Mini reproductive system on a chip mimics human menstrual cycle

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Researchers create models of organs such as a uterus and cervix in the laboratory.

• Sara Reardon

28 March 2017

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Human organ systems on chips aren't just ideas now, with the introduction of an artificial female reproductive system.

In the quest to study human reproduction, scientists have built a rudimentary model of the female system in the lab. Every 28 days, the 'ovary', cultured on a small plastic chip, releases an egg and starts producing hormones to prepare for pregnancy. The hormones travel through a series of tiny channels that mimic Fallopian tubes and into a uterus-like chamber made of human tissue.

The system, described in a study¹ published on 28 March in Nature Communications, is the latest in a series of organs-on-chips — miniature devices seeded with human tissues and cells that are engineered to model biological functions.

Researchers hope that the synthetic reproductive system will provide another avenue for studying diseases such as cervical cancer, and allow them to test new contraceptives and fertility treatments before being used in people. There is no good animal model for the 28-day human reproductive cycle, says Teresa Woodruff, a reproductive scientist at Northwestern University in Chicago, Illinois, and a co-author of the study. The artificial system fills an “urgent unmet need for us”, she says.

All together now

Woodruff and her colleagues named their system Evatar — a portmanteau  of Eve and avatar. It contains five ‘organs’ linked together by a blood-like liquid carrying hormones, cell signalling molecules and drugs. The Fallopian tubes, uterus and cervix are made from human tissues obtained from women undergoing hysterectomies. The ovaries, however, are from mouse tissue, because healthy ovaries are rarely removed from women. Tissue for the fifth ‘organ’, the liver, which metabolizes drugs, comes from humans.

Courtest of Northwestern Medicine

EVATAR can fit in the palm of the hand.

To start the reproductive cycle, the researchers added follicle-stimulating hormone to the Evatar system, which drove the mouse ovaries to produce oestrogen. Fourteen days later, the researchers added luteinizing hormone, which stimulated the ovaries to release an egg and begin to produce progesterone.

The egg stayed in the ovary chamber, but a second chamber lined with tissue from human Fallopian tubes began to act as though the egg were passing through it. (In the model, as in women, the tissue in the Fallopian tubes contain hair-like structures called cilia, which beat back and forth to waft the egg to the uterus.) The third and fourth chambers, lined with human uterine and cervical tissue, respectively, then produced receptors for the hormones. The researchers connected Evatar to a human liver-on-a-chip, which can metabolize drugs that the researchers are testing.

Forming connections

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“I think this is as an extraordinarily important, beautiful piece of work,” says John Wikswo, a physiologist at Vanderbilt University in Nashville, Tennessee. He has been leading an effort to link at least 10 organ systems together to form a complete human-on-a-chip. The simulated organs in the Evatar system function correctly only when the right amounts of signalling factors and hormones are carried in the right amount of fluid, he says, and each organ plays a part.

Jon Hennebold, a reproductive scientist at Oregon Health and Science University in Portland, says that the main advantage of the new system is that it will allow researchers to quickly screen several drugs at once, testing them for toxicity and for their effects on the reproductive system. But he says that even an integrated set of organs-on-chips can’t entirely replace animal or clinical studies, because it is impossible to know which organs will be relevant in a disease or during drug treatments.

Woodruff says that her lab is planning to study various diseases by seeding the Evatar system with cells from people with conditions such as ovarian cancer, or by infecting Evatar with human papilloma virus, which can cause cervical cancer. The group is also making a male reproductive system called Adatar, and a testis–prostate system called DudeKube. The researchers plan to eventually link these systems with 10 other organs, including brains-on-a-chip, which produce signalling steroids and hormones, and the surprisingly complex system of human fat-on-a-chip, which can affect metabolism, the immune system and the reproductive cycles.

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Police: Trucker Drove Cross Country Nonstop Fueled By Meth, LSD And Cocaine

March 29, 2017 3:36 PM

Filed Under: Deerfield, Drugs

The man who drove this truck cross country was arrested for OUI drugs (Image from Deerfield PD)

DEERFIELD (AP) — Police have arrested a trucker they say drove nonstop from Seattle to Massachusetts fueled by crystal meth, LSD and cocaine.

Deerfield police say they responded to a convenience store parking lot off Interstate 91 on Tuesday for reports of a trucker who appeared to be despondent after locking himself out of his cab.

Officer Adam Sokoloski tells The Recorder of Greenfield that responding officers determined the driver was displaying signs of drug use.

The driver allegedly told police of his drug use and was reluctantly taken to the hospital after “quite the struggle.”

The driver, identified as Gary Robbins, of Homer, Alaska, was charged with operating under the influence of drugs and several motor vehicle violations.

He will be summoned to court and could not be reached for comment.

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found by Caitlin

Addiction Specialists Ponder a Potential Aid: Pot

Nikolas Michaud, 27, lighting a joint at High Sobriety in Los Angeles during treatment for heroin addiction.CreditJenna Schoenefeld for The New York Times

LOS ANGELES — Nine days after Nikolas Michaud’s latest heroin relapse, the skinny 27-year-old sat on a roof deck at a new drug rehabilitation clinic here. He picked up a bong, filled it with a pinch of marijuana, lit the leaves and inhaled.

All this took place in plain view of the clinic’s director.

“The rules here are a little lax,” Mr. Michaud said.

In almost any other rehab setting in the country, smoking pot would be a major infraction and a likely cause for being booted out. But here at High Sobriety — the clinic with a name that sounds like the title of a Cheech and Chong comeback movie — it is not just permitted, but part of the treatment.

The new clinic is experimenting with a concept made possible by the growing legalization of marijuana: that pot, rather than being a gateway into drugs, could be a gateway out.

Continue reading the main stor

A small but growing number of pain doctors and addiction specialists are overseeing the use of marijuana as a substitute for more potent and dangerous drugs. Dr. Mark Wallace, chairman of the division of pain medicine in the department of anesthesia at the University of California, San Diego, said over the last five years he has used marijuana to help several hundred patients transition off opiates.

“The majority of patients continue to use it,” he said of marijuana. But he added that they tell him of the opiates: “I feel like I was a slave to that drug. I feel like I have my life back.”

...

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When a President says, "I'll Kill You".

More disturbing video from the philippines
https://nyti.ms/2mDP0MR

Dying patients want easier access to experimental drugs. Here's why experts say that's bad medicine

Former firefighter Mike DeBartoli is a man desperate to rescue himself. He suffers from amyotrophic lateral sclerosis, the degenerative nerve disorder better known as Lou Gehrig’s disease, which usually kills within five years. He has already spent one year in a clinical trial, taking four pills a day that may have been a placebo. It didn’t help.

DeBartoli walks with difficulty and falls frequently. He’s losing his ability to breathe on his own. Now the 55-year-old from Tracy, Calif., has pinned his hopes on an experimental drug made by Genentech — and a new “right-to-try” law that allows desperate patients to take medications before they’ve been fully vetted by the Food and Drug Administration.

At a time when agreement on any subject seems impossible, the movement to give sick people more access to potentially lifesaving drugs is a rarity. Right-to-try laws have been adopted in 33 states and are under consideration in the remaining 17, with support from across the political spectrum.

The measure’s newest fan is President Trump, who said the FDA’s caution in granting dying patients access to some medications has “always disturbed” him.

But for all its populist appeal, the push for right-to-try laws has raised the ire of ethicists, drug-safety experts and a former FDA commissioner. They say the laws do virtually nothing to expand patients’ access to effective drugs.

DeBartoli doesn’t see it that way. Since California’s law went into effect on Jan. 1, all he needs to get his hands on Genentech’s GDC-0134 is the company’s cooperation and the backing of two physicians.

...

Critics counter that the state measures undermine an FDA program that balances patients’ need for options, drug companies’ desire to protect their investments, and the government’s duty to evaluate drug safety and effectiveness.

The FDA’s “compassionate-use” program could be improved, said Dr. Andrew von Eschenbach, who led the agency from 2006 to 2009. But the right-to-try laws don’t do that.

A federal version could also pave the way for controversial FDA reforms to speed drug approvals by relaxing some requirements. Dr. Scott Gottlieb, Trump’s nominee to lead the agency, has said he would favor a faster vetting process.

“We’re going to be changing a lot of the rules,” Trump told drug makers who visited the White House.

Under the right-to-try measures, a dying patient can seek access to an experimental drug if it is an active candidate for FDA approval and has successfully passed a Phase 1 clinical trial to explore its safety, at various doses, in healthy human volunteers.

That standard falls well short of proof that a drug will work, or that it won’t have side effects that could harm a patient or increase the discomfort of his or her final days.

Drug makers are under no obligation to provide experimental medication.

...

Right-to-try laws offer patients an alternative to the compassionate use, or expanded access, program the FDA has had in place for more than two decades. As many as 1,821 applications are filed each year, and about 99% of them are approved, according to the agency.

Emergency requests “are usually granted immediately over the phone, and non-emergencies are processed in a median of four days,” Dr. Peter Lurie, associate FDA commissioner, told a Senate committee in September. The application process was streamlined in June, reducing the required documentation from eight attachments to one, which can be completed in 45 minutes, he said.

But right-to-try supporters complain the process takes too long and is too restrictive. More broadly, they say, people should not need to petition a government agency in the first place.

When a patient is fighting for his or her life, “you shouldn’t have to fight your government too,” said Starlee Coleman of the libertarian Goldwater Institute, who drafted the model right-to-try legislation for states.

“This is the most fundamental liberty we have: the right to save your own life,” she added.

Vice President Mike Pence, who signed a right-to-try bill as governor of Indiana, recently said he expected to have a federal measure on Trump’s desk soon.

That bill, as currently written, differs from the FDA program in important ways.

Among them: It forbids the FDA from considering the experiences of right-to-try patients when deciding whether to approve experimental drugs. Currently, the agency can halt ongoing clinical trials or delay approval if a drug hastens a patient’s death or causes serious side effects.

That makes it all but impossible for drug makers to grant requests from patients such as DeBartoli, Coleman said. The predictable death of a compassionate-use patient would jeopardize a company’s multimillion-dollar investment, she said.

Lurie disputed this. When deaths occur, the FDA takes a patient’s dire state into account, he said.

In more than 11,000 compassionate-use cases over the last decade, patient deaths have halted a drug’s progress only twice, he said. Both times the medications got back on track after a brief delay.

...

The real reason companies aren’t eager to provide experimental drugs is that they “don’t want to get involved,” said New York University bioethicist Arthur Caplan. That problem won’t be fixed by right-to-try laws, he added.

Pharmaceutical companies are set up to get their products through the FDA’s rigorous approval process, not to get drugs to patients ahead of FDA approval, Caplan said. Many wouldn’t know what dose to recommend, let alone how they’d distribute them or how much they should charge. And for unscrupulous companies, the measure’s “completely vague” language on what drug makers can charge provides an opening to fleece desperate patients, he added.

Moreover, most companies have limited quantities of these drugs on hand and no policies to allocate them among all who want them, Caplan said.

Finally, when a patient dies or suffers adverse effects from an experimental medication, companies are much less afraid of the FDA finding out than they are of investors getting wind of the setback.

...

Almost two-thirds of drugs that enter clinical trials make it out of the first stage of safety testing and are eligible for right-to-try requests. But few are ultimately helpful, Dudley said.

Among 108 drug candidates abandoned after a Phase 2 clinical trial — where safety and preliminary effectiveness are explored — 20% failed because they were unsafe for sick patients and just over half were dropped because they seemed ineffective, according to a 2011 study.

More drugs failed in Phase 3 trials, where effectiveness is rigorously tested. At this stage, 21% missed the cut because of safety issues and two-thirds were abandoned because they didn’t seem to work.

“There isn’t some vast pool of drugs that, if only the FDA would get out of the way and let patients at them, would help them,” Dudley said.

“There are patients who are passionate about it, and there’s no way not to feel sympathetic toward them,” he added. But “doctors and nurses know that side effects can be horrible, making a peaceful death impossible. They think of it as pretty much a false hope.”

DeBartoli said he’d rather have false hope than no hope at all.

“You gotta try something,” he said.

Found by Serenity

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Deadly, drug-resistant Candida yeast infection spreads in the US

Candida auris causes multidrug-resistant infections that can result in organ failure

Kateryna Kon/SCIENCE PHOTO LIBRARY

By Chelsea Whyte

An emerging fungus could become the latest hospital-acquired infection we have to worry about. On 16 March, the US Centers for Disease Control and Prevention (CDC) reported that 53 people in the US have been taken ill with Candida auris – most of them in New York state. A further 27 healthy carriers of the fungus have been identified in three states where clinical cases were detected.

People at highest risk are those with weak immune systems including premature babies, people with diabetes, people on dialysis, and those who have had recent transplants or other invasive surgery.

Unlike most common yeast infections, C. auris doesn’t usually cause thrush, but results in bloodstream, wound or ear infections instead – triggering organ failure in the worst cases.

Although information isn’t available for all patients, the death rate could be as high as 60 per cent.  However, because patients usually contract the infection while hospitalised with other major illnesses, it’s difficult to be sure whether any deaths can be attributed solely to C. auris.

Global spread

C. auris was first identified in Japan in 2009. Since then, infections have also been reported in countries including Canada, Colombia, Germany, India, Israel, Kenya, Kuwait, Norway, Pakistan, Spain, South Africa, South Korea, the United Kingdom and Venezuela. Between May 2013 and August 2016, the first 13 cases were reported in the US. Since then, the number of infections has tripled, signalling a spike in reported cases.

Some strains of the fungus are resistant to all three major classes of antifungal drugs. “It’s pretty difficult to find new antibiotics. It’s harder to find new antifungals,” says David Denning at the University Hospital of South Manchester, UK.

Humans and fungi share many common metabolic pathways, so lots of agents that kill fungi are too toxic for human use.  “C. auris has the potential to be a really difficult problem,” Denning says.

However, he stresses that the majority of people don’t need to worry about becoming infected. “The ordinary person coming into the hospital to have a hernia operation or have a breast lump or their diabetes checked is not at risk. Neither are patients out in the community.”

Few drug manufacturers are currently focusing on developing antifungal compounds, but Denning says some promising oral and intravenous treatments are being developed in the UK, Japan and Sweden. It remains to be seen whether they will work against this stubborn infection.

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Door-Busting Drug Raids Leave a Trail of Blood

Using SWAT officers to storm into homes to execute search warrants has led time and again to avoidable deaths, gruesome injuries and costly legal settlements.

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Patients Lose Sight After Stem Cells Are Injected Into Their Eyes

By DENISE GRADYMARCH 15, 2017

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The left eye of a patient showing hemorrhages 13 days after stem-cell injection. CreditDr. Thomas Albini

Three women suffered severe, permanent eye damage after stem cells were injected into their eyes, in an unproven treatment at a loosely regulated clinic in Florida, doctors reported in an article published Wednesday in The New England Journal of Medicine.

One, 72, went completely blind from the injections, and the others, 78 and 88, lost much of their eyesight. Before the procedure, all had some visual impairment but could see well enough to drive.

The cases expose gaps in the ability of government health agencies to protect consumers from unproven treatments offered by entrepreneurs who promote the supposed healing power of stem cells.

The women had macular degeneration, an eye disease that causes vision loss, and they paid $5,000 each to receive stem-cell injections in 2015 at a private clinic in Sunrise, Fla. The clinic was part of a company then called Bioheart, now called U.S. Stem Cell. Staff members there used liposuction to suck fat out of the women’s bellies, and then extracted stem cells from the fat to inject into the women’s eyes.

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Hidden HIV reservoirs exposed by telltale protein

NATURE | NEWS

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The discovery helps to identify dormant infected cells and could one day lead to a cure.

• Amy Maxmen

15 March 2017

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Current HIV drug therapies target human cells actively producing virus particles (pictured): they can't effectively deal with dormant infected cells.

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Are Teenagers Replacing Drugs With Smartphones?

CREDITJASON HENRY FOR THE NEW YORK TIMES

The use of smartphones and tablets has exploded over the same period that drug use has declined among American teens. Researchers say the correlation is worth exploring.

Article

... But researchers are starting to ponder an intriguing question: Are teenagers using drugs less in part because they are constantly stimulated and entertained by their computers and phones?

... Nora Volkow, director of the National Institute on Drug Abuse, described interactive media as “an alternative reinforcer” to drugs, adding that “teens can get literally high when playing these games.”

...  “People are carrying around a portable dopamine pump, and kids have basically been carrying it around for the last 10 years,” said David Greenfield, assistant clinical professor of psychiatry at the University of Connecticut School of Medicine and founder of The Center for Internet and Technology Addiction.

Alexandra Elliott, 17, a senior at George Washington High School in San Francisco, said using her phone for social media “really feels good” in a way consistent with a “chemical release.” A heavy phone user who smokes marijuana occasionally, Alexandra said she didn’t think the two were mutually exclusive.

However, she said, the phone provides a valuable tool for people at parties who don’t want to do drugs because “you can sit around and look like you’re doing something, even if you’re not doing something, like just surfing the web.”

“I’ve done that before,” she explained, “with a group sitting around a circle passing a bong or a joint. And I’ll sit away from the circle texting someone.”

A Possible Clue in Jane Austen’s Glasses. Did Arsenic Kill Her?

By CHRISTOPHER D. SHEA and JENNIFER SCHUESSLERMARCH 9, 2017

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A portrait of Jane Austen, who died in 1817.CreditMorgan Library & Museum

LONDON — The cause of Jane Austen’s mysterious death at the age of 41 has been much pondered over the years. Was it a hormonal disorder? Cancer? Complications from drinking unpasteurized milk?

New research by the British Library suggests a more dramatic possibility: arsenic poisoning.

Researchers at the library, working with the London optometrist Simon Barnard, recently examined three pairs of glasses believed to have belonged to Austen, and said that they show evidence that her vision severely deteriorated in her final years.

That kind of deterioration further suggests cataracts, and cataracts may indicate arsenic poisoning, Sandra Tuppen, a curator of archives and manuscripts at the library, wrote in a blog post on the library’s website on Thursday.

“If Austen did develop cataracts,” as the glasses indicate, Dr. Tuppen wrote, one likely cause is “accidental poisoning from a heavy metal such as arsenic.”

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