Researchers identify brain ion channel as new approach to treating depression

Researchers from the Icahn School of Medicine at Mount Sinai have identified a drug that works against depression by a completely different mechanism than existing treatments.
Their study showed that ezogabine (also known as retigabine), a drug that opens KCNQ2/3 type of potassium channels in the brain, is associated with significant improvements in depressive symptoms and anhedonia in patients with depression. Anhedonia is the reduced ability to experience pleasure or lack of reactivity to pleasurable stimuli; it is a core symptom of depression and associated with worse outcomes, poor response to antidepressant medication, and increased risk of suicide.
Ezogabine was approved by the U.S. Food and Drug Administration in 2011 as an anticonvulsant for epilepsy treatment but had not been previously studied in depression. The research results, published March 3 in the American Journal of Psychiatry, provide initial evidence in humans for the KCNQ2/3 channel as a new target for novel drug discovery for depression and anhedonia.
“Our study is the first randomized, placebo-controlled trial to show that a drug affecting this type of ion channel in the brain can improve depression and anhedonia in patients. Targeting this channel represents a completely different mechanism of action than any currently available antidepressant treatment,” says James Murrough, MD, PhD, Associate Professor of Psychiatry, and Neuroscience, Director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, and senior author of the paper.
The new drug target, the KCNQ2/3 channel, is a member of a large family of ion channels referred to as the KCNQ (or Kv7) family that act as important controllers of brain cell excitability and function in the central nervous system. These channels affect brain cell function by controlling the flow of the electrical charge across the cell membrane in the form of potassium (K+) ions. Researchers at Mount Sinai, including study co-author Ming-Hu Han, PhD, Professor of Pharmacological Sciences, and Neuroscience, had previously conducted a series of studies in mice showing that changes in the KCNQ2/3 potassium channel play an important role in determining if the animals show depression and anhedonic-like behavior following chronic stress in an experimental model of depression. In particular, mice that appear to be resistant to developing depression in the face of stress show an increase in KCNQ2/3 channels in the brain.
“We viewed enhanced functioning of the KCNQ channel as a potential molecular mechanism of resilience to stress and depression,” said Dr. Han, who also discovered that if he gave a drug that could increase the activity of this channel, such as ezogabine, to mice that had become depressed in the stress model, the mice no longer showed the depression and anhedonic behaviors; in other words, the drug acted as an antidepressant.
The current study was a two-site, double-blind, randomized, placebo-controlled proof of concept clinical trial designed as a preliminary test of the hypothesis that increasing KCNQ2/3 channel activity in the brain is a viable new approach for the treatment of depression. Forty-five adult patients diagnosed with a depressive disorder were assigned to a five-week treatment period with daily dosing of either ezogabine or matching placebo. All participants underwent clinical evaluations and functional magnetic resonance imaging (fMRI) during a reward task at baseline and at the end of the treatment period. Compared to patients treated with placebo, those treated with ezogabine showed a significant and large reduction in several key measures of depression severity, anhedonia, and overall illness severity. For example, significant improvements following treatment with ezogabine compared to placebo was observed using the Montgomery-Asberg Depression Rating Scale (MADRS), the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), the Snaith-Hamilton Pleasure Scale (SHAPS), and the Temporal Experience of Pleasure Scale (TEPS)-Anticipatory Subscale. The ezogabine group showed also a trend towards an increase in response to reward anticipation in the brain compared to placebo although this effect did not reach statistical significance.
“The fundamental insight by Dr. Han’s group that a drug that essentially mimicked a mechanism of stress resilience in the brain could represent a whole new approach to the treatment of depression was very exciting to us,” said Dr. Murrough.
In collaboration with Dr. Han, Dr. Murrough carried out a series of studies in patients with depression to begin to test if the observations in mice could be translated to humans. An initial open-label (no placebo) study in patients with depression led by Dr. Murrough provided initial evidence that ezogabine could improve symptoms of depression and anhedonia in a manner that was associated with changes in brain function.
“I think it’s fair to say that most of us on the study team were quite surprised at the large size of the beneficial effect of ezogabine on clinical symptoms across multiple measures related to depression. We are greatly encouraged by these findings and the hope they offer for the prospect of developing novel, effective treatments for depression and related disorders. New treatments are urgently needed given that more than one-third of people suffering from depression are inadequately treated with currently approved therapeutics.”
This research was supported by the National Institute of Mental Health. Additional funding was provided by the Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai and the Ehrenkranz Laboratory for Human Resilience, a component of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai.
Study authors James Murrough, MD, PhD and Ming-Hu-Han, PhD, are named inventors on a pending patent application for the use of ezogabine and other KCNQ channel openers to treat depression and related disorders.

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How to Get a Peloton-Style Workout Without Splurging

#masthead-section-label, #masthead-bar-one { display: none }At HomeWatch: ‘WandaVision’Travel: More SustainablyFreeze: Homemade TreatsCheck Out: Podcasters’ Favorite PodcastsAdvertisementContinue reading the main storySupported byContinue reading the main storyTech FixHow to Get a Peloton-Style Workout Without SplurgingDon’t want to pay $1,900 for a Peloton bike, plus a subscription fee for classes? Here are ways to reduce the cost of using tech to exercise at home.Lisa Whitney of Reno, Nev., has created her version of a do-it-yourself Peloton bike. Credit…Max Whittaker for The New York TimesMarch 3, 2021, 5:00 a.m. ETLisa Whitney, a dietitian in Reno, Nev., came across the deal of a lifetime about two years ago. A fitness studio was going out of business and selling its equipment. She scored an indoor exercise bike for $100.Ms. Whitney soon made some additions to the bike. She propped her iPad on the handlebars. Then she experimented with online cycling classes streamed on YouTube and on the app for Peloton, a maker of internet-connected exercise devices that offers interactive fitness classes.Ms. Whitney had no desire to upgrade to one of Peloton’s $1,900-plus luxury exercise bikes, which include a tablet to stream classes and sensors that track your speed and heart rate. So she further modified her bike to become a do-it-yourself Peloton, buying sensors and indoor cycling shoes.The grand total: about $300, plus a $13 monthly subscription to Peloton’s app. Not cheap, but a significant discount to what she might have paid.“I’m happy with my setup,” Ms. Whitney, 42, said. “I really don’t think upgrading would do much.”The pandemic, which has forced many gyms to shut down, has driven hordes of people to splurge on luxury items like Peloton’s bikes and treadmills so they can work out at home. Capitalizing on this trend, Apple last year released Apple Fitness Plus, an instructional fitness app that is exclusively offered to people who own an Apple Watch, which requires an iPhone to work.But all of that can be expensive. The minimum prices of an Apple Watch and iPhone add up to $600, and Apple Fitness Plus costs $10 a month. Then to stream classes on a big-screen TV instead of a phone while you exercise, you need a streaming device such as an Apple TV, which costs about $150. The full Peloton experience is even pricier. With the economy in a funk, many of us are trying to tighten our spending while maintaining good health. So I experimented with how to minimize the costs of doing video-instructed workouts at home, talked to tinkerers and assessed the pros and cons.Here’s what I learned.To measure her energy output, Ms. Whitney added a sensor that tracks the bike’s rotations per minute.Credit…Max Whittaker for The New York TimesShe also straps a heart rate monitor to her arm as part of her routine.Credit…Max Whittaker for The New York TimesThe Pros and Cons of FreeTo start my experiment for working out at home on the cheap, the first question I tackled was whether to subscribe to a fitness app or stream classes from YouTube for free. Both largely provide videos of instructors guiding you through workouts.So I bought an $8 yoga mat and a $70 pair of adjustable dumbbells and turned on my TV, which includes the YouTube app. I then subscribed to three of the most popular YouTube channels that have free content for exercising at home: Yoga With Adriene, Fitness Blender and Holly Dolke.One immediate downside was almost too much content — often hundreds of videos per YouTuber — making it difficult to pick a workout. Even when I finally chose a video, I learned I had to brace myself for some quality issues.In the Yoga With Adriene channel, for instance, I selected the video “Yoga for When You Feel Dead Inside,” which felt appropriate for the time we are living in. The video looked good, but at times the instructor’s voice sounded muffled.Production problems were more visible in the Holly Dolke channel, which has a collection of intense workouts that you can do without any equipment. When I tried the video “Muffin Top Melter,” an instructor in the background demonstrated how to do a more challenging version of each exercise, but the other instructor, in the foreground, constantly blocked her.Then there were the ads. As I lifted weights while following a 10-minute fat-burning workout from Fitness Blender, YouTube interrupted the video to play an ad for Dawn soap. That left me holding a dumbbell above the back of my neck while I waited for the ad to end.Those issues aside, I was able to do all of the exercises demonstrated by these YouTubers, and they left me winded and sweaty. For the cost of free, I can’t complain much. Most important, Yoga With Adriene succeeded in making me feel less dead inside.What You Get When You PayTo compare the free YouTube exercise videos with the paid experience, I subscribed to Peloton and Apple Fitness Plus on my Apple TV set-top box. I did workouts using both products for the last two months.Peloton and Apple Fitness Plus addressed many of the problems plaguing the free exercise content.For one, workouts were organized into categories by the type of workout, including yoga, strength training and core, and then by the difficulty or duration of the workout. It took little time to choose a workout.Peloton’s app organizes workouts by category, difficulty and duration.Credit…Brian X. ChenIn both Peloton and Apple Fitness Plus, video and audio quality were very clear, and the workouts were shot at various angles to get a good look at what the instructors were doing. The bonus of Fitness Plus was that my heart rate and calories burned were displayed on both my Apple Watch and the TV screen.In short, paying those subscriptions provided convenience and polish, which led to a more pleasant workout. I concluded that Peloton’s videos were worth paying $13 a month. And $10 a month is reasonable for Apple Fitness Plus, but only if you already have an Apple Watch and iPhone.Apple Fitness Plus on an iPhone and Apple Watch.Credit…AppleMaking a D.I.Y. PelotonSo what about exercise equipment like spin bikes? If you want the tech frills of a Peloton but don’t want to spend on the equipment, there were two main approaches.To go the cheapest route, you can make use of a bicycle you already have. Here’s where home tinkerers can be especially crafty and resourceful.Take Omar Sultan, a manager at the networking company Cisco. He modified his road bike with a few add-ons: a bike trainer, which secured the rear wheel and bike frame and costs roughly $100; a $40 Wahoo cadence sensor that tracked his energy output and speed and transmitted the data to a smartphone; and a heart rate monitor that strapped around his chest, such as the $90 Polar H10. Then he used a streaming device to follow Peloton classes on his TV.“The D.I.Y. setup is 80 percent of the way there” to a Peloton, Mr. Sultan said.The more expensive option was to buy an indoor exercise bike and use a tablet or phone to stream cycling classes via YouTube or the Peloton app, as Ms. Whitney did. The $700 IC7.9, for example, includes a cadence sensor and a holder for your tablet. You could then buy a heart rate monitor and a pair of $100 indoor cycling shoes that clip into the pedals.But if you use your own bicycle or a modified spin bike and try Peloton’s app, you won’t be able to participate in the app’s so-called leader board, which shows a graphic of your progress compared with other Peloton users online.With a D.I.Y. bike, it can also be difficult to figure out how to shift gears to simulate when the instructor is telling you to turn up the resistance — like when you are pretending to ride up a hill.Nicole Odya, a nurse practitioner in Chicago who modified a high-end indoor bike, the Keiser M3i, said there were major upsides to the D.I.Y. route. Using her own iPad, she has the flexibility to choose whatever fitness apps she wants to use, such as Zwift and mPaceLine. It also gave her the freedom to customize her bike, so she swapped out the stock pedals for better ones.“I didn’t want to be locked into their platform,” she said of Peloton.AdvertisementContinue reading the main story

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How Exercise Enhances Aging Brains

AdvertisementContinue reading the main storySupported byContinue reading the main storyPhys EdHow Exercise Enhances Aging BrainsSedentary, older adults who took aerobic dance classes twice a week showed improvements in brain areas critical for memory and thinking.Volunteers who participated in pre-pandemic dance classes in Newark, N.J., showed improvements in memory centers in the brain.Credit…Rutgers UniversityMarch 3, 2021, 5:00 a.m. ETExercise can change how crucial portions of our brain communicate as we age, improving aspects of thinking and remembering, according to a fascinating new study of aging brains and aerobic workouts. The study, which involved older African-Americans, finds that unconnected portions of the brain’s memory center start interacting in complex and healthier new ways after regular exercise, sharpening memory function.The findings expand our understanding of how moving molds thinking and also underscore the importance of staying active, whatever our age.The idea that physical activity improves brain health is well established by now. Experiments involving animals and people show exercise increases neurons in the hippocampus, which is essential for memory creation and storage, while also improving thinking skills. In older people, regular physical activity helps slow the usual loss of brain volume, which may help to prevent age-related memory loss and possibly lower the risk of dementia.There have been hints, too, that exercise can alter how far-flung parts of the brain talk among themselves. In a 2016 M.R.I. study, for instance, researchers found that disparate parts of the brain light up at the same time among collegiate runners but less so among sedentary students. This paired brain activity is believed to be a form of communication, allowing parts of the brain to work together and improve thinking skills, despite not sharing a physical connection. In the runners, the synchronized portions related to attention, decision making and working memory, suggesting that running and fitness might have contributed to keener minds.But those students were young and healthy, facing scant imminent threat of memory loss. Little was known yet about whether and how exercise might alter the communications systems of creakier, older brains and what effects, if any, the rewiring would have on thinking.So, for the new study, which was published in January in Neurobiology of Learning and Memory, Mark Gluck, a professor of neuroscience at Rutgers University in Newark, N.J., and his colleagues decided to see what happened inside the brains and minds of much older people if they began to work out.In particular, he wondered about their medial temporal lobes. This portion of the brain contains the hippocampus and is the core of our memory center. Unfortunately, its inner workings often begin to sputter with age, leading to declines in thinking and memory. But Dr. Gluck suspected that exercise might alter that trajectory.Helpfully, as the director of the Aging & Brain Health Alliance at Rutgers, he already was leading an ongoing exercise experiment. Working with local churches and community centers, he and his collaborators previously had recruited sedentary, older African-American men and women from the Newark area. The volunteers, most of them in their 60s, visited Dr. Gluck’s lab for checks of their health and fitness, along with cognitive testing. A few also agreed to have their brain activity scanned.Some then started working out, while others opted to be a sedentary control group. All shared similar fitness and memory function at the start. The exercise group attended hourlong aerobic dance classes twice a week at a church or community center for 20 weeks.Now, Dr. Gluck and his research associate Neha Sinha, along with other colleagues, invited 34 of those volunteers who had completed an earlier brain scan to return for another. Seventeen of them had been exercising in the meantime; the rest had not. The groups also repeated the cognitive tests.Then the scientists started comparing and quickly noticed subtle differences in how the exercisers’ brains operated. Their scans showed more-synchronized activity throughout their medial temporal lobes than among the sedentary group, and this activity was more dynamic. Portions of the exercisers’ lobes would light up together and then, within seconds, realign and light up with other sections of the lobe. Such promiscuous synchronizing indicates a kind of youthful flexibility in the brain, Dr. Gluck says, as if the circuits were smoothly trading dance partners at a ball. The exercisers’ brains would “flexibly rearrange their connections,” he says, in a way that the sedentary group’s brains could not.Just as important, those changes played out in people’s thinking and memories. The exercisers performed better than before on a test of their ability to learn and retain information and apply it logically in new situations. This kind of agile thinking involves the medial temporal lobe, Dr. Gluck says, and tends to decline with age. But the older exercisers scored higher than at the start, and those whose brains displayed the most new interconnections now outperformed the rest.This study involved older African-Americans, though, a group that is underrepresented in health research but may not be representative of all aging people. Still, even with that caveat, “it seems that neural flexibility” gained by exercising a few times a week “leads directly to memory flexibility,” Dr. Gluck says.AdvertisementContinue reading the main story

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Covid: Joe Biden promises vaccines will be available for every US adult by end of May

SharecloseShare pageCopy linkAbout sharingimage copyrightReutersThe US will have enough coronavirus vaccines for every adult by the end of May, President Joe Biden has said.This will be two months earlier than previously expected, but Mr Biden said the vaccination drive must be extended, too, and people convinced to take it.And he warned people to “stay vigilant” because “this fight is far from over”, with new variants a major concern.His caution is at odds with some states, which are relaxing restrictions in order to boost their economies.Although there has been a sharp fall in cases since the start of the year, in some areas that drop has been levelling off, fuelling fears of another wave.Covid-19 variants pose ‘real threat’ to vaccine progress, CDC warnsBiden calls 500,000 death toll a heartbreaking milestoneThe US has recorded 28.7 million infections and 516,000 deaths related to Covid-19 since the pandemic began, according to Johns Hopkins University research.More than 76 million vaccination doses have been administered – covering 15.3% of the population and the US remains on track to meet Mr Biden’s pledge of delivering 100 million Covid-19 vaccine doses in his first 100 days in office.What was in Mr Biden’s latest announcement?The president said that drug manufacturer Merck – which this year discontinued work on its own vaccine – would now be helping Johnson & Johnson to produce its newly approved one-shot drug.”We’re now on track to have enough vaccine supply for every adult in America by the end of May,” he said, adding it was “the type of collaboration between companies we saw in World War Two”.But the president acknowledged that supply was only one issue, with the nation needing to extend its vaccination drive and convince people to take the shots.”We need vaccinators, people who put the shots in people’s arms, millions of Americans’ arms,” he said.”Great news, but stay vigilant,” Mr Biden said. “It’s not over yet.”Another key announcement was the pledge to give every teacher at least one shot by the end of March, and speed up the reopening of schools.But on a general reopening, he was more cautious, saying he was unsure when a return to normal would be possible, although he did then say before “this time next year”.What are the states doing on reopenings?Some are now relaxing rules, despite a warning from top federal health officials last week not to ease up.Mr Biden repeated that, saying: “We cannot let our guard down now or assure that victory is inevitable. We can’t assume that.”The governor of Texas on Tuesday issued an executive order, effective from 10 March, that rescinds most of the coronavirus measures he imposed earlier in the pandemic.image copyrightReutersGreg Abbott lifted the regulation ordering people to wear masks and said businesses would be allowed to resume full capacity next week, “It is now time to open Texas 100%,” the Republican said. “Too many small business owners have struggled to pay their bills. This must end.”He said that with increased vaccinations and improved treatment for Covid-19, the state was “in a far better position now”.The Democratic party in the state said the “crazy” move would throw away all of the gains.Mississippi has followed Texas in removing the order on mask wearing, but it will come into effect even earlier – from Wednesday.Other states, including Michigan and Louisiana, have also announced relaxation of some rules.Michigan, which has a Democratic governor, is to ease capacity limits on restaurants, and on public and residential gatherings.Individual states are in charge of public health policy in the US. At the start of the coronavirus pandemic, most introduced restrictions on businesses and travel.About 35 required face coverings to be worn in public places, although enforcement of these mask mandates has been patchy.Health officials have warned that the pandemic is far from over and cases could pick up if curbs are lifted too soon.On Monday the director of the US Centers for Disease Control and Prevention (CDC) warned of a “potential fourth surge of cases” if the country lapsed into complacency. Covid-19 data shows that, while infections and deaths have declined in recent weeks, they are still at high levels relative to other countries.The emergence of new variants could also require booster shots for those already vaccinated.How has Covid affected the US?The 28.7 million total confirmed US infections is nearly double that of second-highest India (11 million) and Brazil (10.5 million), according to Johns Hopkins University researchBut the US ranks ninth in terms of deaths per 100,000 population, behind countries such as the UK and ItalyAt least 90,000 more Americans are expected to have died with the virus by 1 June, an Institute for Health Metrics and Evaluation (IHME) projection says. By late May, the virus will kill around 500 Americans per day – down from approximately 2,000 now

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Coronavirus: Texas and other states ease rules despite warnings

SharecloseShare pageCopy linkAbout sharingimage copyrightReutersTexas will lift its mask requirement and allow businesses to reopen at full capacity next week, Governor Greg Abbott has announced.”It is now time to open Texas 100%,” the Republican said on Tuesday.Texas is the largest US state to end its mask mandate. Mr Abbott has faced criticism from his party over the measure, which was imposed last July.But the administration of US President Joe Biden has made it clear coronavirus restrictions are still necessary.The announcement in Texas came as similar rules were lifted in other states, including Michigan, Louisiana, and Mississippi, which also ended its mask mandate.The roll-out of vaccinations against Covid-19 has boosted confidence in a return to pre-pandemic life in the US.On Tuesday, President Biden said the US was on track to have enough vaccines for every adult in the country by the end of May.Yet the wave of reopenings has put states at odds with the Biden administration and its senior health officials, who have reacted with dismay to the relaxation of coronavirus measures at a precarious time in the pandemic.Covid-19 variants pose ‘real threat’ to vaccine progress, CDC warnsBiden calls 500,000 death toll a heartbreaking milestoneOn Monday the director of the US Centers for Disease Control and Prevention (CDC) warned of a “potential fourth surge of cases” if the country lapsed into complacency. Covid-19 data shows that, while infections and deaths have declined in recent weeks, they are still at high levels relative to other countries.In total, the US has recorded more than 28 million infections and 516,000 deaths related to Covid-19, according to data collated by Johns Hopkins University.What did the Texas governor announce?Mr Abbott issued an executive order that rescinded most of the coronavirus measures he imposed earlier in the pandemic.The new executive order, which is to take effect on 10 March, lifts all mask requirements and forbids local authorities from penalising residents who do not wear a face covering. It removes all restrictions on businesses in counties without a high number of Covid-19 patients in hospital.image copyrightReuters”Too many Texans have been sidelined from employment opportunities,” Mr Abbott said in a speech at the Chamber of Commerce in the city of Lubbock. “Too many small business owners have struggled to pay their bills. This must end.”He said that with increased vaccinations and improved treatment for Covid-19, the state was “in a far better position now”.But, he added, “Covid has not suddenly disappeared”. Following weeks of decline, coronavirus infections and related deaths are creeping up again in Texas, data from the Covid Tracking Project showed.Texas has recorded more than 43,000 deaths related to Covid-19, the third-highest state toll in the US.Texas puts White House relations to the testAngelica Casas, reporting from San Antonio, TexasGovernor Abbott’s announcement was no surprise to Texans. After all, the state’s pandemic response has been political from the start.The state’s Republican leadership favoured former President Donald Trump’s relatively relaxed approach to imposing restrictions. But that created tension with local officials in the state’s major cities, which all lean Democrat.It was control of the disease vs control of the economy. Mask requirements vs maintaining personal liberties. And when the surges came, state politicians were more reactive than proactive.A year later, not much has changed. The state’s death toll and current case rate are still among the highest in the US. That’s why critics say Governor Abbott’s decision does not follow the science.So the decision will be a test to the state – but also to Mr Abbott’s relationship with President Biden, who has addressed the pandemic with more urgency than his predecessor.What about other US states?Individual states are in charge of public health policy in the US. At the start of the coronavirus pandemic, most introduced restrictions on businesses and travel.About 35 required face coverings to be worn in public places – either or outdoor – although enforcement of these mask mandates has been patchy.With cases and deaths falling sharply in recent weeks, several states have begun easing the restrictions.Shortly after Mr Abbott’s announcement, Mississippi Governor Tate Reeves said he would do the same in an even shorter time frame.”Starting tomorrow, we are lifting all of our county mask mandates and businesses will be able to operate at full capacity without any state-imposed rules,” Mr Reeves said.Health experts have warned that the pandemic was far from over and cases could pick up if curbs were lifted too soon.image copyrightReutersPresident Biden – in contrast with his predecessor Mr Trump – has made fighting the virus a priority for his administration.On Tuesday, Mr Biden said he was upbeat about reaching his goal of delivering 100 million Covid-19 vaccine doses in his first 100 days in office, but urged Americans to remain vigilant in wearing masks and observing social distancing.”Today’s announcements are a huge step in our effort to beat this pandemic,” Biden said in a televised statement from the White House. “But I have to be honest with you. This fight is far from over.”How has Covid affected the US?The 28.7 million total confirmed US infections is nearly double that of second-highest India (11 million) and Brazil (10.5 million), according to Johns Hopkins University researchBut the US ranks ninth in terms of deaths per 100,000 population, behind countries such as the UK and ItalyAt least 90,000 more Americans are expected to have died with the virus by 1 June, an Institute for Health Metrics and Evaluation (IHME) projection says. By late May, the virus will kill around 500 Americans per day – down from approximately 2,000 nowHospital admission rates have fallen sharply since JanuaryThe growing number of new variants, which could spark further outbreaks, remains a concern

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Covid-19: Dolly Parton marks vaccination with Jolene rewrite

SharecloseShare pageCopy linkAbout sharingCountry star Dolly Parton has been given a Covid-19 vaccine dose, after urging others to follow her example by reimagining one of her hit songs.Parton, 75, sang an adapted version of Jolene before receiving the shot at Vanderbilt University Medical Center in Nashville, Tennessee on Tuesday.”Vaccine, vaccine, vaccine, vaccine, I’m begging of you, please don’t hesitate,” Parton sang in a video.She was injected with a vaccine developed by Moderna.Parton was credited with helping fund the Moderna vaccine after donating $1m (£716,000) to Vanderbilt University Medical Centre.A portion of the singer’s money went towards funding an early stage-trial of the Moderna vaccine. In trials, the Moderna vaccine was found to offer nearly 95% protection against severe Covid-19.image copyrightReutersThe Grammy-winning musician said she had been “waiting a while” for her vaccination.”I’m old enough to get it and I’m smart enough to get it,” the singer told fans in a video posted from the university.Last month Parton told the Associated Press she wanted to wait until vaccines were more widely available because “I don’t want it to look like I’m jumping the line”.Now vaccine supply has increased – in the US at least – Parton said she “wanted to encourage everybody” to get theirs.Dolly Parton ‘honoured and proud’ to help Covid-19 battleModerna: Covid-19 vaccine shows nearly 95% protection”I just want to say to all of you cowards out there – don’t be such a chicken squat. Get out there and get your shot,” she said.The 9 to 5 singer is the latest star to promote coronavirus vaccinations.Other celebrities who have had a Covid-19 vaccine include:- Sir David AttenboroughThe naturalist and broadcaster, 94, received the Covid-19 jab in January, months after speaking of the “immense suffering” caused by the pandemic.- Jane FondaThe Academy Award-winning actress, 83, shared the news of her jab in an Instagram post in February, posting: “It doesn’t hurt”. View this post on Instagram A post shared by Jane Fonda (@janefonda)- Sir Ian McKellenThe veteran actor, 81, was vaccinated at Queen Mary’s University Hospital in London, saying afterwards that he felt “euphoric”.- Arnold SchwarzeneggerThe former politician and action hero, 73, had his jab in January in Los Angeles and nodded to one of his best-known movie lines when he said: “Come with me if you want to live.”Today was a good day. I have never been happier to wait in a line. If you’re eligible, join me and sign up to get your vaccine. Come with me if you want to live! pic.twitter.com/xJi86qQNcm— Arnold (@Schwarzenegger) January 20, 2021
The BBC is not responsible for the content of external sites.View original tweet on Twitter- Bette Midler The Broadway singer and actress, 75, announced she got the Pfizer vaccine on US talk show Jimmy Kimmel Live in February.- Sir Elton John and Sir Michael CaineThe pair urged the public to get vaccinated against coronavirus in an National Health Service (NHS) advert released in February.I am proud to join forces with @themichaelcaine to promote the fantastic @NHSEngland #COVIDVaccine program, demonstrating how quick and easy it is to get vaccinated and why it’s so important. Let’s all come together and do our bit in the fight against this wretched disease. pic.twitter.com/Ub7npvyF6U— Elton John (@eltonofficial) February 10, 2021
The BBC is not responsible for the content of external sites.View original tweet on Twitter

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Biden Vows Enough Vaccine ‘for Every Adult American’ by End of May

#masthead-section-label, #masthead-bar-one { display: none }The Coronavirus OutbreakliveLatest UpdatesMaps and CasesRisk Near YouVaccine RolloutNew Variants TrackerAdvertisementContinue reading the main storySupported byContinue reading the main storyBiden Vows Enough Vaccine ‘for Every Adult American’ by End of MayThe pharmaceutical giant Merck & Co. agreed to help manufacture Johnson & Johnson’s coronavirus vaccine, in a deal partly brokered by the White House.President Biden said his administration had provided support to Johnson & Johnson that would enable the United States and its partners to make coronavirus vaccines around the clock. Credit…Doug Mills/The New York TimesSheryl Gay Stolberg, Sharon LaFraniere, Katie Thomas and March 2, 2021, 7:48 p.m. ETWASHINGTON — President Biden said on Tuesday that the United States was “on track” to have enough supply of coronavirus vaccines “for every adult in America by the end of May,” accelerating his effort to deliver the nation from the worst public health crisis in a century.In a brief speech at the White House, Mr. Biden said his administration had provided support to Johnson & Johnson that would enable the company and its partners to make vaccines around the clock. The administration had also brokered a deal in which the pharmaceutical giant Merck & Co. would help manufacture the new Johnson & Johnson coronavirus vaccine.Merck is the world’s second-largest vaccine manufacturer, though its own attempt at a coronavirus vaccine was unsuccessful. Officials described the partnership between the two competitors as historic and said it harks back to Mr. Biden’s vision of a wartime effort to fight the coronavirus, similar to the manufacturing campaigns when Franklin D. Roosevelt was president.“As a consequence of the stepped-up process that I’ve ordered and just outlined, this country will have enough vaccine supply — I’ll say it again — for every adult in America by the end of May,” Mr. Biden said. “By the end of May. That’s progress — important progress.”He also said he wanted all teachers vaccinated by the end of this month.The president’s time table, if it comes to pass, provides a bright light at the end of a long, dark tunnel, though he acknowledged that the nation remained in a tenuous situation. The announcement on Tuesday came days after the Food and Drug Administration gave Johnson & Johnson emergency authorization for its vaccine, which unlike the two others that are available requires just one dose.Public health officials fear a fourth surge of the coronavirus pandemic, fueled by worrisome new variants, as states like Texas and Mississippi rush to fully reopen. While daily caseloads have undergone a steep drop since January, the decline appears to be leveling off, and top federal health officials warned governors last week against relaxing coronavirus restrictions.“We cannot let our guard down now or assure that victory is inevitable,” Mr. Biden said. “We can’t assume that.”He had previously said that there would be enough coronavirus vaccines for every American by the end of July. While the president’s remarks on Tuesday set a new marker against which he will be measured, his administration and his predecessor’s had already laid the groundwork to cover the 260 million eligible adults by the end of May.Two other vaccine manufacturers, Moderna and Pfizer BioNTech, pledged last month to deliver together enough to cover 200 million Americans by that date. Johnson & Johnson’s $1 billion contract, negotiated last year when Donald J. Trump was president, calls for the company to deliver enough doses for another 87 million Americans by the end of May, which would have given the country enough vaccine for all adults 18 and older.But Johnson & Johnson and its partners fell behind in their manufacturing. The company was supposed to deliver its first 37 million doses by the end of March, but it has said it would be able to deliver only 20 million doses by that date, which made Biden aides nervous.In late January, Jeffrey D. Zients, Mr. Biden’s coronavirus response coordinator, and Dr. David Kessler, who is managing vaccine distribution for the White House, reached out to top officials at the company, including Alex Gorsky, its chief executive, with a blunt message: This is unacceptable.That led to a series of negotiations in February in which administration officials repeatedly pressured Johnson & Johnson to accept that they needed help, while urging Merck to be part of the solution, according to two administration officials who participated in the discussions.In a statement on Tuesday, Merck said the federal government would pay it up to $269 million to adapt and make available its existing facilities to produce coronavirus vaccines. Michael T. Nally, the executive vice president of human health at Merck, said in an interview that the company had been in talks with multiple companies and governments, including officials in the former Trump administration.“I think we all recognize that every day counts,” he said.Mr. Nally declined to provide an estimate for how many doses of vaccine the company could ultimately produce, saying only that it would be “substantial.” The expanded supply from Merck, though, is not likely to become available for months.One federal official, who spoke on the condition of anonymity, said other steps the administration took would move up Johnson & Johnson’s manufacturing timeline.Those steps, said Jen Psaki, the White House press secretary, included providing a team of experts to monitor manufacturing and logistical support from the Defense Department. In addition, the president will invoke the Defense Production Act, a Korean War-era law, to give Johnson & Johnson access to supplies necessary to make and package vaccines.Mr. Biden said he would also invoke the law to help Merck retrofit one of two manufacturing plants that would be used in the production process.The Coronavirus Outbreak

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Weight loss drug hope for patients with type 2 diabetes

Patients with type 2 diabetes that were treated with a weekly injection of the breakthrough drug Semaglutide were able to achieve an average weight loss of nearly 10kg, according to a new study published in The Lancet today.
Led by Melanie Davies, Professor of Diabetes Medicine at the University of Leicester and the Co-Director of the Leicester Diabetes Centre, the study showed that two thirds of patients with type 2 diabetes that were treated with weekly injections of a 2.4mg dose of Semaglutide were able to lose at least 5% of their body weight and achieved significant improvement in blood glucose control.
More than a quarter of patients were able to lose more than 15% of their body weight — far above that which has been observed with any other medicine administered to people with diabetes.
Professor Melanie Davies said: “These results are exciting and represent a new era in weight management in people with type 2 diabetes — they mark a real paradigm shift in our ability to treat obesity, the results bring us closer to what we see with more invasive surgery.
“It is also really encouraging that along with the weight loss we saw real improvements in general health, with significant improvement in physical functioning scores, blood pressure and blood glucose control.”
This global multi-centre trial was conducted at 149 sites in 12 countries across North America, Europe, South America, the Middle East, South Africa and Asia, involving 1,210 patients with type 2 diabetes whose current treatment was not achieving sufficient blood sugar control, for instance through diet and exercise, or through the use of metformin and other glucose lowering medicines used to control the disease.
It is one of a portfolio of studies conducted as part of the Semaglutide Treatment Effect for people with obesity Programme (STEP) programme. Professor Davies has been involved in all four of the STEP clinical trials involving Semaglutide for weight management completed so far, where the medication was shown to help patients achieve an average weight of loss of between 10kg and 17kg of body weight.
Being overweight or obese is a significant contributor to type 2 diabetes. Many patients can manage their type 2 diabetes by eating a healthy diet, taking regular exercise, and using medications to help control blood sugar, or achieve glycemic control but for a significant minority of patients who have not seen much improvement in spite of these methods, semiglutide is a promising development.
This study was also supported by the NIHR Leicester Biomedical Research Centre, of which Professor Davies is the Director.

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Materials provided by University of Leicester. Note: Content may be edited for style and length.

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Cooperative eco-driving automation improves energy efficiency and safety

Imagine you’re driving up a hill toward a traffic light. The light is still green so you’re tempted to accelerate to make it through the intersection before the light changes. Then, a device in your car receives a signal from the controller mounted on the intersection alerting you that the light will change in two seconds — clearly not enough time to beat the light. You take your foot off the gas pedal and decelerate, saving on fuel. You feel safer, too, knowing you didn’t run a red light and potentially cause a collision in the intersection.
Connected and automated vehicles, which can interact vehicle to vehicle (V2V) and between vehicles and roadway infrastructure like traffic signals and stop signs (V2I), promise to save energy and improve safety. In a new study published in Transportation Research Part B, engineers from Michigan Technological University propose a modeling framework for V2V and V2I cooperative driving.
Cooperative driving helps cars and their drivers safely and efficiently navigate. The framework uses an eco-driving algorithm that prioritizes saving fuel and reducing emissions. The automated algorithm calculates location-based traffic control devices and roadway constraints using maps and geographic information. The research is led by Kuilin Zhang, associate professor of civil and environmental engineering and affiliated associate professor of computer science at Michigan Tech, along with Shuaidong Zhao ’18, now a senior quantitative analyst at National Grid.
For the past three years, Houghton, Michigan, has been home to roadside units installed on five of the city’s traffic signals that make V2I communication possible. Zhang conducted a simulation analysis using real traffic signal phasing and timing messages from the Ann Arbor connected vehicle test environment and plans to expand testing in the Houghton area.
“The whole idea of cooperative driving automation is that the signals in the intersection tell your car what’s happening ahead,” Zhang said. “The sensor at the intersection can benefit all connected vehicles passing through the intersection. The automated eco-driving algorithm improves the driving decisions of the connected and automated vehicles.”
The simulation results show that the cooperative automated eco-driving algorithm saves energy — 7% under light traffic and 23% under heavy traffic along the corridor.
“The stop and go, stop and go, it may use a lot of energy,” Zhang said. “The concept of eco-driving incorporates how the vehicle makes driving decisions using data not only from vehicles in front of it, but also with information given from a traffic signal.”
Zhang’s model pulls in high-definition (HD) maps, which use a connected vehicle’s hardware and software to provide down-to-the-centimeter accuracy in navigation. HD maps incorporate multiple types of environmental sensing: long-range radar, lidar, camera footage, short/medium-range radar and ultrasound.
Zhang said for autonomous driving, it’s important to know landmarks to control the car’s driving, as well as hill grades; using a hill to slow or accelerate a car can also increase energy savings. It’s easy to conserve energy on a straight highway; on busy arterial streets with traffic and stoplights, energy conservation isn’t so simple. On city streets, Zhang and Zhao’s online predictive connected and automated eco-driving model considers traffic control devices and road geometry constraints under light and heavy traffic conditions.

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Materials provided by Michigan Technological University. Original written by Kelley Christensen. Note: Content may be edited for style and length.

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