You’re More Like Your Mother Than You Know

May 24, 2015 by

May 22, 2015

By Medical Discovery News

Photo of mother and child

While the benefits of breast feeding have been well-documented, scientists were surprised to learn of another one: breast milk contains a mother’s stem cells that become a part of different organs of the baby’s body.

Breast feeding protects infants against infections early in life and reduces their risk of juvenile diabetes, heart disease, and cancer as children. It also helps mothers lose weight after giving birth and lowers their risk of osteoporosis and uterine and ovarian cancer.

In addition, seven years ago scientists discovered the presence of mammary stem cells in breast milk. The mammary gland is unique in its ability to go through different stages in anticipation of producing milk, then a period of milk secretion followed by a return to the non-lactating state. All of this can occur as many times as necessary. This massive restructuring of the breast suggested the presence of stem cells.

Human breast milk contains about 14,000 cells in each milliliter. Most of these are the epithelial cells that are abundant in the breast and cells of the immune system. Some of the cells in breast milk had a molecule called nestin on the surface, which in adults is a marker for multipotent stem cells that can develop into many different types of cells, like those in the brain, pancreas, liver, skin, and bone marrow. When scientists transplanted a single nestin-positive stem cells into the fat pad of a grown mouse, it reconstituted a functional mammary gland. Scientists wondered if such cells were serving the same function in humans.

However, further research revealed quite a surprise. First, they genetically modified mice to produce a protein that makes the cells glow red under fluorescent light. Mothers with this new feature were given normal pups to nurse. When they were examined as adult mice, they had cells that glowed red like the mice they had nursed from in their blood, brain, thymus, pancreas, spleen, and kidneys. These cells became functional cells within these organs, so the ones in the brain behaved like neurons and those in the liver made albumin. Based on this experiment, breast milk stem cells travel into the baby’s blood and become functional parts of various organs, at least in mice.

In the laboratory, these stem cells have also shown the ability to differentiate into breast cells that produce milk in a petri dish, as well as bone cells, joint cells, brain cells, heart cells, liver cells, and pancreatic cells that synthesize insulin. In addition, this study may have also discovered a non-invasive, ethical, and sustainable source of multipotent stems.

We don’t yet fully understand the role of these cells in offspring, whether they maintain a tolerance for the mother’s milk, play a role in normal growth and development, or both. Until then, know that your mother is more a part of you than you ever realized.

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Sweet Stem Cells

May 11, 2015 by

May 8, 2015

By Medical Discovery News

Stem Cells

Diabetes may be common, but it’s serious business. Diabetes is repeatedly in the top 10 causes of death for Americans, killing or contributing to the deaths of 300,000 Americans in 2010. An estimated one in 10 people have it, but about one-third of them are undiagnosed. Diabetes costs the country $250 billion. But scientists are working on some good news for diabetics with the help of stem cells.

Type 1 diabetes is largely associated with children and represents about 5 percent of all diabetes cases. The more common form, type 2 diabetes, mostly affects adults and manifests when cells do not use insulin effectively so higher levels are needed (also called insulin resistance). Insulin is a molecule of protein, made and secreted by beta cells in the pancreas, an organ that regulates glucose levels in the blood.

Diabetes is a multifaceted disease that leads to a host of medical conditions and complications, such as high blood pressure, elevated cholesterol, blindness, cardiovascular disease, and kidney problems. Those with diabetes are two times more likely to die of a heart attack and one and half times more likely to die of a stroke. Diabetes is the leading cause of kidney failure, leading to transplants and dialysis. Almost 60 percent of lower extremity amputations are the result of diabetes.

Administering insulin is a common treatment for the disease and there are many different forms that can be used. Insulin can be injected by a syringe or delivered via an automated pump. There are also different pharmaceuticals used in oral treatments for diabetes. Biomedical scientists are developing other methods to treat diabetes, such as transferring insulin-producing beta cells from a donated pancreas into a diabetic patient. This works well, but the cells stop working over time. Transplanting a whole pancreas is also an option that relieves the need to administer insulin, but there is always a short supply of donated organs and the possibility that the new body will reject it.

However, recent stem cell experiments by multiple groups working independently show promise. These cells, called S7, produce insulin and regulate the level of glucose in the blood and successfully eliminated diabetes in an animal model in about 40 days. Unlike organ transplants, there is no limit to the supply of these stems cells, no long wait for a donation that’s a good fit, and no need for immunosuppressant drugs.

But the method is not perfect. First, S7 cells react slower to glucose than natural beta cells and do not make as much insulin. There are also questions as to whether this approach could be used to treat Type 1 diabetes, because the insulin-producing cells are destroyed in an autoimmune process, which might destroy the transplanted cells as well.

It’s premature to claim this innovation is a victory over diabetes, but its development will definitely be worth following.

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The Berlin Patient

February 22, 2015 by

Feb. 27, 2015

By Medical Discovery News

Millions of people around the world are infected with HIV, the virus that causes AIDS, but only one has ever been cured. Known as the “Berlin Patient,” Timothy Ray Brown is a 48-year-old American living in Germany. Scientists and physicians have wondered how he was cured, and some recently published studies in monkeys have provided one clue.

Brown had been HIV positive since 1995. When HIV infects the body’s cells, it integrates its genetic information into cells, making the virus a permanent part of the host’s genetic information. Brown’s HIV was held at bay by antiretroviral drugs that have made this infection survivable.  However, in 2006 he was diagnosed with acute myeloid leukemia (AML), a cancer unrelated to HIV. AML affects a group of blood cells in bone marrow called the myeloid cells. Brown underwent grueling chemotherapy that failed. In the hope of saving his life, he received two bone marrow transplants. The year of his first transplant, he stopped taking the antiretrovirals, which would normally cause a patient’s HIV levels to skyrocket.

Yet, years later, there is no sign of the virus returning. Only traces of HIV’s genetic material have been found in his blood, and those pieces are unable to replicate. The big question now is: how was this accomplished?

His treatment for AML included three different factors that could have individually or collaboratively resulted in curing his HIV infection. First, in preparation for a bone marrow transplant, a patient is treated with a combination of chemotherapy and whole body radiation to eliminate the entire immune system in preparation for receiving a new one. Second, Brown received blood stem cell transplants from a person with a defective cell surface protein, CCR5, which is what HIV uses to enter cells. People with a CCR5 mutation are resistant to HIV infection. Third, his new immune system may have eliminated the virus and remnants of his old immune system that harbored it in something called a graft versus host reaction.

In an experiment to determine how Brown was cured of HIV, scientists isolated blood stem cells from three Rhesus Macaque monkeys and put them into cold storage. They then infected those monkeys as well as three control monkeys with an engineered version of HIV. Soon after infection, all six monkeys were treated with a cocktail of drugs, and just like in humans, the levels of the virus soon declined. A few months later, the first three monkeys underwent radiation treatments to eliminate their immune systems, and then their immune systems were restored using their own stem cells from storage. Months later, the antiretroviral drugs were withheld from all six monkeys, and the virus came roaring back in five of them. One of the monkeys who underwent the stem cell transplant did not have the virus return in its blood, but it was detected in some tissues.

This experiment established that the destruction of immune system prior to bone marrow transplant was not sufficient to eliminate the virus, so the selection of bone marrow cells resistant to HIV infection and/or the graft versus host reaction may be the reason Brown was cured of HIV. Further studies are needed before we will know exactly how HIV can be cured.

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Shining a Light on Cavities

October 5, 2014 by

Oct. 3, 2014

By Medical Discovery News

For all those who cringe at the thought of going to the dentist or hearing the word cavity, there is hope. Apparently, when low-power laser light is focused onto damaged teeth, it stimulates the regrowth of dentin to correct the damage. The laser light stimulates the stem cells that are already in teeth to differentiate and repair damage from within, so that someday dentists can repair or even regrow teeth without fillings.

Teeth consist of four different tissues, three of which are harder than bone (enamel, dentin, and cementum) while one (dental pulp) is soft. Enamel, the hardest material in the body, is the outer surface of the crown of a tooth. Once enamel has completely formed it cannot be repaired, but it can remineralize. It allows teeth to withstand large amounts of stress, pressure, and temperature differences.

Dentin lies beneath enamel and forms the main portion of a tooth through numerous microscopic channels called dentin tubules. These tubules house dentinal fibers, which are the trouble-makers responsible for transmitting pain stimuli. Cementum is a thin layer of tissue surrounding the root of a tooth. Within the center of the tooth is the pulp, which provides nutrition to the tooth and mediates dentin repair. The pulp contains nerves, blood vessels, lymph vessels, connective tissue, cells that produce dentin, and stem cells.

By adding specific molecules, stem cells are coaxed into regenerating or repairing tissues. Growth factors or chemicals, among others, stimulate them to differentiate into the types of cells that make up tissues. It is a challenge to stimulate stem cells in the body without them growing uncontrollably. As a result, most approaches to stem cells involve removing them from the body, manipulating them in the lab, and then returning them. However, scientists have found that lasers promote regeneration in the heart, skin, lung, and nervous tissues. The idea was that since teeth contain stem cells, laser light might be able to stimulate them to regenerate tooth tissue and repair damaged teeth.

To test this theory, scientists drilled holes in the dentin in the teeth of rats and then shined a non-ionizing, low-power laser on the damaged area and the pulp just above the stem cells. They then capped the damaged teeth to keep the animals comfortable and healthy. With just a single five-minute treatment, new dentin formed in the damaged area in 12 weeks. The laser seems to create micro-injuries and induce highly reactive oxygen species, which indirectly activate stem cells.

They also proved that dentin production could be stimulated with lasers in cultured human dental stem cells. However, this treatment still needs some work before it could benefit people, since the stem cells that produce enamel are not present in mature teeth. And dentists would still play a role in repairing damaged teeth.

Before this experiment, results of laser treatments have generally been inconsistent, making these results that much more significant. It is the first time scientists have been able to determine how low-power laser treatment works on the molecular level. Scientists aim to advance this study into human clinical trials and even use this approach to regenerate other tissues.

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Aging and Our Biological Clock

May 9, 2014 by

May 9, 2014

By Medical Discovery News

Unlike a mechanical clock our biological clocks do not run at a constant speed

The questions of how we age and how our bodies know what to do during that process have puzzled scientists for years. The answers lay in our biological clocks, which aren’t fully understood. Some scientists think that if we can learn how our biological clocks work, we would hold the key to slowing down or even reversing aging.

A group from the University of California, Los Angeles (UCLA) achieved astounding results that offer insight into the mechanisms of aging. They used existing sets of data to compare DNA patterns in normal and cancerous tissue samples from humans. They examined almost 8,000 samples from more than 50 different people that were taken from various places in or on the body. This allowed them to take a comprehensive look at the changes that occur throughout the body during the aging process and how tissues of the body keep time. 

Most, but not all, tissues had a biological age that matched their chronological age. The biological age of a tissue is the age it appears to be or behaves at. Chronological age is just a person’s overall age.

For example, women’s breast tissues age much faster than the rest of their bodies. In a healthy woman, breast tissues had a biological age two to three years older than the woman’s age. In a woman who had breast cancer, the cancer cells were an astounding 36 years older than the rest of her body! And even the healthy tissues surrounding those cancer cells were affected – they were up to 12 years older than the rest of the body. Maybe this age difference explains why breast cancer is so prevalent in women.

The results also show that biological clocks do not run at a constant rate. The clock advances much faster from birth through adolescence. When we reach our 20s the clock slows to a steadier rate.

Stem cells, cells that are basically clean slates and can develop into any type of cell in the body, are age zero according to the biological clock. This makes sense since embryos and umbilical cords have stem cells. So, if adult cells can be reprogrammed into stem cells, their biological clocks could potentially be reset as well. Could this be the key to being forever young?

This discovery could possible reverse the aging process, a scientific Fountain of Youth.  But first, the actual connection between the biological clock and aging still needs to be defined more precisely. Then we can move on to questions like whether slowing the aging process also reduces the incidence of cancerous diseases.

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Organ Farming

March 15, 2014 by

March 14, 2014

By Medical Discovery News

Imagine that a patient needs an organ, like an airway to their lungs called a trachea. A scientist harvests some of the patient’s cells and attaches them to a scaffold the proper shape and size for the tube. The cells and scaffolds are placed into a tissue reactor and – ta da! – in a week or two there is an organ ready for the surgeon to transplant into the patient. While it sounds like a chapter from “Brave New World,” this science fiction scenario is a growing reality.

Bladders and ears have been grown in the laboratory, and hearts, eyes, and kidneys and other organs are in progress. These organs are close to the natural ones they’re copying – some even have their own immune system. In April 2013, surgeons at the Children’s Hospital of Illinois implanted a bioengineered trachea into a two-year-old child. This was the first surgery of its kind in the United States and one of only six worldwide.

The patient receiving the transplant was a girl named Hannah Warren who was born without a trachea, commonly called a windpipe. Since birth, she’s had a plastic pipe inserted in her mouth that went down into her lungs, allowing her to breathe. She could not eat normally or even speak. With few options available, this type of congenital defect has always meant an early death; only a few children live past the age of six.  

Bioengineered organs could change that. The key is stem cells – cells that are at an early stage of development and through the influence of their environment can produce the many specialized cells of organs and tissues. In this case, doctors harvested the girl’s immature stem cells from the marrow inside her bones. The stem cells were taken to the lab and allowed to adhere to a plastic fiber model precisely the size (about one-half inch in diameter) and structure of the trachea she needed. Once placed in an incubator called a tissue bioreactor, the stem cells colonized the plastic and started growing. While they were growing, cells communicated with neighboring cells and worked together to produce all the cells needed for a functioning trachea. 

At the end of this process, Dr. Paolo Macchiarini implanted the trachea with promising results. Since the cells in the bioengineered trachea were based on ones from her body, her immune system didn’t recognize it as foreign and reject it, a big worry for transplant recipients. Without a plastic pipe in her mouth, Hannah was able to smile for the first time.

Unfortunately, while her trachea functioned well after the surgery, her esophagus never recovered. She underwent a second surgery to fix her esophagus and died from complications. Macchiarini said that her death was not due to the implanted trachea but her own “very fragile” tissue. He called Hannah a “pioneer” in the field of regenerative medicine and plans to conduct similar operations.

The next step for bioengineered organs is clinical trials leading to Food and Drug Administration approval. This would give more scientists and physicians the opportunity to improve organ “farming” and extend this field into a therapy that could benefit many.

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Cancer Has Stem Cells

January 11, 2013 by

Jan. 11, 2013

By Medical Discovery News

Facing cancer once is daunting enough, but the shock of relapse often leaves a person feeling overwhelmed and depressed. Now three separate studies seem to confirm scientists’ suspicions that so-called cancer stem cells drive the growth and regrowth of tumors. If true, this changes the whole approach to cancer therapy.

For years scientists have debated the existence of cancer stem cells, which exhibit stem cell characteristics by producing tumor cells or additional cancer stem cells. Studies are beginning to show tumors contain a small number of cancer stem cells that are often quiescent, shielding them from chemotherapy treatments that normally target and kill tumor cells.

This means after treatment and enough time, the surviving cancer stem cells divide, producing more cancer stem cells as well as differentiating into the variety of cells found in a tumor. The ability to produce cells with varying characteristics could also help explain metastasis, the migration and adaptation of tumor cells to other organs.

The new studies produced the best evidence yet that cancer stem cells do exist in the tumors of the brain, skin, and gut of mice. One group from the University of Texas Southwestern Medical Center in Dallas was able to mark brain tumor (glioblastoma) stem cells using a neuronal stem cell marker. When all the tumor cells were treated with chemotherapy, the only cells that survived were the ones identified by the stem cell marker. When chemotherapy was given along with treatment to repress cancer stem cell activity, the tumors shrank.

Another scientist, Hans Clevers from the Hubrecht Institute in the Netherlands, focused on gut tumor cells. His team found a way to mark cancer stem cells in benign intestinal tumors. They then introduced a gene that would make the cancer stem cells glow the color green, which gave rise to more green-colored cancer stem cells as well as all the other types cells in that tumor. To further prove stem cells fuel tumors, Clevers triggered all the stem cells colored green to switch to either yellow, red, or blue, and they produced stem cells and tumor cells in that same color.

The third study, led by Belgian scientists, did not specifically label cancer stem cells, but rather labeled individual skin tumor cells so that they could be tracked during tumor development. The tumor cells were allowed to reproduce and did so in two ways. The majority of cells divided a few times then died out. The others continued to grow and divide, supporting the belief that a small subset of tumor cells spurs cancer growth, and could indeed be cancer stem cells. The more aggressive the tumor cell type, the more likely it was to produce more cells that continue to divide.

These findings provide strong evidence cancer stem cells exist and are the continuous origin of tumor cells. Scientists have opportunity to develop therapies that target and kill cancer stem cells and combine these with current, effective chemotherapies that kill tumors cells.

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Nobel in Physiology or Medicine

December 15, 2012 by

By Medical Discovery News

Dec. 15, 2012

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Every person begins as just one cell – a fertilized egg. That cell rapidly divides, forming a cluster of cells that will eventually become all the types of cells in all the organs needed to create a whole human being. This cluster of embryonic stem cells has the unique ability to differentiate into any kind of cell in the body, such as brain cells or skin cells.

Scientists had long believed that once stem cells turned into a specific type of cell, they were mature and forever locked in that role. But this year’s Nobel Prize winners in physiology or medicine, John B. Gurdon and Shinya Yamanaka, disproved this dogma by discovering that specialized, fully developed cells can be reprogrammed back into undifferentiated states. This discovery has revolutionized the understanding of human development and holds great promise for future medical treatments.

Fifty years ago, Gurdon was an assistant lecturer of zoology at the University of Oxford and began experimenting with eggs from a frog species called Xenopus. He destroyed the nucleus of a Xenopus egg with ultraviolet light and then transferred into that cell the nucleus of a fully differentiated frog intestinal cell. He wondered if the nucleus from the differentiated intestinal cell retained the information for pluripotency, the ability to form all cell types and subsequent tissues. If so, the egg would still grow into a tadpole, but if the information was irreversibly lost when a stem cell became specialized then the egg would not be able to develop further.

Amazingly, the egg became a tadpole. This proved that fully differentiated cells retain all the necessary information to produce a complete living organism. The scientific world did not immediately embrace this shocking and controversial discovery. However, as others used and refined Gurdon’s techniques the method became known as somatic cell nuclear transfer, which was used to produce the first cloned mammals like Dolly the sheep.

Years later and thousands of miles away, Yamanaka, a professor with the Institute for Frontier Medical Sciences in Kyoto, Japan, took the idea one step further by questioning whether a fully differentiated cell could be reprogrammed back to a pluripotent state. In a remarkable set of experiments, he transferred the genes for 24 transcription factors, specialized proteins which in this case were active in embryonic stem cells, into mouse skin cells called fibroblasts. As a result, some of these cells changed to a shape and size similar to stem cells. Next, he painstakingly reduced the transcription factors one by one to identify the four key factors required for cellular reversion, proving these factors could induce pluripotent embryonic stem cells.

Despite spanning decades and continents, these two discoveries together will pave the way for treating diseases with regenerative medicine, replacing damaged human organs or tissues with new, functioning ones. In addition, this will allow scientists to work with induced stem cells without facing the ethical concerns of harvesting stem cells from human embryos. Doctors Gurdon and Yamanaka were honored at a ceremony in Stockholm on Dec. 10.

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I Can See Again

November 26, 2012 by

By Medical Discovery News

Nov. 24, 2012

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Blind mice don’t only exist in nursery rhymes, but in scientific laboratories. Scientists have been able to restore the vision of some such mice that were impaired by the same family of eye diseases that cause blindness in millions of Americans. The landmark study successfully transplanted immature photoreceptor cells, which are nerve cells in the retina responsible for sight.

Photoreceptor cells gradually die off in people with certain degenerative eye diseases. Once enough of the cells are gone, a person goes blind and no treatment can reverse the damage.

The research team from University College London Institute of Ophthalmology proved they can reverse the damage in adult mice with nonfunctioning rods. Rods and cones are the two types of photoreceptor nerve cells that make up the retina. These nerve cells convert light energy into signals that travel the optic nerve to the brain. Cones detect such things as color and detail and provide the center field of vision. Rods detect black and white and enable peripheral and low-light vision.

In the study, researchers took mice without functioning rods and injected their retinas with immature rod receptor cells from young, healthy mice. In four to six weeks, one in six of the mice with transplanted rod precursor cells seemed to be functioning nearly as well as mice with normal rod photoreceptors. These transplanted cells formed nerve connections resembling normal rod cells and generated signals that were transmitted to the brain for visual processing.  This is the first time that transplanted photoreceptor cells have been shown to integrate into the circuitry of the retina and improve vision.

To test their results, researchers placed treated mice and diseased mice into a dimly lit water maze. Recall the diseased mice do not have functioning rods, which means they can’t see in low light. If the transplant works, the mice with new rods should be able to spot a visual cue for a hidden platform and get out of the water. The mice with implants had no difficulty finding the platform and climbing out. The untreated, diseased mice took much longer and did a thorough search of the maze before finding the platform.

Researchers say the study’s success was due to the large number of photoreceptor cells they implanted – 200,000 compared to less than 1,000 cells in other studies. Next, researchers plan to test whether the procedure is as successful in transplanting precursor cones in mice.

A similar but separate study in humans is already undergoing clinical trials involving 12 patients with Stargardt disease, the most common form of inherited juvenile macular degeneration. By age 50, half are legally blind. The participants have been injected with 50,000 to 200,000 embryonic stem cells. The aim of these early clinical trials is to determine if the implant of embryonic stem cells is safe and well tolerated. So far, the trials are promising.

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Eggs for Life

September 24, 2012 by

By Medical Discovery News

Sept. 22, 2012

Eggs for Life

Women who want to conceive but cannot often find it an emotionally wrenching experience. Since scientists believed that women only produce a limited amount of eggs before menopause, they face the predicament of having few options. A new study has revealed a possible way to replenish this numbered reserve.

Researchers at Massachusetts General Hospital isolated stem cells in adult ovaries that could potentially become eggs. They first isolated stem cells in rat ovaries back in 2004, called oogonial stem cells (OSCs). OSCs have a protein on their surface called DDX4. Using fluorescent antibodies that bind to this marker protein, they isolated OSCs from mouse ovaries using a cell sorting machine called a Fluorescence Activated Cell Sorter. These cells not only went on to become eggs, but could be fertilized with sperm and become embryos.

Recently the team was able to apply the same technology to donated human ovaries from Japanese women undergoing gender reassignment surgery. Just as with the mice, researchers isolated OSCs and grew them in a Petri dish until they became immature eggs, called oocytes.  When implanted in mice that had human ovarian tissue grafted inside, they matured into eggs, as confirmed by several surface markers they expressed.

U.S. laws forbid fertilization of human eggs in research, so it wasn’t possible to determine whether the eggs could actually develop into embryos. Even if they could, there’s still the question of whether they would be viable embryos capable of producing healthy babies.  Researchers say the same technology could also be used to boost the health of a woman’s existing eggs by transferring mitochondria, the powerhouse of a cell, from OSCs, making the renewed eggs more capable of fertilization. More work would have to be done on both approaches to determine if either actually works.

Only a very small number of cells were isolated in this study, of which only a few became fertilized and produced minimally formed embryos. In mice, the OSCs make up only about 0.014 percent of all cells in the ovary. In addition, many cells grown in the laboratory developed abnormalities, an important problem that would have to be overcome.

What’s provocative about this study is that it shows technology can stimulate new egg production for infertile women. More importantly, it suggests that perhaps women retain the potential to produce eggs later in life, which goes against what scientists have always believed – that egg production is lost soon after birth.

While women start with 1 million eggs, by age 51, they end up with few or none. Having the ability to produce new eggs would make motherhood possible for older women and for the 15 percent of reproductive-age couples who are infertile. That’s 10 million couples in the U.S., of whom about 2 million seek infertility treatments.

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