lroot on June 15th, 2017

Toxins in Your Tap Water

America has a drinking water crisis. An NRDC study has found that contaminants that may harm human health are found in tap water in every state in the nation. This is a problem even for people who don’t drink tap water since water borne toxins can be absorbed through the skin and lungs while bathing and into food if used for cooking.

Established in 1974, the Safe Drinking Water Act is one of the bedrock environmental laws in the United States, consisting of rules that regulate about 100 contaminants found in drinking water. NRDC has documented serious problems with our outdated and deteriorating water infrastructure, widespread violations and inadequate enforcement of the Safe Drinking Water Act for more than 25 years.

The study shows that in 2015 alone, there were more than 80,000 reported violations of the Safe Drinking Water Act by community water systems. Nearly 77 million people were served by more than 18,000 of these systems with violations in 2015. These violations included exceeding health-based standards, failing to properly test water for contaminants, and failing to report contamination to state authorities or the public. What’s worse, 2015 saw more than 12,000 health-based violations in some 5,000 community water systems serving more than 27 million people.

In 2016, the publication “What’s in Your Water: Flint and Beyond” detailed the lead crisis in Flint, Michigan, and contextualized a larger, national crisis around lead in drinking water. The new study picks up where that one left off, detailing a stunning number of violations of the Safe Drinking Water Act around the nation.

1. Combined Disinfectants and Disinfection Byproducts

Exposure to these contaminants can lead to cancer and may be linked to reproductive impacts such as miscarriages and birth defects. In 2015, there were 11,311 violations (4,591 health-based) at community water systems serving 25,173,431 people (12,584,936 health-based). Formal enforcement measures were taken in 12.4 percent of all cases and 23.0 percent of health-based cases.

2. Total Coliform

The presence of coliforms in drinking water indicates that possible presence of organisms that can cause diarrhea, cramps, nausea, and headaches in otherwise-healthy people. These impacts can be much more serious and even life-threatening for children, the elderly, and immune-compromised people. In 2015, there were 10,261 violations (2,574 health-based) at community water systems serving 17,768,807 people (10,118,586 health-based). Formal enforcement was taken in 8.8 percent of cases (and 8.3 percent of health-based cases).

3. Combined Surface, Ground Water, and Filter Backwash Rules

Exposure to some of these pathogens, such as Cryptosporidium or Giardia, can cause severe gastrointestinal distress, nausea, and diarrhea. They can cause serious, life-threatening infections for the very young, elderly, and immune-compromised. In 2015 there were 5,979 violations (1,790 health-based) at community water systems serving 17,312,604 people (5,336,435 health-based). Formal enforcement was taken in 13.7 percent of cases (28.2 percent of health-based cases).

4. Nitrites and Nitrates

Exposure can lead to blue baby syndrome in infants (potentially leading to death in extreme cases), developmental effects, and cardiovascular disease. In extreme cases, blue baby syndrome can be severe and lead to death. In 2015, there were 1,529 violations (459 health-based) at community water systems serving 3,867,431 people (1,364,494 health-based). Formal enforcement action was taken in 11.3 percent of all cases (and 27.9 percent of health-based cases).

5. Lead and Copper

Exposure to lead is particularly toxic to children and can cause serious, irreversible damage to their developing brains and nervous systems. Lead exposure can also cause miscarriages and stillbirths in pregnant women, as well as fertility issues, cardiovascular and kidney effects, cognitive dysfunction, and elevated blood pressure in healthy adults. In 2015, there were 8,044 violations (303 health-based) by systems serving 18,350,633 people (582,302 health-based). Formal enforcement action was taken in 12.0 percent of the cases (and in 14.2 percent of health-based cases).

6. Radionuclides

Exposure can lead to cancers and compromised kidney function. In 2015, there were 2,297 violations (962 health-based) in community water systems serving 1,471,364 people (445,969 health-based). Formal enforcement was taken in 11.7 percent of all cases (and 16.1 percent of health-based cases).

7. Arsenic

A known human carcinogen, exposure can lead to cancers, development effects, pulmonary disease, or cardiovascular disease. In 2015, there were 1,537 violations (1,135 health-based) at community water systems serving 1,842,594 people (358,323 health-based). Formal enforcement was taken in 28.9 percent of cases (37.1 percent of health-based cases).

8. Synthetic Organic Contaminants

Exposure can lead to cancers, developmental effects, central nervous system and reproductive difficulties, endocrine issues, or liver and kidney problems. In 2015 there were 6,864 violations (17 health-based) serving 2,669,594 people (301,099 health-based). Formal enforcement action was taken in 7.3 percent of cases (and 5.9 percent of health-based cases).

9. Inorganic Contaminants

Exposure can lead to increased cholesterol, kidney damage, hair loss, skin irritation, and cancer. In 2015, there were 1,505 violations (291 health-based) in community water systems serving 1,312,643 people (83,033 health-based). Formal enforcement was taken in 5.2 percent of cases (15.1 percent of health-based cases).

10. Volatile Organic Contaminants

Exposure can lead to cancers; developmental, skin, and reproductive issues; and cardiovascular problems. Exposure can also cause adverse effects on the liver, kidneys, and immune and nervous systems. In 2015 there were 10,383 violations (15 of them health-based) at community water systems serving 3,451,072 people (5,276 health-based). Formal enforcement was taken in 6.1 percent of cases (and 26.7 percent of health-based cases).

11. Public Notification

All community water systems are required to directly deliver information about their drinking water quality to each customer once a year. In 2015 there were 13, 202 violations by community water systems serving 8,381,050 people. Formal enforcement action was taken in 10.3 percent of cases.

The take away from this is to either install a water purifier or use natural spring water. Purifiers are also available for showers and are typically installed between the shower head and pipe.

Walking my way to 100

New research from Brigham Young University reveals you may be able to slow one type of aging the kind that happens inside your cells. As long as you’re willing to sweat.

“Just because you’re 40, doesn’t mean you’re 40 years old biologically,” Tucker said. “We all know people that seem younger than their actual age. The more physically active we are, the less biological aging takes place in our bodies.”

The study, published in the medical journal Preventive Medicine, finds that people who have consistently high levels of physical activity have significantly longer telomeres than those who have sedentary lifestyles, as well as those who are moderately active.

Telomeres are the protein endcaps of our chromosomes. They’re like our biological clock and they’re extremely correlated with age; each time a cell replicates, we lose a tiny bit of the endcaps. Therefore, the older we get, the shorter our telomeres.

Exercise science professor Larry Tucker found adults with high physical activity levels have telomeres with a biological aging advantage of nine years over those who are sedentary, and a seven-year advantage compared to those who are moderately active. To be highly active, women had to engage in 30 minutes of jogging per day (40 minutes for men), five days a week.

“If you want to see a real difference in slowing your biological aging, it appears that a little exercise won’t cut it,” Tucker said. “You have to work out regularly at high levels.”

Tucker analyzed data from 5,823 adults who participated in the CDC’s National Health and Nutrition Examination Survey, one of the few indexes that includes telomere length values for study subjects. The index also includes data for 62 activities participants might have engaged in over a 30-day window, which Tucker analyzed to calculate levels of physical activity.

His study found the shortest telomeres came from sedentary people–they had 140 base pairs of DNA less at the end of their telomeres than highly active folks. Surprisingly, he also found there was no significant difference in telomere length between those with low or moderate physical activity and the sedentary people.

Although the exact mechanism for how exercise preserves telomeres is unknown, Tucker said it may be tied to inflammation and oxidative stress. Previous studies have shown telomere length is closely related to those two factors and it is known that exercise can suppress inflammation and oxidative stress over time.

“We know that regular physical activity helps to reduce mortality and prolong life, and now we know part of that advantage may be due to the preservation of telomeres,” Tucker said.

Reference: Larry A. Tucker. Physical activity and telomere length in U.S. men and women: An NHANES investigation. Preventive Medicine, Volume 100, July 2017, Pages 145–151

Bone Fracture

A Cedars-Sinai-led team of investigators has successfully repaired severe limb fractures in laboratory animals with an innovative technique that cues bone to regrow its own tissue. If found to be safe and effective in humans, the pioneering method of combining ultrasound, stem cell and gene therapies could eventually replace grafting as a way to mend severely broken bones.

“We are just at the beginning of a revolution in orthopedics,” said Dan Gazit, PhD, DMD, co-director of the Skeletal Regeneration and Stem Cell Therapy Program in the Department of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute. “We’re combining an engineering approach with a biological approach to advance regenerative engineering, which we believe is the future of medicine.”

Gazit was the principal investigator and co-senior author of the research study, published in the journal Science Translational Medicine.

More than 2 million bone grafts, frequently necessitated by severe injuries involving traffic accidents, war or tumor removal, are performed worldwide each year. Such injuries can create gaps between the edges of a fracture that are too large for the bone to bridge on its own. The grafts require implanting pieces from either the patient’s or a donor’s bone into the gap.

“Unfortunately, bone grafts carry disadvantages,” said Gazit, a professor of surgery at Cedars-Sinai. “There are huge unmet needs in skeleton repair.”

One problem is that enough healthy bone is not always available for repairs. Surgeries to remove a bone piece, typically from the pelvis, and implant it can lead to prolonged pain and expensive, lengthy hospitalizations. Further, grafts from donors may not integrate or grow properly, causing the repair to fail.

The new technique developed by the Cedars-Sinai-led team could provide a much-needed alternative to bone grafts.

In their experiment, the investigators constructed a matrix of collagen, a protein the body uses to build bones, and implanted it in the gap between the two sides of a fractured leg bone in laboratory animals. This matrix recruited the fractured leg’s own stem cells into the gap over a period of two weeks. To initiate the bone repair process, the team delivered a bone-inducing gene directly into the stem cells, using an ultrasound pulse and microbubbles that facilitated the entry of the gene into the cells.

Eight weeks after the surgery, the bone gap was closed and the leg fracture was healed in all the laboratory animals that received the treatment. Tests showed that the bone grown in the gap was as strong as that produced by surgical bone grafts, said Gadi Pelled, PhD, DMD, assistant professor of surgery at Cedars-Sinai and the study’s co-senior author.

“This study is the first to demonstrate that ultrasound-mediated gene delivery to an animal’s own stem cells can effectively be used to treat nonhealing bone fractures,” Pelled said. “It addresses a major orthopedic unmet need and offers new possibilities for clinical translation.”

The study involved six departments at Cedars-Sinai, plus investigators from Hebrew University in Jerusalem; the University of Rochester in Rochester, New York; and the University of California, Davis.

“Our project demonstrates how scientists from diverse disciplines can combine forces to find solutions to today’s medical challenges and help develop treatments for the patients of tomorrow,” said Bruce Gewertz, MD, surgeon-in-chief and chair of the Department of Surgery at Cedars-Sinai.

Reference: Maxim Bez, Dmitriy Sheyn, Wafa Tawackoli, Pablo Avalos, Galina Shapiro, Joseph C. Giaconi, Xiaoyu Da, Shiran Ben David, Jayne Gavrity, Hani A. Awad, Hyun W. Bae, Eric J. Ley, Thomas J. Kremen, Zulma Gazit, Katherine W. Ferrara, Gadi Pelled, Dan Gazit. In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs. Science Translational Medicine, 2017; 9 (390): eaal3128 DOI: 10.1126/scitranslmed.aal3128

lroot on June 2nd, 2017

Liver

Among all the organs in the human body, the liver is something of a superhero. Not only does it defend our bodies against the liquid toxins we regularly ingest, it has the ability to regenerate itself, and, as new research shows, it increases its size by nearly half over the course of a day.

Working in mice, researchers in Switzerland documented this process of regular stretching and shrinking, watching as liver cells swelled in size and contracted up to 40 percent along with the mice’s daily activities. There’s a catch though, a kind of hepatological kryptonite. Their livers only exhibited this ability when the mice followed their normal cycles of eating and resting. They’re nocturnal creatures, and if they began eating during the day when they usually rest, their livers stubbornly refused to grow.

The liver is the only organ known to display such significant cyclical growth, although it does make sense. During the half of the day when we’re not eating, our organs have far less to do. By growing and shrinking to meet demand, our livers are actually trying to save us wasted energy.

The Swiss researchers say that they observed hepatocytes, the main kind of cell in livers, growing during the night when mice were active, something they they attribute largely to an increase in ribosomes, structures in cells that take RNA instructions and use them to produce proteins, among other things. The liver takes material from the food and converts it into useful proteins and other molecules crucial for bodies to function, so possessing more ribosomes means they’re that much better at their jobs. When their daily cycle comes to a close, livers begin breaking down the ribosomes again, like street vendors packing up for the night.

It makes sense that livers would swell when they have to work the hardest. What the researchers found, though, was that it’s not just food intake that tells the liver to ramp up ribosome production — it’s also dependent on what time of day it is. Cells in our livers are also sensitive to circadian rhythms and they found that mouse livers would only begin to grow at night when they ate. Mice fed during the day did not exhibit the same kind of liver growth that their nocturnal counterparts did. The cues that tell the liver to begin preparing for action don’t just come from our food, in other words, they also come from the environment.

Because a bigger liver can work faster and pull out nutrients more efficiently, there’s an obvious advantage to maintaining this kind of cycle. In mice kept nocturnal, there was a noticeable smooth curve of growing and shrinking, and the researchers noticed a 1.6-fold difference in the level of proteins in the liver between the two extremes. In day-fed mice, there was no difference, indicating that their livers weren’t able to produce as much. They published their work Thursday in Cell.

There is evidence that human livers may exhibit the same ability based on a 1986 study that used ultrasound to measure people’s livers over the course of six hours. They found variations of around 20 percent, although they didn’t take any measurements during the night, when our bodily rhythms slow down.

These findings in the liver add to a mounting case for returning to sleep cycles based on environmental cues. Illuminating the night with artificial brilliance has been tied to disrupted sleep cycles in humans, as well as an increased risk for obesity, diabetes, depression and some types of cancer. For millennia, our bodies regulated themselves with the daily rising and setting of the sun, ramping us up when it was light and settling us back down when it got dark. Now, it appears that this extends to our digestive systems as well.

Our livers cleanse toxins from our bodies, produce proteins and chemicals necessary for digestion, recycle old red blood cells and regulate glycogen levels in our bodies. If they aren’t working properly, we can die. While the authors don’t address the implications of their work for humans, their findings could help to explain why it’s unhealthy to go to bed late at night.

Reference: Flore Sinturel, Alan Gerber, Daniel Mauvoisin, Jingkui Wang, David Gatfield, Jeremy J. Stubblefield, Carla B. Green, Frédéric Gachon, Ueli Schibler. Diurnal Oscillations in Liver Mass and Cell Size Accompany Ribosome Assembly Cycles. Cell, Volume 169, Issue 4, 651 – 663

lroot on June 1st, 2017

Watson Super Computer doctor

Many people know Watson as IBM’s world Jeopardy champion on the television show. Now IBM is turning it’s artificially intelligent supercomputer into a medical genius.

“Watson, the supercomputer, basically went to med school after it won Jeopardy,” MIT’s Andrew McAfee, coauthor of The Second Machine Age, said recently in an interview with Smart Planet. “I’m convinced that if it’s not already the world’s best diagnostician, it will be soon.”

Watson is already capable of storing far more medical information than doctors, and unlike humans, its decisions are all evidence-based and free of cognitive biases and overconfidence. It’s also capable of understanding natural language, generating hypotheses, evaluating the strength of those hypotheses, and learning not just storing data, but finding meaning in it.

As IBM scientists continue to train Watson to apply its vast stores of knowledge to actual medical decision-making, it’s likely just a matter of time before its diagnostic performance surpasses that of even the sharpest doctors.

Back in 2011, McAfee wrote on his blog about why a diagnosis from “Dr. Watson” would be a game changer.

It’s based on all available medical knowledge. Human doctors can’t possibly hold this much information in their heads, or keep up it as it changes over time. Dr. Watson knows it all and never overlooks or forgets anything.

It’s accurate. If Dr. Watson is as good at medical questions as the current Watson is at game show questions, it will be an excellent diagnostician indeed.

It’s consistent. Given the same inputs, Dr. Watson will always output the same diagnosis. Inconsistency is a surprisingly large and common flaw among human medical professionals, even experienced ones. And Dr. Watson is always available and never annoyed, sick, nervous, hung over, upset, in the middle of a divorce, sleep-deprived, and so on.

It has very low marginal cost. It’ll be very expensive to build and train Dr. Watson, but once it’s up and running the cost of doing one more diagnosis with it is essentially zero, unless it orders tests.

It can be offered anywhere in the world. If a person has access to a computer or mobile phone, Dr. Watson is on call for them.

An April study estimated that as many as 1 in 20 U.S. adults are misdiagnosed by their human doctors each year, so it’s an area ripe for improvement and competition.

That’s one reason IBM has been pumping Watson full of medical knowledge a subject area that’s actually significantly more contained than “all the world’s general knowledge,” which is what Watson tried to learn for Jeopardy.

Watson has “read” dozens of textbooks, all of PubMed and Medline (two massive databases of medical journals), and thousands of patient records from Memorial Sloan Kettering. All together, “Watson has analyzed 605,000 pieces of medical evidence, 2 million pages of text, 25,000 training cases and had the assist of 14,700 clinician hours fine-tuning its decision accuracy,” Forbes reported in 2013.

And it’s getting “smarter” every year. So how would Dr. Watson work in practice? Here’s how IBM describes the process:

First, the physician might describe symptoms and other related factors to the system. Watson can then identify the key pieces of information and mine the patient’s data to find relevant facts about family history, current medications and other existing conditions. It combines this information with current findings from tests, and then forms and tests hypotheses by examining a variety of data sources such as treatment guidelines, electronic medical record data and doctors’ and nurses’ notes, as well as peer reviewed research and clinical studies. From here, Watson can provide potential treatment options and its confidence rating for each suggestion.

So far, IBM’s most high-profile AI partnerships are with MD Anderson Cancer Center and WellPoint, where Watson helps the insurer evaluate doctors’ treatment plans.

Watson is not yet able to leverage all the information it has absorbed, so it still has a ways to go before it catches up with our best human diagnosticians, whose versatility and agility is difficult to match. But Watson’s ability to learn, analyze, and apply knowledge suggests that it’s only a matter of time before is surpasses the best human doctors.

“If and when Dr. Watson gets as good at diagnosis as Watson is at Jeopardy I want it as my primary care physician,” McAfee wrote, back in 2011.

That day may come sooner than we imagined.

Tibetan Singing Bowls

A recent study conducted at Baycrest Health Sciences has uncovered a crucial piece into why playing a musical instrument can help older adults retain their listening skills and ward off age-related cognitive declines. This finding could lead to the development of brain rehabilitation interventions through musical training.

The study, published in the Journal of Neuroscience, found that learning to play a sound on a musical instrument alters the brain waves in a way that improves a person’s listening and hearing skills over a short time frame. This change in brain activity demonstrates the brain’s ability to rewire itself and compensate for injuries or diseases that may hamper a person’s capacity to perform tasks.

“Music has been known to have beneficial effects on the brain, but there has been limited understanding into what about music makes a difference,” says Dr. Bernhard Ross, senior scientist at Baycrest’s Rotman Research Institute (RRI) and senior author on the study. “This is the first study demonstrating that learning the fine movement needed to reproduce a sound on an instrument changes the brain’s perception of sound in a way that is not seen when listening to music.”

This finding supports Dr. Ross’ research using musical training to help stroke survivors rehabilitate motor movement in their upper bodies. Baycrest scientists have a history of breakthroughs into how a person’s musical background impacts the listening abilities and cognitive function as they age and they continue to explore how brain changes during aging impact hearing.

The study involved 32 young, healthy adults who had normal hearing and no history of neurological or psychiatric disorders. The brain waves of participants were first recorded while they listened to bell-like sounds from a Tibetan singing bowl (a small bell struck with a wooden mallet to create sounds). After listening to the recording, half of the participants were provided the Tibetan singing bowl and asked to recreate the same sounds and rhythm by striking it and the other half recreated the sound by pressing a key on a computer keypad.

“It has been hypothesized that the act of playing music requires many brain systems to work together, such as the hearing, motor and perception systems,” says Dr. Ross, who is also a medical biophysics professor at the University of Toronto. “This study was the first time we saw direct changes in the brain after one session, demonstrating that the action of creating music leads to a strong change in brain activity.”

The study’s next steps involve analyzing recovery between stroke patients with musical training compared to physiotherapy and the impact of musical training on the brains of older adults.

With additional funding, the study could explore developing musical training rehabilitation programs for other conditions that impact motor function, such as traumatic brain injury.

Reference: Bernhard Ross, Masihullah Barat, Takako Fujioka. Sound-making actions lead to immediate plastic changes of neuromagnetic evoked responses and induced beta-band oscillations during perception. The Journal of Neuroscience, 2017; 3613-16 DOI: 10.1523/JNEUROSCI.3613-16.2017

Stem Cells

The emergency call issued by the American Red Cross earlier this year was of a sort all too common: Donations of platelets were needed, and desperately. But a new discovery from the University of Virginia School of Medicine may be the key to stopping shortages of these vital blood-clotting cells.

The UVA researchers have identified a “master switch” that they may be able to manipulate to overcome the obstacles that have prevented doctors from producing platelets in large quantities outside the body. “The platelet supply is limited and the demand is growing,” said researcher Adam Goldfarb, MD, of UVA’s Department of Pathology. “The quantities we can produce outside the body are very, very small, and the inability to scale up right now is a major roadblock. We think that our understanding of this pathway is actually a critical step toward fixing that problem.”

Scientists also may be able to use this master switch to battle neonatal thrombocytopenia, a condition that complicates the care of babies who are already at great risk. “It turns out in premature infants and newborns that [the platelet] reserve is compromised. They are less capable of responding to distress and the demand for increased platelet production,” Goldfarb said. “A goodly percentage of those babies, these tiny little babies, require platelet transfusions to keep their platelets up.”

The switch discovered by Goldfarb’s team controls whether the bone marrow produces cells called megakaryocytes of the type seen in adults or of the sort found in infants. This is important because the adult and infantile versions have very different specialties: Adult megakaryocytes are great at making platelets. Lots and lots of them. Infantile megakaryocytes, on the other hand, are much smaller cells, and they concentrate on dividing to produce more megakaryocytes.

The ability to toggle between the two could be a huge asset for doctors. Now, doctors cannot produce large quantities of platelets in the lab and instead must rely on platelet donations for patients. The new finding, however, may help change that. “It’s thought that in our bodies every single megakaryocyte produces like a thousand platelets, and when you do it in culture [outside the body] it’s like 10,” he said. “We think the pathway we’re studying enhances the efficiency of platelet release, and this pathway, we think, could be manipulated in both directions: to suppress the pathway to promote the growth [of megakaryocytes] and then to activate the pathway at some point to enhance the efficiency of platelet release.”

For example, babies might be given a drug that would prompt their bodies to make more platelets. Researcher Kamal Elagib, MBBS, PhD, noted that the research team already has identified compounds that can flip the switch in the lab, but that those compounds likely aren’t the best option for treatment: “Those inhibitors have multiple effects, so there would be side effects,” he said.

The researchers, however, have already identified other drugs that look much more promising. “Our future efforts that Kamal is working on now are to identify better, cleaner, more effective approaches at flipping this switch,” Goldfarb said. “Understanding this process could really enhance the future approaches towards treating patients with low platelet counts.”

Reference: Kamaleldin E. Elagib, Chih-Huan Lu, Goar Mosoyan, Shadi Khalil, Ewelina Zasadzi?ska, Daniel R. Foltz, Peter Balogh, Alejandro A. Gru, Deborah A. Fuchs, Lisa M. Rimsza, Els Verhoeyen, Miriam Sansó, Robert P. Fisher, Camelia Iancu-Rubin, Adam N. Goldfarb. Neonatal expression of RNA-binding protein IGF2BP3 regulates the human fetal-adult megakaryocyte transition. Journal of Clinical Investigation, 2017; DOI: 10.1172/JCI88936

lroot on April 28th, 2017

heart

Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists. Now, Johns Hopkins researchers report success in creating them in the laboratory by implanting stem cells taken from a healthy adult or one with a type of heart disease into newborn rat hearts.

The researchers say the host animal hearts provide the biological signals and chemistry needed by the implanted immature heart muscle cells to progress and overcome the developmental blockade that traditionally stops their growth in lab culture dishes or flasks.

In a summary of the work published Jan. 10 in Cell Reports, the researchers say their method should help advance studies of how heart disease develops, along with the development of new diagnostic tools and stem cell treatments.

“Our concept of using a live animal host to enable maturation of cardiomyocytes can be expanded to other areas of stem cell research and really opens up a new avenue to getting stem cells to mature,” says Chulan Kwon, Ph.D., associate professor of medicine and member of the Johns Hopkins University School of Medicine’s Institute for Cell Engineering, who led the study.

According to Kwon, cell biologists have been historically unable to induce heart muscle cells to get past the point in development characteristic of newborns, even when they let them mature in dishes for a year.

Those neonatal heart cells, Kwon explains, are smaller and rounder than mature adult heart cells and generate very low pumping force. As a result, he adds, they aren’t the best model for heart muscle diseases, nor do they accurately mimic the biology and chemistry of adult heart tissue.

Kwon’s group recently showed that cells kept and grown in lab dishes weren’t turning on the proper genes needed to let the cells transition to maturity, a phenomenon they attributed to the artificial conditions of growing cells in a dish. But they also found that those genes were similar to those activated, or turned on, in the hearts of newborn rats.

In their initial experiments designed to overcome the developmental roadblock, the researchers first created a cell line of immature heart cells taken from mouse embryonic stem cells. They next tagged these cells with a fluorescent protein and injected about 200,000 of the cells into the ventricle or lower heart chamber of newborn nude rats — rats with deficient immune systems that wouldn’t attack and reject the newly introduced cells.

After about a week, Kwon reports, the fluorescent cells were still rounded and immature-looking. After a month, however, the cells looked like adult heart muscle cells — elongated with striped patterns.

When the researchers compared 312 genes in the individual mouse cells grown in the rat hearts to the genes found in both immature heart cells and adult heart muscle cells, they found the cells grown in the rat hearts had more in common with genetics of adult heart muscle cells.

The investigators confirmed that the new heart-grown cells could contract or beat like normal adult heart muscle cells using a type of optical microscopy.

In the next set of proof-of-concept experiments, Kwon’s team worked with human adult skin cells from a healthy human donor that were chemically converted back into a stem cell-like state known as induced pluripotent stem cells. A month after these cells were implanted into newborn rat hearts, the healthy human donor cells appeared rod-shaped and mature.

Kwon cautions that clinical use of these lab-grown cells is years away. But, he says, “The hope is that our work advances precision medicine by giving us the ability to make adult cardiomyocytes from any patient’s own stem cells.” Having that capability, he says, means having a way to test each patient for old and new drug sensitivities and value, and to have a scalable process to create large cell sources for heart regeneration.”

Reference: 1.Gun-Sik Cho, Dong I. Lee, Emmanouil Tampakakis, Sean Murphy, Peter Andersen, Hideki Uosaki, Stephen Chelko, Khalid Chakir, Ingie Hong, Kinya Seo, Huei-Sheng Vincent Chen, Xiongwen Chen, Cristina Basso, Steven R. Houser, Gordon F. Tomaselli, Brian O’Rourke, Daniel P. Judge, David A. Kass, Chulan Kwon. Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy. Cell Reports, 2017; 18 (2): 571 DOI: 10.1016/j.celrep.2016.12.040

lroot on April 25th, 2017

Woman Lifting Dumbbells

A study led by the University of Sydney in Australia has found that gradually increasing muscle strength through activities such as weightlifting improves cognitive function.

The study was conducted in collaboration with the Centre for Healthy Brain Aging at the University of New South Wales and the University of Adelaide.

The results have been published in the Journal of American Geriatrics.

The trial involved a Study of Mental and Resistance Training carried out on patients with mild cognitive impairment between 55-68 years old. Patients with the condition have a higher risk of developing dementia and Alzheimer’s disease.

The findings are particularly significant given the high incidence of dementia and Alzheimer’s disease among the aging population. According to the 2016 World Alzheimer Report, 47 million people worldwide have dementia and this number is expected to triple by 2050.

In the United States, the figure predicted for people with Alzheimer’s disease in 2050 is 13.8 million.

Due to the high cost of care for patients with dementia, the World Alzheimer Report recommends moving beyond specialist care. The report suggests a holistic approach that focuses on improving the quality of life for people living with the condition.

Seen in this context, a link between physical training and improving brain function might be a step in the right direction.

How a disciplined weightlifting schedule can improve cognition

The trial looked at progressive resistance training such as weightlifting and the functioning of the brain.

The study examined 100 older adults living with mild cognitive impairment which refers to older patients who have cognitive difficulties that are noticeable but not significant enough to interfere with their daily activities.

Eighty percent of patients diagnosed with mild cognitive impairment develop Alzheimer’s disease after approximately 6 years.

For the trial, patients with mild cognitive impairment were divided into four groups and assigned a range of activities. These included a combination of resistance exercise including weightlifting and placebo resistance in the form of seated stretching. Activities also included computerized cognitive training and its placebo equivalent.

The cognitive training and placebo activities did not yield cognitive improvements.

However, the study did demonstrate a proportional relation between improvement in brain function and improvement in muscle strength.

Previous studies have shown a positive link between physical exercise and cognitive function, but the trial led by Dr. Mavros provides further information on the type, quality, and frequency of exercise needed to get the full cognitive benefits.

In the trial, participants did weightlifting sessions twice a week for 6 months, working to at least 80 percent of their peak strength. The weights were gradually increased as participants got stronger, all the while maintaining their peak strength at 80 percent.

“The more we can get people doing resistance training like weightlifting, the more likely we are to have a healthier aging population,” says Dr. Mavros. “The key, however, is to make sure you are doing it frequently, at least twice a week, and at a high intensity so that you are maximizing your strength gains. This will give you the maximum benefit for your brain.”

This is also the first time a study has shown a clear causal link between increasing muscle strength and improving brain function in patients over 55 years old who have MCI.

It has been suggested that exercise indirectly helps prevent the onset of Alzheimer’s disease and lowers the risk of cognitive impairment. Exercise helps with physiological processes such as glucoregulation and cardiovascular health. When these are sub-optimal, they increase the risk of cognitive impairment and Alzheimer’s disease.

Exercise also improves other cognitive processes, such as selective attention, planning, organizing, and multitasking.

Some studies have also suggested a connection between an increase in the size of certain brain areas and exercise training.

With age, the hippocampus is known to reduce in size, which leads to cognitive impairment. However, aerobic exercise has shown an increase in the size of the anterior hippocampus by 2 percent, which can improve spatial memory.

Earlier this year, a team of researchers that included Dr. Mavros released a similar test where they noticed cognitive improvement after weightlifting.

Using functional magnetic resonance, they analyzed changes in the brain after 6 months of progressive resistance training and computerized cognitive training in older adults. They found that progressive resistance training such as weightlifting “significantly improved global cognition.”

Authors of this study pointed out that it remains unclear whether physical training in itself stops the degenerative effects of old age, or whether they boost some other mechanisms that support cognition.

Although muscle strength seems to be clearly connected with cognitive impairment, the mechanism behind it is still not entirely evident.

In the future, Mavros and team hope to uncover it by connecting the increases in brain size to muscle strength and cognitive improvement.

lroot on April 17th, 2017

Adult Stem Cells

Wellcome Trust Sanger Institute scientists and their collaborators at the University of Cambridge have created a new technique that simplifies the production of human brain and muscle cells allowing millions of functional cells to be generated in just a few days. The results published in Stem Cell Reports open the door to producing a diversity of new cell types that could not be made before.

Human pluripotent stem cells offer the ability to create any tissue, including those which are typically hard to access, such as brain cells.

In a human, it takes nine to twelve months for a single brain cell to develop fully. To create human brain cells, including grey matter (neurons) and white matter (oligodendrocytes) from an induced pluripotent stem cell, it can take between three and twenty weeks using current methods. However, these methods are complex and time-consuming, often producing a mixed population of cells.

The new platform technology, OPTi-OX, optimises the way of switching on genes in human stem cells. Scientists applied OPTi-OX to the production of millions of nearly identical cells in a matter of days. In addition to the neurons, oligodendrocytes, and muscle cells the scientists created in the study, OPTi-OX holds the possibility of generating any cell type at unprecedented purities, in this short timeframe.

To produce the neurons, oligodendrocytes, and muscle cells, scientists altered the DNA in the stem cells. By switching on carefully selected genes, the team “reprogrammed” the stem cells and created a large and nearly pure population of identical cells. The ability to produce as many cells as desired combined with the speed of the development gives an advantage over other methods. The new method opens the door to drug discovery, and potentially therapeutic applications in which large amounts of cells are needed.

An author of the study, Dr Ludovic Vallier from the Wellcome Trust Sanger Institute said: “What is really exciting is we only needed to change a few ingredients — transcription factors — to produce the exact cells we wanted in less than a week. We over-expressed factors that make stem cells directly convert into the desired cells, thereby bypassing development and shortening the process to just a few days.”

OPTi-OX has applications in various projects, including the possibility to generate new cell types which may be uncovered by the Human Cell Atlas. The ability to produce human cells so quickly means the new method will facilitate more research.

Joint first author, Daniel Ortmann from the University of Cambridge, said: “When we receive a wealth of new information on the discovery of new cells from large scale projects, like the Human Cell Atlas, it means we’ll be able to apply this method to produce any cell type in the body, but in a dish.”

Mark Kotter, lead author and Clinician from the University of Cambridge, said: “Neurons produced in this study are already being used to understand brain development and function. This method opens the doors to producing all sorts of hard-to-access cells and tissues so we can better our understanding of diseases and the response of these tissues to newly developed therapeutics.”

Reference: Matthias Pawlowski, Daniel Ortmann, Alessandro Bertero, Joana M. Tavares, Roger A. Pedersen, Ludovic Vallier, Mark R.N. Kotter. Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes. Stem Cell Reports, 2017; DOI: 10.1016/j.stemcr.2017.02.016