SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has accepted the companys supplemental Biologics License Application (sBLA) and granted Priority Review for Tecentriq (atezolizumab) as adjuvant treatment following surgery and platinum-based chemotherapy for people with non-small cell lung cancer (NSCLC) whose tumors express PD-L11%, as determined by an FDA-approved test. The FDA is reviewing the application under the Real-Time Oncology Review pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. The FDA is expected to make a decision on approval by December 1, 2021.

New treatment options are urgently needed in early-stage non-small cell lung cancer to help the nearly 50% of people who currently experience a recurrence following surgery, said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. Tecentriq is the first cancer immunotherapy to show a clinically meaningful benefit in the adjuvant lung cancer setting, and were working closely with the FDA to bring this significant advancement to patients as quickly as possible.

This application is based on disease-free survival (DFS) results from an interim analysis of the Phase III IMpower010 study, the first and only Phase III study of a cancer immunotherapy to demonstrate positive results in the adjuvant lung cancer setting. The study showed that treatment with Tecentriq following surgery and platinum-based chemotherapy reduced the risk of disease recurrence or death (DFS) by 34% (hazard ratio [HR]=0.66, 95% CI: 0.50-0.88) in people with Stage II-IIIA NSCLC whose tumors express PD-L11%, compared with best supportive care (BSC). In this population, median DFS was not yet reached for Tecentriq compared with 35.3 months for BSC. Follow-up on the IMpower010 trial will continue with planned analyses of DFS in the overall intent-to-treat (ITT) population, including Stage IB patients, which at the time of analysis did not cross the threshold, and overall survival (OS) data, which were immature at the time of interim analysis. Safety data for Tecentriq were consistent with its known safety profile and no new safety signals were identified. Results from the IMpower010 trial were presented at the 2021 ASCO Annual Meeting.

About the IMpower010 study

IMpower010 is a Phase III, global, multicenter, open-label, randomized study evaluating the efficacy and safety of Tecentriq compared with BSC, in participants with Stage IB-IIIA NSCLC (UICC 7th edition), following surgical resection and up to 4 cycles of adjuvant cisplatin-based chemotherapy. The study randomized 1,005 people with a ratio of 1:1 to receive either Tecentriq (up to 16 cycles) or BSC. The primary endpoint is investigator-determined DFS in the PD-L1-positive Stage II-IIIA, all randomized Stage II-IIIA and ITT Stage IB-IIIA populations. Key secondary endpoints include OS in the overall study population, ITT Stage IB-IIIA NSCLC.

About lung cancer

According to the American Cancer Society, it is estimated that more than 235,000 Americans will be diagnosed with lung cancer in 2021, and NSCLC accounts for 80-85% of all lung cancers. Today, about half of all people with early lung cancer still experience a cancer recurrence following surgery, but treating lung cancer early, before it has spread, may help prevent the disease from returning and provide people with the best opportunity for a cure.

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

Tecentriq U.S. Indications

Tecentriq is a prescription medicine used to treat adults with:

A type of lung cancer called non-small cell lung cancer (NSCLC).

A type of lung cancer called small cell lung cancer (SCLC).

It is not known if Tecentriq is safe and effective in children.

Important Safety Information

What is the most important information about Tecentriq?

Tecentriq can cause the immune system to attack normal organs and tissues in any area of the body and can affect the way they work. These problems can sometimes become severe or life threatening and can lead to death. Patients can have more than one of these problems at the same time. These problems may happen anytime during their treatment or even after their treatment has ended.

Patients should call or see their healthcare provider right away if they develop any new or worse signs or symptoms, including:

Lung problems

Intestinal problems

Liver problems

Hormone gland problems

Kidney problems

Skin problems

Problems can also happen in other organs.

These are not all of the signs and symptoms of immune system problems that can happen with Tecentriq. Patients should call or see their healthcare provider right away for any new or worse signs or symptoms, including:

Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include:

Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if patients undergo transplantation either before or after being treated with Tecentriq. A healthcare provider will monitor for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider will check patients for these problems during their treatment with Tecentriq. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may also need to delay or completely stop treatment with Tecentriq if patients have severe side effects.

Before receiving Tecentriq, patients should tell their healthcare provider about all of their medical conditions, including if they:

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used alone include:

The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:

Tecentriq may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of Tecentriq. Patients should ask their healthcare provider or pharmacist for more information about the benefits and side effects of Tecentriq.

Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.

Report side effects to Genentech at 1-888-835-2555.

Please see http://www.Tecentriq.com for full Prescribing Information and additional Important Safety Information.

About Genentech in cancer immunotherapy

Genentech has been developing medicines to redefine treatment in oncology for more than 35 years, and today, realizing the full potential of cancer immunotherapy is a major area of focus. With more than 20 immunotherapy molecules in development, Genentech is investigating the potential benefits of immunotherapy alone, and in combination with various chemotherapies, targeted therapies and other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system.

In addition to Genentechs approved PD-L1 checkpoint inhibitor, the companys broad cancer immunotherapy pipeline includes other checkpoint inhibitors, individualized neoantigen therapies and T cell bispecific antibodies. For more information visit http://www.gene.com/cancer-immunotherapy.

About Genentech in lung cancer

Lung cancer is a major area of focus and investment for Genentech, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have five approved medicines to treat certain kinds of lung cancer and more than 10 medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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FDA Grants Priority Review to Genentech's Tecentriq as Adjuvant Treatment for Certain People With Early Non-small Cell Lung Cancer - Business Wire

Recommendation and review posted by Bethany Smith

The day before he was euthanized by veterinarians in March of 2018, Sudan collapsed in the dirt at the Ol Pejeta Conservancy in Kenya, where he had lived since 2009. He was worn out and in pain.

At age 45, Sudan was the final progenitor of the earths most endangered animal species: the northern white rhinoceros. As the last male northern white in the world, he was both a global icon for conservation and a two-and-a-half-ton targetbecause the horn of even the most precious rhino is not safe from poachers. He lived out his final years under 24/7 armed protection at the conservancy, along with two of his female relatives.

Half a world away, Barbara Durrant felt it. She had never met Sudan, but she knew Nola. Most people in San Diego knew Nola, though not the way Durrant did. Nola was a northern white rhinoceros, one of only four that remained by the middle of the last decade, along with Sudan and his kin. She lived at the Nikita Kahn Rhino Rescue Center, located at the San Diego Zoo Safari Park, about 30 miles north of the city, and not far from where Durrant reports to work every day at the zoos Wildlife Biodiversity Bank.

Nola had also been euthanized, after age and infection caught up with her, in 2015. She was 41.

She was just the most amazing animal, says Durrant, recalling Nolas wide mouth, her skin the color of clay stone, and her distinctive horn, which curved toward the ground. Its not only losing that animal that you know personally and you love; its another step in losing the whole species.

Damon Casarez

Durrant is director of reproductive sciences at the San Diego Zoo Wildlife Alliance and one of a handful of scientists around the world who are trying to save the northern white rhino. In Europe, another group, under the direction of wildlife researcher Thomas Hildebrandt, is also working on the problem. And while their scientific approaches may be slightly divergent, the scientists end goal is the same: to rescue the northern white rhino before the bell of extinction rings.

Hildebrandt is the project head for BioRescue, an international consortium of scientists and conservationists. His group is harvesting eggs from female rhinos in Kenya; eventually the team hopes to create embryos using the frozen sperm of long-deceased northern white rhino males.

Meanwhile, Durrants team in San Diego is undertaking an ambitious bioengineering challenge. Inside the Wildlife Biodiversity Bank is the Frozen Zoo, a cryopreserve where 10,000 still-living skin cells from 1,100 different animal species are stored in tanks of liquid nitrogen at extremely low temperatures. Among them are 12 cell lines taken from 12 different northern white rhinos, dating back to 1979.

The Frozen Zoo is a cryopreserve where 10,000 still-living skin cells from 1,100 different animal species are stored in tanks of liquid nitrogen.

As recently as two decades ago, the next step amounted to the stuff of science fiction: taking those skin cells, reprogramming them into sperm and egg, combining them in a test tube, and then implanting that embryo into a surrogate host. Recreating a whole new northern white rhino. And then another, and another, and then, once nature took its course, dozens more. Breathing life back into that which is dead. De-extinction, in other words, the purposeful resurrection of animals that have died off. Animals like Sudan.

People are seeing a species go extinct right before their eyes, says Durrant. Can we really even make a dent? The answer is, well, we have to. We have to do this.

Astronomical costs and enormous risks stand in the way. An investment of at least $20 million is required to realize the ultimate goal of reconstituting a population of wild northern white rhinoceroses. Retrieving oocytes (eggs) is a delicate endeavor, because if scientists puncture blood vessels near the uterus, the animal will bleed to death. And preserving a species through bioengineering is a fraught, messy process, one that calls into question the sophistication of current reproduction techniques and the merits of meddling with nature.

If the project succeeds, it would be a scientific breakthrough like no other. What was once outside the realm of possibility is almost within our grasp. At some point in the not-too-distant future, a rhinoceros calfa cultivated northern whitemay very well take its first steps.

Ann and Steve Toon / Alamy Stock Photo

Of the worlds five rhino species, the northern whiteone of two subspecies of white rhinosdrew the short straw. Northern whites once roamed East and Central Africa, enjoying an herbivorous lifestyle with few natural predators. Humans prized them for their horns, which can grow over four feet. In Europe circa 1900, rhino horn was fashioned into ornamental accoutrements, like walking sticks and pistol grips. It remains a common ingredient in traditional Chinese medicine, which prescribes powdered rhino horn mixed with boiling water as a cure for fever, gout, and rheumatism.

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Poaching and war rapidly thinned their numbers, from the thousands to the hundreds to the tens. Nola arrived in San Diego in 1989; by the end of that decade, fewer than 40 northern whites remained in the northeast corner of what is today the Democratic Republic of the Congo. The last northern white was spotted in the wild in 2006. By then, the only survivors were those that had been relocated to zoos in the 1970s. They included Sudan, his daughter, Najin, her daughter, Fatu, and another bull, Suni, who were all taken to Kenyas Ol Pejeta Conservancy in 2009. They were the eligible breeders, yet no calves were born. Suni died four years before Sudan.

Four became three, then three became two, and now only Najin and Fatu remain. They are old and getting older, and even if they could mate, veterinarians have determined that neither is capable of carrying a pregnancy to term. Its a foregone conclusion then, yes? The line of northern white rhinos dies with Najin and Fatu.

TONY KARUMBAGetty Images

Sometimes we feel kind of helpless, says Durrant. Were battling such a huge wave of extinction.

Southern white rhinos, on the other hand, largely escaped their cousins misfortune. There were fewer than 100 remaining in the late 1800s, but a tenacious conservation effort followed and continues today. More than 20,000 of these rhinos currently roam the earth, mostly in South Africa. The San Diego Zoo Wildlife Alliance has six females, which will play a crucial role in its effort to produce a pure northern white rhino. Summarizing the idea is easy enough: An embryo made of northern white sperm and egg is implanted into a surrogatea female southern white rhino. Sixteen months later, a northern white calf is born.

I can say pretty clearly that this would be the first time a robot has ever been used in animals like this.

Durrant and her colleagues have already cleared several hurdles in the past five years. Using ultrasound technology, the team deciphered the inner workings of the rhinos reproductive system. Mapping the cervix was a key first step. A rhino cervix is a tight, convoluted maze of rings, a foot of anatomy thats fairly common to the two subspecies. Navigating it can be tricky. To practice, the zoo artificially inseminated two southern white females in 2018 using preserved southern white male sperm. Two healthy calves, Edward and Future, were born in 2019.

Damon Casarez

When female rhinos are ovulating, circulating estrogen helps relax the rings of the cervical tissue. For that reason, Durrant and her team were able to inseminate the zoos rhinos by hand. The future embryo transfer, however, will be much tougher. Once the team has produced a viable pure northern white rhino embryo, they will stimulate ovulation in one of the southern white rhinos residing at the Safari Park. Then theyll have to wait another 10 days to let the embryo mature in vitro before implantation. But the surrogates estrogen levels will have decreased by then, causing her cervix to tighten once more. Navigating it by hand will be impossible, because the risk of severely damaging cervical tissue is too great. Instead, Durrant and her team are currently collaborating with roboticists at the University of California San Diego to develop a workaround.

I can say pretty clearly that this would be the first time a robot has ever really been used in animals in any kind of major computation effort like this, says Michael Yip, a professor of electrical and computer engineering at UCSD and director of the Advanced Robotics and Controls Laboratory.

Courtesy UCSD Jacobs School of Engineering

Yips lab is outfitting a noodlelike catheter with miniaturized robotic controls. Imagine a tiny metal cylinder, thinner than the circumference of a headphone jack and sheathed in a flexible filament. A camera on one end will give zoo workers a view of where theyre going, while a PlayStation-like controller will bend the catheter with sub-millimeter precisionenough to ensure that they can navigate the rings without scraping tissue or puncturing blood vessels.

Well do very little, if any, tissue damage, but well be able to get through that tightened-down cervix, Durrant says.

In March 2020, Durrant completed the zoos first oocyte pickups. Because the scientists had already done the ultrasound mapping, they had a clear idea of where the ovaries and follicles were located.

Eggs were collected from each of their six southern white females using a four-foot-long double-lumen (two channeled) needle, which is capable of flushing out the follicles and sucking out the oocytes. They collected a total of 22; in the lab, each oocyte was fertilized with a single sperm. In the end, while half of the fertilized oocytes matured, none developed into blastocysts, the final stage of embryo growth. But the effort allowed the researchers to start piecing together some novel rhino science: What nutrients do rhino embryos need, in vitro, to mature?

This was a critical juncture in the teams de-extinction work, as valuable practice for the fertilization procedure to come. You dont transfer an embryo on the initial try. Fail to navigate the cervical maze, and you might damage tissue, imperiling the pregnancy. Fail to mature a reprogrammed egg into a blastocyst, and theres no embryo to even transfer. Everything Durrants team has done with southern whites is a dress rehearsal for the premiere event, when it finally comes time to make a southern white female the surrogate mother of the main character: a northern white rhino embryo.

Damon Casarez

Damon Casarez

The task of generating the sperm and egg falls to the San Diego Zoo Wildlife Alliances Marisa Korody, a conservation geneticist who is trying to create stem cells from the functionally extinct northern white rhinos. She starts with cryopreserved fibroblasts, cells that compose the connective structural tissue of all animals. The Frozen Zoo has fibroblasts generated from skin samples of 12 different northern whiteseight of which are unrelatedthat contain enough genetic diversity to save the species. These fibroblasts are then reprogrammed into induced pluripotent stem cellsthat is, cells that can turn into any cell type in the body. By directing these stem cells to specific developmental paths, the researchers can generate primordial germ cells, precursors to what eventually become sperm and eggs.

This is as far as the science goesat least for now, and at least with rhinos. Korody is optimistic shes managed to generate the germ cells. Generating northern white rhino sperm and northern white rhino egg, though, is a long-term process, one that involves figuring out the hormones and growth signals needed to get the germ cells to differentiate further.

Maybe in 10 years or so, well be close, she says.

Damon Casarez

Its a different strategy from the one Thomas Hildebrandt and BioRescue are focused on right now. While the team in San Diego is trying to generate northern white rhino embryos from cells, BioRescue is attempting to fertilize eggs collected from Fatu and Najin with cryopreserved northern white rhino sperm.

We can use this approach to transfer the embryos into a southern white rhino surrogate, and then let the calf grow up with Najin and Fatu, says Hildebrandt, who also leads the department of reproduction management at the Leibniz Institute for Zoo and Wildlife Research in Germany.

In 2019, Hildebrandts team accomplished a scientific first: It transferred a rhino embryo fertilized in vitro into the uterus of a female rhino. In this case, it was a southern white. As of July 2021, BioRescue has completed seven southern white rhino embryo transfers.

In the next few years, Hildebrandt says, BioRescue will be ready to transfer a northern white rhino embryo into a surrogate southern white female.

In the 55-million-year evolutionary history of the rhino, 10 years is nothing but a heartbeat. In the here and now, however, a decade is enough time to exacerbate an annihilation crisis thats already underway.

In 2019, a landmark report from the United Nations revealed that a million animal and plant species are careening toward extinction. A subsequent report issued by the World Wildlife Fund in 2020 indicated that wildlife populations have declined by two-thirds in the past half century due to human activities; deforestation, insecticides, and poaching are all complicit. Various species we hardly think of but are nonetheless important for humans and ecosystems to thrive are in the crosshairs.

If we can think of this as a leaky bucket right now, the bucket is pouring out water and more and more species are falling out, says Tierra Curry, a senior scientist with the nonprofit Center for Biological Diversity, based in Arizona. Trying to put a couple more species back in the bucket isnt going to fix the problem.

Criticism of de-extinction efforts often begins with something like Currys premise. Her preference would be to fight like hell for everything still alive. After all, the natural world is at the brink, but animals arent the problem.

Instead, the ultimate problem is uniquely and definitely humans, says Ross MacPhee, a curator in the mammalogy department of the American Museum of Natural History in New York City. Theres no way to guarantee that a population of northern white rhinos wouldnt need around-the-clock protection the way Najin and Fatu do today. Southern white rhinos, despite their resurgence, are already considered a species on the way to endangered, as lust for rhino horn continues unabated. Some horns fetch a purse of $300,000. How much might a rare northern white rhino horn go for?

While the San Diego Zoo Wildlife Alliance hopes to generate a self-sustaining population of northern white rhinos back in part of their native range, Durrant says that would only happen if its safe to put the animals there. But not making the effort isnt an option, she says.

Everything is connected, says Durrant. When you take any species, plant or animal, out of an ecosystem, it starts to unravel.

As it stands now, most of the African species of rhinosthe southern white and black rhinosare concentrated mainly in southern Africa. Very few black rhinos are roaming around central Africa where northern white rhinos once predominated: The pointed mouth of the black rhino is good for eating branches and leaves, while the wide mouth of the white rhino is better adapted for grazing on grass.

Scientists keenly interested in saving the northern white rhino often cite the good that such a keystone species provides. A megafauna creature like the white rhino directly and indirectly affects the well-being of dozens of other creatures. By eating long grass, they help keep vegetation at a reasonable level so predators can see their prey. Their feet carve avenues in the grass so prey can escape. Their droppings fertilize the grass and provide nutrients for insects. Its a tiny biosphere where nonhuman life thrives. Upset the balance, and that life has to migrate elsewhere. Maybe to urban ecosystems. Maybe carrying disease.

Damon Casarez

Under any other circumstances, a group of people kneeling around Fatu inside the Ol Pejeta Conservancy would be a cause for concern. But on this Sunday in December 2020, the scientists and veterinarians in attendance were monitoring Fatu as she lay under general anesthesia. Near her backside was Hildebrandt. He was collecting eggs.

Over the past two years, with the permission of the Kenyan government, Hildebrandt and BioRescue have performed six separate egg pickups on Najin and Fatu. The latest one, in December 2020, yielded 14 oocytes from Fatu. Collection is done by anesthetizing the rhino and then inserting an ultrasound wand into the rectum. The wand is there only to provide a picture, a way to guide the needle that flushes out the rhinos follicles and grabs the eggs. Both times the eggs were rapidly transported to Avantea, an advanced biotechnology lab in Italy. There they were fertilized with frozen semen that had been extracted from Suni before he died. To date, BioRescue has cryopreserved nine embryos that combine northern white sperm and northern white egg.

The rhino hasnt failed in evolution. Its at the brink of extinction because humans have poached it and killed it.

Its a monumental step, one that represents the closest any group of scientists has come to bringing a northern white rhino calf into the world. Hildebrandt doesnt just consider it fascinating science; he likens it to a moral imperative. Picking and choosing which animals to de-extinct is easy when nature hasnt selected against them.

The rhino hasnt failed in evolution. Its at the brink of extinction because humans have poached it and killed it, he says. So it is actually our human responsibility to fix this problem, because we have caused it.

Courtesy Leibniz Institute for Zoo and Wildlife Research

While BioRescues current endeavor is separate from the work being conducted by Durrant, Korody, and others at the San Diego Zoo Wildlife Alliance, the two groups are working toward common goals. Hildebrandt and his counterparts in San Diego held the first international conference on rescuing the northern white rhino in 2015 in Vienna. He says the work being conducted on pluripotent stem cells in San Diego is an important component of the overall effort. BioRescue has created embryos made with eggs from Najin and Fatu and sperm from Suni; the embryos the San Diego team hopes to create will come from multiple other northern white rhinos, which will increase the genetic diversity of a future population. In turn, that should help improve the animals overall health by serving as a safeguard against disease.

Yet Hildebrandt wants to bring a baby northern white rhino into the world as quickly as possible. While the two subspecies are related, northern white rhinos are wider, with straighter backs, flatter skulls, and a different neck structure. The differences are stark enough that a baby northern white rhino might not learn how to graze properly if it comes up in a herd of its southern white cousins. Hildebrandt wants the animal to socialize with Najin and Fatu before they, too, die. Sudans granddaughter is only in her early 20s and still playful. Najin, on the other hand, is in her early 30s, and lives with a large tumor on her abdomen.

Theres a lot of things morphologically which are links to behaviors, says Hildebrandt. The social knowledge, how to behave as a northern white rhino, is something we can preserve. But there is no way to do that unless we produce a calf very soon.

Still, a de-extinction project inevitably requires two finite resources: time and money. Hildebrandt thinks it will take about 20 years to reintroduce a healthy population of the animals back to Africa, at a cost of approximately $1 million per calf. But how much is one northern white rhino worth to the world?

Damon Casarez

Damon Casarez

Depending on BioRescues progress this year, there might be a baby northern white rhino walking with Najin and Fatu within two years. The bioengineering tools required to accomplish the incredibleresurrecting a herd of 6,000-pound animalsare here, in the hands of Durrant, Korody, Hildebrandt, and their respective teams of researchers.

We have the technology. We can rebuild them. Now comes the hardest question of all: Should we?

Its perhaps too soon to tell if a new birth in a species that is on the brink of extinction would be heralded as a success. After all, humans nearly killed off every northern white rhino in existence. Whats to say that people wont poach the animals for their horns, and do it flippantly, openly, even expectantly? You created a bunch of northern white rhinos before, we may cry out. Just do it again. This, we might incorrectly believe, is the promise of something like the Frozen Zoo. We preserve natural history, only to reanimate it according to our whims.

Yes, science can save species. But dont rely on science to save species, says Durrant. We cant do this for every species. We dont want to do this for every species. We want species to be preserved in their native habitats before they go extinct.

Cryopreservation and embryo transfers arent blueprints for managing the planet. But they might preserve a legacy that the death of Sudan left behind. If were paying attention, maybe one new rhino will wake us up.

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The Bioengineering Gambit to Save the Northern White Rhino - Popular Mechanics

Recommendation and review posted by Bethany Smith

July13, 20216 min read

Opinions expressed by Entrepreneur contributors are their own.

On June 13, Laura Wilkinson did not qualify in her attempt to join this years U.S. Olympic Diving Team finishing inonly 10th place at the final qualifying event in Indianapolis.

But Lauras performance was so inspiring that she received a standing ovation from everyone who attended. Why? Because at age 43, Laura is now more than twice as old as she was when she won her gold medal at the 2000 Olympics in Sydney.

While it may not be surprising that she didnt qualify for this years team, the very idea that she was in shape to compete at all clearly shows how much progress weve made in not only extending longevity, but also living healthier as we age. In the last century alone, average life expectancy in the U.S. has increased from around 60 to nearly 80 years.

At this rate, it wont be long before 100 years old becomes "the new 60."

Indeed, new scientific discoveries and innovative research into health and medicine continueto reveal new insights into how the human body works and how we can delay the impact of aging many that we couldnt even imagine only a few short years ago.

Related:Former Quarterback Jim McMahon Calls AdvancedStem-Cell Therapy 'Truly Miraculous'

As the CEO of BioXcellerator, a leading stem-cell treatment and research center, Ive made it my mission to work with a team of talented scientists and physicians to further progress to help everyone worldwide live longer and enjoy better health.

Weve long known about the benefits of a healthy lifestyle and diet. And physicians now have access to more advanced surgical procedures and new medications. But as it turns out, the secret to maintaining excellent health and vitality isnt so secretive at least at the cellular level.

You see, your body already knows how to heal itself, through a natural process based on stem cells. Youre not aware of it, of course, but all of the cells in your body neurons in your brain, cardiac cells in your heart, immune cells that circulate through your bloodand all other cells are constantly being replaced with new cells.

Yet even though each type of cell functions differently, they all begin as stem cells created in your bone marrow, then differentiated to become a specific type of cell.

As we age, however, stem-cell production declines. Thats why stem-cell therapy is such an exciting frontier in medicine today:After an infusion of millions of high-potency stem cells, your body goes right to workusingthose cells to heal damaged tissue, reduce inflammation, improve immunity, and boost vitality and performance.

Even damage from injuries sustained many years ago can be healed from an infusion of stem cells.

Related:This Is HowStem-CellTherapy Treats Serious Brain Injuries

Although more effective medical treatments for various diseases and disorders certainly benefits humanity, heres a better approach: Prevent disease in the first place. Yes, nutrition and exercise make a big difference, but recent studies clearly show how enhancing immunity and reducing chronic inflammation can add even more years to our lives and improve our health.

Yet, while were aware of what we eat and our level of physical activity, we dont fully appreciate the battle our immune cells fight every minute of every day 24/7. Theyre constantly on patrol throughout your body, seeking out and destroying various viruses and other microbes that threaten our health and lives. That may seem overly dramatic, but one things for sure:Without immunity, there would be no humanity. Our species couldnt exist.

Another battle that rages inside us comes in the form of inflammation. Although inflammation is the bodys natural signaling system that various tissues need repair and healing, when continued ongoing inflammation becomes chronic, it can actually cause even more serious damage throughout the entire body. Recent studies suggest that while an anti-inflammatory diet and other lifestyle choices (for example, getting enough sleep) can reduce excess inflammation, stem cells also provide anti-inflammatory benefits and boost immunity too.

At BioXcellerator, we offer stem-cell therapy to treat a wide range of diseases and injuries, but regardless of what patients get treated for, one common resultrings loud and clear:Patients report that they feel better. They have more vitality, moreenergy, enhanced cognitive function and a greater overall sense of well-being.

After all, the body doesnt know why its receiving new stem cells, so it uses those cells to both heal specific damage and better modulate the immune system and regulate inflammation.

Related:High-Potency 'GoldenCells' Offer Hope to Those With Severe Brain Injuries

With even more advanced testing now available, such as whole-body and brain MRIs, genome sequencing andliquid biopsy using cell-free DNA, we can detect the onset of many serious diseases and disorders far earlier, including heart disease, cancer, and autoimmune and degenerative conditions.

Theres overwhelming evidence that many cancers and heart disease can be treated more effectively when detected at an early stage. These more accurate and precise tests also enable us to provide personalized recommendations forchanges in diet and lifestyle that can help prevent or delay the onset of many diseases and conditions altogether.

Many athletes turn to stem cells to maintain peak performance duringtheir careers, and to extend them;they also receive treatment after they retire to alleviate chronic pain from injuries suffered over many years.

No, its not so miraculous. Its all based on science. As we learn more about extending longevity, immunityand performance, Im more convinced than ever that age 100 will become the new 60.

Excerpt from:
The Future of Health: Why Age 100 Will Soon Become 'the New 60' - Entrepreneur

Recommendation and review posted by Bethany Smith

Introduction

Profilin 1 (PFN1) is a ubiquitous small-molecule protein that exists in all eukaryotes.1 PFN1 was first identified as a G-actin sequestering molecule,2 and subsequently, its true functions in actin polymerization and F-actin dynamics were revealed.3 In the following decades, the structure of PFN1 was recognized to have 3 domains: an actin-binding domain,4 a poly-L-proline (PLP)-binding domain,5 and a phosphoinositide-binding domain.6

PFN1 plays a vital role in many cell functions, including membrane trafficking, endocytosis, cell cycle, motility, proliferation, cell survival, transcription, stemness, and autophagy (Figure 1). Abnormal expression or deletion of PFN1 can affect the normal physiological activity of cells and lead to disease development. PFN1 has been deeply studied in a variety of diseases, some genetic (eg, amyotrophic lateral sclerosis)7 and some chronic (eg, hypertension).8

In the past 10 years, PFN1s role in cancer has received increasing attention. In this review, we summarize the studies of PFN1 in cancer that have been completed in recent years, discuss the roles of PFN1 in cancer, and discuss the implications for tumor diagnosis and therapy in the future.

Early diagnosis of cancers is still a major challenge worldwide, and early detection can notably reduce their associated morbidity and mortality.9 PFN1, a critical actin-binding protein, is found to be dysregulated in many cancers, which makes it possible to use it as a biomarker for diagnosis and prognosis. PFN1 mainly plays a role in the cytoplasm, but it can also be found in the nucleus and can even be secreted into the extracellular space. The rich knowledge in the proteomics field makes the detection of proteins for new diagnostic markers and targets for therapy possible.10

In some tumor types (such as renal cell carcinoma [RCC], gastric cancer, and others), high expression of PFN1 indicates later stage and worse prognosis. Via differential proteomics, PFN1 has been identified in metastatic and primary RCC, and further analysis indicated that high PFN1 expression was associated with poor outcome and that PFN1 could be used as a potential prognostic marker in RCC.11 In clear-cell RCC (ccRCC), the expression of PFN1 was decreased in early-stage tumors compared with normal tissues. However, its expression in stage IV ccRCC was significantly increased. PFN1 was selected as a candidate marker of late-stage ccRCC.12 Results of a recent study determined that the vast majority of ccRCC tumors tend to be selectively PFN1-positive in stromal cells only; dramatic transcriptional upregulation of PFN1 was found in tumor-associated vascular endothelial cells in clinical specimens of ccRCC.13 Tissue microarray results also showed that PFN1 was increased in metastatic ccRCC compared with primary tumors. Univariate analysis suggested that higher PFN1 expression was associated with shorter disease-free survival (HR, 7.36; P = .047) and lower overall survival.14

In gastric cancer, Tanaka et al found that PFN1 was highly expressed in fetal rat stomach. Additionally, PFN1 was overexpressed in some human and rat gastric cancers.15 The results of later studies indicated that PFN1 expression was higher in gastric cancer tissues than in adjacent normal tissues. High PFN1 expression was correlated with tumor infiltration, lymph node metastasis, and tumor-node-metastases (TNM) stage. Functional assays confirmed that silencing PFN1 could inhibit the invasion and migration of gastric cancer cell lines.16

In addition, PFN1 expression was higher in nonsmall cell lung cancer (NSCLC). Lower expression of PFN1 was associated with better prognosis and a higher survival rate in NSCLC.17 Proteomic analysis revealed that PFN1 was differentially expressed in laryngeal carcinoma tissues compared with adjacent normal tissues. Further study results revealed that PFN1 was increased in laryngeal carcinoma tissues compared with adjacent normal tissues, indicating that PFN1 was a novel potential biomarker for the diagnosis of laryngeal carcinoma.18

However, in some other tumors (such as colorectal cancer [CRC], oral carcinoma, and others), the opposite is true. PFN1 was downregulated in pancreatic cancer.19-20 Lower expression of PFN1 was significantly associated with a shorter survival period.20 In late-stage oral squamous cell carcinoma, PFN1 expression was lower than that in normal oral epithelium, and loss of PFN1 expression was related to invasion into and metastasis of lymph nodes.21 PFN1 was also decreased in late advanced hepatocellular carcinoma (HCC) and was associated with a poor survival rate of patients.22-23 In addition, PFN1 was found to be downregulated in nasopharyngeal carcinoma24 and breast cancer.25 Combined with another 4 actin-binding proteins, PFN1 could be used to construct a model for predicting poor prognosis of esophageal squamous cell carcinoma.26

Under normal physiological conditions, PFN1 is involved in multiple cellular functions, such as cell motility, migration, adhesion, and transduction signaling pathways.27 PFN1 is differentially expressed in various types of tissues and cells, which may explain its variable tumorigenic mechanisms in different tumors, even in different stages of the same cancer (Figure 2). Because PFN1 plays important roles in tumorigenesis and progression, targeting PFN1 dysregulation could to some extent influence the prognosis of patients with cancer. Determining the expression of PFN1 could thus be used to distinguish high-risk disease from lower-risk disease. Combination with other indices could further improve the diagnostic and prognostic value of PFN1.

In addition to dysregulation in tumor tissues, PFN1 was also found to bedifferentially expressed in the serum, urine, and extracellular vesicles of patients with cancer, which makes it possible to utilize PFN1 in liquid biopsy analysis of tumors. Compared with tumor tissue biopsy, liquid biopsy is a more practical method for real-time monitoring of patients with cancer.28 In addition, PFN1 was detected in the supernatants of cultured cells.

It has been shown that PFN1 gene expression is increased in peripheral blood cells of patients with HCC compared with healthy controls.29 A 9-gene expression system (including PFN1) was used to discriminate patients with HCC from healthy people.30 Proteomic analysis of serum proteins showed that PFN1 was increased in patients with gallbladder cancer. The expression difference between these patients and healthy controls was more than 2-fold.31 PFN1 was differentially expressed in the urine of patients with invasive and noninvasive bladder cancer. Further studies confirmed that PFN1 was notably decreased in the epithelium of invasive bladder tumors compared with noninvasive tumors, which was associated with the clinical outcomes of bladder cancer.32 In in vitro pancreatic cancer cell lines, PFN1 was downregulated in secretomes compared with nonneoplastic pancreatic ductal cells.33 In invitro cultured RCC cell lines, PFN1 was differentially regulated in the supernatant. Further studies revealed that PFN1 was upregulated in RCC tissues.34 Apart from its dysregulation in serum and urine, PFN1 was found to be downregulated in the circulating leukocytes of patients with breast cancer compared with healthy controls, which provides a new paradigm for highly sensitive and less invasive approaches for the diagnosis of breast cancer.35 Studies have already revealed that PFN1 can be secreted via exosomes or other secretory pathways.36-38

Extracellular PFN1 in the tumor microenvironment can be taken up by recipient cells and execute its function in recipient cells, which in turn may influence the biological behavior of cells in the microenvironment, ultimately affecting tumorigenesis and progression of cancers. As mentioned above, PFN1 is expressed differentially in the serum and urine of patients with cancer, which enables its application as a biomarker for diagnosis and prognosis in liquid biopsy (Table 1).

Cell motility involves membrane protrusion, cell matrix adhesion, cell body translocation, and rear detachment. Many of these processes require the actin cytoskeleton and its regulators. By facilitating the exchange of ATP for ADP on G-actin, PFN1 plays a major role in actin polymerization, thus influencing motility in numerous cells.39 PFN1 also participates in cell motility by regulating actin polymerization and interactions with other regulators of actin cytoskeletons, such as ARP3, VASP, and proteins of cell signaling pathways. Cell-cell adhesion and cell-matrix adhesion are critical contributors to maintaining tissue architecture. Dysregulation of cell-cell adhesion is an important sign in tumor initiation and progression of malignancy. PFN1 can modulate cell adhesion and epithelial-to-mesenchymal transition (EMT) in cancer cells. However, the mechanisms by which PFN1 regulates cell adhesion are still not very clear. Undoubtedly, learning more about the roles of PFN1 in cell adhesion and motility will help us better understand its roles in modulating tumor invasion and migration.

Since PFN1 plays a critical role in actin polymerization, it is an indispensable regulator of cell motility. PFN1 participates in the invasion and metastasis of multiple cancers. However, the roles of PFN1 in regulating cell motility are context specific.27 Exogenous PFN1 with intact actin-binding abilities can ameliorate the adherence and spreading capabilities of cancer cells and exert tumor-suppressive effects in breast cancer.40 Consistent with the results of the study by Wittenmayer et al, Zou et al found that PFN1 overexpression could revert MDA MB-231 cells to an epithelioid phenotype, with restored adherence junctions.41 In addition, PFN1 overexpression could promote AMPK activation and p27 phosphorylation, which in turn induces epithelial morphological reversion of mesenchymal breast cancer through restoration of adherens junctions.42 These studies highlighted the involvement of PFN1 in epithelial adhesion and differentiation, which helped us better understand its roles in cancer cell motility.

Invadopodia are actin-driven membrane protrusions that can deliver matrix metalloproteinases to degrade the matrix and support invasion and dissemination of tumor cells. Any dysregulation of the actin cytoskeleton can impair the formation and maturation of invadopodia.43-46 PFN1 can regulate PI(3,4)P2, which in turn negatively regulates lamellipodin at the leading edge of breast cancer cells and thus inhibits those cells motility.47 The depletion of PFN1 leads to an increase in the level of PI(3,4)P2 in invadopodia and its interacting adaptor Tks5. The interaction of PI(3,4)P2-Tks5 has been shown to promote the anchorage, maturation, and turnover of invadopodia, which in turn enhances the invasiveness and motility of breast cancer.48 Breast cancer is an invasive adenocarcinoma, and numerous studies have found that PFN1 is downregulated in breast cancer tissues.49-54 Overexpression of PFN1 reduces the invasion and migration of breast cancer cells, while loss of PFN1 significantly enhances breast cancer cell motility and invasion. Mechanisms involved in PFN1s negative roles in breast cancer metastasis include Enabled (Ena)/vasodilator stimulated phosphoprotein (VASP)-dependent lamellipodial protrusion,51 miRNA-182 regulation,52 and regulation of PFN1 degradation.53 Mouneimne et al found that PFN1 knockdown (KD) could increase F-actin bundles and enhance stress fiber formation. In that study, the numbers of protrusions in PFN1-KD cells were markedly decreased, and PFN1-KD could inhibit the motility of breast cancer.55 Moreover, Liu et al indicated that the interaction of LMO2-PFN1 and LMO2-ARP3 could promote the formation of lamellipodia/filopodia in basal-type breast cancer cells.56 Ena/VASP is a critical regulator of the actin cytoskeleton at the leading edge of cells, which controls membrane protrusions and cell motility. Cell-substrate adhesion and downregulation of Protein Kinase A (PKA) promote interactions of PFN1 with VASP, which is another mechanism by which PFN1 regulates cell motility.57-58 Knockdown of PFN-1 has been shown to abrogate the inhibitory effect of tyrphostin A9, suggesting that modulating PFN1 expression could have therapeutic potential in the treatment of metastatic breast cancer.59

As in breast cancer, PFN1 was found to be a suppressor of migration in HCC.22,23,60 All-trans retinoic acid60 and guttiferone K22 could inhibit hepatocellular cell migration and proliferation by upregulating the expression of PFN1. In prostate cancer, cathepsin X can inactivate PFN1, thus promoting adhesion, invasion, and migration of cancer cells.61 In CRC, elevated expression of PFN1 obviously inhibited invasion and migration. PFN1 was suppressed by the HLA-F-AS1/miRNA-330-3p/PFN1 or HCP5/miRNA-299-3p/PFN1/AKT axis.62-63

Interestingly, Ding et al showed that in the early stages of metastasis, breast cancer cells exhibit a hyperinvasive phenotype characterized by upregulation of MMP-9 and by faster invasion when PFN1 expression is downregulated. However, in the late stages of metastasis, loss of PFN1 markedly inhibits the growth of metastatic colonies of breast cancer cells.54 Rizwani et al reported that PFN1 expression was elevated in breast cancer tissues and that overexpression of PFN1 could inhibit the migration of breast cancer cells. The phosphorylation of S137 mutants abrogated PFN1s promotion of migration. These studies provided a different vision of PFN1s role in breast cancer metastasis.64

In gastric cancer, silencing PFN1 inhibited the invasion and migration of cells, and the PFN1 expression level in cancer tissue was positively correlated with tumor infiltration and lymph node metastasis.16 However, different conclusions were drawn from the study of Ma et al. The authors found that PFN1 expression was inversely correlated with lymph node metastasis.65 In the lung cancer cell line A549, downregulation of PFN1 inhibited migration.17 In addition, in vitro studies support the importance of PFN1 in the proliferation and migration of RCC cells, and treatment with a novel computationally designed PFN1-actin interaction inhibitor reduced the proliferation and migration of RCC cells in vitro and RCC tumor growth in vivo.13 Additional studies have demonstrated that downregulation of PFN1 can also suppress the migration of laryngeal cancer18 and bladder cancer.66

Although more studies on PFN1 have been completed recently, its roles in cancer metastasis are still unclear. The concentrations of actin and PFN1 are time- and space-specific, and so is the regulation of the actin cytoskeleton (Table 2). Additional thorough studies are needed to comprehend the mechanisms and laws regulating the actin cytoskeleton. More importantly, in addition to actin dependence, PFN1 affects cell migration in an actin-independent manner by interacting with proteins with PIP2 or PLP domains. Furthermore, lncRNAs and microRNAs also modulate the functions of PFN1. All of these proteins and RNAs interact with PFN1 and indirectly influence the functions of cancer cells, which makes understanding the roles of PFN1 in cancer metastasis and other functions more complicated (Table 3).

In yeast, the gene encoding PFN1 is essential for cytokinesis.67 Early studies revealed that PFN1/ embryos died as early as the 2-cell stage, while PFN1/+ embryos displayed reduced survival during embryogenesis compared with wild-type embryos; this indicates that PFN1 is essential for cell division and survival during embryogenesis.68 PFN1 silencing in endothelial cells inhibits proliferation.69 In addition, homozygous deletion of PFN1 in chondrocytes failed to complete abscission at late-stage cytokinesis.70 The results of all these studies imply that PFN1 plays a role in cell proliferation. In breast cancer, PFN1 overexpression (PFN1-OE) has been shown to inhibit cell growth and exert an inhibitory effect on tumorigenesis,25,40,52,71-75 and PFN1-OE suppresses the activation of AKT, which in turn inhibits the growth of tumor cells.71 PFN1-OE cells arrested at the G1 phase, which was partly attributed to the upregulation of P27kip1.72 miRNA-182 could downregulate PFN1 expression and promote triple-negative breast cancer cell proliferation.52 However, Yap et al put forward opposite views. The authors research results revealed that silencing PFN1 resulted in a multinucleation phenotype of breast cancer cells, thus inhibiting proliferation.76 Recent studies from Chakraborty et al also reported that PFN1 knockdown could upregulate SMAD3 and inhibit the proliferation of breast cancer.77 Results of single-cell studies on the extracellular matrix revealed that stiff extracellular matrix led to upregulation of PFN1, possibly promoting the proliferation of breast cancer.78 Apart from breast cancer, PFN1 was also found to suppress proliferation in pancreatic adenocarcinoma,20 endometrial cancer,79 and HCC.23,60 In gastric cancer, silencing PFN1 caused cell cycle arrest at G0/G1 phase, thus restraining cell proliferation.16 Knockdown of PFN1 could also inhibit the proliferation of laryngeal cancer.18 Our previous studies found that overexpression of PFN1 could promote the proliferation of multiple myeloma cells by accelerating the cell cycle from G1 to S phase.80 PFN1 is indispensable for cytokinesis. Nevertheless, PFN1 is involved in regulating cell proliferation not only by impacting cytokinesis but also by modulating cell cyclerelated proteins. Otherwise, PFN1 could also interact with cell signaling pathways and indirectly influence cell proliferation.

Tumor growth is not only about uncontrolled proliferation but also resistance to apoptosis.81 Actin dynamics have notable impacts on multiple stages of apoptosis.82 PFN1, as a critical actin-binding protein, is an indispensable regulator of actin dynamics, through which PFN1 participates in regulating apoptosis. PFN1 overexpression could upregulate the most common tumor-associated hotspot mutation of p53p53R273Hthus sensitizing cancer cells to apoptosis via the intrinsic apoptotic pathway.83 PFN1 has been shown to facilitate apoptosis of breast cancer cells, thus exerting a suppressive effect on tumorigenesis.73,75,83,84 By inducing apoptosis and reducing autophagy, PFN1 has also been shown to sensitize pancreatic cancer cells to irradiation. Additionally, overexpression of PFN1 can significantly elevate apoptotic markers such as cleaved caspase-3 and cleaved PARP after irradiation, suggesting that PFN1 can modulate radiosensitivity partly by regulating apoptosis.85

Given that PFN1 is involved in cell proliferation and apoptosis, it is not difficult to understand its roles in the drug resistance of tumor cells. PFN1 was found to be downregulated in butyrate-treated CRC cells,86 and proteomics studies revealed that PFN1 was differentially expressed in erinacine Atreated CRC cells,87 which suggested the roles of PFN1 in drug-mediated cell death and inhibition of proliferation. In addition, proteomics showed that PFN1 was differentially expressed in mitotane-treated adrenocortical carcinoma,88 and PFN1 was found to be increased in tocotrienol-treated MDA-MB-231 cells,89 indicating its roles in predicting the response to anticancer therapies. Compared with temozolomide (TMZ)-treated glioblastoma cells, PFN1 was downregulated in OKN-007 combined with TMZ-treated glioblastoma cells. Further study results revealed that PFN1 is involved in TMZ resistance.90 Results of our previous studies showed that PFN1 could interact with the Beclin 1 complex and participate in bortezomib resistance in multiple myeloma.80 Since PFN1 is involved in multiple cell processes, including proliferation, apoptosis, and proteomics, it was recognized as a biomarker for therapy sensitivity, and it is worth further exploring its roles in drug resistance. In addition, PFN1 was found to participate in angiogenesis,91-92 initiation of tumors,93 and autophagy.80 Loss of PFN1 in A549 cell lines resulted in fewer early apoptotic cells after treatment with piperlongumine, and PFN1 sensitized A549 cells to anticancer agents.17 PFN1 serves as a bridge for actin-cytoskeleton and cell signaling pathways and is involved in multiple biological and physiological processes. Dysregulation of PFN1 in cancer cells has a notable impact on sensitivity to chemotherapy or radiotherapy and may be a new target for the treatment of drug-resistant or radioresistant patients.

Studies have already confirmed that PFN1 is essential for cell survival in early embryos, as PFN1-KN could induce Drosophila embryos to die at the 2-cell stage.94 For further investigation of PFN1s roles in tissue-specific stem cells, Zheng et al established PFN1flox/flox mice that inducibly delete PFN1 in HSCs. Results showed that PFN1 was essential for the retention and metabolism of mouse hematopoietic stem cells in bone marrow partially through the axis of PFN1/G13/EGR1.95 These study results implied important roles of PFN1 in stem cell function, which were still unclear and deserved further research. Later study results have found that both overexpression and depletion of PFN1 could reduce the stem-like phenotype of MDA-MB-231 (MDA-231) triple-negative breast cancer cells, suggesting that a balanced expression of PFN1 was required for maintenance of optimal stemness and tumor-initiating ability of breast cancer cells.93 Considering that tumor heterogeneity is still an ongoing challenge for cancer treatment and that cancer stem cells (CSC) are considered to be a determining factor of tumor heterogeneity,96 intensive studies on PFN1s roles in CSC may provide us new insight into tumor initiation.

As mentioned above, PFN1 has been shown to be a critical participator of actin dynamics and to play important roles in cell migration. For cytotoxic T lymphocytes (CTLs), migration abilities are essential for patrolling tissues and locating targeted cells.97-98 Schoppmeyer et al thus studied PFN1s roles in CTL functions. The authors found that PFN1 negatively regulated CTL-mediated elimination of target cells and that PFN1 downregulation promoted CTL invasion into a 3D matrix in vitro. In patients with pancreatic cancer, PFN1 expression was substantially decreased in peripheral CD8+ T cells.99 However, considering the complexity of immune responses in vivo, the exact roles of PFN1 in tumor immunity remain unclear and need to be further explored.

Based on previous studies, we found that PFN1participates in multiple biological processes of tumor development and progression. Meanwhile, it is noteworthy that PFN1 plays opposite roles in different tumors and at different periods of tumor, potentially leading to the conclusion that PFN1s function in tumor has spatial and temporal specificity. Future studies on PFN1 should take this into account. PFN1 was shown to be of great significance for diagnosis and prognosis prediction and for monitoring the therapeutic effect of anticancer drugs, and PFN1s roles in tumor stemness and immunity may provide a new avenue for cancer therapy. Although much research has been done on PFN1 and cancer, puzzles still need to be solved. With deepening research, the function of PFN1 in cancer would be further clarified and its clinical value would be more prominent.

Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

Conflicts of Interest: Authors declare no conflicts of interest for this article.

Acknowledgment: The authors are thankful for financial support from the Doctoral Fund Project of Hunan Provincial Peoples Hospital (program number BSJJ201812).

References

1. Witke W. The role of profilin complexes in cell motility and other cellular processes. Trends Cell Biol. 2004;14(8):461-469. doi:10.1016/j.tcb.2004.07.003

2. Carlsson L, Nystrm LE, Sundkvist I, Markey F, Lindberg U. Actin polymerizability is influenced by profilin, a low molecular weight protein in non-muscle cells. J Mol Biol. 1977;115(3):465-483. doi:10.1016/0022-2836(77)90166-8

3. Goldschmidt-Clermont PJ, Furman MI, Wachsstock D, Safer D, Nachmias VT, Pollard TD. The control of actin nucleotide exchange by thymosin beta 4 and profilin: a potential regulatory mechanism for actin polymerization in cells. Mol Biol Cell. 1992;3(9):1015-1024. doi:10.1091/mbc.3.9.1015

4. Yarmola EG, Bubb MR. How depolymerization can promote polymerization: the case of actin and profilin. BioEssays. 2009;31(11):1150-1160. doi:10.1002/bies.200900049

5. Boukhelifa M, Moza M, Johansson T, et al. The proline-rich protein palladin is a binding partner for profilin. FEBS J. 2006;273(1):26-33. doi:10.1111/j.1742-4658.2005.05036.x

6. Lassing I, Lindberg U. Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin. Nature. 1985;314(6010):472-474. doi:10.1038/314472a0

7. Wu C-H, Fallini C, Ticozzi N, et al. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature. 2012;488(7412):499-503. doi:10.1038/nature11280

8. Hassona MD, Abouelnaga ZA, Elnakish MT, et al. Vascular hypertrophy-associated hypertension of profilin1 transgenic mouse model leads to functional remodeling of peripheral arteries. Am J Physiol Heart Circ Physiol. 2010;298(6):H2112-H2120. doi:10.1152/ajpheart.00016.2010

9. Eccles SA, Welch DR. Metastasis: recent discoveries and novel treatment strategies. Lancet. 2007;369(9574):1742-1757. doi:10.1016/S0140-6736(07)60781-8

10. Cifani P, Kentsis A. Towards comprehensive and quantitative proteomics for diagnosis and therapy of human disease. Proteomics. 2017;17(1-2):10.1002/pmic.201600079. doi:10.1002/pmic.201600079

11. Masui O, White MA, DeSouza LV, et al. Quantitative proteomic analysis in metastatic renal cell carcinoma reveals a unique set of proteins with potential prognostic significance. Mol Cell Proteomics. 2013;12(1):132-144. doi:10.1074/mcp.M112.020701

12. Neely BA, Wilkins CE, Marlow LA, et al. Proteotranscriptomic analysis reveals stage specific changes in the molecular landscape of clear-cell renal cell carcinoma. PLoS One. 2016;11(4):e0154074.doi:10.1371/journal.pone.0154074

13. Allen A, Gau D, Francoeur P, et al. Actin-binding protein profilin1 promotes aggressiveness of clear-cell renal cell carcinoma cells. J Biol Chem. 2020;295(46):1563615649. doi:10.1074/jbc.RA120.013963

14. Karamchandani JR, Gabril MY, Ibrahim R, et al. Profilin-1 expression is associated with high grade and stage and decreased disease-free survival in renal cell carcinoma. Hum Pathol. 2014;46(5):673-680. doi:10.1016/j.humpath.2014.11.007

15. Tanaka M, Sasaki H, Kino I, Sugimura T, Terada M. Genes preferentially expressed in embryo stomach are predominantly expressed in gastric cancer. Cancer Res. 1992;52(12):3372-3377.

16. Cheng Y-J, Zhu Z-X, Zhou J-S, et al. Silencing profilin-1 inhibits gastric cancer progression via integrin 1/focal adhesion kinase pathway modulation. World J Gastroenterol. 2015;21(8):2323-2335.doi:10.3748/wjg.v21.i8.2323

17. Gagat M, Haas-Winiewska M, Zieliska W, Izdebska M, Grzanka D, Grzanka A. The effect of piperlongumine on endothelial and lung adenocarcinoma cells with regulated expression of profilin-1. Onco Targets Ther. 2018;11:8275-8292. doi:10.2147/OTT.S183191

18. Li L, Zhang Z, Wang C, et al. Quantitative proteomics approach to screening of potential diagnostic and therapeutic targets for laryngeal carcinoma. PLoS One. 2014;9(2):e90181. doi:10.1371/journal.pone.0090181

19. Liang J-W, Shi Z-Z, Shen T-Y, et al. Identification of genomic alterations in pancreatic cancer using array-based comparative genomic hybridization. PLoS One. 2014;9(12):e114616. doi:10.1371/journal.pone.0114616

20. Yao WT, Ji SR, Qin Y, et al. Profilin-1 suppresses tumorigenicity in pancreatic cancer through regulation of the SIRT3-HIF1 axis. Mol Cancer. 2014;13:187. doi:10.1186/1476-4598-13-187

21. Adami GR, OCallaghan TN, Kolokythas A, Cabay RJ, Zhou Y, Schwartz JL. A loss of profilin-1 in late-stage oral squamous cell carcinoma. J Oral Pathol Med. 2017;46(7):489-495. doi:10.1111/jop.12523

22. Shen K, Xi ZC, Xie JL, et al. Guttiferone K suppresses cell motility and metastasis of hepatocellular carcinoma by restoring aberrantly reduced profilin1. Oncotarget. 2016;7(35):56650-56663.doi:10.18632/oncotarget.10992

23. Wang Z, Shi Z, Zhang L, Zhang H, Zhang Y. Profilin 1, negatively regulated by microRNA-19a-3p, serves as a tumor suppressor in human hepatocellular carcinoma. Pathol Res Pract. 2019;215(3):499-505. doi:10.1016/j.prp.2018.12.012

24. Chan CML, Wong SCC, Lam MYY, et al. Proteomic comparison of nasopharyngeal cancer cell lines C666-1 and NP69 identifies down-regulation of annexin II and beta2-tubulin for nasopharyngeal carcinoma. Arch Pathol Lab Med. 2008;132(4):675-683. doi:10.1043/1543-2165(2008)132675:PCONCC]2.0.CO;2

25. Janke J, Schlter K, Jandrig B, et al. Suppression of tumorigenicity in breast cancer cells by the microfilament protein profilin 1. J Exp Med. 2000;191(10):1675-1686. doi:10.1084/jem.191.10.1675

26. Peng Z-M, Yu W, Xie Y, et al. A four actin-binding protein signature model for poor prognosis of patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 2014;7(9):5950-5959.

27. Ding Z, Bae YH, Roy P. Molecular insights on context-specific role of profilin-1 in cell migration. Cell Adh Migr. 2012;6(5):442-449. doi:10.4161/cam.21832

28. Vaidyanathan R, Soon RH, Zhang P, Jiang K, Lim CT. Cancer diagnosis: from tumor to liquid biopsy and beyond. Lab Chip. 2019;19(1):11. doi:10.1039/c8lc00684a

29. Zhang P-J, Wei R, Wen X-Y, et al. Genes expression profiling of peripheral blood cells of patients with hepatocellular carcinoma. Cell Biol Int. 2012;36(9):803-809. doi:10.1042/CBI20100920

30. Xie H, Xue Y-Q, Liu P, et al. Multi-parameter gene expression profiling of peripheral blood for early detection of hepatocellular carcinoma. World J Gastroenterol. 2018;24(3):371-378. doi:10.3748/wjg.v24.i3.371

31. Tan Y, Ma S-Y, Wang F-Q, et al. Proteomic-based analysis for identification of potential serum biomarkers in gallbladder cancer. Oncol Rep. 2011;26(4):853-859. doi:10.3892/or.2011.1353

32. Zoidakis J, Makridakis M, Zerefos PG, et al. Profilin 1 is a potential biomarker for bladder cancer aggressiveness. Mol Cell Proteomics. 2012;11(4):M111.009449. doi:10.1074/mcp.M111.009449

33. Grnborg M, Zakarias Kristiansen T, Iwahori A, et al. Biomarker discovery from pancreatic cancer secretome using a differential proteomic approach. Mol Cell Proteomics. 2006;5(1):157-171. doi:10.1074/mcp.M500178-MCP200

34. Minamida S, Iwamura M, Kodera Y, et al. Profilin 1 overexpression in renal cell carcinoma. Int J Urol. 2011;18(1):63-71. doi:10.1111/j.1442-2042.2010.02670.x

35. Braun M, Fountoulakis M, Papadopoulou A, et al. Down-regulation of microfilamental network-associated proteins in leukocytes of breast cancer patients: potential application to predictive diagnosis. Cancer Genomics Proteomics. 2009;6(1):31-40.

36. Ji H, Greening DW, Kapp EA, Moritz RL, impson RJ. Secretome-based proteomics reveals sulindac-modulated proteins released from colon cancer cells. Proteomics Clin Appl. 2009;3(4):433-451.doi:10.1002/prca.200800077

37. Makridakis M, Vlahou A. Secretome proteomics for discovery of cancer biomarkers. J Proteomics. 2010;73(12):2291-2305. doi:10.1016/j.jprot.2010.07.001

38. Pavlou MP, Diamandis EP. The cancer cell secretome: a good source for discovering biomarkers? J Proteomics. 2010;73(10):1896-1906. doi:10.1016/j.jprot.2010.04.003

39. Small JV, Stradal T, Vignal E, Rottner K. The lamellipodium: where motility begins. Trends Cell Biol.2002;12(3):112-120. doi:10.1016/s0962-8924(01)02237-1

40. Wittenmayer N, Jandrig B, Rothkegel M, et al. Tumor suppressor activity of profilin requires a functional actin binding site. Mol Biol Cell. 2004;15(4):1600-1608. doi:10.1091/mbc.e03-12-0873

41. Zou L, Hazan R, Roy P. Profilin-1 overexpression restores adherens junctions in MDA-MB-231 breast cancer cells in R-cadherin-dependent manner. Cell Motil Cytoskeleton. 2009;66(12):1048-1056. doi:10.1002/cm.20407

42. Jiang C, Veon W, Li H, Hallows KR, Roy P. Epithelial morphological reversion drives Profilin-1-induced elevation of p27(kip1) in mesenchymal triple-negative human breast cancer cells through AMP-activated protein kinase activation. Cell Cycle. 2015;14(18):2914-2923. doi:10.1080/15384101.2015.1069929

43. Beaty BT, Wang Y, Bravo-Cordero JJ, et al. Talin regulates moesinNHE-1 recruitment to invadopodia and promotes mammary tumor metastasis. J Cell Biol. 2014;205(5):737-751. doi:10.1083/jcb.201312046

44. Beaty BT, Sharma VP, Bravo-Cordero JJ, et al. 1 integrin regulates Arg to promote invadopodial maturation and matrix degradation. Mol Biol Cell. 2013;24(11):1661-1675,S1-S11. doi:10.1091/mbc.E12-12-0908

45. Mader CC, Oser M, Magalhaes MAO, et al. An EGFRSrcArgcortactin pathway mediates functional maturation of invadopodia and breast cancer cell invasion. Cancer Res. 2011;71(5):1730-1741. doi:10.1158/0008-5472.CAN-10-1432

46. Oser M, Yamaguchi H, Mader CC, et al. Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation. J Cell Biol. 2009;186(4):571-587. doi:10.1083/jcb.200812176

47. Baea YH, Dinga ZJ, Das T, Wells A, Gertler F, Roy P. Profilin1 regulates PI(3,4)P2 and lamellipodin accumulation at the leading edge thus influencing motility of MDA-MB-231 cells. Proc Natl Acad Sci U S A.2010;107(50):21547-21552. doi:10.1073/pnas.1002309107

48. Valenzuela-Iglesias A, Sharma VP, Beaty BT, et al. Profilin1 regulates invadopodium maturation in human breast cancer cells. Eur J Cell Biol. 2015;94(2):78-89. doi:10.1016/j.ejcb.2014.12.002

49. Roy P, Jacobson K. Overexpression of profilin reduces the migration of invasive breast cancer cells. Cell Motil Cytoskeleton. 2004;57(2):84-95. doi:10.1002/cm.10160

50. Zou L, Jaramillo M, Whaley D, et al. Profilin-1 is a negative regulator of mammary carcinoma aggressiveness. Br J Cancer. 2007;97(10):1361-1371. doi:10.1038/sj.bjc.6604038

51. Bae YH, Ding Z, Zou L, Wells A, Gertler F, Roy P. Loss of profilin-1 expression enhances breast cancer cell motility by Ena/VASP proteins. J Cell Physiol. 2009;219(2):354-364. doi:10.1002/jcp.21677

52. Liu H, Wang Y, Li X, et al. Expression and regulatory function of miRNA-182 in triple-negative breast cancer cells through its targeting of profilin 1. Tumour Biol. 2013;34(3):1713-1722. doi:10.1007/s13277-013-0708-0

53. Choi YN, Lee SK, Seo TW, Lee JS, Yoo SJ. C-terminus of Hsc70-interacting protein regulates profilin1 and breast cancer cell migration. Biochem Biophys Res Commun. 2014;446(4):1060-1066.doi:10.1016/j.bbrc.2014.03.061

54. Ding Z, Joy M, Bhargava R, et al. Profilin-1 downregulation has contrasting effects on early vs late steps of breast cancer metastasis. Oncogene. 2014;33(16):2065-2074. doi:10.1038/onc.2013.166

55. Mouneimne G, Hansen SD, Selfors LM, et al. Differential remodeling of actin cytoskeleton architecture by profilin isoforms leads to distinct effects on cell migration and invasion. Cancer Cell. 2012;22(5):615-630.doi:10.1016/j.ccr.2012.09.027

56. Liu Y, Wu C, Zhu T, Sun W. LMO2 enhances lamellipodia/filopodia formation in basal-type breast cancer cells by mediating ARP3-profilin1 interaction. Med Sci Monit. 2017;23:695-703. doi:10.12659/msm.903261

57. Gau D, Veon W, Shroff SG, Roy P. The VASPprofilin1 (Pfn1) interaction is critical for efficient cell migration and is regulated by cellsubstrate adhesion in a PKA-dependent manner. J Biol Chem.2019;294(17):6972-6985. doi:10.1074/jbc.RA118.005255

58. Gau D, Ding ZJ, Baty C, Roy P. Fluorescence resonance energy transfer (FRET)-based detection of profilinVASP interaction. Cell Mol Bioeng. 2011;4(1):1-8. doi:10.1007/s12195-010-0133-z

59. Joy ME, Vollmer LL, Hulkower K, et al. A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities. PLoS One. 2014;9(2):e88350.doi:10.1371/journal.pone.0088350

60. Wu N, Zhang W, Yang Y, et al. Profilin 1 obtained by proteomic analysis in all-trans retinoic acidtreated hepatocarcinoma cell lines is involved in inhibition of cell proliferation and migration. Proteomics.2006;6(22):6095-6106. doi:10.1002/pmic.200500321

61. Pear Fonovi U, Jevnikar Z, Rojnik M, et al. Profilin 1 as a target for cathepsin X activity in tumor cells. PLoS One. 2013;8(1):e53918. doi:10.1371/journal.pone.0053918

62. Huang Y, Sun H, Ma X, et al. HLA-F-AS1/miR-330-3p/PFN1 axis promotes colorectal cancer progression. Life Sci. 2019;254:117180. doi:10.1016/j.lfs.2019.117180

63. Bai N, Ma Y, Zhao J, Li B. Knockdown of lncRNA HCP5 suppresses the progression of colorectal cancer by miR-299-3p/PFN1/AKT axis. Cancer Manag Res. 2020;12:4747-4758. doi:10.2147/CMAR.S255866

64. Rizwani W, Fasim A, Sharma D, Reddy DJ, Bin Omar NAM, Singh SS. S137 phosphorylation of profilin 1 is an important signaling event in breast cancer progression. PLoS One. 2014;9(8):e103868.doi:10.1371/journal.pone.0103868

65. Ma Y, Li Y-F, Wang T, Pang R, Xue Y-W, Zhao S-P. Identification of proteins associated with lymph node metastasis of gastric cancer. J Cancer Res Clin Oncol. 2014;140(10):1739-1749. doi:10.1007/s00432-014-1679-2

66. Frantzi M, Klimou Z, Makridakis M, et al. Silencing of Profilin-1 suppresses cell adhesion and tumor growth via predicted alterations in integrin and Ca2+ signaling in T24M-based bladder cancer models. Oncotarget.2016;7(43):70750-70758. doi:10.18632/oncotarget.12218

67. Balasubramanian MK, Hirani BR, Burke JD, Gould KL. The Schizosaccharomyces pombe cdc3+ gene encodes a profilin essential for cytokinesis. J Cell Biol. 1994;125(6):1289-1301. doi:10.1083/jcb.125.6.1289

68. Witke W, Sutherland JD, Sharpe A, Arai M, Kwiatkowski DJ. Profilin I is essential for cell survival and cell division in early mouse development. Proc Natl Acad Sci U S A. 2001;98(7):3832-3836.doi:10.1073/pnas.051515498

69. Ding Z, Lambrechts A, Parepally M, Roy P. Silencing profilin-1 inhibits endothelial cell proliferation, migration and cord morphogenesis. J Cell Sci. 2006;119(Pt 19):4127-4137. doi:10.1242/jcs.03178

70. Bttcher RT, Wiesner S, Braun A, et al. Profilin 1 is required for abscission during late cytokinesis of chondrocytes. EMBO J. 2009;28(8):1157-1169. doi:10.1038/emboj.2009.58

More:
Profilin 1 Protein and Its Implications for Cancers - Cancer Network

Recommendation and review posted by Bethany Smith

After closing a merger with GX Acquisition Corp., Celularity Inc., a clinical-stage cellular medicine company, is taking the next step in its evolution to enable further development of novel, off-the-shelf allogeneic placentaderived cellular therapies.1

Celularity aims to transform the way we approach the treatment of cancer and other diseases by harnessing the versatility, unique immune biology, and innate stemness of placental-derived cells, Robert J. Hariri, MD, PhD, found, chairperson, and chief executive officer of Celularity, stated in a press release. We are immensely proud of our clinical development results so far as well as the state-of-the-art manufacturing capabilities we built to support rapid scaling and a competitive cost structure for our placental-derived cell therapeutics. We believe off-the-shelf, allogeneic cell therapies will drive a paradigm shift in how clinicians approach the treatment of cancer and other serious diseases.

CYNK-001, the companys lead product candidate, is the only cryopreserved, allogeneic, off-the-shelf natural killer (NK) cell therapy to be developed from placental hematopoietic stem cells. The agent expresses perforin and granzyme B, has showcased cytotoxic activity against hematological tumors and solid tumor cell lines, and can secrete immunomodulatory cytokines in the presence of tumor cells.

The novel therapy is under investigation as a potential option in multiple myeloma, acute myeloid leukemia (AML), and glioblastoma multiforme; it is also being evaluated in infectious diseases like COVID-19 (NCT04365101).

An ongoing, open-label, multi-dose, phase 1 trial (NCT04310592) is examining the maximum-tolerated dose (MTD) or maximum planned dose of CYNK-001 in an estimated 22 patients with acute myeloid leukemia (AML).2 To participate, patients need to have primary or secondary AML and be in first or second morphological clinical response (CR), morphological CR with incomplete hematologic recovery, or a morphologic leukemia-free state per European LeukemiaNet recommendations for AML Response Criteria.

Patients also need to have MRD positivity, be aged between 18 and 80 years old, have an ECOG performance status of 0 to 2, and be able to be off immunosuppressive therapy for at least 3 days before infusion with the therapy. Patients who previously had central nervous system involvement are allowed to enroll if they had been treated and their cerebral spinal fluid is clear for at least 2 weeks before undergoing lymphodepletion.

Exclusion criteria include significant medical conditions, laboratory abnormalities, bi-phenotypic acute leukemia, acute promyelocytic leukemia, unacceptable organ function, autoimmune disease, uncontrolled graft-vs-host disease (GVHD), and GVHD that requires corticosteroids.

Participants are first given cyclophosphamide plus fludarabine. Then, they are administered CYNK-001 at 3 varying dose levels1.8 billion, 3.6 billion, and 5.4 billion CYNK-001 cellson days 0, 7, and 14. The primary objectives of the research include dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and frequency and severity of adverse effects. Important secondary objectives include the number of patients who convert from MRD-positive to -negative status; time to, and duration of, MRD response; progression-free survival; time to progression; duration of morphologic complete remission; and overall survival.

In June 2021, the study was expanded to include patients with relapsed/refractory AML following a case of conversion to MRD negativity, when the therapy was delivered at its highest dose level.3

The decision to expand the trial followed observations of a patient with NPM-1positive, FLT3-negative AML and good-risk cytogenetics who had been administered 5.4 billion CYNK-001 cells. The patient converted from MRD-positive to -negative status, without experiencing any DLTs.

For this patient, primary induction treatment with 7+3 chemotherapy had failed, and so they had gone on to receive second induction therapy followed by high-dose cytarabine consolidation. At this time point, the patient achieved a complete CR, but MRD was found to be persistent; it did not clear following 4 months of treatment with azacitidine. MRD positivity was confirmed on a marrow biopsy.

The patient went on to enter the phase 1 trial, where they received lymphodepletion, and then received 1.8 billion CYNK-001 cells on days 0, 7, and 14 in the outpatient setting, which totaled to 5.4 billion CYNK-001 cells. On day 28, the patient had converted from MRD positivity to negativity. CYNK-001 cells were present in both the peripheral blood and bone marrow.

Notably, no DLTs have been observed with the therapy at any of the dose levels examined thus far.

The company also shared plans to continue dose escalation with the therapy in the MRD indication up to 9.0 billion CYNK-001 cells. To strengthen the persistence of the treatment, the expansion arms of MRD and relapsed/refractory AML will include an augmented lymphodepletion protocol comprised of cyclophosphamide at 3600 mg and fludarabine at 120 mg over 4 days vs cyclophosphamide at 900 mg plus fludarabine at 75 mg over 3 days.

In April 2021, the FDA granted an orphan drug designation to CYNK-001 as a potential therapeutic option for patients with malignant gliomas.4 As such, the therapy is also under investigation in patients with glioblastoma multiforme as part of another phase 1 trial (NCT04489420).5

To be eligible for enrollment, patients need to have historically confirmed disease at first or second relapse, measurable disease, a Karnofsky performance status of 60 or higher, and acceptable organ function, among other criteria.

Patients who previously received radiation within 12 weeks of their screening MRI; those who were on growth factors with less than 4 weeks of a washout period; those treated with radiotherapy, chemotherapy, or other investigational drugs within 4 weeks; those who received prior cellular or gene therapy; and those with active autoimmune disease, were excluded.

Cohort 1A of the trial will enroll up to 6 patients with recurrent glioblastoma multiforme who will receive intravenous CYNK-001 at a dose of 1.2 x 109 cells on days 0, 7, and 14. From the initial infusion of therapy, patients will be followed for a 42-day DLT period. No other interventions are planned between the last day of treatment.

If DLTs are experienced, cohort 1C, the de-escalation cohort, will include up to 6 patients with recurrent glioblastoma multiforme who will receive the therapy at a dose of 600 x 106 cells on days 0, 7, and 14. These patients will also be followed for DLTs for 42 days post infusion. Cohort 1B, the surgical cohort, will also enroll up to 6 patients, who will be given CYNK-001 at a maximum safe dose of either 1.2 x 109 cells or 600 x 106 cells at days 0, 7, and 14. Patients in this cohort will undergo resection following the last dose of the therapy in the DLT period.

Treatment of cohorts 2A or 2C will only begin after the safety data from cohorts 1A or 1C are determined to be acceptable. Here, patients will first have the Ommaya catheter placement in accordance with institutional policy within 1 week before CYNK-001 infusion on day 0. Cohort 2A will enroll up to 6 patients with recurrent glioblastoma multiforme who will be given the therapy at a dose of 200 x 106 cells +/- 50 x 106 cells intratumorally on day 0, 7, and 14.

Cohort 2C will also include up to 6 patients with recurrent disease who will receive the product at a dose of 200 x 106 cells +/- 50 x 106 cells intratumorally on day 0 and day 7. Lastly, cohort 2B, the surgical intratumoral cohort, will include 6 patients with glioblastoma multiforme who will receive the cellular therapy at a maximum safe dose of either 200 x 106 cells +/- 50 x 106 cells on day 0 and 7.

The primary objectives of the trial are to examine the number of patients who report DLTs with the therapy and toxicities. Important secondary objectives are to evaluate the overall response rate, duration of response, progression-free survival, time to progression, and overall survival.

The safety and efficacy of the cell therapy is also being explored in newly diagnosed patients with multiple myeloma after autologous stem cell transplant, as part of another phase 1 trial (NCT04309084).6 The objective of the program is to achieve durable responses with the therapy in these patients with multiple myeloma who are eligible for transplant in the first-line setting.

Another novel agent in the pipeline is CYNK-101, which is manufactured from NK cells extracted from postpartum placentas. The cells are then genetically engineered to boost cell-killing activity when given with a monoclonal antibody.7 Preclinical data with the product in combination with an antibody showed that the regimen resulted in cell-killing activity when administered to lymphoma cells in vitro.

Additionally, CYNK-CAR products are being developed as allogeneic, off-the-shelf strategies by modifying genes of the human placental hematopoietic stem cellderived NK cells. Several CAR constructs that are designed to target hematologic and solid tumor indications are currently under investigation.

Read more:
Developmental Interest in Allogeneic PlacentaDerived Cell Therapies Expands - OncLive

Recommendation and review posted by Bethany Smith

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Thank you dear subscribers, we are overwhelmed with your response.

Your Turn is a unique section from ThePrint featuring points of view from its subscribers. If you are a subscriber, have a point of view, please send it to us. If not, do subscribe here:https://theprint.in/subscribe/

The word Pandemic instantly takes me to the days of medical school, where we studied it as if it was a fictional entity, while never expecting to implement the knowledge in practice. Metaphors sound frivolous the way things have unfurled over past couple of months.

Everyone has been affected. With so many lives lost and many families left in despair and misery, this is perhaps the most shocking crisis of many peoples lives.

While for the larger population, this disease is all about lockdowns, keeping safe, protecting families and making ends meet; its implication for doctors is multifaceted. Without any immunity from the disease and with constant threat of violence, doctors bracedfor the unseen enemy since the beginning. As our country catapulted into the deadly second wave this summer, the challenges became even more stark. What they were dealing with was a mutant virus with high infective potential, failing health infrastructure and a billion plus unvaccinated population.

But this became the period when complacence overtook good sense, thirst for power overlooked greater good and the concept of shared responsibility was binned. Conveniently ignored was the fact that we had never touched baseline of normalcy and many places in world were still battling with subsequent waves. Poor planning and unscientific outlook were recipe for disaster.

A plethora of treatment options started being circulated amongst general population on social media platforms. Where a person with no medical background is free to administer treatment, doctors are being questioned over injudicious of some drugs. Where faltering oxygen supply and drug shortage is taking lives, doctors are harassed for loss of lives due to known complications of diseases. Where propaganda alternative medicine is portrayed as a panacea for COVID, doctors are asked to prove beyond doubt the rationale behind use of experimental drugs! Doctors have been facing this disease in its most horrendous forms. They have lost loved ones too. The plight of dying patients and distraught families has left their psyches scarred. Notwithstanding all this, their hope thrives on recovery of patients. Those who serve you do not yearn to be called Warriors or God; we just want patients to understand that our every effort we make is for your well-being. Every doctor believes in Do No Harm. The disbelief towards our intent is disconcerting. And when fear rather than care and compassion becomes our guiding principle, it is death knell for the medical system.

There are thousands of diseases in the world, but Medical Science only has an empirical cure for twenty-six of them. The rest is. guesswork. These words of Erich Segal in his famous novel Doctors so aptly described the state of medical science way back in 1988. We have come a long way since then. There has been phenomenal advancement in diagnostics and therapeutics in all specialities. It is for these advances in medicine, today we have options to treat COVID patients and save lives. Researchers came up with effective vaccines in unprecedented time. Modern medicine is evidence based.

A medical practitioner selects treatment options for specific cases based on the best research, patient preferences, and individual patient characteristics. But it is not an absolute science. Drugs that are effective in some patients might be ineffective in others; treatment of choice for diseases change as more insight into pathophysiology and imaging is attained. Hundreds of hours of scientific researches and deliberations are needed to develop a drug molecule and still more to prove its safety and efficacy. It took years of massive outreach programmes to eradicate few viral diseases. And despite every effort, there are still diseases that leave us intrigued and crippled. We too look forward to the day when gene therapy would eradicate blindness in young retinitis pigmentosa patients and new treatment options will likewise emerge for diseases that are still untreatable.

We doctors have been trained on ethical and humanitarian grounds. Hippocrates never prepared us for war-like situations, but that didnt deter any doctor in these perilous times. It is ironical that anything that is on social media is accepted to be the truth, whereas every word of doctors is scrutinized. The blabbering of self-promoting, fame mongers against the noble profession is an affront to our dedication and service. The development of alternate forms of medicine doesnt mandate disregard of the existing, proven and life saving modern medicine. The myopic policies for health and collective consciousness against doctors are corrosive to the future of this nation already compromised by the wrath of COVID19. If this catastrophic period doesnt change anything, nothing ever will.History will repeat with this denial of culpability and inaction at the highest level. The blind spots in sight must not taint ones vision. Its time to prioritize health and be prepared for any incipient third wave.

Also read: SubscriberWrites: Effective mechanism needed for providing ex-gratia to families of Covid victims

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SusbcriberWrites: Covid proves that systems need to change and its time to prioritise health - ThePrint

Recommendation and review posted by Bethany Smith

Amidst a global push for mass vaccination as the battle against COVID-19 rages on many people are still afraid to be vaccinated.

People remain concerned about the perceived experimental nature of vaccines, whether they should be worried about short term risks such as blood clotting and myocarditis; and long term risks including side effects relating to DNA changes, fertility and reproduction, and other unknown long term chronic illnesses and side effects further down the track.

A lot of people continue to wonder whether the risks of vaccination outweigh the benefits.

Greek City Times spoke to trained scientist and medical professional Dr. Nicholas Lelos in our search for answers to some of the questions currently circulating around the controversial topic of vaccination, and here is what he had to say.

The science is constantly changing and there are multiple new sources of information. I think the most important thing to establish is that people need to be wary of sources, as there is a lot of anecdotal evidence and misinformation.

The most rife one, unfortunately, is that provided by several individuals that are prefaced by Dr. when this could be a PhD of certain institutions, a higher degree into a non-medical specialty (such as a nutritionist), or from institutions that have lax criteria in awarding the title. These individuals go on and publish their opinions and evidence that they highly cherry-pick on their own website, or some other sites of little to no accreditation or peer-reviewing, whereupon they then reference and draw whatever conclusions they wish.

Even a fully trained medical doctor, however, is not immune to various influences, and of having an agenda.

This is particularly evident in the United States, where a lot of authoritative narratives come with sponsoring from either competing pharma companies, anti-vaxxer sites or organisations, or even religious bodies that are trying to alter the narrative.

My personal advice, as a trained scientist before doing medicine just because it is published, available online, or even appears in a Journal, do not ever take anything as established fact: the key skill here is critical appraisal. This involves finding many different sources, checking their credentials and biases/conflicts of interests, then assessing the quality and level of evidence they furnish.

Critical appraisal is a difficult and lengthy task and a lot of people have confirmation bias, where if they see something that vaguely echoes their existing beliefs or ideas they are most likely to jump on it and not question it. It is important to look at patterns and identify various factors that can impact the question studied.

My own personal declaration is that I have no vested interests in the writing of this article, I receive no money or endorsement from institutions or of big pharma.

I only offer my experience and knowledge as someone who is a front-line clinician, and I am at the very forefront of the pandemic since the very beginning a protected population is everyones priority, from my patients to my friends and family.

Let us move with the questions.

Some have suggested that safe and effective early treatment alternatives exist such as hydroxychloroquine and ivermectinin place of vaccination. Is it true that the refusal of health authorities to issue early treatment guidance has contributed to the mortality rate of the disease?

To paraphrase another colleague there is a difference for clinical care involving individual patients, where you can see a lot of horrible side effects and consequences, and public health or epidemiology, which is the study of entire populations.

Public health is about finding solutions for multiple populations, whilst also looking into environmental impacts on health, genetics, historical cultural effects and even governmental.

The individual effect of a single drug can do miracles for an individual, or even 10 or 100, or your relatives, or even work well for one doctor or a group of doctors using it at a specific location with certain groups of patients this will not, however, mean that it will work across the entire population. And this is what the policy is made of, and what the World Health Organisation (WHO) are basing their decisions from.

The refusal of these health authorities basically entailed not using their population as test subjects for medications that have never been tested for this purpose. It would have been acceptable in Victorian times but there was also a really high accepted death risk which most people may struggle with nowadays.

So to answer your question there is currently no evidence that these medications work in severe or life threatening COVID.

Dexamethasone, a steroid, works when patients are gravely ill and about to be mechanically ventilated this has been studied, reduces mortality and ventilation needs.

Supplements and vitamins boost the immune system, so they help generally in health- but they do not treat COVID. And you need to have deficiencies of vitamins to benefit from supplementation anyway.

Hydroxychloroquine is a hideously potent medication used for malaria and immunosuppression, and has a relatively narrow window for it to do its effects before becoming toxic. A single tablet can kill children below 6 years of age. Definitely not a good option to have lying around the household. Here is a summary of the current state of these so-called remedies https://www.bmj.com/content/370/bmj.m3379

Here is an excellent live article that is getting constantly updated as new information gets out with other treatments for COVID and the evidence https://www.bmj.com/content/370/bmj.m2980

If it is true that there are safe and effective early treatment alternatives such as hydroxychloroquine and ivermectin, why the push for global vaccination?

So as stated above there are no other effective early treatment alternatives. Even steroids that work for severe COVID, when studied for mild cases, did not have a benefit.

Vaccinations, on the other hand, have worked time and time again small pox and polio have been eradicated, and measles was almost controlled until the rise of vaccination hesitancy when people did not have the stark reminders of their children dying on them or having life-long disabilities (such as with polio).

Global vaccination has worked in the past.

What is herd immunity and how does it relate to the COVID vaccine?

Herd immunity is a principle where a certain amount of the population needs to be immune in order for the disease to not be able to spread. As it requires hosts to go and infect more people, if enough people have immunity then the disease can not make the jump to infect new hosts and thus protect even people with no immunity, such as the newborn, the immunocompromised or people who develop allergies to the vaccine.

The problem that has come up with this pandemic, is that the different strains of the virus, and individuals immune systems, can elicit a different response in people studies have shown that even getting the virus and having a small course of illness means that you do not generate enough antibodies to protect yourself for long.

Meaning that you can get re-infected, or hit with a different strain.

The concept of vaccination is that it causes a sufficiently strong immune reaction that not only stays for longer but is also more effective against multiple strains. So just getting COVID may not protect someone enough, compared to getting a vaccination or boosters.

This is an approach that has been used very effectively for hepatitis B as well.

The vaccine has been referred to as experimental is this true and should we be concerned?

The technology has actually been around for 40 years. So I would hardly call it new.

Experimental would be accurate in the sense that the vaccines that we use did not have a large period of time to be tested, compared to other medications or treatments but this is usually how any medication or treatment made its debut.

Usually wars and pandemics lead to rapid progress of medical sciences because there is more of a drive to not let people die. Penicillin started in a similar fashion and it is one of our most effective and life saving medications. One of my friends was actually in the Oxford drug trials now she is fully protected.

I have to say, the difference though in this scenario and the past is stark big pharma drug and medication research and development, because of our extremely tight regulatory environment, used to take a long time to assess for safety, but also a lot of the data was not made public. So that the companies could make money.

Now, entire countries are being exposed, but the data is transparent and available to all, an extraordinary achievement in the sense that they are not allowed now to sweep mishaps or issues under the carpet anymore.

Also, external agents and scientists are able to look at the effectiveness data and how well vaccines work without interference from the parent company.

In the push for vaccination the government mentions informed consent. Informed consent must be given prior to administration of the vaccine. Is this a way for the government to avoid responsibility for any future side effects down the track considering that there is not enough data for anyone to ascertain long term effects on the body of vaccination?

Informed consent is one of the linchpins of medical practice you need to let people know about ALL the possible side effects before administering a treatment or procedure, no matter how exceedingly rare they can be. This has always been the case, and is not new.

We have been using vaccination as a principle for nearly 100 years the side-effects of getting COVID, on the other hand, are pretty immediate and quite dramatic.

Which groups should not be vaccinated? (For example those who have recovered from COVID-19 and many groups have no possibility of benefiting from the vaccine, including younger individuals, pregnant women, women of childbearing potential, and those with immunodeficiencies) and why?

So as for who should get it, this is where we are still learning Israel has managed to vaccinate its entire adult population and will be proceeding to reduce the age to include children so more information will be available.

So the very young will probably not be vaccinated at this point, the elderly definitely, emphatically should, as they are the population with the highest complications.

Pregnancy and being of childbearing potential has not shown any impacts at this stage. The numbers that we have for clots are extremely small from the vaccines whereas pregnancy and cancer, or even COVID, increases your risk several orders of magnitude up.

Immunodeficiencies such as HIV or immunocompromised patients due to organ transplants or renal dialysis, however, are still at the forefront of research because they do not seem to generate the immune response that the vaccine requires to provide protection. There is a recent initiative to see whether 3 doses are required for these patients. More information coming soon!

What do you think about claims that the global push towards vaccination is a strategy aimed at securing emergency use authorization (EUA) for COVID gene therapies? Why are some people referring to the vaccines as COVID gene therapies? Is this what they are?

I believe this is the usual rhetoric to trigger people, such as GMO food it does not mean what people think.

Gene therapy has a very specific goal replacing the patients genes, who are usually having defects causing diseases such as cystic fibrosis, with the gene sequences that aims to correct the areas that cause the diseases. Or to enhance the gene structure to provide protection against diseases, such as the recent case with the scientist in China who was aiming for producing resistance to HIV. All of them rely on being able to affect directly the patients DNA structure.

To date, this approach has not been successful the closest we have come is to identify what is missing from the body (proteins) and to provide them to the patient.

These vaccines are definitely not gene therapies they do not affect the DNA.

They work by providing mRNA, which is the blueprints that our cells in our body use to make proteins we are using it ourselves for our own proteins. So vaccinating provides our body with the ability to produce, from ourselves, a component of the virus, which on its own can not infect you.

This is in contrast with previous vaccines, such as the tetanus one, which used to give chopped components of the organisms, or of the live attenuated vaccines, which use the actual virus but weaken it so it does not have the strength to infect the host.

Those have been used extensively over the decades, but have inherently more risk for allergic reactions, or of reactivation.

This mRNA delivery is far more elegant, and far more efficient in providing to the body what it needs to mount an efficient immune response without putting it at risk of getting the infection in the first place.

What is mean by a toxin spike protein factory? Do you think that this what is happening to the bodies of those being vaccinated? Do the vaccines coat our DNA or change our DNA?

So this is complete balderdash the mRNA from the vaccines would need to penetrate the core of our cells, and be transcribed into our DNA which is impossible on its own without several other components.

mRNA is what comes from the DNA being read in order to synthesize proteins. Once it is read, it produces the spike proteins that are coating the outside of the virus it is what it needs to hook into our cells and infect them.

So it is both a key component of the virus, and hence important for our immune system to recognise quickly and efficiently, but also quite useless on its own it is like having a key without a hand behind it to insert it into the lock.

This is what the spike protein factory refers to our own cells have protein factories, this is how our DNA is used we are just borrowing our manufacturing ability to give us copies of these keys to prime our own immune system.

HIV, on the other hand, has got a reverse transcriptase that integrates it into our own DNA which is why no vaccines have been able to be made for it all these years.

Do the COVID vaccines trick the body into making the spike protein of the virus? Is it true that the vaccine is distributed in an uncontrolled way throughout the body and can potentially affect different organs of the individuals depending on where their body makes the spike protein? Could this potentially effect the reproductive organs?

I would like to highlight something interesting here the words used. Tricked. There is no tricking the body gets given blueprints to make the same components as the virus to identify it and use it for a better immune response before getting infected.

It is the virus way into the hosts cell it is not, by itself, causing the disease. Otherwise everyone who got a vaccine would be getting COVID. And this is the problem that we highlighted earlier the single case by case scenario can be different between patients or a group of patients, but when we are talking about populations you look at the big picture.

The disease control centre in the US is currently reviewing evidence about whether the vaccine is causing neurological conditions, such as Guillain-Barre Syndrome. My last reading of the data was about 100 cases reported in 12.5 million vaccines. The average background rates in the US are 10 in 1 million of population, because this condition is usually caused by viral infections.

The direct consequences of COVID are much, much higher and can cause direct neurological damage because you dont just get the spike protein but the whole package.

https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2779759

No correlation has been found so far with the reproductive organs, and pregnant women have been vaccinated without any different effects to the ones that are not pregnant.

This is really important, as the initial trials did not include pregnant or lactating women so this is real world data with about 30000 vaccinated pregnant women that were studied and are being followed up.

Should we be worried about other long term health effects of being vaccinated?

It is only sensible to worry about the unknown or new treatments that have not been around for long enough on the other hand COVID poses a very real and documented risk both for short term and long term consequences.

Long COVID has been found to be quite devastating as it affects the heart, the lungs as well as possibly the brain.

Should we be Worried about DNA Changes, Cancer and Chronic Illness as Possible Side Effects?

Of course we should be worried, and of course big pharmaceutical companies pumping the entire population full of substances that are potentially harmful should make us cautious.

All our cells have a place in how they operate reverse transcription would indeed make it possible to get components integrated into our DNA. There are cells that need to do partially such operations, like the cells of our immune system in order to store the memory of this information so it can recall it when the body gets infected with COVID.

For the entire DNA of every single cell of our body to be changed, or at least the stem cells or germ cells that turn into sperm and eggs, to cause a permanent DNA mutation, would involve a level of technology or exposure of something that currently is only present in science fiction movies.

As highlighted before, this would be gene therapy. And the argument is vacuous the body generates the spike proteins. The virus also has these proteins.

So whether you are getting them from the vaccine or the virus the vaccine does not cause the infective consequences of the virus. These proteins can not be incorporated into the DNA.

Also any cell that has a deviation from the original program gets identified and destroyed by the body anyway this is the whole reason why we do not have more cancer or immune diseases.

Should we be concerned about our children being vaccinated and damaging long term effects on their health or for example reproduction or passing on DNA changes to babies?

For the reason mentioned above, as the vaccine has no ability to affect the germ cells, the answer is currently no.

But everyone is exerting the highest amount of caution before wanting to try it with children the current variants up until now seem to not cause them much distress but reports have been coming of some new strains that have been infectious and cause injury to younger age groups too Watch this space!

Should we be concerned about the vaccine ingredients? Some theories include that the ingredients include fetal cells can you please explain this further and should we be concerned about this?

No concerns about the vaccine ingredients now more than ever. Even the minute concentrations of metals that were used in vaccines decades ago have all been switched to inactive inert substances (see table I below).

Fetal cell lines have been used since the 1960s to trial many of our established treatments and vaccines in the past such as rabies and hepatitis A no parts of the cells or the DNA is in the vaccine, but they have been used to trial whether they worked or not. They were not used to produce the vaccines.

The fetal cell line usage, incidentally, has even been accepted by the Catholic church as able to be used for the common good and re-ratified in 2017. The benefits from these cells have saved millions of lives.

Does the Oxford/AstraZeneca vaccine contain animal/ chimpanzee DNA?

No this is patently false.

It uses an adenovirus (common cold virus) that has its ability to replicate snipped and replaced with the instructions for our body on how to make the spike proteins. So similar outcome to Pfizer or Moderna, but by using a carrier instead.

There have been videos circulating showing metal such as spoons and coins sticking to the injection site on the arm as if magnetised. Why is this happening? Do the vaccines contain any ingredients that would cause this? Is this cause for concern?

Unfortunately, as someone who is working in the front lines as an essential worker, therefore receiving both shots as a priority, and surrounded by colleagues, I have to report that neither myself nor any of my thousand colleagues that I worked with have developed super powers or magnetic abilities.

I would love to see such feats in person.

Why are some people still vulnerable to the virus even after vaccination?

Because the vaccination does not make you immune it does however decrease your risk of dying or being hospitalised from it by 100%.

The problem is when you have only received one shot and your immunity is not fully primed or immunocompromised.

The current scientific theory is about a partially vaccinated person with HIV being the source of one of the current strains in the UK as the virus has more chances to evolve in a partially protected individual and get more ways to infect us.

And people on dialysis or with solid organ transplants are always at risk because of the immune system deficiencies they have or acquire.

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The Search For Answers In The Global Push For Mass Vaccination - Greek City Times - GreekCityTimes.com

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In the past 18 months, there is one thought that has crossed the mind of nearly everyone in the world: if I get sick, whats the best way to get help? Medical care, unfortunately, is not evenly distributed, but there are a handful of companies that are making improvements to various processes within healthcare.

Singapore is home to more than 60 multinational medtech firms. The city-state is one of the leaders in medtech R&D in the Asia Pacific region, which is the worlds second largest medtech market with a compound annual growth rate of 9%.

Here are a few medtech companies rooted in Singapore that have caught our eye.

Biofourmis was founded by Kuldeep Singh Rajput in Singapore in 2015 before the company shifted its headquarters to Boston in 2019. The firm mines patient physiology data to provide insights for healthcare providers and pharmaceutical companiesand provides predictive suggestions for optimized personalized care regimens.

Heres how Rajput described Biofourmis work to KrASIA: In the most basic terms, Biofourmis enables clinicians to better manage patients at home by predicting bad outcomes before they happen.

The founder referenced heart disease, the leading cause of death in the world, and said less than 1% of heart failure patients are on the optimal dose of their medication and less than 25% of eligible patients receive all of their goal-directed medical therapy. To address this issue, Biofourmis BiovitalsHF platform uses wearable sensors that monitor patients vital signs at home and feeds data to an AI-powered algorithm, which in turn reports symptoms and other information through an app that can be accessed by patients. This also makes it possible for clinicians to address symptoms even before they manifest.

Another useful platform is Biovitals [emailprotected], which was co-developed by Biofourmis and Brigham and Womens Hospital, a Harvard teaching hospital, for use in Brighams Home Hospital Program. Patients that are part of this initiative had 70% lower readmission rates, a 32% increase in physical activity, and 38% lower costs than patients admitted to hospital facilities, according to a study published in the Annals of Internal Medicine.

With a flexible R&D process, Biofourmis was able to adapt to changing conditions in the past year and a half. At the onset of the pandemic, the company was contacted by a research partner at Queen Mary Hospital in Hong Kong who inquired about a remote patient monitoring solution. The goal was to help clinicians safely mange patients who had contracted the coronavirus. Biofourmis didnt have such a product at the time, but its team of engineers was able to develop its Biovitals Sentinel system, which uses machine learning to create a correlation between multiple vital signs during the patients daily activity and build an individualized biometric signature. The system was added onto the modular Biovitals platform, and then the Singapore Ministry of Health and Australian government also deployed it to monitor and manage COVID-19 patients.

Biofourmis counts a handful of notable investors as stakeholders, including SoftBank, Sequoia Capital, Openspace Ventures, SGInnovate, and EDBI, the private equity and venture capital arm of Singapore Economic Development Board.

Think of Doctor Anywhere as a virtual clinic. The company makes telehealth possible thanks to a team of online licensed medical professionals ready to attend to patients online within minutes. The service keeps people with medical conditions in contact with medical care providers at a time when it is crucial to hunker down and prevent community transmission of COVID-19. Founder and CEO Wai Mun Lim told KrASIA that Doctor Anywhere had around 50,000 cumulative users in January 2019, and that count is now 1.5 million in July 2021.

The company went from having a network of 1,000 medical providersgeneral practitioners, psychologists, psychiatrists, nutritionists, physiotherapists, chiropractors, specialists, and moreat the start of 2020 to nearly 2,500 now.

Lim cites EDBI as a helpful ally in its quest to expand across the region. As a Singapore-based company, the endorsement from the Singapore governments investment arm EDBI is especially meaningful. Their vote of confidence sends a very clear message to the public that Doctor Anywhere has a strong and trusted service. Their in-depth experience within the healthcare and tech space is especially valuable too, as they provide guidance on how to navigate the space to growing companies like ours. The EDBI network is also a very good way for the company to connect the dots within the healthcare and tech sectors across Southeast Asia, the founder said.

Beyond Singapore, Doctor Anywhere already operates in Thailand, Vietnam, Malaysia, and the Philippines. The company has tech hubs in India and Vietnam.

Originally a business that served cleanroom operations, Esco Lifesciences shifted direction around two decades ago. It now designs and makes a range of equipment used for scientific research, medical testing, and healthcare in areas such as fertility, cancer research, genomics, COVID-19 diagnostics, and more. Its machinery and equipment have been sold to medical, testing, and research facilities in more than 100 countries, and is a testament to the companys ingenuity and go-getter attitude.

Escos tools and services are in demand at a critical time when medical research will determine how all nations can move past the pandemic.

CEO XQ Lin describes the current era as the century of biology. He told KrASIA that Esco represents a proxy for growth for the Asian biopharma sector and the company supplies essential tools to major biotech and pharmaceutical companies for research and manufacturing.

Esco has a new facility in Singapore for its contract development manufacturing organization line of business that focuses on gene therapies and cultured meat. The company has production capabilities for established equipment lines in the United States, Europe, and China.

To meet overall demand, Esco raised a record-setting USD 200 million in May from Vivo Capital, Novo Holdings A/S, China Investment Corporation, EDBI, and other investors. The global nature of our investor syndicate also reflects our global ambitions, Lin said.

Hummingbird Bioscience is creating new therapies against cancer and autoimmune diseases by using data-driven methods to identify antibodies. The goal is to create treatment regimens for patients who are not served by current approaches. All of this depends on Hummingbirds proprietary discovery platform, which utilizes computational biology to generate fresh insights about serious diseases.

One landmark discovery made by Hummingbird was a new understanding of HER3, a well-known drug target involved in cancer that was difficult to inhibit, Ingram said. Hummingbirds researchers were able to generate a general solution to finding antibodies that bind specific regions of target proteins, making it possible to develop new drugs that hit hard targets with key roles in diseases.

Hummingbird started with two employees in 2015 and now has a team of 70, of which 90% are in Singapore, co-founder and CEO Piers Ingram said to KrASIA. He cited Singapores pool of highly skilled professionals and a high degree of internationalism in the labor market as core reasons behind establishing the company in the city-state.

Few domains are as international as science. Drug discovery and development is a perfect example of thiswith a need to attract and retain colleagues with both deep technical expertise, insights into disease biology, as well as the processes of taking a drug from concept to the clinic. Singapore fortunately established itself over many years as a highly attractive place to live and do great work, which makes it easy for us build an exceptionally strong team, Ingram said.

In particular, EDBI, the CEO said, has an unparalleled global network in the broader biotech ecosystem, making it possible for Hummingbird to enmesh itself with other stakeholders in the sector.The company has operations in the United States too, and may reshape medical professionals understanding of how to manage previously untreatable diseases.

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These 4 Singaporean companies are changing healthcare as we know it - KrASIA

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Special patient population needs special attention, especially those who undergo HCT

Patients with cancer have been particularly hard hit by the Covid-19 pandemic, both clinically with a higher infection risk and logistically with delays in care delivery. Several recent studies have taken a closer look at how SARS-CoV-2, and the vaccines against the virus, have impacted patients with cancer, particularly those with hematologic malignancies who underwent transplant therapy.

As more transplant physicians are now resuming normal functioning of their transplant units, possibilities of absolute increase in the number of transplant patients getting infected with Covid-19 is expected to rise, cautioned Kamal Kant Sahu, MD, and Ahmad Daniyal Siddiqui, MBBS, both of Saint Vincent Hospital in Worcester, Massachusetts, in a 2021 review. While our understanding about Covid-19 has improved dramatically, a special population such as [hematopoietic stem cell transplant] patients remains at high risk and needs special attention.

HCT and Covid-19

Patients who had hematogenic/hematopoietic stem cell transplant (HCT) or cellular therapy were at significant risk of increased mortality and morbidity due to Covid-19, according to Sibgha Gull Chaudhary, MD, of University of Kansas Medical Center in Kansas City, and co-authors in a publication-only study at the 2021 American Society of Clinical Oncology (ASCO) virtual meeting.

They conducted a systematic review and meta-analysis evaluating the outcomes of Covid-19 in HCT patients, settling on six studies with 1,619 patients (median age 63; 59% men), 646 of whom underwent HCT.

The authors reported that the median days for autologous HCT (autoHCT) was 690 days while it was 450 days for allogeneic HCT (alloHCT). The average follow-up duration after Covid-19 was 24 days.

Gull Chaudharys group found that Covid-19 mortality in HCT patients was 20% (95% CI 0.17-0.23) in a pooled analysis, with a 19% (95% CI 0.15-0.24) mortality rate among those who received autoHCT and 21% (95% CI 0.17-0.25) in those who got alloHCT.

There is a need to prioritize HCT patients for Covid-19 vaccination, close surveillance, and aggressive management, they concluded.

In another ASCO study, the same authors reported that patients who received HCT and CAR-T cell therapy were at an increased risk of moderate-to-severe Covid-19-related pneumonia, and a higher mortality rate with Covid-19.

Muhammad Umair Mushtaq, MD, from the Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, and co-authors conducted a prospective study of 40 patients (median age 58; 67.5% male) at their institution who were diagnosed with Covid-19 from April 2020 to January 2021. Of those, 25 underwent alloHCT with a median time since treatment of 12.4 months.

While the authors found that >42% of the patients in the study had mild-to-moderate Covid-19, nearly 63% had pneumonia, and that the mortality rate was 12.5% in all patients and 20% in alloHCT patients. They also reported that significant predictors of Covid-19 severity included alloHCT, concurrent immune suppression (65% of those with severe disease received this), and elevated inflammatory markers, such as a mean neutrophil-lymphocyte ratio of 19.7 in those with moderate-to-severe Covid-19.

Mushtaq and co-authors concluded that the findings confirm the need for continuing vigilance with social distancing and masks, and the results join data from other groups that offer similar conclusions: patients with hematologic malignancies undergoing HCT need special handling.

Researchers from the University of Michigan Rogel Cancer Center in Ann Arbor conducted a retrospective study of adult patients who received alloHCT or autoHCT and were subsequently diagnosed with moderate-to-severe Covid-19 infection between March and December 2020.

They found that the majority were either on immunosuppression or had significant comorbiditiesmost commonly diabetes and hypertension, according to a separate study from Braziland that all patients with chronic graft-versus-host disease (GVHD) required hospitalization. They advised that the potential relationship between Covid-19 infection and GVHD development or exacerbation needed more clarity.

A group from the Dana Farber Cancer Center in Boston reported that they had no cases of nosocomial Covid-19 infections in HCT or CAR-T patients at their single center, indicating that these therapies can be safely administered during this [pandemic] period. They also found that in alloHCT patients, cryopreservation of unrelated donor products does not appear to negatively affect early clinical outcomes.

However, they did have one patient with myelodysplastic syndrome (MDS) whose transplant was deferred and whose disease transformed to acute myeloid leukemia, highlight[ing] the risk associated with delaying treatment of hematologic malignancies and the benefit of proceeding with definitive therapy during the pandemic, as long as appropriate safeguards are implemented.

Akshay Sharma, MBBS, of St. Jude Childrens Research Hospital in Memphis, Tennessee, and co-authors conducted an observational study of cases reported to the Center for International Blood and Marrow Transplant Research, and found that recipients of autoHCT and alloHCT with Covid-19 had poor overall survival. We found that in [alloHCT] recipients, age >50 years, male gender, and having received their transplantation within the last 12 months were all associated with worse survival, Sharma explained to VJHemOnc at the 2021 Transplantation & Cellular Therapy (TCT) meeting.

Vaccine Safety

The two-dose mRNA-based Covid-19 vaccine BNT162b2 was deemed to be safe and achieve satisfactory serologic status in patients with cancer, although the study authors noted that there was a pronounced lag in antibody production compared with the rate in noncancer controls; however, the second dose did lead to seroconversion.

The prospective-study cohort consisted of 232 patients (median age 68; 57% male) with solid tumors (27% gastrointestinal; 21% genitourinary; 18% breast) who got IV treatment administered at the infusional ambulatory unit of the oncology center, or inpatient service, at the Rambam Health Care Campus (RHCC) in Haifa, Israel. Nearly three-fourths of the patients had metastatic disease and >70% received immunotherapy or a biological agent. Hematologic malignant neoplasms are treated in a different institution so these patients were not included in the study, explained Irit Ben-Aharon, MD, PhD, of RHCC, and co-authors in JAMA Oncology.Study enrollment and follow-up took place from January to March 2021. All patients were on active treatment and received both doses of the vaccine. They were age-matched with healthy healthcare workers (n=261) who formed the control group.

Serum samples were collected after each vaccine dose and in cases of seronegativity, and electronic health records were reviewed for documentation of Covid-19 infection and results of blood cell counts, liver enzyme levels, and imaging studies, according to Ben-Aharons group.

They reported that after the first dose of 29% of the patients were seropositive versus 84% of the controls (P<0.001), while after the second dose, the seropositive rate reached 86% in the patients.

Testing rate ratios/1,000 person-days after the first dose were 12.5 (95% CI 3.4-45.7) for the patients and 48.5 (95% CI 37.2-63.2) for the controls. The authors also found that patients getting chemotherapy showed reduced immunogenicity (odds ratio 0.41, 95% CI 0.17-0.98). Additionally, the rate of documented absolute leukopenia in seronegative patients reached 39%.

No Covid-19 cases were documented throughout the study period, but there were two cases in the patients immediately after the first dose. In the general U.S. population, a little over 10,000 post-vaccine breakthrough infections were reported by April 2021, according to the CDC.

For adverse events (AEs), 69% of the patients reported injection-site pain, followed by fatigue (24%). Also, elevation of liver enzyme levels >1.5 times from baseline levels was documented in 24 patients up to 6 weeks after the first vaccine dose, the authors reported, but the AE spontaneously resolved in 37% of those patients.

As to whether the specific type of cancer treatment had any role in seroconversion, Ben-Aharons group explained that patients with breast cancer comprised 29% of the seronegative group, and 74% of these patients were treated with chemotherapy, and the treatments were diverse. Hence, we cannot assume that a specific class of drugs may hamper immunogenicity but rather that lymphosuppressive agents may induce a lack of effective seroconversion.

Study limitations included the older population and the fact that cancer patients are generally more adherent to public health and safety measures. Finally, the study lacked a control group of unvaccinated patients.

During a January 2021 European Society of Medical Oncology (ESMO) roundtable, Ravindran Kanesvaran, MRCP, MD, of the National Cancer Centre Singapore, noted that both the mRNA and adenoviral vaccines induce both humoral and cellular immunity, which might be a good thing thinking about this population of patients that is often older or has comorbidities. The immunogenicity data that weve seen on older trial participants is promising and it might also work on the slightly immunocompromised population. We dont know the correlate of protection yet, so its hard for us to predict what type of immunosuppressive therapy would impact the vaccine efficacy.

Ben-Aharon and co-authors pointed out that [a]lthough the immunogenicity pattern was gradual and slower than in the noncancer population, after the second dose most patients were seropositive Our study lends credence to the widely adopted recommendation to prioritize patients with cancer for SARS-CoV-2 vaccination.

But many cancer patients have expressed vaccine hesitancy. For instance, a June 2021 survey-based study in Mexican breast cancer patients reported that over a third were uncertain about vaccination, while more than a fourth said they wanted to see the vaccines AEs in others, and 4% said they would only take the jab if it became mandatory. The study authors called for the active participation of oncologiststo educate cancer patients on the benefits of Covid-19 immunization and to endorse vaccination.

Its a message that cancer care specialists have been driving home. Health experts and federal agencies like the CDC all agree Covid vaccination is especially important for people with cancer. Even if the vaccine might be a little bit less effective in someone who is undergoing cancer treatment its actually even more important to take that vaccine, noted Welela Tereffe, MD, chief medical executive, of the MD Anderson Cancer Center in Houston.

In the same YouTube video, David Tweardy, MD, also of MD Anderson, emphasized that itll be important for cancer patients to work with your doctors to decide when to receive the vaccine in relation to when youre receiving chemotherapy or other treatments for your cancer.

ESMO President Solange Peters, MD, PhD, of the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, suggested that all patients under chemo, under immuno-oncology, under hormone therapy, under antibody therapy should be vaccinated. Some of my colleagues would say, If you can avoid giving the vaccine on the day of high-dose cancer therapy, it might be preferable but even if you have to do thatdo that. That is my main message, for the time being we shouldnt compromise this [Covid-19] protection.

Shalmali Pal, Contributing Writer, BreakingMED

Gull Chaudhary and Mushtaq reported no relationships relevant to the contents of this paper to disclose. Co-authors reported relationships with, and/or support from, TherapeuticsMD, Incyte, Seattle Genetics, AbbVie, Acetylon Pharmaceuticals, Astellas Pharma, Celgene, Millennium, Therakos, AlloVir, Juno Therapeutics, Kite/Gilead, Magenta Therapeutics, EcoR1 Capital, Fresenius Biotech, Gamida Cell, Novartis, and Pluristem Therapeutics.

The study by Ben-Aharons group was supported by the Israel Cancer Research Fund.

Ben-Aharon reported no relationships relevant to the contents of this paper to disclose. A co-author reported a relationship with Pfizer.

Cat ID: 118

Topic ID: 78,118,570,633,730,933,118,125,190,926,192,927,151,928,925,934,172

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Blood Cancer Patients and Covid-19: Higher Risks but Vaccine Ready - Physician's Weekly

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Gail Devers is best known as an American track-and-field star who won a gold medal in the 1992 Summer Olympics and two more in 1996. Competing in the 100 meters, 100 meter hurdles, and 100 meter relay, Devers wowed the crowds with her speed, strength, and agility, not to mention her signature long, colorful fingernails.

But her first Olympics, in Seoul, South Korea, in 1988, didnt go so well. In fact, it almost didnt happen, even though just months earlier, Devers had broken the American record in the 100 meter hurdles with a time of 12.61.

Soon after setting that record, Devers began feeling tired and had trouble training. Every time I stepped on the track, she says, every race that I ran, every practice, every time I warmed up was just taking more and more out of me.

Devers managed to qualify for the U.S. Olympic track-and-field team in the hurdles, but not for the 100 meter race, as she had hoped, and she was eliminated in the semifinals.

Things just got worse from there: Her hair starting falling out, her fingernails became brittle, she lost weight, she developed sores on her skin, she started having trouble sleeping, she had headaches and tremors, and she started having memory problems. On top of that, her eyes were bulging and irritated.

To say these symptoms were upsetting would be an understatement. I actually covered my mirrors, because I couldn't stand looking at that person. That image was not me, says Devers.

But even while she and those around her could clearly see that something was very wrong, the doctors she consulted had no answers.

It wasnt until Devers visited her old team physician at the University of California in Los Angeles, where she attended college, that anyone mentioned the word thyroid or suggested she get a thyroid-stimulating hormone (TSH) test.

Two days later she had a doctors appointment, but given how many doctors had already told her nothing was wrong, Devers was nervous.

This time was different: The doctor looked at me and he said, I can tell you're a walking thyroid disorder.

And not surprisingly, The tears just started flowing. I was like, Oh, my gosh. After two and a half years, somebody finally, finally, finally, finally saw what was going on!

Devers was diagnosed with Graves disease, an autoimmune disease thats the most common cause of hyperthyroidism.

In Graves disease, the immune system produces an antibody that stimulates the thyroid gland to produce more thyroid hormone than the body needs.

When this happens, the thyroid gland enlarges an enlarged thyroid gland is called a goiter and makes excessive amounts of thyroid hormone, leading to the symptoms of hyperthyroidism.

RELATED: Treatments for Hyperthyroidism: Medications, Surgery, and Other Therapies

Once Devers started treatment for Graves disease, she was able to start training and competing again, and in some respects, the rest is a gold-medal studded history of Olympic wins and World Championships.

But something still wasnt right.

Devers still had eye pain and cloudy vision, and she was constantly needing to use eye drops. The blurriness was so bad that when she was racing she couldnt even see the hurdles.

How did she make it through an event? I know its eight steps from the blocks to the first hurdle, three steps in between, five steps off the last hurdle to the finish line, Devers recounts.

It took Devers 30 years to find out she had a second condition in addition to Graves disease: Graves ophthalmology, also known as thyroid eye disease.

Thyroid eye disease is caused by inflammation in the tissues surrounding the eyes.

The disease typically occurs along with Graves disease, although it can occur on its own.

Symptoms of thyroid eye disease can include redness, a feeling of grittiness in the eyes or constant eye watering, sensitivity to light, swelling or puffiness, bulging eyes, difficulty closing the eyes fully, double vision, and vision loss.

Several forms of treatment can help to relieve symptoms and treat the inflammation in the eyes.

Generally, treatment of thyroid eye disease includes:

On a Mission to Educate

Now that Devers knows whats going on with her health, she wants to make sure it doesnt take other people with Graves disease as long as it took her to find out about thyroid eye disease.

I feel like I've suffered for everyone in the world, she says. No one should have to go through what I went through. And the way to alleviate that suffering is education.

As the onetime relay runner says, You pass the baton from one person to the other. So what we can do as a community is to pass that baton of knowledge and education.

Devers is a strong believer in writing things down symptoms, questions, concerns and bringing those notes to doctor appointments so you can have a conversation and help your doctor help you. If you don't tell them everything, how can they make a proper diagnosis? she asks.

Deverss running goals helped her push through the challenges that Graves disease and thyroid eye disease put in her path. As she says, I'm a very goal oriented person.

Now that she's 53, Deverss goals have changed, but shes still up for a challenge. Right before the COVID-19 pandemic, somebody suggested she train for a half-marathon to coincide with the Olympic marathon trials in Atlanta, where she lives.

Her first response was, You do know I'm a sprinter. Distance for me is anything over 105 meters. But she trained for it and ran 13.1 miles in 1 hour and 53 minutes.

When shes not running, Devers can be found bicycling, dancing, skating, walking, or volunteering at her kids school. I love to stay fit, she says, and I think my life is about service.

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Why Gail Devers Is on a Mission to Educate About Graves' Disease and Thyroid Eye Disease - Everyday Health

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Living with ADHD while going through menopause can be challenging, but there are ways to manage both.

What do ADHD and menopause have in common other than mood changes and inattention?

Though some symptoms are observable on the outside, folks around you may not understand even half of what youre handling internally, let alone that youre managing both at the same time.

Living with attention deficit hyperactivity disorder (ADHD) comes with its own challenges. And if youre going through perimenopause or menopause, you may face more difficulties.

ADHD is a neurocognitive disorder that has three presentations:

People can receive a diagnosis early in childhood as well as late in life.

Dr. Ellen Littman, a clinical psychologist in New York state, explains that estrogen has powerful effects on brain chemistry throughout your lifetime.

Menopause is among the top biggest events to change estrogen in your body, among starting your period and becoming pregnant.

Estrogen is considered neuroprotective, in that high levels increase the availability of neurotransmitters (brain messengers) like dopamine and serotonin, which enhance cognition, mood, sleep, verbal memory, and even ADHD symptoms, Littman says, who is publishing an upcoming review article about the female hormonal effects on ADHD.

However, your levels of estrogen decline beginning in perimenopause and are spent during menopause.

While people face some symptoms off and on during menopause, Littman says those who also have ADHD experience intensified symptoms.

By understanding the relationship between menopause and increased ADHD symptoms, they are less likely to be ambushed by the amplified difficulties they experience, she says.

Both ADHD and menopause are known for patternless shifts in brain activity and hormone changes.

So, you might begin to see how overlapping symptoms happening concurrently or one after the other can worsen the experience of both conditions and make them difficult to manage.

A 2016 study even looks at the effectiveness of using ADHD medication to treat people experiencing executive function issues during menopause.

While going through menopause when you have ADHD can feel overwhelming, there are ways you can manage both conditions.

Finding a psychiatrist whos well versed and experienced in treating ADHD in people going through menopause can help you get the care you deserve.

While it might not be easy to find a psychiatrist with experience in this area, start by asking your current mental health professional or gynecologist for recommendations.

If you cant find a psychiatrist whos familiar with research demonstrating hormone involvement in ADHD symptoms, Littman suggests sharing information or articles (like this one) with them.

If you feel that your credibility is being questioned, its important to feel entitled to finding the clinician who best fits your needs, she says.

Littman suggests finding a gynecologist whos experienced in treating people going through menopause, and who will also work with the doctor who treats your ADHD.

Since women now spend about a third of their lives in menopause, it is critical to find a treatment regimen tailored to your specific needs, she says.

According to a 2019 survey of postgraduate resident trainees in family medicine, internal medicine, and obstetrics and gynecology in U.S. residency programs, only 6.8% of them reported feeling just adequately prepared to manage women experiencing menopause.

No one clinician is knowledgeable about all aspects of each individual experience, but Littman says finding doctors who will collaborate and communicate with your gynecologist can help tailor treatment.

For instance, if your ADHD medications need adjusting, as well as your decreasing estrogen levels, having both your gynecologist and doctor who treats your ADHD collaborate could help.

While pharmacologists often adjust the dosage to meet the new challenges, increased estrogen could address both menopausal and ADHD symptoms. Bioidentical hormone replacement therapy (HRT) is one route to increased estrogen for many women, Littman says.

Although your doctors may be hesitant to communicate with each other, being assertive and informing them of your conditions, as well as bringing information from each doctor to your appointments, can help ensure theyre in tune with whats going on with your body.

While theres a wide range of menopausal symptoms that occur on a continuum, Littman points out that ADHD can worsen symptoms like impaired cognition and mood.

In fact, a 2019 research paper suggests that ADHD symptoms, and even concurrent symptoms from other conditions, are also vulnerable to the hormonal changes experienced during menopause, says Littman.

Both conditions can muddle with your executive functions, a clinical term for your:

If you find that these areas of your life are becoming more difficult to manage, coming up with a plan to help navigate them can make your days easier.

For instance, if keeping and organizing appointments and commitments is difficult, setting an email calendar reminder so you get notifications on your phone, tablet, and desktop can help you stay on track.

If self-monitoring is a blind spot as of late, you could try leaning on your inner circle to gently give you a signal if agitation or strong emotions are coming off more than intended.

You might also look into present moment awareness to reconnect with mindfulness and strengthen your self-awareness.

In addition to seeing a professional, Littman suggests pursuing your own psychoeducation. Consider bookmarking the following resources:

The more you can understand about the relationship between your [brains response to ADHD] and your body in menopause, the more you can be an active participant in your treatment. And the more your support network understands about your challenges, the more supportive and compassionate they can be, Littman says.

While managing your ADHD while going through menopause can be challenging at times, there are ways to make the process easier.

Littman says that on the clinical front, new research brings hope for better treatments ahead.

Were on the brink of an exciting new understanding of the experience of women with ADHD, she says. As new studies continue to implicate the powerful role of hormones in womens experience of ADHD, the potential for more comprehensive and successful treatments may be on the horizon.

You can stay tuned for Littman and teams upcoming study on ADHD and estrogen, titled: ADHD in Females Across the Lifespan and the Role of Estrogen. It publishes August 2021 in The ADHD Report.

Original post:
Tips to Manage when You're in Menopause with ADHD - PsychCentral.com

Recommendation and review posted by Bethany Smith

Local health-care providers are being asked to fill out a survey to help make it easier for people who are transgender to access care in Hamilton.

The Hamilton Trans Health Coalition is calling on primary care providers to explain what barriers they face in providing gender-affirming care for patients who are trans.

Gender-affirming care includes things that are related to transitioning, like HRT (hormone replacement therapy) or surgery, but also includes doctors recognizing their patients pronouns and chosen names, and not making assumptions about their sexual history or sexual orientation.

Cole Gately, chair of the coalition, said the goal of the survey is to determine what kind of barriers and motivators are impacting Hamiltons health-care providers when they have a patient who is trans.

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We just want to know what are the barriers, whats getting in the way? Why arent you doing it and how can we help? There are lots of resources out there. Maybe youre not aware of them.

Since introducing a project co-ordinator earlier this year, the coalition has heard from some doctors, but its also heard from many trans Hamiltonians who are travelling outside of the city to get basic health care that their own doctors are capable of providing.

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Gately said some people are being told by their doctors to seek out specific care on their own and then theyll write a referral, but he said that burden shouldnt be on the patient if providing that care is well within the doctors own abilities.

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What I said to somebody yesterday was, imagine if you broke your wrist and you went into the doctor and the doctor said, Well, you find an orthopedic surgeon and then Ill make the referral. That doesnt happen. The doctor finds the orthopedic surgeon for you and makes the referral because the doctor is the expert.

The survey is open until July 28 and the coalition is urging any and all primary care providers in Hamilton including family doctors, registered nurses, nurse practitioners and physician assistants to fill it out.

2021 Global News, a division of Corus Entertainment Inc.

Link:
Primary care providers called on to respond to survey to improve trans health care in Hamilton - Global News

Recommendation and review posted by Bethany Smith

Arianna Sholes-Douglas remembers the moment her body was in the grips of perimenopause though she didnt recognize it for what it was at the time, despite being an OB-GYN and integrative health physician focusing on womens health. Sholes-Douglas was performing a C-section, a surgery she estimates she had done over a thousand times, and her brain just blanked.

I had a total brain freeze. I couldnt remember what to do, she recalled. It was very scary, and I didnt know who to talk to or what to do.

At first, she worried it was early-onset Alzheimers. But the big changes shed been experiencing in cognitive function were hormonal. She was going through perimenopause, the transitional period before menopause when a womans body starts making less estrogen until eventually her ovaries stop releasing eggs.

And shes not alone about being in the dark. Many Gen X women and cusp millennials who are at the age range when perimenopause has begun or could soon start have far too little support and information.

We havent been educated. Patients havent been educated. Doctors havent been educated. There really hasnt been a resource thats been reliable for women, so they are caught off-guard, said Sholes-Douglas, who went on to write the book The Menopause Myth: What Your Mother, Doctor, and Friends Havent Told You About Life After 35.

Because in their minds, theyre thinking menopause is an old lady issue, she added. They think its only relevant when they stop having a period.

But thats not true. So here are three important things Xennial women should know about perimenopause:

It can start in your 30s or 40s.

There arent lines around when perimenopause begins, in part because it varies by individual and also because the types of symptoms are so broad. The term perimenopause really just means around menopause.

Its also a stretch of time that can drag on for a while. Many women start to experience symptoms five or even 10 years before they stop having a period (though the average is about four years). And given that full menopause can happen when women are in their 40s or 50s, perimenopause can begin when theyre in their early 40s or even mid-30s.

Since 5% to 7% of women are fully menopausal by age 45 (theyve gone that magical full year without a period), they could be experiencing these symptoms at age 40, not thinking a thing about menopause because these symptoms can be very vague and dont come with a big sign You are entering perimenopause, said Mary Jane Minkin, an OB-GYN with Yale University and founder of the informational website Madame Ovary.

Youre still able to get pregnant during perimenopause.

If youre a woman in your 30s or 40s who is planning to have children (and many women are) and youre fretting that you might instead enter perimenopause, dont freak out. Its very much still possible for women to get pregnant during this phase, though its definitely worth bringing up with your doctor if you have concerns.

The symptoms go way beyond hot flashes.

When most people think menopause, they think of hot flashes. And many (if not most) women getting closer to menopause will experience hot flashes, or brief feelings of being overheated, at some point ranging from pretty mild to really severe.

But there are so many other symptoms that can come along with perimenopause, including missed periods or periods that are heavier or lighter than usual, mood swings, changes in cholesterol levels and bone density, urinary incontinence and cognitive fuzziness.

Many [women] get disrupted sleep usually falling asleep quickly as they are exhausted, but are then up at 1 a.m., sometimes with a hot flash, sometimes without. They may have headaches, they may be achy, they may have some vaginal dryness or urinary leakage (although that usually comes later), Minkin said.

Perimenopause can affect your sexual health and well-being, as well. The sexual aspect part of perimenopause is something I deal with a lot, Sholes-Douglas said. Women are very much caught off-guard when they experience a decline in libido, vaginal pain, vaginal dryness and they dont know why.

But while the possible symptoms associated with perimenopause are wide-ranging, they all really come back to the hormonal changes women go through in the run-up to menopause, as estrogen and progesterone levels fall or rise and fall in uneven spikes.

The Good Brigade via Getty Images

Finding adequate care and support can still be difficult.

Though theres far more information available to women and health care providers now than had been the case a few decades ago, and many active support communities have flourished, perimenopause is still something women arent adequately educated about, according to experts.

Minkin said Gen X women are probably slightly better prepared, but not dramatically so. Sholes-Douglas was more emphatic: Most women are just not prepared.

There are a few reasons for this, one of which is that there simply isnt a test doctors can perform to see if women have entered perimenopause.

Hormone levels may not show much, Minkin said. For example, a doctor might do an estradiol test to check your estrogen levels, but since normal levels during a menstrual cycle range wildly (from 45 to 350 picograms per milliliter), its hard to know where your level should be.

Lets say we draw a blood level of 50. Well, is that normal? It may be. But if your level should be 300, thats low, Minkin explained.

Its a tough diagnosis to make at the time, she added. When the patient goes that year without the period, you can then say, Well, hey that was all perimenopausal!

On top of which there is a lack of consensus about how to treat symptoms of perimenopause even if it is clear thats the issue. Hormone therapy, which involves taking supplemental hormones, is one option, but some past studies have indicated it can come with other health risks. Some doctors might recommend lifestyle changes to help manage symptoms; in other cases, women might take medications to more directly address such symptoms as vaginal dryness or mental health changes.

Unfortunately, a lot of this ends up falling on women. They end up needing to connect the dots in their own symptoms and find health care providers who have experience dealing with perimenopause. Which is why it is so important for Xennial women to be aware of whats happening in their bodies now, or what lies just ahead.

Ive had countless patients tell me they went to the doctor and told them they suspected they were perimenopausal, and the doctor said: Oh, youre too young for that. Youre too young for that, Sholes-Douglas said.

You should not assume that your doctor is going to know more about this than you do, she added. On some level, obviously they will. But dont underestimate the power you have.

More:
Perimenopause: The Women's Health Issue No One's Talking About Enough - HuffPost

Recommendation and review posted by Bethany Smith

I am a 77-year-old woman. I am 5 feet, 2 inches tall and weigh 107 pounds. I take no medication. When I went to the doctor last week, he found that my alkaline phosphatase was 176, my ALT 10, and my AST 11. He told me I had fatty liver and to get a scan, but I had no way to get to the place to have it done. He did not say anything else about it. I have no symptoms. Does this sound like fatty liver to you? I did not really like my doctor, but with my insurance it is hard to change doctors. If I do have fatty liver, is there anything I can do for it?

Fatty liver is an increasingly common problem. Risk factors include being overweight and having diabetes, high blood pressure and abnormal blood cholesterol levels.

Alcohol use is also a cause of fatty liver, and all people with fatty liver are strongly recommended to abstain from alcohol entirely. The primary treatment is diet and weight loss.

It sounds like there was some missed communication between you and your doctor. Fatty liver is a possibility; however, it does not seem likely to me, as you have not identified any of the risk factors, and you are certainly not overweight if anything, you are a bit underweight.

Further, although the alkaline phosphatase can be elevated in fatty liver yours is just a bit high it is more common for AST and ALT to be elevated, which yours are not.

An ultrasound scan is a good, but not definitive, way of looking for fatty liver. A liver biopsy is still the definitive test, but its often not done in people whose history, physical exam and ultrasound are all suggestive.

A slightly abnormal alkaline phosphatase does not necessarily mean you have a liver problem. Bone issues fractures, Pagets disease of bone, high thyroid and parathyroid hormone levels can cause a high alkaline phosphatase, too.

Additional liver tests checking the GGT level or specifically what kind of alkaline phosphatase you have, by isoenzyme analysis can make the source of the elevated alkaline phosphatase clearer.

Getting an ultrasound scan and additional blood tests is a reasonable place to start. Unfortunately, lack of confidence in your physician is a different problem.

If you really cant get a new doctor, then you need to have a conversation about proceeding with evaluation in such a way that you can do so while being confident that you are getting good advice.

A few years ago, I read that the herbal supplement feverfew may help with some migraines. Having suffered with severe migraine for over 50 years, I decided to try it. I take one capsule four times a day, and it has completely rid me of my migraines. Would you please mention it again?

Feverfew is a common herbal remedy to prevent migraine, and although not all trials have shown benefit, the majority of studies I have read showed that it is more effective than a placebo and the side effect risk is very small.

Other nonprescription treatments that have been shown in most studies to be beneficial include magnesium, riboflavin and coenzyme Q10. They are generally safe and well-tolerated, and I hope others may get the same relief you have found.

View original post here:
To Your Good Health: What is treatment for a fatty liver? - Agri News

Recommendation and review posted by Bethany Smith

Delayed mammograms and breast cancer diagnoses during the COVID-19 pandemic may have a small long-term impact on breast cancer mortality rates up to 2030, according to results of a study with simulation modeling.

Findings from this study published in the Journal of the National Cancer Institute highlight the importance of continuing breast cancer screenings and evaluations in symptomatic women.

Some women simply skipped their mammogram if they were scheduled to undergo a mammogram during the pandemic, said Oguzhan Alagoz, who holds a PhD in industrial engineering and is a professor of industrial and systems engineering at University of Wisconsin-Madison, in an interview with CURE. What we are suggesting is rather than skipping the mammogram and waiting for your next mammogram whether it is in two years or next year this suggests you need to make up that missed mammography exam as soon as possible. Thats the primary means of undoing the impact of the pandemic.

When the COVID-19 pandemic first started, screening mammography and diagnostic mammography declined up to 80%, according to the studys introduction. There were also changes in breast cancer treatment protocols, which led to treatment delays and lower rates of chemotherapy administration.

In this short term, there was a huge reduction in the number of screenings (and) diagnoses, Alagoz said. The concern is if we have these short-term declines in breast cancer control activities, what will be the impact in the long term? Breast cancer is an interesting disease, where if you delay mammography, youre not going to see the full effect of it in six months or 12 months. Sometimes, some of these effects are seen in five years, 10 years.

To assess the potential long-term impact of breast cancer control disruptions during the COVID-19 pandemic, researchers used three established breast cancer models to simulate reductions in mammogram screenings, delays in the diagnosis of cancer in symptomatic patients and reductions in chemotherapy treatments for women with early-stage breast cancer. These scenarios were assessed within the first six months of the pandemic, when reduced screening rates were observed, following a return to patterns similar to before the pandemic.

Alagoz provided the reason as to why researchers only focused on the first six months of the pandemic rather than the entire pandemic.

By the end of the summer of 2020, many practices, clinics and health systems actually made up all of the missed mammography exams, Alagoz said. We have seen the screening volumes basically reach almost 100% capacity back in the summer. I (spoke) with our radiologist collaborators, (who) are telling me that they scheduled additional weekend and weeknight mammographic screenings.

Based on the model projections, researchers found that by 2030, there could be 950 cumulative excess breast cancer deaths related to reduced screenings during the COVID-19 pandemic. In addition, there could be 1,314 deaths from the delayed diagnosis of symptomatic patients and 151 deaths linked with reduced chemotherapy in women with hormone-positive, early-stage cancer. Collectively, there may be an estimated 2,487 excess breast cancer deaths, which represents a 0.52% increase in deaths by 2030 compared with models indicating breast cancer deaths without the effect of the COVID-19 pandemic.

Although any increase in mortality rates isnt ideal, Alagoz mentioned that these results were a pleasant surprise for his research team.

Before I started this study, I was really expecting a significant number of breast cancer mortality over the next 10 years due to the pandemic, Alagoz said. Fortunately, the impact is actually relatively small (in magnitude). I was expecting maybe 10,000 additional deaths, 15,000 additional (deaths), but our modeling suggests that we are going to see an additional 2,500 deaths over the next 10 years due to the pandemic.

He mentioned that these lower-than-expected increases in mortality rates are a somewhat positive finding of the study.

I think the silver lining in this unfortunate paper is that the impact is not as high as I was scared it would be, which is good news, Alagoz said. Primarily, that is because many practices after the initial shock of the pandemic and many patients were able to actually make up the exams and did resume the normal operations within a six-month period.

Alagoz added that delays during the COVID-19 pandemic did not greatly affect women who were already diagnosed with breast cancer.

Our findings show that disruptions didnt affect (these women) too much, Alagoz said. In other words, anybody who was supposed to get surgery, radiotherapy or chemotherapy, they already got the treatment. Oncologists aware of the really terrible potential effect of delaying the treatment or stopping the treatment didnt really change treatment practices very much. The patients who were already diagnosed with breast cancer prior to the pandemic, the effect of the pandemic on their care or mortality, we found, is limited.

Although there are some effects of the COVID-19 pandemic that can be undone, such as making up missed mammograms sooner rather than later, Alagoz said there are some consequences that cannot.

For example, many women during their self-exam (or) during their annual physician visit, they observe a palpable lump in their breast and then they go and visit the clinic, Alagoz said. And those cases dropped significantly during the pandemic. There is very little we can do to undo those effects. Those women already came for a delayed diagnosis, maybe like three months (or) six months later, and, unfortunately, there is not much we can do to undo that. But at least for the screening mammography exams that women (missed), we can certainly mitigate the impacts of the pandemic.

For more news on cancer updates, research and education, dont forget tosubscribe to CUREs newsletters here.

Continue reading here:
Disruption in Breast Cancer Care During COVID-19 Pandemic May Slightly Increase Long-Term Mortality - Curetoday.com

Recommendation and review posted by Bethany Smith

Insulin resistance, also known as impaired insulin sensitivity, is when someone has built a tolerance to insulin, the hormone responsible for regulating blood sugar levels.

Although insulin resistance precludes the development of type 2 diabetes, not everyone who has the condition will develop type 2 diabetes or its precursor, prediabetes. In fact, insulin resistance can be reversed with proper diet and exercise.

Here is what causes insulin resistance, how to recognize it, and the best treatment options.

Insulin resistance occurs when the cells in your muscles, fat, and liver are less responsive to insulin and therefore struggle to absorb glucose aka sugar in the blood.

Typically, you get a boost of sugar in your blood after you eat something containing carbohydrates. This boost signals to your pancreas to release insulin, which then helps your cells absorb the sugar and convert it to energy so you can function normally. Insulin resistance disrupts that process.

"When cells in the body become insulin resistant, more insulin is required to do the same job [aka lower blood sugar levels]," says Daniel Vatner, MD, an endocrinologist at Yale School of Medicine. "A person with insulin resistance needs to make much more insulin after a meal, or they will not be able to store and use sugar properly."

However, your body can only produce so much insulin on its own. So, there's a critical tipping point where your cells become so insulin resistant that they lose control over your blood sugar, and you end up with dangerous, chronically high blood sugar levels.

When there's too much sugar in your blood for too long, your body eventually stores it as fat. That's why insulin resistance increases the risk of being overweight and obesity-related conditions like:

Insulin resistance rarely comes with any noticeable symptoms. And most tests designed to detect insulin resistance are complicated and expensive.

Therefore, a healthcare provider will usually rely on tests that assess your blood sugar levels. These tests include:

All of these tests can also be used to diagnose prediabetes.

In rare cases, some people with insulin resistance may also develop a skin condition called acanthosis nigricans. This condition causes the skin to develop thick, dark, purplish patches, typically in the underarms, groin, or on the back of the neck.

Being overweight or obese can significantly increase your risk of insulin resistance, says Vatner.

"As an individual gains weight, fat can accumulate where it doesn't belong, as in the liver or the muscle," he says.

As fat gets into the cells, it can interfere with the cells' ability to respond to insulin, forcing the pancreas to make more insulin to compensate.

However, people of any size can also become insulin resistant.

You should regularly monitor blood sugar if you have risk factors for insulin resistance, such as obesity, a sedentary lifestyle, or a family history of type 2 diabetes . Even if you don't have these risk factors, you should start getting tested at the age of 45, says Mark Schutta, MD, medical director of the Penn Rodebaugh Diabetes Center.

Exercising and eating healthy are the most effective strategies for reversing insulin resistance. Even just a 5% to 10% loss in body weight can help to reverse insulin resistance, says Vatner.

Exercise not only plays an important role in weight management but can also help people with insulin resistance manage blood sugar. A 2016 review found that regular, moderately-intense physical activity like walking or biking for at least 30 minutes, three to five days a week was associated with improved insulin sensitivity as well as blood sugar control.

Schutta advises starting with a brisk 30- to 45-minute walk several days a week and then working your way up to 150 minutes of weekly moderate to vigorous aerobic exercise.

Important: Always consult with your physician before starting a new exercise program especially if you've been sedentary and/or have any pre-existing conditions to avoid injury.

Diet also plays a crucial role in managing and reversing insulin resistance. If you have insulin resistance, physicians may suggest you follow the Mediterranean diet, a plant-based diet, or a low-carb diet, like the Atkins diet.

In general, Schutta recommends limiting your intake of:

Schutta also recommends eating more:

Vatner says insulin-resistant patients with co-occurring conditions may be prescribed the following medications:

Insulin resistance is a serious, but treatable condition. If left untreated it could develop into prediabetes, metabolic syndrome, or type 2 diabetes, all of which increase your risk of heart disease and stroke.

While insulin resistance does not have any symptoms, it can be diagnosed through a blood sugar test.

To treat and reverse insulin resistance, eat a healthy diet full of fruits, vegetables, lean proteins, and whole grains while exercising for at least 150 minutes a week.

The rest is here:
How to reverse insulin resistance through diet and exercise - Insider

Recommendation and review posted by Bethany Smith

With the normal pressures of work compounded by the pandemic, stress and burnout are proliferating in the business world. Even before Covid-19, stress and burnout were ravaging the health of Americans. The number of hours worked is said by the non-profit American Institute of Stress to be the main source of job stress and this makes work especially problematic in the United States where Americans have a work ethic that is second to none.

A report a few years ago by the International Labor Organization showed that US workers averaged nearly 2,000 hours of work every year (40 hours per week x 52 weeks = 2,080 hours), or nearly 350 more hours per year (nine more weeks) than Europeans.

This is important because reducing stress is still the most important thing we can do for our health. Among other things, stress increases the risk of heart disease by 40 percent and the risk of stroke by 50 percent, and the American Institute of Stress tells us that three out of four doctors visits are for stress related ailments, and that stress is the basic cause of 60 percent of all disease and illness.

Whats the solution?

Many advocate shortening the work week. In Iceland, a trial from 2015 to 2019 of almost 3,000 people found that shortening the work week from 40 hours to 35 or 36 hours with no reduction in pay resulted in productivity either remaining the same or increasing over the working period, while perceived stress and burnout went down.

Microsoft Japan tried a four-day work week without a pay reduction over five weeks and reported happier workers and a 40% increase in productivity. And in 2018 Perpetual Guardian in New Zealand tried a four-day work week over 8 weeks for 240 of its staff. Employees there reported enjoying a better work-life balance and reported their stress levels decreased by 7%. The studies show that the workers reported less stress, but, of course, workers are motivated to praise shorter work weeks without pay reductions, and they may even be inspired to greater productivity during their working hours.

But there are doubters about this as a permanent solution, and, of course, some people find happiness in their work and dont want or need a shorter week. In all events, shortening the work week isnt a complete solution to stress and stress-induced disorders because of the myriad potential sources of stress that we encounter at work, at home, and in all our interactions. Is there then something we can add to better equip people to deal with the stresses and strains of life?

First, we should define stress to understand how we can best overcome it. Conversationally, we speak of the stress of the job or the stress of a divorce, ascribing the stress that people experience to an external event. However, more scientifically, stress refers to the internal bodily reactions to those events that are so disruptive to health.

The external events that are potentially stress-producing in the body are known as stressors or just stressful situations, to which individuals react very differently. One person in a given situation may suffer a stressful reaction such as a fight-or-flight response or a hormonal imbalance that can precipitate disease, whereas at least some people handle the situation with ease. Unfortunately, the latter appear to be in the minority.

A recent article in the Washington Post (What burnout really means, and what bosses and employees can do about it) tells us that the pandemic has caused prolonged stress to many, leading to burnout. Technically burnout is a combination of emotional exhaustion, and a reduced sense of personal accomplishment, and often a take this job and a shove it attitude. The author of the Post article says that experts say companies need to allow staff to set their own schedules, have meeting free days, proactively address rude workplace behavior, and avoid praising or normalizing working around the clock.

But these strategies, and even a shorter work week, seek to eliminate the stressors, but dont directly address the internal disorder that is stress, and they dont enhance our resilience to stressful stimuli. While eliminating stressors (if we can) may help in reducing future disruptions of the employees physical state, it does nothing to address the current internal disorder that leads to the headaches, stomach problems, high blood pressure, insomnia, and other stress-related disorders. And, of course, changing the work environment wont succeed for those companies unwilling or unable to change their environment. So, how do we overcome workplace stress?

Much stress is eliminated through night-time sleep. Although our bodies incur a heavy stress load on a regular basis, stress is a physical abnormality, which the body normalizes or heals whenever it is given the opportunity. When we become ill, we may relieve the symptoms with medicines, but Sir Hans Krebs, a Nobel Laureate in physiology, says The physician and the patient can do no more than assist nature, by providing the very best conditions for your body to defend and heal itself.

The rest we gain during sleep is a crucial requirement for assisting nature and allowing the body to heal itself. In fact, sleep is so important, it is part of every physicians prescription for virtually every disorder. However, while we naturally eliminate a lot of stress through sleep, the statistics tell us that most people are not winning their fight against stress and have come to accept being stressed as normal. We manage our stress with an increasing number of pharmaceuticals as we get older and think nothing of a full medicine cabinet to deal with our many disorders. If assisting nature is the key, what more can we do to help our bodies eliminate stress? How do we supplement our sleep if rest is so beneficial to health? This is where the yogis approach comes into play.

Research by co-author Dr. Wallace first published in Science and Scientific American in the 1970s showed that the meditation technique he analyzed, the Transcendental Meditation (TM) technique, produced a unique state of rest and orderliness in the mind and body, correcting physical disorders beyond what sleep had accomplished. His research showed that during the TM meditation session, the body gained a profound and unique state of rest. During the TM practice, even though the meditator was alert, the research showed remarkable decreases in oxygen consumption and respiration, reduced concentrations of blood lactate levels (high blood lactate is associated with anxiety), and a marked increase in skin resistance (associated with relaxation).

Later studies by Wallace and his colleagues showed reductions in cortisol (the stress hormone), as well as increases in serotonin (the happiness hormone), increases in blood flow to the brain, and perhaps most importantly, a marked coherence in the functioning of the brain. Sleep heals by creating order where there is disorder, but, interestingly, the rest during the Transcendental Meditation practice has been found to create more coherence, so in some respects it is more profound than what occurs during sleep.

The charts above show EEG brain wave measurements during sleep and the Transcendental Meditation technique. The mountains or spindles show periods when there is especially high coherence in the brain wave activity. High brain wave coherence is associated with memory, concept learning, creativity, high self-esteem, and reduced anxiety, depression, and other disorders, whereas abnormally low brain wave coherence is associated with autism, schizophrenia, Alzheimers, and other mental disorders. This is why researchers are so interested in studying brain waves.

And as can be seen from the charts, the individual who has been practicing TM for four months has significantly more brain wave coherence during the TM session than during sleep. And the five-year meditator has extremely high levels of brain wave coherence both during the meditation session and before and after meditating when just sitting with the eyes closed (see the EC or eyes closed period in the meditators charts). This is a level of coherence not found in other meditation practices.

Being resilient in the face of stress is also important since we cant possibly eliminate all the stressors in our lives. An article by Dr. Wallace recently published in Medicina describes a series of studies on TM that investigated the meditators response pattern to stressful stimuli as compared to a relaxation control group.

The meditators heart rates and other physiological measurements increased appropriately in response to stressful stimuli, but the meditators recovered much more quickly than the non-meditators, basically brushing off a situation that would tend to have a lasting effect on the non-meditators and disrupt their nervous systems. Dr. Wallace coined the phrase neuroadaptability to refer to the more resilient physiology that can better withstand stressful events.

Another interesting analysis by Dr. David Orme-Johnson, a former professor at Maharishi International University in Iowa (where all the students learn TM), determined that the number of medical visits of about 2,000 TM meditators were just a fraction of the number of visits of non-meditators of comparable age, gender, and profession, who had similar health insurance policies. Over the five-year study period, the TM meditators had significantly fewer incidents of illness in 17 medical treatment categories, including 87 percent less hospitalization for heart disease, 87 percent less for nervous system disorders, 73 percent less for nose, throat and lung diseases (including virus caused diseases), 65 percent less for metabolic disease, including diabetes, and 55 percent less for cancer.

Our new book, The Coherence Effect (Armin Lear Press, 2020), has many personal accounts of business people overcoming stressful work situations. Josh Griffith is one good example. He went from being burned out on the job to having the enthusiasm of a new hire. Josh has been the head writer for the popular daytime TV shows Days of Our Lives and The Young and the Restless. In 2013, he was having serious stress issues at work, and he started looking into meditation practices. Co-author Marcus interviewed Josh a few years ago after he had tried other techniques and had been practicing TM for a year. Josh said:

I saw a celebrated doctor on television and decided to try a meditation he said would help. So, I tried his meditation for about a year . . . . It was kind of helping, but then the work issues got worse and I was still feeling the same way that I had before.

Then Josh saw an interview about TM on television, and he decided to try it. He said:

In the world of daytime TV, youre having to create five shows a week. As head writer [The Young and the Restless] I was responsible for all the stories that aired. I walked away from it a few years ago because I felt burned out. It was too much of an output, and I didnt feel the quality of the output was something I could be proud of. It was taking such a toll on me that I walked away.

Then I started doing TM. I thought I was a meditator before starting TM. Boy, was I wrong. I was offered the head job on Days of Our Lives, and I agreed to take it because with TM I already felt sort of a creative energy bubbling back inside of me. So, I stepped back in, and it was sort of the case where I felt like Im back at the beginning of the career.

I felt like I had the energy that I had when I first started doing daytime. I was able to come in and the ideas flowed nonstop, whereas before I didnt know if I would be able to finish this. I was thinking I dont know what Im going to do Ive hit a wall. TM allowed me to generate so many story ideas that it was, in a way, sort of like a rebirth. You know Ive had a 30-year career. And the changes happened within a month of practicing TM. I feel like Im starting [my career] now. I feel like a 25-year-old again.

In years past, businesses have been slow to adopt meditation as a tool. That is changing and will change even more once businesses use brain-wave coherence as a means of evaluating different meditation programs. We have referred to some of the findings on Transcendental Meditation, a technique that we have each practiced for about 50 years. If you are interested in trying a meditation program, there are many to choose from, but we suggest letting science be the guide in selecting one, and we say the principal criterion needs to be the degree to which the program creates coherence in the mind and body, especially in the brain. Because the brain is the control center of the body, when the EEG activity is coherent, it has a maximum effect in creating the orderly and neurologically adaptive state that counteracts stress and makes us more resilient.

Written by Jay B. Marcus.

Read more from the original source:
A Yogi's Take on Stress and Burnout - CEOWORLD magazine

Recommendation and review posted by Bethany Smith

Females in Action South Coast is a Fall River-based organization for women that formed11 months ago during the COVID-19 pandemic.

Its member work out together at North Park in Fall River twice a week, Wednesdays at 6:15 p.m. and Saturdays at 8 a.m. There is no registration fee; just show up and get involved.

In addition to the workouts, members are also building friendships and helping their community along the way.

Organizer Caitlin Botelho and member Andrea Silvasaid this week on Townsquare Sunday that Females in Action is all about fitness, friendships, and philanthropy. The group has been involved in various charitable efforts during its first year.

Now the organization is looking to increase its numbers and expand to New Bedford.

Females in Action is actually a national programwith active groups in 20 states. It first began in North Carolina in 2013.

Caitlin Botelho, a Fall River native, was living in Tennessee at the time and became involved. She returned home in 2019 and started what's believed to be the first FiA chapter in the Northeast.

Both Caitlin and Andrea spoke about their experiences with FiA, and their hopes of getting more women involved. Their interview can be heard here:

Townsquare Sunday is a weekly public affairs program which airs Sunday at 6 a.m. and 11 am. on 1420 WBSM. The program highlights individuals and organizations working to make the SouthCoast a better place to live and work.

If you would like your organization featured on Townsquare Sunday, please e-mail the host at jim.phillips@townsquaremedia.com.

Read the original:
Fall River's Females in Action Hopes to Expand [TOWNSQUARE SUNDAY] - wbsm.com

Recommendation and review posted by Bethany Smith

TestoPrime is a dietary supplement that can help struggling with low testosterone levels. Testosterone is very important for overall male health as it can contribute to ones energy levels, stress response, muscle growth, sexual health and much more. It is common for men above the age of 40 to experience some sort of decline in their natural testosterone level. Issues such as erectile dysfunction, a lack of libido, weight gain, and low energy become common over time and even some younger people can suffer from the same problems. Taking a natural supplement that can boost the bodys natural testosterone levels can have a significant impact on ones overall health. TestoPrime is another addition to a long list of supplements that claim to boost natural testosterone levels in the body. Is the supplement worth purchasing? Does it work? Here is everything you need to know about TestoPrime.

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TestoPrime is a natural supplement that anyone over the age of 18 can use. The supplement is intended for those men that are suffering from low testosterone levels as it can help bring them back to the level they need to be.

If youre experiencing some form of erectile dysfunction, low sex drive, low energy levels, fat gain, symptoms of depression, loss of body hair, chronic fatigue, and are extremely unmotivated, then you may be suffering from low testosterone levels. Testosterone is a very important hormone for male health, and it should not be overlooked.

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While many male enhancement supplements tend to have nasty side-effects, that is not the case with TestoPrime. The supplement consists of different antioxidants, minerals, and other nutrients that help improve the different mechanisms within the body for optimal health. Since the composition of the formula relies on natural ingredients, there are no side-effects making the supplement safe to consume. Although a prescription is not required to use TestoPrime, you should still consult your doctor if you are suffering from any other underlying health problem.

Overall, TestoPrime looks like the answer to the common problems faced by most men. If you are facing any of the problems mentioned above, then consider TestoPrime as its a safe and affordable option.

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How Does It Work?

TestoPrime works by using a natural formula full of different powerful ingredients that support the bodys natural testosterone production mechanisms. However, thats not the only thing the supplement does, otherwise it would just be another testosterone booster. The ingredients inside the supplement also target the different things inside the body that could be contributing to low testosterone levels.

For example, stress is a big contributor to low T-levels and the supplement works inhibit the stress hormone cortisol to reduce the impact it has on the bodys testosterone levels. Similarly, there are different mechanisms inside the body that are responsible for converting testosterone into DHT (an androgen derived from testosterone), and estrogen. The ingredients inside the supplement work to reduce such mechanisms and prevent the conversion of testosterone. By reducing the rate at which testosterone is converted, and by promoting natural production of testosterone, TestoPrime can help support healthy T-levels in the body for fantastic health benefits.

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Moreover, everything about TestoPrime is 100% safe and natural. As youll see listed below, the supplement uses a completely natural formula full of different ingredients that you may have already heard of. The manufacturers simply bring all the best ingredients under one supplement and use their purest and most potent forms for the best results. There are no side-effects of taking TestoPrime, and the manufacturing process also follows all the good manufacturing practices which helps keep the quality high.

Therefore, if youre in the market for a supplement that can help improve your health naturally, then TestoPrime might be the right choice for you. However, its recommended that one does their own research as well in order to make an informed decision.

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Pricing and Refund Policy

TestoPrime is a reasonably priced supplement that comes in three differently priced bundles priced as follows:

The price per bottle decreases as you go for the multi-bottle deals, and they become even better value for money thanks to the two free e-books that come with them. Each purchase of TestoPrime is also protected by the manufacturers 100% satisfaction guarantee. You can use the supplement for yourself and if you feel like it is not working out for you, then you can opt for a full refund; no questions asked.

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TestoPrime has potential to be one of the best supplements out there. Men all over the world face many problems with their health due to low T-levels and the supplement can help counter that with its natural formula. TestoPrime can help improve muscle growth, reduce stress, promote fat loss, and much more thanks to a safe, and natural formula. The supplement also comes with two free guides that can help amplify its benefits. No side-effects, and the fact that the manufacturer is offering a money-back guarantee speaks volumes about the confidence they have in their product. Therefore, TestoPrime seems like a risk-free investment and worth a buy if youre looking to naturally boost your testosterone levels. You can purchase it from here.

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Disclaimer

Please note that any guidelines and advice given here are not a substitute for medical advice. Please consult your physician if you are under medication or have doubts following the advice/instructions given. Individual results may vary.

View post:
TestoPrime Reviews - Testo Prime Testosterone Booster - The Ritz Herald

Recommendation and review posted by Bethany Smith

DUBLIN, July 15, 2021 /PRNewswire/ -- The "Stem Cell Banking Market: Global Industry Trends, Share, Size, Growth, Opportunity and Forecast 2021-2026" report has been added to ResearchAndMarkets.com's offering.

The global stem cell banking market exhibited strong growth during 2015-2020. Stem cell banking is one of the most promising as well as the fastest growing segment of the next-generation stem cell therapy. It is the process of extracting, freezing and storing stem cells for potential future use. Some of the sources through which stem cells are obtained include embryo, umbilical cord, cord blood, placenta and bone marrow. These cells are used for treating a number of different diseases including diabetes, thalassemia, leukemia, sickle cell anemia and cardiac diseases. Moreover, they are also employed for generating platelets, red blood cells and white blood cells. The potential of stem cells to regenerate has led to their applications in tissue engineering, gene therapy and regenerative medicines. Looking forward, the publisher expects the global stem cell banking market to reach a value of US$ 21.5 Billion by 2026.

Global Stem Cell Banking Market Drivers:

Competitive Landscape:

The market is fragmented in nature with the presence various international as well as regional players.

Some of the leading players operating in the market are:

Key Topics Covered:

1 Preface

2 Scope and Methodology

3 Executive Summary

4 Introduction

4.1 Overview

4.2 Properties

4.3 Key Industry Trends

5 Global Stem Cell Banking Market

5.1 Market Overview

5.2 Market Performance

5.3 Impact of COVID-19

5.4 Market Breakup by Product Type

5.5 Market Breakup by Service Type

5.6 Market Breakup by Bank Type

5.7 Market Breakup by Utilization

5.8 Market Breakup by Application

5.9 Market Breakup by Region

5.10 Market Forecast

6 Market Breakup by Product Type

6.1 Adult Stem Cells

6.1.1 Market Trends

6.1.2 Market Forecast

6.2 Human Embryonic Cells

6.2.1 Market Trends

6.2.2 Market Forecast

6.3 IPS Cells

6.3.1 Market Trends

6.3.2 Market Forecast

7 Market Breakup by Service Type

7.1 Sample Preservation and Storage

7.1.1 Market Trends

7.1.2 Market Forecast

7.2 Sample Analysis

7.2.1 Market Trends

7.2.2 Market Forecast

7.3 Sample Processing

7.3.1 Market Trends

7.3.2 Market Forecast

7.4 Sample Collection and Transportation

7.4.1 Market Trends

7.4.2 Market Forecast

8 Market Breakup by Bank Type

8.1 Private

8.1.1 Market Trends

8.1.2 Market Forecast

8.2 Public

8.2.1 Market Trends

8.2.2 Market Forecast

9 Market Breakup by Utilization

9.1 Used

9.1.1 Market Trends

9.1.2 Market Forecast

9.2 Unused

9.2.1 Market Trends

9.2.2 Market Forecast

10 Market Breakup by Application

10.1 Personalized Banking Applications

10.1.1 Market Trends

10.1.2 Market Forecast

10.2 Research Applications

10.2.1 Market Trends

10.2.2 Market Forecast

10.3 Clinical Applications

10.3.1 Market Trends

10.3.2 Market Forecast

11 Market Breakup by Region

11.1 North America

11.1.1 Market Trends

11.1.2 Market Forecast

11.2 Europe

11.2.1 Market Trends

11.2.2 Market Forecast

11.3 Asia Pacific

11.3.1 Market Trends

11.3.2 Market Forecast

11.4 Middle East and Africa

11.4.1 Market Trends

11.4.2 Market Forecast

11.5 Latin America

11.5.1 Market Trends

11.5.2 Market Forecast

12 Global Stem Cell Banking Industry: SWOT Analysis

12.1 Overview

12.2 Strengths

12.3 Weaknesses

12.4 Opportunities

12.5 Threats

13 Global Stem Cell Banking Industry: Value Chain Analysis

14 Global Stem Cell Banking Industry: Porters Five Forces Analysis

14.1 Overview

14.2 Bargaining Power of Buyers

14.3 Bargaining Power of Suppliers

14.4 Degree of Competition

Read more here:
Insights on the Stem Cell Banking Global Market to 2026 - by Product Type, Service Type, Bank Type, Utilization, Application and Region - WFMZ...

Recommendation and review posted by Bethany Smith

Scientists say that base editing proved itself efficient in correcting a mutation in patient cells with the monogenic disease Alpha-1 antitrypsin deficiency (AATD). The disorder is a common inherited disease that affects the liver and the lungs.

Base editing is different from other forms of editing, including CRISPR, because the base editors do not induce a break in the DNA, which helps prevent double strand breaks, potential off-target editing, and unwanted mutations during cell repair.

Researchers at Boston Medical Center and Boston University used patient-derived liver cells (iHeps) that mimic the biology of liver hepatocytes, the main producers of alpha-1 antitrypsin protein in the body. The base editing technology corrected the Z mutation responsible for AATD and reduced the effects of the disease in the hepatocytes, demonstrating successful base editing in human cells.

The study (Adenine Base Editing Reduces Misfolded Protein Accumulation and Toxicity in Alpha-1 Antitrypsin Deficient Patient iPSC-Hepatocytes), published inMolecular Therapy,can help pave the way for future human trials, according to the research team.

AATD is most commonly caused by the Z mutation, a single base substitution that leads to AAT protein misfolding and associated liver and lung disease. In this study, we apply adenine base editors to correct the Z mutation in patient-induced pluripotent stem cells (iPSCs) and iPSC-derived hepatocytes (iHeps), wrote the investigators.

We demonstrate that correction of the Z mutation in patient iPSCs reduces aberrant AAT accumulation and increases its secretion. Adenine base editing (ABE) of differentiated iHeps decreases ER stress in edited cells as demonstrated by single-cell RNA sequencing. We find ABE to be highly efficient in iPSCs and do not identify off-target genomic mutations by whole genome sequencing.

These results reveal the feasibility and utility of base-editing to correct the Z mutation in AATD patient cells.

This study shows the successful application of base editing technology to correct the mutation responsible for AATD in liver cells derived from patients with this disease, said Andrew Wilson, MD, a pulmonologist at Boston Medical Center and an associate professor of medicine at the Boston University School of Medicine, who served as the studys corresponding author. I am hopeful that these results will create a pathway to use this technology to help patients with AATD and other monogenic diseases.

Base editors created by Beam Therapeutics were applied to induced pluripotent stem cells (iPS cells) from patients with AATD, and then again in hepatocytes that were derived from iPS cells. This was done to study the correction of the Z mutation of the gene responsible for AATD in human cells.

The Z mutation in the SERPINA1 gene is responsible for causing chronic, progressive lung and liver disease in AATD. In patients with AATD, the mutant AAT proteins misfold and form aggregates of protein that build up inside the hepatocytes and cause damage.

For this study, researchers started with mutant (ZZ) iPSCs created from a patient with AATD. After the base editing process was completed, the DNA from the edited cells was sequenced to determine if the SERPINA1 gene had been corrected. Clonal populations of cells with either one (MZ) or both copies (MM) of the corrected gene were expanded and then differentiated over the course of 25 days to generate hepatocytes.

After sequencing the entire genome of the edited cells, there was no evidence of inadvertent mutations in the genome from the base editors, and the misfolding and associated protein buildup was partially corrected in MZ cells and completely in MM normal cells.

The process was repeated using hepatocytes derived from the mutant iPSCs. Two base editors were used in different conditions to test the efficiency of this process. In the best conditions, about 50% of the mutant genes were successfully edited. The cells were then analyzed to see if they still appeared hepatic and if there were fewer signs of the disease in the edited cells, compared to mutant ZZ cells.

Findings showed the base editing did not alter the hepatic program, and the liver cells still expressed hepatic genes and proteins at normal levels. In addition, there was less accumulation of aggregated misfolded Z AAT protein, showing less evidence of disease in the edited cells.

While augmentation therapy has been shown to slow the progression of lung disease in AATD patients, there are currently no treatments available for AATD-associated liver disease. Emerging treatment strategies have focused on the correction of the Z mutation.

Base editing is being evaluated as a treatment modality for a variety of monogenic diseases, according to the scientists. Alpha-1 antitrypsin deficiency is a prime target for base editing, likely to be one of the earlier diseases in which base editors are tried in human studies. Additional disease targets include retinal disease, hereditary tyrosinemia, sickle cell anemia, progeria, cystic fibrosis, and others.

Findings of this study suggest that future research may explore the usefulness of base-editors in editing other quiescent cell populations. Additionally, it has recently been shown that base-editors can edit RNA in addition to DNA in immortalized cell lines and warrants further investigation.

By quiescent, we are referring to differentiated cells (in this case hepatocytes) that are not stem cells or cells that are actively dividing. Basically, [we are talking about] any differentiated cell type, Wilson toldGEN. This is relevant because many of the cell types in the body that you would want to target are already differentiated cells. It is in many cases easier to edit an actively dividing cell, which is why we mention this. There are many examples of a differentiated cell type in the body, such as cardiac cells, lung cells, skin cells, etc., that you might want to target.

One of the major things researchers worry about in the field of gene editing is the possibility of off-target effectsunintended consequences of applying the editing machinery.

The most likely off-target effect, in this case, would be editing of DNA somewhere in the genome other than what we intended to edit, continued Wilson. When we looked by whole genome sequencing, we didnt see evidence of this in iPS cells. However, in addition to editing DNA, it has been reported that base editors can also edit RNA. This could have unintended consequences even if the DNA sequence isnt changed.

We didnt look in this study to see if this occurred, which is why we mentioned itjust to be up front about possible unintended consequences/toxicities that could be present and that we didnt exclude. It isnt something specific to our study or gene of interest but generalizable to the entire field of base editing.

Read more:
Base Editing as Therapy for Common Inherited Lung and Liver Disease Shows Promise - Clinical OMICs News

Recommendation and review posted by Bethany Smith

SAN DIEGO--(BUSINESS WIRE)--Stemson Therapeutics announced today the closing of a DCVC Bio-led $15 million Series A financing to advance development of Stemsons proprietary therapeutic solution to cure hair loss. Genoa Ventures, AbbVie Ventures and other investors join in supporting Stemsons efforts to restore human hair growth with a novel cell regeneration technology using the patients own cells to generate new hair follicles.

In addition, Kiersten Stead, Ph.D., Co-Managing Partner at DCVC Bio and Jenny Rooke, Ph.D., Managing Director at Genoa Ventures will join Stemsons Executive Chairman Matt Posard and Chief Executive Officer and co-founder Geoff Hamilton on the board of directors. Dr. Stead invests in early-stage companies that build novel deep tech businesses in the life sciences. Stead received a Ph.D. in Molecular Biology & Genetics and an MBA in finance from the University of Alberta. Dr. Rooke is founder and Managing Director at Genoa Ventures where she specializes in early-stage companies innovating at the convergence of technology and biology. Rooke received a Ph.D. in Genetics from Yale University and a degree in physics from the Georgia Institute of Technology.

We are excited and honored to welcome DCVC Bio and a fantastic syndicate of investors to the Stemson team. The Series A funding will help us optimize our solution for human skin structure and environment so we can go into our first human clinical trial with high confidence for a positive outcome. We have the technical and biological building blocks to successfully address hair loss that overcomes failures of past therapies, said Hamilton. The addition of key venture capital investors DCVC Bio, Genoa Ventures and AbbVie Ventures broadens and strengthens our investor base. DCVC Bio and Genoa Ventures are successful early-stage development investors, and I am pleased to welcome Dr. Stead and Dr. Rooke, our newest board members, to the team. In addition, the AbbVie Venture investment comes on the heels of an initial seed investment from Allergan Aesthetics in 2020, and the continued industry interest in our technology is encouraging.

Globally, hundreds of millions of men and women suffer from various forms of hair loss. Though there are many possible causes of hair loss, including chemotherapy, autoimmune disease, scarring, and genetics, all can result in a loss of self-esteem and cause depression, anxiety and other mental health disruption for those affected. The hair restoration market is expected to exceed $13.6 billion by 2028, and no solution today is capable of generating an unlimited new supply of healthy follicles for patients in need.

Almost 30 years have passed since the last FDA-approved hair loss treatment, yet millions still suffer the physical and mental impact of losing their hair each year, stated Dr. Stead. Stemsons novel stem cell engineering platform has the potential to cure hair loss once and for all, treating not only the physical symptoms of this complex problem, but the mental burden as well.

"The team at Genoa is impressed with Stemsons vision to blend biology and technology and apply it beyond traditional biotech," added Dr. Rooke. "By combining exciting advancements in iPSCs with novel technologies in materials and data sciences, Stemson exemplifies the kind of chimeric teams Genoa seeks to support on their journey to become a category-defining company."

The Series A financing brings the total funding raised to date to $22.5 million and allows Stemson to further the next stage of research and development of its cell engineering platform, where is it being combined with bioengineered material and robotic delivery as a novel solution for natural hair replacement. Currently, Stemsons research and development efforts are focused on developing an optimized solution for human skin structure environment in larger animal models. Stemsons Induced Pluripotent Stem Cell (iPSC) based technology is capable of producing the cell types required to initiate hair follicle growth and have been successfully tested in small animal models.

About Cell Regeneration Technology

Human Induced Pluripotent Stem Cells (iPSC) have the unique capability to replicate indefinitely and give rise to all cell types of the human body, including the cell types required for repair. iPSC-based technology is capable of producing the cell types required to initiate hair follicle growth. As a new therapeutic platform, iPSCs represent an emerging area of regenerative cell therapy. Stemson is one of a growing number of companies at the forefront in developing iPSC-based treatments.

About DCVC Bio

For over twenty years, DCVC and its principals have backed brilliant entrepreneurs applying Deep Tech, from the earliest stage and beyond, to pragmatically and cost-effectively tackle previously unsolvable problems in nearly every industry. DCVC Bio specializes in supporting life sciences platform companies at the intersections of engineering and therapeutics, industrial biotechnology and agriculture. For more information, please visit https://www.dcvc.com/companies.html#dcvc-bio

About Genoa Ventures

Genoa Ventures invests in early-stage companies working at the convergence of biology & technology to accelerate the pace of innovation, transform industries, and solve some of the most fundamental challenges to life. Genoa, identifies opportunities early and focuses its investments and expertise to empower the next great category-defining companies. The Genoa team has a unique chimeric blend of experience from scientific research and discovery to executive management in the life sciences and technologies sectors. The team applies this diverse experience to provide expert guidance to its companies and stellar returns to its investors.

About AbbVie Ventures

AbbVie Ventures is the corporate venture capital group of AbbVie. We are a strategic investor, investing exclusively in novel, potentially transformational science aligned with AbbVie's core R&D interests. We measure success primarily by the extent to which our investments foster innovation with potential to transform the lives of patients that AbbVie serves. AbbVie Ventures enables its portfolio companies with both funding as well as access to AbbVie's internal network of experts across all phases of drug development, from drug discovery through commercialization. For more information, please visit http://www.abbvie.com/ventures

About Stemson Therapeutics

Stemson Therapeutics is a pre-clinical stage cell therapy company founded in 2018 with a mission to cure hair loss by leveraging the regenerative power of Induced Pluripotent Stem Cells. Based on the breakthrough innovation by Stemson Therapeutics co-founder, Dr. Alexey Terskikh, Stemson uses iPSC to regenerate the critical cells required to grow hair and which are damaged or depleted in patients suffering from hair loss. The iPSC-derived cells are used to grow de novo hair follicles, offering a new supply of hair to treat people suffering from various forms of Alopecia. Today, there are no available treatments capable of growing new hair follicles. Stemsons world class team of scientists, advisors and collaborators are passionate about delivering a scientifically based, clinically tested cure for hair loss to the millions of hair loss sufferers who seek help for their hair loss condition. Stemson Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.stemson.com.

Read the original:
Stemson Therapeutics Secures $15M Series A Funding to Cure Hair Loss - Business Wire

Recommendation and review posted by Bethany Smith

Some people involved in a class action against two fertility services over the use of a non-invasive test which may have incorrectly classifiedembryos as abnormalhave been told their embryos are still being stored.

The lawyer representing about 200 affected parties in Victoria's Supreme Court saidthe mistake hadresulted in some women choosing to beimplanted with another person's embryo, while others have lost precious months of fertility.

The class action launched lastDecember alleges Melbourne-based Monash IVF and Adelaide-based Repromed breachedtheir duty of care by failing to tell patients about the pitfalls of a type of testing that does not require a biopsy.

There are two ways to conduct such testing: the first method is through a biopsy, which involves taking a tissue sample from an embryo, a method that is considered invasive.

The second method is called non-invasive pre-implantation genetic testing and involves collecting DNA from the culture that the embryo has been growing in while in the laboratory.

The inaccuracy of the test used by the two services between May 2019 and October 2020 was discovered last October.

Patients were informed of the issue after manyhad already made the choice to donatethe embryos to science or destroy them.

Lawyer Michel Margalit said some clients had discovered last week that some oftheir embryos were still in storage.

Supplied

Those that had been donated could still be retrieved, but the others were lost forever.

"They acted on the advice that their embryos were abnormal or had been destroyed," Ms Margalit said.

"Some people obtained donor embryos and are now pregnant with children that aren't necessarily genetically related to them, or that had a whole host of other treatments, so it's a very painful time for our clients."

She said they were not told about the pitfalls of the experimental testing regime.

"In this case, there was an alternative a reliable test, a biopsy method and women were steered away from that method, to this non-invasive method and they just didn't know the mess they were walking into," she said.

Monash IVF and Repromed have now stopped using non-invasive pre-implantation genetic testing.

Repromed medical directorProfessor Kelton Tremellen said the test turned out to be not as accurate as the company had hoped.

He said some of the embryos that could now be used might still be abnormal.

Supplied: Repromed

"What we're trying to do is say, look, unfortunately, we've now recognised that the test is not as accurate as it was originally portrayed to us and that we want to give these individuals the opportunity to make a decision nowwhat they want to do with those embryos," he told ABC Radio Adelaide.

"Some people will say 'I simply don't want to use them, we've moved on'.

"Others will say, 'look, we'll accept the risk and transfer them and effectively consider them to be embryos that haven't been tested at all'."

He said he and other scientists had "lost sleep" worrying about the effect on patients.

"Rather than hide this stuff from patients, our staff have contacted them saying, 'look, those embryos are still in storage, we've now found out this test is not as accurate as we'd hoped, what would you like to do with them?'" he said.

"Rather than sweeping it under the carpet, we're trying to be open and socially responsible by having full disclosure."

Continue reading here:
IVF patients suing over inaccurate genetic tests find out some of their embryos were not discarded - ABC News

Recommendation and review posted by Bethany Smith

Small-cell lung cancer (SCLC) occurs almost exclusively in smokers and appears to be most common in heavy smokers. Historically, SCLC has been rare in never smokers. However, certain inherited mutations may increase the likelihood of developing SCLC.

It is very important to note that having inherited a genetic mutation does not mean a person will develop SCLC.

Although there are several different kinds of lung cancer, around 95% of lung cancers are either SCLCs or non-small cell lung cancers (NSCLCs).

What distinguishes SCLC from NSCLC is its rapid growth and the early development of widespread metastases. Although SCLC is initially very responsive to chemotherapy and radiation, the majority of patients will relapse within a few months to 1 year from initial therapy.

This article will look at whether SCLC is hereditary and whether a person can undergo genetic testing. It will also discuss the causes of and risk factors for SCLC.

SCLC occurs when certain cells in the lungs grow quickly and uncontrollably, forming a tumor.

Cancers begin to develop when genetic mutations affect the genes that control the growth and division of cells or repair DNA that is damaged.

The majority of lung cancer cases are due to genetic changes known as somatic mutations, which are not hereditary. A person acquires them during their lifetime.

The National Organization for Rare Disorders notes that the two main somatic mutations related to SCLC affect the genes TP53 and RB1.

The TP53 gene provides instructions for creating a protein called p53, and the RB1 gene provides instructions for making pRB. Both proteins are tumor suppressors, which means they regulate cell growth and division.

However, in 2021, a group of researchers published a scientific paper that looked at 87 people with SCLC.

After analyzing 607 genes from each individual, the researchers found genetic mutations that increased the likelihood of developing SCLC in 43.7% of the study participants. Around 10% of these are heritable genetic mutations.

The authors of the paper conclude that certain heritable genetic mutations could make some people more likely to develop SCLC.

It is of note that if a person inherits a genetic mutation, this can increase their risk of developing cancer. It does not mean, however, that they will definitely develop cancer.

In addition, the American Cancer Society states that, although genes can play a role in the development of lung cancer, few lung cancers occur due to inherited mutations alone.

Genetic testing is when healthcare professionals look for potential inherited genetic mutations that may increase a persons risk of developing certain kinds of cancer.

For some cancer types, a healthcare professional can also suggest genetic testing as a part of the diagnostic and staging process. This can help determine a persons outlook and whether particular treatment options might be helpful.

Currently, however, doctors do not use genetic testing to diagnose SCLC. The Memorial Sloan Kettering Cancer Center notes that healthcare professionals and researchers know less about the genetic mutations that can lead to SCLC than they do about other genetic changes.

Smoking is the primary cause of SCLC. Tobacco smoke contains cancer-causing chemicals, or carcinogens, which damage the DNA in cells.

According to a 2020 review, 85% of lung cancer cases are the result of smoking.

Other risk factors include exposure to:

There are several ways in which a person may be able to lower their risk of developing SCLC.

Smoking tobacco is such a common cause of SCLC that the most effective preventive strategy is to not begin smoking.

However, for those who do smoke, quitting can lower the likelihood of developing SCLC. If a person quits before cancer develops, the lung tissue can begin to gradually repair itself.

A 2018 study looked at a group of people who have smoked 21.3 packs of cigarettes per year on average. The researchers compared the lung cancer rates of those who currently smoke and those who had quit within the previous 5 years.

They found that the individuals in the latter group were 39.1% less likely to develop lung cancer.

Learn about 11 tips for giving up smoking here.

Other ways of lowering the risk of SCLC include reducing exposure to secondhand smoke, asbestos, and radon. However, this may sometimes be outside of a persons control.

At the moment, doctors do not use genetic testing to diagnose SCLC.

Instead, a person should contact a healthcare professional if they experience any of the following symptoms:

If a healthcare professional suspects the cause of the above symptoms is SCLC, they may perform the following diagnostic tests:

Cancer occurs due to genetic mutations that lead to an uncontrollable growth and division of cells.

A person can acquire these genetic mutations throughout their life. In some cases, certain hereditary genes can increase the risk of developing SCLC.

However, inherited genetic mutations are often not enough to cause cancer by themselves. Having inherited a genetic mutation does not mean a person will develop cancer. It means that it can increase the likelihood of that happening.

Smoking is the primary cause of SCLC. To help lower the risk of developing this type of cancer, a person should avoid smoking.

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Is small-cell lung cancer hereditary? What to know - Medical News Today

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NEW YORK Foundation Medicine and Flatiron Health announced this week that Foundations comprehensive genomic profiling tests will be available to order through Flatiron's OncoEMR platform. The integration will allow clinicians to electronically order, track, and receive Foundations test through OncoEMR, the companies said. Both Flatiron and Foundation are planning further integrations with the others comprehensive genomic profiling tests and electronic medical record systems, respectively.

Myriad Genetics this week said it has completed the sale of its Myriad RBM unit which specializes in providing laboratory research services to pharmaceutical companies to IQVIA subsidiary Q2 Solutions. When Myriad announced its intent to sell this business unit in May, it did not disclose the deal's financial details.

GenetronHealth said this week that it has entered a new partnership with the World Economic Forum under its Health and Healthcare Platform, where it is contributing its research insights, technologies, and industry experience. The platform's overall goal is to ensure worldwide equal access to the highest standards of health and healthcare.Genetroniscurrentlyparticipating in a sub-project,dubbedMoving Genomics to the Clinic, which seeks to promote the use of genetic testing in routine clinical practices by proving its utility and efficacy.

AccessHope, a City of Hope subsidiary, said this week that it has partnered with the Dana-Farber Cancer Institute to bring the latest cancer care expertise to patients and oncologists in the community. By partnering withAccessHope, Dana-Farber's experts will support oncologistswiththe latest advances in oncology,includingpersonalized treatments, clinical trials, promising investigational medications, and molecular testing. Patients in Massachusetts, Maine, New Hampshire, Vermont, Connecticut, Rhode Island, New York,and New Jersey, as well asthosein other parts of the country,can access these services through their employee benefits programs. City of Hope and Northwestern University's Robert H. Lurie Comprehensive Cancer Center are also foundational members ofAccessHope.

Molecular breath analysis startup Deep Breath Intelligencesaid this week that it has entered a collaboration with Lwenstein Medical, a sleep and respiratory medicine firm based inRheinland-Pfalz, Germany.Rotkreuz, Switzerland-based DBI said that it is applying artificial intelligence to identify breath biomarkers related to obstructive sleep apnea syndrome. DBIsaid ithas initiated a study on OSASin collaboration with Lwenstein Medical,using participantsbreath samples and applying DBIs patterned analytical algorithms to provide results.

Enable Biosciences said this week it is partnering with the California Department of Public Health to survey state residents for the presence of antibodies against SARS-CoV-2. As part of the program, more than 200,000 households in California will be invited to submit dried blood samples collected at home using kits developed by Enable Bio andtheCDPH. The samples will then be tested by Enable Bio for the presence of antibodies against SARS-CoV-2 to distinguish antibody response fromviralinfection versusresponse fromvaccination. Test results will provide information about the spread of COVID-19 in California and the uptake of vaccines for the disease, South San Francisco, California-based Enable Bio said. The project is a collaboration betweenthe company,theCDPH, Stanford University, and Gauss Surgical. The first survey period concluded June 15 with the second and third enrollment periods slated tobeginat the start of 2022.

NeoGensaid this week that it has extended itsglobalanimal genomicspartnership withGencove. Thepartnership allowsNeoGento offerGencove'sSkimSeeklow-pass sequencing technology to customers in the agricultural sector, including those in the bovine, canine,poultry, and swine industries. UsingGencove'ssequencingimputationplatform,NeoGensaid it can deliver increased genomics data with improved accuracy and flexibility.

Bioceptsaid this week ithas been added to the Russell Microcap Index. Michael Nall, Biocept's president and CEO,called the nodexceptionally exciting, as a driver ofawarenessfor the cancer liquid biopsy firm within thelargerglobal investment community.

Immunoviasaid this week that its American subsidiary hasreceived a CLIA Certificate of Registration,which isan important step in the accreditation of its laboratory in Marlborough, Massachusetts, and a prerequisite to receiving clinical laboratory licensure fromtheMassachusetts Department of Public Health. Clinical laboratory licensure is required beforeImmunoviacan begin testing patients with itsImmrayPanCan-d test, the firm said.According to the Centers for Medicare and Medicaid Services, a Certificate of Registration allows a laboratory toconduct moderate and/or high complexity testing until it is inspected to determine its compliance with the CLIA regulations.

In Brief This Week is a selection of news items that may be of interest to our readers but had not previously appeared onGenomeWeb.

Continued here:
In Brief This Week: Foundation Medicine, Myriad Genetics, Genetron Health, and More - GenomeWeb

Recommendation and review posted by Bethany Smith