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Neurodegenerative disorders that cause dementia increase the risk of contracting severe COVID-19 and dying from the disease. For people with Alzheimer’s the risk is three times greater. It can be six times greater if they are over 80, according to a study conducted in Brazil by researchers at the University of São Paulo (USP) and Butantan Institute in partnership with colleagues at the Federal University of Rio de Janeiro (UFRJ).

An article on the study, which was supported by FAPESP, is published in Alzheimer’s & Dementia: The Journal of the Alzheimer's Association.

“We found that all causes of dementia are risk factors for severity and death in COVID-19 and that these risks are more pronounced for Alzheimer’s patients,” Sérgio Verjovski-Almeida, principal investigator for the project and a professor at USP’s Chemistry Institute, told Agência FAPESP.

Dementia had already been identified as a risk factor for COVID-19, alongside other comorbidities, such as cardiovascular and respiratory diseases, high blood pressure, diabetes, obesity, and cancer. One of the reasons is age: patients with dementia tend to be older, and many live in care homes where the risks of infection and viral transmission are greater.

However, no studies had previously been conducted to find out whether people with neurodegenerative disorders that cause dementia, such as Alzheimer’s and Parkinson’s, are more infected by the novel coronavirus and run a greater risk of progressing to the severe form of COVID-19 or dying from the disease, and none so far had set out to see whether old age heightens this risk.

To answer these questions, the researchers investigated data on positive diagnoses, hospitalizations and deaths from COVID-19 for a cohort of 12,863 patients over 65, who tested positive or negative for SARS-CoV-2. The data was included between March and August 2020 in UK Biobank, a biomedical database containing genetic and health information collected from half a million patients since 2006 by a team led by Rory Collins, Professor of Medicine and Epidemiology at the University of Oxford. 

Of the nearly 13,000 subjects, 1,167 tested positive for COVID-19 by RT-PCR. To control for a possible bias associated with younger asymptomatic individuals who were not tested, the researchers excluded subjects aged 49-65 and included only those aged 66 and older, stratifying them into three age groups: 66-74 (6,182), 75-79 (4,867), and 80-86 (1,814). 

“The advantages of using clinical data from UK Biobank include the amount of detail, as the records refer to all pre-existing diseases and whether the patient tested positive, was hospitalized and died from COVID-19,” Verjovski-Almeida explained. “This enabled us to assess the risk factors associated with infection, severity and death from the disease, including all causes of dementia, especially Alzheimer’s and Parkinson’s.”

Statistical analysis showed that all causes of dementia, especially Alzheimer’s, were risk factors for severity of the disease and death in the case of hospitalized patients, regardless of age.

Alzheimer’s specifically did not increase the risk of hospitalization compared with chronic comorbidities. After admission to hospital, however, Alzheimer’s patients ran a threefold risk of developing severe COVID-19 or dying from the disease compared with patients who did not have Alzheimer’s. For Alzheimer’s patients over 80 the risk was six times greater compared with patients in younger age groups.

“Some factor that hasn’t yet been identified increases the predisposition of Alzheimer’s patients to progress to severe COVID-19 and die from the viral disease,” Verjovski said. “The results of our study point to a need for special attention to these patients when hospitalized.”

Diagnostic hypotheses 

A possible explanation for the observed outcomes is that chronic inflammatory conditions or defective immune responses due to aging of the immune system (immunosenescence) may increase the vulnerability of these patients and reduce their capacity to mount an effective response to infection by the virus.

Another hypothesis is that Alzheimer’s alters the permeability of the blood-brain barrier, making infection of the central nervous system more likely.

Recent research has shown that SARS-CoV-2 is able to invade the central nervous system via the olfactory mucosa and that the presence of the virus in this region results in a local inflammatory immune response. The same study detected the virus in the brainstem, which comprises the primary cardiovascular and respiratory control center, raising the possibility that infection of the central nervous system may mediate or aggravate respiratory and cardiovascular problems in COVID-19 patients.

“We will now analyze these patients’ genomes, also available from UK Biobank, to find out which genes are mutated and may be implicated in the augmented risk of severe COVID-19 and death for Alzheimer’s patients,” Verjovski-Almeida said.

ITHACA, N.Y. - Water regulation in leaves is vital to a plant's health, affecting its growth and yield, disease susceptibility and drought resistance.

A breakthrough technology developed by Cornell University researchers uses nanoscale sensors and fiber optics to measure water status just inside a leaf's surface, where water in plants is most actively managed.

The engineering feat provides a minimally invasive research tool that will greatly advance the understanding of basic plant biology, and opens the door for breeding more drought-resistant crops. The technology could eventually be adapted for use as an agronomic tool for measuring water status in crops in real time.

The study in maize plants, "A Minimally Disruptive Method for Measuring Water Potential In-Planta Using Hydrogel Nanoreporters," published June 1 in the Proceedings of the National Academy of Sciences.

"One of the goals is to have tools that allow internal biology to be expressed out into the world in a way that can be captured and digitized," said senior author Abraham Stroock, professor in the Smith School of Chemical and Biomolecular Engineering in the College of Engineering.

"Current techniques for measurements of water potential require destructive sampling of leaves or disrupting leaf function," said co-first author Piyush Jain, a doctoral student in mechanical engineering. The new method, he said, "provides minimally disruptive and spatially and temporally resolved measurements of water potential in leaves of intact plants."

Outside of leaves' transport tissues, called xylem (the veins), lies an interior zone called the mesophyll, where most of the plant's photosynthesis and water stress occurs. Biologists suspect that signals are sent from here to the rest of the plant for managing water. Also, at the surfaces of leaves and stems, pores called stomata open and close to control the rate of exchange of gasses, mostly water vapor and carbon dioxide.

The new technology works in this microscopic zone.

"We are now sensing water right at that terminal place," Stroock said. "We've shown that by getting such a localized measurement, we can dissect the dynamics of water in the tissues" in minimally invasive ways, he said.

The technique involves injecting a nanoparticles formed of a soft synthetic hydrogel, called AquaDust, for measuring a leaf's water potential. The hydrogel, which occupies the interstitial spaces between cells in the mesophyll, is water-absorbent, swelling and shrinking based on water availability in the leaf.

The AquaDust contains dyes whose interactions allow it to fluoresce at different wavelengths depending on how close the dye molecules are to each other. By using fiber optics, the researchers can shine a light and get a spectrum back, which provides a measurement of water potential inside the leaf.

In the study, the researchers injected the AquaDust in multiple places along meters-long maize leaves and then measured the water gradients both along the length of the leaves and through the mesophyll. These measurements allowed them to develop a model of the tissue response to water stress and accurately predict the dynamics observed in the field.

This technology may have commercial applications for crop research, production agriculture, and manufacturing industries, but for now the researchers' focus is on the invaluable measurements of very local physiology of water management in plants. As a research tool, it allows plant biologists to better understand extremes of water stress, which could lead to breeding more water-efficient crops.

Sickle Cell Disease (SCD) is a genetically inherited group of red blood cell disorders. According to the CDC, an estimated 90,000 to 100,000 people in the United States live with this disease, and it disproportionately affects Black or African Americans; it occurs in roughly 1 in every 500 individuals in this demographic.

Researchers from the University of Pittsburgh Swanson School of Engineering used a unique and powerful MRI device to study the disease's impact on the brain and published their results in Neuroimage: Clinical. They discovered that SCD can have a severe effect on specific subfields of the hippocampus - a highly complex part of the human brain that controls learning and memory and is very susceptible to injury or disorders.

"This is a first-of-its-kind project that uses our lab's whole-body 7-Tesla magnetic resonance imager (7T MRI) alongside our optimized Tic Tac Toe RF head coil system to get clear and quality neural images of patients affected by SCD," said Tamer Ibrahim, professor of bioengineering and director of the Radiofrequency (RF) Research Facility and the 7-Tesla Bioengineering Research Program (7TBRP).

Individuals with SCD have red blood cells that contain an abnormal hemoglobin. This can cause the red blood cells to become hard, sticky and mutate into a unique crescent shape which inhibits the cell's passage through small blood vessels. These blockages affect blood and oxygen flow and consequently cause tissue damage -- the source of many SCD complications.

7-Tesla imaging has revealed abnormalities in the hippocampus for other neurodegenerative and neuroinflammatory diseases, so Ibrahim and his collaborators investigated SCD to see if it has a similar effect.

"Our findings support and extend previous reports of reduced hippocampal volume in SCD patients but provide more insights on the specific hippocampal subfields that are impacted," Ibrahim explained. "The subfields are tiny structures within the hippocampus which can only be seen in ultrahigh resolution acquisitions -- a feature of 7-Tesla imaging -- and enhanced with the 'Tic-Tac-Toe' antenna technology."

The next steps of this research are to investigate the mechanisms that lead to these structural changes in addition to electrical changes in the brain and how they relate to cognitive performance in SCD patients.

Advancing "Tic-Tac-Toe"-Themed MRI Technology

Ibrahim continues to improve the lab's 7-Tesla imaging technology, which is leveraged in 28 active collaborative projects funded by the National Institutes of Health. It is the most widely-used RF coil system in a given 7-Tesla site.

This advanced technology can provide higher resolution and enhanced contrast human MRI images, but its operational frequency (~?297 MHz) remains an obstacle in realizing the device's full potential. Ibrahim's group published recent findings related to their technology in Scientific Reports.

"The major challenge of the 7-Tesla imaging is the inhomogeneities, or lack of uniformity, of the RF fields inside the human head, resulting in brain images with voids in certain anatomical regions," said Tales Santini, a postdoctoral associate in the RF Research Facility. "In the past 12 years, our lab has developed innovative RF antenna designs which greatly increase the homogeneity of the fields, thus, enabling high resolution whole-brain images with minimal or no voids."

You would not be surprised to see an elephant in the savanna or a plate in your kitchen. Based on your prior experiences and knowledge, you know that is where elephants and plates are often to be found. If you saw a mysterious object in your kitchen, how would you figure out what it was? You would rely on your expectations or prior knowledge. Should a computer approach the problem in the same way? The answer may surprise you. Cold Spring Harbor Laboratory Professor Partha Mitra described how he views problems like these in a "Perspective" in Nature Machine Intelligence. He hopes his insights will help researchers teach computers how to analyze complex systems more effectively.

Mitra thinks it helps to understand the nature of knowledge. Mathematically speaking, many data scientists try to create a model that can "fit an elephant," or a set of complex data points. Mitra asks researchers to consider what philosophical framework would work best for a particular machine learning task:

"In philosophical terms, the idea is that there are these two extremes. One, you could say "rationalist," and the other "empiricist" points of view. And really, it's about the role of prior knowledge or prior assumptions."

Rationalists versus empiricists

A rationalist views the world through the lens of prior knowledge. They expect a plate to be in a kitchen and an elephant in a savanna.

An empiricist analyzes the data exactly as it is presented. When they visit the savanna, they no more expect to see an elephant than they do a plate.

If a rationalist came across this set of data points in the kitchen, they might at first be inclined to view it as a plate. Their prior knowledge states that a plate is likely to be found in a kitchen; it is highly unlikely to find an elephant. They have never seen this situation before, nor have they ever learned that such a situation could occur. Although their result takes in a certain amount of the data, it leaves out other parts. In this case, their methods have produced an incorrect result: a plate.

When an empiricist sees the same data, they will analyze it without regard to whether they are in the savanna or their kitchen. They will piece together an image from as many data points as possible. In this case, their result is a jagged image. It doesn't tell the empiricist if they are looking at an elephant, a plate, or anything else.

Neither the empiricist nor the rationalist is wrong. Both approaches work for various kinds of problems. However, in this case, if there is an elephant in the kitchen, it would pay to figure it out as quickly as possible. A middle ground between purely empirical and purely rationalist approaches may be best. With some prior knowledge of what an elephant looks like, you may notice the trunk and legs. And although the chances of an elephant being in your kitchen are low, it is certainly not impossible. Therefore, you would come to the conclusion that there is indeed an elephant in your kitchen, and you probably should leave--fast.

Predictable but wrong

Data scientists face this sort of problem all the time. They train computers to recognize new objects or patterns. Some machine learning programs may be able to process a lot of information and make many rules to fit the presented data, like the jagged image above. The jagged image might be reproducible when the same rules are applied to another similar data set. But just because the pattern is reproducible, that doesn't mean it accurately represents what is happening (the elephant).

There are historical examples of this dilemma. Two thousand years ago, Ptolemy developed a model of the universe that yielded excellent predictions for the movements of the moon and planets. His model was used successfully for centuries. However, Ptolemy used the wrong prior information: he placed the Earth at the center of the solar system and prioritized the circular motions of celestial objects. Johannes Kepler questioned this view in the 17th century and ultimately rejected Ptolemy's approach, which eventually led to Newton's law of universal gravitation. Although Ptolemy's complex model fit his own observations exceptionally well, it did not accurately represent what was happening. Mitra warns that "if you want to be an extreme empiricist, you really do need a lot of data. We now understand why under certain circumstances, such an approach can, in fact, succeed in a mathematically rigorous setting. Biological brains, on the other hand, are halfway in between. You do learn from experience, but you're not entirely data-driven."

Mitra hopes that data scientists will look to brain circuitry for inspiration when developing next-generation machine learning approaches. Vertebrate brains have circuits of different sizes, including medium-sized (mesoscale) ones. Those circuits are encoded with priors (known information, such as what animals look like, where they are found, or how to escape quickly from a charging elephant). At the same time, your brain is highly flexible, classifying new information and weighing the importance of different priors based on experience--elephants may not belong in a kitchen, but somehow, you have one anyway. Mitra concludes in his article:

"This points to the possibility of a new generation of intelligent machinery based on distributed circuit architectures which incorporate stronger priors, possibly drawing upon the mesoscale circuit architecture of vertebrate brains."

HOUSTON - (June 3, 2021) - Postpartum women in bad romantic relationships are not only more likely to suffer symptoms of depression, they are also at greater long-term risk of illness or death, according to new research from Rice University, Ohio State University and the University of California, Irvine.

"Longitudinal changes in HRV across pregnancy and postpartum: Effect of negative partner relationship qualities" will appear in the July 2021 edition of Psychoneuroendocrinology. The researchers examined how relationships and partner behavior are linked to depression and heart rate variability (HRV) in women between the third trimester of pregnancy and one year postpartum.

"The quality of relationship with one's spouse considerably affects one's mental health as well as biological health and physiology," said Lisa Christian, an associate professor of psychiatry and behavioral health at Ohio State University and a co-author of the study. "We were interested in learning more about the effects of relationship quality on health during the postpartum period, due to substantial changes occurring physically, mentally and in social and interpersonal lives at this time."

The researchers used the Positive and Negative Quality in Marriage Scale to measure negative relationship qualities and the Center for Epidemiologic Studies Depression Scale to evaluate mental health. The researchers also monitored HRV during regular check-ins with the study participants throughout the first year postpartum.

During pregnancy, HRV naturally drops. The researchers found that postpartum women who had poor relationships with their spouses or partners were more likely to report symptoms of depression. These were linked to HRV that was more likely to remain low following pregnancy.

This matters because HRV has a significant link to long-term health and wellness, said Ryan Linn Brown, a Rice psychology graduate student and Biobehavioral Mechanisms Explaining Disparities (BMED) lab researcher. She is the study's lead author.

"High HRV is good. It means your body is well-equipped to deal with and recover from stressors," she said. "Low HRV means your body isn't as capable of managing stress, and previous research has demonstrated that poorly managed stress can put you at greater risk of a host of health problems."

Brown said the research demonstrates a clear link between the quality of spousal relationships during pregnancy and postpartum depression and HRV, which ultimately can impact long-term wellness and mortality of new mothers.

The researchers hope the study findings will aid the development of mental health interventions that will help postpartum women live healthier lives.

RESEARCHERS at the University of Huddersfield have warned there is an urgent need for the country's mental health interventions to create strategies optimising the use of antidepressants after conducting a study which has highlighted an alarming rise in relation to usage and costs.

The open-access study, published by the international DARU Journal of Pharmaceutical Sciences, is entitled 'Surging trends in prescriptions and costs of antidepressants in England amid COVID-19' and has investigated the trends in prescriptions and costs of various antidepressants in England during the COVID-19 pandemic.

The researchers discovered that the total number of antidepressant prescriptions drugs dispensed during 2020 had increased by four million items since 2019 costing NHS England £139 million more than in the previous year.

This is attributed to the active pharmaceutical ingredient shortages witnessed during COVID19 coupled with a significantly higher cost of generic drugs during the pandemic, with just one product alone sertraline, an SSRI antidepressant drug, accounting for a majority of the additional costs.

While an increase in the number of prescriptions had been predicted because of the pandemic, said the University's Dr Syed Shahzad Hasan, one of the co-authors of the study, it was the sharp rise in antidepressant prescription costs which was a potential cause for concern and highlighted the urgent need for mental health interventions in the country and strategies to optimise the use of antidepressants.

The study also observes a meta-analysis of 100,000 patients using antidepressants which concluded that the risk of suicide doubled in children and adolescents.

"These findings are particularly important in the context of the COVID-19 pandemic," said Dr Hamid Merchant from the University. "Observational data suggest that young adults, up to 25 years of age, were impacted by the mental health issues during the pandemic, and hence, were more likely to use antidepressants."

Recommendations

The research recommends that further studies are needed to assess the age distribution of antidepressant prescriptions particularly focusing on adolescents and young adults who are at a higher risk of experiencing life-threatening adverse effects.

"It is, therefore, important to optimise the safe use of antidepressants, particularly in young adults," added Dr Merchant. "Not only to help with mental health but also in preventing the associated side-effects that may further increase the morbidity and mortality associated with depression in younger adults."

A new study by ecologist André de Roos* shows that differences between juveniles and adults of the same species are crucial for the stability of complex ecological communities. The research, published in Proceedings of the National Academy of Sciences, represents a major advance in ecological modeling at a time when biodiversity is declining and species around the world are rapidly going extinct.

Up to now, ecological models have focused exclusively on the interactions between species, ignoring the variations within them. The dragonflies, frogs, trout, and phytoplankton in a freshwater pond, for example, would be represented as nodes in a network, connected by edges that represent how each species feeds on the others. 

Using computer simulations, de Roos was able to model both the number of total species in a community and key variations within the same species, accounting for differences between juveniles and adults. He says these differences arise not only because adults reproduce, while juveniles grow and mature, but also because juveniles, being of smaller body size, are generally more limited by food availability than adults and run a much greater risk of being captured by predators. These differences lead to variations over time in the ratio of juveniles to adults, which tip the entire community from instability to stability.

"On the basis of the network of species interactions alone the simulated communities are predicted to be wildly unstable," he writes, "but these destabilizing forces are swamped and fully attenuated by the stabilizing effects of the dynamics of juvenile and adult densities."

The study advances a long-running debate in ecology over the relationship between species diversity and ecosystem stability. (A debate which, de Roos notes, was fueled by a 1972 paper by the late ecologist Robert May).  

"Ecologists have long intuited that diversity can stabilize ecosystems, and even protect them against collapse," de Roos says. "Theoretically, however, we struggled with a good explanation for that idea. What we're now discovering through computation and quantitative analysis is that our existing theories fall short, because diversity is more than just a number of species connected by a network of interactions. The interplay between different types of complexity is what determines the function of the system."

HAMILTON, ON (June 3, 2021) - A novel longitudinal study on heavy drinking in young adults and the psychological impacts of COVID-19 has revealed some unexpected findings that challenge preconceived notions regarding pandemic-related alcohol use.

In a sample of nearly 500 young adults ranging in age from 18 to 25, researchers saw a reduction in problematic drinking and alcohol consequences during the initial phase of the pandemic for both men and women. This is in contrast to many anecdotal reports of increased drinking and increased household spending on alcohol during that time period.

More startling, however, were the additional findings that showed increased rates of depression and anxiety symptoms among young women - increases that were not observed to a significant degree among male participants.

"These results reveal the complexity of the pandemic impacts," said senior author James MacKillop. MacKillop is the director of the Peter Boris Centre for Addictions Research of McMaster University and St. Joseph's Healthcare Hamilton, as well as a professor of psychiatry and behavioural neurosciences at McMaster.

Researchers suspect that restrictions on socializing contributed to the reduction of risky alcohol use observed in this age group. With a decreasing proportion of individuals living with roommates or in group living arrangements, peer influence - usually a strong predictor of alcohol misuse - has decreased.

"The study participants were young people, who typically drink in social settings," said Meenu Minhas, lead author of the study and a postdoctoral fellow at the Peter Boris Centre for Addictions Research. "If you take away bars, restaurants, and group events, like parties, it's not surprising that binge drinking in this group goes down too."

Conversely, the reported increase of mental health symptoms in the study illustrates some of the negative consequences associated with the pandemic. Among study participants, women showed a substantial increase in the odds of meeting the threshold for clinical depression from pre- to intra-pandemic. A similar effect was not found in male participants.

"We saw high levels of pandemic-related stress, irritability, sadness, which unfortunately were felt more strongly by females," said Minhas.

"Although certain public health measures were important in controlling the spread of the virus, the benefits of social support and interaction, which often act as buffers against the effects of stress, have also been reduced due to the pandemic," explained MacKillop.

Pandemic-related income loss was also found to be attributed to increased depression scores, with those reporting greater than 50 percent income loss experiencing significant increases in depressive symptoms. Researchers see this as a direct link between economic impacts and adverse mental health outcomes. They argue that government strategies that provide economic assistance may effectively act like an antidepressant when it comes to pandemic impacts on mental health.

Other studies on substance use during the pandemic have tended to use cross-sectional designs, meaning they do not account for changes over time. In contrast, the present study used a longitudinal design that tracked the same cohort before and during the pandemic.

"Collectively, these results indicate the importance of critical thinking and considering population subgroups when it comes to COVID-19's psychological impacts," said MacKillop. "Rather than uniform increases or decreases, it's increasingly clear that subgroups will show very different patterns, including both negative and, in some cases, positive changes."

TAMPA, Fla. -- There are several new treatment options available for patients with advanced melanoma. While these therapies have greatly improved the prognosis for patients, each person can respond to the treatments differently. Treatment of melanomas that have spread to the central nervous system is especially challenging. In a new article published in Clinical Cancer Research, Moffitt Cancer Center researchers reveal how different therapies impact the surrounding immune environment of metastatic melanoma tumors according to location and identify a rare population of immune cells that is associated with improved overall survival.

Different types of cancer tend to spread to specific sites throughout the body. Common sites of melanoma metastases are the brain, lungs, liver and bones. Approximately 40% to 60% of melanoma patients develop metastatic disease within the central nervous system, while 5% of patients develop metastatic disease within the area of the leptomeninges, the two innermost layers of tissue that cover the brain and spinal cord, and the cerebrospinal fluid. Patients with leptomeningeal melanoma metastases have a very poor prognosis, with a mean survival of only eight to 10 weeks. Despite this poor prognosis, a handful of patients with leptomeningeal melanoma metastases show increased survival, but the reasons for this are unclear.

"Overall, we know very little about the tumors at this site or why they prove to be so deadly. We hope these insights will lead to the development of novel therapies, with the ultimate goal of improving clinical outcomes of patients with leptomeningeal melanoma metastases," said Inna Smalley, Ph.D., first author on this study and assistant member of the Cancer Physiology Department.

Moffitt researchers want to improve their understanding of why some metastatic melanoma patients respond better than others and determine which cellular factors contribute to these improved responses across different metastatic sites. They analyzed the RNA expression patterns of individual melanoma and immune cells from 26 patients with metastatic melanoma of the skin, brain and leptomeninges/cerebrospinal fluid, and used this information to determine the specific immune cell types that were present within each sample. They discovered that the types of cells within the tumor microenvironment varied according to the site of metastasis. Leptomeningeal melanoma metastases were characterized by an immune-suppressed environment, with a high percentage of dysfunctional CD4 and CD8 T cells that are incapable of mounting an immune response, and low levels of B cells. Alternatively, samples from brain and skin metastases were much more alike in their immune environment, with an enrichment for activated CD4 T cells.

The researchers analyzed how the immune environment of metastatic sites is modulated by different regimens and what types of immune cells are associated with better responses. They compared data from a patient with leptomeningeal melanoma metastases who had a good response to treatment and survived for more than 38 months, to data from five patients who had poor responses to treatment. They found that the long-term survivor had an immune environment that was more like patients without leptomeningeal disease, whereas poor responding patients had immune environments characterized by immunosuppressive myeloid cells and exhausted lymphocytes, a recipe for diminished antitumor responses. Samples derived after treatment revealed that the long-term survivor had cells characteristic of an active immune response, and patients who responded poorly to therapy did not have these cells present.

A further analysis of dendritic cells that play an important role in therapy response showed that a subpopulation, called DC3s, were associated with improved overall survival and the presence of an active T cell immune response, regardless of the site of metastasis or treatment history. The researchers confirmed the importance of DC3s to patient outcomes through preclinical studies in mouse models.

"Our study provides the first insights into the immune microenvironment of patients with leptomeningeal melanoma metastases and helps to clarify why these individuals do so poorly," said Keiran Smalley, Ph.D., director of the Donald A. Adam Melanoma and Skin Cancer Center of Excellence at Moffitt. "The tissue microenvironments of brain and leptomeningeal metastatic sites are very distinct and show differential responses to systemic therapy."

KINGSTON, R.I. - June 3, 2021 - Scientists from the University of Rhode Island have taken the first steps toward understanding the function of microbes that live on and in Eastern oysters, which may have implications for oyster health and the management of oyster reefs and aquaculture facilities.

"Marine invertebrates like oysters, corals and sponges have a very active microbiome that could potentially play a role in the function of the organism itself," said Ying Zhang, URI associate professor of cell and molecular biology. "We know very little about whether there are resident microbes in oysters, and if there are, what their function may be or how they may help or bring harm to the oyster."

Zhang and doctoral student Zachary Pimentel extracted the DNA of microbes living in or on the gut, gill, inner shell, mantle and other tissues of oysters to identify the microbes that live there. They then applied a metagenomics technology to reconstruct the genome of the most abundant microbes to better understand the nature of the oyster microbiome and the function of some of the microbes.

"This was the first overview of what microbes live in certain parts of Eastern oysters," said Pimentel, the lead author on a paper about the study published in May by the American Society for Microbiology. "In humans, we know that the microbes that live in the gut versus the skin are quite different. But we didn't know about the compartmentalization of certain microbes in certain oyster tissues."

The researchers identified one microbe, a bacterium in the class Mollicutes, that gains energy from the consumption of chitin, a substance found throughout the marine environment. It was most abundant in the gut of the oysters and appears to be an indicator of a healthy oyster, but when found in other tissues, it may be correlated with infections.

"When they're abundant in the gut of healthy oysters, that may indicate that the oysters are happy to have them," Zhang said. "But when the microbe gains abundance in other tissues, that may be a sign that the oyster is not doing well, maybe because the immune system is freaked out."

The same microbe was also discovered to consume arginine, an amino acid found in all organisms that is used to create proteins.

"We're really interested in that one because it has potential implications for the immune system of oysters," Pimentel said. "Oysters rely on arginine for its immune response. A pathogen has been found to steal the arginine to hide from the oyster's immune system, so it's really interesting that there's another microbe that uses arginine and has potential implications for oyster immunity."

Once the researchers have identified the function of key beneficial microbes, the next step is to learn when and where the microbes are acquired.

"One microbe was found to be abundant in adult oysters but very rare in larval samples," Zhang said. "So they could be acquired at some point in their growth, but when and how they are acquired is a big question. If we know they are important and we can identify the source of where they came from, then perhaps we can help preserve the population of this specific microbe."

According to Zhang and Pimentel, oysters play an important role in building reefs, filtering water, and providing other ecological functions, in addition to their role in supporting the aquaculture industry. Further research about the microbiome of oysters could be beneficial to understanding more about oyster health and the health of their ecosystem.

"We know for other organisms that the microbiome is a really important factor when considering health and disease, so we're laying the groundwork for future research that might implicate certain microbes in important processes related to health and disease," Pimentel said.

"The more we know about oysters and their interactions with microbes, the more we'll understand about how to conserve them," added Zhang.

MEMPHIS, Tenn. - Cardiovascular imaging demonstrated no evidence of myocardial injury or myocarditis in athletes after COVID-19 infection, according to a research letter published in Circulation by Le Bonheur Children's Hospital and the University of Tennessee Health Science Center cardiologists. The screening and evaluation was conducted by the Le Bonheur Children's Heart Institute Sports Cardiology team, Benjamin S. Hendrickson, MD, Ranjit R. Philip, MD, and Ryan E. Stephens, NP-C, MBA, and Le Bonheur Director of Cardiac MRI Jason N. Johnson, MD, MHS. Researchers say this study confirms existing recommendations that cardiovascular screening can be deferred in COVID-19 positive athletes who are asymptomatic or have milder symptoms.

"Concern for cardiovascular disease as a result of COVID-19 brought about recommendations for evaluating athletes after infection," said Johnson. "Our results show that none of the athletes who underwent cardiac MRI had abnormal findings."

137 collegiate athletes from three universities competing across the National Collegiate Athletic Association (NCAA) Divisions 1, 2 and 3 were evaluated in sports cardiology clinic no sooner than 10 days after testing positive. The athletes were young adults from a broad range of sports and various racial ethnic backgrounds - 48% black, 47% white and 7% Hispanic.

Le Bonheur Children's and UTHSC cardiologists used an algorithm-guided screening to evaluate the athletes. Regardless of symptoms or illness severity, cardiologists obtained a 12-lead electrocardiogram (ECG), transthoracic echocardiogram and conventional cardiac troponin I (cTn) level from each COVID-19 positive athlete. If any of these tests were abnormal or the athlete had a clinical evaluation of concern, they were referred for cardiac MRI (CMR). Athletes with normal evaluations and negative tests or negative CMR had exercise slowly reintroduced and eventually returned to full participation.

Study findings include:

Most athletes (82%) were symptomatic and experienced mild (67%) or moderate (33%) symptoms. None of the athletes had severe COVID-19 illness.

Only five (3.6%) athletes had abnormal testing that required CMR. Of these five, none had abnormal CMR results consistent with myocardial injury or myocarditis.

None of the athletes had new symptoms or other health problem after resuming exercise and normal competition.

"On the basis of the outcomes and follow-up in our cohort, it is reasonable to defer cardiovascular screening in asymptomatic athletes or those with milder COVID-19," said Philip. "Cardiac screening, testing and imaging can be guided by the severity of symptoms and illness in an athlete."

The North American mockingbird is famous for its ability to imitate the song of other birds. But it doesn't just mimic its kindred species, it actually composes its own songs based on other birds' melodies. An interdisciplinary research team has now worked out how exactly the mockingbird constructs its imitations. The scientists determined that the birds follow similar musical rules as those found in human music, from Beethoven to Kendrick Lamar.

The song of the mockingbird is so complex that to investigate it required a joint effort of experts from very different fields. Neuroscientist Tina Roeske of the Max Planck Institute for Empirical Aesthetics, field biologist Dave Gammon of Elon University, and the music philosopher David Rothenberg of the New Jersey Institute of Technology combined their different approaches and areas of expertise to conduct this highly unusual study, the findings of which have just been published in the open-access journal Frontiers in Psychology.

Lead author Tina Roeske designed the algorithms used in testing the team's hypotheses.

"When you listen for a while to a mockingbird," she explains, "you can hear that the bird isn't just randomly stringing together the melodies it imitates. Rather, it seems to sequence similar snippets of melody according to consistent rules. In order to examine this hunch scientifically, however, we had to use quantitative analyses to test whether the data actually supported our hypotheses."

The results were unambiguous. The authors identified four compositional strategies that mockingbirds use in transitioning from one sound to the next: changing timbre, changing pitch, stretching the transition (lengthening it in time), and squeezing it (shortening it in time). The complex melodies they create are music to the ears not only of other birds but of humans as well. So, it should come as no surprise that (human) composers of varied musical styles use similar techniques in their work.

As co-author David Rothenberg explains in a YouTube video, the Tuvan throat singing group Huun-Huur-Tu presents examples of timbre change, and pitch change can be heard in the famous opening of Beethoven's Fifth Symphony; the song "Show Yourself" from the Disney film Frozen 2 itself shows the stretching of sound transitions; and if you listen very closely to Kendrick Lamar's song "Duckworth" from the album Damn, you'll hear transitions being squeezed, or shortened.

COVID-19 continues to claim lives across the world and is infecting millions more. Although several vaccines have recently become available, making significant strides towards preventing COVID-19, what about the treatment of those who already have the infection? Vaccines aren't 100% effective, highlighting the need--now more than ever--for effective antiviral therapeutics. Moreover, some people can't receive vaccines due to health issues, and new variants of SARS-CoV-2, the virus that causes COVID-19, that can penetrate vaccine-conferred immunity, are being reported, indicating that we need to think beyond prevention.

Given this need, a team of researchers based in Japan, the US, and the UK launched a project to develop effective therapeutics. This team included several researchers based at Tokyo University of Science: Visiting Professor Koichi Watashi, Dr. Hirofumi Ohashi, Professor Shin Aoki, Professor Kouji Kuramochi, and Assistant Professor Tomohiro Tanaka. Their goal was clear and simple: finding a cure for COVID-19.

To achieve this goal, the researchers first established an experimental system for screening drugs that may help to control infections. This system used a type of cells called VeroE6/TMPRSS2 cells, which were manipulated to efficiently be infected with and produce SARS-CoV-2. "To determine whether a drug of interest could help combat infection by SARS-CoV-2, we simply had to expose VeroE6/TMPRSS2 cells to both the drug and SARS-CoV-2 and then observe whether the drug's presence served to hinder the virus's efforts to infect cells," explains Professor Watashi.

The researchers used this experimental system to screen a panel of drugs that are already approved for clinical use, including drugs like remdesivir and chloroquine that have already being approved or are being trialed as treatments for COVID-19. In an exciting outcome, the researchers found two drugs that provided effective SARS-CoV-2 suppression: cepharanthine, which is used to treat inflammation, and nelfinavir, which is approved for the treatment of HIV infection.

Cepharanthine inhibited the entry of the virus into cells by preventing the virus from binding to a protein on the cell membrane, which it uses as a gateway. In contrast, nelfinavir worked to prevent the virus from replicating inside the cell by inhibiting a protein that the virus relies on for replication. Given that these drugs have distinct antiviral mechanisms, using both of them together could be especially effective for patients, with computational models predicting that combined cepharanthine/nelfinavir therapy can hasten the clearance of SARS-CoV-2 from a patient's lungs by as few as 4.9 days.

So, does this mean we will be seeing these new drugs in COVID-19 treatment centers? Of course, the drug duo isn't ready to be rolled out into healthcare systems just yet. These findings justify further research into the clinical potential of cepharanthine/nelfinavir therapy, and only following this can we say for sure that it is useful and helpful.

Nevertheless, given the ongoing nature of the COVID-19 pandemic and the ever-increasing death toll, the development of cepharanthine/nelfinavir therapy may provide clinicians and patients with a much-needed new treatment option.

People who use methamphetamine are more likely to have health conditions, mental illness, and substance use disorders than people who do not use the drug, according to a new study by researchers at the Center for Drug Use and HIV/HCV Research (CDUHR) at NYU School of Global Public Health. The findings are published in the Journal of General Internal Medicine.

The use of methamphetamine--a highly addictive and illegal stimulant drug--has increased in recent years, as have overdose deaths. Methamphetamine can be toxic for multiple organs including the heart, lungs, liver, and neurological system, and injecting the drug can increase one's risk for infectious diseases.

"Methamphetamine can complicate the management of existing chronic illnesses, but we know little about the chronic disease profile of people who use it," said study author Benjamin Han, MD, a clinician-researcher in the Division of Geriatrics, Gerontology, and Palliative Care in the Department of Medicine at the University of California San Diego.

Using data from the 2015-2019 National Survey on Drug Use and Health, a nationally representative survey of U.S. adults, the researchers estimated the prevalence of medical conditions, mental illnesses, and other substance use among those who reported using methamphetamine within the past year.

Compared to adults who do not use the drug, people who use methamphetamine were nearly twice as likely to have medical multimorbidity (two or more chronic medical conditions), more than three times as likely to have mental illness, and more than four times as likely to have a substance use disorder. Many have a combination of medical, mental, and substance use issues, including all three concurrently.

Of the chronic illnesses studied, people using methamphetamine had a higher prevalence of liver disease (hepatitis or cirrhosis), lung disease (COPD or asthma), and HIV/AIDS. The researchers also found that those using methamphetamine had a considerably higher likelihood of substance use disorders for all drugs studied, including heroin, prescription stimulants, prescription opioids, cocaine, and sedatives.

"Our results certainly do not suggest that meth use causes most of these conditions, but they should inform clinicians that this population is at risk. Future studies are needed to determine how dose and frequency of use relate to these conditions--for instance, occasional use on a night out versus chronic use that can lead to a host of adverse effects on the body," said study author Joseph Palamar, PhD, an associate professor of population health at NYU Grossman School of Medicine and a CDUHR researcher. "We also confirmed the well-known link between meth use and HIV, which can result from injection drug use or sexual transmission, but more research is needed to determine the extent to which meth use increases risk for STDs due to the drug's libido-enhancing effects."

The researchers note the importance of a harm reduction and patient-centered approach to care for people who use methamphetamines, and one that can coordinate management of mental illness, medical disease, and substance use disorders.

"Methamphetamine use adds complexity to the already-challenging care of adults who have multiple chronic conditions," added Han, who is also a CDUHR researcher. "Integrated interventions that can address the multiple conditions people are living with, along with associated social risks, are needed for this population."

Facing the triple threat of climate change, loss of nature and pollution, the world must deliver on its commitment to restore at least one billion degraded hectares of land in the next decade - an area about the size of China. Countries also need to add similar commitments for oceans, according to a new report by the UN Environment Programme (UNEP) and the Food and Agriculture Organization of the UN (FAO), launched as the UN Decade on Ecosystem Restoration 2021-2030 gets underway.

The report, #GenerationRestoration: Ecosystem restoration for People, Nature and Climate, highlights that humanity is using about 1.6 times the amount of services that nature can provide sustainably.

That means conservation efforts alone are insufficient to prevent large-scale ecosystem collapse and biodiversity loss. Global terrestrial restoration costs - not including costs of restoring marine ecosystems - are estimated to be at least USD 200 billion per year by 2030. The report outlines that every 1 USD invested in restoration creates up to USD 30 in economic benefits.

Ecosystems requiring urgent restoration include farmlands, forests, grasslands and savannahs, mountains, peatlands, urban areas, freshwaters, and oceans.

Communities living across almost two billion of degraded hectares of land include some of the world's poorest and marginalized.

"This report presents the case for why we must all throw our weight behind a global restoration effort. Drawing on the latest scientific evidence, it sets out the crucial role played by ecosystems, from forests and farmland to rivers and oceans, and it charts the losses that result from a poor stewardship of the planet," UNEP Executive Director, Inger Andersen, and FAO Director-General, QU Dongyu, wrote in the report's foreword.

"Degradation is already affecting the well-being of an estimated 3.2 billion people - that is 40 percent of the world's population. Every single year we lose ecosystem services worth more than 10 percent of our global economic output," they added, stressing that "massive gains await us" by reversing these trends.

Ecosystem restoration is the process of halting and overturning degradation, resulting in cleaner air and water, extreme weather mitigation, better human health, and recovered biodiversity, including improved pollination of plants. Restoration encompasses a wide continuum of practices, from reforestation to re-wetting peatlands and coral rehabilitation.

It contributes to the realization of multiple Sustainable Development Goals (SDGs), including health, clean water, and peace and security, and to the objectives of the three 'Rio Conventions' on Climate, Biodiversity, and Desertification.

Actions that prevent, halt and reverse degradation are necessary to meet the Paris Agreement target of keeping global temperature rise well below 2 degrees Celsius.

Restoration, if combined with stopping further conversion of natural ecosystems, may help avoid 60 percent of expected biodiversity extinctions. It can be highly efficient in producing multiple economic, social and ecological benefits concurrently - for example, agroforestry alone has the potential to increase food security for 1.3 billion people, while investments in agriculture, mangrove protection and water management will help adapt to climate change, with benefits around four times the original investment.

Reliable monitoring of restoration efforts is essential, both to track progress and to attract private and public investments. In support of this effort, FAO and UNEP also launch today the Digital Hub for the UN Decade, which includes the Framework for Ecosystem Restoration Monitoring.

The Framework enables countries and communities to measure the progress of restoration projects across key ecosystems, helping to build ownership and trust in restoration efforts. It also incorporates the Drylands Restoration Initiatives Platform, which collects and analyses data, shares lessons and assists in the design of drylands restoration projects, and an interactive geospatial mapping tool to assess the best locations for forest restoration.

Restoration must involve all stakeholders including individuals, businesses, associations, and governments. Crucially, it must respect the needs and rights of Indigenous Peoples and local communities, and incorporate their knowledge, experience and capacities to ensure restoration plans are implemented and sustained.