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Most human cells are able to repair damage by dividing at wounds.
But mature nerve cells (neurons) in our brain are different. If they attempt division, they will likely die — and this is what happens during brain injury, or in conditions such as Alzheimer’s Disease (AD). Now new research led by the University of Plymouth has uncovered a pathway that has shed new light on how these divisions may be triggered.
The research, published today in Cell Reports, has focused on intracellular structures called microtubules — which are found in most animal cells, and can be damaged by a build-up of a protein called Tau in the brain during AD.
The study was conducted in fruit flies, with comparison to postmortem brain samples of AD patients.
The paper shows that when the microtubules of neural cells in fruit flies are damaged, division is triggered via activating the small signalling kinases, Tak1 and Ik2. Strikingly, activation of these molecules can also be seen in AD brains.
Why is this important?
By understanding how the damaged microtubules behave, scientists have a valuable opportunity to potentially prevent neuronal death following brain injury, or upon neurodegeneration, such as in Alzheimer’s Disease.

Can you remember the smell of flowers in your grandmother’s garden or the tune your grandpa always used to whistle? Some childhood memories are seemingly ingrained into your brain. In fact, there are critical periods in which the brain learns and saves profound cognitive routines and memories. The structure responsible for saving them is called the perineuronal net.
This extracellular structure envelops certain neurons, thereby stabilizes existing connections — the synapses — between them and prevents new ones from forming. But what if we could remove the perineuronal net and restore the adaptability of a young brain? The neuroscientist Sandra Siegert and her research group at IST Austria now published two promising techniques to do so.
In defining periods of development, the brain re-organizes connections between its neurons more freely than in its adult form. Researchers have now discovered two methods to reopen such plasticity: repeated ketamine anesthesia and non-invasive 60 hertz light flickering. The  findings may have the potential to become a therapeutic tool applicable to humans.
Taking Ketamine or Flashing Lights
It all began four years ago when the researchers at IST Austria found that microglia cells in mice become very reactive after they had anesthetized animals with the drug ketamine. Microglia are typically seen as the brain’s immune cells. However, recent studies have shown that they also interact with the neurons. The reactive microglia have the ability to eat synapses and even entire neurons, which is often seen in the late phases of Alzheimer’s disease.
“The strong response of the microglia upon ketamine anesthesia surprised us,” explains Alessandro Venturino, leading author in the study and member of the Siegert group. “But we did not see any synapses or dead neurons vanishing. So, we were puzzled, what the microglia were actually eating.” It turned out to be the perineuronal net that protects and stabilizes the connections between neurons.

The urgency to remember a dangerous experience requires the brain to make a series of potentially dangerous moves: Neurons and other brain cells snap open their DNA in numerous locations — more than previously realized, according to a new study — to provide quick access to genetic instructions for the mechanisms of memory storage.
The extent of these DNA double-strand breaks (DSBs) in multiple key brain regions is surprising and concerning, said study senior author Li-Huei Tsai, Picower Professor of Neuroscience at MIT and director of The Picower Institute for Learning and Memory, because while the breaks are routinely repaired, that process may become more flawed and fragile with age. Tsai’s lab has shown that lingering DSBs are associated with neurodegeneration and cognitive decline and that repair mechanisms can falter.
“We wanted to understand exactly how widespread and extensive this natural activity is in the brain upon memory formation because that can give us insight into how genomic instability could undermine brain health down the road,” said Tsai, who is also a professor in the Department of Brain and Cognitive Sciences and a leader of MIT’s Aging Brain Initiative. “Clearly memory formation is an urgent priority for healthy brain function but these new results showing that several types of brain cells break their DNA in so many places to quickly express genes is still striking.”
Tracking breaks
In 2015, Tsai’s lab provided the first demonstration that neuronal activity caused DSBs and that they induced rapid gene expression. But those findings, mostly made in lab preparations of neurons, did not capture the full extent of the activity in the context of memory formation in a behaving animal and did not investigate what happened in cells other than neurons.
In the new study published July 1 in PLOS ONE, lead author and former graduate student Ryan Stott and co-author and former research technician Oleg Kritsky sought to investigate the full landscape of DSB activity in learning and memory. To do so, they gave mice little electrical zaps to the feet when they entered a box, to condition a fear memory of that context. They then used several methods to assess DSBs and gene expression in the brains of the mice over the next half hour, particularly among a variety of cell types in the prefrontal cortex and hippocampus, two regions essential for the formation and storage of conditioned fear memories. They also made measurements in the brains of mice who did not experience the foot shock to establish a baseline of activity for comparison.

A research collaboration based in Kumamoto University (Japan) has shown that lysine-specific demethylase 1 (LSD1), an enzyme involved in gene expression, produces individualized metabolism depending on the type of acute myeloid leukemia cells. Cancer cells are known to have a unique ability to metabolize substances differently from normal cells, and this ability is considered to be a promising therapeutic target. The new research findings may contribute to the safe and effective use of LSD1 inhibitors as potential anticancer agents, and to the development of highly specific treatments for various leukemia types.
Acute myelogenous leukemia (AML) occurs when hematopoietic stem cells become tumors rather than differentiating into white or red blood cells. The various types of AML develop according to which stage of differentiation they become cancerous. Those that develop when differentiating into red blood cells are classified as erythroblastic leukemia (EL). Although pathology-specific targeted molecular therapies have been developed for some forms of AML, and have improved treatment outcomes, many forms of the disease, including EL, have high mortality rates due to the lack of individualized therapies. Thus, therapies based on disease type and molecular pathology are desired.
Recent studies have revealed that the inherent metabolic capacity of cancer cells contributes significantly to tumor formation, metastasis and resistance to treatment. Therefore, therapeutic strategies that target nutrient transport and metabolic pathways active in cancer cells have been devised, but it has also been pointed out that metabolic characteristics vary depending on the type and progression of cancer. The metabolic characteristics of AML have not been fully investigated and, in particular, the differences that depend on the disease type and their mechanisms have not been clarified.
Gene expression is regulated by the epigenome. Chemical modifications, such as DNA methylation and methylation of the histone proteins around which the DNA wraps, act as markers to shape the epigenome. There are many differences in the epigenome between cancer cells and normal cells, which in turn generate the differences in gene expression patterns.
Previously, the Kumamoto University research collaboration showed that LSD1, a demethylase that removes methyl groups from methylated histones, is involved in the regulation of energy metabolism in various cell types (Nature Communications 2012, Cancer Research 2015, Nucleic Acids Research 2018). Therefore, they decided to test the possibility that LSD1 is involved in the metabolic regulation of AML cells. Although it has been shown that LSD1 inhibitors may be effective in the treatment of AML, not much is known about the differences in efficacy depending on the disease type. Thus, in this study, the researchers decided to focus on the metabolic differences depending on AML disease type and the role of LSD1.
They first analyzed the gene expression database of AML patients and AML-derived cultured cell lines, and found that both LSD1 and glycolytic genes are highly expressed in EL among AML patients. Then, when they tested the inhibition of LSD1 function using EL cell lines, they found that LSD1 promoted glucose uptake into cells and the glycolytic system. An integrated omics analysis revealed that heme synthesis, a characteristic metabolic pathway of normal red blood cells, is also activated by LSD1. The mechanism was found to be that LSD1 activates glycolytic and heme synthesis gene expression by preventing the degradation of GATA1 protein, an erythroid transcription factor.
Furthermore, under LSD1 functional inhibition, the expression of CEBP/?, a transcription factor of the granulocyte-monocyte lineage of leukocytes, was dramatically up-regulated, inhibiting metabolic regulation by GATA1. These results indicate that LSD1 regulates the balance of transcription factors involved in hematopoietic cell lineage, thereby generating the metabolic phenotype characteristic of EL. Additionally, analysis of clinical data covering various forms of AML showed that the expression of LSD1, GATA1, and glycolytic and heme synthesis genes showed a significant positive correlation. This suggests that regulation of cellular lineage by LSD1 may generate the diversity of metabolic types of AML.
“Based on our research, a combination of LSD1 inhibitors, metabolic target drugs, and conventional therapies may be highly effective in treating patients with EL who express high levels of LSD1,” said Associate Professor Shinjiro Hino, who led the study. “It may also be an important clue for selecting patients who may benefit from LSD1 inhibitors in clinical trials.”
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While this isn’t the fountain of youth, scientists may have improved healing in our joints — even in areas that become weaker as we grow older. The meniscus is a durable, yet flexible tissue found in joints like our wrist and knees that helps them absorb shock during movement. Occasionally tears can occur in the meniscus due an awkward movement or structural weakness from old age. When we are young, there is plenty of blood flowing to this area allowing for quick healing, but as we get older, the meniscus receives less and less blood — with the inner most area becoming avascular. Tears in this area do not heal normally, often requiring surgery. Surgeons can draw fibrin, a protein involved in blood clotting, from peripheral blood (PB) or bone marrow aspirate (BMA), and implant a fibrin blood clot into the injured area to help with healing. However, little was known about the differential effectiveness of fibrin from the PB and BMA areas.
Scientists from the Graduate School of Medicine, Osaka City University, have evaluated the clinical results of a meniscal repair using BMA-derived fibrin clots and found that rates of clinical and anatomic failure, and re-tear were 10%, 6.7%, and 3.3% respectively — well below their PB counterpart. The results were published in Arthroscopy: The Journal of Arthroscopic & Related Surgery.
“There are various methods of meniscal repair that try to prevent re-tear” states Lecturer Yusuke Hashimoto, “but the re-tear rate still exceeds 20%.” To see if BMA can bring this number down, the research team had to first understand the levels of growth factors involved in tissue repair found in BMA and then see the effects BMA-derived fibrin clots had when sutured into tissue during meniscal surgery.
Collecting bone marrow fluid and peripheral blood from 5 patients undergoing meniscal surgery, the team prepared fibrin clots for cytokine measurement. “Cytokine are proteins that stimulate the reparative process” states Professor Hiroaki Nakamura, “and through them we are able to gauge the levels of growth factors like bFGF, TGF?, and SDF-1.” Cell count evaluations found that BMA was more abundant in these growth factors than PB.
Next, as a 2-year follow-up post-surgery, they examined pre- and post-operative clinical results and the healing rate of meniscus in 30 cases of meniscal surgery that was combined with a BMA fibrin clot. MRI results showed significant improvements in the condition of the meniscus compared to the preoperative results and x-ray evaluation showed no significant progression of knee deformity.
“PB clots have been widely reported as a material to enhance meniscal healing,” states Hashimoto. However, with a reported 20% of meniscal repairs having reoperation at long-term follow up, “our method of introducing BMA-derived fibrin clots into the injured area may become a treatment for meniscus injuries that until now have not been curable.”
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Three mutations in the Epsilon coronavirus spike protein dampen the neutralizing potency of antibodies induced by current vaccines or past COVID infections.
The mutations give this coronavirus variant of concern a means to totally evade specific monoclonal antibodies used in clinics and reduce the effectiveness of antibodies from the plasma of vaccinated people.
To better understand the exact immune escape strategies at work here, the scientists visualized this variant’s infection machinery to see what is different from the original configuration of the pandemic coronavirus, and what the implications of these changes are.
The international project was led by David Veesler’s lab in the Department of Biochemistry at the University of Washington in Seattle and by Luca Piccoli and Davide Corti of Vir Biotechnology.
For several years, the Veesler lab and its collaborators have been exploring the molecular conformation and infection mechanics of SARS-like coronaviruses. They also examine how antibodies attempt to block infection mechanisms, and how variants come up with new dodges.
Their latest data shows that the Epsilon variant “relies on an indirect and unusual neutralization-escape strategy,” according to the researchers.

Researchers at Karolinska Institutet in Sweden publish new findings in the journal Cancer Discovery showing how pharmacological activation of the protein p53 boosts the immune response against tumours. The results can be of significance to the development of new combination therapies that will give more cancer patients access to immunotherapy.
Given its ability to react to damage to cellular DNA and the key part it is thought to play in preventing tumour growth, the protein p53 has been dubbed the “guardian of the genome.” Half of all tumours have mutations in the gene that codes for the protein, and in many other tumours, p53 is disabled by another protein, MDM2.
It has long been known that p53 is able to silence certain sequences in our genome called endogenous retroviruses (i.e. DNA elements evolutionarily inherited from viruses), thus preventing genome instability. The researchers now show that the protein can also activate these sequences in cancer cells, leading to anti-tumour immune response.
“This was an astonishing discovery. When we blocked the suppressor MDM2, p53 activated endogenous retroviruses which induced antiviral response and boosted the production of immune-activating interferons,” says lead investigator Galina Selivanova, Professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.
The results were obtained when the researchers blocked MDM2 in mouse models using a substance coded as ALRN-6924 from the US company Aileron Therapeutics. The increase of interferon response was also seen in tumour samples from two patients taking part in the company’s clinical trials of ALRN-6924.
“This shows that there are synergies that should be exploited between substances that block MDM2 and modern immunotherapies,” Professor Selivanova continues. “A combination of these can be particularly important for patients who don’t respond to immunotherapy.”
Immunotherapy, or immuno-oncology, is described as a revolution in modern cancer treatment in the way it triggers the body’s immune system to fight cancer cells. However, it does not work with all patients, and the presence of interferons could be a biomarker for whether or not immunotherapy will prove efficacious.
“If we can increase the level of interferons, we can therefore increase the chances that the immunotherapy will succeed.”
Professor Selivanova is a pioneer in research on how mutated p53 can be re-activated using special molecules, one of which, APR-246, is undergoing clinical studies under the name Eprenetapopt at Aprea Therapeutics, a company that she co-founded.
“We now want to examine if Eprenetapopt produces the same interferon boost and can have the same potential to increase access to immunotherapy for patients with severe forms of cancer,” she says.
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SharecloseShare pageCopy linkAbout sharingDr Seuj Kumar Senapati vividly remembers the afternoon in early June he thought he would die. It was his first job and his second day at work at a Covid care centre in Hojai district, in India’s north-eastern state of Assam. He was asked to check on a patient who had been admitted that morning. When he did, he found him unresponsive. The patient’s family was furious when he told them the man had died. In moments, Dr Senapati recalled, all hell broke loose. He said they started hurling chairs around the room, breaking windows and abusing staff.Dr Senapati ran for cover, but soon more people joined the family and they found him. A horrific video of the attack shows a group of mostly men kicking Dr Senapati and hitting him on the head with a bedpan – then they drag him outside and continue to beat him. Dr Senapati, bloodied and shirtless, can be heard howling in pain and fear. “I thought I wouldn’t survive,” he said. ‘There were no doctors. They had run away’Women in rural India hesitant to take Covid vaccinesSince the start of the pandemic in India last year, several doctors have been attacked by families of Covid patients. The recurring complaint: their loved ones weren’t treated properly or weren’t allotted a bed on time. Doctors have protested and gone on strike demanding stricter laws, as well as more staffing and better infrastructure to relieve the pressure on them. Hospitals too are ill-prepared. When Dr Senapati was being attacked, no-one came to his rescue because the remaining staff were also being beaten up or hiding. A lone guard was helpless against the mob. “My clothes were torn, my gold chain was snatched and my mobile phone and spectacles were smashed. But after about twenty minutes, I managed to escape,” Dr Senapati said.He drove straight to the local police station and registered a complaint. The video of the attack, which has since been shared on social media, caused a furore. The state government promised swift action and 36 people, including three minors, have been charged for the assault. image copyrightGetty ImagesWhile attacks on healthcare workers have been spotlighted during Covid, they occurred at alarming regularity before the pandemic too. Yet most incidents don’t lead to police complaints or investigations. When they do, the accused are often released on bail quickly and the case is settled outside court. Earlier this year, the family of a Covid patient who died in India’s devastating second wave damaged property and abused staff at Apollo Hospital in the capital, Delhi. Despite being a prominent private hospital, it did not press charges. In fact, hospital administrations rarely get involved in such cases, leaving staff more vulnerable. Doctors say one problem is that there is no specific law protecting them. “We have found that existing laws are not effective and that is why they are not a deterrent. A strong law is urgently needed so people understand that there will be consequences for beating doctors,” said Dr Jayesh Lele, secretary general of the Indian Medical Association (IMA). With more than 330,000 doctors as members, the IMA has been campaigning hard for a stringent law to deter attacks against healthcare professionals. ‘Think about ICU workers before you party”We try to save a patient until the last breath’But can a law fix the problem? “Such violence is not premeditated, but more an outcome of an emotional trigger caused by death. Hence, laws don’t work as a deterrent,” said Shreya Shrivastava, who has been tracking violence against doctors. Ms Shrivastava is part of a research team at the Vidhi Centre for Legal Policy that studied newspaper reports of 56 attacks between January 2018 and September 2019 to understand what had caused them and how they can be curbed. She said the government introduced a jail term of up to seven years as punishment for attacks on health workers treating Covid patients. But that hasn’t helped. image copyrightGetty ImagesDr Vikas Reddy, a doctor at Gandhi Hospital in the southern city of Hyderabad, was attacked with iron and plastic chairs in June last year by relatives of a man who had died due to Covid. He filed a police complaint, but no-one has been arrested yet.”It was difficult to go back to work,” Dr Reddy said. “I was in the same acute medical care ward, seeing critical patients. I got flashes of the attack in my mind.”He said he spent a lot of time thinking about what happened. “I was in a dilemma,” he said. He wanted to know how to explain the diagnosis or break tragic news better to prevent another attack. “I realised that we have to spend time with patients and their families to explain the things we can and can’t do. And if they disagree, they need to take the patient to another hospital. But we don’t have that kind of time. I see 20-30 patients in a day.”India has one of the worst doctor-patient ratios globally. In 2018, there were 90 physicians per 100,000 people, according to World Bank estimates. That’s far lower than China (200), the US (260) or Russia (400).And the pandemic has stretched an already thin workforce.Ms Shrivastava’s research revealed that attacks on healthcare workers usually happened when patients were in emergency wards or ICUs, shifted from one hospital to another or when they died. And all of this has become more frequent during the pandemic.”Being inside a Covid ward is like being at war,” said Dr Lele.Then there is the issue of trust. A largely unregulated and an expensive private sector provides two-thirds of all healthcare services in India. Ms Shrivastava said people have been dying of Covid despite costly care, weakening trust in the system. And media reports of medical negligence, which tend to outnumber stories of doctors’ struggles, make people more suspicious. “The best we can do is give our best to the patient,” Dr Reddy said. “We can’t expect every patient [or family] to be nice [to us], just that they respect us as professionals and respect that we chose this profession to save lives.”You might be interested in:

The company faces declining sales and thousands of lawsuits claiming it knowingly sold its trendy vaping products to minors. Soon the F.D.A. will decide whether it can keep selling them at all.Sales have plunged by $500 million. The work force has been cut by three-quarters. Operations in 14 countries have been abandoned. Many state and local lobbying campaigns have been shut down.Juul Labs, the once high-flying e-cigarette company that became a public health villain to many people over its role in the teenage vaping surge, has been operating as a shadow of its former self, spending the pandemic largely out of the public eye in what it calls ‘reset’ mode. Now its very survival is at stake as it mounts an all-out campaign to persuade the Food and Drug Administration to allow it to continue to sell its products in the United States.The agency is trying to meet a Sept. 9 deadline to decide whether Juul’s devices and nicotine pods have enough public health benefit as a safer alternative for smokers to stay on the market, despite their popularity with young people who never smoked but became addicted to nicotine after using Juul products.Major health organizations, including the American Heart Association, American Lung Association, American Academy of Pediatrics and the American Cancer Society’s Cancer Action Network, have asked the agency to reject Juul’s application.“The stakes are high,” said Eric Lindblom, a senior scholar at the O’Neill Institute for National and Global Health Law at Georgetown University, and a former F.D.A. adviser on tobacco. “If the F.D.A. blows it on this one, they will face public health lawsuits.”Juul is sparing no expense to push back. Last week, the company agreed to pay $40 million to settle just one lawsuit (with North Carolina) out of thousands lodged against it, avoiding a looming jury trial. The company had urgently sought the deal to avoid courtroom testimony from parents and teenagers while the F.D.A. is reviewing its vaping products.Juul has not made its 125,000-page application to the agency public. But it paid $51,000 to have the entire May/June issue of the American Journal of Health Behavior devoted to publishing 11 studies funded by the company offering evidence that Juul products help smokers quit. (A spokesman for Juul said the editors had rejected one of the company’s submissions.) That fee included an extra $6,500 to have the subscription journal open access to everyone. Three editorial board members of the journal resigned over the arrangement. And Juul’s federal lobbying has remained robust. It spent $3.9 million on federal lobbying in 2020, according to the Center for Responsive Politics, which tracks political spending. Altria, the big tobacco company that owns a chunk of Juul, spent nearly $11 million.Juul’s share of the vaping market has shrunk significantly, to 42 percent last year, according to analysts, from a high of 75 percent in 2018. But some public health experts say they are concerned that F.D.A. approval will lay the groundwork for the company to rise and expand its reach again.Juul has long denied that it knowingly sold its products to teenagers, and it has been pledging publicly for the last few years to do all it can to keep them away from minors. In its settlement with North Carolina, the company did not admit intentionally targeting youths.In an interview, Joe Murillo, Juul’s chief regulatory officer, said, “We have a bigger opportunity to convert smokers than ever before, but we will get that opportunity if and only if we continue to combat underage usage and continue to act like the highly regulated company that we are.”The company is seeking approval for its iconic vaping device, once dubbed the iPhone of e-cigarettes, with tobacco- and menthol-flavored pods in two nicotine strengths: five percent, which is equivalent to the nicotine in an average pack of cigarettes, and three percent.The decision is one of a number of critical issues the F.D.A. has been wrestling with — including the agency’s recent approval of a controversial Alzheimer’s drug and decisions on thousands of vaping products made by companies other than Juul — without a permanent commissioner in place. President Biden has yet to announce a nominee.Recently, a House panel questioned the acting commissioner, Dr. Janet Woodcock, about the agency’s plans for Juul. She said the agency would base its decision on sound science, and that she couldn’t prejudge the application, which is still under review.The decision will be based in large part on the answer to two questions: Will more smokers use Juul products as an off-ramp from traditional cigarettes than nonsmokers will use it as an on-ramp to nicotine? And can Juul really keep the products away from kids?K.C. Crosthwaite, Juul’s CEO, a former tobacco executive, testifies on Capitol Hill in February 2020.Ting Shen for The New York TimesThe bulk of Juul’s published research in the journal edition it bought tracks the 12-month experience of 55,000 adults who purchased a Juul starter kit. The researchers, all of whom were paid by Juul, concluded that 58 percent of the 17,000 smokers who stayed in the study had stopped smoking at 12 months. Twenty-two percent remained dual users of both traditional and e-cigarettes but cut their smoking by at least half. Elbert D. Glover, who was editor and publisher of the journal, but retired soon after the issue came out, said the journal followed its standard protocol for, scientists who vet studies before publication.The steady decline in Americans who smoke has been a public health success story. The rate has dropped from 42 percent in 1965 to 14 percent in 2019. Yet smoking remains the leading cause of preventable death, with some 480,000 people dying from smoking-related diseases each year, according to the Centers for Disease Control and Prevention. E-cigarettes, which emerged in the early 2000s, were designed to give smokers the nicotine fix they craved without the carcinogens that come from burning cigarettes. But until Juul launched in 2015, no e-cigarette had caught on widely with the public.Juul’s sleek design, and its novel use of nicotine salts in its pods created a high-nicotine, low- irritant experience in mango, mint and other flavors, that quickly became a fad, especially among high school and middle school students. Public health officials worried that rather than helping adults quit smoking, Juul was hooking a new generation on nicotine, with potentially harmful heath effects on their developing brains and posing other health risks.Juul’s rapid growth stayed under the F.D.A.’s radar until 2018, when the agency declared a youth vaping epidemic.“The F.D.A. left in place a wide open, Wild West marketplace around these vaping products and unfortunately Juul and others dove in and exploited it,” said Clifford E. Douglas, director of the University of Michigan Tobacco Research Network. “What took place then screwed up a genuine extraordinary public health opportunity for harm reduction. It’s our obligation to come back to that to serve the public health.”Mr. Douglas believes that Juul is marketing its vaping products more responsibly now, and that they could play a role in reducing harm to cigarette smokers.Mr. Lindblom, the former F.D.A. tobacco adviser, has been highly critical of Juul, but believes the F.D.A. cannot take past bad behavior into account.“The F.D.A. has to evaluate this in a forward-looking way and can’t really punish Juul, but it can certainly take into consideration how popular Juul is among youth,” he said. Many of Juul’s critics do not believe the company deserves another chance. They are wary of the company’s ‘reset,’ announced in September 2019 when K.C. Crosthwaite, a top executive of Altria, maker of Marlboro cigarettes, became Juul’s chief executive.The sleek design of Juul’s devices made them attractive for teenaged who never smoked as well as for adults trying to quit traditional cigarettes.Joshua Bright for The New York TimesMr. Crosthwaite pulled the plug on some of Juul’s controversial state and city lobbying campaigns. He closed shop in Juul’s foreign markets across the world, except for Britain and Canada, although Juul is still sold through distributors in Ukraine, Russia, Italy and the Philippines. Under public pressure, he took mint- flavored pods, which accounted for 70 percent of sales, off the market. And he suspended all U.S. advertising.“We must put earning trust at the center of everything we do,” he wrote in an email to company staff last summer.Critics contend that most of these changes were made at gunpoint — undertaken after the F.D.A. threatened to shut down the business if teenagers continued to have access to Juul. To these public health advocates, Altria’s purchase of a $12.8 billion stake in Juul in December 2018 makes them even more distrustful.“The Marlboro man road into Juul and now wants us to trust them,” said Matthew L. Myers, president of the Campaign for Tobacco-Free Kids. The Federal Trade Commission is now trying to unravel the Altria-Juul deal, alleging that the two companies entered into a series of agreements that eliminated competition in violation of antitrust laws.The commission contends that Altria and Juul started as competitors in the e-cigarette markets, but that as Juul became more popular, Altria dealt with its competitive threat by discontinuing its Mark Ten e-cigarette in exchange for a share of Juul’s profits. Both companies have denied the charges. Even if the F.D.A. approved Juul products, perhaps with restrictions, the company would face considerable business hurdles.When Juul was forced to discontinue its fruity flavor pods, new competitors, sometimes nicknamed Juulalikes, flooded the vacuum with cheap, disposable e-cigarettes in flavors like Cherry Frost and Dinner Lady Lemon Tart. Altria now estimates Juul’s value at under $5 billion, a fraction of its $38 billion valuation when Altria bought 35 percent of the business in the 2018 deal.New York Attorney General Letitia James displays Juul ads that critics believe were aimed at young people, as she announces a lawsuit against the company in 2019.Spencer Platt/Getty ImagesIf Juul survives, the company will likely spend the next few years trying to settle thousands of lawsuits. Fourteen states and the District of Columbia, have sued Juul, seeking money to pay for combating the youth vaping crisis. . A criminal investigation of the company by the Justice Department is still underway.There is also multi-district litigation in a federal court in California, which has combined nearly 2,000 cases under the purview of one judge, similar to the treatment of opioid cases.Whether there would be any company left to collect from if plaintiffs prevail is up the F.D.A.

Face masks will no longer be legally required at the final stage of England’s Covid lockdown roadmap, Boris Johnson has confirmed.But in which situations will the prime minister and his advisers, Prof Chris Whitty and Sir Patrick Vallance, continue to use face coverings?