Culture

Frailty is the medical term for becoming weaker or experiencing lower levels of activity or energy. Becoming frail as we age increases our risk for poor health, falls, disability, and other serious concerns.

Aging increases the risks for becoming frail. As more of us live longer, it's likely that frailty will pose a larger public health problem in the near future. Experts in geriatrics (the field of health care focused on care for older adults) suggest that maintaining a healthy lifestyle may reduce your chances of becoming frail.

One aspect of a healthy lifestyle is getting regular physical activity. However, studies on the association between physical activity and frailty among older adults show different results. Some studies suggest that regular physical activity could delay frailty and reduce its severity, but other studies do not. And most of the studies have examined people aged 50 to 70, so the information we have for people over age 70 is limited.

To address this gap, researchers conducted a new study as part of a European project that promotes healthy aging in older adults. They examined the benefits of assistance that helps older adults follow their prescribed medications and prevent falls, frailty, and loneliness. The participants received care at study sites in five European countries (Spain, Greece, Croatia, the Netherlands, and the United Kingdom). The study results were published in the Journal of the American Geriatrics Society.

Among other questions, the participants were asked, "How often do you engage in activities that require a low or moderate level of energy such as gardening, cleaning the car, or taking a walk?"

Researchers considered that "regular frequency" was engaging in such activities more than once a week; "low frequency" involved engaging in these activities once a week or less.

Of the participants, 1,215 adults over the age of 70 were included in the group that received assistance. 1,110 received no intervention but were followed for comparison. Participants in the first group received a risk assessment, shared decision-making, and care aimed at reducing their fall risk, inappropriate medication use, loneliness, and frailty.

Compared with participants who were moderately active at the start of the study, participants who were moderately active once a week or less were significantly more physically, psychologically, and socially frail at the study's follow-up period.

The participants who were regularly, moderately active were the least frail, and participants who were moderately active less than once a week were the most frail.

The researchers learned that people over 70 who were physically active on a regular basis, as well as people who increased their level of activity to a regular basis, were able to improve or maintain their level of frailty--not only physically, but also psychologically and socially.

Every time you hear a deep rumble and feel your house shake when a big truck roars by, that's partly because the weight of heavy vehicles causes a slight deflection in the road surface under them. It's enough of a dip to make a difference to the trucks' overall fuel efficiency.

Now, a theoretical study by MIT researchers suggests that small changes in roadway paving practices could reduce that efficiency loss, potentially eliminating a half-percent of the total greenhouse gas emissions from the transportation sector, at little to no cost.

The findings are detailed in a paper in the journal Transportation Research Record, by MIT postdoc Hessam Azarijafari, research scientist Jeremy Gregory, and principal research scientist in the Materials Research Laboratory Randolph Kirchain. The study examined state-by-state data on climate conditions, road lengths, materials properties, and road usage, and modeled different scenarios for pavement resurfacing practices.

They found that that one key to improving mileage efficiency is to make pavements that are stiffer, Kirchain explains. That reduces the amount of deflection, which reduces wear on the road but also reduces the slightly uphill motion the vehicle constantly has to make to rise out of its own depression in the road.

"When we as individuals walk on pavements, they seem like perfectly rigid things. They're not responding to us," he says. "But for trucks, that is not the case. There is enough of a deflection in that surface that some amount of energy is expended to overcome the little divot that you create as you drive along." He likens it to the difference between walking on a hard surface versus walking on sand, which takes more effort because you sink in with each step.

Looking to the future, Kirchain says that while projections show a slight decline in passenger car travel over coming decades, they show an increase in truck travel for freight delivery -- the kind where pavement deflection could be a factor in overall efficiency.

There are several ways to make roadways stiffer, the researchers say. One way is to add a very small amount of synthetic fibers or carbon nanotubes to the mix when laying asphalt. Just a tenth of a percent of the inexpensive material could dramatically improve its stiffness, they say. Another way of increasing rigidity is simply to adjust the grading of the different sizes of aggregate used in the mix, to allow for a denser overall mix with more rock and less binder.

"If there are high quality local materials available" to use in the asphalt or concrete mix, "we can use them to improve the stiffness, or we can just adjust the grading of the aggregates that we are using for these pavements," says Azarijafari. And adding different fibers is "very inexpensive compared to the total cost of the mixture, but it can change the stiffness properties of the mixture significantly."

Yet another way is to switch from asphalt pavement surfaces to concrete, which has a higher initial cost but is more durable, leading to equal or lower total lifecycle costs. Many road surfaces in northern U.S. states already use concrete, but asphalt is more prevalent in the south. There, it makes even more of a difference, because asphalt is especially subject to deflection in hot weather, whereas concrete surfaces are relatively unaffected by heat. Just upgrading the road surfaces in Texas alone, the study showed, could make a significant impact because of the state's large network of asphalt roads and its high temperatures.

Kirchain, who is co-director of MIT's Concrete Sustainability Hub, says that in carrying out this study, the team is "trying to understand what are some of the systemic environmental and economic impacts that are associated with a change to the use of concrete in particular in the pavement system."

Even though the effects of pavement deflection may seem tiny, he says, "when you take into account the fact that the pavement is going to be there, with thousands of cars driving over it every day, for dozens of years, so a small effect on each one of those vehicles adds up to a significant amount of emissions over the years." For purposes of this study, they looked at total emissions over the next 50 years and considered the reductions that would be achieved by improving anywhere from 2 percent of road surfaces to 10 percent each year.

With a 10 percent improvement rate, they calculated, a total of 440 megatons of carbon dioxide-equivalent emissions would be avoided over the 50 years, which is about 0.5 percent of total transportation-related emissions for this period.

The proposal may face some challenges, because changing the mix of materials in asphalt might affect its workability in the field, perhaps requiring adjustments to the equipment used. "That change in the field processing would have some cost to it as well," Kirchain says.

But overall, implementing such changes could in many cases be as simple as changing the specifications required by state or local highway authorities. "These kinds of effects could be considered as part of the performance that's trying to be managed," Kirchain says. "It largely would be a choice from the state's perspective, that either fuel use or climate impact would be something that would be included in the management, as opposed to just the surface performance of the system."

Interferons and other cytokines produced by the immune system are important defenses against viral infections, but as we have seen in COVID-19, they can also contribute to damaging, potentially life-threatening lung inflammation. Recent evidence suggests that one type of interferon, known as type III interferon or interferon lambda (λ), can fight viral infection while limiting this inflammatory damage. That has led to clinical trials to test type III interferon as a treatment for COVID-19.

But in the journal Science, researchers at Boston Children's Hospital, with collaborators in Italy, now provide evidence that type III interferons can increase the risk of life-threatening bacterial "superinfections" in the lung. Superinfections can occur in both influenza and COVID-19, and the investigators caution that type III interferons given later in the course of COVID-19 could do more harm than good.

"Our data indicate that SARS-CoV-2 inhibits interferon production in the upper airways, weakening the immune response and helping the virus survive," says senior investigator Ivan Zanoni, PhD, an immunologist at Boston Children's. "But when the virus reaches the lower airways, there is an exuberant immune response, including upregulation of type III interferons that we think is harmful."

The team first tested samples from patients with severe COVID-19 and healthy controls. Interferon III was not much increased in the patients' nasopharyngeal swab samples, but was markedly elevated in their lung fluid.

The researchers then exposed mice to synthetic viral RNA to mimic the effects of SARS-CoV-2 infection in the lower airways. They showed that interferon III levels rose markedly in the animals' lungs as compared with control mice, and that sustained production of interferon III prevented the lungs from maintaining their protective surface barrier. This, in turn, made the animals more susceptible to lethal bacterial infections from Staphylococcus aureus: experiments showed increased amounts of bacteria and higher mortality as compared with control mice.

"There's still a lot to understand, but it looks like location and timing of interferon production are key," says Zanoni. "Early during SARS-CoV-2 infection, when the virus is in the upper airways, it might be important to intervene with recombinant interferons and other antivirals. But later on, when inflammation is highly increased in the lower airways, it will be important to block the signaling cascade initiated by interferons and other inflammatory cytokines, possibly with the anti-inflammatory drugs."

Banks and bookstores. Gyms and juice bars. Dental offices and department stores. The Covid-19 crisis has shuttered some kinds of businesses, while others have stayed open. But which places represent the best and worst tradeoffs, in terms of the economic benefits and health risks?

A new study by MIT researchers uses a variety of data on consumer and business activity to tackle that question, measuring 26 types of businesses by both their usefulness and risk. Vital forms of commerce that are relatively uncrowded fare the best in the study; less significant types of businesses that generate crowds perform worse. The results can help inform the policy decisions of government officials during the ongoing pandemic.

As it happens, banks perform the best in the study, being economically significant and relatively uncrowded.

"Banks have an outsize economic impact and tend to be bigger spaces that people visit only once in a while," says Seth G. Benzell, a postdoc at the MIT Initiative on the Digital Economy (IDE) and co-author of a paper published Wednesday that outlines the study. Indeed, in the study, banks rank first in economic importance, out of the 26 business types, but just 14th in risk.

By contrast, other business types create much more crowding while having far less economic importance. These include liquor and tobacco stores; sporting goods stores; cafes, juice bars, and dessert parlors; and gyms. All of those are in the bottom half of the study's rankings of economic importance. At the same time, cafes, juice bars, and dessert parlors, taken together, rank third-highest out of the 26 business types in risk, while gyms are the fifth-riskiest according to the study's metrics -- which include cellphone location data revealing how crowded U.S. businesses get.

"Policymakers have not been making clear explanations about how they are coming to their decisions," says Avinash Collis PhD '20, an MIT-trained economist and co-author of the new paper. "That's why we wanted to provide a more data-driven policy guide."

And if the Covid-19 pandemic worsens again, the research can apply to shuttering businesses again.

"This is not only about which locations should reopen first," says Christos Nicolaides PhD '14, a digital fellow at IDE and study co-author. "You can also look at it from the perspective of which locations should close first, in another future wave of Covid-19."

The paper, "Rationing Social Contact During the COVID-19 Pandemic: Transmission Risk and Social Benefits of U.S. Location," appears in Proceedings of the National Academy of Science, with Benzell, Collis, and Nicolaides as the authors. Benzell is about to start a new position as an assistant professor at Chapman University; in July, Collis will become an assistant professor at the University of Texas at Austin; Nicolaides is also a faculty member at the University of Cyprus.

Cumulative risk

To conduct the study, the team examined anonymized location data from 47 million cellphones, from January 2019 through March 2020. The data included visits to 6 million distinct business venues in the U.S. The 26 types of businesses in the study accounted for 57 percent of those visits, meaning the study covers a broad swath of the economy.

By examining the location data over an extended time period, the scholars were able to determine what the typical crowding level is for all business types in the study.

The study also used payroll, revenue, and employment data from U.S. Census Bureau to rate the centrality of different industries to the economy. Businesses in the study represented 1.43 million firms, 32 million employees, $1.1 trillion in payroll, and $5.6 trillion in revenues. The researchers also added a survey of 1,099 people people to gauge public preferences about different types of business.

A key to the researchers' approach is recognizing that during the pandemic, many consumers are trying to limit trips that generate interaction with strangers, while still needing to get essential and useful transactions done.

As Benzell notes, "The idea was, how can we think about rationing social contacts in a way that gives us the most bang for our buck, in terms of meetings, while keeping the risk of Covid transmission as low as possible?"

The study also rates risk on the basis of aggregate public exposure, per business type. On an individual basis, spending a couple of hours in a movie theater with strangers might seem quite risky. But in February 2020, movie theaters had about 17.6 million consumer visits in the U.S., whereas sit-down restaurants had almost 900 million visits in the same month. As a business category, sit-down restaurants would likely generate much more total transmission of Covid-19.

"It's not danger per visit, but it's a cumulative danger," Nicolaides explains. "If you look at movie theaters, they seem dangerous, but not that many people go to the movies every day ... and restaurants are a good counter-example."

Outlier: Liquor stores staying open

In many cases, the researchers say, policymakers have made reasonable decisions about which types of businesses should be open and closed. But there are exceptions to this. Take liquor stores, which have been deemed an "essential" business in many U.S. states.

"What really jumps out at us is liquor and tobacco stores," Benzell says. "Most states have allowed liquor stores to remain open. This is a bit of a bad call from our perspective, because liquor stores don't create a lot of social value. If you ask people which stores they want to be open, liquor stores are near the bottom of that list. They don't have that many receipts or employees, and they tend to be these small, crowded places where people are up against each other trying to navigate."

In the study, liquor stores rate 20th out of the 26 business types in economic importance, but 12th highest in risk.

By contrast, the researchers are more bullish about the public health dynamics of college and universities, which they rank 8th out of the 26 business types in economic importance, but just 17th in terms of risk. If campus living arrangements could be made more safe, the researchers think, the other parts of university life could offer relatively reasonable conditions.

"Colleges and universities actually have the potential to offer pretty good social contact tradeoffs," Benzell says. "They tend to be places with big campuses, they tend to be [composed of] consistently the same group of young people, visiting the same places. When people are worried about colleges and universities, they're mostly worried about dormitories and parties, people getting infected that way, and that's fair enough. But [for] research and teaching, these are big spaces, with pretty modest groups of people that produce a lot of economic and social value."

The scholars note that the study contains national ratings, and acknowledge that there might be some regional variation in effect as well.

"If a local government would like to apply this paper [to their policies], it may be a better idea to put in their own data to make decisions," says Nicolaides. That said, the study did not indicate significantly different results for urban and rural settings, something the researchers evaluated.

To be sure, some businesses are adapting to the pandemic by using new protocols or safety measures, such as limited customers in hair salons or safety partitions at supermarket checkout counters. Studying business venues with such safety measures in place would also be valuable, the scholars note.

"Moving forward, an interesting exercise would be to see how dangerous these locations are once you implement these mitigation strategies." Collis says. "Those are all interesting open questions, seeing which business adapt. And some of these adaptations will probably be temporary changes, but other business practices may stick in the Covid age."

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

Multigroup, Adaptively Randomized Trials Are Advantageous for Comparing COVID-19 Interventions

Authors from University of Washington and Fred Hutchinson Cancer Research Center say that broader use of outcome-adaptive randomization when designing clinical trials is especially appropriate to test multiple COVID-19 interventions. This design potentially reduces the number of deaths or other adverse outcomes incurred during a trial. They argue that if interventions are tested separately over the next few months, additional time will be required to conduct direct comparison of the most effective treatments. A collaborative effort will help clinicians to widely implement the most effective treatments as quickly as possible, and with potentially more persons receiving the most effective treatments. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-2933.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author, Amalia S. Magaret, PhD, can be reached directly at amag@uw.edu.

Roughly half of Earth's ice-free land remains without significant human influence, according to a study from a team of international researchers led by the National Geographic Society and the University of California, Davis.

The study, published in the journal Global Change Biology, compared four recent global maps of the conversion of natural lands to anthropogenic land uses to reach its conclusions. The more impacted half of Earth's lands includes cities, croplands, and places intensively ranched or mined.

"The encouraging takeaway from this study is that if we act quickly and decisively, there is a slim window in which we can still conserve roughly half of Earth's land in a relatively intact state," said lead author Jason Riggio, a postdoctoral scholar at the UC Davis Museum of Wildlife and Fish Biology.

The study, published June 5 on World Environment Day, aims to inform the upcoming global Convention on Biological Diversity -- the Conference of Parties 15. The historic meeting was scheduled to occur in China this fall but was postponed due to the coronavirus pandemic. Among the meeting's goals is to establish specific, and higher, targets for land and water protection.

Approximately 15 percent of the Earth's land surface and 10 percent of the oceans are currently protected in some form. However, led by organizations including Nature Needs Half and the Half-Earth Project, there have been bold global calls for governments to commit to protecting 30 percent of the land and water by 2030 and 50 percent by 2050.

Intact natural lands across the globe can help purify air and water, recycle nutrients, enhance soil fertility and retention, pollinate plants, and break down waste products. The value of maintaining these vital ecosystem services to the human economy has been placed in the trillions of U.S. dollars annually.

CONSERVATION AND COVID-19

The coronavirus pandemic now shaking the globe illustrates the importance of maintaining natural lands to separate animal and human activity. The leading scientific evidence points to the likelihood that SARS-CoV2, the virus that causes the disease COVID-19, is a zoonotic virus that jumped from animals to humans. Ebola, bird flu and SARS are other diseases known to have spilled over into the human population from nonhuman animals.

"Human risk to diseases like COVID-19 could be reduced by halting the trade and sale of wildlife, and minimizing human intrusion into wild areas," said senior author Andrew Jacobson, professor of GIS and conservation at Catawba College in North Carolina.

Jacobson said that regional and national land-use planning that identify and appropriately zone locations best suited to urban growth and agriculture could help control the spread of human development. Establishing protections for other landscapes, particularly those currently experiencing low human impacts, would also be beneficial.

FROM THE TUNDRA TO THE DESERT

Among the largest low-impact areas are broad stretches of boreal forests and tundra across northern Asia and North America and vast deserts like the Sahara in Africa and the Australian Outback. These areas tend to be colder and/or drier and less fit for agriculture.

"Though human land uses are increasingly threatening Earth's remaining natural habitats, especially in warmer and more hospitable areas, nearly half of Earth still remains in areas without large-scale intensive use," said co-author Erle Ellis, professor of geography at the University of Maryland-Baltimore County.

Areas having low human influence do not necessarily exclude people, livestock or sustainable management of resources. A balanced conservation response that addresses land sovereignty and weighs agriculture, settlement or other resource needs with the protection of ecosystem services and biodiversity is essential, the authors note.

"Achieving this balance will be necessary if we hope to meet ambitious conservation targets," said Riggio. "But our study optimistically shows that these targets are still within reach."

Local governments are often innovators of public health policymaking--the first smoke-free air acts, menu labeling laws, and soda taxes were all implemented locally. However, states are increasingly limiting local control over public health issues by passing laws that overrule local regulations, a practice known as preemption.

A new study by researchers at NYU School of Global Public Health, published in the American Journal of Preventive Medicine, takes a closer look at the strategies state legislatures use--often behind closed doors--to pass preemptive laws that limit local government control.

"These strategies used by state policymakers obscure public debate about preemption and the underlying public health and human rights issues at stake," said Jennifer Pomeranz, assistant professor of public health policy and management at NYU School of Global Public Health and the study's lead author. "By preempting local regulations, state legislatures concentrate power at state capitals, limit the capacities of local governments to protect their residents from public health harms, and minimize the nation's ability to learn from local policy successes."

While legal scholars know that various strategies are used by state legislatures to pass laws limiting local control, the NYU researchers sought to gain a more detailed understanding of how preemptive laws are enacted. They analyzed bills from which preemptive laws passed over a five-year period (2014-2018), with a focus on five policy areas: tobacco control, firearms, paid sick leave, food and nutrition, and civil rights.

The research identified five methods state legislators used to pass and support preemption:

Pass preemptive bills quickly: The most common strategy for passing preemptive laws was to do so quickly--sometimes getting a bill passed on the same day it was proposed. Passing bills quickly minimizes open debate on the purpose of the bill, reduces opponents' ability to organize, and limits legislators' ability to consult with constituent groups.

Conceal preemption: The researchers found that states hid preemptive measures by adding them to existing bills on unrelated topics (in Ohio, for instance, paid sick leave preemption was added to a bill outlawing "puppy mills"), using a misleading title for a bill that does not reflect its substance, or bundling preemption of multiple unrelated topics. While the bundling method violates rules found in many state constitutions requiring bills to focus on single subjects, the researchers write that most single-subject violations go unchallenged because it is resource intensive to bring legal challenges and courts struggle to interpret the requirements in these laws.

Repeal and replace preemption: North Carolina's controversial "bathroom bill" asserting that an individual must use the bathroom corresponding with the sex on their birth certificate--effectively discriminating against transgender people--was passed in 2016, preempting local civil rights and paid sick leave laws. A year later, it was replaced with a bill using different language--but with the same preemptive effect.

Preempt litigation: Utah enacted a law protecting the firearm industry from lawsuits. "By preempting lawsuits against entire industries, legislatures have reduced the policy agenda-setting and transparency benefits of litigation," the authors write.

Punitive preemption: Several states allow for lawsuits against local governments and officials for acting in a way the state deems preemptive regarding firearms--for example, local regulations excluding licensed gun owners from buildings. The authors note that even the threat of litigation, including the related costs and fees, intimidates localities with limited resources and reduces the likelihood that these topics will ever be openly discussed in communities.

The study also suggests state legislators are strategically adding preemptive measures to bills on topics with broad support, making it more difficult for opponents to contest or ultimately defeat the bill.

"It appears that the use of these strategies sneaking in preemption may be accelerating," said Diana Silver, associate professor of public health policy and management at NYU School of Global Public Health and the study's coauthor. "We need increased transparency in state lawmaking, especially on matters of public health, which directly affect all of our lives."

While the study analyzed bills through 2018, the findings on preemption are particularly relevant to the current COVID-19 pandemic, which has brought about tensions between local and state governments on closures and "stay at home" orders. Florida's governor, for instance, signed an executive order in April overruling local regulations and forcing local governments to adhere to the state's restrictions.

CLEVELAND, Ohio (June 10, 2020)--Sex hormones influence the structure and function of the brain, but little is known about the effect of hormone therapies (HT) on changes in the brain during menopause. A new study shows smaller increases in structural brain changes related to aging were associated with hormone-level changes from transdermal estradiol or oral conjugated equine estrogen. Study results are published online in Menopause, the journal of The North American Menopause Society (NAMS).

Age-related changes in learning and memory have been associated with changes in the structure of the brain. Visually, such structural changes can be seen through magnetic resonance imaging in what appear as bright white spots in the brain (known as white matter hyperintensities). These changes in brain structure and in cognitive function may, in part, be related to the lower estrogen levels resulting from menopause.

In a new study involving participants from the Kronos Early Estrogen Prevention Study, researchers investigated the link between the changes in hormone levels (from both the brain and the ovary) with different HT formulations and structural changes in the brain associated with aging compared with placebo. They found that smaller increases in these age-related structural brain changes were linked to decreases in follicle-stimulating hormone in women taking transdermal estradiol and higher levels of estrone (a particular form of estrogen commonly found in postmenopausal women) in women in both HT groups (transdermal estradiol and oral conjugated equine estrogens).

Researchers theorized that the differences may likely be in how the various HT formulations are metabolized. Although an oral administration is further metabolized in the liver, the transdermal hormones are absorbed directly into the peripheral circulation before being metabolized in the liver. Additional research is needed to evaluate the effect of different doses of various oral and transdermal hormones on the change in white matter hyperintensities.

Study results appear in the article "Associations of pituitary-ovarian hormones and white matter hyperintensities in recently menopausal women using hormone therapy."

"This study found that pituitary and ovarian hormone levels are linked to structural brain changes associated with aging in recently menopausal women using hormone therapy and that there are differences in these associations depending on the hormone therapy formulation used. Additional study is needed to determine whether dosages of hormone therapy also affect these associations and to determine what the clinical implications of these findings are for menopausal women," says Dr. Stephanie Faubion, NAMS medical director.

Chicken is the most consumed protein in the United States. According to the National Chicken Council, the U.S. produced more than 9.2 billion broiler chickens in 2019. US consumers spent more than 95 billion dollars on chicken products.

All these broilers - chickens raised for meat - need millions of tons of litter, or bedding material. Reusing chicken litter can save costs. There exists some health and safety concerns though.

A new study shows that the environment in reused poultry litter can deter growth of pathogens like Salmonella.

"When you read or hear that broiler litter is reused to raise multiple flocks of chickens, the typical reaction is that it must be bad for food safety," says Adelumola Oladeinde, a co-author of the recent study. "Our study demonstrates the exact opposite."

Oladeinde is a researcher at the USDA's National Poultry Research Center in Athens. He and his colleagues found that 'good' bacteria in used poultry litter can hinder Salmonella growth.

"It may be worthwhile to invest time and resources to characterize the bacteria in reused litter," says Oladeinde. "We can develop the promising ones into beneficial microbes for better chicken gut health."

The study also explored litter characteristics, such as moisture and ammonia levels. These characteristics can dramatically affect the litter microbiome - the mix of bacteria, fungi, and viruses in litter.

"Our findings provide new information on the relationship between the physical environment of broiler litter and its microbiome," says Oladeinde. "Management techniques that account for both factors may help reduce Salmonella in chickens."

Chicken litter plays a big role in determining broiler health. After a broiler chick gets to a farm, it usually spends the next several weeks pecking and living on litter.

In fact, chicks begin to eat litter even before eating from feeding troughs or drinking. The microbiome present in the litter likely become the 'first settlers' in the guts of the chicks.

"These first microbes play a key role in determining gut health," says Oladeinde. "Therefore, it is critical to determine what a beneficial litter microbiome looks like."

The team collected samples of reused poultry litter from the University of Georgia Poultry Research Center. The litter was used to raise three flocks of broiler chickens under conditions like those used in broiler farms. "Each sample represents a unique broiler litter environment," says Oladeinde.

In the lab, researchers measured characteristics of the litter samples. Then they added Salmonella to each sample. After that, the samples were tested for levels of Salmonella, other bacteria, and physical characteristics.

Within two weeks of adding Salmonella, most samples developed predictable microbiomes. Certain microbes, such as Nocardiopsis bacteria, seemed to reduce growth of Salmonella.

That makes sense, according to Oladeinde. Some species of Nocardiopsis bacteria are known to produce antibiotics and toxins. These compounds could be keeping Salmonella levels low in the litter samples.

A key aspect of reusing broiler litter is how long to wait before reuse. This waiting period is called litter downtime.

"For farmers, a shorter downtime will result in growing more birds through the year," says Oladeinde. However, we know little about how downtime affects litter microbiome.

Results from the study show that surveying levels of specific bacteria could help determine if litters have had enough downtime. That could be of big help to farmers.

"Poultry litter is a complex environment to study," says Oladeinde. "We showed that the reused litter after two weeks of downtime had a microbiome that was unfavorable to Salmonella."

Oladeinde aims to repeat these experiments with litter from various sources. He also wants to test for multiple Salmonella strains. "These studies will tell us about the underlying mechanisms behind reusing litter and reducing Salmonella," he says.

The COVID-19 pandemic and resulting stay-at-home orders have taken a toll on many facets of physical and mental health in recent months. But according to new University of Colorado Boulder research, one silver lining may exist.

Some of us are sleeping better.

"Even though we are living through this incredibly stressful time which is changing our behaviors drastically, we are seeing changes to sleep behaviors that are for the most part positive," said lead author Ken Wright, an Integrative Physiology professor and director of the Sleep and Chronobiology Laboratory.

For the study, published online June 10 in the journal Current Biology, Wright and co-authors at the University of Washington set out to assess how student sleep habits were changing in the wake of widespread stay-at-home orders and social distancing guidelines put into place in mid-March.

Wright had already collected sleep data from 139 CU Boulder students for a week from Jan. 29 to Feb. 4 as part of a class project. When all instruction switched to online learning March 16, he saw a once-in-a-lifetime research opportunity.

"This is an unprecedented time for research, but when it comes to sleep, not a lot of people have access to data on what people were doing before," he said. "We did."

When Wright repeated the week-long survey in the same students from April 22 to 29, researchers found that, on average, the students were devoting 30 more minutes per weekday and 24 more minutes per weekend to sleep. Those students who had been skimping on sleep the most pre-pandemic saw the greatest improvements, with some sleeping as much as two more hours nightly.

The students also kept more regular sleep and wake times and experienced less "social jetlag," or that groggy feeling that occurs when people stay up late and sleep later on the weekends and must resume an earlier schedule on Monday.

Post pandemic, significantly more students - or 92% - also got the minimum seven hours per night of sleep as recommended by the Centers for Disease Control and Prevention. Typically, about one-third of U.S. college students fail to sleep that much.

He said that sleep is particularly critical now, as studies have shown that inadequate sleep weakens the immune system, leaving people more vulnerable to viral infections and less responsive to vaccines.

"We know that when you don't meet the recommendations for sleep it can contribute to a lot of negative health problems," said Wright, noting that insufficient and irregular sleep and social jetlag have all been shown to boost risk of heart disease, obesity, diabetes and mood disorders.

"The fact that a lot of these sleep measures are improving is a good sign."

One finding, however, was not so good.

Compared to February, students are going to bed about 50 minutes later during the week and 25 minutes later during the weekend and waking up later, too.

"Generally, later sleep timing is associated with poor health outcomes," said Wright, who advises people to try to shift their wake-sleep cycle earlier by getting bright light exposure in the morning and dimming the lights two hours before bedtime.

More research is necessary to determine whether similar shifts are occurring among the general public and, if so, why. Wright did note that Boulder residents, generally speaking, are better sleepers to begin with. One prior study of the largest 500 cities in the U.S. found that pre-pandemic, Boulder had the lowest percentage of adults who got fewer than seven hours of sleep per night, or ~25%.

Wright suspects the new findings likely do apply more broadly to college students nationwide.

The key now: To identify ways to keep those good sleep habits going once school resumes in person again.

Health care professionals who die by suicide are more likely to be older and nearing the end of their careers, or be of Asian or Pacific Islander ancestry, or confronting physical, mental health or medical malpractice issues, according to a new study from Massachusetts General Hospital.

In a study published in JAMA Surgery, researchers identified modifiable and behavioral risk factors that can lead to burnout and suicide among three groups of health care providers (surgeons, nonsurgeon physicians and dentists) as a way of informing hospitals and residency training programs of potential areas for intervention through increased screening and treatment.

"Our study highlights the fact we have to be concerned about a larger physician population than we originally thought, including individuals facing civil legal, marital and cultural risk factors, as well as those receiving treatment for mental illness," says Yisi Daisy Ji, DMD, with the Department of Oral and Maxillofacial Surgery and lead author of the study.

"Providers are comfortable advising patients when to seek help but are often reluctant to do so themselves. Part of that is the perceived stigma of being a health care professional with a mental health problem, as well as concern it could adversely affect their medical licensure."

The ongoing COVID-19 pandemic raises the importance of physician mental health and suicide prevention. "With physicians across the country facing uncharted challenges in working conditions, redeployment and physical and emotional stress, we must be more vigilant than ever," emphasizes Faith Robertson, MD, with the Department of Neurosurgery, and co-author of the study. "We are calling on all physicians to recognize the signs of mental health difficulties in their colleagues, as well as in themselves, and take early action."

To determine which physicians are most at risk, researchers examined data from the National Violent Death Reporting System from 2003 though 2016. Of the more than 170,000 individuals who died of suicide, 767 were health care professionals.

The Mass General study is the first national evaluation of suicide risk factors and outcomes in the health care provider sub-groups of surgeons, nonsurgeon physicians and dentists.

Some Unexpected Findings

Among the surprising findings of the retrospective study was that physicians who died of suicide were substantially older (mean age, 59.6 years) compared to the general population of suicide victims (mean age, 46.8) years. "This is a previously unrecognized demographic to be at risk," notes Ji.

"Our hypothesis is that the transition into a senior career position or retirement introduces new and often unsettling challenges of purpose, finances and restructuring of routine and family dynamics."

Another unexpected finding by the team was that physicians of Asian and Pacific Islander ancestry were at higher risk of suicide than those of white ancestry. Researchers theorized that the cultural stigma of experiencing mental health problems among this health care population may contribute to low rates of diagnosis and treatment.

Civil legal problems were also found to be a significant risk factor for suicide in physicians compared to the general population, and more so in the nonsurgeon than the surgeon cohort.

The reason, the study suggested, is that physicians in specialties where malpractice litigation is less common (such as nonsurgical) may experience more emotional distress when claims occur, compounded by the duration and uncertainty of each case.

The researchers propose that hospitals would benefit from offering additional psychological as well as legal and human resource support to physicians during times of litigation-induced stress.

With reported cases of physician burnout on the rise nationwide, the study emphases the need for more intense screening and support of health care professionals across all high risk groups.

The paper cited a model educational program at the University of California, San Diego focused on destigmatizing mental health issues and promoting help-seeking behavior and treatment, including an anonymous, interactive online screening program for all medical students and faculty.

Harvard Medical School, too, maintains a robust program that allows physicians under stress to confidentially seek and receive treatment.

"Our study underscores the need for more targeted intervention and support to fit the risk factors of health care professionals," says Ji. "And that support, including mental health screenings and more open conversations among colleagues about warning signs, needs to continue throughout the physician's career if we're going to mitigate burnout and decrease the rate of suicides in the field of medicine."

Kanazawa, Japan - One of the main functions of the liver is to detoxify compounds including drugs and toxicants to reduce toxic actions and to eliminate from the human body, requiring a molecular interplay within a network of proteins. In a new study published in Biochemical Pharmacology, researchers from Kanazawa University identified the protein solute carrier family 35 member B1 (SLC35B1) as a key molecular actor within the complex process of detoxification.

The goal of glucuronidation, one of detoxification processes, is to make molecular compounds water-soluble so that they can be eliminated from the body through urine or feces more easily. This is mainly achieved by UDP-glucuronosyl transferase (UGT) family, which involves the transfer of glucuronic acid from UDP-glucuronic acid (UDPGA) to the compounds including drugs and toxicants. This process mainly takes place in the endoplasmic reticulum (ER) of liver cells, which are specific compartments inside of the cell. While action site of UGT is located at inside of the ER membrane, UDPGA has to be transported into the ER to be available as a glucuronic acid donor, a process that has caused much scientific controversy in the past.

"While a number of SLC35 proteins have been suggested to be part of this process, it is not yet clear which one contributes most significantly to the transport of UDPGA into the ER," says corresponding author of the study Hiroshi Arakawa. "The goal of our study was to understand how exactly UDPGA is transported into the ER to facilitate glucuronidation."

To achieve their goal, the researchers first showed that the activity of UGT depends on the presence of UDPGA, a finding which they used to their favor in subsequent experiments. By measuring UGT activity, they could now infer whether UDPGA was transported into the ER. They then individually knocked down the expression of 23 members of the SLC35 family in HEK cells expressing human UGT, and found that only the reduction of SLC35B1 and SLC35E3 affected the activity of UGT. The researchers then showed that the activity of UGT significantly decreased when SLC35B1 but not SLC35E3 was knocked down in HepaRG cells, a human cell line. Interestingly, they showed that SLC35B1 was expressed highly variably in human liver samples, reaching an almost 40-fold difference between samples.

"These are striking results that show how the complex process of glucuronidation is regulated at the molecular level," says the last author of the study professor Miki Nakajima. "Our findings could shed light on the inter-individual differences in eliminating substances from the body."

Muscle stem cells, the reserve stem cell in the skeletal muscles, are responsible for muscle repair after damage. They are the 'regenerative medicine' to cure muscle diseases and muscle damages. In a healthy uninjured condition, muscle stem cells are in quiescence, a dormant state, to preserve them well. Whenever there is muscle damage, they will wake up instantly, contribute themselves to build new muscles.

If this dormant state is loosely controlled, muscle stem cells will be wasted when there is no need for repair. If this dormant state is kept too tight, the muscle stem cells could not wake up when they are needed to contribute to muscle repair.

How muscle stem cells control this balance of quiescence remains a topic of heightened interest. Recently, a team of scientists at the Hong Kong University of Science and Technology revealed that intron detention (IR) is a key to the mechanism; when stem cell enters quiescence exit, Dek releases conserved introns, which allow the cell to be activated.

"Using skeletal muscle stem cells, also called satellite cells (SCs), we demonstrated prevalent intron retention (IR) in the transcriptome of quiescent SCs (QSCs)," said Prof. Tom CHEUNG, lead researcher of the team and SH Ho Associate Professor of Life Science at HKUST. "Intron-retained transcripts found in QSCs are essential for fundamental functions including RNA splicing, protein translation, cell-cycle entry, and lineage specification. Our analysis reveals that phosphorylated Dek protein modulates IR during SC quiescence exit."

While Dek protein is not present in QSCs, Dek overexpression in vivo results in a global decrease of IR, quiescence dysregulation, premature differentiation of QSCs, and undermined muscle regeneration. The researchers also found in their IR analysis on hundreds of public RNA-seq data that IR is conserved among quiescent adult stem cells, which suggests that IR functions as a conserved post-transcriptional regulation mechanism that plays an important role during stem cell quiescence exit.

Their findings were published online in the journal Developmental Cell on June 4, 2020.

"IR has emerged as an important post-transcriptional regulatory mechanism supporting the complexity of gene expression regulation and cell-state transition," noted Prof. Cheung. "We observed around 1,200 genes possessing IR in QSCs, but in many transcripts, only selective introns were retained. The prevalence of IR among quiescent adult stem cells implies its functional importance in stem cell quiescence. Findings in the study will play a fundamental role in the field as scientists continue the quest to map out the mechanism of stem cell quiescence and stem cell-mediated tissue regeneration."

The genetic variability of immunity lies particularly in the genes of the HLA (Human Leukocyte Antigen) system. These genes produce HLA molecules that are positioned on the surface of cells. When a virus infects an organism, the invader's proteins are first cut into small fragments called peptides. The HLA molecules then bind on to these fragments and expose them to the surface of the cells, thereby triggering a cascade of immunity reactions designed to eliminate the virus.

Alicia Sanchez-Mazas, a professor at the Anthropology Unit in UNIGE's Faculty of Sciences, explains: "From the 450 or so most common HLA molecules in hundreds of populations worldwide, we tried to identify the ones that are most strongly bound to the peptides of the new coronavirus." Over 7,000 peptides can be derived from all of the viral proteins of the coronavirus.

The Geneva-based researcher and her international team used bioinformatic tools to perform the analysis. These can predict the binding affinities between the HLA molecules and the viral peptides on the basis of their physical and chemical properties. The scientists then turned to statistical models to compare the frequencies of these HLA variants in different human populations.

Classification of HLA molecules

The study classified the approximately 450 HLA molecules according to their relative capacity to bind the coronavirus peptides. It provides an essential reference inventory for identifying the genetic resistance or susceptibility of individuals to the virus. The study has also shown that the frequencies of these HLA variants differ significantly from one population to the next.

José Manuel Nunes, a researcher at the Anthropology Unit - and co-author of the article - further explains: "We were surprised to find that Indigenous populations in America had both the highest frequencies of HLA variants that bind the most strongly to the peptides and the lowest frequencies of those that bind the least strongly." However, as José Manuel Nunes continues, we should not draw too hasty a conclusion from these results: "HLA molecules contribute to the immune response but they are far from being the only element that can be used to predict effective or ineffective resistance to a virus. This is also verified on the ground since America's Indigenous populations are apparently no less affected than others by COVID-19."

"Generalist" molecules

In the same study, the authors also analysed the HLA-peptide bindings for all of the proteins of the six other viruses with pandemic potential (two other coronaviruses, three influenza viruses and the HIV-1 virus of AIDS). This showed that many HLA variants are capable of binding strongly to the peptides of all seven viruses studied. Others do the same for all respiratory-type viruses (coronavirus and influenza). This means that there are numerous "generalist" HLA molecules that are effective against a number of different viruses.

"The differences between populations observed in this study are actually differences in the frequencies of the generalist HLA variants that do not bind specifically to the coronavirus but also to other pathogens", points out professor Sanchez-Mazas. "This is what makes us think that the current differences between populations are the result of past adaptations to different pathogenic pressures, which is extremely informative for understanding the genetic evolution of our species."

A logical follow-up to the study will be to determine precisely which coronavirus peptides are most strongly bound to the HLA molecules. It is these peptides that will have the highest chances of triggering an effective immune reaction. Identifying them will be vital for developing a vaccine.

Known as the French paradox, a low incidence of coronary heart disease despite substantial intake of saturated fats is thought to be due to a diet rich in polyphenols. Polyphenols are abundant in plant based foods such as fruits and vegetables. Procyanidins are polyphenols with antioxidant, anti-obesity and anti-inflammatory properties. In this study, PCB2DG, (procyanidin B2 3,3"-di-O-gallate) was examined to see how it inhibits the cytokine production in T cells. Specifically, to understand the mechanism underlying the regulation of tumor necrosis factor (TNF)- α.

The Tanaka Food Immunology Laboratory at Shinshu University has long studied the polyphenol PCB2 and its immunoregulatory function. PCB2DG is a dimer of epicatechin, and is structurally different from other polyphenols which makes it an interesting subject of study. Polyphenols have properties that decrease inflammation and have anti-oxidation properties. Autoimmune diseases such as colitis and rheumatoid arthritis are said to be alleviated by decreasing TNF-α production and signaling because TNF-α is a protein that causes inflammation in the body.

Immune functions and energy metabolism are closely related. Abnormality found in the energy metabolism of immune cells are known to be related to the onset of immune diseases. This is why research continues into the cell metabolism targeted immune suppressant drugs. Polyphenols have been known to have immunosuppressant activities but their cell metabolism was not known. This study succeeded in showing for the first time that PCB2DG, a type of polyphenol supresses cytokine production by inhibiting glycolysis and the mTOR/HIF-1 pathway. Glycolysis is the process of breaking glucose down for the body to use as fuel.

The T helper (Th) cells, also referred to as CD4+ T cells, play a central role in modulating immune responses, and are differentiated into subsets; Th1, Th2, Th17, and regulatory T cells (Treg). The Th1 cells produce TNF-α and interferon (IFN)-γ. Activated Th1 cells cause a metabolic shift toward glycolysis, which is largely regulated by the mammalian target of rapamycin (mTOR) and hypoxia inducible factor 1 (HIF-1) signaling.

Procyanidin B2 (PCB2) gallate; specifically, PCB2 3,3''-di-O-gallate (PCB2DG), inhibits cytokine production in T cells. However, the molecular interactions and partners of PCB2DG underlying this suppression of cytokine production are unclear. The present study aimed to elucidate mechanisms underlying regulation of TNF-α production by PCB2DG. To elucidate the mechanism by which PCB2DG suppresses cytokine production, two points are set as problems: (1) whether PCB2DG acts directly on T cells or (2) whether cytokine production is suppressed by inhibiting glycolysis of T cells. The group hypothesized that the specific inhibitory effect of PCB2DG on cytokine production was due to inhibition of T cell glycolysis and mTOR/HIF-1 pathway. As they proceeded with the verification of this hypothesis, they were able to confirm the decreased expression of mTOR/HIF-1 pathway-related protein by Western blotting analysis.

Dr. Tanaka's group found that production of TNF-α and glycolytic activity in activated CD4+ T cells were suppressed by PCB2DG treatment. The inhibition of TNF-α production was found to be mediated by mTOR and HIF-1 pathway, as PCB2DG suppressed the expression of HIF-1α, p-mTOR, and p-p70S6K (a downstream of the mTOR complex, mTORC1). Moreover, suppression of TNF-α production was mediated by regulation of the glycolytic enzyme lactate dehydrogenase (LDH) at the post-transcriptional level.

These results suggest that PCB2DG regulates TNF-α production by inhibiting glycolytic activity via the mTOR/HIF-1 pathway. This study is the first to report the mechanism by which PCB2DG, a dimeric polyphenol including a gallate group, controls cytokine production. Based on their findings, molecular studies of cellular molecules which interact with PCB2DG are needed to elucidate further mechanisms. Moreover, studies on the effects of PCB2DG in terms of amelioration of TNF-α-mediated pathology using a mouse model would be informative. In the future, PCB2DG may become available as a therapeutic for the treatment and prevention of TNF-α-mediated autoimmune diseases.

Interestingly, a compound with two gallate groups added to PCB2 (PCB2DG) was found to suppress immune cell activation. In addition, the group found that PCB2DG suppresses the production of cytokines involved in the inflammatory response. However, since the mechanism of PCB2DG suppression was unknown, the group decided to tackle this issue.

In order to evaluate the effect of PCB2DG on cytokine production, protein level and gene level of cytokine were analyzed. As a result, although suppression at the protein level was confirmed by the addition of PCB2DG, suppression at the gene level was not confirmed. Usually, cytokines are known to show the same changes at the protein level and at the gene level, so the group thought that there were some deficiencies in the experiment, and repeated experiments were conducted. However, no matter how many times the experiment was carried out, the protein decreased and the gene remained unchanged. Therefore, by changing the approach, the group hypothesized that PCB2DG regulates post-transcriptional protein expression rather than regulating the cytokine gene, and proceeded with verification. The research group eventually were able to prove that this hypothesis was correct, though it was very difficult to get there.

The lab hopes to be able to prevent illness with food in the future. Many foods that are consumed in everyday life regulate immune function. The researchers would like to scientifically demonstrate their usefulness and prove their effectiveness in preventing diseases. In the future, Dr Tanaka would like to identify the target molecule of PCB2DG. She hopes to collaborate with researchers who are analyzing proteins that bind to polyphenols in order to elucidate the matter further.