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His death leaves only one family physician in Greenfield, Mo. He died of complications of Covid-19.This obituary is part of a series about people who have died in the coronavirus pandemic. Read about others here.For the past 15 years, there were only two family physicians in Greenfield, Mo., a town with 1,371 residents about 40 miles northwest of Springfield. One of them was Dr. Michael Bennett, who opened his practice, the Greenfield Medical Center, in 2005.He was a vigorous proponent of wearing masks and of social distancing during the coronavirus pandemic, though he faced resistance to his calls from some townspeople, and he offered free Covid-19 testing to his patients with funding help from the federal C.A.R.E.S. Act.Dr. Bennet took precautions in treating infected patients but nevertheless tested positive for the coronavirus in late December. He was soon hospitalized in St. Louis and spent 50 days connected to a ventilator and an ECMO (extracorporeal membrane oxygenation), a machine that acts as an artificial lung. He died of Covid-19 on March 6, his former wife, Teresa Bennett, said. He was 52.Since the start of the pandemic, Dade County, Mo., where Greenfield is situated, has recorded 715 positive tests and 31 deaths, most of the fatalities nursing home residents, according to Pamela Cramer, the administrator of the county health department. “It’s really hit us, but not as hard as other areas,” she said on Wednesday.Nationwide, 452,706 health care workers have tested positive for the coronavirus, and 1,505 have died as of March 26, according to the Centers for Disease Control and Prevention.Michael Keith Bennett was born on Feb. 15, 1969, in New London, Mo., in the northeast part of the state. His father, Bob, was a farmer; his mother, Meredith (Arnold) Bennett, most recently helped manage her son’s clinic.A head injury from a car accident when he was in high school changed Dr. Bennett’s career path.“He was hurt pretty badly, and during that stay in the hospital he decided he wanted to be a doctor,” Ms. Bennett said by phone. “He was into auto mechanics before that.”After earning a bachelor’s degree in biology from the University of Missouri in Columbia, he received his medical degree from its medical school. And after finishing his residency at Cox Medical Center South in Springfield, he worked at St John’s Hospital in nearby Willard, Mo.In addition to his medical practice, which has been shuttered, Dr. Bennett had a 500-acre farm with beef cattle, and he enjoyed fishing and hunting.“I think one of the reasons his patients loved him is he was a good old boy,” said Ms. Bennett, who managed her former husband’s practice until 2012, when they divorced.In addition to his parents, he is survived by his son, Austin; his daughter, Shelby Bennett; his sister, Veronica Bennett; his brother, Damon; and his girlfriend, Haley Hendrixson.Dr. Bennett worked closely with Ms. Cramer, the county official, and suggested to her last year that the town adopt a mask-wearing mandate after several Covid-related nursing home deaths. But the idea did not advance.After learning that Dr. Bennett had tested positive for Covid-19, Ms. Cramer tried to stay in contact. In his final text to her from the hospital, on Jan. 8, he wrote: “I’m hanging in there. Will stay in touch.”

With case numbers still high, coronavirus testing remains essential, experts say, but the goals and approach will change as vaccines roll out.Last May, the city of Los Angeles turned a fabled baseball park into a mass testing site for the coronavirus. At its peak, Dodger Stadium was testing 16,000 people a day for the virus, making it the biggest testing site in the world, said Dr. Clemens Hong, who oversees coronavirus testing in Los Angeles County.But in January, the city pivoted, converting the stadium into an enormous, drive-through vaccination site. Local demand for coronavirus testing has plummeted, Dr. Hong said. He said that he saw the evidence firsthand recently when he visited a community hospital: “The testing site had three people and the vaccine site had a line around the block.”Los Angeles is not an anomaly. Across the nation, attention has largely shifted from testing to vaccination. The United States is now conducting an average of 1.3 million coronavirus tests a day, down from a peak of 2 million a day in mid-January, according to data provided by the Johns Hopkins Coronavirus Resource Center.In some ways, the decline is good news, and can be attributed, in part, to falling case numbers and the increasing pace of vaccination. But the drop-off also worries many public health experts, who note that the prevalence of Covid-19 remains stubbornly high. More than 50,000 new cases and 1,000 deaths are being tallied every day and just 14 percent of Americans are fully vaccinated.“We are very much worried about resurgence,” said Jennifer Nuzzo, an epidemiologist at Johns Hopkins University. “Everybody mentally moved on to vaccines. Obviously, vaccines are quite important. But as long as the majority of us are not protected, then testing remains essential.”The $1.9 trillion stimulus package signed into law this month includes $47.8 billion earmarked for testing, tracing and monitoring the virus.But as society begins to reopen and vaccines roll out more widely, testing strategies are evolving. Here are four reasons that testing still matters, and how officials see the next months, and years, playing out.Diagnosing people who are sickCase numbers remain high, and clinicians still need to identify individuals who have contracted the virus so that these people can receive proper treatment and care. The gold standard for diagnosing Covid-19 is the polymerase chain reaction, or P.C.R., test, which can identify even small traces of genetic material from the coronavirus.This kind of testing will be needed as long as there are Covid-19 cases, but as the disease becomes less common, diagnostic testing is likely to become less centralized.Testing at a site by the 24th Mission Bart Station in San Francisco in early March.Mike Kai Chen for The New York Times“The game has changed a little bit,” Dr. Hong said. “Before, we just had infection popping up everywhere, and we just needed broad, blanket testing access. Now we need to be much more targeted.”Diagnostic testing is shifting from large, government-run sites to smaller, more distributed sites that are spread across local communities, Dr. Hong said. Ultimately, when vaccination rates are high enough and cases are low enough, dedicated testing sites will not be needed at all. “Then we just return testing to the health care system,” he said, and coronavirus tests will simply be one of many options on the menu at the doctor’s office.Slowing the spreadTesting is important not just for identifying individual patients who need treatment but also for public health. When the system is working, a timely Covid-19 diagnosis is what triggers contact tracing and quarantining and can stop virus transmission in its tracks.“The vaccine — marvelous, miraculous as it is — is not in and of itself going to contain this pandemic,” said A. David Paltiel, a professor of health policy and management at Yale School of Public Health.Slowing transmission means fewer people will get sick but it also gives the virus fewer opportunities to mutate. And that reduces the odds that dangerous new variants — some of which may be able to evade vaccine-induced immunity — will emerge.Keeping community spread low will help give vaccines “a fighting chance,” Dr. Paltiel said. “The less work we give the vaccine to do, the better.”As schools and offices reopen, routine screening of asymptomatic people will help minimize viral spread. These screening programs are now beginning to ramp up. Many will rely on rapid antigen tests, which are less sensitive than P.C.R. tests but are cheaper and can return results in 15 minutes. (Antigens are molecules, like the well-known spike protein, that are present on the surface of the coronavirus and trigger the immune system to produce antibodies.) When antigen tests are used routinely and frequently, they can be effective in identifying infectious individuals and reducing viral transmission, several analyses suggest.As vaccination rates increase, these screening programs may become more targeted. If 70 percent to 80 percent of Americans are vaccinated, the prevalence of Covid-19 plummets, and outbreaks are not emerging in group settings, then it may be possible to ease up on widespread screening, said Dr. Mary K. Hayden, an infectious disease specialist at Rush University Medical Center in Chicago. “Then, yes, I think we could relax surveillance testing,” she said before adding, “But it’s a lot of ‘ifs.’”.css-yoay6m{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}@media (min-width:740px){.css-yoay6m{font-size:1.25rem;line-height:1.4375rem;}}.css-1dg6kl4{margin-top:5px;margin-bottom:15px;}.css-k59gj9{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-direction:column;-ms-flex-direction:column;flex-direction:column;width:100%;}.css-1e2usoh{font-family:inherit;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-box-pack:justify;-webkit-justify-content:space-between;-ms-flex-pack:justify;justify-content:space-between;border-top:1px solid #ccc;padding:10px 0px 10px 0px;background-color:#fff;}.css-1jz6h6z{font-family:inherit;font-weight:bold;font-size:1rem;line-height:1.5rem;text-align:left;}.css-1t412wb{box-sizing:border-box;margin:8px 15px 0px 15px;cursor:pointer;}.css-hhzar2{-webkit-transition:-webkit-transform ease 0.5s;-webkit-transition:transform ease 0.5s;transition:transform ease 0.5s;}.css-t54hv4{-webkit-transform:rotate(180deg);-ms-transform:rotate(180deg);transform:rotate(180deg);}.css-1r2j9qz{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-e1ipqs{font-size:1rem;line-height:1.5rem;padding:0px 30px 0px 0px;}.css-e1ipqs a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;}.css-e1ipqs a:hover{-webkit-text-decoration:none;text-decoration:none;}.css-1o76pdf{visibility:show;height:100%;padding-bottom:20px;}.css-1sw9s96{visibility:hidden;height:0px;}#masthead-bar-one{display:none;}#masthead-bar-one{display:none;}.css-1cz6wm{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;font-family:’nyt-franklin’,arial,helvetica,sans-serif;text-align:left;}@media (min-width:740px){.css-1cz6wm{padding:20px;width:100%;}}.css-1cz6wm:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-1cz6wm{border:none;padding:20px 0 0;border-top:1px solid #121212;}Frequently Asked Questions About the New Stimulus PackageThe stimulus payments would be $1,400 for most recipients. Those who are eligible would also receive an identical payment for each of their children. To qualify for the full $1,400, a single person would need an adjusted gross income of $75,000 or below. For heads of household, adjusted gross income would need to be $112,500 or below, and for married couples filing jointly that number would need to be $150,000 or below. To be eligible for a payment, a person must have a Social Security number. Read more. Buying insurance through the government program known as COBRA would temporarily become a lot cheaper. COBRA, for the Consolidated Omnibus Budget Reconciliation Act, generally lets someone who loses a job buy coverage via the former employer. But it’s expensive: Under normal circumstances, a person may have to pay at least 102 percent of the cost of the premium. Under the relief bill, the government would pay the entire COBRA premium from April 1 through Sept. 30. A person who qualified for new, employer-based health insurance someplace else before Sept. 30 would lose eligibility for the no-cost coverage. And someone who left a job voluntarily would not be eligible, either. Read moreThis credit, which helps working families offset the cost of care for children under 13 and other dependents, would be significantly expanded for a single year. More people would be eligible, and many recipients would get a bigger break. The bill would also make the credit fully refundable, which means you could collect the money as a refund even if your tax bill was zero. “That will be helpful to people at the lower end” of the income scale, said Mark Luscombe, principal federal tax analyst at Wolters Kluwer Tax & Accounting. Read more.There would be a big one for people who already have debt. You wouldn’t have to pay income taxes on forgiven debt if you qualify for loan forgiveness or cancellation — for example, if you’ve been in an income-driven repayment plan for the requisite number of years, if your school defrauded you or if Congress or the president wipes away $10,000 of debt for large numbers of people. This would be the case for debt forgiven between Jan. 1, 2021, and the end of 2025. Read more.The bill would provide billions of dollars in rental and utility assistance to people who are struggling and in danger of being evicted from their homes. About $27 billion would go toward emergency rental assistance. The vast majority of it would replenish the so-called Coronavirus Relief Fund, created by the CARES Act and distributed through state, local and tribal governments, according to the National Low Income Housing Coalition. That’s on top of the $25 billion in assistance provided by the relief package passed in December. To receive financial assistance — which could be used for rent, utilities and other housing expenses — households would have to meet several conditions. Household income could not exceed 80 percent of the area median income, at least one household member must be at risk of homelessness or housing instability, and individuals would have to qualify for unemployment benefits or have experienced financial hardship (directly or indirectly) because of the pandemic. Assistance could be provided for up to 18 months, according to the National Low Income Housing Coalition. Lower-income families that have been unemployed for three months or more would be given priority for assistance. Read more.Even then, however, officials may want to maintain some level of surveillance testing in high-risk settings, like nursing homes, or of high-risk individuals, like travelers, she said.Assessing our progressTesting can help public health officials gauge whether efforts to end the pandemic are paying dividends.A line of cars waiting for a turn at testing at Dodger Stadium in Los Angeles in December.David Walter Banks for The New York Times“Do we want to know how well vaccines are working? We’re going to have to test,” said David O’Connor, a virologist at the University of Wisconsin, Madison. “How are we going to know whether the variants are more contagious? We’re going to have to test. How are we going to know if the vaccines are effectively controlling the variants? We’re going to have to test.”Large screening programs may also help institutions assess the effectiveness of their risk-reduction strategies. If cases begin to rise, schools and offices may find they need to change their mask policies, enforce greater social distancing or boost their ventilation rates.Testing might also help uncover worrisome case clusters, which can signal that a community has not yet reached herd immunity and might benefit from targeted a vaccination campaign.Preventing the next pandemicMany experts now believe that the coronavirus is unlikely to ever disappear completely. But even if the virus continues to circulate only at very low levels, it will be important to keep tabs on it.“It becomes less about trying to interrupt the transmission of the disease and more to understand, Where is the virus?” Dr. Nuzzo said. “What are we missing? And, you know, what could be coming down the road?”The virus will continue to mutate, and new genetic variants will emerge. Some level of continued testing, even years down the line, could help scientists catch worrisome variants early.Tests aren’t perfect, of course, and can produce false negatives and positives. But they provide a critical window into the activity of a pathogen too small to see.“We’re going to want to make sure that after people are vaccinated, it’s not going to bubble up in some other unpredictable way that’s going to put us back where we started,” Dr. O’Connor said.

A machine that acted as an artificial lung kept her eligible for a transplant as she dealt with cystic fibrosis. She went on to compete again in marathons.Liesbeth Stoeffler’s doctors had a bold decision to make in 2009. Ms. Stoeffler was on a ventilator and deeply sedated after cystic fibrosis had destroyed the lungs that had once given her the ability to run and hike.She needed a double-lung transplant, but doctors worried that prolonged time on the respirator might render her too weak or malnourished to stay eligible for one.So doctors at Columbia University Irving Medical Center took her off the ventilator after about a day and hooked her to an extracorporeal membrane oxygenation machine, or ECMO, which pumped blood from her body, removed carbon dioxide from it and sent oxygen-rich blood flowing back into her. In effect, it acted as an artificial lung.It was a rarely known and risky deployment of the machine, but not only did it allow Ms. Stoeffler to awaken from sedation; it also allowed her to eat, speak on her smartphone, exercise in bed and walk in place while she was connected to it — for an unusually long 18 days, until the transplant took place.“The ECMO was the bridge between my respiratory failure and the transplant,” Ms. Stoeffler told USA Today in 2009.ECMO — a treatment for lung-damaging viruses — has proved extremely helpful in the past with cases of H1N1 flu (or swine flu) and is now being widely used at major medical centers in the Covid-19 pandemic, according to data from Columbia and other ECMO centers around the world. A study published in the medical journal The Lancet last September showed that 62.6 percent of 1,035 severely ill Covid-19 patients survived after receiving ECMO treatments.Ms. Stoeffler’s transplanted lungs worked well for nearly a decade, enabling her to hike in the mountains near her childhood home in Austria and finish two New York City Marathons,half-marathons, an Ironman bicycle course and a sprint triathlon.But her body eventually rejected the transplanted lungs, and she underwent another transplant in 2019. It did not work as well or last as long. Ms. Stoeffler died of cystic fibrosis on March 4 at the Irving Medical Center, her brother Ewald Stoffler said. She was 61.Liesbeth Stoeffler was born on June 18, 1959, in Hermagor, Austria, a town at the foot of the Carnic Alps. Her father, Johann, was a truck driver; her mother, Margarethe (Strempfl) Stoeffler, was a homemaker.After finishing trade school, she left Austria in 1977 for an au pair job in Manhattan, where she had hoped to move since she was young, her brother said in an email.“During the first three years Liesbeth spent in New York, she refused to speak a single word of German,” Mr. Stoeffler wrote, “so she can learn English as fast and as good as possible.”She took classes in computers and graphic design and was hired by Deutsche Bank, the Blackstone Group and finally the investment management firm Sanford C. Bernstein (now AllianceBernstein). She worked there for nearly 20 years, rising to vice president and presentation specialist and creating graphics for marketing and sales documents.She began to experience breathing problems while at Bernstein and learned she had cystic fibrosis in 1995. But she kept it largely to herself.“She was always coughing, causing her co-workers to ask her to check it out,” said Christina Restivo, a close friend who had met her at Bernstein and was the leader of a support team of friends who looked after her. “She kept it private until she was so far along that the only way to live was with a double transplant.”In June 2009, after a routine blood test at the hospital, Ms. Stoeffler felt too exhausted to return home. One of her doctors, David Lederer, a pulmonologist, admitted her.“Within 48 hours, she was in the I.C.U., on a ventilator,” he said in a video about her case made by the Irving Medical Center. He added, “She wasn’t really improving on the vent support we were providing for her, so we knew we had to do something for her.”Using the ECMO helped her remain eligible for the transplant. “About five days into it, she told me it was the best she’d felt in years,” Dr. Matthew Bacchetta, who also treated Ms. Stoeffler, told a Columbia online publication.In less than two years, Ms. Stoeffler began running races in earnest. Starting with the Fred Lebow Classic, a five-mile race in Central Park in January 2011 (named after the founder of the New York City Marathon), she finished 47 different races hosted by the New York Road Runners club. Her last one was an 8-kilometer event in August 2017.Ms. Restivo said that her friend’s running had probably extended the life of her transplanted lungs.“Because your immune system is so suppressed by having a transplant, she was told not to exercise in a gym, where she could pick up bacteria,” she said. “She used the outdoors to exercise her lungs.”In addition to her brother Ewald, Ms. Stoeffler is survived by three sisters, Gabriele and Birgit Stoeffler and Waltraud Wildpanner; and another brother, Hannes.Ms. Restivo, who is the executor of Ms. Stoeffler’s will, said Ms. Stoeffler would sometimes text with instructions to give the doctors. Another text arrived on her last day.“I got a call to go to the hospital at 3:30 a.m. in the morning,” she said. “Liesbeth, with her oxygen mask on, was still alert, texting me as usual, telling me what to do and keeping me advised of her status. Fully cognizant at all times.”

How do different parts of the body communicate? Scientists at St. Jude are studying how signals sent from skeletal muscle affect the brain.
The team studied fruit flies and cutting-edge brain cell models called organoids. They focused on the signals muscles send when stressed. The researchers found that stress signals rely on an enzyme called Amyrel amylase and its product, the disaccharide maltose.
The scientists showed that mimicking the stress signals can protect the brain and retina from aging. The signals work by preventing the buildup of misfolded protein aggregates. Findings suggest that tailoring this signaling may potentially help combat neurodegenerative conditions like age-related dementia and Alzheimer’s disease.
“We found that a stress response induced in muscle could impact not only the muscle but also promote protein quality control in distant tissues like the brain and retina,” said Fabio Demontis, PhD, of St. Jude Developmental Neurobiology. “This stress response was actually protecting those tissues during aging.”
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Materials provided by St. Jude Children’s Research Hospital. Note: Content may be edited for style and length.

For people with tooth decay, drinking a cold beverage can be agony.
“It’s a unique kind of pain,” says David Clapham, vice president and chief scientific officer of the Howard Hughes Medical Institute (HHMI). “It’s just excruciating.”
Now, he and an international team of scientists have figured out how teeth sense the cold and pinpointed the molecular and cellular players involved. In both mice and humans, tooth cells called odontoblasts contain cold-sensitive proteins that detect temperature drops, the team reports March 26, 2021, in the journal Science Advances. Signals from these cells can ultimately trigger a jolt of pain to the brain.
The work offers an explanation for how one age-old home remedy eases toothaches. The main ingredient in clove oil, which has been used for centuries in dentistry, contains a chemical that blocks the “cold sensor”protein, says electrophysiologist Katharina Zimmermann, who led the work at Friedrich-Alexander University Erlangen-Nürnberg in Germany.
Developing drugs that target this sensor even more specifically could potentially eliminate tooth sensitivity to cold, Zimmermann says. “Once you have a molecule to target, there is a possibility of treatment.”
Mystery channel
Teeth decay when films of bacteria and acid eat away at the enamel, the hard, whitish covering of teeth. As enamel erodes, pits called cavities form. Roughly 2.4 billion people — about a third of the world’s population — have untreated cavities in permanent teeth, which can cause intense pain, including extreme cold sensitivity.

University of Maryland School of Medicine (UMSOM) researchers have identified the most toxic proteins made by SARS-COV-2 — the virus that causes COVID-19 — and then used an FDA-approved cancer drug to blunt the viral protein’s detrimental effects. In their experiments in fruit flies and human cell lines, the team discovered the cell process that the virus hijacks, illuminating new potential candidate drugs that could be tested for treating severe COVID-19 disease patients. Their findings were published in two studies simultaneously on March XX in Cell & Bioscience, a Springer Nature journal.
“Our work suggests there is a way to prevent SARS-COV-2 from injuring the body’s tissues and doing extensive damage,” says senior author of the study Zhe “Zion” Han, PhD, Associate Professor of Medicine and Director of the Center for Precision Disease Modeling at UMSOM. He notes that the most effective drug against Covid-19, remdesivir, only prevents the virus from making more copies of itself, but it does not protect already infected cells from damage caused by the viral proteins.
Prior to the pandemic, Dr. Han had been using fruit flies as a model to study other viruses, such as HIV and Zika. He says his research group shifted gears in February 2020 to study SARS-COV-2 when it was clear that the pandemic was going to significantly impact the U.S.
SARS-COV-2 infects cells and hijacks them into making proteins from each of its 27 genes. Dr. Han’s team introduced each of these 27 SARS-CoV-2 genes in human cells and examined their toxicity. They also generated 12 fruit fly lines to express SARS-CoV-2 proteins likely to cause toxicity based on their structure and predicted function.
The researchers found that a viral protein, known as Orf6, was the most toxic killing about half of the human cells. Two other proteins (Nsp6 and Orf7a) also proved toxic, killing about 30-40 percent of the human cells. Fruit flies that made any one of these three toxic viral proteins in their bodies were less likely to survive to adulthood. Those fruit flies that did live had problems like fewer branches in their lungs or fewer energy-generating power factories in their muscle cells.
For the remaining experiments, the researchers focused on just the most toxic viral protein, so they could figure out what cell process the virus hijacks during infection. Dr. Han’s team found that the virus’ toxic Orf6 protein sticks to multiple human proteins that have the job of moving materials out of the cell’s nucleus — the place in the cell that holds the genome, or the instructions for life.
They then discovered that one of these human moving proteins, targeted by the virus, gets blocked by the cancer drug selinexor. The researchers tested selinexor on human cells and fruit flies making the toxic viral protein to see if the drug could help reverse the damage. Selinexor, like many cancer drugs is itself toxic. However, after accounting for its toxic effects, the drug improved human cell survival by about 12 percent. Selinexor prevented early death in about 15 percent of the flies making the toxic viral protein. The drug also restored branches in the lungs and the energy-generators in the muscle cells. Selinexor is FDA-approved to treat certain blood cancers.
“More than 1,000 FDA-approved drugs are in clinical trials to test as treatments for Covid-19, and luckily a trial testing selinexor, the drug used in our study, is being performed already,” says Dr. Han. “If this trial proves to be successful, our data will have demonstrated the underlying mechanism for why the drug works.”
Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, University of Maryland Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine, commented, “Although we now have vaccines, it may still be a while before we will have Covid-19 infections under control, especially with the new variants emerging. We will need to tap into every tool in the arsenal available to protect people from needless sickness, disability or even death, and this study guides us towards a new target for potential therapeutics.”
These two studies were funded by a University of Maryland COVID-19 Accelerated Translational Incubator Pilot Grant, the University of Maryland, the Baltimore Institute for Clinical and Translational Research, and the University of Maryland School of Pharmacy Mass Spectrometry Center.
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Materials provided by University of Maryland School of Medicine. Original written by Vanessa McMains. Note: Content may be edited for style and length.

Researchers figured out how a jolt of discomfort gets from the damaged outside of your tooth to the nerves inside it.There’s nothing quite like the peculiar, bone-jarring reaction of a damaged tooth exposed to something cold: a bite of ice cream, or a cold drink, and suddenly, that sharp, searing feeling, like a needle piercing a nerve.Researchers have known for years that this phenomenon results from damage to the tooth’s protective outer layer. But just how the message goes from the outside of your tooth to the nerves within it has been difficult to uncover. On Friday, biologists report in the journal Science Advances that they have identified an unexpected player in this painful sensation: a protein embedded in the surface of cells inside the teeth. The discovery provides a glimpse of the connection between the outer world and the interior of a tooth, and could one day help guide the development of treatments for tooth pain.More than a decade ago, Dr. Katharina Zimmerman, now a professor at Friedrich-Alexander University in Germany, discovered that cells producing a protein called TRPC5 were sensitive to cold. When things got chilly, TRPC5 popped open to form a channel, allowing ions to flow across the cell’s membrane.Ion channels like TRPC5 are sprinkled throughout our bodies, Dr. Zimmerman said, and they are behind some surprisingly familiar sensations. For instance, if your eyes start to feel cold and dry in chilly air, it’s a result of an ion channel being activated in the cornea. She wondered which other parts of the body might make use of a cold receptor such as TRPC5. And it occurred to her that “the most sensitive tissue in the human body can be teeth” when it comes to cold sensations.Within the protective shell of their enamel, teeth are made of a hard substance called dentin that’s threaded with tiny tunnels. At the heart of the dentin is the tooth’s soft pulp, where nerve cells and cells called odontoblasts, which manufacture dentin, are intertwined.The prevailing theory for how teeth sense cold had been that temperature changes put pressure on the fluid in dentin’s tunnels, somehow provoking a response in those concealed nerves. But there was little detail about how exactly that could be happening and what could be bridging the gap between them.Dr. Zimmerman and her colleagues looked to see whether mice engineered to lack the TRPC5 channel still felt tooth pain as normal mice did. They were intrigued to find that these mice, when they had damage to their teeth, did not behave as if anything was amiss. They looked, in fact, about the same as if they had been given an anti-inflammatory painkiller, Dr. Zimmerman said.Her co-author Dr. Jochen Lennerz, a pathologist at Massachusetts General Hospital, checked human teeth for signs of the ion channel and found it in their nerves and other cells. That suggested that the channel might have a role in a person’s perception of cold.Over many years, the researchers constructed a way to precisely measure the nerve signals traveling out of a mouse’s damaged molar. They tested their ideas with molecules that could block the activity of various channels, including TRPC5.The picture they slowly assembled is that TRPC5 is active in the odontoblasts. That was a bit of a surprise, as these supporting cells are best known for making and maintaining dentin, not aiding in perception. Within the odontoblasts, Dr. Lennerz said, TRPC5 pops open when the signal for cold comes down the dentin tunnels, and this results in a message being sent to the nerves.As it happens, one substance that keeps TRPC5 from opening is eugenol, the main ingredient in oil of cloves, a traditional treatment for toothache. Though the Food and Drug Administration in the United States is equivocal about eugenol’s effectiveness, if it does lessen the pain for some people, it may be because of its effect on TRPC5.Perhaps the knowledge that this channel is at the heart of cold-induced pain will lead to better treatments for dental pain down the road — better ways to keep that message from becoming overwhelming.

A slew of new ads show sloppy kisses. Air travel is ticking back up. And impending vaccination can seem like a ticket back to normalcy for 20-somethings in the United States, many of whom feel desperate to get back to their 2019 social lives. Cramped parties. Strobe-lit dance floors. The ability to spontaneously text a friend: Want to grab a drink?Younger adults have played a disproportionate role in spreading the coronavirus. A report from the Centers for Disease Control and Prevention showed that from June to August 2020, Covid infections among 20- to 29-year-olds surged, accounting for more than 20 percent of the country’s total cases. Shortly after, data showed that those cases then led to an increase in infections among middle-aged and older people, potentially contributing to a national surge in cases.Now, as older adults have been prioritized for vaccination and about two-thirds of those over 65 have received at least one dose, their risk of getting severely ill after catching the virus from an infected young person has decreased significantly.But that doesn’t mean it’s completely safe to party like it’s 2019.How you calculate your risk of passing the virus onto more vulnerable people will hinge on your individual circumstances: whether you live with parents or people in their 20s, whether there are people at risk for severe outcomes of Covid in your social circle. “There’s not a simple red light, green light,” said Dr. William Schaffner, an infectious disease expert at Vanderbilt University.Here are some answers to common questions about what, in general, younger adults who are low risk can do when they’re fully vaccinated.Can we just go back to normal?A return to a kind of normal is coming, experts stressed, but there are still many unknowns about how the next few months will play out. While rising vaccination rates and falling cases are encouraging, said Dr. Schaffner, there are three situations that could hamper or negate that progress: if people refuse vaccination, if community transmission rates stay high and if virus variants render vaccines less effective.“If the older and younger adults get vaccines, and the variants are not too variant, then we could have lots of pool parties,” he said. “Bars could open up.”“The movement back to normal life should be a slow step-by-step,” said Tara Kirk Sell, a senior associate at the Johns Hopkins Center for Health Security, who researches large-scale health events. She recommended that people pick out one riskier activity they’ve been craving during the pandemic — seeing friends, going out to eat — and do that to celebrate their vaccination. “Then it should be a gradual move forward, rather than this huge explosion of, ‘I’m free!’,” she said.Lelanie Foster for The New York TimesLelanie Foster for The New York TimesBut much of that is dependent on how much virus is circulating in your community.“Once you get to a combination of hardly any cases in the community and a high proportion of people vaccinated — then, everything changes,” said Dr. Paul E. Sax, an infectious disease specialist at Brigham and Women’s Hospital in Boston. “That’s really what we’re looking forward to. Then you say, ‘Sure, I’ll take the chance of going to a restaurant. My chance of going to a restaurant and getting sick from Covid is no higher than the risk of getting sick from a regular cold.’ That’s a risk people should be very willing to take.”“People have to keep their eyes on the Covid landscape the way they do the weather,” said Dr. Peter Chin-Hong, an infectious disease expert at the University of California, San Francisco. He recommended that people monitor vaccination rates in their community and cases per 100,000. Dr. Carlos del Rio, an infectious disease specialist at Emory University, recommended the Covid ActNow site to check case numbers per county; The New York Times also tracks risk level by county.If your area has fewer than 10 cases per 100,000, it’s safer to go to a party or hang out indoors in a larger group of all vaccinated people. A far less safe scenario would be to participate in the kinds of spring break-related parties that are drawing attention in Florida, which reported 22 cases per 100,000 in the past seven days and is thought to have a large concentration of B.1.1.7, the more contagious and possibly more lethal virus variant first identified in Britain.Can we make out with strangers?Experts interviewed for this piece said that kissing and other intimate contact with someone you don’t know once you’ve been vaccinated is likely to be safe as long as you can confirm that they are also vaccinated.Even without that confirmation, making out with a stranger is likely to be a lower risk activity than going into a crowded setting like a club or party, said Dr. David Rubin, a professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania. “It’s one of those events best left to the individual person, to make that choice and not judge it,” he said.“If you’re in a controlled setting and you’re just with that person, and you want to take a chance on making out with that person and you think that person doesn’t have any risk of getting bad Covid — from the C.D.C. guidance, you can go ahead and make out with that person all you want,” said Dr. Chin-Hong.If you’re vaccinated but can’t confirm the vaccination or medical status of the person you want to kiss, it will be OK for most young people, he said.“The name of the game here is control,” he said. “The more noses and mouths that get together, the potentially riskier it is for transmission.”There’s also the obvious logistical quandary: It can be hard to casually and quickly verify that someone is fully vaccinated and low-risk. One dating app, Coffee Meets Bagel, recently added an option to include vaccine status on dating profiles, although it does not require verification.Can we gather in groups?The C.D.C. released recommendations earlier this month that said that it’s safe for vaccinated adults to gather in small groups without masks or social distancing. A C.D.C. spokeswoman said in an email that those guidelines applied to all people living in the United States, and that there were no additional considerations for younger adults.Practically, that means it’s OK for a group of about five to 10 vaccinated friends to hang out without precautions. But the larger the gathering, the more likely it is that someone in the group will be unvaccinated. While all three vaccines seem to be effective at preventing severe illness from the virus, we don’t yet know if they’ll prevent people from transmitting the virus to others.What about indoor bars?Dr. Ashish K. Jha, dean of the Brown University School of Public Health, predicted that most bars will be open across the country this summer. He also predicted that they’ll be a major source of viral spread among unvaccinated people, though they should be mostly safe for those who have received the vaccine.“The bottom line is, if you want to go to a bar, you want to go to a club — you can, and you’ll be pretty safe” once you’ve been vaccinated, Dr. Jha said. But other experts cautioned that there are still too many unknowns — about variants, about whether you can still transmit the virus after you’ve been vaccinated — to fully encourage people to flock back to indoor bars.Outdoor bars can be safer, depending on their setup and particularly if community transmission is low. Just be sure to stick to a small group of friends, rather than a large crowd.What about outdoor concerts?Experts agreed that outdoor concerts could be safe, particularly if attendees wear masks and keep distanced. Outdoor activities can support much larger groups of vaccinated people, Dr. Sax said.“People were wondering why there weren’t more cases after the protests this summer,” he said. “Well, it’s because they took place outside. That’s going to be true about outdoor concerts, also — I’d be very surprised if there were any major spreader events linked to an outdoor concert.”Do young people need to get vaccinated?Experts expressed concerns about vaccine hesitancy among young people. In January, the U.S. Census Bureau released survey data that showed that Americans under 44 were most reluctant to get vaccinated.“We’ve been selling the vaccine to older individuals as a way to protect against hospitalization and death,” Dr. del Rio said. “Most young people, if they get infected, they get a mild disease. We need to be able to communicate very clearly that there’s an advantage to getting the vaccine for young people, besides saying, ‘You’re not going to die.’”“The faster we vaccinate people, the more likely we are to have a more normal life,” he said.

Scientists at the University of Bonn and the caesar research center have isolated a molecule that might open new avenues in the fight against SARS coronavirus 2. The active ingredient binds to the spike protein that the virus uses to dock to the cells it infects. This prevents them from entering the respective cell, at least in the case of model viruses. It appears to do this by using a different mechanism than previously known inhibitors. The researchers therefore suspect that it may also help against viral mutations. The study will be published in the journal Angewandte Chemie but is already available online.
The novel active ingredient is a so-called aptamer. These are short chains of DNA, the chemical compound that also makes up chromosomes. DNA chains like to attach themselves to other molecules; one might call them sticky. In chromosomes, DNA is therefore present as two parallel strands whose sticky sides face each other and that coil around each other like two twisted threads.
Aptamers, on the other hand, are single-stranded. This allows them to form bonds with molecules to which conventional DNA would not normally bind and to influence their function. This makes them interesting for research into active ingredients, especially since it is now very easy to produce huge libraries of different aptamers. Some of these libraries contain millions of times more potential active ingredients than there are people living on Earth. “We used such a library to isolate aptamers that can attach to the spike protein of SARS coronavirus 2,” explains Prof. Dr. Günter Mayer of the LIMES Institute (the acronym stands for “Life and Medical Sciences”) at the University of Bonn.
Spike is essential for the infection
The spike protein is essential for the virus: It uses it to dock onto the cells it attacks. In the process, the protein binds to a molecule on the surface of its victims called ACE2, which effectively locks into the spike protein, much like a ski boot in a ski binding. The virus then fuses with the cell and reprograms it to produce numerous new viruses. “The vast majority of antibodies we know today prevent docking,” Mayer explains. “They attach to the part of the spike protein responsible for recognizing ACE2, which is the receptor binding domain, or RBD.”
The now isolated aptamer with the abbreviation SP6 also binds to the spike protein, but at a different site. “SP6 does not prevent viruses from docking to target cells,” explains Prof. Dr. Michael Famulok of the LIMES Institute, who also works at the caesar research center in Bonn. “Nevertheless, it reduces the level of cell infection by the virus; we do not yet know which mechanism is responsible for this.” The researchers did not use real coronaviruses in their experiments, but so-called pseudoviruses. These carry the spike protein on their surface; however, they cannot cause disease. “We now need to see if our results are confirmed in real viruses,” Famulok therefore emphasizes.
New Achilles heel of coronavirus?
If so, in the medium term the work could for instance result in a kind of nasal spray that protects against coronavirus infection for a few hours. The necessary studies will certainly take months to complete. Irrespective of this, however, the results may help to better understand the mechanisms involved in infection. This is all the more important because the existing active ingredients mainly target the receptor domain. In the so-called “British mutation,” this domain is altered so that it binds more strongly to ACE2. “The more such mutations accumulate, the greater the risk that the available drugs and vaccines will no longer work,” stresses Günter Mayer. “Our study may draw attention to an alternative Achilles’ heel of the virus.”
The results are also evidence of successful cooperation: Mayer and his postdoctoral researcher Dr. Anna Maria Weber were primarily responsible for characterizing the aptamer. Prof. Famulok’s group at the caesar research center was responsible for conducting the pseudovirus experiments, which were led by his colleague Dr. Anton Schmitz. Famulok and Mayer are members of the Transdisciplinary Research Areas “Life & Health” and “Building Blocks of Matter and Fundamental Interactions.” Mayer also heads the Center of Aptamer Research and Development (CARD) at the University of Bonn.
The study was funded by the German Federal Ministry of Education and Research (BMBF) and the German Research Foundation (DFG).
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Materials provided by University of Bonn. Note: Content may be edited for style and length.

Research has found that obesity and mental disorders such as depression and anxiety seem to often go hand in hand. Researchers at Baylor College of Medicine and collaborating institutions are providing new insights into this association by identifying and characterizing a novel neural circuit that mediates the reciprocal control of feeding and psychological states in mouse models.
Similar to human patients, mice that consumed a high-fat diet not only became obese, but also anxious and depressed, a condition mediated by a defective brain circuit. When the researchers genetically or pharmacologically corrected specific disruptions they had observed within this circuit, the mice became less anxious and depressed and later lost excess body weight.
Interestingly, weight loss was not the result of lack of appetite, but of the animals’ change of food preference. Before the treatment, the mice naturally preferred to eat a high-fat diet, but after the treatment they turned their preference toward a healthier diet with reduced fat and abundant protein and carbohydrates. The findings, published in the journal Molecular Psychiatry, for the first time, not only reveal a key regulatory mechanism for coinciding obesity and mental disorders, but also suggest the possibility of a pharmacological treatment.
“Reports indicate that 43% of adults with depression are obese and that adults with mental illness are more likely to develop obesity than those who are mentally healthy,” said corresponding author Dr. Qi Wu, a Pew Scholar for Biomedical Sciences, Kavli Scholar and assistant professor in pediatrics-nutrition at Baylor’s Children’s Nutrition Research Center. “Factors such as hormonal dysregulation, genetic deficiency and inflammation have been proposed to be involved in the connection between obesity and mental disorders. Here we provide evidence that supports the involvement of a neural component.” To investigate the neuronal circuits that could be involved in reciprocally regulating weight gain and depression or anxiety, the researchers provided mice with a high-fat diet. As expected, the animals became obese. They also developed anxiety and depression. In these mice, the team studied the function of neuronal circuits.
“We discovered in normal mice that two groups of brain cells, dBNST and AgRP neurons located in separate brain areas, form a circuit or connection to each other by extending cellular projections,” said co-first author Dr. Guobin Xia, postdoctoral associate in the Wu lab. “This newly discovered circuit was malfunctioning in mice that were both obese and depressed.”
“Using genetic approaches, we identified specific genes and other mediators that were altered and mediated the circuit’s malfunction in the obese and depressed mice,” said co-first author Dr. Yong Han, postdoctoral associate in the Wu lab.
“Importantly, genetically restoring the neural defects to normal eliminated the high fat diet-induced anxiety and depression and also reduced body weight,” Xia said. “We were surprised to see that the animals lost weight, not because they lost their appetite, but because genetically-aided readjustment of the mental states changed their feeding preference from high-fat to low-fat food.”
“Keeping in mind translational applications of our findings to the clinic, we investigated the possibility of restoring the novel circuit pharmacologically,” Wu said. “We discovered that the combination of two clinically-approved drugs, zonisamide and granisetron, profoundly reduced anxiety and depression in mice and promoted weight loss by synergistically acting upon two different molecular targets within our newly identified brain circuit. We consider that our results provide convincing support for further studies and future clinical trials testing the value of a cocktail therapy combining zonisamide and granisetron (or a selection of their derivatives) to treat metabolic-psychiatric diseases.”
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Materials provided by Baylor College of Medicine. Original written by Homa Shalchi. Note: Content may be edited for style and length.