Publisher Health

By cracking open a cellular membrane, Northwestern University synthetic biologists have discovered a new way to increase production yields of protein-based vaccines by five-fold, significantly broadening access to potentially lifesaving medicines.
In February, the researchers introduced a new biomanufacturing platform that can quickly make shelf-stable vaccines at the point of care, ensuring they will not go to waste due to errors in transportation or storage. In its new study, the team discovered that enriching cell-free extracts with cellular membranes — the components needed to made conjugate vaccines — vastly increased yields of its freeze-dried platform.
The work sets the stage to rapidly make medicines that address rising antibiotic-resistant bacteria as well as new viruses at 40,000 doses per liter per day, costing about $1 per dose. At that rate, the team could use a 1,000-liter reactor (about the size of a large garden waste bag) to generate 40 million doses per day, reaching 1 billion doses in less than a month.
“Certainly, in the time of COVID-19, we have all realized how important it is to be able to make medicines when and where we need them,” said Northwestern’s Michael Jewett, who led the study. “This work will transform how vaccines are made, including for bio-readiness and pandemic response.”
The research will be published April 21 in the journal Nature Communications.
Jewett is a professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and director of Northwestern’s Center for Synthetic Biology. Jasmine Hershewe and Katherine Warfel, both graduate students in Jewett’s laboratory, are co-first authors of the paper.
The new manufacturing platform — called in vitro conjugate vaccine expression (iVAX) — is made possible by cell-free synthetic biology, a process in which researchers remove a cell’s outer wall (or membrane) and repurpose its internal machinery. The researchers then put this repurposed machinery into a test tube and freeze-dry it. Adding water sets off a chemical reaction that activates the cell-free system, turning it into a catalyst for making usable medicine when and where it’s needed. Remaining shelf-stable for six months or longer, the platform eliminates the need for complicated supply chains and extreme refrigeration, making it a powerful tool for remote or low-resource settings.
In a previous study, Jewett’s team used the iVAX platform to produce conjugate vaccines to protect against bacterial infections. At the time, they repurposed molecular machinery from Escherichia coli to make one dose of vaccine in an hour, costing about $5 per dose.
“It was still too expensive, and the yields were not high enough,” Jewett said. “We set a goal to reach $1 per dose and reached that goal here. By increasing yields and lowering costs, we thought we might be able to facilitate greater access to lifesaving medicines.”
Jewett and his team discovered that the key to reaching that goal lay within the cell’s membrane, which is typically discarded in cell-free synthetic biology. When broken apart, membranes naturally reassemble into vesicles, spherical structures that carry important molecular information. The researchers characterized these vesicles and found that increasing vesicle concentration could be useful in making components for protein therapeutics such as conjugate vaccines, which work by attaching a sugar unit — that is unique to a pathogen — to a carrier protein. By learning to recognize that protein as a foreign substance, the body knows how to mount an immune response to attack it when encountered again.
Attaching this sugar to the carrier protein, however, is a difficult, complex process. The researchers found that the cell’s membrane contained machinery that enabled the sugar to more easily attach to the proteins. By enriching vaccine extracts with this membrane-bound machinery, the researchers significantly increased yields of usable vaccine doses.
“For a variety of organisms, close to 30% of the genome is used to encode membrane proteins,” said study co-author Neha Kamat, who is an assistant professor of biomedical engineering at McCormick and an expert on cell membranes. “Membrane proteins are a really important part of life. By learning how to use membrane proteins effectively, we can really advance cell-free systems.”
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Materials provided by Northwestern University. Original written by Amanda Morris. Note: Content may be edited for style and length.

Although colorectal cancer is the second most frequent cause of cancer-related death in the United States, about one-third of eligible American adults have never completed a colorectal cancer screening test, explained lead author Zhu. Zhu added that colorectal cancer screening is particularly underutilized by individuals experiencing socioeconomic disadvantages, racial and ethnic minorities, and certain age groups.
The U.S. Preventive Services Task Force (USPSTF) recommends several colorectal cancer screening methods for adults ages 50 to 75 with an average risk for this disease, and the USPSTF draft guideline update released in October 2020 recommends lowering the age of screening initiation to 45. The three most common tests are an annual fecal immunochemical test or fecal occult blood test (FIT/FOBT) that detects blood in the stool; the multitarget stool DNA (mt-sDNA) test (Cologuard), completed every three years, which detects altered DNA from cancer cells, precancerous polyps, or blood in the stool; and a colonoscopy every 10 years, which involves a gastroenterologist examining the colon with a camera and removing any precancerous polyps while a patient is under sedation.
“Previous research has shown that fewer patients complete colorectal cancer screening when only colonoscopy is recommended compared to when stool-based options are also recommended,” said Zhu.
In this study, Zhu and colleagues evaluated patient preferences for colorectal cancer screening through a survey conducted in collaboration with the National Opinion Research Center at the University of Chicago. The survey included short descriptions of FIT/FOBT, mt-sDNA, and colonoscopy, and asked a nationally representative sample of adults ages 40 to 75 to choose between two options presented at a time. A total of 1,595 respondents completed the survey. The researchers focused their analysis on a subgroup of 1,062 respondents aged 45 to 75 with an average risk of colorectal cancer.
When presented with a choice, 66 percent of respondents said they preferred mt-sDNA over colonoscopy, and 61 percent said they preferred FIT/FOBT over colonoscopy. When asked to choose between the two stool-based options, 67 percent indicated a preference for mt-sDNA over FIT/FOBT.
The investigators also examined differences in patient preferences across sociodemographic characteristics, access to health care, awareness of colorectal cancer screening, and prior experience completing a test. While mt-sDNA was preferred over colonoscopy for all age groups examined, a larger proportion of older adults (ages 65 to 75 years) said they preferred colonoscopy compared to those in younger age groups (ages 45 to 54 years).
Similarly, the preference for mt-sDNA over colonoscopy was higher among non-Hispanic white individuals compared with non-Hispanic Black and Hispanic individuals. Half of Hispanic and non-Hispanic Black respondents preferred stool-based tests over colonoscopy, with a preference for mt-sDNA over FIT/FOBT. Zhu said the observed differences among age and racial/ethnic groups might have reflected variations in preferences or disparities in access to information about newer testing methods.
Respondents without insurance were 2.5 times more likely to prefer less expensive stool-based tests over colonoscopy. The overall awareness of stool-based tests was about 60 percent, compared to 90 percent for colonoscopy, indicating that there is an opportunity to improve patient education about stool-based options, Zhu noted. Study participants who were aware of stool-based tests were two times more likely to prefer mt-sDNA over FIT/FOBT, and those who had previously had a stool-based test were 2.8 times more likely to choose FIT/FOBT over colonoscopy. By contrast, those who had previously had a colonoscopy were less than half as likely to prefer a stool-based test over colonoscopy and those who had a provider recommend colonoscopy in the past 12 months were 40 percent less likely to prefer mt-sDNA over colonoscopy.
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Despite the urgent need for treatments to slow or stop Alzheimer’s disease, finding patients for clinical trials has been difficult and frustrating.Patients are often older. Their doctors may not be part of a research network. And many with dementia never get a diagnosis — their doctors do not tell them what is wrong or they avoid finding out that they have the dreaded disease.“How do you recruit when patients do not realize they are eligible?” said Michelle Papka, director of the Cognitive and Research Center, a clinical trial site in Springfield, N.J.Her center is one of 290 now seeking participants for a new study by the drugmaker Eli Lilly and Company that plans to enroll 1,500 patients. The company hopes it will confirm results from its smaller study, lasting 76 weeks, of 257 patients. It found the experimental drug donanemab significantly slowed the progress of Alzheimer’s — the first time a study of a disease-modifying Alzheimer’s drug met its primary goals.“I will be shocked if it is not a popular study,” said John Dwyer, president of the Global Alzheimer’s Platform Foundation, a network of clinical trial sites hired by Lilly to help speed the recruitment of patients.But where will patients come from?They have to have just the right amount of brain deterioration — too much and it probably is too late. Too little and it may take too long to see a drug effect, if there is any. They often have to find out about the study on their own. They have to agree to have regular infusions of what might be a placebo for more than a year.On top of all that, if they or their family members have been paying attention to the state of Alzhemier’s drug research, they would know that study after study of what looked like a promising treatment for Alzheimer’s has failed, to such an extent that some companies, after spending billions in futile attempts, decided to get out of the business of developing Alzheimer’s drugs.Three who arrived at a clinical trial site in New Jersey on March 26, a misty Friday morning provide some answers about who might enroll, and why.HE SAID, “NO WAY, NOT ME”Michael Gross, a lifelong Yankees fan, was unnerved when he forgot the name of one of the team’s former managers — Casey Stengel — and was determined to keep it in his memory.Jackie Molloy for The New York TimesA few years ago, Michael Gross, 73, of Mahwah, N.J., began to realize something was wrong. “I was confused about words,” he said, “and it continued to get worse.”But Mr. Gross, the retired head of an advertising agency, was taken aback when a doctor suggested a spinal tap to look for proteins that are a sign of Alzheimer’s. He could not have that disease, Mr. Gross thought.“I said, ‘No way, not me,’” he said.But he did.He wept, he despaired.Then he asked, What could he do about it?He switched to the Mediterranean diet. He started exercising. He began doing crossword puzzles and subscribed to a challenging brain-training program. He found a study in mice claiming a bright light shined at their heads helped with Alzheimer’s. He bought the light.The disease kept progressing. Now he cannot remember the details of a news story as he reads it.Mr. Gross, a lifelong Yankees fan, was unnerved the day he forgot the name of the team’s former manager, Casey Stengel, and became determined to keep it in his memory.“Every day I wake up and tell myself ‘Casey Stengel, Casey Stengel,’” he says.Then he forgot the word “sardines,” a staple of his Mediterranean diet. “For a week I said to myself, ‘sardines, sardines,’” Mr. Gross said.But what he really wanted was a treatment powerful enough to stop Alzheimer’s in its tracks.Mr. Gross saw an ad on Facebook for the Lilly clinical trial. That Friday morning he arrived for a test to see if he was eligible. It consisted of a brain scan for a protein, tau, that is found in dead and dying brain neurons. If he had too little tau, he would not be eligible.He had another test, an M.R.I. scan of his brain and discovered that he was accepted for the trial.And now, if he does not get the drug? Or if the drug fails?Then he will look for other trials, Mr. Gross said. He would even consider a treatment he recently heard about. “They shoot something into your nostril, and it supposedly cures you,” he said.His wife, Peggy, chimed in.“We haven’t gotten to a point where we admitted there is no help for him,” she said.“IT GOT TO A POINT WHERE IT WAS VERY, VERY REAL”The next patient to arrive was a 63-year-old woman who is enrolled in the trial and has already had two infusions of either the drug or the placebo. She and her husband asked that their names not be used because they have not yet revealed her diagnosis to their friends and family.She’s a bubbly optimist, but because of her disease, let her husband do most of the talking. When her memory started faltering a few years ago, she and her husband attributed it to the stress of her job as an occupational therapist.“I don’t think we thought about Alzheimer’s,” her husband said.But her memory problems continued, even after she left her job. She would go grocery shopping, taking a list with her, and forget things on the list. She would forget appointments.“It got to a point where it was very, very real,” her husband said.Dr. Michelle Papka, the director of the Cognitive and Research Center in New Jersey. “How do you recruit when patients do not realize they are eligible?” she said of the difficulty in finding participants for clinical trials of Alzheimer’s drugs.Jackie Molloy for The New York TimesHe took his wife to a neurologist who administered a battery of tests. The results were not good.“For the first time it went from a memory issue to something alarming,” the husband said. On March 6, a spinal tap confirmed the likely diagnosis: Alzheimer’s.The man and his wife were distraught. No drug, no lifestyle change, had been shown to alter the course of the disease. Their doctor did not refer them to a clinical trial, but their oldest son, a second-year medical student, found the Lilly trial for them.The woman does not expect a cure, but she said, “I hope I don’t decline any farther. I don’t want to turn into a babbling idiot. If I can stay like this, I would be happy. I crochet, I color, I walk the dog.”Her husband tries not to think of the future.“I don’t know if I am in denial or what, but I haven’t fully grasped what life will be like five, 10 years down the road.”“THERE WOULDN’T BE A COVID VACCINE IF PEOPLE HAD NOT VOLUNTEERED”Marlene Lippman and Bob Lippman outside their home in Summit, N.J. Bob Lippman is a patient of a new Alzheimer’s clinical trial.Jackie Molloy for The New York TimesBob Lippman, 78, of Summit, N.J., got his Alzheimer’s diagnosis in November 2017 after a year and a half of mounting symptoms. He learned about the Lilly trial from Dr. Papka and was accepted. He had his second infusion at the New Jersey center that Friday morning.Conversation is difficult for Mr. Lippman now, so his wife, Marlene, told his story.“He was repeating things a lot and asking me the same things over and over,” she said. “He was forgetting whole conversations. At first I thought it was normal aging.”But after she heard a speaker from the Alzheimer’s Association at Sage Eldercare, a nonprofit organization near their home in Summit, N.J., she realized that what her husband was experiencing was not normal.Memory tests confirmed those fears, and a brain scan that detects amyloid, the stiff balls of plaque that are the hallmark of Alzheimer’s disease, cinched the diagnosis.It was life-shattering news.“Bob had a very strong intellect,” Ms. Lippman said. “It is hard that that part of him is being attacked.”She started making plans — redoing wills and power of attorney. She found a support group for caregivers at Sage. And she found the Lilly trial.Ms. Lippman is cleareyed about what to expect. If her husband is getting the drug and not the placebo and if the drug is as effective as it was in the initial small study, “at best it might delay the course of his decline,” she said. “It certainly is not going to cure him.”“Our main incentive is to help other people and to move research forward,” Ms. Lippman added. “There wouldn’t be a Covid vaccine if people had not volunteered.”Bob and Marlene Lippman in their home. “Bob had a very strong intellect,” Ms. Lippman said. “It is hard that that part of him is being attacked.”Jackie Molloy for The New York Times

Science shows that the risk of viral transmission outside is very low. The “two-out-of-three rule” can help you decide whether to mask up.As more people get vaccinated and spring weather and sunshine beckon us outdoors, one question may be nagging at you: Do we still need to wear masks outside?More than a year into pandemic life, many people remain confused about the risk of spending time outdoors around other people. A growing body of research shows that transmission of Covid-19 is far less likely outdoors than inside, and the risk will get even lower as more people get vaccinated and cases continue to decline. But many states have yet to lift strict outdoor mask mandates. In Massachusetts, for instance, outdoor masking is required at all times, even when nobody else is around.Recently the online magazine Slate stirred controversy when it suggested an end to outdoor mask rules. The article won support from top public health experts and even The New England Journal of Medicine blog but prompted a fierce backlash from readers, who noted that while the risk of outdoor transmission may be low, it’s not zero.“Shallow and selfish take,” wrote one reader on Twitter. “You have blood on your hands. You should feel ashamed,” posted another.After a year in which many of us have learned to dutifully wear masks and look askance at anyone who does not, it’s understandable that people remain fearful when they cross paths with the unmasked. So how do you make the right decision about when to wear a mask outside?Many virus and public health experts say the guidance hasn’t changed — spending time with others outside during the pandemic has always been safer than indoors. But whether a mask is needed outdoors depends on the circumstances, including local public health rules. Brief encounters with an unmasked person passing you on the sidewalk or a hiking trail are very low risk, said Linsey Marr, a professor of civil and environmental engineering at Virginia Tech. Viral particles quickly disperse in outdoor air, and the risk of inhaling aerosolized virus from a jogger or passers-by are negligible, she said. Even if a person coughs or sneezes outside as you walk by, the odds of you getting a large enough dose of virus to become infected remain low, she said.“I think the guidelines should be based on science and practicality,” said Dr. Marr. “People only have so much bandwidth to think about precautions. I think we should focus on the areas that have highest risk of transmission, and give people a break when the risk is extremely low.”Dr. Marr uses a simple two-out-of-three rule for deciding when to wear a mask. In every situation, she makes sure she’s meeting two out of three conditions: outdoors, distanced and masked. “If you’re outdoors, you either need to be distanced or masked,” she said. “If you’re not outdoors, you need to be distanced and masked. This is how I’ve been living for the past year. It all comes down to my two-out-of-three rule.”Use the 2-out-of-3 RuleTo lower risk for Covid-19, make sure your activity meets two out of the following three conditions: outdoors, distanced and masked.Outdoors + Distanced = No Mask NeededOutdoors + No Distance = Mask NeededNot Outdoors + Distanced = Mask NeededWhen masks are needed outdoorsIf you stop to have an extended conversation with someone who isn’t vaccinated, masks are recommended. Even outdoors, your risk of breathing someone else’s air increases the longer and closer you stand to them. One of the few documented cases of outdoor transmission happened in China early in the pandemic, when a 27-year-old man stopped to chat outside with a friend who had just returned from Wuhan, where the virus originated. Seven days later, he had his first symptoms of Covid-19.And masks are still advised if you find yourself in an outdoor crowd. Standing shoulder to shoulder with strangers during an outdoor concert or a protest could increase risk, particularly for the unvaccinated.Recently while hiking without a mask, Dr. Marr said she still made an effort to keep her distance from large groups when the trail got crowded.“If I was passing by a solo hiker it didn’t concern me,” said Dr. Marr. “But if I passed by a group of 10 hikers in a row, I stepped further off the path. The risk is still low, but at some point there could be a large enough pack of people that the risk could become appreciable.”When outdoor risk is lowestWalking your dog, riding a bike, hiking on a trail or picnicking with members of your household or vaccinated friends are all activities where the risk for virus exposure is negligible. In these kinds of situations, you can keep a mask on hand in your pocket, in case you find yourself in a crowd or need to go indoors..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-rqynmc{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.9375rem;line-height:1.25rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-rqynmc{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-rqynmc strong{font-weight:600;}.css-rqynmc em{font-style:italic;}.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-16ed7iq{width:100%;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-box-pack:center;-webkit-justify-content:center;-ms-flex-pack:center;justify-content:center;padding:10px 0;background-color:white;}.css-pmm6ed{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;}.css-pmm6ed > :not(:first-child){margin-left:5px;}.css-5gimkt{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.8125rem;font-weight:700;-webkit-letter-spacing:0.03em;-moz-letter-spacing:0.03em;-ms-letter-spacing:0.03em;letter-spacing:0.03em;text-transform:uppercase;color:#333;}.css-5gimkt:after{content:’Collapse’;}.css-rdoyk0{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;-webkit-transform:rotate(180deg);-ms-transform:rotate(180deg);transform:rotate(180deg);}.css-eb027h{max-height:5000px;-webkit-transition:max-height 0.5s ease;transition:max-height 0.5s ease;}.css-6mllg9{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;position:relative;opacity:0;}.css-6mllg9:before{content:”;background-image:linear-gradient(180deg,transparent,#ffffff);background-image:-webkit-linear-gradient(270deg,rgba(255,255,255,0),#ffffff);height:80px;width:100%;position:absolute;bottom:0px;pointer-events:none;}#masthead-bar-one{display:none;}#masthead-bar-one{display:none;}.css-1pd7fgo{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;}@media (min-width:740px){.css-1pd7fgo{padding:20px;width:100%;}}.css-1pd7fgo:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-1pd7fgo{border:none;padding:20px 0 0;border-top:1px solid #121212;}.css-1pd7fgo[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-1pd7fgo[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-1pd7fgo[data-truncated] .css-5gimkt:after{content:’See more’;}.css-1pd7fgo[data-truncated] .css-6mllg9{opacity:1;}.css-1rh1sk1{margin:0 auto;overflow:hidden;}.css-1rh1sk1 strong{font-weight:700;}.css-1rh1sk1 em{font-style:italic;}.css-1rh1sk1 a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;text-underline-offset:1px;-webkit-text-decoration-thickness:1px;text-decoration-thickness:1px;-webkit-text-decoration-color:#ccd9e3;text-decoration-color:#ccd9e3;}.css-1rh1sk1 a:visited{color:#333;-webkit-text-decoration-color:#ccc;text-decoration-color:#ccc;}.css-1rh1sk1 a:hover{-webkit-text-decoration:none;text-decoration:none;}“I think it’s a bit too much to ask people to put the mask on when they go out for a walk or jogging or cycling,” said Dr. Muge Cevik, a clinical lecturer of infectious disease and medical virology at the University of St. Andrews School of Medicine in Scotland, where outdoor masking has never been required. “We’re in a different stage of the pandemic. I think outdoor masks should not have been mandated at all. It’s not where the infection and transmission occurs.”“Let me go for my run, maskless. Mask in pocket,” tweeted Dr. Nahid Bhadelia, an infectious diseases physician and the medical director of the special pathogens unit at Boston Medical Center. “Given how conservative I have been on my opinions all year, this should tell you how low risk is, in general, for outdoors transmission for contact over short periods — and lower still after vaccination. Keep the masks on you for when you are stationary in a crowd and headed indoors.”To understand just how low the risk of outdoor transmission is, researchers in Italy used mathematical models to calculate the amount of time it would take for a person to become infected outdoors in Milan. They imagined a grim scenario in which 10 percent of the population was infected with Covid-19. Their calculations showed that if a person avoided crowds, it would take, on average, 31.5 days of continuous outdoor exposure to inhale a dose of virus sufficient to transmit infection.“The results are that this risk is negligible in outdoor air if crowds and direct contact among people are avoided,” said Daniele Contini, senior author of the study and an aerosol scientist at the Institute of Atmospheric Sciences and Climate in Lecce, Italy.Even as more-infectious virus variants circulate, the physics of viral transmission outdoors haven’t changed, and the risk of getting infected outdoors is still low, say virus experts. Pay attention to the rates of infection in your community. If case counts are surging, your risk of encountering an infected person goes up.When outdoor fun moves indoorsDr. Cevik notes that debates about outdoor masking and articles showing photos of crowded beaches during the pandemic have left people with the wrong impression that parks and beaches are unsafe, and distracted from the much higher risks of indoor transmission. Often it’s the indoor activities associated with outdoor fun — like traveling unmasked in a subway or car to go hiking, or dropping into a pub after spending time at the beach — that pose the highest risk. “People hold barbecues outdoors, but then they spend time indoors chatting in the kitchen,” said Dr. Cevik.As more people get vaccinated, decisions about going maskless outdoors will get easier. While no vaccine offers 100 percent protection, the rate of breakthrough infections so far has been exceedingly low. The U.S. Centers for Disease Control and Prevention recently reported just 5,800 cases of breakthrough infections among 75 million vaccinated people. And the C.D.C. has said vaccinated friends and family members can safely spend time together, without masks.But it’s OK to keep wearing your mask outdoors if you prefer it. After a year of taking pandemic precautions, it may be hard for people to adjust to less restrictive behaviors. Sarit A. Golub, a psychology professor at Hunter College of the City University of New York, said it’s important for both the media and public health officials to communicate the reasons people can modify some behaviors, like outdoor masking.“In the coming months, ‘normal life’ will begin to become safer, but I worry that some people won’t be willing or able to relax pandemic restrictions in ways that makes sense,” Dr. Golub said. “I worry that folks have internalized the fear messaging without understanding the reasons behind specific behavioral recommendations, and therefore, the reasons that they can be modified as circumstances change.”Gregg Gonsalves, assistant professor of epidemiology at the Yale School of Public Health, said he recently was with a group of parents, including many vaccinated physicians, who met in a New Haven park to celebrate a child’s first birthday. “We’re all just standing around, everybody was masked, and then we started asking, ‘When’s the time we can be outside and take off our masks?’” Dr. Gonsalves said. “If people are vaccinated and you’re outdoors, masks are probably superfluous at this point.”But Dr. Gonsalves said he understands why some people may be reluctant to give up their masks outdoors. “Some of this is Covid hangover,” he said. “We’ve been so traumatized by all of this. I think we need to have a little bit of compassion for the people having trouble letting go.”Illustrations by Eden Weingart

April 22, 2021Pain Is Inevitable. Suffering Is Not.Here are five ways to get unstuck.As a psychologist, I often teach clients in my clinical practice the difference between pain and suffering. Pain on its own can be difficult. But it’s only when you don’t accept it that it turns into suffering.Of course, more than a year into the Covid-19 pandemic, pain and suffering are understandable emotions. But as a compassionate gesture to yourself, it may be liberating to consider how you approach your own anguish, and if there are ways you can ease it a bit.After validating my clients’ legitimate distress, I encourage them to deal with challenges by embracing something called radical acceptance. It is a component of the kind of treatment I practice, dialectical behavioral therapy, which was developed by the psychologist Marsha Linehan. Many people know the term from the popular book “Radical Acceptance” by the meditation teacher, psychologist and podcast host Tara Brach.Radical acceptance means recognizing your emotional or physical distress — whether around minor issues, like traffic, or more significant challenges, such as navigating a chronic illness — and wholeheartedly practicing acceptance.Though it sounds counterintuitive, accepting negative circumstances can help you feel better. “Life regularly and inevitably involves emotional stress, anger, fears around health, shame around failed relationships,” Dr. Brach told me in an interview, “but anything short of fully accepting our human experience will keep us caught in those emotions.”One reason is that the habitual ways we deal with difficult situations, like pretending that everything is fine, acting pleasant when feeling resentful or even trying to acquiesce as a way to avoid truly feeling our emotions, are ultimately depleting, not restorative. That’s where the radical bit of radical acceptance comes in. In this case, the word means being all in rather than going halfway, which will feel phony to you and those around you. It’s the difference between accepting you’re anxious and avoiding, and being willing to feel anxious while approaching meaningful opportunities.Many of my clients initially confuse accepting with resigning themselves to feeling bad, but that couldn’t be further from what this practice intends. Psychologically, acceptance is an active stance that actually promotes change by helping us manage our emotions so we can solve problems. For instance, emotional eating can be a response to feeling bad about excess weight, but in fact, once you compassionately let go of berating yourself it can be easier to make healthy food choices.One trick to approaching radical acceptance, according to Dr. Brach, is to keep the acronym RAIN in mind. RAIN stands for: Recognize and pause to notice; Allow, or accept your current experience; Investigate, by pinpointing what is happening in your mind and body; then Nurture, by bringing compassion to yourself.By choosing acceptance in tense situations, you’ll get into the habit of bringing mindfulness to moments in your life when you need it most. As a bonus, studies have also shown that therapies incorporating acceptance reduce suicidality, substance use, anxiety, chronic pain, and improve relationships and subjective well-being.If becoming a more accepting person feels like an extreme makeover of your personality, research suggests that low-effort self-help exercises, similar to the ones I suggest below, can help you improve peace of mind and quality of life.Step 1Scan your mind for judgmental thoughtsTo begin to bring more acceptance into your life, rather than passively falling into negative thinking, notice thoughts, like “Why me?,” that thwart your ability to cope. Then come back to seeing the present as it is, not as you think it should be. When you’re lost in thoughts about life being unfair or terrible — even if it is — it’s impossible to be effective.For instance, if your child is up hours after bedtime, you may tell yourself, “I can’t take this!” But instead of falling into an emotional spiral, try to recognize what is actually true, such as, “I’m exhausted and crave some time for myself.” Besides easing your frustrations with your child (which will be more conducive to setting the mood for sleep), thinking factually offers more perspective.Step 2Honor your emotionsWhile acceptance will help you feel better, know that it isn’t a way to escape your feelings. Emotions communicate information to us and can motivate useful actions when based on realities, rather than stories our minds churn. That’s why it’s important to allow yourself to experience whatever you’re feeling.Experiment with accepting your emotions and utilizing them to inspire you. If you’re feeling lonely, rather than passively scrolling on social media and thinking you’re never going to have a relationship as amazing as your friends’ posts suggest they have, honor your sadness as a sign that you’re a social being. Let it propel you to reach out, and just as important, ease your pain in the moment. You may be surprised by how much acceptance helps, as fighting emotions by suppressing them often backfires.Step 3Release the tension in your faceOne simple way to amplify acceptance in situations where you want to feel more accepting is to bring your attention to your face. Many experts say that, along with your thoughts and approach to your emotions, your expression influences how you feel. According to something known as the facial feedback hypothesis, the faces we make impact our emotions, which is why I teach my clients who yearn to be more accepting how to go from a scowl to “half smiling.”So in moments when you want to improve your ability to accept what is rather than raging against it, try adopting a more relaxed, serene facial expression. If you are frustrated while waiting in a long line, try a half-smile, ever-so-slightly raising your lips, which automatically releases tension in your forehead and jaw to ease your resentment. Not to be confused with forcing a smile for others, the half-smile is for yourself. By subtly changing your face in a way that feels less taxing, you can begin to feel more accepting from the outside in. “When we soften our eyes, we quiet our minds,” said Dr. Brach.Step 4Act willinglyTrue acceptance also extends to your behavior. Dr. Linehan teaches that in any moment you can either choose willfulness — by refusing to tolerate something or needing to be in control — or opt for willingness — by behaving as if you’re saying yes to participating in reality. Since life is full of activities we dread (doing yet another Zoom meeting), choosing to do so with pep can feel nicer than dragging your feet.So, during your next video call, turn on your camera, close all distracting browsers and see how that compares to attending in a grudging way. As I coach my clients, the challenging and the liberating aspect of radical acceptance is being genuine by aligning your mind and behavior. But it turns out, that’s also the liberating part.Step 5Work on your U-turnsFinally, know that defaulting to fight or flight reactions is normal. It’s unrealistic to think that you’ll decide to radically accept and immediately find enduring bliss. But that’s OK — when you find yourself thinking judgmentally, tensing up or holding back from ultimately helpful actions, you can notice it and try “turning the mind” back to accepting, as Dr. Linehan teaches, without blaming yourself for the detour. Acceptance, I tell my clients, is not merely a one-time choice; you have endless opportunities. At any moment, you can choose to find more freedom.Jenny Taitz is an assistant clinical professor in psychiatry at the University of California, Los Angeles, and the author of “How to be Single and Happy: Science-Based Strategies for Keeping Your Sanity While Looking for a Soul Mate” and “End Emotional Eating.”

SharecloseShare pageCopy linkAbout sharingIndia has reported 314, 835 new coronavirus cases in the last 24 hours, the highest one day tally ever recorded. Deaths rose by 2,104 in the same time period, the worst daily toll. It brings the country’s total number of confirmed infections close to 6 million. India is in the grip of a vicious second wave and an acute oxygen shortage is raising more fears about the country’s overwhelmed health care system. Delhi’s highest court in has publicly criticised the central government for its handling of the oxygen crisis in the city.The court was hearing a petition by the owner of six private hospitals.It ordered the government to ensure safe passage of oxygen supplies from factories to hospitals across India.”This is ridiculous. We want to know what the centre is doing with regard to oxygen supply across India,” the judges said while reading out the verdict, adding that it was the responsibility of the government to “beg, borrow…steal” to ensure oxygen supplies. A number of people across the country have died while waiting for oxygen though it is not possible to know how many. Indian social media has also been filled with appeals for oxygen.Crowds are gathering outside hospitals in major cities which are filled to capacity. Health services are struggling to cope. image copyrightEuropean Pressphoto AgencyAuthorities in the western state of Maharashtra – which is the worst affected state- announced a series of additional restrictions starting from Thursday evening, as it battles a steep surge in cases. It was already under partial lockdown from 14 April. Maharashtra is India’s richest state and home to its financial hub, Mumbai. It’s also been a Covid hotspot since the start of the pandemic.It now accounts for a quarter of India’s more than 15 million Covid cases.Maharashtra has also reported more deaths from the virus than any other state – 67, 468. India has confirmed more than 180,000 deaths so far. Although deaths have been rising, the fatality rate remains relatively low. India has seen a rapid rise in case numbers over the past month, driven by lax safety protocols, and a Hindu festival attended by millions and variants of the virus, including a “double mutant” strain. It was detected in 61% of samples tested in Maharashtra, according to the National Institute of Virology. Huge election rallies – including by Prime Minister Narendra Modi – were also not halted in the state of West Bengal which has been going to polls in phases. Voters will be out on Thursday as well, for the sixth stage of voting. The government has defended the decision to continue with the polling. Critics have also pointed to the lagging vaccination drive in the country, which experts say needs to pick up quickly to contain the spread. India has so far administered more than 130 million doses, but the drive has so far been restricted to health workers, frontline staff and those above the age of 45 and anyone with comorbidities. From 1 May, people above 18 will also be eligible for the vaccine. But a supply crunch, which is already affecting the drive, could slow it down further.

Next time you make a salad, you might want to consider adding mushrooms to it. That’s because higher mushroom consumption is associated with a lower risk of cancer, according to a new Penn State study, published on March 16 in Advances in Nutrition.
The systematic review and meta-analysis examined 17 cancer studies published from 1966 to 2020. Analyzing data from more than 19,500 cancer patients, researchers explored the relationship between mushroom consumption and cancer risk.
Mushrooms are rich in vitamins, nutrients and antioxidants. The team’s findings show that these super foods may also help guard against cancer. Even though shiitake, oyster, maitake and king oyster mushrooms have higher amounts of the amino acid ergothioneine than white button, cremini and portabello mushrooms, the researchers found that people who incorporated any variety of mushrooms into their daily diets had a lower risk of cancer. According to the findings, individuals who ate 18 grams of mushrooms daily had a 45% lower risk of cancer compared to those who did not eat mushrooms.
“Mushrooms are the highest dietary source of ergothioneine, which is a unique and potent antioxidant and cellular protector,” said Djibril M. Ba, a graduate student in epidemiology at Penn State College of Medicine. “Replenishing antioxidants in the body may help protect against oxidative stress and lower the risk of cancer.”
When specific cancers were examined, the researchers noted the strongest associations for breast cancer as individuals who regularly ate mushrooms had a significantly lower risk of breast cancer. Ba explained that this could be because most of the studies did not include other forms of cancer. Moving forward, this research could be helpful in further exploring the protective effects that mushrooms have and helping to establish healthier diets that prevent cancer.
“Overall, these findings provide important evidence for the protective effects of mushrooms against cancer,” said coauthor John Richie, a Penn State Cancer Institute researcher and professor of public health sciences and pharmacology. “Future studies are needed to better pinpoint the mechanisms involved and specific cancers that may be impacted.”
Paddy Ssentongo, Joshua Muscat, Robert Beelman and Xiang Gao from Penn State also contributed to this research. The researchers declare no conflicts of interest or specific funding support.
Story Source:
Materials provided by Penn State. Original written by Tracy Cox. Note: Content may be edited for style and length.

Much of common pharmaceutical development today is the product of laborious cycles of tweaking and optimization. In each drug, a carefully concocted formula of natural and synthetic enzymes and ingredients works together to catalyze a desired reaction. But in early development, much of the process is spent determining what quantities of each enzyme to use to ensure a reaction occurs at a specific speed.
New collaborative research from Northwestern University could expedite, or even eliminate, the need for scientists to manually adjust bioproduction reaction conditions at all. Using ideas conceived by graduate students across three labs, Northwestern researchers developed technology that allows microbes to produce drugs with feedback control systems, dialing down or amping up protein concentration as needed.
Implications for this research are vast. With the knowledge that microbial feedback control systems could be used more generally to produce other drugs and products, the ability for microbes to be self-regulating means other important classes of therapeutics may be newly accessible to developers. Currently, because production pathways can be toxic to cells at certain levels, scientists have faced hurdles to engineering such microbes that leverage these pathways. But with the help of tools from the lab of Julius B. Lucks, an associate professor at the McCormick School of Engineering, this barrier may soon be nil.
“We first demonstrated our concept by making the precursor of the anti-cancer drug taxol,” said Lucks, a corresponding author on the paper. “This was a great model target to try because there’s challenges and complicated chemistry, but we hope the technology we developed is general in a sense, and there’s a whole array of products where you’d prefer to have microbial production.”
The research was published earlier this month in the journal ACS Synthetic Biology.
Synthetic biology has been a growing field over the past several decades and has entered the public sphere with the popularization of CRSPR genome editing and development of COVID-19 vaccinations with the use of engineered RNA molecules. Now in its fifth year, the Center for Synthetic Biology at Northwestern houses professors and students across majors and schools. Lucks said the center operates unlike others he’s been a part of because “it’s not top-down”; students are empowered to do awesome stuff.

In an early analysis of coronavirus vaccine safety data, researchers at the Centers for Disease Control and Prevention have found no evidence that the Pfizer-BioNTech or Moderna vaccines pose serious risks during pregnancy.The findings are preliminary and cover just the first 11 weeks of the U.S. vaccination program. But the study, which included self-reported data on more than 35,000 people who received one of the vaccines during or shortly before pregnancy, is the largest yet on the safety of the coronavirus vaccines in pregnant people.During the clinical trials of the vaccines, pregnant women were excluded. That left patients, doctors and experts unsure whether the shots were safe to administer during pregnancy.“There’s a lot of anxiety about whether it’s safe and whether it would work and what to expect as far as side effects,” said Dr. Stephanie Gaw, a maternal-fetal medicine specialist at the University of California, San Francisco.The new data, Dr. Gaw said, demonstrate that “a lot of pregnant people are getting the vaccine, there isn’t a significant increase in adverse pregnancy effects at this point, and that side effect profiles are very similar to nonpregnant people.”“I think that’s all very reassuring,” she said, “and I think it will really help providers and public health officials more strongly recommend getting the vaccine in pregnancy.”Covid-19 poses serious risks during pregnancy. Pregnant women who develop symptoms of the disease are more likely to become seriously ill, and more likely to die, than nonpregnant women with symptoms.Because of those risks, the C.D.C. has recommended that coronavirus vaccines be made available to pregnant women, though it also suggests that they consult with their doctors when making a decision about vaccination.The new study, which was published on Wednesday in The New England Journal of Medicine, is based largely on self-reported data from V-safe, the C.D.C.’s coronavirus vaccine safety monitoring system. Participants in the program use a smartphone app to complete regular surveys about their health, and any side effects they might be experiencing, after receiving a Covid-19 vaccine.The researchers analyzed the side effects reported by V-safe participants who received either the Pfizer or Moderna vaccine between Dec. 14, 2020, and Feb. 28, 2021. They focused on 35,691 participants who said that they had been pregnant when they received the vaccine or became pregnant shortly thereafter.After vaccination, pregnant participants reported the same general pattern of side effects that nonpregnant ones did, the researchers found: pain at the injection site, fatigue, headaches and muscle pain..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-rqynmc{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.9375rem;line-height:1.25rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-rqynmc{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-rqynmc strong{font-weight:600;}.css-rqynmc em{font-style:italic;}.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-16ed7iq{width:100%;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-box-pack:center;-webkit-justify-content:center;-ms-flex-pack:center;justify-content:center;padding:10px 0;background-color:white;}.css-pmm6ed{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;}.css-pmm6ed > :not(:first-child){margin-left:5px;}.css-5gimkt{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.8125rem;font-weight:700;-webkit-letter-spacing:0.03em;-moz-letter-spacing:0.03em;-ms-letter-spacing:0.03em;letter-spacing:0.03em;text-transform:uppercase;color:#333;}.css-5gimkt:after{content:’Collapse’;}.css-rdoyk0{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;-webkit-transform:rotate(180deg);-ms-transform:rotate(180deg);transform:rotate(180deg);}.css-eb027h{max-height:5000px;-webkit-transition:max-height 0.5s ease;transition:max-height 0.5s ease;}.css-6mllg9{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;position:relative;opacity:0;}.css-6mllg9:before{content:”;background-image:linear-gradient(180deg,transparent,#ffffff);background-image:-webkit-linear-gradient(270deg,rgba(255,255,255,0),#ffffff);height:80px;width:100%;position:absolute;bottom:0px;pointer-events:none;}#masthead-bar-one{display:none;}#masthead-bar-one{display:none;}.css-1pd7fgo{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;}@media (min-width:740px){.css-1pd7fgo{padding:20px;width:100%;}}.css-1pd7fgo:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-1pd7fgo{border:none;padding:20px 0 0;border-top:1px solid #121212;}.css-1pd7fgo[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-1pd7fgo[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-1pd7fgo[data-truncated] .css-5gimkt:after{content:’See more’;}.css-1pd7fgo[data-truncated] .css-6mllg9{opacity:1;}.css-1rh1sk1{margin:0 auto;overflow:hidden;}.css-1rh1sk1 strong{font-weight:700;}.css-1rh1sk1 em{font-style:italic;}.css-1rh1sk1 a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;text-underline-offset:1px;-webkit-text-decoration-thickness:1px;text-decoration-thickness:1px;-webkit-text-decoration-color:#ccd9e3;text-decoration-color:#ccd9e3;}.css-1rh1sk1 a:visited{color:#333;-webkit-text-decoration-color:#ccc;text-decoration-color:#ccc;}.css-1rh1sk1 a:hover{-webkit-text-decoration:none;text-decoration:none;}Women who were pregnant were slightly more likely to report injection site pain than women who were not, but less likely to report the other side effects. They were also slightly more likely to report nausea or vomiting after the second dose.Pregnant V-safe participants were also given an opportunity to enroll in a special registry that tracked pregnancy and infant outcomes.By the end of February, 827 of those enrolled in the pregnancy registry had completed their pregnancies, 86 percent of which resulted in a live birth. Rates of miscarriage, prematurity, low birth weight and birth defects were consistent with those reported in pregnant women before the pandemic, the researchers report.“This study is of critical importance to pregnant individuals,” Dr. Michal Elovitz, a maternal-fetal medicine specialist at the University of Pennsylvania, said in an email. “It is very reassuring that there were no reported acute events in pregnant individuals” over the course of the study, she said.But the report has several limitations and much more research is needed, experts said. Enrollment in the surveillance programs is voluntary and the data are self-reported.In addition, because the study period encompassed just the first few months of the U.S. vaccination campaign, the vast majority of those enrolled in the pregnancy registry were health care workers. And there is not yet any data on pregnancy outcomes from people who were vaccinated during the first trimester of pregnancy.“I think we can feel more confident about recommending the vaccine in pregnancy, and especially with pregnant people that are at risk of Covid,” Dr. Gaw said. “But we do need to wait for more data for complete pregnancy outcomes from vaccines early in pregnancy.”