A Familys Race to Cure a Daughters Genetic Disease

One July afternoon last summer, Matt Wilsey distributed small plastic tubes to 60 people gathered in a Palo Alto, California, hotel. Most of them had traveled thousands of miles to be here; now, each popped the top off a barcoded tube, spat in about half a teaspoon of saliva, and closed the tube. Some massaged their cheeks to produce enough spit to fill the tubes. Others couldn’t spit, so a technician rolled individual cotton swabs along the insides of their cheeks, harvesting their skin cells—and the valuable DNA inside.

One of the donors was Asger Vigeholm, a Danish business developer who had traveled from Copenhagen to be here, in a nondescript lobby at the Palo Alto Hilton. Wilsey is not a doctor, and Vigeholm is not his patient. But they are united in a unique medical pursuit.

Wilsey’s daughter, Grace, was one of the first children ever diagnosed with NGLY1 deficiency. It’s a genetic illness defined by a huge range of physical and mental disabilities: muscle weakness, liver problems, speech deficiencies, seizures. In 2016, Vigeholm’s son, Bertram, became the first child known to die from complications of the disease. Early one morning, as Bertram, age four, slept nestled between his parents, a respiratory infection claimed his life, leaving Vigeholm and his wife, Henriette, to mourn with their first son, Viktor. He, too, has NGLY1 deficiency.

Grace and her mother, Kristen Wilsey.

BLAKE FARRINGTON

The night before the spit party, Vigeholm and Wilsey had gathered with members of 16 other families, eating pizza and drinking beer on the hotel patio as they got to know each other. All of them were related to one of the fewer than 50 children living in the world with NGLY1 deficiency. And all of them had been invited by the Wilseys—Matt and his wife Kristen, who in 2014 launched the Grace Science Foundation to study the disease.

These families had met through an online support group, but this was the first time they had all come together in real life. Over the next few days in California, every family member would contribute his or her DNA and other biological samples to scientists researching the disease. On Friday and Saturday, 15 of these scientists described their contributions to the foundation; some studied the NGLY1 gene in tiny worms or flies, while others were copying NGLY1 deficient patients’ cells to examine how they behaved in the lab. Nobody knows what makes a single genetic mutation morph into all the symptoms Grace experiences. But the families and scientists were there to find out—and maybe even find a treatment for the disease.

That search has been elusive. When scientists sequenced the first human genome in 2000, geneticist Francis Collins, a leader of the Human Genome Project that accomplished the feat, declared that it would lead to a “complete transformation in therapeutic medicine” by 2020. But the human genome turned out to be far more complex than scientists had anticipated. Most disorders, it’s now clear, are caused by a complicated mix of genetic faults and environmental factors.

And even when a disease is caused by a defect in just one gene, like NGLY1 deficiency, fixing that defect is anything but simple. Scientists have tried for 30 years to perfect gene therapy, a method for replacing defective copies of genes with corrected ones. The first attempts used modified viruses to insert corrected genes into patients’ genomes. The idea appeared elegant on paper, but the first US gene therapy to treat an inherited disease—for blindness—was approved just last year. Now scientists are testing methods such as Crispr, which offers a far more precise way to edit DNA, to replace flawed genes with error-free ones.

Certainly, the genetics revolution has made single-mutation diseases easier to identify; there are roughly 7,000, with dozens of new ones discovered each year. But if it’s hard to find a treatment for common genetic diseases, it’s all but impossible for the very rare ones. There’s no incentive for established companies to study them; the potential market is so small that a cure will never be profitable.

Which is where the Wilseys—and the rest of the NGLY1 families—come in. Like a growing number of groups affected by rare genetic diseases, they’re leapfrogging pharmaceutical companies’ incentive structures, funding and organizing their own research in search of a cure. And they’re trying many of the same approaches that Silicon Valley entrepreneurs have used for decades.

At 10:30 on a recent Monday morning, Grace is in Spanish class. The delicate 8-year-old with wavy brown hair twisted back into a ponytail sits in her activity chair—a maneuverable kid-sized wheelchair. Her teacher passes out rectangular pieces of paper, instructing the students to make name tags.

Grace grabs her paper and chews it. Her aide gently takes the paper from Grace’s mouth and puts it on Grace’s desk. The aide produces a plastic baggie of giant-sized crayons shaped like cylindrical blocks; they’re easier for Grace to hold than the standard Crayolas that her public school classmates are using.

Grace’s NGLY1 deficiency keeps her from speaking.

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At her school, a therapist helps her communicate.

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The other kids have written their names and are now decorating their name tags.

“Are we allowed to draw zombies for the decorations?” one boy asks, as Grace mouths her crayons through the baggie.

Grace’s aide selects a blue crayon, puts it in Grace’s hand, and closes her hand over Grace’s. She guides Grace’s hand, drawing letters on the paper: “G-R-A-C-E.”

Grace lives with profound mental and physical disabilities. After she was born in 2009, her bewildering list of symptoms—weak muscles, difficulty eating, failure to thrive, liver damage, dry eyes, poor sleep—confounded every doctor she encountered. Grace didn’t toddle until she was three and still needs help using the toilet. She doesn’t speak and, like an infant, still grabs anything within arm’s reach and chews on it.

Her father wants to help her. The grandson of a prominent San Francisco philanthropist and a successful technology executive, Matt Wilsey graduated from Stanford, where he became friends with a fellow undergraduate who would one day be Grace’s godmother: Chelsea Clinton. Wilsey went on to work in the Clinton White House, on George W. Bush’s presidential campaign, and in the Pentagon.

But it was his return to Silicon Valley that really prepared Wilsey for the challenge of his life. He worked in business development for startups, where he built small companies into multimillion-dollar firms. He negotiated a key deal between online retailer Zazzle and Disney, and later cofounded the online payments company Cardspring, where he brokered a pivotal deal with First Data, the largest payment processor in the world. He was chief revenue officer at Cardspring when four-year-old Grace was diagnosed as one of the first patients with NGLY1 deficiency in 2013—and when he learned there was no cure.

At the time, scientists knew that the NGLY1 gene makes a protein called N-glycanase. But they had no idea how mistakes in the NGLY1 gene caused the bewildering array of symptoms seen in Grace and other kids with NGLY1 deficiency.

Wilsey’s experience solving technology problems spurred him to ask scientists, doctors, venture capitalists, and other families what he could do to help Grace. Most advised him to start a foundation—a place to collect money for research that might lead to a cure for NGLY1 deficiency.

As many as 30 percent of families who turn to genetic sequencing receive a diagnosis. But most rare diseases are new to science and medicine, and therefore largely untreatable. More than 250 small foundations are trying to fill this gap by sponsoring rare disease research. They’re funding scientists to make animals with the same genetic defects as their children so they can test potential cures. They’re getting patients’ genomes sequenced and sharing the results with hackers, crowdsourcing analysis of their data from global geeks. They’re making bespoke cancer treatments and starting for-profit businesses to work on finding cures for the diseases that affect them.

“Start a foundation for NGLY1 research, get it up and running, and then move on with your life,” a friend told Wilsey.

Wilsey heeded part of that advice but turned the rest of it on its head.

In 2014, Wilsey left Cardspring just before it was acquired by Twitter and started the Grace Science Foundation to fund research into NGLY1 deficiency. The foundation has committed $7 million to research since then, most of it raised from the Wilseys’ personal network.

Many other families with sick loved ones have started foundations, and some have succeeded. In 1991, for instance, a Texas boy named Ryan Dant was diagnosed with a fatal muscle-wasting disease called mucopolysaccharidosis type 1. His parents raised money to support an academic researcher who was working on a cure for MPS1; a company agreed to develop the drug, which became the first approved treatment for the disease in 2003.

But unlike Dant, Grace had a completely new disease. Nobody was researching it. So Wilsey began cold-calling dozens of scientists, hoping to convince them to take a look at NGLY1 deficiency; if they agreed to meet, Wilsey read up on how their research might help his daughter. Eventually he recruited more than 100 leading scientists, including Nobel Prize-winning biologist Shinya Yamanaka and Carolyn Bertozzi, to figure out what was so important about N-glycanase. He knew that science was unpredictable and so distributed Grace Science’s funding through about 30 grants worth an average of $135,000 apiece.

Two years later, one line of his massively parallel attack paid off.

Matt Wilsey, Grace’s father.

BLAKE FARRINGTON

Bertozzi, a world-leading chemist, studies enzymes that add and remove sugars from other proteins, fine-tuning their activity. N-glycanase does just that, ripping sugars off from other proteins. Our cells are not packed with the white, sweet stuff that you add to your coffee. But the tiny building blocks of molecules similar to table sugar can also attach themselves to proteins inside cells, acting like labels that tell the cell what to do with these proteins.

Scientists thought that N-glycanase’s main role was to help recycle defective proteins, but many other enzymes are also involved in this process. Nobody understood why the loss of N-glycanase had such drastic impacts on NGLY1 kids.

In 2016, Bertozzi had an idea. She thought N-glycanase might be more than just a bit player in the cell’s waste management system, so she decided to check whether it interacts with another protein that turns on the proteasomethe recycling machine within each of our cells.

This protein is nicknamed Nerf, after its abbreviation, Nrf1. But fresh-made Nerf comes with a sugar attached to its end, and as long as that sugar sticks, Nerf doesn’t work. Some other protein has to chop the sugar off to turn on Nerf and activate the cellular recycling service.

Think of Nerf’s sugar like the pin in a grenade: You have to remove the pin—or in this case, the sugar—to explode the grenade and break down faulty proteins.

But nobody knew what protein was pulling the pin out of Nerf. Bertozzi wondered if N-glycanase might be doing that job.

To find out, she first tested cells from mice and humans with and without working copies of the NGLY1 gene. The cells without NGLY1 weren’t able to remove Nerf’s sugar, but those with the enzyme did so easily. If Bertozzi added N-glycanase enzymes to cells without NGLY1, the cells began chopping off Nerf’s sugar just as they were supposed to: solid evidence, she thought, that N-glycanase and Nerf work together. N-glycanase pulls the pin (the sugar) out of the grenade (the Nerf protein) to trigger the explosion (boom).

The finding opened new doors for NGLY1 disease research. It gave scientists the first real clue about how NGLY1 deficiency affects patients’ bodies: by profoundly disabling their ability to degrade cellular junk via the proteasome.

As it turns out, the proteasome is also involved in a whole host of other diseases, such as cancer and brain disorders, that are far more common than NGLY1 deficiency. Wilsey immediately grasped the business implications: He had taken a moon shot, but he’d discovered something that could get him to Mars. Pharmaceutical companies had declined to work on NGLY1 deficiency because they couldn’t make money from a drug for such a rare disease. But Bertozzi had now linked NGLY1 deficiency to cancer and maladies such as Parkinson’s disease, through the proteasome—and cancer drugs are among the most profitable medicines.

Suddenly, Wilsey realized that he could invent a new business model for rare diseases. Work on rare diseases, he could argue, could also enable therapies for more common—and therefore profitable—conditions.

In early 2017, Wilsey put together a slide deck—the same kind he’d used to convince investors to fund his tech startups. Only this time, he wanted to start a biotechnology company focused on curing diseases linked to NGLY1. Others had done this before, such as John Crowley, who started a small biotechnology company that developed the first treatment for Pompe disease, which two of his children have. But few have been able to link their rare diseases to broader medical interests in the way that Wilsey hoped to.

He decided to build a company that makes treatments for both rare and common diseases involving NGLY1. Curing NGLY1 disease would be to this company as search is to Google—the big problem it was trying to solve, its reason for existence. Treating cancer would be like Google’s targeted advertising—the revenue stream that would help the company get there.

But his idea had its skeptics, Wilsey’s friends among them.

One, a biotechnology investor named Kush Parmar, told Wilsey about some major obstacles to developing a treatment for NGLY1 deficiency. Wilsey was thinking of using approaches such as gene therapy to deliver corrected NGLY1 genes into kids, or enzyme replacement therapy, to infuse kids with the N-glycanase enzyme they couldn’t make on their own.

But NGLY1 deficiency seems particularly damaging to cells in the brain and central nervous system, Parmar pointed out—places that are notoriously inaccessible to drugs. It’s hard to cure a disease if you can’t deliver the treatment to the right place.

Other friends warned Wilsey that most biotech startups fail. And even if his did succeed as a company, it might not achieve the goals that he wanted it to. Ken Drazan, president of the cancer diagnostics company Grail, is on the board of directors of Wilsey’s foundation. Drazan warned Wilsey that his company might be pulled away from NGLY1 deficiency. “If you take people’s capital, then you have to be open to wherever that product development takes you,” Drazan said.

But Wilsey did have some things going for him. Biotechnology companies have become interested of late in studying rare diseases—ones like the type of blindness for which the gene therapy was approved last year. If these treatments represent true cures, they can command a very high price.

Still, the newly approved gene therapy for blindness may be used in 6,000 people, 100 times more than could be helped by an NGLY1 deficiency cure. Wilsey asked dozens of biotechnology and pharmaceutical companies if they would work on NGLY1 deficiency. Only one, Takeda, Japan’s largest drug company, agreed to conduct substantial early-stage research on the illness. Others turned him down flat.

If no one else was going to develop a drug to treat NGLY1 deficiency, Wilsey, decided, he might as well try. “We have one shot at this,” he says. “Especially if your science is good enough, why not go for it?”

“Matt was showing classic entrepreneurial tendencies,” says Dan Levy, the vice president for small business at Facebook, who has known Wilsey since they rushed the same Stanford fraternity in the 1990s. “You have to suspend a little bit of disbelief, because everything is stacked against you.”

At 11 am, Grace sits in a classroom with a speech therapist. Though Grace doesn’t speak, she’s learning to use her “talker,” a tablet-sized device with icons that help her communicate. Grace grabs her talker and presses the icons for “play” and “music,” then presses a button to make her talker read the words out loud.

The "talker" used for Grace’s therapy.

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“OK, play music,” her therapist says, starting up a nearby iPad.

Grace watches an Elmo video on the iPad for a few moments, her forehead crinkled in concentration, her huge brown eyes a carbon copy of her dad’s. Then Grace stops the video and searches for another song.

Suddenly, her therapist slides the iPad out of Grace’s reach.

“You want ‘Slippery Fish,’” her therapist says. “I want you to tell me that.”

Grace turns to her talker: “Play music,” she types again.

The therapist attempts one more time to help Grace say more clearly which particular song she wants. Instead, Grace selects the symbols for two new words.

“Feel mad,” Grace’s talker declares.

Grace working with a therapist in one of their therapy rooms.

BLAKE FARRINGTON

There’s no denying how frustrating it can be for Grace to rely on other people to do everything for her, and how hard her family works to meet her constant needs.

Matt and Kristen can provide the therapy, equipment, medicines, and around-the-clock supervision that Grace needs to have a stable life. But that is not enough—not for Grace, who wants "Slippery Fish," nor for her parents, who want a cure.

So last summer, Wilsey raised money to bring the Vigeholms and the other NGLY1 families to Palo Alto, where they met with Grace’s doctors and the Grace Science Foundation researchers. One Japanese scientist, Takayuki Kamei, was overjoyed to meet two of the NGLY1 deficiency patients: “I say hello to their cells every morning,” he told their parents.

And because all of these families also want a cure, each also donated blood, skin, spit, stool, and urine to the world’s first NGLY1 deficiency biobank. In four days, scientists collected more NGLY1 deficiency data than had been collected in the entire five years since the disease was discovered. These patient samples, now stored at Stanford University and at Rutgers University, have been divvied up into more than 5,000 individual samples that will be distributed to academic and company researchers who wish to work on NGLY1 deficiency.

That same month, Wilsey closed a seed round of $7 million to start Grace Science LLC. His main backer, a veteran private equity investor, prefers not to be named. Like many in Silicon Valley, he’s recently become attracted to health care by the promise of a so-called “double bottom line”: the potential to both to make money and to do good by saving lives.

Wilsey is chief executive of the company and heavily involved in its scientific strategy. He’s looking for a head scientist with experience in gene therapy and in enzyme replacement therapy, which Mark Dant and John Crowley used to treat their sick children. Gene therapy now seems poised to take off after years of false starts; candidate cures for blood and nervous system disorders are speeding through clinical trials, and companies that use Crispr have raised more than $1 billion.

Wilsey doesn’t know which of these strategies, if any, will save Grace. But he hopes his company will find an NGLY1 deficiency cure within five years. The oldest known NGLY1 deficient patient is in her 20s, but since nobody has been looking for these patients until now, it’s impossible to know how many others—like Bertram—didn’t make it that long.

“We don’t know what Grace’s lifespan is,” Wilsey says. “We’re always waiting for the other shoe to drop.”

But at 3 pm on this one November day, that doesn’t seem to matter.

School’s out, and Grace is seated atop a light chestnut horse named Ned. Five staff members lead Grace through a session of equine therapy. Holding herself upright on Ned’s back helps Grace develop better core strength and coordination.

Grace on her horse.

BLAKE FARRINGTON

Grace and Ned walk under a canopy of oak trees. Her face is serene, her usually restless legs still as Ned paces through late-afternoon sunshine. But for a little grace, there may be a cure for her yet.

Read more: https://www.wired.com/story/a-familys-race-to-cure-a-daughters-genetic-disease/

Would You Trust a 3D-Printed Mini Organ to Test Your Drugs?

No one wanted to believe it, said molecular geneticist Hans Clevers.

In 2009, Clevers and his team had demonstrated an unusual new method of creating tiny, out-of-the-body replicas of human organs that could be used to study disease. These replicas were 3-dimensional organoids generated from human cells that perfectly replicated the structure of cells lining the intestine, and therefore could be studied and tested without using human volunteers.

(While it might seem as if this was a guaranteed winner in the books in terms of science innovation, Clevers and his team were rejected by several publications, before Nature finally published the report.)

Organoids could be a genius scientific workaround on a basic problem: How do we effectively, scientifically, but safely run experiments about humans? The little organs are poised to be a gamechanger in figuring out how cures to diseases could be derived. In fact, volunteers organoids can act as proxies that will stand in for them.

Testing new drugs and medical treatments is perilous, cumbersome, and time-consuming. More than 80 percent of new drugs tested in the U.S. to determine if they are safe for patient use fail during clinical trials because they prove to be ineffective. More than 30 percent are found to be toxic. There is an urgent need for improved systems to accurately predict the effects of drugs, chemicals, and biological agents on the human body, Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine, said.

Which makes organoids seem like a lifesaver that can speed up and ensure the safety of the drug testing process. Innovations that generate organoids, in addition to bioprinting, include organ-on-a-chip technology and tissue-chips, which situate the organoid on a microchip.

In addition to generating organoids using bioprinters, other methods of creating organoids are being researched. Some organoids are created in lab dishes. Others use stem cells and other cellular materials to create organoids include placing tiny, testable organs on a microchip. These are called tissue-chips, which are not to be confused with organ-on-a-chip technologyboth use different combinations of humans cells and materials to create either miniature organs or tissues.

One limitation of testing drugs on organoids alone is that they are isolated from the nervous system and blood system, whereas the drug could impact the related processes. To address this, scientists are linking organs-on-a-chip together, so that they form a body-on-a-chip. In this way, they are joined together on chips just as they are joined together inside the human body.

The U.S. Food and Drug Administration has not yet approved any of these methods, but is reviewing them. The FDA partners with the National Center for Translational Sciences (NCATS), part of the National Institutes of Health, via NCATS Tissue Chip for Drug Screening program. Tissue chips are poised to deliver a paradigm shift in drug discovery, Dr. Danilo Tagle, associate director of Special Initiatives at NCATS/NIH explained in an email.

As organoid research moves ahead on many fronts, including stem cells, 3D bioprinting has proven to be cost-efficient. A pioneer in the field, Dr. Aleksander Skardal of the Wake Forest School of Medicines Institute for Regenerative Medicine, has observed, The liver and cardiac organoids that we bioprinted into tissue-on-a-chip constructs far surpassed the functionality of alternatives.

That 80 percent fail-rate of current testing demands something new. For one thing, animal rights proponents would welcome the end of clinical trials that dont involve running experiments on mammals.

Dr. Todd Evans is a professor of surgery and associate dean for research at New Yorks Weill Cornell Medicine. Evans and his colleagues have generated stem-cell-derived organoids from colon cancer, and a platform for testing drugs that block disease caused by patient-specific mutations.

Organoids represent a very important advance for modeling human disease, since they recapitulate at least to some extent the 3D architecture of an organ and thereby much better represent a tissue compared to standard 2D cell culture systems, Evans wrote to The Daily Beast in an email.

Evans has observed how its possible to screen pharmaceutical compounds for effectiveness as candidates for drugs, because organoids can mimic some aspects of cell biology. However, there are clearly limitations and these approaches will never replace clinical trials, Evans wrote. They are still an in vitro (in a laboratory) approach and do not take into account cross-organ communication or a multitude of human physiological and metabolic parameters. This might in the future be somewhat better achieved by organ-on-a-chip method.

Despite limitations, any method that ferrets out weaker drug candidates could save pharmaceutical companies, as well as taxpayers who fund the FDA, millions of dollars. Allevi, one of the pioneer research firms that developed bioprinters, designed a desktop bioprinter that measures 12 inches cubed and costs $10,000.

Other companies are jumping in. Pfizer Inc. is collaborating with Cambridge-based research firm Draper to develop liver, gastrointestinal, and other organ models. Colgate-Palmolive is another Draper partner, researching models of gum tissue for testing oral care products.

Use of organ models is much more predictive than using animals, Dr. Joseph Charest, Drapers Biomedical Solutions program manager and director of the Human Organ Initiative, told The Daily Beast in a phone interview.

What these models are able to do is recreate a disease state, Charest said. We can screen a lot of different drugs and compounds, in varying amounts, and we can do this fairly early in the pipeline, which allows you to rule out the bad ones and continue testing the good ones.

Draper develops multiple organs-on-chips. Weve been able to recreate the various organs that form the female reproductive system, and put them on chips. That is one example of how we connect organs, Charest said. The system has various pieces of tissue that communicate with each other.

Shortening the time required to get a drug to the clinic is really the point of all this science and research.

Heart-on-a-chip causes most live hearts to skip a beat. People are not going to get upset about making a pancreas, Stanford Universitys Bioethics Law professor Henry Greely told The Scientist in 2016. But the closer you come to making a human brain, the more issues get raised. Bodies-on-a-chip seem too Frankenstein-esque for some.

Nonetheless, plans include using human cells from several hundred, if not thousands of individuals, that represent the diverse demographics of the general population for use as surrogate clinical trials on chips, according to Tagle. Such platforms hold promise to reduce the cost and time it takes to bring drugs into market but also to minimize risk to patients.

Read more: https://www.thedailybeast.com/would-you-trust-a-3d-printed-mini-organ-to-test-your-drugs

The FDA has approved a blood sugar monitor that doesnt require a finger prick

Further proof the U.S. Food and Drug Administration has been warming up to modern technology — it has just approved the first continuous blood sugar monitor that doesn’t require the user to prick themselves over and over for a blood sample.

Today, the FDA cleared Abbot’s FreeStyle Libre Flash Glucose Monitoring System, a device that uses a small sensor wire inserted under the skin to determine glucose levels in adult diabetics. Another wand-like device is then waved over the sensor to measure and give a readout of those glucose levels.

This is a milestone move for the FDA as diabetes affects nearly 30 million people in the United States who currently have to test their blood sugar by pricking themselves several times throughout the day and every time they eat.

However, the idea for a prickless blood sugar monitor isn’t new. Tech companies have increasingly shown an interest in the massive diabetics market over the past few years. Apple is rumored to be working on such a device and its CEO Tim Cook has even been spotted wearing a possible prototype that could connect to the Apple Watch.

Other companies endeavor to build something similar, including Glucowise, which has a device still under development.

However, it seems it’s not so easy to create a needleless blood sugar detector. Google tried to build a contact lens that could detect glucose but it seems the project has gone nowhere since drug company Novartis licensed the tech in 2014. Another FDA-approved device for glucose monitoring without the prick called the GlucoWatch was approved in the early 2000’s, but consumers found it cumbersome and it happened to cause a bad rash in some.

But there’s new hope today that the Freestyle monitor has worked out all the kinks. The device is intended for those 18 and older and, after a 12-hour start-up period, can be worn for up to 10 days, according to a statement on the FDA’s website.

“The FDA is always interested in new technologies that can help make the care of people living with chronic conditions, such as diabetes, easier and more manageable,” said FDA spokesperson Donald St. Pierre. “This system allows people with diabetics to avoid the additional step of finger stick calibration, which can sometimes be painful, but still provides necessary information for treating their diabetes—with a wave of the mobile reader.”

Read more: https://techcrunch.com/2017/09/28/the-fda-has-approved-the-first-blood-sugar-monitor-that-doesnt-require-a-finger-prick/

You Lied Your Way Into A Job As A Surgeon! Can You Avoid Killing Anyone Long Enough To Collect Your First Paycheck?

Surgeons. The masters of the flesh. The gatekeepers of the organs. The doctors who get to shave patients.

These are the green-wearing gods who know that the human body is but a chessboard, and that the nipples are the king and queen, and the belly button is the opposing king or queen.

Today, finally, you are beginning your journey as one of them.

You have already gone through the arduous process of becoming a surgeon. After calling the hospital over and over every day for three weeks straight and praising Tylenol in the deepest voice you could muster to whoever picked up, being hung up on by countless doctors and nurses, you finally hit the big time.

Yesterday, you managed to get the chief of medicine on the line, who offered you a job after a mere 50 minutes of you bellowing to her about the white-and-red pill. Congratulations!

Okay. Being a surgeon is sweet as hell. You get to wear patients’ clothes around a hospital once the chemicals put them to sleep, you can eat as many tortilla chips as you want, and you can hide all of your favorite DVDs and family heirlooms inside toxic waste bins, the one place thieving pricks are too grossed out by to steal from.

Cool. But the best part of being a surgeon, bar none, is that incredible surgeon paycheck.

It’s no secret that surgeons are paid well, as every single day at 8 p.m., hardworking surgeons all over the world reap the fruits of their labor: a plastic bag filled with $600, given to them by their chief of medicine on their way out the door, in addition to a goodnight kiss on the forehead.

Exactly. So now that you’re a surgeon, you better do everything in your power to make it your $600 payday, because there is one universal stipulation that could jam you up: If a surgeon kills someone, everything completely goes to shit.

1) For starters, once a surgeon kills someone, they are NEVER allowed back in a hospital, ever. Even if you just want to go to hang out or to meet new lovers.

2) Your professional reference completely goes out the window. If a new job calls to ask about you, instead of a recommendation, the HR department hands the phone off to the absolute sickest pervert patient they have, and lets them air out whatever they’ve got kickin’ around up in their minds.

3) Lastly—and this one is the worst of all—you don’t get paid a dime, which would mean all of your efforts to become a surgeon were for NOTHING.

So, if you want to get to that sweet paycheck, you’re going to have to make it through one entire day as a surgeon without killing someone.

The hospital. The place where people come when they are bored to take off their pants and scream. This will be your new surgeon home, and today is your first day of work. As far as anyone inside is concerned, you are now a fully qualified surgeon, so if you want those 600 clams, you’re going to have to hold your own and stay off everyone’s radar.

“Please give me a surgery.”

Ah, shit. A sick kid is waiting for you right inside the lobby, and he looks all kinds of fucked up.

“I need a surgery pronto. I am dying, and it feels like none of my bones are connected to my other bones. I also have a rash that comes and goes. Please do surgery to me with your other doctor friends.”

“If you don’t give me a surgery right now, I will scream. I will scream so loud and for so long, and I will point at you the whole time. It will go on for so long that the rest of the doctors here will have no choice but to send you to jail.”

That was close. You’ve pissed your pants real good, and now you’re in the bathroom splashing your pants with water, the best way to clean pants that you’ve urinated in.

“You sure know your way around cleaning a pair of pissed pants, sport. Not bad at all.”

You look over and see that it’s the hospital’s janitor talking to you. He somehow opened the door in perfect silence while you were inside splashing your pants, and has been watching you for upwards of 90 full seconds.

“I’ve been watching you for upwards of 90 full seconds, and I can tell just by looking at you, you’re no surgeon.”

“Easy, easy. I’m not gonna rat you out. I’m gonna help you.

I take it that you’re in here lying to be a surgeon, hoping to get ‘The $600 Bag Treatment,’ huh? Well, you’ve got a friend in me. I’ve seen it before, and I’ll see it again. All you gotta do is make it until 8 p.m. without killing a soul and you’re in the clear. So whadya say you come lay low with me for the rest of the day, spend some time hanging with a new bud so you don’t end up killin’ no one before you get that money?”

“I, uh, how do you mean?” he says, visibly becoming self-conscious about the entire interaction so far. “I’m just tired today, so if I’m acting weird, that’s what that’s about, probably. Allergies are being weird, too.”

“Follow me!” the janitor says before sprinting down the hallway. You do your best to keep up with him as he weaves in and out of patients and doctors before you finally arrive at a huge metal door. He slides open the rusty door to reveal a set of long, winding stairs that lead to a dark, desolate basement, and turns to you with a half smile.

“It’s not delivery, it’s DiGiorno,” he says before letting out a quick, uncertain laugh, looking over his shoulder at you to kind of check in and see if you’re laughing or anything at what must have been some sort of joke.

“That was dumb, never mind,” the janitor says, shaking his head as his shoulders slump, trying to explain his joke before slowly progressing into full-blown self-deprecation. “I was thinking, like, how in the old commercials, I’d be the delivery guy and you’re the pizza—I don’t know, forget it. It was dumb. Sorry.”

You follow the janitor down the stairs and into the basement of the hospital, and lo and behold, it’s a full-blown bachelor’s pad! The janitor has stocked the place with some of the best things: a ping-pong table, a “Forever 27” poster, an old-timey popcorn machine, and a bunch of orange pill bottles filled with Frosted Cheerios.

“This is my chill zone. I’m down here almost all the time, which is why the hospital is filthy and patients always seem to get sick immediately after they get better.”

“We got all day, brother, so we could either sit down and talk about that important-looking guitar I have mounted on the wall over there, or we could stand near the stairs and wonder if Slash has ever signed a guitar and sold it for $20,000 online before, or maybe we could lay down on the ground and trade stories about the most expensive thing we’ve ever mounted on a wall. Your call.”

“I can’t lift my arms above my waist because of a power-washer accident.”

“You got a good eye, kid,” he says as though you brought it up completely unprompted, proudly looking up at the guitar he somehow mounted unnecessarily high on his wall.

“Believe it or not, Slash signed that guitar, and I was lucky enough to spend all of the money I have on it. I usually don’t do this for anyone, but for you, I’ll climb all the way up there and get it if you want to hold it.”

“I’d climb anywhere for one of my boys.”

“I’ll put a very wet towel over them. I’m sure that will be fine.”

You’ve killed! You’ve killed!

You put the janitor in grave danger by selfishly asking him to grab his Slash guitar off the wall. After the janitor put a soaking-wet towel on top of his countless basement wires in order to walk over to the wall and begin his climb, he was immediately electrocuted and fell crashing to the ground without the ability to raise his arms and break his fall. It’s unclear if it was the electricity surging through his body that did him in, or if it was the way his neck snapped on a nearby stool because of the horrible, unnatural way he fell. But either way, he is definitely dead, and it is your fault.

You’re no longer a surgeon, and you can kiss that bag of $600 goodbye.

As you go back up the stairs and start heading toward the lobby, you can hear that he starts to follow you, but then locks himself in the bathroom you were in earlier and begins screaming at himself in the mirror for messing up what could’ve been a nice day. His screaming gets louder and louder before it comes to a halt after you hear the sound of him snapping his mop over his knee in fury.

“I need you to give me a surgery right now.”

Ah, damn. It’s the sick kid from earlier.

“I feel like I’m on a boat at all hours of the day, and my elbows are dry. I need you to cut me open and drain me out, if that’s what it takes, and to please get me home by later today.”

You pick the kid up, throw him over your shoulder, and walk through the hospital looking for a good room to cut him open in. After 20 minutes, you finally find the room with all of the surgeons in it, and you slam the kid down on the empty table they’re all staring at.

Now all eyes are on you. You’re going to have to step up and say something pretty incredible to get all of these surgeons on your side.

You’ve killed! You’ve killed!

After you said that ridiculous, dumbass comment, every surgeon in the room became furious at you and began hammering you with questions about your qualifications. You tried mumbling through more Tylenol facts, which went much worse in person than it did on the phone, and somewhere during your 25-minute verbal beatdown from the other surgeons, the kid died on the table.

You are no longer a surgeon, and you will never get a plastic bag filled with $600.

Share Your Results

Everyone starts nodding and smiling and patting each other on the back. Good shit.

“Ha, nice,” a woman says, whose voice you recognize from the phone as the chief of medicine at the hospital. She quickly anesthetizes the patient to finally stop him from grabbing and clawing at everyone’s surgical masks, and within seconds the little spaz is sleeping.

At that moment, the tallest doctor you’ve ever seen walks into the door wearing a backwards hat and confidently drinking Barq’s Root Beer out of a 2-liter bottle.

“I’ve never seen you around here,” he says after putting the root beer down firmly into the lap of the unconscious kid and eyeing you up and down suspiciously. “Enlighten us, fresh meat. Now, what surgery are we performing on this little man, exactly?”

Ah, this guy is onto you. Need something big here to throw everyone off your tracks.

“Doctors, you two can be mean to each other in the parking lot all day long if you want to, but that’ll be enough fighting in my hospital,” says the chief of medicine after banging her fist down onto the kid’s chest like a gavel to get everyone’s attention.

“This little boy is in dire need of a heart transplant. We need to start immediately.”

“Doctors, that’ll be enough talk about whether or not there are actually types of surgeries or not, because there simply is not a correct answer,” says the chief of medicine after banging her fist down onto the kid’s chest like a gavel to get everyone’s attention.

“This little boy is in dire need of a heart transplant. We need to start immediately.”

“Doctors, please stop winking at each other,” says the chief of medicine after banging her fist down onto the kid’s chest like a gavel to get everyone’s attention.

“This little boy is in dire need of a heart transplant. We need to start immediately.”

After noticing that no one is reacting to you pissing yourself, you look around and realize that every surgeon in the room has also already pissed themselves. Then you remember that surgeons are constantly pissing themselves during surgery, like bicyclists during races, for reasons completely unknown.

The chief of medicine takes out a toolbox from underneath the surgery-room sink and hands each surgeon a tool. She takes each tool out one by one and starts passing them down the line. One doctor gets a small shovel, one gets a large knife, another gets a pickax, and on and on it goes, until you finally end up with the flashlight!

“Um, yeah, that’s my flashlight, pal. I’m always the flashlight man around here,” says the root-beer doctor.

“No,” interjects the chief. “New guy can hold the flashlight today. I have a good feeling about this.”

Your new rival is stunned. He shoots you a dirty look, threateningly crosses his thumb over his neck, and then does it again with his other thumb, but slower. Then he quietly mouths something that you didn’t really get a good read on, but from what you did see, your best guess is that he was saying something like “Fracking mountains,” or “Simply delicious.” Then he is handed the worst tool: the blood napkin, the tool that wipes up all the loose goo and pus.

“Ah, c’mon, man. Quit it. What the hell.”

The surgery is now well under way. The chief is slicing and dicing and moving parts around left and right. It’s pretty much a one-woman show.

Most of the other doctors are using their tools just to kind of scrape some bones and stuff when they feel like they should get in the mix, usually after not doing anything for a couple minutes straight and getting nervous that someone will notice how they’re not really that crucial to the operation.

You’re getting bored by the whole thing at this point, but at least you’re holding your own with these docs and, most importantly, haven’t killed anyone yet.

Surgery still going. Getting kind of repetitive. A couple doctors shuffled out for a minute and came back with crackers, but the crackers are all gone now. You didn’t even notice they had crackers until there were only, like, four left in the sleeve, so at that point, asking for some really wouldn’t have been cool.

Surgery is getting boring.

Surgery is boring as hell.Your arms got tired from holding the flashlight up, so you put it down for a minute and no one seemed to notice. You’re back up now.

Kid woke up and started screaming LOUD, but now he’s sleeping again.

“You were scared!” “No, you were scared!” “I wasn’t scared, you were scared!” The surgeons are all ragging on each other and having fun again. Finally got some juice in the room. Whole crew got a good laugh out of that one.

Woah, wait a minute. Oh, man. You see something inside the kid’s body. Wedged deep in between his rib cage and his liver, there looks to be something shining and throbbing, and you’re pretty sure you’re the only one who sees it.

Two doctors broke away from the surgery about 15 minutes ago to arm wrestle on a nearby stool, and the rest of the surgeons have all one-by-one walked over to form a circle around them so they can gamble. Meanwhile, the chief is still hacking away at this kid’s organs with all of her might, and seems way too dialed-in to notice the game changer you’ve found.

You’ve killed! You’ve killed!

You thought you were being a hero by yanking out what you thought were some sort of wet, shining metals, but were actually the poor kid’s veins. You are no longer a surgeon, and can go ahead and kiss that sweet paycheck goodbye.

“Those are veins. They are not ‘evil copper and metals sticking out of this poor bastard’s guts.’ Do not call them that.”

Damn. Misread that one. The chief is totally onto you now.

“But I appreciate you speaking your mind when you think something is amiss,” she continues, looking up and making eye contact with you for the first time. “That takes a commitment to the job that some of my other doctors lack at times,” she says, motioning to the doctors across the room who are now attempting to disguise their arm-wrestling gambling ring by draping a hospital gown over the two meaty, dueling arms.

The chief reciprocates your unblinking eye contact and begins nodding in perfect unison with your nodding. This goes on for a good 20 seconds or so, the grunts of the two arm wrestlers and the slaps of cold, hard cash hitting the tile becoming the only sounds in the room.

At that moment, you and the chief simultaneously feel a romantic charge between you, and it feels beautiful and right. But that romantic feeling is immediately followed by a simultaneous paternal feeling, but it’s unclear who is the parent and who is the child. Then the two feelings of physical attraction and familial protectiveness fuse together into one singular emotion, and it feels disgusting to both of you.

“Yeah, yeah, go catch up with them. I’ll hold it down over here, cool,” the chief kind of half-mutters to herself and to you while shaking her head and getting back to surgery.

You walk over to the gambling circle and see the two exhausted surgeons pulling and pushing as hard as they can to win. The two doctors are so evenly matched that their arms aren’t moving or shaking in the slightest. If it weren’t for the veins about to explode out of their temples and the tears streaming down their faces, you’d have no idea how intense the duel was.

All of the other surgeons are quietly going apeshit. Almost all of them are either gently pounding their chests, gingerly slapping the ground, or shaking their fists in the air, all the while whispering bad arm-wrestling advice like “Win the skin!” or “Make him smooth!”

It’s definitely a pretty sweet scene, and you decide that you want to get in the mix.

As you go to ask the doctor next to you, your rival doctor steps in front and interrupts:

“Looking to get in on the action but lacking the funds, newbie? Don’t worry, fresh meat. I got you covered. Also, we’re rival doctors, just in case that wasn’t clear.”

Whoa, pretty cool to get a rival doctor on your first day on the job. That probably usually takes years.

“That’s my coat over there,” he says, pointing to a white lab coat being worn by one of the arm-wrestling surgeons. “Go ahead and take my wallet out of the pocket and take out as much money as you want.”

He then lets out a weird little laugh and looks around to see if anyone else is laughing. One other doctor did laugh, but he’s in the middle of a conversation with another surgeon, so you’re pretty sure the laugh had nothing to do with your rival.

“I have coats all over this hospital that you wouldn’t know a thing about,” he says, raising his fist up to your chin real quick, trying to get you to flinch. You stand your ground and don’t flinch at all, though, and he sheepishly brings his fist back down to his side.

You’ve killed! You’ve killed!

In a brilliantly executed scheme, your rival tricked you into reaching into the coat of one of the doctors who is arm wrestling. When the arm wrestler saw you trying to steal his wallet, his mix of adrenaline and dangerously high blood pressure caused his heart to explode.

Your misconduct has resulted in a death, meaning you can no longer be a surgeon, and you will never see that sweet, sweet bag o’ cash.

The Pill and Libido (Sexual Health for Women)





 

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The Miracle Cure Gwyneth Paltrow Accidentally Got Right

Gwyneth Paltrow, Oscar-winner and dubious lifestyle guru, is under fire again. At issue this time: Body Vibes, the small stickers that can be placed on the upper arms to promote healing, rebalance energy frequencies, smooth out physical tension and anxiety, and boost cell turnover.

Paltrow wasnt criticized because her website Goop was again peddling a product that couldnt prove any of its claims or outright dangerous. Or because oneboosting cell turnoversounded like something that no one should ever want. Rather she was slapped for the biological basis on which these claims were made: Paltrow said the healing power of Body Vibes came from NASA space science. Its inventors had supposedly used the same conductive carbon material that NASA uses to line space suits so they can monitor an astronauts vital [signs] during wear. According to GOOP, the technology developed by NASA used a biofrequency that resonates with the bodys natural energy field.

NASA immediately debunked Paltrows claim, stating that spacesuits do not have any conductive carbon material lining. (And Goop subsequently removed it.)

Although many have been quick to dismiss Goops latest miracle cure, Body Vibe stickers do offer the same thing that alternative healers typically promisea chance to benefit from the placebo response.

One of the first demonstrations of the power of the placebo took place on the battlefields of World War II, where a nurse ran out of morphine. Unable to tell a wounded soldier that she had nothing to treat his pain, she said the saltwater she had just given him was actually morphine. To her surprise, the soldiers pain disappeared. Researchers have since found that people can learn to release their own endorphins: powerful, morphine-like, pain-relieving chemicals made by the pituitary gland and hypothalamus. Indeed, the biological basis of pain relief from acupuncture has nothing to do with where the healer puts the needlesor even whether the needles enter the skinand everything to do with some patients releasing their own endorphins.

The placebo response isnt limited to pain relief.

In 1957, John Imboden and colleagues at Johns Hopkins School of Medicine performed a landmark experiment. They administered a series of psychological tests to military personnel working at Fort Detrick, Maryland. A few months later, an influenza pandemic swept across the camp. Imboden found that recruits who were depressed had symptoms of influenza that lasted longer and were more severe than those in recruits who werent depressed. In other words, mood determined illness. The mind, wrote John Milton in Paradise Lost, can make a heaven of hell and a hell of heaven.

In 1975, Robert Ader and Nicholas Cohen from the University of Rochester School of Medicine took Imbodens observations one step further. They found that rats given cyclophosphamide (an immune-suppressive drug) in saccharin-flavored water developed an inability to respond to foreign proteins. Weeks later, their immune systems recovered. That wasnt surprising. What was surprising was that when these same rats were later given saccharin-flavored water only, they again had a lesser immune response. The rats, by pairing the taste of saccharin with an immune-suppressive drug, had learned to suppress their own immune systems. Amazing.

The next question: Could researchers teach people to suppress their immune response? Again, Robert Ader took the lead. Working with a teenager with the autoimmune disease lupus, he paired cyclophosphamide with a distinct taste (cod liver oil) and smell (rose perfume). Like the rats, the boy learned to suppress his immune response, requiring less-frequent dosing of the steroid necessary to control his disease. Other researchers replicated Aders findings. And it worked both ways; not only could people learn to suppress their immune responses, they could learn to enhance them.

Which brings us back to Gwyneth Paltrows Body Vibes. If people believe that Body Vibe patches are giving them more energy or relieving tension, whos to say that this belief cant result in healing? If people can learn to release their own endorphins or up-regulate or down-regulate their own immune systems, why cant Body Vibe patches offer some benefit? And, unlike antidepressants or mood-elevating drugs, these patches have no side effects.

Another thing. Although the cost of Body Vibe patches$60 for a pack of 10is no doubt logarithmically greater than the cost of manufacture, according to the theory of cognitive dissonance, the more expensive the better. This concept was first tested at a racetrack in the 1960s. Researchers asked bettors to rate their horse as they walked toward or away from the betting window. Bettors faced two conflicting facts: 1) Any horse could win the race, 2) I bet a lot of money on only one horse. To resolve the conflict, bettors rated their horse much higher after placing their bets. (Heres that study.) In another, researchers from MIT tested the capacity of two sugar pills to relieve pain. One group was told that the pill cost 10 cents, the other that it cost $2.50. Participants experienced less pain with the pill that was said to be more expensive.

But is it ethical for Body Vibes marketers to deceive?

In fairness, all practitionersmainstream or otherwiseemploy some form of deception. They know that a positive attitude, reassuring demeanor, and air of competence are important. We use the placebo effect all the time, says Art Caplan, professor of bioethics at New York Universitys Langone Medical Center. Ive got a bowtie. I wear a white coat. You come to a big building that looks pretty impressive. I expect someday to see billboards go up in cities that say we have a really big machine and it makes a lot of noise and we dont know how it works but you can only get it from us so come on down.

Indeed, it would be more honest if mainstream doctors walked into a patients room and said, Look, we will definitely know more about how to treat your illness a hundred years from now. Frankly, I suspect doctors in the future will look back on some of the things that were doing today and laugh. Although our understanding of many diseases is excellent, for some were just treading water, and for others were completely lost. No clinicians (in their right mind) say this. From the days of shamans and witch doctors to the modern-day physician, everybody has their props, their deceptions. In fact, studies have shown that when physicians claim that one particular medicine will be more effective, the patient will later perceive that medicine as being more effective.

The line that cannot be crossed, however, is recommending placebo therapies that are potentially harmful. Unfortunately, in several instances, Goop has crossed that line, including touting vaginal steaming with mugwort to balance female hormone levels and cleanse the uterus, which, apart from the fact that mugwort isnt a hormone and vaginal steam (absent pressure) will never reach the uterus, could cause burns or bacterial infections. Or promoting placing $66 jade eggs the size of golf balls in the vagina in hopes of boosting orgasms, enhancing kidney strength, improving physical appearance, and increasing vaginal tone, hormonal balance, and feminine energyas well as the risk of bacterial infections, including toxic-shock syndrome. Or even cleansing the colon with enemas to remove toxins, boost energy, and enhance the immune system. These have no proven benefit in otherwise healthy people, and can cause dehydration, infections, vomiting, and, worst of all, bowel perforations.

Although Gwyneth Paltrow should be held accountable for therapies that are potentially dangerous, Body Vibe patches dont fall into that category. And Paltrow could reasonably argue that believing that you are benefiting from the patches might trigger a physiological response that is actually beneficial. Belief is a powerful medicine.

Paul A. Offit is the director of the Vaccine Education Center at the Childrens Hospital of Philadelphia and the author of Do You Believe in Magic? The Sense and Nonsense of Alternative Medicine (HarperCollins, 2013).

Read more: http://www.thedailybeast.com/the-miracle-cure-gwyneth-paltrow-accidentally-got-right

Birth control app Nurx now delivers to the contraceptive deserts of Texas

About half the counties in Texas dont have the number of public clinics required to meet the contraceptive needs of the population. So Nurx, an at-home birth control delivery app, decided to give women in the state the option to get birth control whenever they want and without ever needing to step into a clinic or even physically see a doctor.

Starting today, those in the Lone Star State will be able to tap the Nurx app and get contraceptives delivered straight to their door.

While Texas isnt the only state with a giant contraceptive desert, or an area withoutat least 1 clinic to every 1,000 women in need of publicly funded contraception, it is certainly the biggest area of land in the United States not meeting these needs.

And with Trumpcare looming, and Trumps recent Religious Freedom order, which allows businesses to deny birth control coverage based on religious reasons, many women could lose access to their publicly funded birth control pills and even more publicly funded clinics could go under, leaving a large and vulnerable population wide open to other, possibly dangerous methods of preventing birth.

While there are plenty of birth control delivery services out on the market, such as Maven, The Pill Club, Lemonaid and BirthControlBuzz, I had a hard time finding any that delivered in Texas (get at me if you do). Thats not to say they wont at some point, as each of them could easily open up shop in this area, but it does seem Nurx,which is not a free birth control delivery service, but does provide the pills at a reasonable cost, may havediscovered a goldmine of people in need, for the time being.

For instance, a little more than half of all pregnancies in Texas were unplannedin 2015, costing taxpayers $2.9 billion that year. However, according to a Guttmacher Institute report, the total gross public savings from preventing unintended pregnancies would have been $2.14 billion if women and couples could be empowered to prevent them. Couple that with the teen birth rate in Texas, which sharply declined by 56 percent over the last two decades, thanks in large part to contraceptives, according to the National Campaign to Prevent Teen and Unplanned Pregnancy.

Couple that with an additional estimate of more than 19 million women living in these contraceptive deserts nationwide and its easy to see adding these types of services could save money at the state level by removing middlemen and increasing access, as well as provide a lucrative area for Nurx and other birth control delivery apps to tap.

Read more: https://techcrunch.com/2017/06/05/birth-control-app-nurx-now-delivers-to-the-contraceptive-deserts-of-texas/

Prevention of Cervical Cancer- Natural Medicine

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Dr. Barrett discusses dietary and lifestyle interventions to help prevent cervical cancer.

Uthman on Cervical Cancer

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Pathologist Ed Uthman, MD, in a short interview about preventing cancer of the cervix. Produced by Stafford Weekly News.

Vaginal Womb Detox Herbal Tampons For Women It Works

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