Metformin use reduces risk of death for patients with COVID-19 and diabetes

metformin

Use of the diabetes drug metformin—before a diagnosis of COVID-19—is associated with a threefold decrease in mortality in COVID-19 patients with Type 2 diabetes, according to a racially diverse study at the University of Alabama at Birmingham. Diabetes is a significant comorbidity for COVID-19.

“This beneficial effect remained, even after correcting for age, sex, race, obesity, and hypertension or chronic kidney disease and heart failure,” said Anath Shalev, M.D., director of UAB’s Comprehensive Diabetes Center and leader of the study.

“Since similar results have now been obtained in different populations from around the world—including China, France and a UnitedHealthcare analysis—this suggests that the observed reduction in mortality risk associated with metformin use in subjects with Type 2 diabetes and COVID-19 might be generalizable,” Shalev said.

How metformin improves prognosis in the context of COVID-19 is not known, Shalev says. The UAB findings suggest that the mechanisms may go beyond any expected improvement in glycemic control or obesity, since neither body mass index, blood glucose nor hemoglobin A1C were lower in the metformin users who survived as compared to those who died.

“The mechanisms may involve metformin’s previously described anti-inflammatory and anti-thrombotic effects,” Shalev said.

The study—first made available in MedRxiv and now published in the peer-reviewed journal Frontiers in Endocrinology—included 25,326 patients tested for COVID-19 at the tertiary care UAB Hospital between Feb. 25 and June 22 of last year. Of the 604 patients found to be COVID-19-positive, 311 were African Americans.

The primary outcome in the study was mortality in COVID-19-positive subjects, and the potential association with subject characteristics or comorbidities was analyzed.

Researchers found that Blacks, who are only 26 percent of Alabama’s population, were 52 percent of those who tested positive for COVID-19, and only 30 percent of those who tested negative. In contrast, only 36 percent of the COVID-19-positive subjects were white, while whites made up 56 percent of those who tested negative, further underlining the racial disparity. Once COVID-19-positive though, no significant racial difference in mortality was observed.

“In our cohort,” Shalev said, “being African American appeared to be primarily a risk factor for contracting COVID-19, rather than for mortality. This suggests that any racial disparity observed is likely due to exposure risk and external socioeconomic factors, including access to proper health care.”

Overall mortality for COVID-19-positive patients was 11 percent. The study found that 93 percent of deaths occurred in subjects over the age of 50, and being male or having high blood pressure was associated with a significantly elevated risk of death. Diabetes was associated with a dramatic increase in mortality, with an odds ratio of 3.62. Overall, 67 percent of deaths in the study occurred in subjects with diabetes.

The researchers looked at the effects of diabetes treatment on adverse COVID-19 outcomes, focusing on insulin and metformin as the two most common medications for Type 2 diabetes. They found that prior insulin use did not affect mortality risk.

However, prior metformin use was a different matter. Metformin use significantly reduced the odds of dying, and the 11 percent mortality for metformin users was not only comparable to that of the general COVID-19-positive population, it was dramatically lower than the 23 percent mortality for diabetes patients not on metformin.

After controlling for other covariates, age, sex and metformin use emerged as independent factors affecting COVID-19-related mortality. Interestingly, even after controlling for all these other covariates, death was significantly less likely—with an odds ratio of 0.33—for Type 2 diabetes subjects taking metformin, compared with those who did not take metformin.

“These results suggest that, while diabetes is an independent risk factor for COVID-19-related mortality,” Shalev said, “this risk is dramatically reduced in subjects taking metformin—raising the possibility that metformin may provide a protective approach in this high-risk population.”

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Dental experts discover biological imbalance is the link between gum and kidney disease

An imbalance of the body’s oxygen producing free radicals and its antioxidant cells could be the reason why gum disease and chronic kidney disease affect each other, a new study led by the University of Birmingham has found.

Periodontitis—or gum disease—is a common, inflammatory disease which causes bleeding gums, wobbly or drifting teeth and can eventually result in tooth loss.

Previous studies have shown a link between the severe oral inflammation caused by gum disease and chronic kidney disease (CKD) which demonstrated that those with worse inflammation of the gums have worse kidney function.

Previous research also showed that patients with CKD and periodontitis experience a drop in survival rates, similar in magnitude to if they had diabetes instead of gum inflammation, suggesting that gum inflammation may casually affect kidney function.

In this latest study, led by researchers at the University of Birmingham, over 700 patients with chronic kidney disease were examined using detailed oral and full-body examinations including blood samples. The aim was to test the hypothesis that periodontal inflammation and kidney function affect each other and to establish the underlying mechanism that may facilitate this.

Results showed that just a 10% increase in gum inflammation reduces kidney function by 3%. In this group of patients, a 3% worsening in kidney function would translate to an increase in the risk of kidney failure over a 5 year period from 32%-34%. Results also showed that a 10% reduction in kidney function increases periodontal inflammation by 25%.

In contrast to current beliefs that inflammation is the link between periodontitis and other systemic diseases, researchers found for the first time, that in this group of patients, the effect was caused by a biological process called ‘oxidative stress’—or, an imbalance between reactive oxygen species and the body’s antioxidant capacity which damages tissues on a cellular level.

Lead author Dr. Praveen Sharma, from the Periodontal Research Group at the University of Birmingham’s School of Dentistry, said, “This is the first paper to quantify the casual effect of periodontitis on kidney function and vice-versa as well as the first to elucidate the pathways involved.

“It showed that even a modest reduction in gum inflammation can benefit renal function. Given the relative ease of achieving a 10% reduction in gum inflammation, through simple measures like correct brushing techniques and cleaning between the teeth, these results are very interesting.

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Vaccination drive enters new phase in US and Britain

The first Americans inoculated against COVID-19 began rolling up their sleeves for their second and final dose Monday, while Britain introduced another vaccine on the same day it imposed a new nationwide lockdown against the rapidly surging virus.

New York State, meanwhile, announced its first known case of the new and seemingly more contagious variant, detected in a man in his 60s in Saratoga Springs. Colorado, California and Florida previously reported infections involving the mutant version that has been circulating in England.

The emergence of the variant has added even more urgency to the worldwide race to vaccinate people against the scourge.

In Southern California, intensive care nurse Helen Cordova got her second dose of the Pfizer vaccine at Kaiser Permanente Los Angeles Medical Center along with other doctors and nurses, who bared their arms the prescribed three weeks after they received their first shot. The second round of shots began in various locations around the country as the U.S. death toll surpassed 352,000.

“I’m really excited because that means I’m just that much closer to having the immunity and being a little safer when I come to work and, you know, just being around my family,” Cordova said.

Over the weekend, U.S. government officials reported that vaccinations had accelerated significantly. As of Monday, the Centers for Disease Control and Prevention said nearly 4.6 million shots had been dispensed in the U.S., after a slow and uneven start to the campaign, marked by confusion, logistical hurdles and a patchwork of approaches by state and local authorities.

Britain, meanwhile, became the first nation to start using the COVID-19 vaccine developed by AstraZeneca and Oxford University, ramping up its nationwide inoculation campaign amid soaring infection rates blamed on the new variant. Britain’s vaccination program began Dec. 8 with the shot developed by Pfizer and its German partner BioNTech.

Brian Pinker, an 82-year-old dialysis patient, received the first Oxford-AstraZeneca shot at Oxford University Hospital, saying in a statement: “I can now really look forward to celebrating my 48th wedding anniversary.”

The rollout came the same day Prime Minister Boris Johnson announced a new lockdown for England until at least mid-February. Britain has recorded more than 50,000 new coronavirus infections a day over the past six days, and deaths have climbed past 75,000, one of the worst tolls in Europe.

Schools and colleges will generally be closed for face-to-face instruction. Nonessential stores and services like hairdressers will be shut down, and restaurants can offer only takeout.

“As I speak to you tonight, our hospitals are under more pressure from COVID than at any time since the start of the pandemic,” Johnson said.

Elsewhere around the world, France and other parts of Europe have come under fire over slow vaccine rollouts and delays.

France’s cautious approach appears to have backfired, leaving just a few hundred people vaccinated after the first week and rekindling anger over the government’s handling of the pandemic. The slow rollout has been blamed on mismanagement, staffing shortages over the holidays and a complex consent policy designed to accommodate vaccine skepticism among the French.

“It’s a state scandal,” Jean Rottner, president of the Grand-Est region of eastern France, said on France-2 television. “Getting vaccinated is becoming more complicated than buying a car.”

Health Minister Olivier Veran promised that by the end of Monday, several thousand people would be vaccinated, with the tempo picking up through the week. But that would still leave France well behind its neighbors.

French media broadcast charts comparing vaccine figures in various countries: In France, a nation of 67 million people, just 516 people were vaccinated in the first six days, according to the French Health Ministry. Germany’s first-week total surpassed 200,000, and Italy’s was over 100,000. Millions have been vaccinated in the U.S. and China.

The European Union likewise faced growing criticism about the slow rollout of COVID-19 shots across the 27-nation bloc of 450 million inhabitants. EU Commission spokesman Eric Mamer said the main problem “is an issue of production capacity, an issue that everybody is facing.”

The EU has sealed six vaccine contracts with a variety of manufacturers. But only the Pfizer-BioNTech vaccine has been approved for use so far across the EU. The EU’s drug regulators are expected to decide on Wednesday whether to recommend authorizing the Moderna vaccine.

In the U.S., Dr. Mysheika Roberts, health commissioner in Columbus, Ohio, said demand has been lower than expected among the people given top priority for the vaccine. For example, the city’s 2,000 emergency medical workers are all eligible, but the health department has vaccinated only 850 of them.

She said some people were hesitant to get the vaccine and wanted to see how others handled it. The vaccine also arrived the week of Christmas, and a lot of people were on vacation and didn’t want to be bothered during the holiday, she said.

“I think we all assumed that people would want this vaccine so badly, that when it became available, people would just come get it,” Roberts said.

Roberts noted there has been no effective mass marketing campaign explaining why people should get vaccinated.

“From the president on down, so many people have been touting the fact that we’re going to have a vaccine and get this vaccine out. But so many of those same people who were talking about it now have gone silent,” she said. “That could help if those same people would be more vocal about it.”

Elsewhere around the globe, Israel appears to be among the world leaders in the vaccination campaign, inoculating over 1 million people, or roughly 12% of its population, in just over two weeks. The effort has been boosted by a high-quality, centralized health system and the country’s small size and concentrated population.







Hoping to spur a halting vaccination effort that has only given about 44,000 shots since the third week of December, Mexico approved the Oxford-AstraZeneca vaccine for emergency use Monday. Previously, the Pfizer vaccine was the only one approved for use in Mexico.

On Sunday, India, the world’s second-most populous country, authorized its first two COVID-19 vaccines—the Oxford-AstraZeneca one and another developed by an Indian company. The move paves the way for a huge inoculation program in the desperately poor nation of 1.4 billion people.

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How and When You’ll Actually Get the COVID Vaccine

Two pharmaceutical companies say they’re ready to begin vaccinating people before the end of December, if their vaccines are authorized by the Food and Drug Administration. What does that mean?

The two companies have applied to the FDA for emergency use authorization of their Covid-19 vaccines immediately.

The FDA will meet on December 10 to discuss approval of the Pfizer/BioNTech vaccine and a week later on December 17 for Moderna’s. But the vaccines may not be widely available to the public until at least April 2021, although the companies have started sending doses for potential distribution already. Last Friday, the first large shipment of the Pfizer/BioNTech vaccine arrived in Chicago and Moderna’s CEO believes they can begin vaccinations by December 21.

But hold onto your masks: we will have a very, very small fraction of the doses we need and, unless you are a healthcare worker or in a higher risk group, you probably won’t be able to get one for a while.

In the best case scenario, only 22.5 million people in the United States will be vaccinated by the end of the year—Moderna says it has 20 million doses and Pfizer 25 million, and both vaccines require two shots to work.

Who gets the vaccine first?

Today, the CDC’s Advisory Committee on Immunization Practices (ACIP) voted for the CDC to recommend that healthcare workers and residents of long-term care facilities should get the vaccine first.

That decision follows the recommendation of experts, such as the National Academies of Sciences, Engineering, and Medicine and the Johns Hopkins Center for Health Security.

Since there will be so few vaccines at first, the question is how to distribute with the maximum impact. The answer was to protect the healthcare workers who are likely to be exposed to the virus and essential to stop it as well as the residents of long-term care facilities where the virus has been merciless.

Nearly one in four coronavirus deaths is linked to a long-term care facility, and the surge of cases in the Midwest is largely due to cases among already vulnerable, older people in close-contact environments.

But a recommendation is just a recommendation, and states are not obligated to obey the CDC.

And just because healthcare workers are waved to the front of the line doesn’t mean they will take the vaccine, unless required by their employer. Only 63% of healthcare workers said they would get the vaccine, according to a CDC survey, reminiscent of the low swine flu vaccination rates for health workers back in 2009.

Even if everyone in this group wanted one, there wouldn’t be enough in December anyway: there are 21 million healthcare workers and 3 million residents of long-term care facilities, meaning it will be January before we have enough vaccines for this first group.

How many people need to get the vaccine for it to have an effect on the pandemic?

The very good news is that both vaccines appear to work very well—Moderna’s is 94.1% effective at preventing the disease and the Pfizer vaccine is 95%. And when people in the study did get the virus, Moderna’s was 100% effective at preventing severe disease.

The very bad news is that a vaccine is no good unless it is actually in people’s bodies, and the vaccine needs to be in a lot of people’s bodies.

Most experts say we need to reach 60 to 70 percent immunity to break coronavirus transmission, and at most, only 10% of the population has coronavirus antibodies right now (and who knows how long they last or who those people are).

This becomes a math problem: at the very least, a 95% effective vaccine needs to be given to 63% of the population to raise the immunity by 60 percent (0.95 times 0.63).

That’s about 207 million people. And don’t forget, they need two doses each. And we don’t yet know if people will need a seasonal booster like the flu shot.

So how long before the sign at your drugstore says “COVID vaccines are available”?

The optimistic answer is by April. That’s according to Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. Alex Azar, the Health and Human Services Secretary, also expects vaccines to be generally available by the spring.

But there’s reason to be pessimistic. Vaccines won’t be widely available unless we solve manufacturing and distribution problems that have been characterized as logistical nightmares more than once. There are bottlenecks in vials and syringes and facilities that can seal the vaccine into sterile containers, according to a report earlier this month from the US Government Accountability Office. And while Moderna’s vaccine can be thawed and stored for a month in a regular refrigerator, the Pfizer vaccine needs to be kept at -70 degrees Celsius (-94 Fahrenheit), while most freezers only get to about -20 degrees Celsius. The wait on a freezer that can keep the Pfizer vaccine is currently six weeks. And the shots need to be cold throughout their journey: there need to be planes and trucks equipped to carry these vaccines at super low temperatures, meaning lots and lots of dry ice.

The path from the pharma factory to your arm goes like this: manufacturers make them and ship them to a distributor, then a distributor ships them to where you’d go to get the shots, such as a hospital or pharmacy. From here, things look a lot more clear.

As part of Operation Warp Speed, the CDC partnered with McKesson Corporation to distribute vaccines, while Pfizer has set up a distribution campaign of its own.

And earlier this month, the Department of Health and Human Services announced a partnership with nineteen pharmacy chains, including CVS, Walgreens, and WalMart. That covers 60 percent of the nation’s pharmacies, according to HHS.

So, after we make hundreds of millions of doses of vaccines, produce an equal amount of vials and syringes, make and pack them with dry ice, equip trucks and planes to move them from A to B to C, purchase enough below-Antartic cold freezers and put them in hospitals across the nation, then it’s smooth sailing. In other words: don’t throw away your masks. It’s going to be a while.

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The Easiest Ways To Organize And Store Your Holiday Decorations

The end-of-the-year rush gets to all of us, often at the expense of our organization tactics. If you’ve ever dumped your decorations into boxes to get the clean-up job done fast, you’re certainly not alone. The good news is that a few simple hacks will have your decorations packed, untangled and secure in the same amount of time. All you have to do is follow a few steps.

First of all, ornament boxes are a must. Instead of quickly wrapping your delicate tree hangings in bubble wrap or paper towel, getting a cheap divider box can make the cleaning process much quicker and safer for your ornaments, Martha Stewart explains. The best part? This container involves few frills and a small budget — it’s a box with cardboard dividers. For more delicate ornaments, you can use a chest with a similar grid lay out, just add paper towel or another buffer to make sure they don’t shatter. “Use an ornament container designed with layers and fill empty space around the ornament with tissue paper to prevent movement,” Lea Schneider, author of Growing Up Organized and a member of The National Association of Professional Organizers, tells This Old House.

For small, miscellaneous items, grab a small organizing case to put ornament hooks, ribbons or other hanging tools. You can use a similar box for your gift-wrapping nick knacks like bows, confetti and name tags, the outlet notes.

Organizing your gift wrap is easy with the right tools

Say goodbye to your box filled with crinkled wrapping paper pieces — it’s time to make things much easier. Grab a clear storage bin long enough to hold wrapping paper rolls, then add tools like tape or bows on the other side of the container, MakeSpace suggests. The key here is the clear lid; this makes it easy to see what’s inside and you can more effectively organize all of your gift-wrapping supplies. For even easier organizing, use a clear garment bag to zip up all of your wrapping paper rolls. Just store, hang and leave it.

As for lights, you’ll need old pieces of cardboard. For each string, wrap the lights in a circle around the piece, tying it off at the end, or taping the ends to the board. The outlet also notes that you can cut little divots in the cardboard to secure the lights into place. Just like for the rest of your decorations, these should have their own clear-lidded storage bin as well. Simply layer them on top of one another.

For other miscellaneous items like wreaths, you can find storage containers made for their unique shapes. This Old House notes that crush-proof wreath cases can be your new best friend, just be sure to order one in time for taking down the decor.

Having different size bins and everyday items like garment bags at your disposal can make your life so much easier this year and next!

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Jessica Simpson and Daughter Max Are 'Twins' in Cute Christmas Pajamas

Jessica Simpson’s Family Album

Picture perfect! A little over a month after she gave birth to her second child with fiance Eric Johnson in June 2013, Jessica Simpson debuted her new family on the cover of Us Weekly. Posing with son Ace, daughter Maxwell, and Johnson at their home in Hidden Hills, Calif., the singer and fashion mogul opened up her busy life as a mom of two.

Related: Jessica Simpson’s Best Instagram Pics of the Kids!

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Christmas in the ICU: Decorations, lights and many tears

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OPELIKA, Ala. — A Christmas tree stands outside the intensive care room where a man stricken by COVID-19 lies unconscious, a machine breathes for him. A few feet away, a plastic snowman adorns the door of another patient whose face is barely visible behind ventilator tubes.

The decorations are "a way to let family members know that we’re trying, and we love these patients and we want them to feel like it’s Christmas as much as we can," nurse Carla Fallin said, standing just outside one of the rooms at East Alabama Medical Center.

Nurses and medical staff make their way through the seventh floor COVID-19 unit at East Alabama Medical Center Thursday, Dec. 10, 2020, in Opelika, Ala. COVID-19 patients occupy most of the beds in ICU in addition to the non-critical patients on the seventh floor.  (AP Photo/Julie Bennett)

While parades, shopping and Christmas tree lightings go on around them, nurses and doctors who've spent agonizing months caring for the ill are doing what they can to get through the holiday season, which many fear will only spread the disease and add to the U.S. death toll that has surpassed 300,000.

The medical center about 60 miles northeast of Montgomery faces an influx of COVID-19 patients as the pandemic intensifies. That means staff members can hang decorations on patients' doors in the ICU but cannot attend after-work Christmas parties. A cheerful Santa doll stands atop the desk at a nursing station, but big gatherings with relatives are out.

ALLERGIC REACTIONS TO VACCINES ARE RARE, SHORT-LIVED

A nurse for five years, Fallin said Christmas just doesn't feel right this year. She and her husband did not take their two young sons to local Christmas events that drew hundreds of people, many without masks. The decorations in the ICU help lighten the mental load a little, she said, if only until another patient nears death.

The red-brick hospital is near Auburn University in the old railroad town of Opelika, a city of 30,000 that decorated its streetlights and overpasses with green garlands and red ribbons for the season. A huge Christmas tree stands near downtown boutiques, salons and restaurants where hundreds of residents crowded together for a holiday program last weekend.

East Alabama Medical Center draws patients from a mostly rural region. Many people in the city wear masks in compliance with a state order, but fewer health precautions are visible in surrounding areas.

The area was an early hot spot for the virus in the spring. Then cases eased before a summertime spike that health officials blamed on backyard cookouts and lake gatherings around July 4.

HEAT MAY EFFECTIVELY KILL COVID ON PLANES, BOEING STUDY FINDS

Just as in other places across the country, a surge in infections linked to Thanksgiving is now filling up beds at the hospital. With vaccines not yet available to the general public, hospital officials dread what might happen in January after families board airplanes for the holidays and spend hours gathered around dinner tables or Christmas trees.

Amid so much suffering and after so many tears, any ray of brightness helps, even if it's just a candy cane sticker on a ICU window, said Dr. Meshia Wallace, a pulmonary physician who works in critical care.

"Families come in, and all they're getting for the most part is bad news: 'Your family member is sick, they've moved down from the seventh floor to the ICU,'" she said. "A little bit of Christmas cheer is not going to hurt. It can only help."

Wallace is skipping her usual Christmas gathering of about 30 relatives and hopes to spend the holiday with an aunt who might drive over from Atlanta if neither is symptomatic. Dr. Ricardo Maldonado, who leads the pandemic response team at East Alabama, knows exactly what he will do for the holiday.

"Work," Maldonado said after visiting patients on a hospital floor full of COVID-19 patients. "There is so much work."

The nonprofit hospital has had to bring in nearly 60 traveling nurses to shore up staffing that has been depleted, yet requests to take on additional COVID-19 patients still come in most days from neighboring states, including Mississippi and Tennessee, said chief executive Laura Grill.

DOCTOR WHO RECEIVED COVID-19 VACCINE WANTS TO BE ‘ROLE MODEL FOR THE COMMUNITY’ IN GETTING THE JAB

Some workers have been sickened by the virus, she said, and others retired or quit. Many, she said, are simply exhausted, both physically and emotionally, and the Christmas season isn't making things easier.

"I sat in a meeting two days ago with the nurse manager of our ICU and she just cried. She said, ‘We don’t know what else to do. We can look at this patient and know that they are not going to get better,'" Grill said.

Marilynn Waldon has felt the strain.

The veteran nurse oversees COVID-19 patients on a floor that has been decorated for Christmas with strings of white lights and stockings. Waldon had planned to retire this month but with the holidays approaching, she prayed and changed her mind.

"I talked to God about it, and he said, ‘You’re not a quitter. No. These patients got to be taken care of, and that's why you went to nursing school. So you need to stay there, do what you can do, until we get over this crisis that we're in,'" Waldon said.

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The Sad Truth About Meghan Markle And Kate Middleton’s Wedding Dress Maker

You’d think anyone associated with creating the jaw-dropping wedding day looks of two of the most famous women in the world, Meghan Markle and Kate Middleton, would be living a lavish lifestyle. But tragically, the dressmaker of the former and current royals is having trouble making ends meet in light of the COVID-19 pandemic (via People). “It’s been horrific,” Chloe Savage, who embroidered Middleton’s memorable gown and Markle’s dramatic veil said, adding, “We’ve had all our work literally dry up.”

Savage went on to share sobering details about just how bad the situation in her family is, telling People, “My 14-year-old daughter is skipping meals to save on the food budget. The stress is getting to her and she is self-harming too. So, she’s now going to Child Mental Health Services (CAMHS) to get support.”

In fact, the woman who helped create Markle’s 16-foot long veil is now on the brink of homelessness (via Insider). According to the Mirror, Savage can only afford to pay one more month’s rent. People reports at this point, she is only making about $250 per month selling embroidery kits.

Chloe Savage's work was a big part of Kate Middleton and Meghan Markle's wedding gowns

“We appliquéd all the lace to her gown and shoes,” Savage recalls of helping to pull off Middleton’s still-talked about look from 2011. She also shared some inside scoop about the future queen of England: “Kate came in a few times. She was lovely. The usual blushing bride. She was excited about the dress, nervous about the day, questioning what we were doing… all that sort of stuff.”

About working on Markle’s white silk tulle veil, the talented embroider noted, “It gave you snow blindness after an hour-or-so because you were constantly working white on white. You start to go a little bit cross-eyed after a while!”

The good news is a GoFundMe page has been set up since Savage’s story has gained international attention. In part, the included story reads, “Through no fault of her own she has been plunged into tragic circumstances and if we all club together we can perhaps provide enough for her to afford food and essentials for herself, her daughter and her young son.”

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Synthetic biology and machine learning speed the creation of lab-grown livers

Researchers at the University of Pittsburgh School of Medicine have combined synthetic biology with a machine-learning algorithm to create human liver organoids with blood- and bile-handling systems. When implanted into mice with failing livers, the lab-grown replacement livers extended life.

The study, published today in Cell Systems, shows that it’s possible to trigger and speed up the maturation of a lab-grown organ without sacrificing precision or control.

“Pregnancy is nine months—it takes that long and even months after birth for new organs to mature—but if a person needs a liver, they may not be able to wait that long,” said study author Mo Ebrahimkhani, M.D., associate professor of pathology and bioengineering, and member of the Pittsburgh Liver Research Center and the McGowan Institute for Regenerative Medicine. “We showed it’s possible to get human liver tissue with four main cell types and vasculature in 17 days. We can mature tissue almost to the third trimester in only three months.”

Other groups have attempted to coax organoid maturation in a dish using growth factors, but it’s expensive, inconsistent and prone to human error, Ebrahimkhani said. Often, there are unwanted tissue or cell types—such as intestine or brain cells growing in the middle of what should be solid liver.

Using genetic engineering is cleaner but also more complex to orchestrate. So, Ebrahimkhani partnered with Patrick Cahan, Ph.D., at Johns Hopkins University to use a machine-learning system that can reverse engineer the genes necessary for human liver maturation.

Then, Ebrahimkhani together with his collaborator at Pitt, Samira Kiani, M.D., applied genetic engineering techniques, including CRISPR, to turn a mass of immature liver tissue—originally derived from human stem cells—into what the team calls “designer liver organoids.”

The more mature the organoids got, the more capillaries and rudimentary bile duct cells snaked their way through the thin sheet of tissue, and the more closely the function of the tiny organ rivaled its full-size natural human model. Energy storage, fat accumulation, chemical transport, enzyme activity and protein production were all closer to adult human liver function, though still not a perfect match.

Ebrahimkhani imagines designer organoids having three main uses: drug discovery, disease modeling and organ transplant. Since the stem cells can come from the patient’s own body, lab-grown organs could be personalized, so there would be no threat of immune rejection.

When transplanted into mice with damaged livers, Ebrahimkhani’s designer liver organoids successfully integrated into the animals’ bodies and continued to work—producing human proteins that showed up in the animals’ blood and prolonging the animals’ lives.

This is a proof-of-principle to show that it’s possible, Ebrahimkhani said. The technique could potentially go much further.

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See Jenna Dewan Kissing Her Son Callum and More Sweet Moments

Bonding with her boy! Jenna Dewan welcomed her and Steve Kazee’s son, Callum, on March 6, 2020, and has been sharing sweet photos of the little one ever since.

“And just like that, our hearts exploded into all of eternity and beyond,” the Flirty Dancing host captioned her infant’s Instagram debut four days after his birth. “Welcome to the world you little angel! Callum Michael Rebel Kazee 3/6/20.”

Kazee added with a post of his own at the time: “In an instant our universe burst wide open and nothing would ever be the same. Welcome to earth star child.”

He went on to explain the meaning behind the little one’s name on Instagram, writing, “Callum: Gaelic for Dove because he has been so sweet and peaceful since landing in our arms. Michael: My middle name. Rebel: I wanted a way to honor my mother. Her name was Reba but from a very young age, her father called her Rebel. And so … Callum Michael Rebel Kazee was born.”

Us Weekly confirmed in October 2018 that the Tony winner and Dewan were dating following her split from Channing Tatum. (She and the Magic Mike star previously welcomed their daughter, Everly, in 2013).

The couple announced their pregnancy news in September 2019, and the Broadway star was worried about becoming a father, he told Us exclusively the following month.

“I’m nervous as can be, but I’m trying to just be calm about it and know that we’ve been doing this for billions of years, millions of years at least, so we’re going to be OK,” the Kentucky native told Us at the time. “There’s no way to even describe how excited you are at this moment, but we’re beyond. We’re very happy. It’s an incredible experience. I’m, like, every day just in awe of the fact that there’s a life growing inside of this human being that I love so much.”

Kazee proposed to the Connecticut native in February 2020 during her baby shower. “A lifetime to love and grow with you,” she captioned their Instagram reveal. “You have my heart.”

Keep scrolling to see Dewan hanging out with her son, from breast-feeding Callum to dressing him up for St. Patrick’s Day.

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