Culture

According to the American Heart Association, heart disease is the leading cause of death worldwide in recent years. During a heart attack, or myocardial infarction (MI), a blocked artery and the resulting oxygen deprivation cause massive cardiac cell death, blood vessel impairment and inflammation. Now, researchers reporting in ACS Biomaterials Science & Engineering have developed a cardiac patch with tiny engineered blood vessels that improved recovery from MI in rats and pigs.

To effectively treat MI, lost heart muscle tissue must regenerate and new blood vessels must form to restore oxygen and nutrients to cells. Scientists have tried to develop patches containing various therapeutic cells to treat MI, but so far most have been too cumbersome to make, or they don't restore both cardiac muscle and blood supply to the injured site. Ke Cheng and colleagues previously developed a relatively easy-to-make pre-vascularized cardiac patch, which contained engineered microvessels in a fibrin gel spiked with cardiac stromal cells. When implanted into rats after an MI, the cells in the patch secreted growth factors that made cardiac muscle and blood vessels regrow. Now, the researchers wanted to test the patch further in rats, as well as in pigs, which have cardiovascular systems more similar to humans than those of rodents.

The researchers implanted the cardiac patch in rats that recently had a heart attack. Four weeks later, rats that received the patch had less scar tissue, increased cardiac muscle and improved cardiac pump function compared with untreated rats. The team observed similar effects in pigs that had undergone MI and were treated with the patches. The patch increased recruitment of the pigs' progenitor cells to the damaged area and enhanced the growth of new blood vessels, as well as decreased cardiac cell death and suppressed inflammation. Although prior studies have used blood vessel-forming cells or natural blood vessels to vascularize cardiac patches, this study is the first to demonstrate the success of pre-vascularized cardiac stromal cell patches using microengineered synthetic blood vessels for treating MI in a large animal model. More studies on the mechanisms, safety and efficacy of patch repair are needed before the technology can be applied to humans, the researchers say.

Dementia and other cognitive disorders now appear to be risk factors for developing severe COVID-19, according to research from the University of Georgia. The findings highlight the need for special care for populations with these preexisting conditions during the pandemic.

In a blind study, the researchers analyzed data from nearly 1,000 diseases and two specific genes to compare the health profiles of COVID-19 patients with those testing negative, looking for commonalities in the COVID-19 patients.

The study, published online in the journal Brain, Behavior and Immunity, relied on data from UK Biobank, a long-term study of more than 500,000 participants investigating the respective contributions of genetic predisposition and environmental exposure to the development of disease.

Beginning in March, the UK Biobank started to report the COVID-19 status of its participants. The team in the Franklin College of Arts and Sciences department of genetics, led by assistant professor Kaixiong Ye and his postdoc, Jingqi Zhou, promptly connected the COVID-19 status to the electronic health data.

"We took a hypothesis-free approach and the most statistically significant ones are the cognitive disorders and Type 2 diabetes," said Ye, the senior author on the study. "Right now, we don't know the mechanisms behind these associations, we only know these are more common in COVID-19 patients."

Analyzing the genetic factors that make some individuals at higher risk for severe COVID-19, the team focused on two genes: ACE2 and TPMPRSS2, known to be critical for the virus to enter into human cells.

"In the TMPRSS2 gene we found that a specific genetic variation is more common in the COVID-19 patient," he said, adding that while the discovery was novel at the time, the team knows more data now exists about host genetic factors than even three months ago.

The research team also found that variations in genes related to SARS-CoV-2 infection may be associated with severe COVID-19 that requires hospitalization.

"And we are starting to understand how those genetic variations are making a difference," he said, noting the extraordinary pace of research worldwide during the pandemic as scientists work on SARS CoV 2. Since they began in spring 2020, Ye's group has been able to follow up on its own earlier work and communicate with peers around the world to contribute to the overall body of knowledge about the disease.

"Working on one disease, the whole field is converging together, around the world, at the same time. It really showcases the power of science," Ye said. "What my group is doing is really just data analysis, large-scale data mining, but from vaccine development to studies in patients, scientists are attacking the disease from different aspects, and that's moving us forward very quickly in combating COVID-19."

DALLAS - Oct. 28, 2020 - Two new studies suggest Medicare's system of penalizing hospitals if too many patients are readmitted within 30 days should also look at whether the patients were well enough to remain in their home during that time.

The studies propose adding a new metric to examine how many of the initial 30 days following hospitalization are actually spent at home - a "risk-adjusted 30-day home time" test to balance the current "30-day risk-standardized readmission rate" measure.

"The current readmission penalty has been a matter of debate," says Ambarish Pandey, M.D., first author of the study published today in JAMA Cardiology, as well as of an earlier study published in Circulation in July.

"Some hospitals that have had lower readmission rates were actually having high mortality rates," says Pandey, assistant professor of internal medicine at UT Southwestern. "If you die, you're not going to be readmitted."

In addition, the current focus on hospital readmissions does not take into account patients who wind up in a skilled nursing facility or intermediate/long-term care facility after hospital discharge, Pandey points out.

A "30-day home time" metric, he says, would paint a more comprehensive picture and be more patient-centered.

The federal Centers for Medicare & Medicaid Services (CMS) tracks readmissions as part of its effort to improve the quality of care in the nation's hospitals. In 2019, CMS penalized almost 2,600 U.S. hospitals by withholding an estimated $563 million in Medicare payments after determining they exceeded the expected number of patient readmissions, according to the Circulation study.

CMS focuses its readmissions standard on cases involving heart failure, myocardial infarction (heart attack), and pneumonia.

The studies examined how applying a 30-day home-time metric would have affected the quality rankings of hospitals treating heart failure (the JAMA Cardiology study) and acute myocardial infarction (Circulation), based on Medicare claims data. In both studies, the researchers found that using the 30-day home-time metric changed the quality ranking a hospital had received under the readmission standard about 30 percent of the time.

The JAMA Cardiology study found that heart failure patients spent a risk-adjusted median of 21.77 days at home in the 30 days after discharge. However, 6.61 days were spent in an intermediate/long-term or skilled nursing facility, and another 1.37 days were lost to death. Readmission accounted for only 1.25 of the days lost.

Similarly, in the Circulation study, patients stayed home a risk-adjusted median of 24.0 days, with 4.7 days subtracted for nursing facilities, 2.5 days for death, and 1.0 days for readmission.

Hospitals with higher 30-day home time were larger and more likely to be academic medical centers, according to the studies.

The findings suggest that the 30-day home-time metric complements the existing readmission rate metric "by not only accounting for post-discharge mortality but also the variability in the post-acute care utilization of intermediate/long-term care facility and [skilled nursing facilities]," according to today's JAMA Cardiology study.

In addition, "a home time metric may be more easily understood by patients and clinicians," the study says.

Fourteen out of every 1,000 COVID-19 patients admitted to hospital experience a stroke, a rate that is even higher in older patients and those with severe infection and pre-existing vascular conditions, according to a report published this week.

COVID-19 has become a global pandemic, affecting millions of people worldwide. In many cases, the symptoms include fever, persistent dry cough and breathing difficulties, and can lead to low blood oxygen. However, the infection can cause disease in other organs, including the brain, and in more severe cases can lead to stroke and brain haemorrhage.

A team of researchers at the Stroke Research Group, University of Cambridge, carried out a systematic review and meta-analysis of published research into the link between COVID-19 and stroke. This approach allows researchers to bring together existing - and often contradictory or under-powered - studies to provide more robust conclusions.

In total, the researchers analysed 61 studies, covering more than 100,000 patients admitted to hospital with COVID-19. The results of their study are published in the International Journal of Stroke.

The researchers found that stroke occurred in 14 out of every 1,000 cases. The most common manifestation was acute ischemic stroke, which occurred in just over 12 out of every 1,000 cases. Brain haemorrhage was less common, occurring in 1.6 out of every 1,000 cases. Most patients had been admitted with COVID-19 symptoms, with stroke occurring a few days later.

Age was a risk factor, with COVID-19 patients who developed stroke being on average (median) 4.8 years older than those who did not. COVID-19 patients who experienced a stroke were on average (median) six years younger than non-COVID-19 stroke patients. There was no sex difference and no significant difference in rates of smokers versus non-smokers.

Pre-existing conditions also increased the risk of stroke. Patients with high blood pressure were more likely to experience stroke than patients with normal blood pressure, while both diabetes and coronary artery disease also increased risk. Patients who had a more severe infection with SARS­CoV­2 - the coronavirus that causes COVID-19 - were also more likely to have a stroke.

The researchers found that COVID-19-associated strokes often followed a characteristic pattern, with stroke caused by blockage of a large cerebral artery, and brain imaging showing strokes in more than one cerebral arterial territory. They argue that this pattern suggests cerebral thrombosis and/or thromboembolism are important factors in causing stroke in COVID-19. COVID-19-associated strokes were also more severe and had a high mortality.

An important question is whether COVID-19 increases the risk of stroke or whether the association is merely a result of COVID-19 infection being widespread in the community.

"The picture is complicated," explained Dr Stefania Nannoni from the Department of Clinical Neurosciences at the University of Cambridge, the study's first author. "For example, a number COVID-19 patients are already likely to be at increased risk of stroke, and other factors, such as the mental stress of COVID-19, may contribute to stroke risk.

"On the other hand, we see evidence that COVID-19 may trigger - or at least be a risk factor for - stroke, in some cases. Firstly, SARS­CoV­2 more so than other coronaviruses - and significantly more so than seasonal flu - appears to be associated with stroke. Secondly, we see a particular pattern of stroke in individuals with COVID-19, which suggests a causal relationship in at least a proportion of patients."

The researchers say there may be several possible mechanisms behind the link between COVID-19 and stroke. One mechanism might be that the virus triggers an inflammatory response that causes thickening of the blood, increasing the risk of thrombosis and stroke. Another relates to ACE2 - a protein 'receptor' on the surface of cells that SARS-CoV-2 uses to break into the cell. This receptor is commonly found on cells in the lungs, heart, kidneys, and in the lining of blood vessels - if the virus invades the lining of blood vessels, it could cause inflammation, constricting the blood vessels and restricting blood flow.

A third possible mechanism is the immune system over-reacting to infection, with subsequent excessive release of proteins known as cytokine. This so-called 'cytokine storm' could then cause brain damage.

The team say their results may have important clinical implications.

"Even though the incidence of stroke among COVID-19 patients is relatively low, the scale of the pandemic means that many thousands of people could potentially be affected worldwide," said Professor Hugh Markus, who leads the Stroke Research Group at Cambridge.

"Clinicians will need to look out for signs and symptoms of stroke, particularly among those groups who are at particular risk, while bearing in mind that the profile of an at-risk patient is younger than might be expected."

While the majority of strokes occurred after a few days of COVID-19 symptoms onset, neurological symptoms represented the reason for hospital admission in more than one third of people with COVID-19 and stroke.

Dr Nannoni added: "Given that patients admitted to hospital with symptoms of stroke might have mild COVID-19-related respiratory symptoms, or be completely asymptomatic, we recommend that all patients admitted with stroke be treated as potential COVID-19 cases until the results of screening in the hospital are negative."

We're told from a young age not to eat too much sugar, but in reality, our bodies are full of the stuff. The surface of every living cell, and even viruses, is covered in a mess of glycans: long, branching chains of simple sugars linked together by covalent bonds. These cell-surface sugars are crucial for regulating cell-cell contact, including the attachment of bacteria to healthy host cells. Glycans are also found on all other biological polymers, including proteins and RNA, and their presence impacts the polymers' stability and function.

Despite their ubiquity and importance, glycans remain poorly understood because of their complexity. Rather than just the four nucleotide "letters" that make up DNA and RNA molecules, glycans have an "alphabet" of hundreds of different monosaccharides that can be strung together into sequences with a seemingly infinite array of lengths and branches. In addition, an individual glycan sequence can be changed due to the interplay of multiple enzymes and conditions both within and outside a cell, without the need for genetic mutations.

Now, a team of scientists from the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Massachusetts Institute of Technology (MIT) has cracked the glycan code by developing new machine learning and bioinformatics methods that enable researchers to systematically study glycans and identify sequences that play a role in the interactions of microbes and their host cells, as well as other still-unknown functions. The tools are presented in a new paper published today in Cell Host & Microbe, and are available online as a free Wyss WebApp that researchers can use to perform their own analyses of thousands of glycans.

"The language-based models that we have created can be used to predict whether and how a given glycan will be detected by the human immune system, thus helping us determine whether a strain of bacteria that harbors that glycan on its surface is likely to be pathogenic," said first author Daniel Bojar, Ph.D., a Postdoctoral Fellow at the Wyss Institute and MIT. "These resources also enable the study of glycan sequences involved in molecular mimicry and immune evasion, expanding our understanding of host-microbe interactions."

Glycan grammar rules

Because glycans are the outermost layer of all living cell types, they are necessarily involved in the process of infection, both in the interaction of a prokaryotic bacterium binding to a eukaryotic host cell, and the interactions between the cells of the immune system. This has created an evolutionary arms race, in which bacterial glycans evolve to mimic those found on their hosts' cells to evade immune detection, and hosts' glycans are modified so that pathogens can no longer use them to gain access. To trace this history of glycan sequence development and identify meaningful trends and patterns, the research team turned to machine learning algorithms -- specifically, natural language processing (NLP), which has previously demonstrated success in analyzing other biopolymers, like RNA and proteins.

"Languages are actually quite similar to molecular sequences: the order of the elements matters, elements that are not next to each other can still influence each other, and their structures evolve over time," said co-author Rani Powers, Ph.D., a Senior Staff Scientist at the Wyss Institute.

First, the team needed to assemble a large database of glycan sequences on which an NLP-based algorithm could be trained. They combed through existing datasets both online and in the academic literature to create a database of 19,299 unique glycan sequences, which they dubbed SugarBase. Within SugarBase they identified 1,027 unique glycan molecules or bonds they termed "glycoletters" making up the glycan alphabet, which could theoretically be combined into "glycowords" that the team defined as three glycoletters and two bonds.

To develop an NLP-based model that could analyze sequences of glycoletters and pick out distinct glycowords, the team chose to use a bidirectional recurrent neural network (RNN). RNNs, which also underlie the "autocomplete" feature of text messaging and email software, predict the next word in a sequence given the preceding words, enabling them to learn complex, order-dependent interactions. They trained their glycoletter-based language model, dubbed SweetTalk, on sequences from SugarBase, and used it to predict the next most probable glycoletter in a glycan sequence based on the preceding glycoletters, in the context of glycowords.

SweetTalk revealed that from the close to 1.2 trillion theoretically possible glycowords, only 19,866 distinct glycowords (~0.0000016%) were present in the database of existing glycans. The observed glycowords also tended to be clustered together in groups with highly similar sequences, partly indicating the taxonomic groups in which the glycowords are found, rather than distributed evenly among all possible sequence combinations. These outcomes likely reflect the high "cost" to an organism of evolving dedicated enzymes to construct specific glycan substructures - in that scenario, it is more evolutionarily efficient to tweak existing glycowords rather than generate completely new ones.

Given the important role glycans play in human immunity, the researchers fine-tuned SweetTalk using a smaller, curated list of glycans that are known from the literature to cause an immune response. When predicting the immunogenicity of glycan sequences from SugarBase, the SweetTalk model achieved an accuracy of ~92%, compared to an accuracy of ~51% for a model trained on scrambled glycan sequences. For example, glycans that are rich in a simple sugar called rhamnose, which is found in bacteria but not in mammals, were unambiguously labeled as immunogenic by SweetTalk. The model's excellent performance indicated that language-based models could be used to study characteristics of glycans on a large scale and with many potential applications, such as the exploration of glycan-immune system interactions.

Pour some sugar on me

Based on the success of their first glycan-focused deep learning model, the team had a hunch that deep learning could also illuminate the "family tree" of glycan sequences. To achieve this, they constructed a language model-based classifier called SweetOrigins. They first pre-trained SweetOrigins with a SweetTalk model, then used the language-like properties of glycans to fine-tune the new model on a different task: predicting the taxonomic group of glycans by learning species-specific features of glycans that indicate their evolutionary history. They replicated this structure for each level of classification, from individual species all the way up to domains (e.g., Bacteria, Eukarya), creating eight SweetOrigins models that were able to classify the taxonomic group of a glycan with high accuracy. For example, the model accurately predicted glycans from the kingdoms Animalia (91.1%) and Bacteria (97.2%), allowing a glycan of unknown origin to be quickly classified as either animal-associated, microbe-associated, or found on both cell types.

The researchers then used SweetOrigins to investigate host-pathogen interactions, reasoning that differences in the glycans associated with various strains of E. coli bacteria could be used to predict how infectious the strains are. They trained a deep learning-based classifier with the same language model architecture as SweetOrigins on E. coli-specific glycan sequences, and were able to predict E. coli strain pathogenicity with an accuracy of ~89%. It also placed the majority of glycans that are associated with E. coli strains of unknown pathogenicity at various places along the spectrum of infectiousness, helping to identify strains that are likely to be pathogenic to humans.

"Interestingly, the glycans that our model predicts are most associated with infection bear a striking resemblance to glycans found on the cells that form the mucosal barriers in animals' bodies, which keep pathogens out," said Diogo Camacho, Ph.D., a co-corresponding author of the paper and Senior Bioinformatics Scientist at the Wyss Institute. "This suggests that the glycans on pathogenic bacteria have evolved to mimic those found on the hosts' cells, facilitating their entry and evasion of the immune system."

To more deeply probe how glycans function in host-microbe interactions, the team developed a glycan sequence alignment method, which compares individual glycan sequences to determine regions that are conserved between glycans and, therefore, likely serve a similar function. They chose a specific polysaccharide sequence from the pathogen Staphylococcus aureus that is known to increase bacterial virulence and hypothesized that this glycan helped the bacterium escape immune detection. When they compared that polysaccharide to similar glycan sequences in the dataset, they found the best alignment result with the enterobacterial common antigen (ECA), a glycan found on the Enterobacteriaceae family of symbiotic and pathogenic bacteria.

The team also found ECA-like sequences associated with bacteria in the Staphylococcus, Acinetobacter, and Haemophilus genera, which are not part of the Enterobacteriaceae family that typically carries the ECA. This insight suggests that, in addition to mimicking the glycans found on their hosts, bacterial glycans can also evolve to mimic those found on other bacteria such as those in our microbiome, and that pathogenicity can arise via glycans on microbes that are not traditionally thought to be dangerous.

"The resources we developed here -- SugarBase, SweetTalk, and SweetOrigins -- enable the rapid discovery, understanding, and utilization of glycan sequences, and can predict the pathogenic potential of bacterial strains based on their glycans," said co-corresponding author Jim Collins, Ph.D., a Wyss Core Faculty member who is also the Termeer Professor of Medical Engineering & Science at MIT. "As glycobiology progresses, these tools can be readily expanded and updated, eventually allowing for the precise classification of glycans and facilitating the glycan-based study of host-microbe interactions at unprecedented resolution, potentially leading to new antimicrobial therapeutics."

"This achievement is yet another example of the power of applying computational approaches to biological problems that have so far defied resolution because of their complexity. I am also very impressed with this team for making their tools openly available to researchers around the world, which promises to accelerate the pace of our collective understanding of glycans and their impact on human health," said Wyss Institute Founding Director Don Ingber, M.D., Ph.D. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at Harvard's John A. Paulson School of Engineering and Applied Sciences.

Ann Arbor, October 28, 2020 - A new study in the American Journal of Preventive Medicine, published by Elsevier, presents new data that address important questions pertaining to the containment of the coronavirus pandemic: When should COVID-19 quarantine really end and which continuing symptoms may be more indicative of a positive test in recovered patients?

The study was conducted by the Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy, where a multidisciplinary healthcare service was established for all patients who have recovered from COVID-19 to study what happens to them after recovery and to assess the impact of the virus on their bodies.

Investigators report that close to 17 percent of patients considered fully recovered from COVID-19 tested positive for the virus in follow-up screening. Patients who continued to have respiratory symptoms, especially sore throat and rhinitis, were more likely to have a new positive test result. This suggests the persistence of these two symptoms should not be underestimated and should be adequately assessed in all patients considered recovered from COVID-19.

"Clinicians and researchers have focused on the acute phase of COVID-19, but continued monitoring after discharge for long-lasting effects is needed," explained lead investigator Francesco Landi, MD, PhD, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, and Catholic University of the Sacred Heart, Rome, Italy.

The study included 131 patients who met the World Health Organization (WHO) criteria for discontinuation of quarantine at least two weeks prior to the follow-up visit. The WHO criteria specify that the patient should be fever-free without fever-reducing medications for three days, show improvement in any symptoms related to COVID-19, be more than seven days past symptom onset, and test negative for the SARS-CoV-2 virus twice, at least 24 hours apart, with reverse transcription PCR (RT-PCR) testing.

A new RT-PCR test was administered at the time of post-acute care admission. Demographic, medical, and clinical information was collected, with an emphasis on the persistence of symptoms and signs related to COVID-19 such as cough, fatigue, diarrhea, headache, smelling disorders, loss of appetite, sore throat, and rhinitis.

Twenty-two (16.7 percent) of the patients tested positive again. There was no significant difference between patients with positive and negative test results in terms of age or sex. None of the patients had fever and all reported improvement in their overall clinical condition. Time since onset of disease, number of days hospitalized, and treatments received while hospitalized were not significant. However, some symptoms such as fatigue (51 percent), labored breathing (44 percent) and coughing (17 percent) were still present in a significant percentage of the patients studied, although there were no significant differences between individuals with a positive or negative test. The only two symptoms that were higher and significantly prevalent in patients with a positive test were sore throat (18 percent vs. 4 percent) and signs of rhinitis (27 percent vs. 2 percent).

Our findings indicate that a noteworthy rate of recovered patients with COVID-19 could still be asymptomatic carriers of the virus," Dr. Landi observed. "The main question for the containment of SARS-CoV-2 pandemic infection that still needs to be answered is whether persistent presence of virus fragments means the patients is still contagious. The RT-PCR test looks for small fragments of viral RNA. A positive swab test can reveal if patients are still shedding viral fragments, but it is not able to discern whether they are or aren't infectious."

Importantly, the investigators recommend that for patients who continue to have symptoms potentially related to COVID-19, it is reasonable to be cautious and avoid close contact with others, wear a face mask, and possibly undergo an additional nasopharyngeal swab.

Stromboli, the 'lighthouse of the Mediterranean', is known for its low-energy but persistent explosive eruptions, behaviour that is known scientifically as Strombolian activity. This feature has long been an attraction for tourists and volcanologists from all over the world.

Occasionally, however, more intense and sudden explosions occur, most recently in July and August last year (2019). These are known as 'Strombolian paroxysms'. During such events several of Stromboli's craters are active simultaneously and much greater volumes of pyroclastic materials are erupted than is usual for the volcano.

In a new study, Major explosions and paroxysms at Stromboli (Italy): a new historical catalog and temporal models of occurrence with uncertainty quantification, published in the journal Nature Scientific Reports, researchers from Italy's National Institute of Geophysics and Volcanology (INGV) and the University of Bristol use historical records to estimate the frequency of these bigger Strombolian paroxysms and investigate if the volcano has its own eruption 'memory' as evidenced, in statistical terms, by a temporal recurrence relationship between one paroxysmal eruption and the next.

The catalogue describes 180 violent explosive events of varying scale that occurred at Stromboli from 1879 to 2020. The researchers critically evaluated events described in past scientific works and information recorded in historical texts, and then determined, on an objective and homogeneous evidential basis, the type and intensity of the explosive events. This involved appraising any narrative hyperbole in the old descriptions.

Massimo Pompilio, senior researcher at INGV and co-author of the study, said: "The new catalogue makes it possible to review the classification of numerous events through the critical analysis of historical sources. From the analysis it emerges that the average annual rate of paroxysms over the last 140 years was, roughly, one event every four years or so". This rate is close to that observed for the last ten years, but is much lower than in the 1940s, when these paroxysmal events were much more frequent.

"The volcano therefore alternates between periods of intense activity and periods of relative quiet. The short span of 56 days observed between the two paroxysms of summer 2019 is not a rare situation. Five times in the past 140 years there have been even shorter inter-event times (intervals between events). Conversely, there have been four periods without paroxysms lasting from between nine to 15 years, and one interval without paroxysms that lasted for 44 years, from 1959 to 2003."

This information is useful in a forecasting context as it can help estimate the probabilities of future occurrence of these volcanic phenomena.

Andrea Bevilacqua, INGV researcher and first author of the study explains: "When a phenomenon such as a volcanic explosion occurs at irregular intervals in time, what is studied is the distribution of the 'inter-event' times, i.e. the times elapsed in passed between one explosion and the next. In particular, the development of inter-event models allows us to calculate the probability of an explosion occurring as a function of the time elapsed since the last event of that type".

"An important finding that emerged from our research concerns the tendency of paroxysms to occur in clusters. On the basis of data from the last 140 years, we have estimated that there is a 50 per cent probability that another Stromboli paroxysm might follow a previous explosion within 12 months, and a 20 per cent probability that it could follow in less than two months; on the other hand, there is a 10 per cent probability that more than ten years could pass without any other paroxysm occurring."

The novelty and uniqueness of this new research will be of great interest to volcanologists and scientists worldwide. Augusto Neri, Director of the Volcanoes Department of the INGV and co-author of the study, said: "The analysis of Stromboli's data suggests the existence of a physical process that influences the recurrence of this volcano's explosions, meaning they not completely random, out-of-the-blue events". Statisticians describe such repeating sequences as 'memory' processes. "Understanding the reasons and physical mechanisms that determine this memory represents a further scientific challenge. But the estimation of the memory in episodes of intense explosive activity of Stromboli will make a significant contribution to the quantification of the likelihood of these dangerous phenomena and, consequently, to the reduction of associated risks".

Willy Aspinall, Emeritus Professor in the School of Earth Sciences at Bristol, added: "Volcano tourism has grown substantially in recent years, and an unexpected eruption at a popular setting can be fatal, as happened last year at White Island/Whakaari volcano, New Zealand. Knowing that a particular volcano exhibits this eruption memory effect means any temporary increase in explosion probability can be appraised and, for example, inform decisions about volcanological fieldwork at the craters. However, it is premature at this stage to discuss possible implications of this research for wider aspects of civil protection on Stromboli."

The University of Cincinnati is decoding the genetics of agricultural pests in projects that could help boost crop and livestock production to feed millions more people around the world.

Joshua Benoit, an associate professor in UC's College of Arts and Sciences, contributed to genetic studies of New World screwworms that feed on livestock and thrips, tiny insects that can transmit viruses to tomatoes and other plants.

It's the latest international collaboration for Benoit, who previously sequenced the DNA for genomes of  dreaded creatures such as bedbugs.

Just in time for Halloween, Benoit's new study subject is no less creepy. The New World screwworm's Latin name means "man-eater." These shiny blue flies with pumpkin-orange eyes lay up to 400 eggs in open cuts or sores of cattle, goats, deer and other mammals. Emerging larvae begin gnawing away on their hosts, feeding on living and dead tissue and creating ghastly wounds.

"Sometimes you'll see a deer missing a chunk of its head. The flies can cause small wounds to become massive injuries," he said.

Benoit and his co-authors sequenced the genome of screwworms and identified ways of slashing populations by targeting particular genes that determine sex and control growth and development or even particular behaviors that help the flies find a suitable animal host.

The study led by entomologist Maxwell Scott at North Carolina State University was published in the journal Communications Biology.

"Our main goal was to use the genomic information to build strains that produce only males for an enhanced sterile-insect program," Scott said.

The New World screwworm is an agricultural menace that causes billions of dollars in livestock losses each year in South America, where it is common. The fly was a scourge in North America as well but was eradicated from the United States in 1982 with intense and ongoing population controls.

Today, a lab operated by Panama and the U.S. Department of Agriculture has established a biological barrier outside Panama City, a geographic choke point between the two continents.

"They rear flies in a lab, sterilize them with chemicals or  radiation and dump  these sterile male flies into the environment from a plane so they mate with the females and produce no offspring," Benoit said.

Year by year, agriculture experts gradually pushed the screwworm out of Texas, Mexico and most of Central America.

"They just used straight brute force and good science ," Benoit said. "They just drove them down all the way to Panama."

Today, Panama and the United States continue to air-drop sterile screwworms by the millions each week over the choke point to prevent the species from moving north.

A 2016 outbreak in the Florida Keys threatened to wipe out endangered Key deer before the USDA intervened, treating infected animals with a parasite medicine and releasing millions of sterile screwworms on the island chain until they disappeared.

"The U.S. still helps pay for control programs in Panama mainly because we don't want screwworms coming back here. It's the cheapest way to prevent potentially billions of dollars in damage," Benoit said.

One possible way to cut costs would be to raise only male screwworms that are intended for release so the lab wouldn't incur the huge costs of feeding female screwworms. UC's genetic study could help scientists cull females before they hatch.

"So you're left with surviving males. Then you sterilize the males and that would save a lot of money because you'd only have to raise the males for release," he said.

Next, Scott said he wants to understand how the livestock-devouring screwworm Cochliomyia hominivorax evolved as a parasitic meat eater while similar species prefer carrion.

Benoit also contributed to a genomic study in the journal BMC Biology for an insect not much bigger than the dot over the letter i. Thrips, a tiny winged insect, are legion around the world and feed on a wide variety of crops, including soybeans, tomatoes -- even cannabis. They can destroy crops both by eating them and transmitting harmful viruses.

In a study led by entomologist Dorith Rotenberg at North Carolina State University, researchers mapped 16,859 genes that helped understand the thrips' sensory and immune systems and the salivary glands that transmit the viruses.

"The genome provides the essential tools and knowledge for developing genetic pest management strategies for suppressing thrips pest populations," Rotenberg said.
 

One thrips virus is a particular agricultural concern: the spotted wilt virus, which studies have found can reduce a crop's yield by as much as 96%.

"We're talking hundreds of millions of dollars in losses," Benoit said. 

The study found that thrips can be finicky eaters and have unique genetic adaptations that likely allows them to feed on many insects. They pierce the plant and suck the juices.

And thrips have surprisingly sophisticated immune systems, the study found. Researchers identified 96 immune genes, more than many other insects studied to date. 

"We mapped the genome, but we also characterized immune aspects and how they feed," Benoit said. "It was the first study of its kind to explain what underlies their reproductive mechanisms. It was far more detailed than previous genomic studies we've done."

The study was funded in part by the National Science Foundation and a UC faculty development research grant.

Benoit said the solution to a thrips infestation predictably has been pesticides. But the UC study could help find better environmental solutions, he said.

"Pesticides do not discriminate at all. The same pesticide that kills a termite can kill a bee. When you spray, it can kill other beneficial insects," Benoit said. "So we don't want to eradicate species as much as find better ways to control them so we don't have to use as much pesticide."

(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