Culture

(New York, NY - October 28, 2020) - The vast majority of individuals infected with mild-to-moderate COVID 19 mount a robust antibody response that is relatively stable for at least five months, according to research conducted at the Icahn School of Medicine at Mount Sinai and published October 28, in the journal Science. Additionally, the research team found that this antibody response correlates with the body's ability to neutralize (kill) SARS-CoV-2, the virus that causes COVID-19.

"While some reports have come out saying antibodies to this virus go away quickly, we have found just the opposite - that more than 90 percent of people who were mildly or moderately ill produce an antibody response strong enough to neutralize the virus, and the response is maintained for many months," said Florian Krammer, PhD, Professor of Vaccinology at the Icahn School of Medicine at Mount Sinai and a senior author of the paper. "Uncovering the robustness of the antibody response to SARS-CoV-2, including its longevity and neutralizing effects, is critically important to enabling us to effectively monitor seroprevalence in communities and to determining the duration and levels of antibody that protect us from reinfection. This is essential for effective vaccine development."

Study findings are based on a dataset of 30,082 individuals, who were screened within the Mount Sinai Health System between March and October, 2020. The antibody test used in this research--an enzyme-linked immunosorbent assay (ELISA)--is based on the virus's telltale spike protein that contains the machinery that enables it to attach and gain entry into our cells. The ELISA assay was developed, validated, and launched at Mount Sinai by a team of internationally renowned researchers and clinicians. The Mount Sinai antibody test detects the presence or absence of antibodies to SARS-CoV-2 and, importantly, is capable of measuring the titer (level) of antibodies an individual has. The high sensitivity and specificity of this test--meaning that a false negative or false positive is highly unlikely--allowed it to be among the first to receive emergency use authorization from New York State and the U.S. Food and Drug Administration.

In late March, Mount Sinai began to screen individuals for antibodies to SARS-CoV-2 in order to recruit volunteer donors for its convalescent plasma therapy program--one of the first such programs in the nation. The Clinical Laboratories of The Mount Sinai Hospital set up antibody test results using distinct dilutions set at 1:80, 1:160, 1:320, 1:960 or ?1:2880. The antibody titer score is generated by the number of times the scientist can dilute a patient's serum and still be able to detect the presence of antibodies. Titers of 1:80 and 1:160 were categorized as low titers; 1:320 moderate; and 1:960 or ? 1:2880 were high.

By early October, Mount Sinai had screened 72,401 individuals with a total of 30,082 being positive (defined as detectible antibodies to the spike protein at a titer of 1:80 or higher). Of the 30,082 positive samples, 690 (2.29 percent) had a titer of 1:80; 1453 (4.83 percent) of 1:160; 6765 (22.49 percent) of 1:320; 9564 (31.79 percent) of 1:960; and 11610 (38.60 percent) of 1:2880. Thus, the vast majority of positive individuals had moderate-to-high titers of anti-spike antibodies.

"Our microbiology colleagues generated great science and tools that were brought from the research lab into the clinical laboratory, where we were able to implement robust and compliant diagnostic tests at an unprecedented pace," said Carlos Cordon-Cardo, MD, PhD, Irene Heinz Given and John LaPorte Given Professor and Chair of Pathology, Molecular and Cell-Based Medicine and last author of the paper. "The tireless efforts of so many have enabled us to uncover knowledge that can help inform COVID-19 policy and aid in vaccine development."

Determining the neutralizing effects of SARS-CoV-2 is critical to understanding the possible protective effects of the immune response. The research team performed a well-established, quantitative microneutralization assay based on authentic SARS-CoV-2 with 120 samples of known ELISA titers ranging from "negative" to ?1:2880. They found that approximately 50 percent of sera in the1:80-1:160 titer range had neutralizing activity; 90 percent in the 1:320 range had neutralizing activity; and all sera in the 1:960 to ?1:2880 range had neutralizing activity.

Another important and outstanding question in the scientific community is the longevity of the antibody response to the spike protein. To answer that question, the team recalled 121 plasma donors at a variety of titer levels for repeat antibody testing at approximately 3 months and 5 months post-symptom onset. When comparing overall titers, they saw a slight drop from a geometric mean titer (GMT) of 764 to a GMT of 690 from the first to second testing time point and another drop to a GMT of 404 for the last testing time point, indicating that a moderate level of antibody is retained by most people 5 months after symptom-onset. In the higher titer range, they observed a slow decline in titer over time. Interestingly, they saw an initial increase in titer for individuals who had originally tested as having low to moderate titer levels. This is in agreement with earlier observations from their study group that indicate seroconversion in mild COVID-19 cases might take a longer time to mount.

"The serum antibody titer we measured in individuals initially were likely produced by plasmablasts, cells that act as first responders to an invading virus and come together to produce initial bouts of antibodies whose strength soon wanes," said Ania Wajnberg, MD, Director of Clinical Antibody Testing at the Mount Sinai Hospital and first author of the paper. "The sustained antibody levels that we subsequently observed are likely produced by long-lived plasma cells in the bone marrow. This is similar to what we see in other viruses and likely means they are here to stay. We will continue to follow this group over time to see if these levels remain stable as we suspect and hope they will."

The Mount Sinai data reveals antibody binding titers to the spike protein correlate significantly with neutralization of SARS-CoV-2 and that the vast majority of individuals with antibody titers of 320 or higher show neutralizing activity in their serum that are stable over a period of at least 3 months with only modest declines at the 5-month time point. Correlates of protection have been established for many different viral infections including influenza, measles, hepatitis A, hepatitis B. These correlates are usually based on a specific level of antibody acquired through vaccination or natural infection that significantly reduces the risk of re-infection. The team will continue following this study cohort over longer intervals of time. Although this cannot provide conclusive evidence that these antibody responses protect from re-infection, the team believes it is very likely that the antibodies will decrease the odds of getting reinfected and may attenuate disease in the case of breakthrough infection. To inform policy for the COVID-19 pandemic and for the benefit of vaccine development, it is imperative to swiftly perform studies to investigate and establish a correlate of protection to SARS-CoV-2. Such investigations are currently being carried out by researchers at the Icahn School of Medicine at Mount Sinai.

CAMBRIDGE, MA -- As people age, they often lose their motivation to learn new things or engage in everyday activities. In a study of mice, MIT neuroscientists have now identified a brain circuit that is critical for maintaining this kind of motivation.

This circuit is particularly important for learning to make decisions that require evaluating the cost and reward that come with a particular action. The researchers showed that they could boost older mice's motivation to engage in this type of learning by reactivating this circuit, and they could also decrease motivation by suppressing the circuit.

"As we age, it's harder to have a get-up-and-go attitude toward things," says Ann Graybiel, an Institute Professor at MIT and member of the McGovern Institute for Brain Research. "This get-up-and-go, or engagement, is important for our social well-being and for learning -- it's tough to learn if you aren't attending and engaged."

Graybiel is the senior author of the study, which appears today in Cell. The paper's lead authors are Alexander Friedman, a former MIT research scientist who is now an assistant professor at the University of Texas at El Paso, and Emily Hueske, an MIT research scientist.

Evaluating cost and benefit

The striatum is part of the basal ganglia -- a collection of brain centers linked to habit formation, control of voluntary movement, emotion, and addiction. For several decades, Graybiel's lab has been studying clusters of cells called striosomes, which are distributed throughout the striatum. Graybiel discovered striosomes many years ago, but their function had remained mysterious, in part because they are so small and deep within the brain that it is difficult to image them with functional magnetic resonance imaging (fMRI).

In recent years, Friedman, Graybiel, and colleagues including MIT research fellow Ken-ichi Amemori have discovered that striosomes play an important role in a type of decision-making known as approach-avoidance conflict. These decisions involve choosing whether to take the good with the bad -- or to avoid both -- when given options that have both positive and negative elements. An example of this kind of decision is having to choose whether to take a job that pays more but forces a move away from family and friends. Such decisions often provoke great anxiety.

In a related study, Graybiel's lab found that striosomes connect to cells of the substantia nigra, one of the brain's major dopamine-producing centers. These studies led the researchers to hypothesize that striosomes may be acting as a gatekeeper that absorbs sensory and emotional information coming from the cortex and integrates it to produce a decision on how to act. These actions can then be invigorated by the dopamine-producing cells.

The researchers later discovered that chronic stress has a major impact on this circuit and on this kind of emotional decision-making. In a 2017 study performed in rats and mice, they showed that stressed animals were far more likely to choose high-risk, high-payoff options, but that they could block this effect by manipulating the circuit.

In the new Cell study, the researchers set out to investigate what happens in striosomes as mice learn how to make these kinds of decisions. To do that, they measured and analyzed the activity of striosomes as mice learned to choose between positive and negative outcomes.

During the experiments, the mice heard two different tones, one of which was accompanied by a reward (sugar water), and another that was paired with a mildly aversive stimulus (bright light). The mice gradually learned that if they licked a spout more when they heard the first tone, they would get more of the sugar water, and if they licked less during the second, the light would not be as bright.

Learning to perform this kind of task requires assigning value to each cost and each reward. The researchers found that as the mice learned the task, striosomes showed higher activity than other parts of the striatum, and that this activity correlated with the mice's behavioral responses to both of the tones. This suggests that striosomes could be critical for assigning subjective value to a particular outcome.

"In order to survive, in order to do whatever you are doing, you constantly need to be able to learn. You need to learn what is good for you, and what is bad for you," Friedman says.

"A person, or this case a mouse, may value a reward so highly that the risk of experiencing a possible cost is overwhelmed, while another may wish to avoid the cost to the exclusion of all rewards. And these may result in reward-driven learning in some and cost-driven learning in others," Hueske says.

The researchers found that inhibitory neurons that relay signals from the prefrontal cortex help striosomes to enhance their signal-to-noise ratio, which helps to generate the strong signals that are seen when the mice evaluate a high-cost or high-reward option.

Loss of motivation

Next, the researchers found that in older mice (between 13 and 21 months, roughly equivalent to people in their 60s and older), the mice's engagement in learning this type of cost-benefit analysis went down. At the same time, their striosomal activity declined compared to that of younger mice. The researchers found a similar loss of motivation in a mouse model of Huntington's disease, a neurodegenerative disorder that affects the striatum and its striosomes.

When the researchers used genetically targeted drugs to boost activity in the striosomes, they found that the mice became more engaged in performance of the task. Conversely, suppressing striosomal activity led to disengagement.

In addition to normal age-related decline, many mental health disorders can skew the ability to evaluate the costs and rewards of an action, from anxiety and depression to conditions such as PTSD. For example, a depressed person may undervalue potentially rewarding experiences, while someone suffering from addiction may overvalue drugs but undervalue things like their job or their family.

The researchers are now working on possible drug treatments that could stimulate this circuit, and they suggest that training patients to enhance activity in this circuit through biofeedback could offer another potential way to improve their cost-benefit evaluations.

"If you could pinpoint a mechanism which is underlying the subjective evaluation of reward and cost, and use a modern technique that could manipulate it, either psychiatrically or with biofeedback, patients may be able to activate their circuits correctly," Friedman says.

MINNEAPOLIS - Studies have suggested that taking part in leisure activities such as playing cards or gardening may be associated with a lower risk of developing dementia. But a new study found no association between taking part in leisure activities at age 56 and the risk of dementia over the next 18 years. The researchers also found that some people who are later diagnosed with dementia stop participating in leisure activities years before they are diagnosed. The study is published in the October 28, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"Of course there are many reasons to participate in leisure activities, and this finding does not question the importance of keeping active for general health and well-being, but it does suggest that simply increasing leisure activity may not be a strategy for preventing dementia," said study author Andrew Sommerlad, Ph.D., of University College London in the United Kingdom. "Our study suggests that changes in the amount of leisure activity may be an early sign of dementia, possibly due to symptoms such as apathy or other social changes or early cognitive difficulties."

The study involved 8,280 people with an average age of 56 years who were followed for an average of 18 years. Their participation in leisure activities was assessed at the beginning of the study, five years later and again 10 years later. Researchers reviewed health records to identify people who developed dementia.

Leisure activities included reading, listening to music, taking classes, participating in clubs, visiting friends and relatives, playing cards or games, taking part in religious activities and gardening. People were placed in low, medium and high groups based on their participation levels.

During the study, 360 people developed dementia. The overall rate of dementia was 2.4 cases for 1,000 person-years. Person-years take into account both the number of people in the study and the amount of time each person spends in the study.

The researchers found no relationship between taking part in more leisure activities at the beginning of the study and having a lower dementia risk nearly 20 years later. There was only a relationship when leisure activity participation in late life was assessed. People who took part in more leisure activities at the average age of 66 were less likely to have dementia diagnosed over the next eight years than people who had lower participation.

With every one standard deviation increase in leisure activities, equivalent approximately to doing three new leisure activities monthly or two activities weekly, people were 18% less likely to be diagnosed with dementia 8 years later. These results took into account other factors that could affect risk of dementia, such as diabetes, high blood pressure and body mass index.

In addition, people whose level of participation dropped over the course of the study were more likely to develop dementia than those whose participation level stayed the same over the years. Of the 1,159 people whose activity decreased, 53, or 5%, developed dementia, compared to 17 of the 820 people, or 2%, whose activity level stayed low over the years.

"More research is needed to confirm these results, but we know that early changes in the brain can start decades before any symptoms emerge," Sommerlad said. "It's plausible that people may slow down their activity level up to 10 years before dementia is actually diagnosed, due to subtle changes and symptoms that are not yet recognized."

A limitation of the study was that dementia diagnoses were gathered from electronic health records rather than assessing each participant, so some cases may not have been diagnosed.

DURHAM, N.C. -- Fall is here, and we see the leaves turning yellow, orange or red thanks to a trick of our vision: our brains categorize colors. Scientists have learned that birds with colorful markings do this too. But what about drab birds that don't rely on color?

According to a new Duke University study, the ability to mentally categorize colors is not a universal avian attribute, and dull-colored birds may see the world in a completely different way than their colorful cousins.

To test whether birds separate colors into categories, a team led by Duke postdoctoral researcher Eleanor Caves selected eight colors varying continuously from orange to red, and made little disks with either one solid color or a combination of two colors. Birds were then trained to flip over only the disks that showed two different colors, in exchange for a food reward.

In previous experiments, the team showed that female zebra finches presented with a continuum of orange to red colors will categorize these into two distinct groups with a clear threshold. These birds have brightly colored orange to red beaks, which may act as a signal of health when females are choosing their mate.

This trick of our brains is called categorical perception, where some sort of continuous variation is binned into categories separated by thresholds. Things on opposite sides of this threshold will appear more distinct than things on the same side of the threshold, even if they are in fact just as different. The zebra finches saw a continuum of colors as just two.

In a new study, appearing Oct. 26 in The American Naturalist, the team turned their attention to Bengalese finches, a species of brown, black and white birds that don't rely on colorful signals when choosing a mate. When presented with the same continuum of colors, Bengalese finches showed no evidence of a threshold between orange and red. Instead, they picked only disks that were on opposite sides of the continuum and differed a lot in hue. They seemed to be paying more attention to differences in brightness than the zebra finches.

"Brightness matters for all of these birds, but it really is what is driving the ability of the Bengalese finch to discriminate among colors, not hue," said Steve Nowicki, a Duke biology professor who is senior author on the study.

In zebra finches, on the other hand, brightness differences simply reinforced differences in hue.

"These birds were a lot more different than we were expecting, given how superficially similar they are," Caves said. This difference in color perception may not be due to peculiarities of the birds' eyes, but rather to how their brains evolved to interpret signals.

In zebra finches, a female needs to identify the healthy red-beaked male. In Bengalese finches, however, females may rely only on male songs to choose their mates, so the orange-red gradient is far less relevant to them.

"It's probably both a matter of their evolutionary environment, what signals and colors they evolved to find important, but also their immediate developmental environment," Caves said.

These results show that vision depends on much more than the eyes. The colors that an animal sees depend on how important that color is for its everyday life.

"A two-species comparison is not much to hang an evolutionary story on," Nowicki said. Nonetheless, these two species are enough to point out flaws in previous assumptions.

"People have often assumed that all of these birds should be more or less the same when it comes to vision," he continued. "To just find one exception shows that that's not necessarily the case."

But the Bengalese finches may be outliers among birds. While both Bengalese finches and zebra finches are domesticated, the Bengalese finches are more distant from their wild cousins. It is possible that the domestication process, where food is readily available and mates are assigned rather than chosen, relaxed the selection on these birds' ability to categorize signals.

"The effect of domestication on various sensory capabilities is pretty understudied," Caves said.

The authors hope that a more comprehensive study with several species will shed light on how the perception of color relates to the presence of colorful signals in birds. What these two species can say, however, is already a breakthrough.

"First we showed that birds can see the rainbow," Nowicki said. "Now we're saying: actually, not all of them do!"

Researchers at the University of São Paulo (USP) in Brazil have discovered that the muscle regeneration promoted by aerobic exercise is mediated by changes in oxygen consumption by satellite cells, also known as skeletal muscle stem cells. The discovery is expected to be used to help people recover from injury and combat the loss of muscle mass associated with aging.

Previous research showed that weight lifting and other kinds of strength training increase the number of satellite cells. In aerobic exercise, muscle tissue is known to increase its capacity but the repair mechanisms associated with satellite cells had not previously been studied.

The USP group found that aerobic exercise boosted the growth of satellite cells and that significant metabolic alterations lay behind the phenomenon. The study was conducted during the PhD research of Phablo Sávio Abreu Teixeira, with the support of a scholarship from São Paulo Research Foundation - FAPESP .

"We noted reduced oxygen consumption in satellite cells, whereas exercise raised the demand for oxygen in all other muscle tissue. This is the first time anyone has managed to observe how aerobic exercise influences mitochondrial metabolism in these cells and how this affects muscle regeneration," Abreu told.

To understand the mechanism, Abreu conducted a number of experiments with animals at USP's Chemistry Institute under the supervision of Professor Alicia Kowaltowski, who has continuously studied mitochondria since the 1990s and is affiliated with the Center for Research on Redox Processes in Biomedicine (Redoxome), one of the Research, Innovation and Dissemination Centers (RIDCs) supported by FAPESP.

The findings are reported in an article published in Journal of Cachexia, Sarcopenia and Muscle.
"We discovered at least part of the mechanism that led to improved muscle regeneration. Fuller knowledge is the first step to being able to intervene in the regeneration process in future," Kowaltowski said.

Several stages

The study was performed in stages, comprising experiments with mice divided into two groups. One group was submitted to a battery of aerobic exercises on a treadmill for five weeks, while the control group remained sedentary.

At the end of this period the researchers tested the mice to see if the exercise had in fact improved their aerobic capacity. In the next stage, muscle tissue in both groups was injured and its regenerative capacity was analyzed.

"First we found that the trained animals had more recently formed muscle fibers, as well as less deposition of fibrous tissue and fewer signs of inflammation," Abreu said. "These findings confirmed that muscle tissue in the trained animals had in fact been better repaired."

After concluding that muscle repair capacity had improved, the researchers investigated the alterations to satellite cells isolated from the animals submitted to the exercise program. Proteins that regulate cell quiescence and activation, enabling self-renewal or differentiation, were augmented in these cells. "They also showed that differentiation had been inhibited, confirming our findings," Abreu said.

Satellite cells are responsible for muscle tissue regeneration and preservation, he explained, but to perform this function they have to remain quiescent in order to maintain tissue homeostasis. Throughout the subject's life, they are activated by injury or by wear-and-tear due to exercise. Some then differentiate into tissue cells, while others self-renew, giving rise to new satellite cells so that the cycle can continue.

"These cells are constantly activated, but over time they can become fatigued and stop self-renewing. This is what happens in muscular dystrophy and diseases involving loss of muscle mass such as cachexia or sarcopenia," Abreu said. "If we have more renewed cells, it means we have more cells capable of regenerating tissue."

In addition to concluding that exercise maintained muscle tissue regeneration capacity and contributed to recovery from injury, the researchers measured satellite cell oxygen consumption in search of an explanation for the phenomenon. "Surprisingly we found them to consume less oxygen, as if they had become more economical," Abreu said.

The findings refuted the researchers' initial hypothesis, which was that because aerobic exercise enhanced muscular oxidative capacity and satellite cells are anchored to the surface of skeletal muscle tissue (hence the name satellite), the oxidative capacity of satellite cells also ought to increase.

The role of mitochondria

Cellular respiration, the process by which chemical energy is released during the oxidation of organic molecules, occurs in mitochondria, organelles thought until recently to be responsible only for energy production. "Scientists have increasingly discovered the extent to which mitochondria are involved in various other processes," Kowaltowski said.

To confirm that mitochondrial oxygen consumption did indeed explain satellite cell self-renewal, Kowaltowski and Abreu performed two more experiments, using drugs to mimic the effect of reduced oxygen consumption on cells grown in the laboratory, and transplanting cells from exercised mice into sedentary mice. The reduction in oxygen consumption was indeed found to enhance satellite cell self-renewal. The rate of repair did not change in transplanted cells, but inflammation diminished, suggesting enhanced muscle recovery.

The researchers now plan to investigate the effects of reduced mitochondrial oxygen consumption and the pathways involved in satellite cell self-renewal. "In short, we need to understand why inhibition of cellular respiration enhances muscle recovery," Kowaltowski said.

It may be possible to replicate this phenomenon in future to treat age-related loss of muscle mass or the same problem resulting from cancer. The process is currently irreversible in many cases.

Irvine, Calif., Oct. 28, 2020 -- Testing a representative sample of Orange County residents for a wide range of coronavirus antibodies, University of California, Irvine researchers found that 11.5 percent of them have antibodies for COVID-19, in contrast to previous estimates of less than 2 percent.

Latino and low-income residents had the highest prevalence of SARS-CoV-02 antibodies with rates of 17 percent and 15 percent, respectively.

UCI researchers led the actOC project in partnership with the OC Health Care Agency, which provided funding, testing sites and input on the study's survey methods and scripts.

Study results appear on the pre-print server site medRxiv: https://www.medrxiv.org/content/10.1101/2020.10.07.20208660v1

"This rigorously designed surveillance study offers important information about how many residents of Orange County have already been exposed to COVID-19," said Bernadette Boden-Albala, director of UCI's Program in Public Health and founding dean of the campus's proposed School of Population Health. "Additionally, the study helps us to understand the impact of disparities."

The results will enable leaders of the sixth-largest county in the U.S. to identify key demographics at higher risk of contracting - and having adverse outcomes from - the virus.

"The greater prevalence of a positive antibody response among Latinx populations is consistent with some of the testing and hospital data that has come out of Orange County and nationwide," said Boden-Albala, a co-principal investigator on the study. "As we look toward the fall and flu season, this data also justifies enhanced planning and resources in communities likely to be hit hardest."

"COVID-19 has had different impacts on different communities across our county. There has been particular concern for communities of color and residents with lower incomes that are disproportionately affected by this virus in terms of infection rates and poorer outcomes. Health equity continues to be paramount, and this study not only confirms the observable trend but also helps inform our strategies and policy recommendations moving forward to help ensure that all of our Orange County neighbors are able to attain access to testing, information and education, as well as the resources they need to care for themselves and their families," said Dr. Clayton Chau, County Health Officer and Director of the OC Health Care Agency.

A groundbreaking process

Working with marketing firm LRW Group to recruit a truly representative sample of Orange County residents, the study enrolled nearly 3,000 random people via phone and email. The participants provided demographic information, revealed whether they had experienced any coronavirus symptoms, and were asked if they'd be willing to undergo blood screening for antibodies.

Those who agreed visited one of 11 drive-thru testing sites - selected based on OC Health Care Agency emergency plans - where medically trained volunteers, primarily UCI students and alumni, collected blood samples using finger pinpricks.

With a UCI-developed imaging platform, the researchers looked for antibody responses to a wide array of respiratory viruses - including SARS-CoV-2, which causes COVID-19. The highly sensitive technology allowed them to identify whether participants had contracted COVID-19 specifically, while many other antibody tests cannot accurately distinguish between it and other coronaviruses. The results were then analyzed and paired with the demographic data.

Researchers are following up every two weeks for four months with a subset of 200 people who tested positive so that they can see how the immune response changes over time.

Potential impact

UCI researchers initiated the study because they had a hunch that the prevalence of COVID-19 had been underestimated, since individuals with few to no symptoms were rarely tested.

"There was this lurking suspicion that there's a large fraction of people who have had it that did not know," said co-principal investigator Tim Bruckner, associate professor of public health. "Either they had symptoms and did not seek care, or they did not have symptoms and had no reason to go."

Recent surveys in other metropolitan regions of the U.S. suggest that infection rates are higher and death rates lower than previously thought and that rates vary significantly from place to place. The results of the actOC project confirm that nearly seven times as many county residents have contracted COVID-19 as had been believed.

It's the first study in California to employ both a truly representative sample and tests for a wide array of viral antibodies, producing an accurate picture of the disease's prevalence in Orange County. The team included OC Health Care Agency partners Dr. Clayton Chau, County Health Officer and Director, and Dr. Matthew Zahn, Medical Director of the OC Health Care Agency's Communicable Disease Control Division; UCI public health researchers Boden-Albala, Bruckner, Daniel Parker, Scott Bartell, Veronica Vieira and Emily Drum; and UCI School of Medicine researchers Saahir Khan and Philip Felgner.

It is not yet clear what levels of antibodies indicate near- or long-term immunity for people who have had COVID-19, but continued follow-up with those who tested positive will provide further data over time. Although 11.5 percent is still substantially below the minimum of 70 percent of residents who would need to have antibodies in order to achieve herd immunity - and given that one county cannot act as a guide for the country as a whole - many researchers hope that representative antibody testing across the U.S. could help guide reopening and public health decisions.

"Our study demonstrates that while a significant number of O.C. residents were already exposed and developed antibodies to COVID-19, much of the county still remains vulnerable to the virus," Boden-Albala said. "For researchers, there is a lot more work to be done, such as understanding the protection of COVID antibodies and identifying and addressing notable disparities associated with this virus."

Announcing a new article publication for BIO Integration journal. In this review article the authors Chenxi Liu, Dian Jiao and Zhe Liu, from Tianjin University, Tianjin, China consider artificial intelligence (AI) aided disease prediction.

Artificial intelligence (AI) is widely used in clinical medicine and is increasingly applied to the fields of AI-aided image analysis, AI-aided lesion determination and AI-assisted healthcare management.

In this article the authors discuss the emerging applications of AI-related medicine and AI-assisted visualized medicine, including novel diagnostic approaches, metadata analytical methods, and versatile AI-aided treatment applications in preclinical and clinical uses. New progress and breakthroughs in AI-aided disease prediction exhibit tremendous potential for clinical use in the future.

Article reference: Chenxi Liu, Dian Jiao and Zhe Liu, (AI)-aided Disease Prediction. BIO Integration, 2020, https://doi.org/10.15212/bioi-2020-0017

WASHINGTON--All adults with endocrine disorders should be tested for high cholesterol and triglycerides to evaluate their risk of heart attack or stroke, according to a Clinical Practice Guideline issued today by the Endocrine Society.

The guideline, titled "Lipid Management in Patients with Endocrine Disorders: An Endocrine Society Clinical Practice Guideline," was published online?and will appear in the December 2020 print issue of The Journal of Clinical Endocrinology & Metabolism (JCEM), a publication of the Endocrine Society. This guideline provides an approach to assessing and treating high cholesterol and triglycerides in patients with endocrine diseases like hypothyroidism, menopause and Cushing's syndrome.

Apart from diabetes, many endocrine diseases are not mentioned in cholesterol management guidelines. Our guideline addresses this gap in information and has three main objectives: describe lipid abnormalities and cardiovascular risk in patients with endocrine diseases; assess whether treatment of the underlying endocrine disorder improves the lipid profile and/or lowers the risk of cardiovascular disease; and discuss the evidence for using cholesterol and triglyceride lowering medications, in addition to diet and exercise, in patients with these endocrine diseases.

"This guideline is the first of its kind. We hope that it will make a lipid panel and cardiovascular risk evaluation routine in adults with endocrine diseases and cause a greater focus on therapies to reduce heart disease and stroke," said Connie Newman, M.D., of the New York University Grossman School of Medicine in New York, N.Y. Newman is the chair of the committee that wrote the guideline.

Recommendations from the guideline include:

Obtain a lipid panel and evaluate cardiovascular risk factors in adults with endocrine disorders.

Start statins earlier in patients with type 2 diabetes and risk factors for cardiovascular disease.

Consider statin therapy at a younger age in adults with type 1 diabetes who have obesity, or vascular complications, or a 20-year history of diabetes.

Rule out hypothyroidism before treatment with lipid-lowering medications. In patients with hypothyroidism, re-evaluate the lipid profile when the patient has thyroid hormone levels in the normal range.

Monitor the lipid profile in adults with Cushing's syndrome and consider statin therapy in addition to lifestyle modifications if Cushing's syndrome persists after treatment.

To treat high cholesterol or triglycerides in post-menopausal women, use statins rather than hormone therapy.

Evaluate and treat lipids and other cardiovascular risk factors in women who enter menopause early (before the age of 40-45 years).

Other members of the Endocrine Society writing committee that developed this guideline include: Michael Blaha of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease in Baltimore, Md.; Jeffrey Boord of the Parkview Health System in Fort Wayne, Ind.; Bertrand Cariou of the Nantes University Hospital in Nantes, France; Alan Chait of the University of Washington in Seattle, Wash.; Henry Fein of the Sinai Hospital in Baltimore, Md.; Henry Ginsberg of the Columbia University in New York, N.Y.; Ira Goldberg of the New York University Grossman School of Medicine; M. Hassan Murad of the Mayo Clinic Evidence-based Practice Center in Rochester, Minn.; Savitha Subramanian of the University of Washington; and Lisa Tannock of the University of Kentucky in Lexington, Ky.

The Society established its?Clinical Practice Guideline Program?to provide endocrinologists and other clinicians with evidence-based recommendations in the diagnosis, treatment, and management of endocrine-related conditions. Each guideline is developed by a writing committee of topic-related experts in the field. Writing committees rely on evidence-based reviews of the literature in the development of guideline recommendations. The Endocrine Society does not solicit or accept corporate support for its guidelines. All Clinical Practice Guidelines are supported entirely by Society funds.

This Clinical Practice Guideline was co-sponsored by the European Society of Endocrinology.

Perfluoroalkyl substances (PFASs) have received intense scrutiny in recent years because of their persistence in the environment and potential endocrine-disrupting effects. However, their estrogenic activities are controversial, with different studies showing apparently contradictory results. Now, researchers reporting in ACS' Environmental Science & Technology have used a combination of laboratory experiments and computer modeling to reveal that PFASs can interact with the estrogen receptor in different ways to influence estrogen-controlled gene expression.

PFASs have been widely used in a variety of household products, including non-stick coatings, polishes, fire-retardant foams and stain-repellant finishes for fabrics. These long-lasting compounds are pervasive in the environment and have been detected in wildlife and humans. In the lab, some PFASs appear to mimic estrogen under certain conditions by binding and activating the estrogen receptor, but they seem to block the hormone's signaling under others. Aiqian Zhang, Jianjie Fu and colleagues wanted to delve deeper into these seemingly contradictory results by studying interactions between various PFASs and the human estrogen receptor, in the presence or absence of the hormone itself. The team reasoned that because estrogen binds much more strongly to its receptor than PFASs, the pollutants probably couldn't completely displace estrogen from the receptor.

The researchers tested the estrogenic and anti-estrogenic behaviors of 10 PFASs using human cells. They found that two of the compounds mimicked estrogen's ability to activate transcription, whereas three others inhibited expression of a reporter gene. However, when the researchers also added estrogen to the cells, all of the compounds blocked the natural hormone's activity. To understand why, the researchers developed a computational model to explore how PFASs bind to the estrogen receptor under different conditions. The model predicted that all of the PFASs could bind to sites on the receptor surface that were distinct from where estrogen binds, including in a groove where coactivators -- which boost the activation of the receptor in the presence of estrogen -- attach. These findings suggest that some PFASs can bind and activate the estrogen receptor when the hormone isn't around, but when it is, the compounds bind to other regions of the receptor, potentially blocking its action, the researchers say.

Nationalistic behaviour by governments may exclude some countries from gaining access to COVID-19 vaccines and cost the global economy up to $1.2 trillion a year in GDP, according to a new study from the not-for-profit research organisation RAND Europe.

If countries demonstrate 'vaccine nationalism' - prioritising their own citizens and insisting on first access to vaccines by signing deals directly with pharmaceutical companies and hoarding supplies - this could mean that, by initially immunising only their own populations, they incur economic penalties for themselves as well as the wider global population.

The study's macroeconomic analysis shows that, as long as the virus is not under control in all regions of the world, there will continue to be a global cost associated with COVID-19 and its prolonged negative impact on certain economic sectors.

Even if only the lowest-income countries were denied equal access to a vaccine and all other countries managed to immunise their populations against the virus, it could still cost the global economy $153 billion a year in GDP terms. The US would lose $16 billion a year, the EU $40 billion a year, the UK $5 billion a year, China $14 billion a year, and other high-income countries collectively $39 billion a year.

The study also notes that there are economic incentives to providing global access to vaccines. Based on previous estimates, it would cost $25 billion to supply lower-income countries with vaccines. The US, UK, EU and other high-income countries combined could lose about $119 billion a year if the poorest countries are denied a supply. If these high-income countries paid for the supply of vaccines, there could be a benefit-to-cost ratio of 4.8 to 1. For every $1 spent, high-income countries would get back about $4.8.

"The study shows that a globally coordinated multilateral effort to fight the pandemic is key, not only from a public health perspective but also an economic one. If too many countries follow a 'vaccine nationalism' approach regarding the development, production and distribution of COVID-19 vaccines, it could seriously hurt globally equitable access for those most at risk," said Marco Hafner, the study's lead author and senior economist at RAND Europe. "Our findings suggest that there are real economic incentives for the higher income countries to drive vaccine development and distribution to ensure that the rest of the world has access to vaccines as soon as possible."

The authors reached their conclusions by comparing the impact on global GDP of physical distancing and changes in consumer behaviour in highly contact-intensive service sectors - such as hospitality, retail and healthcare - to that of a hypothetical baseline scenario where every country manages to sufficiently immunise its population and physical distancing rules and regulations can be eased.

The study also examined the economic costs if no vaccine is developed against the disease. According to the analysis, the global economic cost associated with COVID-19 could be $3.4 trillion a year in lost GDP, compared to a scenario in which all countries can sufficiently inoculate their population.

Hafner said: "Given the substantial economic loss caused by COVID-19, investing heavily in the research and development and upscaling of vaccine manufacturing is key to finding a way out of the pandemic."

Beyond the economic implications, the global competition for vaccines may lead to preventable deaths if vulnerable people in certain countries receive the vaccine after those at low risk in other countries. The study recommends that enforceable frameworks for vaccine development and distribution be established, ensuring equitable access across the world and supporting a programme of inoculation over time.

To mask or not to mask - and which mask to use? With public health guidance about masks in the United States confused by political hedging, clarity around mask use is increasingly important, especially as the western U.S. battles the twin crises of wildfire smoke and COVID-19.

"The CDC is the gold standard of where we find guidance to protect our health, but it's also really important for that information to be spread in ways that people can access and understand it," said Francisca Santana, a PhD student at Stanford University and lead author of a perspective review on mask use published in Environmental Research Letters Oct. 28. "Unfortunately, just a website online may not be effective at communicating that information."

The researchers analyzed studies on large-scale responses to epidemics, drivers of human behavior and reactions to wildfire smoke exposure. Based on what scientists have gleaned in aggregate, they have outlined recommendations for communicating mask use guidelines. For U.S. government agencies, their suggestions include:

Reconciling evidenced-based messaging from federal and local organizations,

Clarifying which masks effectively protect against COVID-19 versus wildfire smoke,

Providing information about mask quantities and where they can be acquired,

Creating infographics or imagery about mask use differences, and

Applying culturally appropriate formats and translating messaging so that it reaches vulnerable groups.

"Even people who understand what they should be doing are not doing it," said senior author Gabrielle Wong-Parodi, an assistant professor of Earth system science at Stanford's School of Earth, Energy & Environmental Sciences (Stanford Earth). "The message needs to be evidence-based, and we need to provide people with behaviorally realistic options that they can actually do and afford."

Social norms

The researchers noted the importance of incorporating the social and psychological influences of mask use behavior - a critical and poorly understood topic they urge scientists to further investigate. "We are social beings, we live in these social contexts and we're not making decisions in isolation, so that's really important to acknowledge in whatever messages are given to the public," Wong-Parodi said. "Just because we put out a great message doesn't mean that people are going to take it up and do it - we need to be sensitive to what people are going through right now."

One pathway to behavior change is through social norms - the shared beliefs within a social group. Common methods for establishing social norms include comparing people's actions to others, providing positive feedback and placing messaging where it is most relevant. That could mean, for example, posting signage about wildfire masks outdoors and COVID-19 masks indoors.

Further investigation is needed to understand if mask wearing can also affect other actions to prevent the spread of infectious disease, such as hand-washing and social distancing, according to the co-authors.

Mistaken behavior

To help fill gaps in research on mask use during wildfires, Santana, a PhD student in the Emmett Interdisciplinary Program in Environment and Resources, interviewed residents affected by wildfire smoke from the 2018 Camp Fire that destroyed Paradise, California.

The discussions indicated that social norms are a powerful driver of mask use, but also revealed instances of maladaptive behavior, when the action taken is ineffective or even harmful. In one interview, Santana learned that during persistent wildfire smoke, someone with asthma wore a mask while sleeping - a practice that can even further stress breathing for people with pre-existing asthmatic conditions. "That highlighted how some of the basic information about how to wear a mask - how to fit it, what conditions should you wear it in - was not permeating all the communities that we were working in," Santana said.

Unlike situations of infectious disease alone, the dual threats of wildfire smoke and COVID-19 have presented a plethora of mask-wearing options with varying effectiveness, depending on the hazard. While an N95 mask is form fitting and must be placed on top of your nose to protect from wildfire smoke, cloth face coverings are advised for indoor COVID-19 protection - and people sometimes wear less-structured cloth masks under their noses, going against the CDC's recommendation to wear them over your nose and mouth to reduce disease transmission.

Social influence

The interviews also revealed a form of social support that is now being repeated during COVID-19: gifting masks to others. While it may or may not actually encourage mask use, that support can influence how people perceive the behaviors of close friends and family.

"Your perception of the behavior of people you're in close contact with matters maybe even more than what they're actually doing, in terms of influencing your own behavior," Wong-Parodi said.

The review also included surveys from China and Japan, where mask-wearing was associated with the perceived threat of pandemics like SARS and H1N1 and strong perceived benefits of masks. More recent research in the U.S. reveals how mask use can indicate political affiliation or fear of racial profiling.

The researchers suggest several areas of study that would help public health communications leverage the social nature of mask use, such as how social norms influence individual health - like the inhalation of smoke - versus collective health such as the spread of COVID-19. Above all, they underscore the importance of communications based on scientific evidence.

"It's really important for public health officials at the local or state level to provide clearer guidance to the public about which masks are appropriate for which events, and to make recommendations for behavior change," Santana said.

PULLMAN, Wash. - Teen-age boys exposed to pro-cannabis advertising and social media posts are more likely than female peers to associate marijuana use with improving sexual activity, new research from Washington State University suggests.

Researchers found that the adolescent males expected cannabis users to be less inhibited and enjoy sex more, leading them to express an intention to use marijuana in the future. Adolescent girls and young women, however, were less swayed to future cannabis use by the messages and perceived links.

"The messages adolescents and young adults are seeing are part of what is having impact, the type of appeal and the content, not just the fact that young people are seeing these messages on social media," said Jessica Fitts Willoughby, lead author on the study and an associate professor with the Murrow College of Communication. "Messages matter."

Beyond the perceived connections between marijuana and sex, the findings show the impact of advertising and social media content that portrays marijuana in a positive light on adolescents as well as young adults, she explained.

Additional conversations between parents and their children, as well as more critical viewing of the content, may be necessary to curb the impact pro-marijuana messages have on the perceptions of viewers, Stacey J.T. Hust, an associate professor with the Murrow College of Communication and a coauthor on the study, said.

"The next step is to identify how advertisements affect people as it relates to sex-related marijuana expectancies as well as the intent for use before and after sex," Hust said.

The WSU team of researchers surveyed two groups as part of the study, more than 300 15-17 year olds and nearly 1,000 college-aged young adults. Each group was asked about their social media habits, exposure to pro-marijuana content, whether in the form of advertisements or user-generated content, their perceived associations between sex and marijuana and their intentions to use marijuana in the future. The young adults were also asked about their past use of marijuana, since it is legal in the state of Washington for people over the age of 21 to consume it.

Regardless of age or gender, researchers found that participants who saw more pro-marijuana content on social media had greater intentions to use cannabis in the future.

Regulating the messages young people see on social media is difficult since the majority of content is user posts, and even content from marijuana businesses often isn't portrayed in the same way it would be in a traditional advertisement, the researchers said.

The authors suggest that these findings indicate more sophisticated regulations around the content of marijuana advertisements, not just where marijuana advertisements are placed, may be necessary. Hust pointed to the alcohol industry's regulatory guidelines that suggest messages should not directly link its products to sexual activity as an example of what may be necessary for marijuana.

Expectations around marijuana and sex wasn't associated with either college-aged men or women's plans to use marijuana in the future.
The study didn't determine why college-aged men weren't influenced in the same way teenage boys were, but the authors said that one possibility is it could be that by college young men typically have more sexual experience to draw on as a means of forming their perceptions of sex and marijuana.

Exposure to pro-marijuana content on social media didn't have the same connections for girls and women related to sex. However, content that was seen as positive of marijuana was still associated with increased intentions to use. The lack of findings related to marijuana and sexual expectations among girls and women could also have to do with concerns related to sexual agency, the authors said.

FAIRFAX, Va. -- Researchers demonstrated the success of a fully implantable wireless medical device, the Stentrode™ brain-computer interface (BCI), designed to allow patients with severe paralysis to resume daily tasks -- including texting, emailing, shopping and banking online -- without the need for open brain surgery. The first-in-human study was published in the Journal of NeuroInterventional Surgery™, the leading international peer-reviewed journal for the clinical field of neurointerventional surgery.

The patients enrolled in the study utilized the Stentrode neuroprosthesis to control the Microsoft Windows 10 operating system in combination with an eye-tracker for cursor navigation, without a mouse or keyboard. The subjects undertook machine learning-assisted training to control multiple mouse-click actions, including zoom and left click.

"This is a breakthrough moment for the field of brain-computer interfaces. We are excited to report that we have delivered a fully implantable, take home, wireless technology that does not require open brain surgery, which functions to restore freedoms for people with severe disability," said Thomas Oxley, MD, PhD, and CEO of Synchron, a neurovascular bioelectronics medicine company that conducted the research. "Seeing these first heroic patients resume important daily tasks that had become impossible, such as using personal devices to connect with loved ones, confirms our belief that the Stentrode will one day be able to help millions of people with paralysis."[1]

Graham Felstead, a 75-year-old man living at home with his wife, has experienced severe paralysis due to amyotrophic lateral sclerosis (ALS). He was the first patient enrolled in the first Stentrode clinical study and the first person to have any BCI implanted via the blood vessels. He received the Stentrode implant in August 2019. With the Stentrode, Felstead was able to remotely contact his spouse, increasing his autonomy and reducing her burden of care. Philip O'Keefe, a 60-year-old man with ALS who works part time, was able to control computer devices to conduct work-related tasks and other independent activities after receiving the Stentrode in April 2020. Functional impairment to his fingers, elbows and shoulders had previously inhibited his ability to engage in these efforts.

The Stentrode device is small and flexible enough to safely pass through curving blood vessels, so the implantation procedure is similar to that of a pacemaker and does not require open brain surgery. Entry through the blood vessels may reduce risk of brain tissue inflammation and rejection of the device, which has been an issue for techniques that require direct brain penetration. Implantation is conducted using well-established neurointerventional techniques that do not require any novel automated robotic assistance.

It is a long journey from harvesting in the field to the cooked dish that reaches the dinner table. The food supply chain covers all those processes and the actors involved in satisfying the consumer's needs. To ensure that the chain is successful requires correct administration of the products in the warehouse, inventory, transport management and coordination between warehouses, transport and destination.

In this sense, the Diverfarming project's research group, framed within work package 6 of the project, in charge of designing and analysing the value chains, and directed by Dr Francisco Campuzano-Bolarín (Universidad Politécnica de Cartagena) has developed a mathematical model that facilitates decision making when planning distribution capacity, and achieves a balance between performance of the inventory and transport in a supply network, taking differing scenarios into account depending on the availability of vehicles.

The model developed is based on the methodology of system dynamics, a recognised way of dealing with problems related to dynamic processes, such as the supply chain. This set of equations, input data and relationships among variables is tested in a frozen products supply chain at national level. This enables to determine the best configuration of parameters to obtain the best decision alternative in terms of costs and inventory levels, optimising the procedure with regard to the costs and stock levels.

This model can be applied to supply chains related with diversified crop systems, which is the objective of the Diverfarming project, financed by the European Commission, and seeks to introduce crop diversification into European agriculture to obtain environmental and economic benefits. To do so, they are also working on the design and analysis of value chains, with the aim of facilitating the adoption and dissemination of diversified agroecosystems. This new model represents a further step towards that objective.

A more sustainable industry 4.0

In the context of the fourth industrial revolution or 'Industry 4.0', understood as the actual trend of automation and data exchange which includes the Internet of things and cloud services, a growth in industrialisation that can upset current industrial systems is foreseen.

The increased consumption of resources, global warming, and climate change that can be derived from this situation make it clear that management practices in the production and supply chain taking sustainability into account (economic, social, and environmental) must be adopted as a strategy to face up to the negative effects derived from industry 4.0.

In this line, the research group in the Diverfarming project, framed within work package 6 of the project, in charge of designing and analysing value chains, and directed by Dr Francisco Campuzano-Bolarín (Universidad Politécnica de Cartagena) has just had a review of the research carried out thus far on the sustainable supply chain in industry 4.0 published in the journal Sustainability. The review concludes that only few studies concern themselves with the social focus of sustainability in industry 4.0., given that the majority tend to focus mainly on habilitating technologies to reduce costs and monitoring. Thus, this work identifies different projects that have adopted sustainability as part of their objectives, as is the case with the H2020 call by the European Commission.

This work, framed within the Diverfarming project, encourages future research lines to centre on referring to a sustainable supply chain from three perspectives: economic, environmental and social, in an integrated manner.

Highly efficient synthesis of ammonia under ambient temperatures and pressures has been drawing increasing attention for wide applications of scientists and industries around the world. Developing highly active and selective materials with transformative catalytic performance for ammonia synthesis is still a giant challenge.

Atomic catalysts (ACs) have long been the research frontier in the field of catalysis because of their unique structures and properties, such as the high atom utilization efficiency, high reaction selectivity and activity, etc. Compared with the traditional single-atom catalysts, graphdiyne (GDY)-based metal ACs feature unique and well-defined chemical and electronic structures, highly catalytic activity and selectivity, which is expected to achieve high selectivity and high yield of ammonia under ambient temperatures and pressures.

Recently, by utilizing the unique properties of GDY, Professor Yuliang Li (Academician of the Chinese Academy of Sciences) published a research paper in National Science Review (NSR), and proposed a new metal ion anchoring-electron transfer-self-reduction strategy for anchoring zero-valent palladium atoms. A free-standing 3D zero-valent atomic catalyst electrode was fabricated and showed high performance in electrocatalysis conversion of nitrogen to ammonia reaction at ambient conditions.

The scanning electron microscopy (SEM), high resolution transmission electron microscopy (TEM), aberration corrected high angle annular dark field (HAADF) scanning transmission electron microscopy (STEM), X-ray near-edge absorption structure (XANES) and extended X-ray absorption fine structure spectrum (EXAFS) results solidly demonstrated that the Pd atoms individually anchored on GDY and exhibited zero-valence state.

This catalyst shows unique advantages such as determined electronic and chemical structure, determined active sites, clear reaction mechanism and process, excellent properties and performance, etc. For example, in neutral conditions, the Pd-GDY catalyst has the highest ammonia yield of 4.45 ± 0.30 mgNH3 mgPd-1 h-1, which is nearly ten orders of magnitude higher than the reported materials; in acidic conditions, its catalytic activity can also reach up to 1.58 ± 0.05 mgNH3 mgPd-1 h-1. The 15N isotope labelling experiments confirmed that the NH3 was formed from the reduction of N2, revealing that the Pd-GDY is highly selective and active toward ammonia synthesis. Moreover, both the ammonia production rate and Faradaic efficiency of the catalyst can be maintained for several cycles without decay, confirming its robust stability.