Mention the pill, and only one kind of drug comes to mind. The claim that oral contraceptives have on that simple noun testifies to the pills singular effect in the United States. Introduced in 1960, the pill gave women reliable access to birth control for the first time. The opportunity to delay having children opened the door to higher education and professional careers for many women.

More than 50 years later, the most commonly used form of reversible contraception in this country is still the pill. Additional methods have been developed for women such as implants, patches, vaginal rings and injectables but most do basically the same thing as the pill: use synthetic versions of sex steroid hormones to suppress ovulation. The method has proved its merit, but the current crop of contraceptives doesnt work for everyone. Some women cant tolerate the side effects stemming from manipulation of the hormones. Others cant use hormonal contraceptives at all, because of underlying health conditions.

In a survey, 62 percent of U.S. women ages 15 to 44 reported using contraception in 2011 to 2013. The pill was the most popular form of birth control, followed by female sterilization (which permanently blocks the fallopian tubes). Rounding out the top five methods were the male condom, long-acting reversible contraception (like intrauterine devices and implants) and male sterilization (vasectomy). In the survey, if women used more than one method, only the most effective method was counted.

And whats new for men? Their main mode of contraception, the condom, has been around for at least 400 years, perhaps longer. Alternatively, men who want to take the lead on family planning can go the surgical route with a vasectomy.

The dearth of alternatives is not due to a lack of research. Reproductive biologists and other researchers have made many exciting discoveries since the pill was introduced. But taking a promising finding in cells or in mice to human testing is hard for any drug. And for contraceptives, theres an extra wrinkle: Youre developing products for very healthy people, so you have to make sure [the drugs] are incredibly safe, and the side effect profile is acceptable, says Diana Blithe, a biochemist and chief of the contraceptive development program at the National Institute of Child Health and Human Development in Bethesda, Md.

Even with the long road to human testing, odds are that by the time the pill turns 75, there will be new options stocking the contraceptive cabinet. Researchers are currently exploring a method that keeps womens eggs in a state of suspended animation for later use. For men, there could be nonhormonal methods that stop sperm from developing and launching their epic journey. The impact of these novel methods might ripple out into society much as the pills once did.

There were 6.1 million pregnancies in the United States in 2011. Forty five percent of them, or a whopping 2.8 million, were not intentional, according to a 2016 report in the New England Journal of Medicine.

Unplanned pregnancies can have consequences for parents and kids, studies find. Womens education can be cut short. Unwanted pregnancies are linked to delayed prenatal care probably because moms dont realize theyre pregnant as well as low birth weight in infants. Postpartum depression is more common for mothers who did not intend to have a baby than for those who did.

The numbers also suggest that the contraceptives available arent meeting everyones needs. Some methods are expensive. And some users have health concerns or just dont stick with an option. In 2008, about 40 percent of unintended pregnancies were in couples that used contraception, but inconsistently, according to the Guttmacher Institute, a reproductive health research and policy organization in New York City.

Proportion of U.S. pregnancies in 2011 that were unplanned

From 2011 to 2013, the most popular reversible contraceptive choice for women ages 15 to 44 was the pill, with use at nearly 26 percent. The pill and other hormonal contraceptives contain the female sex steroid hormones estrogen and progesterone, or progesterone alone, usually in synthetic forms. These hormones prevent ovulation by suppressing the brains release of follicle-stimulating hormone and luteinizing hormone.

Some women find that hormonal contraceptives work well; other women experience side effects such as headaches, nausea, mood changes and acne. Oral contraceptives also increase the risk of blood clots, taking the drugs off the table for women with a history of blood clots, stroke or cardiovascular disease. The pill is also a no-go for women with severe hypertension or who have ever had breast cancer.

Relying on hormones to halt sperm production can also work. A new hormone-based gel for men, applied to the skin, is in human testing. It combines the male sex steroid testosterone with a synthetic progesterone. Plans are under way for couples to test the gel as their only form of birth control. But giving men hormones can come with side effects, such as reduced muscle mass and a drop in sexual function.

Discoveries that are beginning to explain the earliest stages of egg development and the finishing touches of sperm growth may lead to steroid-free alternatives.

Hormonal contraception disrupts ovulation, and the egg that was scheduled for departure from an ovary dies. But what if there was a method that preserved the egg for later?

When women are born, their ovaries have a full set of oocytes, or eggs a million or so. Each is housed within a sac of cells called a follicle. The outer portion of each ovary is filled with the earliest, dormant form of these egg-carrying follicles, called primordial follicles. The sleeping cells are waiting to be woken up, so they can begin growing in preparation for ovulation. But why the alarm clock goes off for one primordial follicle and not another is an open question, says reproductive biologist David Ppin of Massachusetts General Hospital and Harvard Medical School.

You could potentially preserve that pool of eggs for later in life, theoretically.

David Ppin

Todays hormonal contraceptives act on ovarian follicles that are already growing, and once that starts, there is no going back if ovulation doesnt happen, the egg dies. Aiming contraception at the sleeping eggs could mean putting off pregnancy, while holding on to the eggs. By preventing that first wake-up call, actually, you keep the egg, Ppin says. You could potentially preserve that pool of eggs for later in life, theoretically.

Meet the biological agent that could keep eggs asleep: Mllerian-inhibiting substance, or MIS. Also known as anti-Mllerian hormone, MIS is not a sex steroid hormone. It is produced in the developing testes and prevents male embryos from growing female reproductive parts. In adult female mice, MIS can also be a perpetual snooze button for primordial follicles, Ppin and colleagues, including Mass General and Harvard pediatric surgeon Patricia Donahoe, reported in the Feb. 28 Proceedings of the National Academy of Sciences.

Hundreds of follicles are estimated to be in various stages of development at any given time. The active growers release MIS locally, which limits the number of primordial follicles that wake up. This process allows the body to control and maintain the supply of eggs over a womans reproductive life span.

Primordial follicles, the sacs that house immature eggs, reside in the outermost region of the ovary. When follicles wake up, they begin to develop and move farther into the ovary. When a womans monthly menstrual cycle begins, follicle-stimulating hormone prompts additional growth of certain developing follicles. A dominant follicle matures. Luteinizing hormone helps the mature follicle open up, and the egg is ovulated and released into the fallopian tube. New experimental approaches to birth control aim to keep the primordial follicles dormant, so they can be available later in a womans life.

In their study, Ppin, Donahoe and colleagues used a virus to introduce a modified version of the MIS gene into certain cells in mice. This permanent change gave the mice a higher dose of MIS protein than is found normally in females. The follicles that had already been growing completed their development, but after that, no new follicles were activated, leaving a collection of sleeping-beauty primordial follicles.

When the researchers paired female mice treated with the gene therapy with males, the females were still able to become pregnant and have healthy babies within the first six weeks, because of those follicles that had already started growing in the ovaries. Once that supply was used up, the females were infertile.

Youre just stopping the horses that havent yet come out of the gate, Donahoe says.

To test a nonpermanent approach, the team gave normal female mice the MIS protein as a twice-daily shot. Activation of primordial follicles stopped. When treatment ended, the ovaries got back to business and follicles began growing again.

Ppin and Donahoe see several uses for MIS as a contraceptive. The permanent gene therapy method could be a nonsurgical contraceptive approach for pets or stray animals. The research team is working with the Cincinnati Zoo to study this method in cats.

Frequent shots of the MIS protein are too expensive for broad use, but they could help protect the reserve of ovarian follicles in young cancer patients. Growing follicles are dividing quite rapidly, so they are very sensitive to chemotherapy, Ppin says. Chemo can kill off the growing follicles, which means there is no more MIS to stop activation of other primordial follicles. Too many follicles wake up, which can deplete a womans egg supply. In mice given chemotherapy drugs, MIS-treated animals were left with more primordial follicles than untreated animals, the researchers found.

Still eager to make an MIS-like contraceptive for all women that is cheap and easy to use, perhaps as a pill, the researchers are searching libraries of small molecules to find one that mimics the action of MIS. Maybe it would be an already existing [U.S. Food and Drug Administration] approved medication thats the first screen we are performing or maybe its a very simple molecule, very cheap to synthesize, Ppin says.

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In the ovary of a normal mouse (left), a large follicle is shown at a late stage of development (a light pink oocyte surrounded by follicular cells, inset). In the ovary of a mouse treated with Mllerian-inhibiting substance, follicle development ceased and only primordial follicles were found (arrows, right).

In men, vitamin A does more than promote healthy eyes. Its essential for sperm production, too. The testes take up vitamin A from carrots and other foods and convert it to retinoic acid. The acid binds to the retinoic acid receptor, which is found in cells throughout the body.

In the 1990s, scientists reported that when they disrupted the gene for one version of the retinoic acid receptor, referred to as alpha, in mice, the animals are fine, but the males are sterile, says geneticist Debra Wolgemuth of Columbia University Medical Center. Wolgemuth and her colleagues, who study the biology of sperm production, set out to find a drug that could interfere with the receptor, rather than permanently knocking out the gene.

Wolgemuth came across a paper from 2001 by a group studying a drug that could bind to all three versions of the receptor, including alpha. The drug inactivates the receptor and shuts down the series of events that typically follow. Although tests in rats showed the drug could be taken orally and broken down safely by the body, the researchers highlighted one notable side effect. They called it testicular toxicity, Wolgemuth says.

Rather than a negative, Wolgemuth saw the toxicity as a sign of a potential male contraceptive. With molecular biologist Sanny Chung of Columbia and colleagues, she gave the drug to male mice for seven days, then examined their testes.

Sperm go through many stages of development as they transition from round germ cells to their final shape with a characteristic head and tail. Before sperm are released to begin their journey through the male reproductive system, says Wolgemuth, they line up like little soldiers in a battalion to leave the testes.

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In healthy mice, normal sperm line up at the center of a part of the testes known as the seminiferous tubule, ready for release (left, arrows). Mice treated with a drug that blocks whats known as the retinoic acid receptor have defective sperm that dont line up (right, arrows).

In mice treated with the drug, the sperm dont align properly, Wolgemuth and colleagues reported in 2011 in Endocrinology. The sperm arent released, so they die in the testes. The researchers found no evidence of harm to other organs. Male mice given the drug once a day for four weeks became infertile by the end of treatment and remained that way for four weeks after treatment stopped. By 12 weeks after treatment, the mice regained their mojo and successfully mated with females.

Later, the team gave mice a smaller dose of the drug for 16 weeks, over a quarter of their reproductive lives, notes Chung. The treated mice became sterile, but once off the drug, they soon became papas to healthy pups that grew into fertile adults, the researchers wrote in Endocrinology last year.

Next step: Wolgemuth plans to test the drug in nonhuman primates. Her group is also collaborating with a team of medicinal chemists to look for compounds that target only the alpha version of the retinoic acid receptor. Even though the tested drug did not lead to side effects, having an option that doesnt interfere with the other two versions of the receptor would be ideal, says Wolgemuth.

Another nonhormonal male contraceptive is the result of a long research career dedicated to such a product. In the late 1960s, Joseph Tash had two tours as a summer student in an obstetrics and gynecological department at Michael Reese Hospital in Chicago. He saw how heavily the burden of birth control fell to women. I felt it was important to try to expand the contraceptive and family planning choices to men, he says.

In 2013, the compound H2-gamendazole became the first nonhormonal contraceptive to receive FDA regulatory guidance, a crucial thumbs-up along the drug development road. Its a kind of checklist of the testing conditions and experiments necessary to proceed with preclinical and human trials.

Tash, now at the University of Kansas Medical Center in Kansas City, and colleagues began with an anticancer drug that, during clinical trials, severely cut down on sperm production. But there were a lot of side effects, Tash says, which would be totally unacceptable to otherwise healthy males. So the researchers designed similar drugs to minimize the side effects, including H2-gamendazole. Rats given a single oral dose of the drug once a week for six weeks became sterile after two weeks of use. By 10 weeks after the dosing stopped, all of the animals were fully fertile again.

The drug interferes with the last stage of sperm development, when the cells acquire their familiar sperm features. At this stage, as well as throughout the developmental process, sperm are tended to by Sertoli cells, which feed and support the growing sperm. The sperm are actually tethered to the Sertoli cells to prevent them from leaving the reef before they can swim.

H2-gamendazole disrupts the junctions between the sperm and the Sertoli cells, releasing the sperm prematurely and leading to their destruction. The testes have a built-in cleaning system, so to speak, that gets rid of the abnormal sperm, Tash says.

Tashs team has also tested H2-gamendazole in mice, rabbits, dogs and monkeys. In each animal, there was a block in sperm production just exactly like we see in the rats, Tash says. The team has also found that the drug can be taken as a pill and is rapidly taken up by the testes, at levels 10 to 20 times higher than in other tissues. I think this explains to a large extent why we havent seen any remarkable side effects, Tash says.

The work on H2-gamendazole, yet to be published, led to the FDAs regulatory guidance, a show of confidence in the drug. If Tash and colleagues can demonstrate to the FDA that the drug is safe and well tolerated, that might pique the interest of pharmaceutical companies to handle the final stages of testing and to take the drug to market. Its going to have to be a squeaky clean compound for pharma to become interested, Tash says.

Birth control methods born of these projects might shake things up outside the bedroom. If further testing finds that eggs kept asleep by an MIS-based contraceptive remain healthy and viable, delaying pregnancy may not necessarily lead to reduced fertility. A lot of women 35 and older are faced with reduced fertility, Ppin says. A method to target the activation of primordial follicles so you could keep them for later I think that would be beneficial.

Any new contraceptive options for men could shift the conversation men and women have about birth control. A multinational survey published in 2005 found more than half of men would be willing to use a new method of male birth control. There is an increasing number of men who are willing to help carry that burden, Tash says.

When that first product gets out there for men, Blithe adds, I think that will be a turning point.Any new contraceptive options for men could shift the conversation men and women have about birth control. A multinational survey published in 2005 found more than half of men would be willing to use a new method of male birth control. There is an increasing number of men who are willing to help carry that burden, Tash says.

This story appears in the Sept. 2, 2017 Science News with the headline, "Access denied: Scientists seek innovative ways to block the union of egg and sperm."

More here:
Birth control research is moving beyond the pill - Science News Magazine

Recommendation and review posted by Bethany Smith

Female patients with locally advanced esophageal cancer that is treated with chemotherapy and radiation therapy before surgery are more likely to have a favorable response to the treatment than male patients are, and women are less likely to experience cancer recurrence, according to a study published online today in The Annals of Thoracic Surgery.

"Esophageal cancer is one of the deadliest cancers in the world," said senior author K. Robert Shen, MD, of the Mayo Clinic in Rochester, MN. "It affects men and women differently. Men are more at risk to develop this cancer, and it appears that women respond better to the treatments."

Esophageal cancer is four times more common in men than in women, according to the American Cancer Society (ACS). The ACS estimates that there will be about 16,940 (13,360 men and 3,580 women) new esophageal cancer cases diagnosed in 2017, with approximately 15,690 deaths (12,720 men and 2,970 women). The lifetime risk to develop esophageal cancer is 1 in 125 for men and 1 in 454 for women.

Dr. Shen and colleagues from the Mayo Clinic analyzed data from all female patients with locally advanced esophageal cancer who underwent chemotherapy and radiation prior to surgery between 1990 and 2013 at all three Mayo Clinic sites (Rochester, MN, Scottsdale, AZ, and Jacksonville, FL). A comparison group of male patients were identified based on matching criteria such as age, pretreatment clinical stage, histologic type, and surgical era. Only patients staged preoperatively with computed tomographic scans and endoscopic ultrasonography were included.

The final cohort included 366 patients (145 women, 221 men). The median age for female patients was 64 years and 61 years for male patients. They had two primary types of esophageal canceradenocarcinoma (cancer originating in gland cells/lower part of the esophagus), found in 105 (72 percent) women and 192 (87 percent) men, and squamous cell carcinoma (cancer starting in cells that line the esophagus), diagnosed in 40 (28 percent) women and 29 (13 percent) men.

"We believe our study represents the largest group of female patients ever studied specifically to analyze the impact of gender on response to treatment and long-term outcomes," said Dr. Shen. "It is also the only one to use a methodology where female and male patients were matched based on certain characteristics to eliminate possible confounding factors."

The study showed that either complete or near complete pathologic response occurred in 84 women (58 percent) vs. 103 men (47 percent). In addition, tumor recurrences occurred in 116 (32 percent) patients (38 female, 69 male), resulting in men having an 80 percent increased risk of recurrence. There also was a trend toward superior 5-year survival for women vs. men (52.1 percent vs. 44.0 percent), but this did not reach statistical significance.

"The results of this study are intriguing because they suggest that by focusing on individualized and targeted approaches to esophageal cancer treatment, we may be more successful in improving outcomes for future patients," said Dr. Shen.

In fact, Dr. Shen explained that the research group recognizes that most cancers affect individuals in different ways, which reflects possible variations in the biology and genetics of the tumor. This remains an active area of research at the Mayo Clinic.

"If the genetic or molecular basis that explains our findings can be elucidated, one can conceive of chemoradiation therapy regimens that are more targeted based on the genetic signatures of each patient's tumors," said Dr. Shen. "An individualized approach to cancer treatment will likely lead to the greatest gains in the treatment of many cancers."

Explore further: Treatment improved overall survival in elderly patients with early-stage esophageal cancer

More information: Phillip G. Rowse et al. Sex Disparities After Induction Chemoradiotherapy and Esophagogastrectomy for Esophageal Cancer, The Annals of Thoracic Surgery (2017). DOI: 10.1016/j.athoracsur.2017.05.030

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Largest study of its kind reveals women have superior response to ... - Medical Xpress

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Diplodus sargus White Sea Bream (protandrous). Credit: University of Salford

Scientists in the UK have observed a fascinating new fact about sex changing fish: the direction of sex change has implication for population numbers.

More than 400 species of fish are sequential hermaphrodites: that's to say, they are born one sex and change to the opposite sex later in life to maximise their number of offspring. Species that change from male-to-female are called protandrous and ones changing female-to-male are termed protogynous.

Marine biologists at the University of Salford explored the influence of the direction of sex change and found population numbers to be smaller for fish that change from female into male than the other way around.

Dr Chiara Benvenuto, from the University of Salford, one of the authors of the study published today in Scientific Reports, said: "Until now, studies have mostly looked at differences between species that change sex or not, but we're interested in the direction of sex change.

"While fecundity and reproductive success are expected to increase with size for both females and males, the fitness advantage can increase more rapidly for one sex than the other: this is when sex change can occur.

"In protandrous species, it is better to be large females, because they produce more eggs, thus small individuals reproduce as males as they grow. In protogynous species, small males cannot compete with large ones, so it is more convenient to be small females first and then turn into large, dominant males later on in life".

The research team, which specialises in marine genetics and behavioural ecology, measured offspring production based on the number of eggs and sperm produced every year, over a lifetime, based on their growth rate and then used the diversity of genes transferred to the next generation, as a proxy for reproductive success.

Both methods concluded that regardless of the direction of sex change, individuals conform to the same strategy, producing more offspring as the second sex, making sex change a successful strategy. But crucially, they found that population numbers are smaller for protogyous species, making them less resilient.

The study co-authored by Professor Stefano Mariani and Dr Ilaria Coscia has serious implications for the fishing industry.

Dr Benvenuto explained: "We should not lump all sex changers is a single category, as male-first and female-first sex changers are quite different. It is vitally important that sex-changing behaviours are understood and accounted for particularly in the selection of those fish taken from the sea."

The next step of the study is to focus on the effect of overfishing on these species, which are commercially important, sought by fishermen and appreciated by consumers.

Explore further: A tale of two fishes: Biologists find male, female live-bearing fish evolve differently

More information: C. Benvenuto et al. Ecological and evolutionary consequences of alternative sex-change pathways in fish, Scientific Reports (2017). DOI: 10.1038/s41598-017-09298-8

Read more from the original source:
Female fish 'more reluctant' to change sex than males - Phys.Org

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Deadly gene mutations removed from human embryos in landmark study, reports The Guardian. Researchers have used a gene-editing technique to repair faults in DNA that can cause an often-fatal heart condition called hypertrophic cardiomyopathy.

This inherited heart condition is caused by a genetic change (mutation) in one or more genes. Babies born with hypertrophic cardiomyopathy have diseased and stiff heart muscles, which can lead to sudden unexpected death in childhood and in young athletes.

In this latest study researchers used a technique called CRISPR-cas9 to target and then remove faulty genes. CRISPR-cas9 acts like a pair of molecular scissors, allowing scientists to cut out certain sections of DNA. The technique has attracted a great deal of excitement in the scientific community since it was released in 2014. But as yet, there have been no practical applications for human health.

The research is at an early stage and cannot legally be used as treatment to help families affected by hypertrophic cardiomyopathy. And none of the modified embryos were implanted in the womb.

While the technique showed a high degree of accuracy, its unclear whether it is safe enough to be developed as a treatment. The sperm used in the study came from just one man with faulty genes, so the study needs to be repeated using cells from other people, to be sure that the findings can be replicated.

Scientists say it is now important for society to start a discussion about the ethical and legal implications of the technology. It is currently against the law to implant genetically altered human embryos to create a pregnancy, although such embryos can be developed for research.

The study was carried out by researchers from Oregon Health and Science University and the Salk Institute for Biological Studies in the US, the Institute for Basic Science and Seoul University in Korea, and BGI-Shenzen and BGI-Quingdao in China. It was funded by Oregon Health and Science University, the Institute for Basic Science, the G. Harold and Leila Y. Mathers Charitable Foundation, the Moxie Foundation and the Leona M. and HarryB. Helmsley Charitable Trust and the Shenzhen Municipal Government of China. The study was published in the peer-reviewed journal Nature.

The Guardian carried a clear and accurate report of the study. While their reports were mostly accurate, ITV News, Sky News and The Independent over-stated the current stage of research, with Sky News and ITV News saying it could eradicate thousands of inherited conditions and the Independent claiming it opens the possibility for inherited diseases to be wiped out entirely. While this may be possible, we dont know whether other inherited diseases might be as easily targeted as this gene mutation.

Finally, the Daily Mail rolls out the arguably tired clich of the technique leading to designer babies, which seems irrelevant at this point. The CRISPR-cas9 technique is only in its infancy and (ethics aside) its simply not possible to use genetic editing to select desirable characteristics - most of which are not the result of one single, identifiable gene. No reputable scientist would attempt such a procedure.

This was a series of experiments carried out in laboratories, to test the effects of the CRISPR-Cas9 technique on human cells and embryos. This type of scientific research helps us understand more about genes and how they can be changed by technology. It doesnt tell us what the effects would be if this was used as a treatment.

Researchers carried out a series of experiments on human cells, using the CRISPR-cas9 technique first on modified skin cells, then on very early embryos, and then on eggs at the point of fertilisation by sperm. They used genetic sequencing and analysis to assess the effects of these different experiments on cells and how they developed, up to five days. They looked specifically to see what proportion of cells carrying faulty mutations could be repaired, whether the process caused other unwanted mutations, and whether the process repaired all cells in an embryo, or just some of them.

They used skin cells (which were modified into stem cells) and sperm from one man, who carried the MYBPC3 mutation in his genome, and donor eggs from women without the genetic mutation. This is the mutation known to cause hypertrophic cardiomyopathy.

Normally in such cases, roughly half the embryos would have the mutation and half would not, as theres a 50-50 chance of the embryo inheriting the male or female version of the gene.

The CRISPR-cas9 technique can be used to select and delete specific genes from a strand of DNA. When this happens, usually the cut ends of the strand join together, but this causes problems so cant be used in the treatment of humans. The scientists created a genetic template of the healthy version of the gene, which they introduced at the same time as using CRISPR-cas9 to cut the mutated gene. They hoped the DNA would repair itself with a healthy version of the gene.

One important problem with changing genetic material is the development of mosaic embryos, where some of the cells have corrected genetic material and others have the original faulty gene. If that happened, doctors would not be able to tell whether or not an embryo was healthy.

The scientists needed to test all the cells in the embryos produced in the experiment, to see whether all cells had the corrected gene or whether the technique had resulted in a mixture. They also did whole genome sequencing on some embryos, to test for unrelated genetic changes that might have been introduced accidentally during the process.

All embryos in the study were destroyed, in line with legislation about genetic research on embryos.

Researchers found that the technique worked on some of the stem cells and embryos, but worked best when used at the point of fertilisation of the egg. There were important differences between the way the repair worked on the stem cells and the egg.

Only 28% of the stem cells were affected by the CRISPR-cas9 technique. Of these, most repaired themselves by joining the ends together, and only 41% were repaired by using a corrected version of the gene.

67% of the embryos exposed to CRISPR-cas9 had only the correct version of the gene higher than the 50% that would have been expected had the technique not been used. 33% of embryos had the mutated version of the gene, either in some or all their cells.

Importantly, the embryos didnt seem to use the template injected into the zygote to carry out the repair, in the way the stem cells did. They used the female version of the healthy gene to carry out the repair, instead.

Of the embryos created using CRISPR-cas9 at the point of fertilisation, 72% had the correct version of the gene in all their cells, and 28% had the mutated version of the gene in all their cells. No embryos were mosaic a mixture of cells with different genomes.

The researchers found no evidence of mutations induced by the technique, when they examined the cells using a variety of techniques. However, they did find some evidence of gene deletions caused by DNA strands splicing (joining) themselves together without repairing the faulty gene.

The researchers say they have demonstrated how human embryos employ a different DNA damage repair system to adult stem cells, which can be used to repair breaks in DNA made using the CRISPR-cas9 gene-editing technique.

They say that targeted gene correction could potentially rescue a substantial portion of mutant human embryos, and increase the numbers available for transfer for couples using pre-implantation diagnosis during IVF treatment.

However, they caution that despite remarkable targeting efficiency, CRISPR-cas9-treated embryos would not currently be suitable for transfer. Genome editing approaches must be further optimised before clinical application can be considered, they say.

Currently, genetically-inherited conditions like hypertrophic cardiomyopathy cannot be cured, only managed to reduce the risk of sudden cardiac death. For couples where one partner carries the mutated gene, the only option to avoid passing it on to their children is pre-implantation genetic diagnosis. This involves using IVF to create embryos, then testing a cell of the embryo to see whether it carries the healthy or mutated version of the gene. Embryos with healthy versions of the gene are then selected for implantation in the womb.

Problems arise if too few or none of the embryos have the correct version of the gene. The researchers suggest their technique could be used to increase the numbers of suitable embryos. However, the research is still at an early stage and has not yet been shown to be safe or effective enough to be considered as a treatment.

The other major factor is ethics and the law. Some people worry that gene editing could lead to designer babies, where couples use the tool to select attributes like hair colour, or even intelligence. At present, gene editing could not do this. Most of our characteristics, especially something as complex as intelligence, are not the result of one single, identifiable gene, so could not be selected in this way. And its likely that, even if gene editing treatments became legally available, they would be restricted to medical conditions.

Designer babies aside, society needs to consider what is acceptable in terms of editing human genetic material in embryos. Some people think that this type of technique is "playing God" or is ethically unacceptable because it involves discarding embryos that carry faulty genes. Others think that its rational to use the scientific techniques we have developed to eliminate causes of suffering, such as inherited diseases.

This research shows that the questions of how we want to legislate for this type of technique are becoming pressing. While the technology is not there yet, it is advancing fast. This research shows just how close we are getting to making genetic editing of human embryos a reality.

More here:
Gene editing used to repair diseased genes in embryos - NHS Choices

Recommendation and review posted by sam

By Mayo Clinic News Network

Removing the normal breast is not required as part of the treatment for your breast cancer. The decision to have a mastectomy on the cancer side and also remove a breast that does not have cancer (the other side) is a very personal one. There are valid reasons some women choose to pursue this surgery. But it will have a long-term effect on your body, so you need to be comfortable with the decision you make.

A mastectomy is surgery that involves removing the majority of breast tissue from a breast as a way to treat or prevent cancer. For cancer prevention, this surgery reduces the risk of developing breast cancer by about 90 to 95 percent. It is not 100 percent because some areas of breast tissue do remain after a mastectomy. Those areas of tissue could develop breast cancer, although the chances of that happening are very small.

When you have a mastectomy to treat cancer in one breast, you could have the breast that does not have cancer removed at the same time. Some women opt to do this because they are anxious about developing cancer in the other breast. But you can also keep the normal breast. Research shows that this decision does not have an impact on overall survival.

Current medical evidence indicates the risk of developing a cancer in the other breast to be reasonably low at about half a percent a year. For women who have hormone therapy after a mastectomy because their tumors are hormone receptor positive, this risk is reduced by about 50 percent.

Certain factors can make a difference in your risk, though. If you have a strong family history of breast cancer or if you have tested positive for a mutation in one of the breast cancer genes, then the chances you will develop cancer in your other breast are significantly higher. Before you make a decision about having a double mastectomy, carefully review your personal risk of breast cancer with your doctor.

If you do not have other factors that raise your risk, there are additional questions to consider. First, if you do have a double mastectomy, are you comfortable with the risks of a more complex and longer operation? Having both breasts removed, rather than just one, increases the possibility of surgical complications such as bleeding and infection.

Second, if you do not have a double mastectomy, are you willing to participate in ongoing monitoring for cancer in your other breast? If you do not have both breasts removed, you will still need regular mammograms once a year on the breast that remains.

Third, how important is it to you that your breasts look similar? If you have one breast reconstructed after a mastectomy, it is unlikely that your remaining breast will match its appearance without some type of cosmetic surgery on the natural breast.

Talk with your doctor about these topics, along with any other concerns or questions you may have. Also, discuss what will happen before, during and after surgery, so you can set your expectations accordingly. Choosing to have a double mastectomy is a big decision. Make sure you are well informed about all the possible benefits and drawbacks for your situation before you move forward. -- Judy C. Boughey, M.D., Surgery, Mayo Clinic, Rochester, Minn.

Source: http://newsnetwork.mayoclinic.org/discussion/tuesday-q-and-a-decision-to-remove-breast-that-does-not-have-cancer-a-personal-one/

Originally posted here:
Decision to remove both breasts is a personal one - News8000.com - WKBT

Recommendation and review posted by simmons

Celeste McCracken had a choice to make.

She could stay in bed for the rest of her life or get better and make a difference in other peoples lives.

After an illness had her bed-ridden for about seven years, Celeste refused to be a victim to her illness anymore and now has one of the top hair salons in Sand Springs groundfloor salon. And shes only been open since June 1.

I decided to go back to school and get my (cosmetology) license. I didnt want my illness to define me. Ive always wanted to be a hair stylist, but I never took the leap. Well I decided to jump.

Despite being healthy all of her life through ballet and dance, Celeste started gaining weight and was diagnosed with hypothyroidism, where her body didnt produce enough of the thyroid hormone. Then, it stopped working all together.

She had her thyroid removed, but the surgeon also removed the parathyroid, which controls the bodys calcium. She had to take synthetic hormones and vitamins, but her body wouldnt absorb them, and she needed eight-hour infusions at least four times a week just to stay alive. Her electrolytes would crash to critical levels, and she also had seizures. She spent the majority of the time at the hospital and couldnt work. When she wasnt at the hospital, she was at home in bed.

However, a trip to the Mayo Clinic in Arizona got her back on track and her medications started working.

Thats when I knew I had to do something. I had to start living again and I wanted to help people, she said.

Going back to school at age 40 wasnt easy, but, for her, cosmetology was easy.

It just clicks with me. Its as easy as making breakfast, she said.

After building a clientele for several years in other towns, Celeste decided to open a salon in Sand Springs, and she said the reception has been amazing.

I wasnt sure at first. We live here and my husband works here, but I didnt know if I could start over in a different town. Well, my fears were put to rest immediately, Celeste said.

She didnt know where she wanted her salon, and she looked at several locations that just werent right. She had one more space to look at, and she knew right away it was the one, but she had help deciding.

When I showed up to look at it, Monte and Betty Box were waiting at the door. I hadnt met Monte before, but my husband had told me about him. We connected right away. He told me this is the place for you, and he was right. Monte and Betty have been amazing, Celeste said.

Located at 401 E. Broadway Court in the Village Square Shopping Center, Celeste specializes in color corrections, womens cuts, mens cuts and childrens cuts.

I think it is my mission to make others look great and feel great about themselves. God gave me a gift and He is the reason I can do this every day. It took a lot of prayer and a lot of hard work, but Im ready to spend the next half of my life being healthy and serving others, she said.

Celeste said she chose the name groundfloor salon because everything has a starting point.

Whether its beauty, faith, your career, relationships, it all starts somewhere. It all starts on the ground floor. It starts here, she said.

Originally posted here:
It all starts at groundfloor salon - Tulsa World

Recommendation and review posted by simmons

Menopause is often associated with troublesome symptoms like hot flashes and mood swings, yet even more serious health issues may be part of this life stage, such as heart disease.

The North American Menopause Society estimates that 2 million 6,U.S. women reach menopause every year.

Women experience a number of changes during menopause due to shifting hormones and lower levels of estrogen, said nationally renowned natural health physician and author, Dr. Fred Pescatore. Hot flashes, night sweats and fatigue can interfere with everyday activities. These symptoms can be severe and can occur for several years as the body adjusts to the reduced level of estrogen. We know that fluctuating hormones can also contribute to increased risk of heart disease and its important to take steps to manage that risk during menopause.

There are several ways for women to manage menopause symptoms and heart health risks, Pescatore said.

Advertisement

A healthy life starts with a nutritious diet, and this becomes even more important during menopause. For women experiencing menopause symptoms, I recommend adopting a diet filled with more vegetables, lean protein, nuts and seeds to support a healthier lifestyle and a healthier heart, he said.

One of the best things you can do to help your body and mind adjust to shifting hormone levels during menopause is to maintain an active lifestyle. Just 30 minutes of cardio each day can really make a difference. Get moving. Try taking a brisk walk or a bike ride. You can even do things in your own home, like jumping jacks, Pescatore said.

A new peer-reviewed clinical study shows that daily supplements of the anti-oxident found in pine bark oligomeric proanthocyanidin compounds, also found in grapeseeds, peanut skin and witch hazel bark (trademarked as Pycnogenol) can help reduce the symptoms of menopause and related heart disease risk factors. This study shows the effectiveness of Pycnogenol in alleviating perimenopause symptoms like hot flashes and night sweats and reducing key cardiovascular risk factors like high blood pressure, Pescatore said.

This new study further expands on previous research conducted on hundreds of patients that shows the benefits of Pycnogenol for minimizing common, disruptive symptoms of menopause including night sweats, hot flashes, depression, anxiety and memory problems by supporting vascular relaxation, which allows the body to rid itself of excess heat. For more information, visit pycnogenol.com.

Herbal extracts that contain natural phytoestrogen compounds that mimic estrogen are also readily available and work for many women. Isoflavones such as those found in soy products and red clover may help, DHEA supplements are another hormone replacement option,and other popular supplements include flax seed oil, black cohosh, dong quai.

Check with your doctor before trying a supplement to be sure its safe for you.

StatePoint

See original here:
How to manage the symptoms of menopause - The Oakland Press

Recommendation and review posted by Bethany Smith

Genomic Revolution is Here: What an Insurance Professional Needs to Know

Dr. Phil Smalley

Is genetic testing ready for prime time use in employee benefits and insurance products? We think so, albeit with some caveats. Other expert opinions are mixed regarding this question, but one thing is for sure, this field of medicine is growing in leaps and bounds. New genetic discoveries are published weekly leading to new treatments, better disease prevention, less drug side effects, and overall improved public health. And actually, genomics is already being used in clinical practice in certain settings as mandated by various professional association clinical guidelines. Some innovative insurance companies have started to offer genetic testing of various forms to their insurance clients and as part of employee health programs in the US and around the world.

The cost of various genetic tests ranging from USD $200 to $5000 is one of the commonly quoted reasons why doctors and patients avoid needed genetic tests. One study of lung cancer patients showed that 41% of patients did not follow the recommended clinical guidelines for genetic testing. They mention uncertainty regarding cost reimbursement as one of the barriers to ordering these tests. (1) This is where genomic based products can play an important role at the time of cancer diagnosis as an employee benefit.

In these next 10 monthly articles, we will explore the topic of genomics as we discuss genetic basics, use of genetics in cancer management, pharmacogenomics, screening with liquid biopsies and disease risk stratification. Because I am a medical doctor working in the insurance industry and not a geneticist, I hope to present a different point of view on this important topic from a practical insurance perspective. We will show you the benefits of incorporating genetic tests of various types into employee benefits and in other insurance products. The emphasis of our work is more in the post-policy issue space rather than entering the political, ethical and regulatory whirlwind surrounding genetic testing at the time of underwriting. Our goal through these articles is to give the insurance professional 5 or 6 key talking points to make the sale to insurance companies and employers on the benefits of genetic testing services. Equally important, these articles will cover some of the challenges associated with going down this road and discuss ways to overcome these obstacles.

In the spirit of full disclosure, I am writing on behalf of a new genetic testing service intermediary, Wamberg Genomic Advisors (WGA) who stand at the crossroads of the insurance and genetic testing industries. They use their collective knowledge and expertise to guide insurance clients in their successful adaptation of this new genetics technology to improve their employees health, to increase sales, maximize return on investment and improve public health and longevity.

A 2016 Harvard T.H. Chan School of Public Health survey reports that 6% of the US population has had some form of genetic testing done and 81% found the information useful. (2) Presently, clinical doctors mostly order genetic tests in patients who have a strong family history of disease or when the patient has symptoms and the genetic test is performed to diagnose a condition or to help decide upon the most appropriate form of treatment. But with the price of genetic testing falling precipitously, we have seen a rapid increase in public access to genetic testing either through their doctor, employee health programs or via direct to consumer genetic testing kits. Insurance companies will need to adapt to this possible asymmetry of information that could lead to anti-selection.

In next months September article, we will get into the real meat of this topic. We will discuss the basics of genetics, the different types of genetic tests and their accuracy. We will cover the benefits of genetic tests and get into some practical example uses of genomics in corporate wellness programs, voluntary benefits and in other insurance products.

I invite you to answer this anonymous one question online survey and see what others think about genetic testing. Also, post your comments and opinions in the comments section below as we start this open discussion.

Certainly yes2 ( 100 % )

Maybe0 ( 0 % )

Not really sure0 ( 0 % )

Likely not0 ( 0 % )

Certainly not0 ( 0 % )

Back

Dr. Phil Smalley is an Internal Medicine specialist with 27 years of experience in insurance medicine. He recently retired from his position as Senior Vice Presidentand Global Chief Medical Officer for RGA International Corporation. Dr. Smalley received his medical degree from the University of Toronto, Canada. He is aFellow of the Royal College of Physicians and Surgeons of Canada and Past President of the Canadian Life Insurance Medical Officers Association. Dr. Smalleywas also Managing Director of the Longer Life Foundation, the not-for-profit research partnership between RGA and Washington University School of Medicine. Dr. Smalley currently lives in Toronto consulting for the insurance industry and is Chief Medical Director for Wamberg Genomic Advisors.

Original post:
Genomic Revolution is Here: What an Insurance Professional Needs to Know - Corporate Wellness Magazine

Recommendation and review posted by simmons

Aug. 21, 2017 -- Jerry Lewis, a consummate performer on stage and screen who used his fame to raise billions of dollars toward a cure for muscular dystrophy and other neuromuscular diseases, died Sunday at his home in Las Vegas. He was 91.

Born Joseph Levitch on March 16, 1926, in Newark, NJ, to vaudeville parents, Lewis wrote, appeared in, and directed 80-plus movies and TV shows over 5 decades in show business. He was memorable for his goofball antics and rubbery face (The Nutty Professor, The Bellboy, and The Ladies Man) and for his capacity for self-parody. Early in his career, he formed half of a comedy team with the late Dean Martin, with whom he hosted "The Martin and Lewis Radio Show" and made 16 films. In 1956, Lewis recorded an album (Jerry Lewis Just Sings) that made the Top 20 on the Billboard charts.

For many people, Lewis will be remembered best for raising awareness and money for the Muscular Dystrophy Association (MDA) during the 50-plus years he hosted the nationally televised Labor Day weekend telethon. In all, the shows raised more than $2 billion.

From 1956 until 2010, Lewis was the face of muscular dystrophy, a relatively rare neuromuscular disease that often begins in childhood and progressively robs a person of mobility. Lewis would wrap up the 21 1/2-hour annual show with a heartfelt version of Youll Never Walk Alone. He would typically sing it in a voice hoarse from hours of urging viewers to contribute to the cause, and probably from smoking on air throughout the broadcast.

In 1977, Lewis was nominated for a Nobel Prize for his 50 years of fighting muscular dystrophy.

(We) will be forever grateful to Jerry Lewis, a world-class humanitarian.

The reason for his stepping down as host of the telethon isnt clear -- The Hollywood Reporter wrote that he was unceremoniously dumped -- but Lewis never seemed to have talked about it publicly.

The MDA, on its website, praised Lewis efforts, saying it will be forever grateful to Jerry Lewis, a world-class humanitarian, for his indefatigable and inspiring work on behalf of kids and families with neuromuscular diseases, and for the countless dollars his commitment helped raise for critical research and services.

Perhaps Lewis left because the telethon, which had shrunk to a 2-hour show, had outlived its usefulness. In May 2015, the MDA announced it would end the telethon because of the expense and the realities of viewership and concentrate its fundraising on social media and other web-based channels.

The MDA raises money for medical research on 40 neuromuscular diseases, including Duchenne/Becker muscular dystrophy, the most prevalent form of MD, and amyotrophic lateral sclerosis (ALS), or Lou Gehrigs disease. In 2015, the organization said it was focusing support on gene therapy research and new drugs.

While Lewis did not suffer from a neuromuscular disease, he struggled with health issues for years. He had type 1 diabetes and pulmonary fibrosis, a condition in which tissue deep in the lungs scar and stiffen, making it more difficult for oxygen to get into the blood and causing shortness of breath. He suffered two heart attacks. He also had prostate cancer surgery in 1982. He had chronic back pain, which led to an addiction to the prescription painkiller Percodan, which he successfully replaced with an implanted device that dulls nerve impulses. In 2003, he had to wean himself off of steroids used to treat his lung disease.

Lewis last performances on stage were in March 2014, when he sold out two shows at La Mirada Theatre in California. He was 88 at the time, although he appeared in the 2016 film The Trust, with Nicolas Cage and Elijah Wood.

Lewis was divorced from Patti Lewis, with whom he had six children, and married SanDee Pitnick in 1983. They adopted a daughter together. In 2009, Lewis youngest son, Joseph, who struggled with drug addiction, committed suicide at age 45. In an interview he gave to The Hollywood Reporter in June 2014, Lewis was broken up by Josephs death, saying, To this day I don't understand it because it's unfair -- not unfair to me, but unfair to him. That he went that way made the unfairness stupidity. But he was my son and he's gone, and there's not a lot I can do about that. I beat myself a thousand times.

He was beloved throughout the world, but the French were particularly enchanted by Lewis. In 2006, for his 80th birthday, Lewis was awarded a medal and induction as a commander into the Legion of Honor, which is considered the highest decoration in France. It is akin to being knighted by the queen in England.

Lewis has two stars on the Hollywood Walk of Fame and received the Jean Hersholt Humanitarian Award at the 2009 Oscars ceremony. He received many other honors throughout this life, both for his humanitarian work and his work as a TV and movie star, and as a producer and director.

IMDb: Jerry Lewis Biography.

Biography.com: Jerry Lewis.

Muscular Dystrophy Association.

The Hollywood Reporter: At Home With Jerry Lewis as He Opens Up About Son's Death, Skirmishes With Fans.

The Associated Press: Jerry Lewis telethon ends decades-long run, fundraising awareness for Muscular Dystrophy Association.

CDC: Facts About Muscular Dystrophy.

Pulmonary Fibrosis Foundation.

CNN.com.

View original post here:
Comic and Telethon Host Jerry Lewis Dies At 91 - WebMD

Recommendation and review posted by Bethany Smith

Pacific Biosciences of California (PACB) is a $480 million market cap company focused on development of innovative technologies and systems that impact diagnosis and treatment of disease and improve the world's food and energy supply. The company developed the Single Molecule, Real-Time (SMRT) Sequencing genomics technology, which enables real-time analysis of DNA synthesis. The company's technology can be used in human biomedical research to resolve heritability and variant types across populations or disease states.

Applications in plant sciences and agriculture include crop and livestock research acceleration via sequencing and transcriptome analysis. PACB technologies can also be used to characterize viruses and microbes of infectious disease, enabling the design of better vaccines and treatments.

So why would the reader be interested in PACB? The market for gene therapy applications are increasing at a CAGR of more than 20%, according to an analysis at Global Market Insights. In 2015, the gene therapy market was reported at over $800 million, and is expected to rise to $1.4 billion by 2024. The following figure depicts what this 20% growth looks like for a potential successful long investor. Nice, isn't it?

But gene therapies alone don't tell the whole story of market applications for genetic research tools. Cell therapy is an industry that plays a large role in applications for genetic analysis. The combined markets for cell and gene therapies are expected to rise from approximately $8 billion in 2018 to $12 billion in 2020. Strong Bio hopes that these predictive trend models can be useful for investors, and rather than focus on a company's pipeline in every article, it is striving to meet the needs of investors by focusing on some backstage players that have immense potential in advancing medical and agricultural research, such as PACB.

The rise in markets for gene therapies and cell therapies is expected to be driven by rapid technological advancement and increased adoption of new genomic techniques. Obviously, the largest market space in cell therapy and gene therapy application is cancer, with inflammatory disease also comprising a significant component of these potential markets. The World Health Organization predicts the number of new cancer cases will rise by as much as 70% over the next 20 years.

That is a lot of patients, and will fuel industry growth. In addition, favorable FDA regulation stances will serve cancer genetics industry growth in a positively weighted manner. Cancer genetics programs will begin to mainstream infrastructure to provide assays, informatics, and gene testing education to patients at hospital sites. Cancer will become a treatment regime reminiscent of chronic disease models, targeting specific molecules involved in specific patient's pathology.

The company sells its SMRT technology as a package product called Sequel System. SMRT supports numerous sequencing applications, bringing unique and novel depth and quality to genetic research. It is applicable in whole genome analysis for total genetic composition data of organisms including microbes, humans, plants, and animals. For instance, the company recently reported improving existing sequencing information for the maize plant genome, including fixing mistakes, reducing gaps, increasing sequence contiguity up to 50-fold, and adding difficult to reach (centromere region) sequences.

SMRT can be applied to produce in-depth analysis of genetic variations in disease models, using targeted approaches. It provides true long read lengths and highest consensus accuracy available, revealing a full spectrum of genetic variation for microbes and virus, and heterologous cell populations such as escaping cancer cell genomes. PACB SMRT technology offers RNA isoform sequencing functions that can produce full-length transcripts (eliminating the need for assembly, useful in transcriptome analyses). Epigenetic characterization of DNA modifications in prokaryotic and eukaryotic models are also possible.

The company recently announced an agreement by Novogene (China) to purchase ten Sequel systems in addition to ten already purchased earlier this year. To date Novogene is the largest user of PACB Sequel systems, and the reordering of technology indicates customer satisfaction and increased productivity.

Novogene and PACB have agreed to co-market and promote genomic applications. The company cites high demand by Novogene as impetus to double its production capacity to meet the orders, driven by a Chinese precision medicine initiative to sequence variants in 1000 individuals. The company is also participating in other world genome discovery projects.

Net loss for 2Q 2017 was $25.5 million, compared to $18.5 million for the second quarter of 2016. Operating expenses for 2Q 2017 was $32.4 million, compared to $28.7 million for 2Q 2016. The company reported $20.1 million in 2Q 2017 product, service, and other revenue compared to $17.2 million for 2Q, 2016. Cash and cash equivalents at end Q2 2017 was $102.6 million, compared to $72.0 million at December 31, 2016. In June 2017, the company did an offering of approximately 15 million shares at $3.10 per share, raising approximately $46 million.

Strong Bio wants to emphasize that the era of gene therapy is upon us, and several candidates are likely to be approved as potential first gene therapy products approved by FDA later this year. Emerging supportive technologies stand to benefit as the medical system and biotechnology investment centers begin to realize the fruits of such endeavors.

PACB is right in there for the upcoming revolution. To give the reader an idea of the power of its technology on client bottom line, the Sequel system was able to do the maize genomic work at a cost of around $20,000 per maize line, compared to the nearly $30 million in cost for the original maize genome reference.

It is well-positioned in the industry, with its technology being referenced in over 35 presentations at annual AGBT 2017 conference, demonstrating customer value. Over 135 references to PACB technology were made in the 2017 annual PAG conference. The stock has jumped a bit after announcing the sale of 10 Sequel units, but would be attractive on a pullback into the gap to the $3.00 offering range, and is thus watchlisted as an exciting prospect. It is also possible that some consolidation in this space could occur, leading to potential merger and acquisition action. Yahoo consensus target of 4 analysts is $5.95 per share.

Risks for investment in PACB include industry dynamics that the high cost of developing new treatments impedes growth in the gene therapy industry. Moreover, no gene therapy products have yet been approved by the FDA. However, advancements in rare diseases using the gene therapy/genomic approach are coming soon. It is clear that cell therapies that involve genomic research will offset the slow-to-start gene therapy development costs impediment, and serve as a catalyst for profitable efforts to fund gene therapies as they enter the market over the coming months and years.

Another risk for investors is that the company is not yet close to a cash-neutral revenue stream, so further dilution could be possible. There is some competition in the genomics industry as well, but Strong Bio regards SMRT as a front-runner in the space. One could have argued 20 years ago that there is no obvious value in sequencing genomes, but given the breakthroughs that are upon us in the upcoming gene therapy era, the time to place investments is rapidly drawing near. The reward to risk ratio for PACB is compelling.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Originally posted here:
Pacific Biosciences Is Advancing Genomics - Seeking Alpha

Recommendation and review posted by sam

Nagpur: For the first time in the city, four patients have undergone treatment for infertility for male hypogonadism. They were put through a therapy conceptualized by endocrinologist Dr Pramod Gandhi following which three of their wives conceived.

On Sunday, Gandhi delivered a talk on 'Male hypogonadism' during a medical conference on 'core endocrinology' which was organized by the Nagpur Diabetes and Endocrine Centre in collaboration with Diabetic Association of India (DAI) and Association of Medical Faculties (AMF) at a city hotel.

Male hypogonadism, a problem not often discussed at such forums, is a condition in which the body doesn't produce enough testosterone. It can occur at any age fetal development, before puberty or during adulthood. Signs and symptoms depend on when the condition develops.

Infertility, erectile dysfunction, obesity, loss of strength, decreased beard and body hair growth, decreased sex drive and weakening of bone are the common symptoms.

"Until now, the city couldn't do much if the patient is suffering from infertility because of hypogonadism," Gandhi told TOI.

Gandhi combined two injections combined human chorionic gonadotrophin (HCG) and human menopausal gonadotrophin (HMG) to treat the four patients. "Until now both of these injections were being used on women for some other purpose," he said.

Continue reading here:
Wives of 3 of 4 patients treated for hypogonadism conceive - Times of India

Recommendation and review posted by simmons

Aarav Appukuttan, born a woman, always felt trapped in his own body. Sukanyeah Krishna, born a man, could exactly identify with the feeling of emotional churn and societal pressure growing up. A three-hour wait at a doctor's clinic for consultation for gender reassignment, and snatches of an overheard conversation turned out to be the factors the brought the two of them together for friendship, love and soon, matrimony.

Aarav, 46, is now a man and Sukanyeah, 22, a woman. According to the Hindustan Times, Aarav spent a large part of his school years uncomfortable in his own skin. He used to have long hair and would sit next to the girls in his class, but "felt unnerved by his attraction to them." His gender identity disorder (GID) only got worse, he told the paper, and after he lost his mother and had to take care of his siblings. He knew that he would have to wait before he got help for himself.

"I had to restrain myself and keep my feelings in check for 45 years. I always behaved like everything was normal," he told the paper.

Things have been tough for Sukanyeah as well. Her mother took her to a doctor who started her on male hormone therapy, according to the report. Both Sukanyeah and Aarav endured humiliation and mockery from strangers growing up for not fully embracing the gender they were born with and the transitioning has been tough.

"No one understood what I was going through. During my Class 10 board exams, I fainted owing to the pressure," she told HT.

Sukanyeah was speaking on the phone at the Mumbai clinic in Malayalam when Aarav overheard parts of the conversation. The two got talking and soon a bond of friendship and understanding grew.

"He went to Kerala and I returned to Bangalore, where I had moved two years ago for my job. A day later, Aarav called me and we discussed our surgeries and our treatment in detail. At first, we would speak once a week, then it became twice a week. Soon, we started talking very day," she told Mid-day.

Their mutual desire to help other children with GID, long conversations on phone, and a familiar history of family troubles brought them closer together. They plan to marry next month.

"We are now planning to get married in a temple, with all the rituals. Both our families are happy for us. We have also decided to adopt a child, since we are aware that post surgery I won't be able to conceive," Aarav, who's a tour manager, told Mid-Day.

"We are India's first complete transgender couple and we are happy," Sukanyeah told the Deccan Chronicle.

Read the rest here:
Indian Trans Couple, Soon To Marry, Finds Love At Mumbai Clinic While Transitioning - Huffington Post India

Recommendation and review posted by Bethany Smith

Harklinikken does not advertise, but the 25-year-old multinational company is beginning an aggressive expansion into the $3.6 billion hair-loss market in the United States, meaning youre likely to hear a lot more about it. A New York clinic opened in June inside the Core Club in Midtown (you dont need to be a member to get an appointment); and in August, Harklinikken consultations became available at some 70 Womens Care Florida obstetrics and gynecology clinics. (Roughly 75 percent of the companys 50,000 active users are female.)

Mr. Skjoth said the plan is to have a presence in every state in the next two years. The company recently opened outposts in Tampa, Fla., and Beverly Hills, Calif.

Panos Vasiloudes, a Tampa dermatologist and Harklinikkens medical director, said the company has double-blind, placebo-controlled studies it hopes to publish next year in peer-reviewed journals. Such studies are the one thing some dermatologists say they need to recommend the product to patients.

For now, Maryanne Senna, a dermatologist and the director of the Hair Academic Innovative Research Unit at Massachusetts General Hospital in Boston, said the best she can tell patients who ask and a lot of them do is that Harklinikken wont do any harm.

Dont get me wrong I really want it to work, said Dr. Senna, who also teaches at Harvard Medical School. There arent a lot of options, and Id love to be able to say to my patients, This is something you can try that is worth the money. But I cant do that yet.

Harklinikkens formula, refined over 20 years, is derived from plants and cows milk. Thats the most Mr. Skjoth will say about it. In the 1990s, clients mixed it with Rogaine, Mr. Skjoth said, and then we took the Rogaine part away and started focusing on the actual liquid.

Small studies have shown the efficacy of various plant-derived ingredients, mostly in mice. But two potential explanations for Harklinikkens success have little to do with its formula.

One is how much emphasis the company places on compliance, the major stumbling block in the efficacy of any treatment, said Dr. Senna, an author of studies on the subject. Prospective users are questioned about their ability to stick to a regimen because the extract must be applied every day, and they are told that the more conscientious they are, the better. Users are also reminded and encouraged with regular check-ins.

Clients must also use the companys shampoo, conditioner and styling products, forsaking all others a psychological as well as a financial buy-in, Dr. Senna said. (Mr. Skjoth, who has a masters degree in nutrition and chemistry but is not a doctor, said this is because other products may clog the scalp, causing hair loss.)

Hair changes about as fast as grass grows, which is to say its extraordinarily slow and not visible to anyone checking impatiently in the mirror every day. But during regular follow-up appointments, Harklinikken uses high-tech equipment to photograph and magnify the scalp and count new hairs and active follicles, which motivates users to adhere to the regimen. Too many people give up on treatments like Rogaine and low-level-light devices before theyve had a chance to work, Dr. Senna said.

Its also possible that some of Harklinikkens users are women whose hair would have grown back even if theyd done nothing. Many women who arrive in a dermatologists office with prior diagnoses of female pattern hair loss actually have whats called telogen effluvium. Thats a period of acute shedding of hair meaning up to 60 percent of hair three months after a triggering event like pregnancy, significant weight loss or starting or stopping hormone medications.

Once that hair has stopped shedding, it does regrow, at a rate of about a centimeter a month, said Dr. Senna, who suffered from the condition after each of her pregnancies. She shares photos of herself with patients, to show she can sympathize. In one, her entire frontal hairline clearly is growing back in. If Id used a treatment, I would have thought it was a miracle drug, she said.

Users of the extract say that one of the strengths of Harklinikken is that it doesnt claim to be a miracle.

It wasnt: Youre going to get a full head of hair, said Jon Centella, 35, of Apollo Beach, Fla., who started seeing peach fuzz after four months. It was: Well give you 30 percent, and thats what made me comfortable enough to give it a shot.

Here is the original post:
Is This Treatment the Cure for Hair Loss? - New York Times

Recommendation and review posted by Bethany Smith

Rare muscular diseases cause the gradual decay of the body but new drug screening could lead to better treatments. Credit: 'Isolated Myofiber' by Doctor William Roman, Instituto de Medicina Molecular

Rare muscle diseases have a devastating impact on the affected individual and their families, but 3-D-drug screening could lead to better medicines being developed which would also relieve the huge economic toll of their treatment.

Therapy for rare skeletal muscle diseases which cause a gradual decay of the human body and often end in death are scant or non-existent, and in spite of their rarity, these diseases pose a huge socio-economic burden.

'These are traumatic disorders,' said Dr William Roman, a cell biologist at the Instituto de Medicina Molecular in Lisbon, Portugal. 'You go from losing the ability to walk, to losing the ability to eat, to losing the ability to breathe.'

Treatments also require significant resources in terms of carers, expensive equipment and costly medicine, while each patient, and sometimes their family members who become carers, leave the workforce.

Dr Roman says that for many rare skeletal muscle diseases there are no cures and where therapies are available, they offer limited positive outcomes. Part of the reason for this is the lack of a way to find promising drugs.

Dr Roman is a post-doctoral researcher working on MUSCLEGUY, a project funded from the EU's European Research Council (ERC), which aims to develop reliable and effective laboratory models for testing high-potential drugs for rare muscle disorders. He plans to use a 3-D-system to reveal new disease pathways, which could lead to better treatments being found, much faster than existing methods.

'There are more or less 30 different types of muscle disorders, and their rarity stems from the fact that they arise from genetic mutation,' he said. 'It's kind of a unique case with every single person, because you have a disease mutation that nobody else has.'

This means that within each category of these muscle diseases there may be many types of different mutations. Dr Roman says that because of this unique situation hardly any new drugs pass regulatory approval and that's a major deterrent for big pharmaceutical companies to develop drugs in the first place.

'Because of the plurality of the diseases, you rarely have the right (laboratory) models to test the drugs,' he said.

The MUSCLEGUY team is currently focusing their method to find potential treatments for centralnuclear myopathy, but they hope their work could extend out to many similar disorders.

'The idea is that we would use our technology for the initial stages of drug discovery starting with thousands of compounds and work down to the promising ones,' said Dr Roman.

As well as the laboratory side, the business and commercial aspect is key to the project. Dr Roman added that their approach might provide a 'better assessment of promising drugs' and avoid discarding potentially useful drugs too early in drug development, which current testing models sometimes do.

'We hope that over time if we can get this to be successful that big pharma becomes reinterested in rare diseases,' said Dr Roman.

Gene therapy

Meanwhile, another EU-funded project known as MYOCURE is focusing directly on possible treatments using gene therapy for two rare diseases: myotubular myopathy (MTM) and glycogen storage disorder type II (GSD II), also known as Pompe's Disease.

MTM is a devastating disease where the diaphragm stops working, leading to early death it has no cure or treatment. In GSD II, the body is unable to break down the complex sugar glycogen into glucose and this can accumulate in cells particularly muscle cells - which manifests as muscle-wasting. Enzyme replacement therapy (ERT) offers some alleviation of the symptoms for this disease, but it's very expensive and does not constitute a permanent cure.

Professor Marinee Chuah, project coordinator of MYOCURE, who is at the Free University of Brussels (VUB), Belgium, said: 'The annual costs for treating GSD II patients with ERT amounts to EUR 0.4 0.7 million per year, per patient, corresponding to an estimated total cost in the EU of EUR 4 7 billion.'

But Prof. Chuah believes that MYOCURE could directly bring down healthcare costs related to ERT, and therefore the knock-on socio-economic burden, and even has hopes their research could lead to a 'one-time treatment'.

Dr Federico Mingozzi, who heads up one of MYOCURE's partner teams at the Pierre and Marie Curie University in Paris, France, says their plan is based on replacing the genes that don't work.

'The rationale is that there are a number of neuromuscular diseases with high medical need which could be addressed by gene therapy, but the problem is that the treatment itself has several limitations in targeting certain tissues,' he explained.

MYOCURE's approach differs from conventional gene therapy in that it aims to be more efficient at targeting specific body tissues where it is needed. For example, MTM gene therapy needs to target the muscle cells of the diaphragm.

To transport desired genes into the cells, gene therapy uses delivery vehicles or 'vectors' derived from viruses and MYOCURE aims to optimise this approach using different methods. For example, one strategy being tested is to shuffle the genetic sequences of various viruses to look for the best and most specific vectors.

If successful, Prof. Chuah says that MYOCURE will help some 20 000 patients currently living with MTM or GSD II within the European Union. But crucially, the team hopes that the findings from the project will extend out to many other neuromuscular diseases.

Explore further: What makes cancer gene therapy so groundbreaking?

Continue reading here:
New 3D-drug screening aims to ease economic burden of rare muscle diseases - Medical Xpress

Recommendation and review posted by simmons

LOS ANGELES In the fight against cardiovascular disease, a new super-weapon is now even closer to deployment and its capabilities are turning out to be beyond expectations.

One of the most notorious killers facing humanity, cardiovascular disease, is responsible for about about 1 in every 3 deaths in the U.S., according to the American Heart Association. A new study aimed at combating the disease finds that stem cells, the controversial darlings of modern biomedical research, are not only showing promise in treating heart failure, but in rats are actually reversing problems associated with old age.

The way the cells work to reverse aging is fascinating, says Dr. Eduardo Marbn,one of the studys primary investigators, in a press release. They secrete tiny vesicles that are chock-full of signaling molecules such as RNA and proteins. The vesicles from young cells appear to contain all the needed instructions to turn back the clock.

Marbn, who serves as director of the Cedars-Sinai Heart Institute, explains this latest study builds on previous lab work and human trials which have shown promise in treating heart failure using cardiac stem cell infusions.

The specific type of stem cells used in the study are known as cardiosphere-derived cells or CDCs. The process to grow these cells was initially developed when Marbn was part of the Johns Hopkins University faculty.

While the latest research involving CDCs indicates possibilities that have previously been in the realm of science fiction, the scientists leading the charge urge restraint in face of the excitement.

This study didnt measure whether receiving the cardiosphere-derived cells extended lifespans, so we have a lot more work to do, says Dr. Lilian Grigorian-Shamagian, the studys first author. We have much to study, including whether CDCs need to come from a young donor to have the same rejuvenating effects and whether the extracellular vesicles are able to reproduce all the rejuvenating effects we detect with CDCs.

Nevertheless, the latest results of stem cell infusions in rats are startling. Not only did rats that received the CDCs experience improved heart function, they also had lengthened heart cell telomeres.

Telomeres, the protective caps at the ends of chromosomes, normally shrink with age. As telomere shrinkage is one of the most studied and least understood phenomenons associated with aging, the effect of CDCs on them is especially fascinating.

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Whats more, the researchers said the rats who received the treatment also had their exercise capacity increase by about 20 percent. They also regrew hair faster than rats that didnt receive the cells.

With these thrilling results only the latest in recent stem cell headlines, researchers caution the public that most treatments are still not ready for prime time.

Indeed, a recent Reuters article warned that stem cell therapy still is not approved to treat heart failure in the U.S., yet many unscrupulous clinics are offering questionable services anyway and charging tens of thousands of dollars for it. In some cases, researchers quoted in the article said these labs may not even be injecting stem cells, but rather a useless and dangerous mix of cellular debris.

The article also noted two patients died and another went blind after stem cell injection procedures in Florida clinics.

Still, the legitimate doctors and scientists working to push the frontier of medicine forward are very optimistic about the real possibilities of the therapy. The Cedars-Sinai team said they are also studying the use of stem cells in treating patients with Duchenne muscular dystrophy and patients with heart failure with preserved ejection fraction, a condition that affects more than 50 percent of all heart failure patients.

Their research on CDCs effects on aging was published this month in the European Heart Journal.

Read the rest here:
Study: Cardiac Stem Cell Injections Reverse Effects of Aging - Study Finds

Recommendation and review posted by simmons

If you have around US$90,000 (S$122,733) to spare and are of a gambling disposition, perhaps your final journey should be to Australia. A company called Southern Cryonics is looking to open a facility in New South Wales this year that will allow its customers to 'freeze' their bodies after death in the hope of one day being resurrected. If it goes ahead, it will make Australia only the third country, after the US and Russia, where such a service is available.

But, especially for those of a futurist bent perhaps, it's as valid a thing to do with one's body as burial or cremation. Last year, a terminally ill 14-year-old girl in the UK became the first and only child so far to undergo the cryonic process. This is technically not freezing but vitrification, in which the body is treated with chemicals and chilled to super-cold temperatures so that molecules are locked in place and a solid is formed. An estimated 2,500 bodies around the world are now stored in this condition.

Supporters concede that the technology to revive the infinitely complex interactions between those molecules may never exist, but are nonetheless hopeful, pointing to shifting conceptions of what irreversible death actually is. If, for example, cessation of a heartbeat used to define it, now hearts can be re-started - today's corpse may be tomorrow's patient. They point to experiments such as that announced last year by 21st Century Medicine, which claimed to have successfully vitrified and recovered an entire mammalian brain for the first time, with the thawed rabbit's brain found to have all of its synapses, cell membranes and intracellular structures intact.

"It's not just cryonics. Stem-cell research, nano-tech, cloning, the science just keeps plugging away towards a future [of reanimating] that may or may not come to exist," says an upfront Dennis Kowalski, president of the Michigan-based Cryonics Institute. His company was launched just over 40 years ago to provide cryostasis services. "Lots of things considered impossible not long ago are possible today, so we just don't know how cryonics will work out. For people who use the service it's really a case of there's nothing to lose."

Naturally, not everyone is hopeful that such processes will ever work out for those in the chiller. "The problem with cryonics is that the perception of it is largely shaped by companies offering a service based on something completely unproven," says Joo Pedro De Magalhes, biologist and principal investigator into life extension at the University of Liverpool, UK, and co-founder of the UK Cryonics and Cryopreservation Network. "You're talking about a fairly eccentric procedure that only a few people have signed up to and into which little reported research is being done. That said, I think the people providing these services do believe there's a chance it may work one day, although I would have to say they're optimistic."

But this is not to say that living longer won't, in time, prove possible as a result of some other method; just that arguably this is more likely to be based around preserving a life that has not experienced death, rather than the promise of reanimating one after its demise. The chasm between the two is all the more pronounced given neuroscience's still scant ideas as to what consciousness or mind is, let alone how it might be saved and rebooted; would the warmed and reanimated you be the you that died, or a mere simulacrum? Your body may well not be the same: many of those opting for cryo-preservation go for the 'freezing' of just their brains.

Certainly while cryonics specifically may remain a largely unexplored field, Google is now investing in anti-ageing science, an area that, as De Magalhes puts it, "now has fewer crackpots and more reputable scientists working in it, with stronger science behind it too". Indeed, as Yuval Noah Harari argues in his best-selling book Homo Deus, humanism's status as contemporary society's new religion of choice, combined with technological advances, makes some form of greatly extended lifespan inevitable for some generation to come. Whether this will be by melding man and machine, by genetic manipulation, by a form of existence in cyberspace or some other fix can only be speculated at, but everything about our civilisation's recent development points to it becoming a reality.

Advances in medicine, after all, have greatly extended average longevity over the last century alone. With this has come a shift in perspective that sees death less as the natural end point to a life so much as a process of disease that could, and perhaps should, be tackled like any other disease that threatens existence. De Magalhes points out that for many working in the field it is less about the pursuit of immortality as of improved health.

"After all, it's not self-evident that we all want to live forever, and there are philosophical arguments for the idea that death is good, that it's necessary to appreciate life," he says. "But it is self-evident that nobody wants Alzheimer's, for example. If you focus on retarding the problems of ageing then inevitably we're going to live longer. The longevity we have now isn't 'normal'; it's already better than what we had not long ago. Extrapolate that to the future and in a century the length of time we live now might be considered pretty bad. One can envisage a time when we might live, if not forever, then perhaps thousands of years - so much longer than we live now that it might feel like forever."

That, naturally, would bring with it profound changes to the way in which we perceive ourselves and to how the world operates and all the more so if living considerably longer became a possibility faster than society was able to inculcate the notion. How would such a long lifespan affect our sense of self? Would institutions and mores such as lifelong marriage and monogamy remain the norm? When would we retire? How would our relationships with the many subsequent generations of our family be shaped? How would population growth be managed? How would such long lives be funded?

Such questions are, for sure, of no concern to those currently in cryostasis. "These people tend to be into sci-fi, and into science too," suggests Kowalski, who has signed up himself, his wife and children for cryonic services when the time comes. "I think for a lot of them it's not necessarily about the fear of death. It's more a fascination with the future. They're optimistic about what it will bring. They're more Star Trek than Terminator."

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This company freezes your body so that you could one day be resurrected - AsiaOne

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Alternative names for hypopituitarism

Hypopit; pituitary insufficiency; partial hypopituitarism; panhypopituitarism (pan referring to all pituitary hormones being affected); anterior hypopituitarism

Hypopituitarism is failure of the pituitary gland to produce one, some, or all of the hormones it normally produces. The pituitary gland has two parts, the anterior pituitary and the posterior pituitary, and hormone production can be affected in both parts.

Below are listed some of the causes of hypopituitarism:

The signs and symptoms of hypopituitarism depend on which of the pituitary gland hormones are involved, to what extent and for how long. It also depends on whether the hormone deficiencies began as a child or later in adult life. Symptoms can be slow at the start and vague.It is worth understanding the normal function and effects of these hormones in order to understand the signs and symptoms of hypopituitarism. (See the article on pituitary gland.) There may also be additional symptoms due to the underlying cause of the hypopituitarism, such as the effects of pressure from a tumour.

Symptoms can include:

Hypopituitarism is rare. At any given time, between 300 and 455 people in a million may have hypopituitarism. A number of endocrinologists believe that hypopituitarism is quite common after brain injuries. If this belief is confirmed, then hypopituitarism may be significantly more common than previously believed.

Most cases of hypopituitarism are not inherited.However, there are some very rare genetic abnormalities than can cause hypopituitarism.

Blood tests are required to check the level of the hormones, which are either produced by the pituitary gland itself, or by peripheral endocrine glands controlled by the pituitary gland. These blood tests may be one-off samples or the patient may require more detailed testing on a day-unit. These are called dynamic tests and they measure hormone levels before and after stimulation to see if the normal pituitary gland is working properly.They usually last between1 to 4 hours.

If it is suspected that there is a lack of anti-diuretic hormone, the doctor may organise a water deprivation test. The patient will be deprived of water for a period of eight hours under very close supervision with regular blood and urine tests.The test may be extended to a 24 hour period if needed, which means an overnight stay in hospital.

Other tests may also be organised to try and identify the underlying cause of the hypopituitarism. These could include blood tests, scans such as computerised tomography (CT) or magnetic resonance imaging (MRI) scans, and tests for vision.

Hypopituitarism is treated by replacing the deficient hormones. Treatment will be tailored to the individual depending on which hormones they are deficient in:

Since the treatment of hypopituitarism only involves replacing hormones that the body should be making but is unable to, there should be no side-effects if the appropriate amounts of hormones are replaced.Patients will be monitored to ensure they are receiving the correct amount of replacement hormones. Some side-effects can occur from hormone replacement if the amount replaced is higher than the individuals body requirements.If the patient has any concerns, they should discuss them with their doctor.

People with long-term hypopituitarism will need to take daily medication and will require regular checks with an endocrinologist at an outpatients clinic.

People with hypopituitarism may have an impaired quality of life.Hypopituitarism is associated with an increased risk of heart disease and strokes as a result of the physical changes that occur in body fat, cholesterol and circulation. Healthy living, a balanced diet and exercise to prevent becoming overweight are essential to reduce this risk.

People with hypopituitarism also have a higher risk of developing osteoporosis or brittle bones and, therefore, have a higher risk of developing fractures from minor injuries. A diet that is rich in calcium and vitamin d along with moderate amounts of weight-bearing exercise and training are helpful in decreasing this risk.

Appropriate pituitary hormone replacement therapy can reduce all these risks.

Last reviewed: Jan 2015

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Hypopituitarism | You and Your Hormones from the Society ...

Recommendation and review posted by simmons

There is truth in the old proverb about apple consumption and medical appointments. Insufficient vitamin C can contribute to leukemia. This observed relationship has now been shown to operate through the regulatory role the vitamin plays in the operation of bone marrow stem cells.

These days messages touting a single ingredient as being capable of curing all ills are more likely to peddleturmeric or cannabis, but a few decades ago it was vitamin C that was hailedas preventing everything from theflu to cancer if you took enough. As exaggerated as most of these claims were, it's certainly true that ascorbate, as it is also known, is vital to our health, sometimes in ways that are still unexplained.

We have known for a while that people with lower levels of ascorbate (vitamin C) are at increased cancer risk, but we havent fully understood why, said Dr Sean Morrison of University of Texas Southwestern. Stem cells clearly played a part, but are so rare in any individual tissue that it is impossible to collect the millions usually used for metabolic analysis. Moreover, most mammals make their own ascorbate, but humans cannot, impeding the use of animal models.

Morrison and his co-authors of a paper published in Nature had to develop new techniques to measure metabolite usage in populations as small as 10,000 stem cells to address the first problem. On applying these techniques the authors discovered each type of blood-forming cell has a distinctive signature to its metabolite consumption. They tackled the second problem using mice that lack ascorbate-producing enzymes.

When given a low vitamin C diet these mice had more, and more active, bone marrow stem cells, increasing blood cell production at the price of higher rates of leukemia. The vitamin C concentration was related to levels of the enzyme Tet2, which regulates blood production. Without enough Tet2, the stem cells behaved like an overheating engine, turning out blood cells at a great rate until they turned cancerous. Something similar is observed when mutations reduce Tet2 production.

The first clinical application of the discovery is for patients with clonal hematopoiesis, a condition that often involves reduced Tet2 production and leukemia. Our results suggest patients with clonal hematopoiesis and a Tet2 mutation should be particularly careful to get 100 percent of their daily vitamin C requirement, Morrison said. These patients... need to maximize the residual Tet2 tumor-suppressor activity to protect themselves from cancer.

Since stem cells are much sparser in the rest of the body than in bone marrow it will be even more challenging to extend the research to other cancers.

The ideal dose of vitamin C remains to be established, although a paper, coincidentally published last week, may indicate benefits beyond current recommendations.

Read more:
Vitamin C Can Suppress Leukemia By Regulating Blood Cell Production - IFLScience

Recommendation and review posted by simmons

TEL AVIV, Israel, Aug 21, 2017 /PRNewswire/ --BioLineRx Ltd. (NASDAQ: BLRX) (TASE:BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, announced today the filing of regulatory submissions required to commence a randomized, controlled Phase 3 registrational trial of BL-8040 for the mobilization of hematopoietic stem cells for autologous transplantation in patients with multiple myeloma. The trial, named GENESIS, is expected to commence by the end of 2017, following receipt of regulatory approvals.

The Phase 3 GENESIS trial is aimed at evaluating the safety, tolerability and efficacy of the combination treatment of BL-8040 and granulocyte colony-stimulating factor(G-CSF), as compared to the control arm of placebo and G-CSF. The trial will be conducted in two parts: The first part, designed to validate the optimal dosing of BL-8040, is a lead-in, open-label, multi-center study that will include 10-30 patients, in order to assess the efficacy and safety of treatment with BL-8040 and G-CSF. This part will be followed by a randomized, placebo-controlled, multi-center study in approximately 180 patients. The primary endpoint will be the proportion of subjects mobilizing 6.0 x 106CD34+ cells/kg with up to 2 apheresis sessions in preparation for autologous transplantation after a single administration of BL-8040 and G-CSF, as compared to placebo and G-CSF.

Philip Serlin, Chief Executive Officer of BioLineRx, stated, "We are excited to move forward with BL-8040 into a Phase 3 registration study. We have previously reported positive results supporting BL-8040 as a one-day dosing and up-to-two-day collection regimen for rapid mobilization of stem cells. This represents a significant improvement over the current treatment, which requires four-to-eight daily injections of G-CSF and one-to-four apheresis sessions. We therefore hope that this Phase 3 trial will further support these results and help improve the standard of care for multiple myeloma patients."

"In parallel, we are continuing to expand the potential of our robust BL-8040 oncology platform, by advancing multiple clinical studies for additional indications that are ongoing or expected to commence during 2017. These include a large, randomized, controlled Phase 2b study in AML, as well as several Phase 2 combination studies with immune checkpoint inhibitors in solid tumors and hematological malignancies," added Mr. Serlin.

About BL-8040

BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and stem cell mobilization. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing cell death (apoptosis). In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

About Stem Cell Mobilization

High-dose chemotherapy followed by stem cell transplantation has become an established treatment modality for a variety of hematologic malignancies, including multiple myeloma, as well as various forms of lymphoma and leukemia. Stem cells are mobilized from the bone marrow using granulocyte colony-stimulating factor (G-CSF), harvested from the peripheral blood by apheresis, and infused to the patient after chemotherapy. This type of treatment often replaces the use of traditional bone marrow transplantation, because the stem cells are easier to collect and the treatment allows for a quicker recovery time and fewer complications.

About BioLineRx

BioLineRx is a clinical-stage biopharmaceutical company focused on oncology and immunology. The Company in-licenses novel compounds, develops them through pre-clinical and/or clinical stages, and then partners with pharmaceutical companies for advanced clinical development and/or commercialization.

BioLineRx's leading therapeutic candidates are: BL-8040, a cancer therapy platform, which has successfully completed a Phase 2a study for relapsed/refractory AML, is in the midst of a Phase 2b study as an AML consolidation treatment and is expected to initiate a Phase 3 study in stem cell mobilization for autologous transplantation; and AGI-134, an immunotherapy treatment in development for multiple solid tumors, which is expected to initiate a first-in-man study in the first half of 2018. In addition, BioLineRx has a strategic collaboration with Novartis for the co-development of selected Israeli-sourced novel drug candidates; a collaboration agreement with MSD (known as Merck in the US and Canada), on the basis of which the Company has initiated a Phase 2a study in pancreatic cancer using the combination of BL-8040 and Merck's KEYTRUDA; and a collaboration agreement with Genentech, a member of the Roche Group, to investigate the combination of BL-8040 and Genentech's Tecentriq (Atezolizumab) in several Phase 1b/2 studies for multiple solid tumor indications and AML.

For additional information on BioLineRx, please visit the Company's website atwww.biolinerx.com, where you can review the Company's SEC filings, press releases, announcements and events. BioLineRx industry updates are also regularly updated onFacebook,Twitter, andLinkedIn.

Various statements in this release concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "may," "expects," "anticipates," "believes," and "intends," and describe opinions about future events. These forward-looking statements involve known and unknown risks and uncertainties that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Some of these risks are: changes in relationships with collaborators; the impact of competitive products and technological changes; risks relating to the development of new products; and the ability to implement technological improvements. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on March 23, 2017. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law.

Contacts:PCG AdvisoryVivian CervantesInvestor Relations+1-212-554-5482rel="nofollow">vivian@pcgadvisory.com

or

Tsipi HaitovskyPublic Relations+972-52-989892rel="nofollow">tsipihai5@gmail.com

View original content:http://www.prnewswire.com/news-releases/biolinerx-announces-regulatory-submission-of-phase-3-registrational-study-for-bl-8040-in-stem-cell-mobilization-300506916.html

SOURCE BioLineRx Ltd.

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BioLineRx Announces Regulatory Submission of Phase 3 Registrational Study for BL-8040 in Stem Cell Mobilization - Markets Insider

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Born a girl and now a man, Aarav Appukuttan, a 46-year-old from Kerala, says he was trapped inside a womans body for years. After undergoing a gender reassignment surgery at a Mumbai hospital, he fell in love with Sukanyeah Krishna 22, a man who underwent surgery at the same clinic to become a woman.

Aarav said he decided to eavesdrop while Sukanyeah was speaking to her family on the phone in Malayalam, as he knew the language. A casual conversation between the two led to them exchanging numbers. Their phone calls became more frequent in the coming months and cupid struck.

Neither of them has had an easy childhood. Aarav said he had long hair when he was 13. He would sit next to girls in his class, but felt unnerved by his attraction to them.

He confided in his mother, who took him to a doctor. The doctor said such problems were likely to happen at the onset of puberty, owing to hormonal imbalances. He asked Aarav to wait for a few years before opting for treatment.

However, Aarav, said his gender identity disorder (GID) only became more severe. In the next few years, he lost his mother and knew he had to take care of his siblings before he could focus on his own problems. My father remarried, he said.

I used to hate my body and wanted to cut it sometimes. But, I had to restrain myself and keep my feelings in check for 45 years. I always behaved like everything was normal, he added.

Sukanyeah said she also experienced GID during her childhood. After her father died, her mother took her to a doctor, who started her on male hormone therapy immediately. With the therapy, my facial and body structure changed. I started developing muscles, my shoulders became broader and I lost a lot of hair on my head, she said.

She said she was put on a high-protein diet, meant to aid her muscle development. No one understood what I was going through. During my Class 10 board exams, I fainted owing to the pressure, she said.She dropped out of school, studied software engineering and now works as a freelance web developer.

As the couple awaits their marriage ceremony, their friends say they expect a grand celebration. We wanted a small marriage ceremony, but our friends are asking for a treat. So, we will have a grand wedding. said Aarav.

He adds that he and Sukanyeah want to counsel those whose children are experiencing GID.

Dr Sanjay Pandey, from Kokilaben Dhirubhai Ambani Hospital, Andheri, who operated both of them said those who experience GID are just as normal and competent as we are. The only difference is that they feel trapped in the body of a gender they do not want to be. This is psychologically and emotionally tough, he said.

He said gender reassignment surgery costs between Rs18 lakh to Rs19 lakh in places such as Thailand, where it is popular. In India, it costs between Rs 4 lakh to Rs5 lakh.

More here:
Woman who was a man to marry man who was a woman - Hindustan Times

Recommendation and review posted by simmons

By HANNAH BEERSUI College of Veterinary Medicine

When a middle-aged, intact female dog comes into the clinic with complaints from her owner that she has been depressed and lethargic, one of the first concerns that likely pops into the veterinarian's mind is a potential pyometra.

"A pyometra is a uterine infection, and it is a true veterinary emergency," said Dr. Gary Brummet, the veterinarian who leads the primary care service at the UI Veterinary Teaching Hospital in Urbana.

What causes pyometras

Pyometras develop as a result of hormonal changes that take place in the reproductive tract during the normal hormonal cycle of a female. After an estrus (often referred to as "heat"), a hormone called progesterone remains elevated to assist the uterine lining in thickening in preparation for a potential pregnancy. Sometimes, if there are multiple cycles that persist without a pregnancy, the uterine lining can continue to thicken and secrete fluids, creating an environment that allows bacteria to grow quite well.

"Often pyometras become evident two to three months after the dog's last heat cycle," Brummet said.

Pyometras are categorized as "open" or "closed." In an open pyometra, infectious material leaks from the uterus; owners may notice a bloody, yellow or cream-colored discharge on their dog's fur near the uterine opening or on their bedding. A closed pyometra means that all the infectious material is trapped inside the uterus and builds up.

Symptoms of pyometras

Pyometras are most often found in dogs of any breed between the age of 6 and 10 and may be more common in dogs that have never had puppies. They do not occur in spayed animals, since a spay surgery involves removing the uterus. In extremely rare instances, pyometras can occur in cats.

"Along with appearing fatigued and depressed, dogs may stop eating, spike fever, have an abdomen that is distended and painful to touch, and urinate and drink more frequently," Brummet said.

Bacteria may release toxins that alter kidney function and impair the kidney's ability to manage and retain fluid. This can cause the increased urine production that is often seen and in turn the increased drinking may be the dog's attempt to compensate for the loss in fluid.

If a pup is showing any of these signs, she should be taken to the veterinarian immediately. There is a risk of sepsis with an untreated pyometra. Sepsis is when bacteria from an infection gets into the blood and thus is spread throughout the body via the circulatory system.

Diagnosis and treatment of pyometras

Your veterinarian may elect to do blood work, take a radiograph (X-ray) and/or perform an ultrasound to diagnose the pyometra. Pyometras are most often treated by surgical removal of the uterus.

"Surgery for removing a uterus that has a pyometra is much more risky than a spay. The uterine wall will be fragile, and there is a chance that it could rupture and introduce infectious material into the dog's abdomen during the procedure," Brummet said.

The only sure way to prevent this emergency is to spay the dog.

"The risk of a pyometra is one of the factors owners need to weigh when making the decision to spay or leave the female intact," Brummet said.

An archive of pet columns from the UI College of Veterinary Medicine is available at vetmed.illinois.edu/petcolumns/. Requests for reprints of this article may be directed to Chris Beuoy at beuoy@illinois.edu.

Link:
Pet Talk: A pyometra is a 'true veterinary emergency' - Champaign/Urbana News-Gazette

Recommendation and review posted by sam

Imagine only being able to see the things in front of you in soft focus, and just in black and white. For people with the genetic eye condition achromatopsia those are just some of the side effects. But, researchers are testing a new treatment designed to cure the condition by fixing the gene responsible.

Each time Tara Cataldo prepares to leave her house, she has to make sure her face is completely shielded from the sun.

"I need to have very dark, very tinted sunglasses to feel comfortable outside and to see really well." Tara said.

Tara has achromatopsia, a genetic condition that makes her eyes incredibly sensitive to light. She is also very nearsighted; even while wearing glasses or contacts, she can only see clearly at a very short distance.

"I cannot drive a car so I rely on public transportation and my bike to get around." she explained.

Christine Kay, MD, a surgical ophthalmologist at the University of Florida said, "There are currently no approved and no effective treatments for achromatopsia."

Surgical ophthalmologist Christine Kay is working to change that. She is one of a handful of experts testing a gene therapy

"For achromatopsia the cells we have to target are cone cells responsible for decreased vision and color vision and those are cells at the very bottom layer of the retina." Dr. Kay explained.

Using a tiny cannula, surgeons deliver a normal copy of one of two mutated genes; the CNGA3 or CNGB3 gene, directly into the eye restoring vision.

Tara's myopia is so severe that her risk of retinal detachment from any retinal surgery is high, which rules her out for the current trial. In the meantime, Tara says she's learned to adapt to achromatopsia and live without limitations.

"And I hope all young achromats learn the same thing," Cataldo said.

Doctor Kay says if the gene could eventually be delivered to the surface of the retina; additional patients, like Tara, could be treated. The biotech company that developed the therapies and several U.S. universities have successfully tested this therapy in dogs and sheep.

See more here:
Potential therapy for eye condition - WTAJ

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VIDEO Life Lessons: Next generation...

When Audrey Lapidus 10-month old son, Calvin, didnt reach normal milestones like rolling over or crawling, she knew something was wrong.

He was certainly different from our first child, said Lapidus, of Los Angeles. He had a lot of gastrointestinal issues and we were taking him to the doctor quite a bit.

Four specialists saw Calvin and batteries of tests proved inconclusive. Still, Lapidus persisted.

I was pushing for even more testing, and our geneticist at UCLA said, If you can wait one more month, were going to be launching a brand new test called exome sequencing, she said. We were lucky to be in the right place at the right time and get the information we did.

In 2012, Calvin Lapidus became the first patient to undergo exome sequencing at UCLA. He was subsequently diagnosed with a rare genetic condition known as Pitt-Hopkins Syndrome, which is most commonly characterized by developmental delays, possible breathing problems, seizures and gastrointestinal problems.

Though there is no cure for Pitt-Hopkins, finally having a diagnosis allowed Calvin to begin therapy.

The diagnosis gave us a point to move forward from, rather than just existing in that scary no-mans land where we knew nothing, Lapidus said.

Unfortunately, there are a lot of people living in that no-mans land, desperate for any type of answers to their medical conditions, said Dr. Stanley Nelson, professor of human genetics and pathology and laboratory medicine at the David Geffen School of Medicine at UCLA. Many families suffer for years without so much as a name for their condition.

What exome sequencing allows doctors to do is to analyze more than 20,000 genes at once, with one simple blood test.

In the past, genetic testing was done one gene at a time, which is time-consuming and expensive.

Rather than testing one sequential gene after another, exome sequencing saves time, money and effort, said Dr. Julian Martinez-Agosto, a pediatrician and researcher at the Resnick Neuropsychiatric Hospital at UCLA.

The exome consists of all the genomes exons, which are the coding portion of genes. Clinical exome sequencing is a test for identifying disease-causing DNA variants within the 1 percent of the genome which codes for proteins, the exons, or flanks the regions which code for proteins, called splice junctions.

To date, mutations in the protein-coding parts of genes accounts for nearly 85 percent of all mutations known to cause genetic diseases, so surveying just this portion of the genome is an efficient and powerful diagnostic tool. Exome sequencing can help detect rare disorders like spinocerebellar ataxia, which progressively diminishes a persons movements, and suggest the likelihood of more common conditions like autism spectrum disorder and epilepsy.

More than 4,000 adults and children have undergone exome testing at UCLA since 2012. Of difficult to solve cases, more than 30 percent are solved through this process, which is a dramatic improvement over prior technologies. Thus, Nelson and his team support wider use of genome-sequencing techniques and better insurance coverage, which would further benefit patients and resolve diagnostically difficult cases at much younger ages.

Since her sons diagnosis, Lapidus helped found the Pitt-Hopkins Syndrome Research Foundation. Having Calvins diagnosis gave us a roadmap of where to start, where to go and whats realistic as far as therapies and treatments, she said. None of that would have been possible without that test.

Next, experts at UCLA are testing the relative merits of broader whole genome sequencing to analyze all 6 billion bases that make up a persons genome. The team is exploring integration of this DNA sequencing with state-of-the-art RNA or gene expression analysis to improve the diagnostic rate.

The entire human genome was first sequenced in 1990 at a cost of $2.7 billion. Today, doctors can perform the same test at a tiny fraction of that cost, and believe that sequencing whole genomes of individuals could vastly improve disease diagnoses and medical care.

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Life Lessons: Next generation testing - WFMZ Allentown

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Christopher Walsh can still remember the day he found a suspicious lump on his groin. He immediately went to the doctor to have the lump biopsied, and results confirmed that Chris had non-Hodgkin lymphoma. He was diagnosed in June 2015, and immediately decided to go to Dana-Farber because he wanted the best to take care of it. As the cancer began to get a bit more complicated, Dr. Davids started Chris on a clinical trial involving chemotherapy a targeted gene therapy. That treatment has not worked to satisfaction, so Chris is now launching into a newer form of treatment: immunotherapy.

He has been married for almost 33 years and has 2 adult children. He is a state legislator representing the 6th Middlesex district in Framingham. Prior to that, he served as an architect for 30 years.Chris says that one of the things that has been incredible is the community support he has experienced. He had a few reservations about publicly coming out with this cancer, but given his role in the community, he did so and he has found that people appreciate the process and struggles he has endured. He has ultimate confidence in Dana-Farbers continued fight for a cure.

After obtaining an A.B. in chemistry at Harvard College, Dr. Davids completed his M.D. at Yale University School of Medicine. He served as an intern, resident, and assistant chief resident in internal medicine at New York-Presbyterian Weill Cornell Medical Center and Memorial Sloan-Kettering Cancer Center in New York City. He then completed his fellowship in hematology and oncology in Dana-Farber/Partners CancerCare, and a Masters in Medical Science (MMSc) at Harvard Medical School.

He is an attending physician in the Lymphoma Program of the Division of Hematologic Malignancies at Dana-Farber, an Assistant Professor of Medicine at Harvard Medical School, and is the Associate Director of the Dana-Farber CLL Center.

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DHK - Representative Chris Walsh, 66, non-Hodgkin lymphoma (a white blood cell cancer), Framingham, with Dr ... - WEEI.com

Recommendation and review posted by sam

UCLA researchers have discovered a new way to activate the stem cells in the hair follicle to make hair grow. The research, led by scientists Heather Christofk and William Lowry, may lead to new drugs that could promote hair growth for people with baldness or alopecia, which is hair loss associated with such factors as hormonal imbalance, stress, aging or chemotherapy treatment.

The research was published in the journal Nature Cell Biology.

Hair follicle stem cells are long-lived cells in the hair follicle; they are present in the skin and produce hair throughout a persons lifetime. They are quiescent, meaning they are normally inactive, but they quickly activate during a new hair cycle, which is when new hair growth occurs. The quiescence of hair follicle stem cells is regulated by many factors. In certain cases they fail to activate, which is what causes hair loss.

In this study, Christofk and Lowry, of Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, found that hair follicle stem cell metabolism is different from other cells of the skin. Cellular metabolism involves the breakdown of the nutrients needed for cells to divide, make energy and respond to their environment. The process of metabolism uses enzymes that alter these nutrients to produce metabolites. As hair follicle stem cells consume the nutrient glucose a form of sugar from the bloodstream, they process the glucose to eventually produce a metabolite called pyruvate. The cells then can either send pyruvate to their mitochondria the part of the cell that creates energy or can convert pyruvate into another metabolite called lactate.

Our observations about hair follicle stem cell metabolism prompted us to examine whether genetically diminishing the entry of pyruvate into the mitochondria would force hair follicle stem cells to make more lactate, and if that would activate the cells and grow hair more quickly, said Christofk, an associate professor of biological chemistry and molecular and medical pharmacology.

The research team first blocked the production of lactate genetically in mice and showed that this prevented hair follicle stem cell activation. Conversely, in collaboration with the Rutter lab at University of Utah, they increased lactate production genetically in the mice and this accelerated hair follicle stem cell activation, increasing the hair cycle.

Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells, said Lowry, a professor of molecular, cell and developmental biology. Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.

The team identified two drugs that, when applied to the skin of mice, influenced hair follicle stem cells in distinct ways to promote lactate production. The first drug, called RCGD423, activates a cellular signaling pathway called JAK-Stat, which transmits information from outside the cell to the nucleus of the cell. The research showed that JAK-Stat activation leads to the increased production of lactate and this in turn drives hair follicle stem cell activation and quicker hair growth. The other drug, called UK5099, blocks pyruvate from entering the mitochondria, which forces the production of lactate in the hair follicle stem cells and accelerates hair growth in mice.

Through this study, we gained a lot of interesting insight into new ways to activate stem cells, said Aimee Flores, a predoctoral trainee in Lowrys lab and first author of the study. The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think weve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; Im looking forward to the potential application of these new findings for hair loss and beyond.

The use of RCGD423 to promote hair growth is covered by a provisional patent application filed by the UCLA Technology Development Group on behalf of UC Regents. The use of UK5099 to promote hair growth is covered by a separate provisional patent filed by the UCLA Technology Development Group on behalf of UC Regents, with Lowry and Christofk as inventors.

The experimental drugs described above were used in preclinical tests only and have not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.

The research was supported by a California Institute for Regenerative Medicine training grant, a New Idea Award from the Leukemia and Lymphoma Society, the National Cancer Institute (R25T CA098010), the National Institute of General Medical Sciences (R01-GM081686 and R01-GM0866465), the National Institutes of Health (RO1GM094232), an American Cancer Society Research Scholar Grant (RSG-16-111-01-MPC), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (5R01AR57409), a Rose Hills Foundation Research Award and the Gaba Fund. The Rose Hills award and the Gaba Fund are administered through the UCLA Broad Stem Cell Research Center.

Further research on the use of UK5099 is being funded by the UCLA Technology Development Group through funds from California State Assembly Bill 2664.

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UCLA scientists identify a new way to activate stem cells to make hair grow - UCLA Newsroom

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