Intermediate embryonic stem cell type could lead to advances in regenerative medicine

A team led by UT Southwestern has derived a new “intermediate” embryonic stem cell type from multiple species that can contribute to chimeras and create precursors to sperm and eggs in a culture dish.

The findings, published online this week in Cell Stem Cell, could lead to a host of advances in basic biology, regenerative medicine, and reproductive technology.

Cells in early embryos have a range of distinct pluripotency programs, all of which endow the cells to create various tissue types in the body, explains study leader Jun Wu, Ph.D., assistant professor of molecular biology.

A wealth of previous research has focused on developing and characterizing “naïve” embryonic stem cells (those about four days post-fertilization in mice) and “primed” epiblast stem cells (about seven days post-fertilization in mice, shortly after the embryo implants into the uterus).

However, says Wu, there’s been little progress in deriving and characterizing pluripotent stem cells (PSCs) that exist between these two stages – largely because researchers have not been able to develop a paradigm for maintaining cells in this intermediate state.

Cells in this state have been thought to possess unique properties: the ability to contribute to intraspecies chimeras (organisms that contain a mix of cells from different individuals of the same species) or interspecies chimeras (organisms that contain a mix of cells from different species) and the ability to differentiate into primordial germ cells in culture, the precursors to sperm and eggs.

For this study, the researchers successfully created intermediate PSCs, which they named “XPSCs” from mice, horses, and humans.

Wu says that these results could eventually lead to an array of advances in both basic and applied research. For example, looking at gene activity in XPSCs from different species and interspecies chimeras could help researchers understand which signatures have been conserved through evolution.

Examining the communication between cells in chimeras may help scientists identify strategies that could be used to accelerate the development of tissues and organs from stem cells used for transplantation.

And using chimera-derived primordial germ cells to create sperm and eggs could aid in preserving endangered animal species and advancing infertility treatments.

These XPSCs have enormous potential. Our study helps open the door to each of these possibilities.”


Jun Wu, PhD, Study Leader and Assistant Professor of Molecular Biology, Virginia Murchison Linthicum Scholar in Medical Research, UT Southwestern Medical Center

Wu notes that developing XPSCs presented a special challenge because the conditions that keep naïve PSCs in a stable state are exactly the opposite of those that stabilize primed PSCs.

While culture conditions for naïve PSCs must activate a WNT cell-signaling pathway and suppress the FGF and TGF-ß pathways, the conditions to maintain primed PSCs must suppress WNT and activate FGF and TGF-ß.

Aiming for the preferred environment for XPSC derivation, Wu and his colleagues placed cells from early mouse embryos into cultures containing chemicals and growth factors that activate all three pathways.

These lab-grown cells were extremely stable in culture and able to multiply

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Development of new stem cell type may lead to advances in regenerative medicine

IMAGE

IMAGE: Drs. Jun Wu, Leqian Yu, Yulei Wei and colleagues isolated a new type of pluripotent stem cell from mice, horses, and humans, named XPSCs, which are capable of generating chimeras…
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Credit: Photo illustration by Leqian Yu

DALLAS – Dec. 3, 2020 – A team led by UT Southwestern has derived a new “intermediate” embryonic stem cell type from multiple species that can contribute to chimeras and create precursors to sperm and eggs in a culture dish.

The findings, published online this week in Cell Stem Cell, could lead to a host of advances in basic biology, regenerative medicine, and reproductive technology.

Cells in early embryos have a range of distinct pluripotency programs, all of which endow the cells to create various tissue types in the body, explains study leader Jun Wu, Ph.D., assistant professor of molecular biology. A wealth of previous research has focused on developing and characterizing “naïve” embryonic stem cells (those about four days post-fertilization in mice) and “primed” epiblast stem cells (about seven days post-fertilization in mice, shortly after the embryo implants into the uterus).

However, says Wu, there’s been little progress in deriving and characterizing pluripotent stem cells (PSCs) that exist between these two stages – largely because researchers have not been able to develop a paradigm for maintaining cells in this intermediate state. Cells in this state have been thought to possess unique properties: the ability to contribute to intraspecies chimeras (organisms that contain a mix of cells from different individuals of the same species) or interspecies chimeras (organisms that contain a mix of cells from different species) and the ability to differentiate into primordial germ cells in culture, the precursors to sperm and eggs.

For this study, the researchers successfully created intermediate PSCs, which they named “XPSCs” from mice, horses, and humans.

Wu says that these results could eventually lead to an array of advances in both basic and applied research. For example, looking at gene activity in XPSCs from different species and interspecies chimeras could help researchers understand which signatures have been conserved through evolution. Examining the communication between cells in chimeras may help scientists identify strategies that could be used to accelerate the development of tissues and organs from stem cells used for transplantation. And using chimera-derived primordial germ cells to create sperm and eggs could aid in preserving endangered animal species and advancing infertility treatments.

“These XPSCs have enormous potential. Our study helps open the door to each of these possibilities,” says Wu, who is a Virginia Murchison Linthicum Scholar in Medical Research.

Wu notes that developing XPSCs presented a special challenge because the conditions that keep naïve PSCs in a stable state are exactly the opposite from those that stabilize primed PSCs. While culture conditions for naïve PSCs must activate a WNT cell-signaling pathway and suppress the FGF and TGF-ß pathways, the conditions to maintain primed PSCs must suppress WNT and activate FGF and TGF-ß.

Aiming for the preferred environment for XPSC derivation, Wu and his

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A Biden win could lead to a mask mandate, more testing: Expert

Dr. Ashish Jha, dean of Brown University’s School of Public Health, told Yahoo Finance Monday a Joe Biden presidency could bring mask mandates and greater investment in treatments and testing to the fore.

If Biden were to take office in January, he said, there would be a far more focused strategy at the federal level.

“I think starting in January, you’re going to see a much bigger push towards testing, towards a national mask mandate,” Jha said, adding that’s what the Biden team has indicated it will do.

In addition, he predicts there’d be more investment in vaccines and treatments than has been made to-date.

“What’s been interesting about the Trump response is for a few months at least … it was a lot of evidence-based approaches. In the last couple of months under Dr. Atlas, it’s very much been a kind of ‘let it go and let people get infected and hope we get to immunity,’ ” Jha said.

The earliest months of the coronavirus outbreak were marked by the formation of the White House coronavirus task force, which included the nation’s top health officials. It’s how Centers for Disease Control director Dr. Robert Redfield, FDA Commissioner Stephen Hahn, Sec. Alex Azar, Ambassador Deborah Birx and NIAID director Dr. Anthony Fauci became household names.

When Operation Warp Speed was launched to coordinate the investment in vaccine efforts, including manufacturing and distribution, it marked a robust public-private partnership that could streamline logistics once a vaccine is authorized or approved.

But that focus on science was derailed when Trump perceived he was losing control of the messaging to the task force’s doctors and brought on Dr. Scott Atlas as a task force advisor, said Jha.

Democratic presidential candidate former Vice President Joe Biden holds up his face mask as he speaks to members of the media outside a voter service center, Monday, Oct. 26, 2020, in Chester, Pa. (AP Photo/Andrew Harnik)
Democratic presidential candidate former Vice President Joe Biden holds up his face mask as he speaks to members of the media outside a voter service center, Monday, Oct. 26, 2020, in Chester, Pa. (AP Photo/Andrew Harnik)

Despite the billions invested in a handful of companies through Operation Warp Speed, investment in treatments and testing has lagged. That was revealed recently from data published by the Biomedical Advanced Research and Development Authority (BARDA), a part of Health and Human Services.

With the lag in treatments, hospitals are amid the latest surge with no new treatments available and are still struggling with protective gear and testing availability. But even if the country has to wait until January for the change — and watch the death toll rise in the interim — Jha believes it won’t be too late to increase investments if Biden wins.

“What would have been reasonable would have been that back in April and May as these new therapeutics … were being tested, the federal government should have stepped in,” and supported production of tens of millions of doses, Jha said. Instead, the U.S. only has tens of thousands of doses to utilize.

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The politics of the pandemic lead Elkhart County, Ind., to face its worst covid-19 outbreak alone

But they also know that’s not going to happen now.

“There’s no help coming before the election,” said Lydia Mertz, the county’s health officer, calling the current situation “extremely alarming.”

“I think right now some elected officials are just looking to get through the first weeks of November before they do anything unpopular,” said Dan Nafziger, chief medical officer at Goshen Hospital, referring to the restrictions seen in the state earlier this year that he believes are needed again.

“Without a doubt the election is a factor,” said Mike Yoder, a Republican county commissioner.

The pandemic has become politics. And on the eve of a contentious national election, with cases of the novel coronavirus surging in many parts of the country, places like Elkhart County — where President Trump is popular — feel they are being left alone to face outbreaks spiraling out of control. Trump has long disparaged efforts to fight the virus, clashing at times with his own public health officials. On Sunday, White House Chief of Staff Mark Meadows reinforced the president’s message, saying during a CNN interview, “We’re not going to control the pandemic.”

The result, according to officials in Elkhart County, is that state and federal authorities in recent weeks have showed little interest in helping them push for the tougher measures needed to control the pandemic — a change from earlier this year, when they worked together on encouraging mask-wearing or limiting public gatherings. And local officials worry they lack the authority or support to go it alone.

“I’ve talked with the mayor, county officials and corresponded with the Indiana State Health Department and the governor, and I’ve asked them to make stronger interventions,” said Rebecca Stoltzfus, president of Goshen College, who is part of the county’s coronavirus fight. “There’s not been much of a response.”

The business community, too, has noticed the lack of action, said Levon Johnson, president of the Greater Elkhart Chamber of Commerce.

“Unfortunately, politics has gotten in the way of the common-sense things that need to be done,” said Johnson.

A spokeswoman for Indiana Gov. Eric Holcomb, a Republican, referred questions from The Washington Post to the state health department. A statement from the state health agency said cities and counties are free to impose, “ANY additional health emergency restriction they determine necessary to control the spread of the virus.” The agency said it has provided advice and funding for testing clinics and education campaigns in Elkhart and across the state.

Elkhart County is rural and conservative, home to 200,000 people, 150 miles north of Indianapolis and best known for a manufacturing base that makes it part of the “RV Capital of the World.” A Democrat hasn’t been elected to county office in years. Trump won nearly 57 percent of the vote here in 2016.

And the area is accustomed to serving as a stage for presidential politics. Barack Obama, when he was president, visited the county in 2009 to highlight how much work was needed to get the

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‘Superspreader’ wedding, birthday party in Long Island lead to 56 infections

Within two weeks, 30 guests had tested positive for covid-19. Suffolk County health officials said an additional 159 people who had potentially been exposed to the virus by wedding attendees had been forced to self-quarantine to prevent further spread of the virus.

“One-third of all of those in attendance,” Suffolk County Executive Steve Bellone said in a news conference Wednesday. “Think about that for a second.”

County officials recommended a fine of $17,000 against the club for violating a county sanitary code as well as a statewide mandate restricting gatherings to no more than 50 people, and the State Liquor Authority told the New York Times it was investigating the incident. The country club did not immediately respond to a request for comment.

A Long Island birthday party that same day limited its guest list to 50 names, but has still led to another 26 coronavirus cases in the last two weeks, Bellone said.

Those ill-fated gatherings were not the only large events to spread the coronavirus across Long Island in recent weeks. Dozens of new cases have been tied to a string of parties in Suffolk County, and hundreds of residents have been forced to quarantine after possible exposure to the virus.

“This type of blatant disregard for the well-being of others is not only extremely disappointing; it will not be tolerated,” Bellone said Wednesday. “If you violate the rules, you’ll be caught and held responsible.”

SUFFOLK COUNTY EXECUTIVE BELLONE TO ANNOUNCE NEW ENFORCEMENT ACTIONS IN RESPONSE TO RECENT COVID-19 SPREADER EVENTS

Posted by Suffolk County Executive Steven Bellone on Wednesday, October 28, 2020

The spread of the virus along Long Island is particularly concerning in the state and county that were once epicenters of the pandemic. More than 500,000 people in New York have tested positive for the virus, and at least 33,219 have died since the start of the pandemic. Even as coronavirus rates have remained low in New York in recent weeks, some social gatherings have led to hot spots.

New York Gov. Andrew M. Cuomo (D) on Wednesday urged residents to avoid even family gatherings as the holidays approach.

“My personal advice is the best way to say, ‘I love you,’ this Thanksgiving, the best way to say, ‘I’m thankful for you,’ is to say, ‘I love you so much, I’m so thankful for you, that I don’t want to endanger you, and I don’t want to endanger our family and I don’t want to endanger our friends. So we’ll celebrate virtually.’” Cuomo said. “But that is my personal opinion.”

Despite admonitions to keep social gathering small and socially distanced, or to avoid them altogether, many people have decided to come together in large groups, especially in Long Island.

A Sweet 16 party hosted at a banquet hall on Sept. 25 became the county’s first “superspreader” event, Bellone said, after 37 guests tested positive for the virus after attending the 81-person soiree. At least 270 people had to quarantine after possibly being exposed to coronavirus

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Audit pans California’s lead cleanup at Exide battery plant

SACRAMENTO, Calif. (AP) — California will need to spend $650 million to clean up a heavily contaminated battery recycling plant in Southern California, but has less than half the money in hand and is behind its estimated schedule for removing dangerous lead dust affecting 100,000 nearby residents, the state auditor said Tuesday.

The Exide plant in Vernon recycled 11 million lead-acid batteries each year until it shut down in 2015. The state Department of Toxic Substances Control has been working since then to remove lead contamination from the surrounding area.

Auditors said the department will need another $390 million it currently doesn’t have to complete the project and is “significantly behind schedule” and unlikely to meet its goal of cleaning up lead contamination from the 3,200 most contaminated properties by next July.

Department director Meredith Williams responded that her agency “has cleaned up more properties, more quickly than any other residential lead cleanup in the nation.” She argued that it could not anticipate some of the developments that have slowed its progress, like rain delays or properties where soil would have to be removed by hand or with specialized equipment.

She called it “the largest, most logistically complex residential cleanup project the state of California has ever undertaken.”


The department has yet to clean up 31 of the 50 sites that are frequented by children who are most at risk, including two schools, three parks and 26 childcare centers, auditors said.

Williams said it has cleaned up seven schools and 17 daycare centers and believes the contaminated soil is contained by grass or mulch at the remaining sites.

Auditors said the state so far lacks even a plan to clean up the remaining 4,600 properties near the plant. Department officials blamed a lack of funding.

Assemblyman Miguel Santiago, a Democrat who represents the area and sought the audit, called the department’s progress “unacceptable” and called on officials to “fix their mistakes and create a realistic plan to clean up every single contaminated property.”

Lead dust, which can cause developmental disabilities, cancer and other long-term illnesses, contaminated the soil around thousands of homes where about 100,000 people live in Boyle Heights, east Los Angeles, Maywood, Huntington Park and Commerce.

The department is likely to drain its initial state funding before it can remove lead from 269 of the 3,200 most contaminated properties, auditors predicted. Auditors said Exide’s bankruptcy “leaves significant questions about the state’s ability to obtain reimbursement for the cleanup.”

They said state officials underestimated the total cost by failing to account for predictable costs including inflation. The department also paid $17 million more than it projected to clean 768 properties because it agreed to pay for cost overruns instead of requiring its largest cleanup contractor to pay any unexpected costs.

Williams said her department has finished more than 2,000 cleanups and recently stepped up its pace to decontaminate at a rate of 24 properties per week.

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Pence should ‘take our lead’ amid WH virus outbreak [Video]

A new coronavirus outbreak at the White House involving Vice President Mike Pence’s staff comes as the United States reported a near-record number of new cases on Saturday (October 24).

The United States reported 79,852 new infections on Saturday, closeclose to the previous day’s record of 84,244 new cases. Hospitalizations are also rising and have hit a two-month high and deaths are also trending upwards, according to a Reuters tally.

Late on Saturday a spokesman for Pence said Marc Short, Pence’s chief of staff, had tested positive for the new coronavirus. Pence and his wife tested negative earlier in the day and the vice president will not alter his schedule as he campaigns ahead of the Nov. 3 election, the spokesman said.

Speaking to reporters in Detroit on Sunday (October 25), Democratic vice presidential nominee Kamala Harris said Pence should adhere to CDC guidelines to avoid contracting and possibly spreading the virus.

“I think what we have modeled the right and good behavior, and they should take our lead, you know,” Harris said.

Earlier in the month, two members of Harris’ staff also tested positive for coronavirus.

Video Transcript

KAMALA HARRIS: Listen. He should be following the guidelines. We’re doing it. I think we have modeled the right and good behavior, and they should take our lead. They are admitting defeat. And I’ve been saying that, and Joe Biden has been saying that since the beginning. This is the greatest failure of any presidential administration in the history of America.

Here in Michigan alone, over 3,000 new cases just yesterday. This week alone, nationally we are breaking records for the number of people that are contracting a deadly virus. And this administration fails to take personal responsibility or responsibility in terms of leading the nation through this dangerous and deadly mass-casualty event. And that’s why they have forfeited their right to a second term in office.

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Rush for results could lead to inferior Covid vaccine, say scientists

Scientists have warned that early adoption of a Covid vaccine with only moderate effectiveness could disrupt efforts to test and create improved versions. Immunising against the disease is not going to be a simple business of turning off the virus once the first vaccine appears, they say. In fact, there could be considerable confusion as researchers struggle to pinpoint the best versions for different vulnerable groups, such as the elderly.



Photograph: David Cheskin/PA


© Provided by The Guardian
Photograph: David Cheskin/PA

“The vaccines coming through fastest are the most experimental. It is possible they won’t be all that great and that others – created using more tried-and-tested but slower methods – might be better,” said Professor Adam Finn of Bristol University. “But to prove that point will become very difficult if lots of individuals have already been given the first vaccine. It will need vast numbers of people to demonstrate which is best or if a different vaccine is more suitable for particular groups, like the elderly.”



Some of the vaccines that are coming through fastest are also the most experimental.


© Photograph: David Cheskin/PA
Some of the vaccines that are coming through fastest are also the most experimental.

Finn said such confusion could cause setbacks in dealing with Covid, adding: “We should be preparing to meet this challenge and work out ways to compare the effectiveness of early vaccines – but at present we are not doing that well enough.”

A total of 198 Covid vaccines are now under development across the globe with four key versions undergoing final phase 3 trials. These include Pfizer’s BNT162b2 and the Oxford AstraZeneca vaccine.

Results of those trials – in which each is compared with a placebo – are expected in weeks or months. Once the first vaccine that shows efficacy in countering Covid-19 is revealed, there will be enormous pressure to use it immediately. Key candidates would be healthcare workers who deal with Covid cases and others at high risk of becoming infected.

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But for groups such as the elderly, who tend to have weaker immune systems, caution will be required.

“The problem is that early vaccine trials are not likely to show how well these products work in these populations,” said Kanta Subbarao, a World Health Organization director, in an editorial in Nature last week. “We know vaccines often work better in young, healthy adults, which is why they are enhanced with a higher dose or an adjuvant to boost immunity for diseases such as flu and shingles. It is also unclear how well clinical trials will assess effectiveness in those in minority ethnic communities.”

In other words, by spring, several vaccines may have passed their trials without any mechanism being in place to select which is the most effective for different groups. Nor is the problem confined to the UK.

“The complexity and chaos and confusion that will happen in a few short months has hardly

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Doctors need to lead by example at the voting booth

As the needle moves past 220,000 deaths from Covid-19 and the Supreme Court prepares to hear California v. Texas, which threatens to eliminate health insurance for almost 20 million Americans, it’s no surprise that health care remains one of the top issues for voters this election.

Historically, doctors vote less than other professionals. From 2006 to 2018, doctors were less likely to vote than the general public, particularly if they were not already registered to vote.

That’s what we found in a study published this week in JAMA Internal Medicine. After reviewing voting histories for more than 100,000 doctors in California, New York, and Texas, we found that 37% of eligible physicians voted in elections over the last decade, compared to 51% of the general population. Half of doctors who were eligible to vote were not registered to vote in the first place.

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While this is troubling, it can be fixed. Programs like Vot-ER and VoteHealth 2020 are working to help doctors register to vote around the country. Some hospitals are also stepping up to the plate. These efforts are important, because we found that doctors who were registered to vote are more likely to show up to the polls than their fellow Americans.

It would help if registering to vote was a simple and secure process. Eleven states, including our home state of Texas, do not permit online voter registration and instead require voters to mail in a physical form. And the majority of states do not allow voters to register and vote on the same day.

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These rules, meant to suppress voting, make it challenging for doctors to maintain civic engagement over a decadelong professional training process. In a survey we published this week in the Journal of General Internal Medicine, we found that a majority of doctors in training — residents — cite long work hours as the most common barrier to voting in this election. Nearly one-quarter of doctors felt that their vote does not make much of an impact, and a smaller group were hindered by not knowing when and where to vote. This is the first study of its kind to analyze barriers to voting for the U.S.’s youngest physicians.

Hospital training programs can do more to facilitate voter engagement among doctors by giving them paid time off to vote early, helping them register to vote by mail where permitted, and even arranging for voting at the hospital. More than 1,600 companies have already joined the Time To Vote campaign, giving employees time off to make their voices heard at the ballot box. Some companies, such as Old Navy, Target, and Warby Parker, are even paying employees to serve as poll workers.

It’s time for hospitals and residency programs to address the culture of prioritizing working over voting, particularly among young doctors. They can help doctors easily register to vote and provide them with information about early voting or how to request absentee ballots. For doctors living in California, Colorado, Maryland,

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Trainerize Launches New On-demand and Live Video Coaching Features, Empowers Personal Trainers and Clubs to Lead the Next Wave of Digital Fitness

Video coaching features keep human connection at the heart of online training, proving a must-have for fitness businesses during the pandemic and beyond

Discover Trainerize’s Video Coaching Features

Trainerize launches new on-demand and live video coaching features designed to help fitness clubs and personal trainers engage their clients in new ways both during the pandemic and beyond.
Trainerize launches new on-demand and live video coaching features designed to help fitness clubs and personal trainers engage their clients in new ways both during the pandemic and beyond.
Trainerize launches new on-demand and live video coaching features designed to help fitness clubs and personal trainers engage their clients in new ways both during the pandemic and beyond.

VANCOUVER, British Columbia, Oct. 19, 2020 (GLOBE NEWSWIRE) — As the leading client engagement app for personal trainers, studios, and clubs, Trainerize is upping the virtual training game with two all-new video features: on-demand video workouts and live 1-on-1 video call appointments.

In the face of gym closures in early 2020, Trainerize moved the fitness industry online, setting up trainers and gyms to train clients and engage members remotely. As the pandemic continues, fitness businesses need to continue to evolve to ensure long-term success, and Trainerize will be there to help make that happen.

With all-new video training features, Trainerize continues to elevate the human connection central to the platform and emphasize their focus on client engagement. Trainers can now provide video training, on-demand classes, and one-on-one video calls within the Trainerize ecosystem.

These new video features offer the most human experience possible, says Trainerize co-founder and Managing Director, Sharad Mohan. “To me, video is the most engaging medium available beyond face-to-face interactions. For us, the relationship between a trainer and their client, and the personalization, accountability, and motivation it enables, is a crucial part of a successful fitness journey.” With these new features, trainers and coaches can provide face-to-face interactions to their clients, safely and conveniently.

On-demand video workouts

With on-demand video workouts, Trainers and studios can transform their clients’ fitness routines by building libraries of video content—accessible by paying clients anytime, anywhere. Perfect for instructor-led workouts or classes, clients get to feel like their trainer is right there with them, whether they’re at the gym or working out in their living room.

For trainers looking to build on-demand, subscription-style business models, on-demand video will power a self-selecting experience for their clientele. The client can browse through the trainer’s offering and choose the workout that appeals most to them.

1-on-1 live video call appointments

Thanks to 1-on-1 video call appointments, trainers can move consultations and assessments to a virtual format, allowing convenient, efficient check-ins that keep trainers and clients connected. This feature also enables 1-on-1 video coaching sessions. Remote sessions, where clients can receive personalized instructions and real-time feedback, will drive accountability and spark motivation. Video calls are hosted in-app, removing the need for another software, accessible from phone, tablet, and desktop.

Monetizing video training

While these new features will undoubtedly shake up online programs, they’ll also change the way trainers and studios structure their businesses and monetize services, providing a new source of revenue. As the industry continues to reel

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