, the most uncommon infections and major vascular events are most likely to be misdiagnosed. Among the 15 diseases analyzed, spinal abscesses (an infection that can compress the spinal cord and cause paraplegia) was the disease most often missed (62.1%). More than one in four aortic aneurysms and dissections have a critical delay in diagnosis (27.9%). More than one in five (22.5%) lung cancer diagnoses are also meaningfully delayed.

The authors say the study should be used to target efforts to improve diagnosis among these conditions. They note that misdiagnoses of major vascular events, infections, and cancers do not appear to have declined over the last several decades. For some conditions, such as stroke and aortic aneurysms, they may even be rising.

"With this insight, health care leaders and clinicians can focus their resources and interventions to target these vulnerabilities," said Dana Siegal, Director of Patient Safety at CRICO Strategies and study co-author.

Credit: 
De Gruyter

Treatment guidance for lung cancer patients during the COVID-19 pandemic

Lung cancer patients are at heightened risk for COVID-19 and the reported high mortality rate among lung cancer patients with COVID-19 has given pause to oncologists who are faced with patients with not one, but two severe, life-threatening diseases.

To help oncologists address the many challenges COVID-19-positive lung cancer patients present, a team of global lung cancer specialists this week published a review of lung cancer treatments for patients with COVID-19 in the current issue of the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer (IASLC).

"The purpose of this manuscript is to present a practical multidisciplinary and international overview to assist in treatment for lung cancer patients during this pandemic, with the caveat that evidence is lacking in many areas," said lead author Chandra Belani, MD, chief science officer for the IASLC, Professor of Medicine and Oncology at the Penn State College of Medicine and Penn State Cancer Institute.

As a group, lung cancer patients tend to be older and have an increased risk of relative immunosuppression from the underlying malignancy and from anti-cancer treatments. Furthermore, patients with lung cancer may have additional comorbidities, including a history of smoking and pre-existing lung disease.

"A major consideration in the delivery of cancer care during the pandemic is to balance the risk of patient exposure and infection with the need to provide effective cancer treatment," Belani writes.

The rapid onset of the COVID-19 infection requires careful consideration of urgent decisions to treat lung cancer. Treatment decisions balancing the risk of exposure with effective care require close multidisciplinary discussions and thorough deliberation between caregivers and patients. The duration and severity of the COVID-19 pandemic are unclear, and treatment delay alone will be insufficient to provide optimal treatment to cancer patients.

"In combination with determining a treatment path for lung cancer, physicians should educate patients to help them prevent further spread of COVID-19 according to WHO and CDC guidelines," Belani urged colleagues.

COVID-19 complicates cancer care further by forcing patients into self-isolation to protect themselves, other patients, providers, and family members.

"Self-isolation goes against best practices for treating cancer patients, which often calls for joining support groups, reaching out to loved ones and family members for assistance and remaining active," Belani said. "The decision regarding immediate vs. delayed treatment during the COVID-19 pandemic should balance the delay of treatment in the presence of existing co-morbidities vs. the possible harm from COVID-19."

Belani and his co-authors include advice to clinicians that intersects with virtually all lung cancer patients, including those with early-stage lung cancer, locally advanced lung cancer, COVID-19 and immunotherapy, advanced stage non-small cell lung cancer and small cell lung cancer.

Credit: 
International Association for the Study of Lung Cancer

Model of critical infrastructures reveals vulnerabilities

image: The beef supply chain and transportation industries are interdependent critical infrastructures and need safeguarding according to a computer simulation model developed by Kansas State University researchers.

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Kansas State University

MANHATTAN, KANSAS -- An interdisciplinary team of Kansas State University researchers developed a computer simulation that revealed beef supply chain vulnerabilities that need safeguarding -- a realistic concern during the COVID-19 pandemic.

Caterina Scoglio, professor, and Qihui Yang, doctoral student, both in electrical and computer engineering, recently published "Developing an agent-based model to simulate the beef cattle production and transportation in southwest Kansas" in Physica A, an Elsevier journal publication.

The paper describes a model of the beef production system and the transportation industry, which are interdependent critical infrastructures -- similar to the electrical grid and computer technology. According to the model, disruptions in the cattle industry -- especially in the beef packing plants -- will affect the transportation industry and together cause great economic harm. The disruptions modeled in the simulation share similarities with how the packing plants have been affected during the COVID-19 pandemic.

"When we first started working on this project, there was a lot of emphasis on studying critical infrastructures; especially ones that are interdependent, meaning that they need to work together with other critical infrastructures," Scoglio said. "The idea is if there is a failure in one of the systems, it can propagate to the other system, increasing the catastrophic effects."

The study included a variety of viewpoints to create a realistic and integrated model of both systems. Co-authors on the paper include Don Gruenbacher, associate professor and department head of electrical and computer engineering; Jessica Heier Stamm, associate professor of industrial and manufacturing systems engineering; Gary Brase, professor of psychological sciences; Scott DeLoach, professor and department head of computer science; and David Amrine, research director of the Beef Cattle Institute.

The researchers used the model to evaluate which supply chain components were more robust and which were not. They determined that packing plants are the most vulnerable. Scoglio said that recent events in the middle of the COVID-19 pandemic raise important issues about how to safeguard the system.

"An important message is that after understanding the critical role of these packers, we need to decide how we could protect both them and the people who work there," Scoglio said. "While the plants are a critical infrastructure and need to be protected, taking care of the health of the workers is very important. How can we design a production process that can be flexible and adaptable in an epidemic?"

According to the paper, the beef cattle industry contributes approximately $8.9 billion to the Kansas economy and employs more than 42,000 people in the state. Since trucks are needed to move cattle, any disruption in either cattle production or transportation almost certainly would harm the regional economy, Scoglio said.

"Packers need to be considered as a critical point of a much longer supply chain, which needs specific attention to make sure it will not fail and can continue working," Scoglio said. "Beef packers are a critical infrastructure in the United States."

The project was supported by the National Science Foundation and focused on southwest Kansas, but the researchers acknowledge that cattle come from outside the region and interruptions may have larger national effects.

Credit: 
Kansas State University

University of Tartu study shows a low prevalence of the coronavirus in Estonia

image: In a cross-sectional study consisting of eight survey waves, the researchers of the University of Tartu will ascertain the actual prevalence of the coronavirus and the progress of the epidemic in Estonia. A random statistical sample of 16,000 to 20,000 people will be studied across Estonia to give the state evidence-based data to form the strategy for the gradual exit from the emergency situation.

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University of Tartu

The results of a study conducted by the University of Tartu on the prevalence of the coronavirus were presented to the Government Committee responsible for the emergency situation on Tuesday. The results from the second week of the study continue to confirm the low prevalence of the virus in Estonia.

In two weeks, based on random selection, a total of 6,024 adult residents have been interviewed and 4,728 tested in the course of the study. A total of 12 cases of the coronavirus have been identified, of which seven had been diagnosed with the virus prior to the study and six had recovered by the time of the study.

The results allow to conclude that the infection is not widely spread in the society, and that the prevalence of the coronavirus remains stable over the weeks. The researchers consider the gradual easing of the restrictions justified.

"We will continue our successful cooperation with the researchers of the University of Tartu, whose study helps us assess the prevalence of the virus in the society. This will be even more important in two weeks, when we can evaluate the impact of the easing of restrictions that come into force this week on the wider spread of the infection," said Prime Minister Jüri Ratas.

The prime minister pointed out that yesterday, another group of researchers from the University of Tartu started work on an antibody-based seroepidemiological study in Saaremaa and Õismäe to help estimate the number of people who have been exposed to the coronavirus. "The work of the researchers is extremely important for us to be prepared for the second wave of the virus outbreak as soon as possible and to be able to respond to it promptly and efficiently," said Ratas.

In the second week of the study, 3,135 interviews were conducted and 2,495 adult residents were tested. The testing revealed eight cases of the coronavirus; six of the infected persons had been diagnosed with the virus prior to the study. The results of the first week were retroactively supplemented with 226 tests, one of them positive.

Professor Ruth Kalda, the head of the study of the University of Tartu, explained that when assessing the actual prevalence of the virus, it must be considered that six infected persons had battled the disease in March or early April and were currently considered healthy. Thus, only half of the positive cases were at risk of spreading the infection at the time of the study.

"As we can say on the basis of the first two waves that the prevalence of the virus in Estonia is low at the moment, we can take a two-week break and then see whether the opening of shopping centres has an impact on the spread of the virus. If necessary, we will conduct another wave of the study before the Midsummer's Day and if the epidemiological situation is stable, we will continue monitoring the spread of the virus in autumn," said Kalda.

The next wave of the study is scheduled to take place from 22 May to 28 May, i.e. almost two weeks after the partial reopening of shopping centres.

Credit: 
Estonian Research Council

Parents that know a child's preferences can assertively guide exercise

image: Parent participating in the activities with the child strengthen exercise motivation for the children.

Image: 
Tuukka Luukkonen / University of Jyväskylä

A parent who knows a child's preferences and participates in the activities can guide the child assertively without diminishing the child's enthusiasm for physical activity and exercise. However, children's enthusiasm to move was most commonly associated with child-centered and stimulating parenting. In an interview study conducted at the Faculty of Sport and Health Sciences of the University of Jyväskylä, children perceived coercion as reducing their motivation for physical activity.

Enthusiasm for physical activity and exercise was most often combined in children's thoughts with parenting that promotes freedom of movement, takes into account interests, offers hobby opportunities, and participates in exercise with the child. Children's enthusiasm for exercise was increased by a parental attitude that showed acceptance for the child's occasional lack of motivation. Parental control, meaning varying degrees of coercion and disregarding the child's role in exercise-related decision-making, was perceived as undesirable and reduced enthusiasm for exercise.

Children aged 7 to 10 years were found to have a clear distinction between parenting that increases and reduces exercise motivation.

"For example, strong, public and overt encouragement in tournaments and games was perceived in some cases as embarrassing and even shameful," explains postdoctoral researcher Arto Laukkanen. "In addition, underestimating and ignoring the temporary cessation of exercise motivation, for example, was perceived as controlling and reducing enthusiasm for exercise."

However, the interviews also highlighted experiences in which the parent's strong guidance and instruction was perceived as acceptable and increasing exercise enthusiasm.

"The children pointed out situations where the parent's actions had initially felt domineering and strict," Laukkanen says. "Common to experiencing such situations positively and strengthening exercise motivation was that the parent participated in the activities with the child. Secondly, these parents sensed the line between coercion and acceptable guidance in the child's mind."

Limiting screen time under the guise of exercise eats up the enthusiasm for exercise

A very typical unpleasant exercise experience for children was related to limiting screen time and the associated command that the child should go out to exercise.

"This is very contradictory, as parents try to take care of the children's screen time and adequate level of exercise, but at the same time they may be contributing to alienation from exercise," Laukkanen says. "Perhaps exercise should not be set in opposition to screen time, but one should strive to organize independent space for both of them in everyday life."

Some of the children's experiences were the opposite. Some felt that they had infinitely flexible and loose boundaries for screen time.

"Limiting screen time independently can be challenging, especially for children," Laukkanen says. "In some cases, children also apply considerable effort and ingenuity to create more screen time for the day."

Combining screen time limitations and adequate physical activity seems like a complex challenge in families with children. Further research on this topic is urgently needed from the perspectives of both children and parents.

The study included 79 first-, second-, and third-grade students. Children's perceptions of parenting that support exercise and physical activity motivation were examined through group interviews. The children participated in audio-recorded interviews lasting about half an hour in groups of an average of five pupils as part of a normal school day. Participation was voluntary.

Credit: 
University of Jyväskylä - Jyväskylän yliopisto

Asthma is associated with longer time on ventilators for younger COVID-19 patients

New data suggests that asthma is associated with longer time on ventilators for hospitalized younger patients with COVID-19. Patients with COVID-19 between the ages of 20 and 59 years old who also had asthma needed a ventilator to assist with breathing for five days more on average than non-asthmatic patients with COVID-19, according to researchers at Rush University Medical Center, who published their findings today in The Journal of Allergy and Clinical Immunology: In Practice.

"Among the patients who developed severe respiratory symptoms requiring intubation (the use of a ventilator), asthma was associated with a significantly longer intubation time in the younger group of patients who would seemingly have a better disease course than patients over the age of 65," said Dr. Mahboobeh Mahdavinia, chief of allergy and immunology in the Department of Internal Medicine at Rush University Medical Center.

"Our findings suggest that younger individuals with asthma may require extra attention, as they could develop a sustained pulmonary failure with COVID-19 infection, leading to prolonged mechanical ventilation."

Some signs and symptoms of COVID-19 are similar to worsening of asthma, which can lead to a late diagnosis of COVID-19 in asthmatics. "Therefore, we looked at a large group of patients to understand the impact of preexisting asthma on the outcome of patients with COVID-19," Mahdavinia said.

"We found that asthma and obesity are connected in COVID-19 patients, which means that obesity coupled with asthma puts a patient at a significantly higher risk. This is the first report, to our knowledge, to study the role of asthma on the outcome of COVID-19 patients."

Mahdavinia's team of physician-scientists, medical residents, basic scientists and students used an electronic medical record algorithm created by the information services team at Rush to identify patients with asthma and COVID-19 who were either hospitalized or tested for COVID-19 at Rush between the dates of March 12 and April 3.

IBM SPSS Statistics for Windows was used for analysis of COVID-19 outcomes in association with asthma and were adjusted for demographic variables and body mass index (BMI).

Initially, data emerged for 1,003 patients who tested positive for COVID-19. Complete data on demographic variables, asthma, and COVID-19 management was available in 935 patients, who were used for analysis. Overall, 241 were found to have an established diagnosis of asthma, which were broken into three groups by age range.

Asthma was significantly associated with longer intubation time in patients between 18 and 49 years of age and between 50 and 64 years of age, but not in the age group 65 years of age and older. Duration of hospitalization was longer among patients with a history of asthma compared to those without this history in patients aged 50 to 64 years, but not in the younger or older age groups. The patients aged 50 to 64 on average spent two more days in the hospital than the non-asthmatics in this age group.

Asthma was not associated with a higher rate of death or with acute respiratory distress syndrome among COVID-19 patients.

"In other studies, both obesity and gender have been shown to affect COVID-19 hospitalization," said Mahdavinia. "In our study, asthma was also associated with female gender and higher BMI."

The analysis, which was adjusted for both obesity and gender, indicates that asthma is independently linked to the amount of time patients needed to be on ventilators.

"We were able to confirm asthma in prior clinical documentation among 73% of patients, but some cases were self-reported upon screening. We think that patients with a history of asthma may have sought out COVID-19 testing more than others due to concern and overlapping symptoms," Mahdavinia said.

Credit: 
Rush University Medical Center

Federal program leads to intensified treatment for high-risk heart patients

DALLAS, May 15, 2020 -- When health care providers enrolled in a federal program that provides financial payments for monitoring and reducing cardiovascular risk in high-risk patients, they assessed patient risk and prescribed cholesterol-lowering and blood pressure-lowering medication more often, according to research presented today at the American Heart Association's Quality of Care & Outcomes Research Scientific Sessions 2020. The virtual conference, May 15-16, is a premier global exchange of the latest advances in quality of care and outcomes research in cardiovascular disease and stroke for researchers, healthcare professionals and policymakers.

As part of a broader initiative to prevent one million heart attacks and strokes in the United States over five years, the Centers for Medicare and Medicaid Services launched the Million Hearts Cardiovascular Disease Risk Reduction Model (Million Hearts®). The model pays health care providers for measuring each of their Medicare patients' risk of having a heart attack and stroke over 10 years and for reducing that risk among their high-risk patients.

The model specifically targets Medicare beneficiaries ages 40-79 who have not had a previous heart attack or stroke. As part of a five-year, cluster-randomized trial, providers calculated their Medicare patients' risk of having a heart attack or stroke within 10 years, and received incentives to provide care to reduce the risk among high-risk patients (those with 30% or higher risk of a cardiovascular event at the beginning of the study).

Analysis of the first two years of the Million Hearts program found:

Within six months of enrollment in the program, people identified as high-risk at a Million Hearts® center were more likely to initiate or intensify statin therapy or anti-hypertensive medications compared to high-risk people in the control group (28% vs. 24%, respectively).

Million Hearts® providers indicated they were nearly twice as likely than the control group of providers to assess risk in at least half of their Medicare patients (71% vs. 39%, respectively).

Overall, 300,550 Medicare beneficiaries were enrolled in the study across 516 primary and specialty practices, health centers and hospitals throughout the U.S. Half of the enrolled centers were assigned to the intervention group and utilized the Million Hearts® Model.

Credit: 
American Heart Association

Indigenous protection

The global reach of COVID-19 is unquestionable. Every day, news reports highlight the disease's increasing toll on countries and major cities around the world.

However, little attention is paid to indigenous populations worldwide who may be especially vulnerable to COVID-19 but are largely excluded from most national or regional efforts to curb the spread of the disease. Even in high-income countries, indigenous groups like the Navajo have been hit hard by COVID-19, with per capita infection rates rivaling those of New York and New Jersey.

A team of anthropologists, physicians and tribal leaders has developed a strategy for mitigating the impact of COVID-19 among the Tsimane, an indigenous population in the Bolivian Amazon. Led by UC Santa Barbara's Michael Gurven and Hillard Kaplan of Chapman University, their multiphase plan brings together relevant stakeholders to best serve Tsmane interests. They hope to provide a general template that can be applied to other indigenous groups, and to promote a wider discussion on how to adapt strategies to local circumstances, with the goal of minimizing harm to indigenous populations due to the SARS-CoV-2 pandemic.

Their work is published in the journal The Lancet.

"In Bolivia, most attention is focused in the cities, where the pandemic first appeared. Indigenous communities have not been part of any organizational plan," said Daniel Eid Rodriguez, the paper's Bolivian co-author and a physician working with the Tsimane Health and Life History Project since 2005. "Although resources in Bolivia and other countries are too limited to create the ideal response plan, there are many people and organizations who are ready to help. Finding and building collaboration is key for the success of any COVID-19 plan."

To reach a wider audience, the authors have published their paper not only in English, but also in Spanish, Portuguese and French -- languages spoken in countries where many indigenous people reside.

"We've been working with the Tsimane and other indigenous groups in Bolivia for almost two decades," said Gurven, co-director of the Tsimane Health and Life History Project. Research operations shut down in mid-March, as did most activity worldwide, but he and his team recognized that indigenous groups living in remote areas may be especially vulnerable to COVID-19, given their limited access to up-to-date information and appropriate health care.

So building on their years of active involvement with Tsimane health care, the researchers initiated conversations with tribal authorities and other local officials. Together, they began working on a plan, first to get folks informed and prepared, and then to act once COVID-19 hit the region.

"After a teenage Yanomami boy died of COVID-19 there was, understandably, a lot of panic about the potential plight of indigenous populations around the world in light of this new, unpredictable threat," Gurven said. "Since our team had already been working with the Tsimane to try and work out a reasonable plan, we thought it would be a great opportunity to move the conversation toward a concrete blueprint that could, hopefully, be adapted to work in similar areas."

While every individual around the world is vulnerable to COVID-19 because it is new and no one has developed any immunity, many indigenous communities are at additional risk because of widespread respiratory illness, including prior history of tuberculosis, bronchitis and lower respiratory tract infections and compromised immune function.

"These could make people more at risk of having COVID-19 complications," said Gurven. According to the World Bank, over 370 million indigenous people inhabit over 90 countries, in both rural and urban areas. Though health clinics may be present in rural areas, access and resources such as medication, portable oxygen and other treatments may be very limited. In Bolivia, the local hospital will likely be overloaded by the time COVID-19 reaches Tsimane villages, and the existing remote health outposts are not yet equipped to diagnose or treat COVID-19.

The potential for higher mortality among infected individuals makes COVID-19 more salient for indigenous populations, Gurven notes, for reasons different from those typically considered. "Indigenous elders are at greater risk because of their age and comorbidity; yet they are crucial for helping to pass on long-standing traditions," Gurven explained. "They are 'walking libraries,' the ones who transmit cultural practices, native language and rituals that are crucial to indigenous identity."

While certain elements of the indigenous populations make them more vulnerable to COVID-19, other factors may foster resilience. "Many indigenous populations maintain the ability to provide their own sustenance through farming, fishing, hunting and foraging activities," said Gurven. "The ability to get food in self-sustaining ways -- both in terms of the know-how and having use rights in native territories -- makes it easier for some indigenous communities to self-isolate and reduce COVID-19 exposure that might otherwise come from visits to nearby town."

"Tribal sovereignty also allows indigenous groups to make their own decisions, especially when it comes to restricting access to their communities," Gurven went on. "Also, strong family bonds and a tradition of community meetings helps provide everyone with the latest COVID-19 information and to coordinate action -- without the kind of political polarization we've seen in the U.S. that seems to shape what people know about COVID-19 and what should be done."

The multiphase plan he and his team developed began taking shape before COVID-19 was confirmed in the Beni region of Bolivia, where the Tsimane reside. The goal of Phase I was education and preparation. "Our team of trained Tsimane visited over 60 villages for awareness campaigns, using a variety of materials such as Centers for Disease Control posters translated to the Tsimane language," Gurven said. "In meetings, each community came up with a specific plan for collective isolation and for quarantining suspected cases."

They also developed a list of material needs to help with the collective isolation of Tsimane communities to minimize reliance on markets and outside merchants. Salt, for example, is used not just to flavor food, but also to preserve meat and fish. "So we made massive deliveries of these items to each community," said Gurven.

Phase II of the plan began when COVID-19 reached the Beni in mid-April. It focuses on implementing collective isolation containment of Tsimane communities, COVID-19 containment and patient management. "Our plan is adapted to a low-tech environment of inadequate hospital facilities and to lower population density where isolation is possible for whole communities," said Kaplan, co-director of the Tsimane Health and Life History Project.

"It prioritizes protecting the elderly, rapid-testing with contact-tracing and patient monitoring with portable oxygen support for those who need it," Kaplan continued. To track the location of disease 'hotspots,' the team will take advantage of a variety of communication methods and their detailed GPS data available on resident structure and social networks.

"Details are likely to change as new ways to diagnose or treat COVID-19 become available," Gurven noted. As of now, he added, no confirmed cases have been reported in the towns closest to Tsimane communities.

The authors hope their paper will serve to affect policy and call for action. "Our article is directed toward the heads of state in countries with indigenous peoples, tribal leaders, scientists, health care workers, missionaries and non-governmental organizations that work with tribal peoples," said Kaplan. "We also hope that charitable organizations and ordinary citizens will be inspired to look for ways to help reduce the wave of death that will occur in the face of inaction."

"History teaches us that the effects of a new infectious disease on a vulnerable population can be devastating," said MemorialCare's David Michalik, a co-author of the paper and a specialist in pediatric infectious disease. "Our protocol seeks to augment already existing plans that countries may have in place, and raise awareness that even in 2020, indigenous communities are at risk of being wiped out if nothing is done."

Credit: 
University of California - Santa Barbara

Voluntary collective isolation is best response to COVID-19 for indigenous populations

image: Tsimane Health and Life History Project Team worked to translate and modify the U.S. Centers for Disease Control informational posters into the local Tsimane language.

Image: 
Tsimane Health and Life History Project Team

Orange, Calif. - A team of anthropologists, physicians, tribal leaders and local government authorities developed and implemented a multi-phase COVID-19 prevention and containment plan among the Tsimane, an indigenous group of forager-horticulturists in the Bolivian Amazon. The collaborative effort is led by Hillard Kaplan, Ph.D., professor of health economics and anthropology and a member of the Economic Science Institute at Chapman University.

The study, published in The Lancet, proposes that indigenous populations worldwide share characteristics that make them especially vulnerable to COVID-19, including higher rates of extreme poverty, poor healthcare access and infrastructure, and widespread respiratory infections. As of May 7, Bolivia had 2,081 confirmed COVID-19 cases and 102 deaths, largely confined to the Santa Cruz and La Paz provinces. As of now, there are no confirmed cases in the towns closest to the Tsimane communities.

The Tsimane Health and Life History Project has been working with Tsimane communities since 2002, studying health and ageing while providing primary health care and biomedical surveillance. Kaplan, co-director of the project, and his team paused research activity in mid-March to redirect their efforts towards reducing the effects of COVID-19 on the tribal populations with whom they work with.

"The disease is spreading rapidly in Bolivia as is the case in many places throughout the developing world but has not yet reached the tribal territories where we work," said Kaplan, the principal investigator of this study. "It is clear from the painful lessons we have learned in this country and in Europe, advance planning is the key to mitigating the devastating effects of the disease."

"After a teenage Yanomami boy died of COVID-19, there was, understandably, a lot of panic about the potential plight of indigenous populations around the world in light of this new, unpredictable threat," said Michael Gurven, Ph.D., professor of anthropology at UC Santa Barbara and co-director of the Tsimane Project with Kaplan. "Since our team had already been working with the Tsimane to try and work out a reasonable plan, we thought it would be a great opportunity to move the conversation toward a concrete blueprint that could, hopefully, be adapted to work in similar areas."

The researchers believe that their approach with the Tsimane can be adapted more generally to tribal and aboriginal populations throughout the world to prevent widespread mortality, and will continue to adjust their plans according to the local circumstances and future COVID-19 discoveries.

Dr. Kaplan and his team developed their COVID-19 strategy based on two guidelines. The first is that preventative measures before mass infection can greatly reduce the burden of morbidity and mortality. The second is that any effective plan must be collaborative among all stakeholders and should involve the indigenous populations in the decision process.

These tribal communities have unique sources of resilience that can be used to prevent the potentially serious effects of COVID-19. The most pertinent is the group's cultural tradition of collective decision- making, where lively two-way discussions are held during village meetings to allow community members to speak up and contribute to a collective decision. The consensus among the Tsimane is that collective isolation is the most viable strategy for minimizing COVID-19 exposure until vaccines or treatments become available. Researchers utilized these community meetings to communicate best practices in collective isolation with the villages.

The research team has a two-phase plan. Phase I -- focused on education, outreach and preparation -- occurred while the novel coronavirus was spreading quickly in Bolivia but before there were confirmed cases in the Beni region where the Tsimane live.

The research team traveled to around 60 villages to hold community meetings. The researchers sent native speakers of the Tsimane language to these meetings to inform the population about the risks of COVID-19 and promote a collective decision-making process on how best to respond to the epidemic. These meetings lead to unanimous agreement by the Tsimanes to collectively isolate the tribal territory and its constituent communities to prevent interaction with the outside world.

The researchers also worked to translate and adapt U.S. Centers for Disease Control informational posters into the Tsimane language for dissemination.

"While some Tsimane people had heard about the existence of coronavirus, most were unaware of its imminent threat, how it is transmitted, who is most vulnerable or whether there was a cure for the disease," said Kaplan.

The research team is currently in Phase II: containment, patient management and quarantine strategies. This is being accomplished through ongoing radio communications about the current rates and areas of infection, coordination of rapid testing and contact-tracing and the provisioning of personal protective equipment for local health care workers. Phase II began in mid-April when COVID- 19 was diagnosed and confirmed in the Beni region.

"Our plan is adapted to a low-tech environment of inadequate hospital facilities and to lower population density where isolation is possible for whole communities and for families and individuals within communities," said Gregory Thomas, MD, a medical director of the Long Beach MemorialCare Heart and Vascular Institute and collaborator of the study.

"The plan places greater emphasis on testing with contact-tracing and whole-family approaches to isolation. For the management and treatment of COVID-19 cases, it emphasizes patient monitoring, especially blood oxygen, and portable oxygen support for those who need it," added David Michalik, MD, pediatric infectious disease specialist at MemorialCare Miller Women's and Children's Hospital Long Beach.

Credit: 
Chapman University

Researchers find the key to preserving The Scream

image: View of the ESRF, the European Synchrotron, Grenoble, France.

Image: 
ESRF/Stef Candé

Moisture is the main environmental factor that triggers the degradation of the masterpiece The Scream (1910?) by Edvard Munch, according to the finding of an international team of scientists led by the CNR (Italy), using a combination of in situ non-invasive spectroscopic methods and synchrotron X-ray techniques. After exploiting the capability of the European mobile platform MOLAB in situ and non-invasively at the Munch Museum in Oslo, the researchers came to the ESRF, the European Synchrotron (Grenoble, France), the world's brightest X-ray source, to carry out non-destructive experiments on micro-flakes originating from one of the most well-known versions of The Scream. The findings could help better preserve this masterpiece, which is seldom exhibited due to its degradation. The study is published in Science Advances.

The Scream is among the most famous paintings of the modern era. The now familiar image is interpreted as the ultimate representation of anxiety and mental anguish. There are a number of versions of The Scream, namely two paintings, two pastels, several lithographic prints and a few drawings and sketches. The two most well-known versions are the paintings that Edvard Munch created in 1893 and 1910. Each version of The Scream is unique. Munch clearly experimented to find the exact colours to represent his personal experience, mixing diverse binding media (tempera, oil and pastel) with brilliant and bold synthetic pigments to make 'screaming colours'. Unfortunately, the extensive use of these new coloured materials poses a challenge for the long-term preservation of Munch's artworks.

The version of the Scream (1910?) that belongs to the Munch Museum (Oslo, Norway) clearly exhibits signs of degradation in different areas where cadmium-sulfide-based pigments have been used: cadmium yellow brushstrokes have turned to an off-white colour in the sunset cloudy sky and in the neck area of the central figure. In the lake, a thickly applied opaque cadmium yellow paint is flaking. Throughout its existence, several elements have played a role in the deterioration of the masterpiece: the yellow pigments used, the environmental conditions and a theft in 2004, when the painting disappeared for two years.

Since the recovery of the painting after the theft, the masterpiece has rarely been shown to the public. Instead, it is preserved in a protected storage area in the Munch Museum, in Norway, under controlled conditions of lighting, temperature (about 18°C) and relative humidity (about 50%).

An international collaboration, led by the CNR (Italy), with the University of Perugia (Italy), the University of Antwerp (Belgium), the Bard Graduate Center in New York City (USA), the European Synchrotron (ESRF, France), the German Electron Synchrotron (DESY, Hamburg) and the Munch Museum, has studied in detail the nature of the various cadmium-sulfide pigments used by Munch, and how these have degraded over the years.

The findings provide relevant hints about the deterioration mechanism of cadmium-sulfide-based paints, with significant implication for the preventive conservation of The Scream.

"The synchrotron micro-analyses allowed us to pinpoint the main reason that made the painting decline, which is moisture. We also found that the impact of light in the paint is minor. I am very pleased that our study could contribute to preserve this famous masterpiece", explains Letizia Monico, one of the corresponding authors of the study.

Hitting the right formula for preservation

Monico and her colleagues studied selected cadmium-sulfide-based areas of The Scream (1910?), as well as a corresponding micro-sample, using a series of non-invasive in-situ spectroscopic analyses with portable equipment of the European MOLAB platform in combination with the techniques of micro X-ray diffraction, X-ray micro fluorescence and micro X-ray absorption near edge structure spectroscopy mainly at the ESRF, the European Synchrotron, in France, the world's most powerful synchrotron. The study of the painting was integrated with investigations of artificially aged mock-ups. The latter were prepared using a historical cadmium yellow pigment powder and a cadmium yellow oil paint tube that belonged to Munch. Both mock-ups had a similar composition to the lake in the painting. "Our goal was to compare the data from all these different pigments, in order to extrapolate the causes that can lead to deterioration", says Monico.

The study shows that the original cadmium sulfide turns into cadmium sulfate in the presence of chloride-compounds in high-moisture conditions (relative humidity, or RH ?95%). This happens even if there is no light.

"The right formula to preserve and display the main version of The Scream on a permanent basis should include the mitigation of the degradation of the cadmium yellow pigment by minimising the exposure of the painting to excessively high moisture levels (trying to reach 45% RH or lower), while keeping the lighting at standard values foreseen for lightfast painting materials. The results of this study provide new knowledge, which may lead to practical adjustments to the Museum's conservation strategy", explains Irina C. A. Sandu, conservation scientist at the Munch Museum.

"Today the Munch Museum stores and exhibits Edvard Munch's artworks at a relative humidity of about 50% and at a temperature of around 20 °C. These environmental conditions will also apply to the new Munch Museum to be opened in Spring 2020. That said, the Museum will now look into how this study may affect the current regime. Part of such a review will be to consider how other materials in the collection will respond to possible adjustments", adds Eva Storevik Tveit, paintings conservator at the Munch Museum.

Cadmium-sulfide-based yellows are not only present in Munch's artwork but also in the work of other artists contemporary to him, such as Henri Matisse, Vincent van Gogh and James Ensor.

"The integration of non-invasive in-situ investigations at the macro-scale level with synchrotron micro-analyses proved its worth in helping us to understand complex alteration processes. It can be profitably exploited for interrogating masterpieces that could suffer from the same weakness", reports Costanza Miliani, coordinator of the mobile platform MOLAB (operating in Europe under the IPERION CH project) and second corresponding author of this study.

Monico and colleagues, especially Koen Janssens (University of Antwerp), have a long-standing collaboration with the ESRF, the European Synchrotron, and in particular with the scientist Marine Cotte, to investigate these pigments and the best way to preserve the original masterpieces.

"At the ESRF, ID21 is one of the very few beamlines in the world where we can perform imaging X-ray absorption and fluorescence spectroscopy analysis of the entire sample, at low energy and with sub-micrometer spatial resolution", explains Janssens.

"EBS, the new Extremely Brilliant Source, the first-of-a-kind high-energy synchrotron, which is under commissioning at the moment at the ESRF, will further improve the capabilities of our instruments for the benefit of world heritage science. We will be able to perform microanalyses with increased sensitivity, and a greater level of detail. Considering the complexity of these artistic materials, such instrumental developments will highly benefit the analysis of our cultural heritage", adds Cotte, ESRF scientist and CNRS researcher director.

"This kind of work shows that art and science are intrinsically linked and that science can help preserve pieces of art so that the world can continue admiring them for years to come", concludes Miliani, coordinator of MOLAB.

Credit: 
European Synchrotron Radiation Facility

Modern sea-level rise linked to human activities

image: Scientists boarding the D/V JOIDES Resolution off New Jersey in 1993. The sea level in an ice-free world would be 66 meters (216.5 feet) higher than now - shoulder-high to the Statue of Liberty.

Image: 
Kenneth G. Miller, James V. Browning and Gregory S. Mountain

New research by Rutgers scientists reaffirms that modern sea-level rise is linked to human activities and not to changes in Earth's orbit.

Surprisingly, the Earth had nearly ice-free conditions with carbon dioxide levels not much higher than today and had glacial periods in times previously believed to be ice-free over the last 66 million years, according to a paper published in the journal Science Advances.

"Our team showed that the Earth's history of glaciation was more complex than previously thought," said lead author Kenneth G. Miller, a Distinguished Professor in the Department of Earth and Planetary Sciences in the School of Arts and Sciences at Rutgers University-New Brunswick. "Although carbon dioxide levels had an important influence on ice-free periods, minor variations in the Earth's orbit were the dominant factor in terms of ice volume and sea-level changes - until modern times."

Sea-level rise, which has accelerated in recent decades, threatens to permanently inundate densely populated coastal cities and communities, other low-lying lands and costly infrastructure by 2100. It also poses a grave threat to many ecosystems and economies.

The paper reconstructed the history of sea levels and glaciation since the age of the dinosaurs ended. Scientists compared estimates of the global average sea level, based on deep-sea geochemistry data, with continental margin records. Continental margins, which include the relatively shallow ocean waters over a continental shelf, can extend hundreds of miles from the coast.

The study showed that periods of nearly ice-free conditions, such as 17 million to 13 million years ago, occurred when the concentration of atmospheric carbon dioxide - a key greenhouse gas driving climate change - was not much higher than today. However, glacial periods occurred when the Earth was previously thought to be ice-free, such as from 48 million to 34 million years ago.

"We demonstrate that although atmospheric carbon dioxide had an important influence on ice-free periods on Earth, ice volume and sea-level changes prior to human influences were linked primarily to minor variations in the Earth's orbit and distance from the sun," Miller said.

The largest sea-level decline took place during the last glacial period about 20,000 years ago, when the water level dropped by about 400 feet. That was followed by a foot per decade rise in sea level - a rapid pace that slowed from 10,000 to 2,000 years ago. Sea-level rise was then at a standstill until around 1900, when rates began rising as human activities began influencing the climate.

Future work reconstructing the history of sea-level changes before 48 million years ago is needed to determine the times when the Earth was entirely ice-free, the role of atmospheric carbon dioxide in glaciation and the cause of the natural fall in atmospheric carbon dioxide before humans.

Rutgers coauthors include Professor James V. Browning, doctoral student W. John Schmelz and professors Robert E. Kopp, Gregory S. Mountain and James D. Wright, the senior author of the study.

Credit: 
Rutgers University

Study finds association between atherosclerosis and changes in the structure, heart function

(Boston)--Even among individuals free of heart failure and myocardial infarction, there appears to be evidence of an association between calcium buildup in the coronary arteries (atherosclerosis) and changes in the structure and function of the heart.

Coronary artery calcium buildup or atherosclerosis is a strong predictor of future coronary heart disease. To date, the evidence suggests that coronary disease interacts and progresses along with the incipient development of myocardial disease, even in the absence of symptoms.

However, data on the association between coronary artery calcium and echocardiographic-based changes of the structure and function of the heart are lacking.

Researchers from Boston University School of Medicine (BUSM) evaluated the association between coronary artery calcification and echocardiographic measurements that quantify these changes in the heart among 2,650 participants (average age 51 years, 48 percent women) from the Framingham Heart Study. They observed that higher coronary artery calcium scores were associated with higher values of left ventricular mass index and aortic root diameter, consistent with potential adverse effects of changes in the size, shape, structure and function of the heart.

"We know that coronary artery disease progresses along with myocardial disease, but these findings suggest that there may be a direct link between coronary artery calcium and structural and functional changes in the heart, emphasizing the need to follow a healthy lifestyle in order to help prevent calcification of the arteries," explained corresponding author Vanessa Xanthakis, PhD, assistant professor of medicine and biostatistics at BUSM and an Investigator for the Framingham Heart Study.

Xanthakis believes additional studies are needed to further clarify the pathophysiological basis of the observed associations and to assess whether coronary artery calcium can be used to predict changes in the structure and function of the heart.

These findings appear online in PLOS ONE.

Credit: 
Boston University School of Medicine