30 Million to Benefit from Health Reform Law

Premium subsidies, bans on higher premiums and coverage denials based on gender, and required maternity and newborn care coverage among most significant in reducing women's exposure to health costs.

Thirty million women will benefit from the new health reform law over the next decade, either through new or strengthened insurance coverage, according to a new report from The Commonwealth Fund.

In the first analysis of its kind, the authors report that the law will stabilize and reverse the growing exposure to health costs that women now experience by subsidizing health insurance for up to 15 million currently uninsured women, and strengthening existing coverage for 14.5 million women who are considered underinsured - those who have health coverage that does not adequately protect them from high medical expenses.

Provisions important to women will expand eligibility for Medicaid; provide subsidies to purchase insurance; limit out-of-pocket spending; prevent insurers from charging higher premiums or denying coverage based on health status or gender; and require new plans to cover maternity and newborn care. These provisions will also help uninsured women who earn too much to qualify for Medicaid or premium subsidies gain comprehensive coverage.

Although women are just as likely to be uninsured as men, their health care needs leave them more vulnerable to high health care costs and problems related to loss of health insurance. Because insurance carriers consider women, particularly those of reproductive age, higher risk than men, women report greater difficulties gaining coverage in the individual insurance market and are charged much higher premiums for the same benefits than men of the same age. Further, most individual policies do not cover pregnancy.

Another important provision that will help an estimated 100,000 uninsured women gain coverage is the Pre-Existing Condition Insurance Plan (PCIP) to provide temporary coverage to adults with pre-existing conditions who are uninsured during 2010 to 2013. Seventeen states and the District of Columbia began enrollment in PCIPs in July, and 12 will begin to enroll adults in August; in the 21 states without a PCIP the federal government began operation of a PCIP July 1st.

"Historically, women have been more vulnerable to high health care costs and have had greater difficulty paying medical bills because of their lower incomes," said Commonwealth Fund President Karen Davis. "This report provides good news to all women, who will be more likely to get the care they need, with reduced risk of incurring the unaffordable medical bills that have affected so many Americans."

Realizing Health Reform's Potential: Women and the Affordable Care Act of 2010 is the first in a series of Fund reports that will focus on how health reform is expected to impact various populations. It describes when provisions of the new law affecting women take effect, and how many women will be affected by specific provisions. Beginning in 2014, Medicaid coverage expansions and subsidized coverage through state health insurance exchanges could assist 15 million working-age women who currently lack insurance. The majority of these gains come from Medicaid coverage expansions that may affect up to 8 million currently insured women who earn up to $14,000 or are in families with incomes up to $29,000.

Women living in states with higher than average uninsurance rates stand to gain the most from the new law: New Mexico and Texas (29% uninsured in 2008); Florida and Louisiana (24% uninsured); and Alaska, Arizona, Arkansas, California, Georgia, Mississippi, West Virginia, Idaho, Kentucky, Nevada and Oklahoma (at least 20% uninsured).

Although women will have to wait until 2014 to begin to reap the greatest benefits from expanded and improved insurance coverage, several early provisions beginning in 2010 will also provide important support, the study shows. These include:

Strengthened and expanded insurance coverage for young adults, through policies that allow adult children up to age 26 to come on, or stay on, their parents' plans, and bans on pre-existing condition exclusions;

Bans on lifetime benefit limits and phase-out of annual limits;

Bans on rescissions of insurance policies;

Coverage of recommended preventive services without cost-sharing including mammograms;

Eligibility for a new plan that covers uninsured people with pre-existing conditions that currently make it difficult for them to gain coverage; and

Rebates to women enrolled in Medicare who reach the "doughnut hole" in their prescription drug plans; women, along with people with diabetes and Alzheimer's or other forms of dementia are most likely to reach this gap in coverage.

Nearly two in five women - an estimated 7.3 million - between the ages of 19 and 64 who tried to buy individual insurance plans over a three-year period were turned down, charged a higher price or had a pre-existing condition excluded from their plan. Beginning in 2014, all insurers must accept everyone who applies for coverage and cannot charge higher premiums based on health status or gender.

In addition, all health plans sold through new state insurance exchanges in both the individual and small group markets will have to cover maternity and newborn care as part of the federally determined benefit packages described below.

"Women who have an individual insurance market policy that charges them higher premiums than men, who have been unable to secure coverage for the cost of a pregnancy, or who have a preexisting health condition excluded from their benefits will ultimately find themselves on a level playing field with men, with a full range of comprehensive benefits, including maternity coverage," said lead study author Sara Collins, a vice president at the Commonwealth Fund.

Uninsured women who earn too much to qualify for Medicaid will be able to purchase policies through state–run exchanges that will offer federally determined essential benefit plans with four levels of cost-sharing with an annual cap on out-of-pocket costs of $5,950 for individuals and $11,900 for families, beginning in 2014. In addition, women with incomes under 400 percent of poverty, or $88,000 for a family of four, will be eligible for subsidies to offset their premiums and out-of-pocket costs. Up to 7 million currently uninsured women may gain subsidized coverage through the exchanges.

"Today many health plans don't provide a comprehensive set of affordable benefits, forcing women to choose between paying out-of-pocket for necessary service or delaying or skipping care. Better information and benefit plans that are easier to understand, along with subsidies to offset their costs, will make a significant difference for American families," said Collins.

Women who own businesses with fewer than 50 or 100 employees, depending on the state, will also be able to purchase a health plan through the exchanges.

The Commonwealth Fund is a private foundation supporting independent research on a high performance health system.

Western Diet Linked to ADHD

Aging and Longevity Tied To Food Scarcity in Brain

Researchers watched two groups of mice, both nearing the end of a two-day fast. One group was quietly huddled together, but the other group was active and alert. The difference? The second set of mice had been engineered so their brains produced more SIRT1, a protein known to play a role in aging and longevity.

“This result surprised us,” says the study’s senior author Shin-ichiro Imai, MD, PhD, an expert in aging research at Washington University School of Medicine in St. Louis. “It demonstrates that SIRT1 in the brain is tied into a mechanism that allows animals to survive when food is scarce. And this might be involved with the lifespan-increasing effect of low-calorie diets.”

Imai explains that the mice with increased brain SIRT1 have internal mechanisms that make them use energy more efficiently, which helps them move around in search of food even after a long fast. This increased energy-efficiency could help delay aging and extend lifespan.

The research findings are published in the July 28 issue of the Journal of Neuroscience.

Imai’s past research demonstrated that SIRT1 is at the center of a network that connects metabolism and aging. A form of the gene is found in every organism on earth. The gene coordinates metabolic reactions throughout the body and manages the body’s response to nutrition. SIRT1 is activated under low-calorie conditions, which have been shown to extend the life spans of laboratory animals.

The researchers found that the key to the mice’s extra activity lies in a small region of the brain called the hypothalamus, which controls basic life functions such as hunger, body temperature, stress response and sleep-wake cycles.

At the start of the research project, the study’s lead author Akiko Satoh, PhD, a postdoctoral research associate in developmental biology, saw that mice on low-calorie diets had increased amounts of SIRT1 in specific regions of the hypothalamus and that neurons in the same regions were activated.

So the research team developed mice that continually produced higher amounts of SIRT1 in their brains to see what the effect would be. That’s when Satoh observed the mice’s unusual level of activity under fasting conditions.

“This is the first time that it has been demonstrated that SIRT1 is a central mediator for behavior adaptation to low-calorie conditions,” Satoh says.

Interestingly, these mice, called BRASTO (brain-specific SIRT1-overexpressing) mice, also maintained higher body temperatures after a 48-hour fast than ordinary mice, which experience a drop in body temperature during fasting.

“The BRASTO mice have a better capability to come up with energy to achieve a higher body temperature and increased activity level when food is restricted,” says Imai, associate professor of developmental biology and of medicine.

The team also examined mice that had no ability to produce SIRT1 in their brains. During diet-restricting conditions, these mice did not increase their activity, and their body temperature dropped more than normal, giving further evidence that SIRT1 was essential for high-activity, high-temperature responses.

As the researchers looked further into the role of SIRT1 in the hypothalamus, they found that during diet restriction, SIRT1 enhanced the production of a specific neural receptor in the hypothalamus involved in regulating metabolic rate, food intake and insulin sensitivity. Furthermore, mice with increased brain SIRT1 had a higher neural response to the gut hormone, ghrelin, which is known to stimulate the hypothalamus during low-calorie conditions. Both findings add weight to a significant role for SIRT1 in the hypothalamic response to a restricted diet.

The scientists are continuing to study the BRASTO mice to see if they live longer than ordinary mice.

Their work suggests that the brain, and particularly the hypothalamus, might play a dominant role in governing the pace of aging. They believe their studies could eventually provide clues for increasing productive aging in people.

“If we can enhance the function of the human hypothalamus by manipulating SIRT1, we could potentially overcome some health problems associated with aging,” Imai says. “One example is anorexia of aging in which elderly people lose the drive to eat. It is possible that enhancing SIRT1 could alleviate behavioral problems like this.”

Satoh A, Brace CS, Ben-Josef G, West T, Wozniak DF, Holtzman DM, Herzog ED, Imai S. SIRT1 promotes the central adaptive response to diet restriction through activation of the dorsomedial and lateral nuclei of the hypothalamus. Journal of Neuroscience. July 28, 2010.

Funding from the National Institute on Aging, the Ellison Medical Foundation, the Longer Life Foundation and the Japan Society for the Promotion of Science supported this research.

Developing Brain Chooses One Neurotransmitter

Cascades of genetic signals determine which neurotransmitter a brain cell will ultimately use to communicate with other cells. Now a pair of reports from biologists at the University of California, San Diego, have shown for the first time that electrical activity in these developing neurons can alter their chemical fate - and change an animal's behavior - by tweaking this genetic program.

Electrical activity within brain cells early in these tadpoles' development helps determine how many serotonin neurons they will have. Credit: Spitzer lab

"When I was a graduate student we were taught that the transmitters that neurons use were fixed and unchanging. It's now clear that the electrical activity of the nervous system that we use for rapid communication also has the effect of changing the transmitters that neurons make and use," said Nicholas Spitzer, a professor in the Division of Biological Sciences who leads the research group that made the discoveries.

The studies, which looked at two different transmitter systems, will appear in the August issues of the journals Neuron and Nature Neuroscience.

Michaël Demarque, a post-doctoral fellow in Spitzer's lab, looked at the development of neurons in the hindbrain of the African clawed frog Xenopus laevis. By the time embryonic frogs have sprouted a tail bud, some of these neurons have already adopted the neurotransmitter serotonin. Others have adopted different neurotransmitters. Although none of them are connected to other neurons, they generate periodic spikes of positively charged calcium ions within the cell that last for seconds and occur a few times each hour.

By altering the frequency of those electrical signals, Demarque could change the number of neurons that used serotonin.

Dampening the calcium spikes increased the number of neurons expressing a particular gene, Lmx1b, with two subsequent effects. More of the neurons in that part of the brain began to make serotonin, and the behavior of the tadpoles changed as well. When placed in a round dish and poked on the tail, tadpoles with more serotonin neurons swam fewer laps before settling down, Demarque and Spitzer report in Neuron.

"Our work illustrates how the environment in which development takes place could affect the maturation of the nervous system," Demarque said. Changes in serotonin function have been implicated in human disorders such as anxiety, depression and autism, highlighting the importance of understanding the developmental pathways that shape the system, the authors wrote.

Post-doctoral fellow Kurt Marek and graduate student Lisa Kurtz, also in Spitzer's lab, found a similar relationship between electrical activity and specification of neurotransmitter in a different neural system, and they were able to pin down the fine details of the molecular interaction, they report in Nature Neuroscience.

In a different species of African clawed frog, Xenopus tropicalis, they looked at neurons in the embryonic spinal cord at a point in development when the choice is between a neurotransmitter that is excitatory, making the neurons it contacts more likely to fire an electrical impulse, or one that is inhibitory.

They found that electrical activity influences development through a genetic switch called tlx3, which determines whether a cell will use the neurotransmitter glutamate, which is excitatory or GABA, which is inhibitory. They also identified a specific molecule that responds to calcium spikes by controlling the activity of the gene.

"We have a molecular pathway connecting calcium activity to a genetic switch that can completely reverse the polarity of the circuit," Marek said.

Both genetic factors and activity determine which neurotransmitter the mature neuron will use, an interaction that likely allows the brain to assemble circuits appropriate to a variable environment, the authors wrote.

The work was supported by a Damon Runyon Cancer Research Foundation fellowship to Kurt Marek, an NIH fellowship to Lisa Kurtz and NIH Grants to Nicholas Spitzer at the Kavli Institute for Brain and Mind.

Protein That Can Lead To Fragile Bones

Too little of a protein called neogenin results in a smaller skeleton during development and sets the stage for a more fragile bone framework lifelong, Medical College of Georgia researchers report.

A developing mouse with neogenin deficits has poorly defined digits and is generally smaller, including having small growth plates, an indicator of future development, said Dr. Wen-Cheng Xiong, developmental neurobiologist in the MCG Schools of Medicine and Graduate Studies and corresponding author of the study published in Developmental Cell. Dr. Zheng Zhou, MCG assistant research scientist, is first author.

Their findings provide new insight into skeletal development as they point toward a potential new direction for treating osteoarthritis, a common, painful and debilitating condition where cartilage between bones is lost, Xiong said.

Neogenin doesn't make bone; rather, it forms a protein complex essential to turning on cartilage-producing genes, the researchers found.

"Each cell type has a master gene. Neogenin is not that, it's more of a modulator," Xiong said. That's why, if it's mutated, like in the mouse, cartilage and bone formation is disrupted – not halted. It's also why neogenin could be a good therapeutic target for turning the tide on cartilage or bone loss that occurs in osteoarthritis, Xiong said.

Skeletal development occurs early, which is why pregnant women need so much calcium. Initially the skeleton consists of soft bone or cartilage, which attracts blood vessels as well as the osteoblasts that replace most cartilage with hard bone over time. After birth, growth plates, where hard and soft bone meet, enable bones to lengthen and children to grow.

After puberty, growth plates go away and bone hardens except for cartilage at the joints that eases movement and provides cushion. While bone cells continue to turn over, bone growth and loss should balance each other out after puberty due to osteoclasts – cells that break down and resorb bone.

Diseases such as osteoporosis and osteoarthritis occur when osteoclasts start winning. Nutrition, inflammation and hormones are among the many factors that impact bone's status.

Neogenin, which Xiong has shown helps direct neurons during brain development and aid in regulation of iron levels, is found throughout bone and cartilage and numerous other tissues. Its pervasiveness reflects its many functions, depending on the stage of life and location, she noted.

Xiong suspects the protein has multiple roles in adulthood as well, albeit slightly different ones. In adulthood, neogenin may become more of an overseer, keeping tabs on functions it influences, such as bone formation. It resumes an instigator role when something goes amiss.

"Every function in the body needs to be able to go up or down," Xiong said, noting that neogenin pathways are likely altered in disease. "I think in the disease condition this molecule could be changed. The pathways are altered, not eliminated, rather increased or decreased abnormally."

Treating problems such as osteoporosis, iron overload and anemia, would require drugs that could keep protein levels high. Meanwhile, she wants to confirm neogenin's influence on cartilage function in adulthood. "In late-stage arthritis, the cartilage function may be completely disrupted but early in the disease process, maybe there is a window for stimulating this protein."

The research, funded by the National Institutes of Health, is also featured in a preview in Developmental Cell titled, "A Skeleton in the Closet: Neogenin Guides Bone Development."

Pool Disinfectants Can Lead to Health Problems

Splashing around in a swimming pool on a hot summer day may not be as safe as you think. A recent University of Illinois study links the application of disinfectants in recreational pools to previously published adverse health outcomes such as asthma and bladder cancer.

Each year, 339 million visits take place at pools and water parks across the United States. Not only is swimming fun, but it's also the second most popular form of exercise in the country. Because of this, disinfection of recreational pools is critical to prevent outbreaks of infectious disease.

However, Michael Plewa, U of I professor of genetics, said negative outcomes can occur when disinfection byproducts form reactions with organic matter in pool water.

Pool water represents extreme cases of disinfection that differ from the disinfection of drinking water as pools are continuously exposed to disinfectants.

"All sources of water possess organic matter that comes from decaying leaves, microbes and other dead life forms," Plewa said. "In addition to organic matter and disinfectants, pool waters contain sweat, hair, skin, urine, and consumer products such as cosmetics and sunscreens from swimmers."

These consumer products are often nitrogen-rich, causing concern that they may contribute to the generation of nitrogenous disinfection byproducts, Plewa added. When mixed with disinfectants, these products may become chemically modified and converted into more toxic agents.

These disinfection byproducts can mutate genes, induce birth defects, accelerate the aging process, cause respiratory ailments, and even induce cancer after long-term exposures. In this study, collections from public pools and a control sample of tap water were evaluated to identify recreational water conditions that could be harmful to your health.

A systematic mammalian cell genotoxicity analysis was used to compare the water samples. Plewa said this sensitive DNA technology examined genomic damage in mammalian cells, allowing researchers to investigate damage at the level of each nucleus within each cell.

The study compared different disinfection methods and environmental conditions. Results proved that all disinfected pool samples exhibited more genomic DNA damage than the source tap water, Plewa said.

"Care should be taken in selecting disinfectants to treat recreational pool water," Plewa advised. "The data suggest that brominating agents should be avoided as disinfectants of recreational pool water. The best method to treat pool waters is a combination of UV treatment with chlorine as compared to chlorination alone."

Plewa recommends that organic carbon be removed prior to disinfection when the pool water is being recycled.

Also, swimmers can help reduce the genotoxicity of pool water by showering before entering the water. Pool owners should also remind patrons about the potential harm caused by urinating in a pool. These simple steps can greatly reduce the precursors of toxic disinfection byproducts, Plewa said.

This research was published in Environmental Science & Technology and supported by grants from the National Science Foundation. Researchers included Michael Plewa and Elizabeth Wagner of the U of I, Danae Liviac of The Universitat Autonoma de Barcelona, and William Mitch and Matthew Altonji of Yale University. 

Log On, Drop Off - More Weight!

Kaiser Permanente study finds interactive, personalized website helps people maintain weight loss

The more people used an interactive weight management website, the more weight loss they maintained, according to a Kaiser Permanente Center for Health Research study published online today in the open access Journal of Medical Internet Research.

The National Institutes of Health-funded study evaluated an Internet-based weight maintenance intervention involving 348 participants. Consistent website users who logged on and recorded their weight at least once a month for two-and-a-half years maintained the most weight loss, the study found.

"Consistency and accountability are essential in any weight maintenance program. The unique part of this intervention was that it was available on the Internet, whenever and wherever people wanted to use it," said study lead author Kristine L. Funk, MS, RD, a researcher at the Kaiser Permanente Center for Health Research in Portland, Ore.

"This study shows that if people use quality weight management websites consistently, and if they stick with their program, they are more likely to keep their weight off," said study co-author Victor J. Stevens, PhD, co-author and senior investigator at the Kaiser Permanente Center for Health Research. "Keeping weight off is even more difficult than losing it in the first place, so the fact that so many people (in the study) were able to maintain a good portion of their weight loss is very encouraging to us."

This internet-based weight maintenance intervention was part of the Weight Loss Maintenance Trial, one of the largest and longest weight maintenance trials ever conducted—lasting three years and including more than 1,600 people at four study sites across the United States. To enroll in the trial, participants had to be overweight or obese based on their Body Mass Index and taking medication for high blood pressure or high cholesterol. For the first six months, participants tried to lose weight by attending weekly group meetings at which they were weighed, encouraged to keep food diaries, and given extensive information about exercise and healthy eating.

Participants had to lose at least nine pounds to remain in the trial for the weight loss maintenance phase, which lasted an additional two-and-a-half years and included three groups of randomized participants: one with no intervention, one that had monthly contact with a personal health coach, and one that was given unlimited access to a weight-maintenance website created specifically for the trial.

The internet group included 348 participants who were encouraged to log in at least once a week. If they didn't, they received e-mail reminders and follow-up automated phone messages. Once on the website, participants were prompted to record their weight, their minutes of exercise, and the number of days they kept food diaries. If they went longer than seven days without recording a weight, the other parts of the website were disabled until they did record their weight. The website included an interactive bulletin board on which participants could talk with others involved in the study and pose questions to nutrition and exercise experts.

During the first six months of the trial, while they were attending group sessions and before they had access to the website, participants who ended up in the internet group had lost an average of 19 pounds. Once they were given website access, their objective was to keep off as much of that weight as possible. Consistent users who logged in and recorded their weight at least once a month for 24 months maintained the greatest weight loss—keeping off an average of nine of the 19 pounds they'd lost during the initial weight loss phase of the trial. Those who logged on less consistently—at least once a month for 14 months—kept off an average of five pounds. Those who logged on less than that kept off an average of only three pounds of their original weight loss.

At the end of the study, 65 percent of the participants were still logging on to the website. The study authors say they are encouraged by this level of participation because they say it is rare to see that kind of commitment – even in shorter-term weight maintenance studies that use the internet.

While the study website is no longer available, there are many useful weight management websites that people can access. The study authors advise consumers to look for these important elements:

Sites that encourage accountability by asking users to consistently record weight, exercise, and calories consumed
Sites that include tailored or personalized information
Sites with interactive features that allow users to communicate with each other and with nutrition and exercise experts
Sites with accurate health information.

To view a PDF of the study website click here: http://www.kpchr.org/research/public/documents/MultimediaAppendix1.pdf

This study was funded by a grant from the National Health, Lung and Blood Institute, which is part of the National Institutes of Health

UCSF's Gene Therapy Method Allays Parkinson’s Symptoms

A novel technique created at UCSF to deliver a growth factor directly to brain cells has shown promising results in treating Parkinson’s symptoms and could enter human clinical trials as early as next year.

The technique is part of an experimental treatment called gene therapy, which is considered a hopeful medical advance for neurodegenerative diseases such as Parkinson’s. Gene therapy involves introducing genetic material into a cell to cause the expression of a particular protein that can replace a missing or defective protein responsible for disease.

The UCSF team demonstrated for the first time that the infusion system they designed successfully spread a targeted protein to critical regions in the primate brain. This resulted, on average, in a 50 percent improvement of symptoms that continued out to two years.

“The approach is among the first shown to be beneficial to animals after they have already developed signs of Parkinson’s,” said Krystof Bankiewicz, MD, PhD, Kinetics Foundation Chair in Translational Research and professor of Neurological Surgery at UCSF. “Our ultimate goal is to reverse this disease in patients, and we hope this method will enable doctors to do exactly that.”

Findings are published online and in the July 14, 2010, issue of the Journal of Neuroscience.

In addition to an improvement in Parkinson’s symptoms, the treated animals also maintained a higher density of neurons that produce the brain chemical dopamine – the same neurons that disappear in Parkinson’s disease. Live imaging of the brain by positron emission tomography (PET) scanning, which has been used to gauge treatment effects in clinical studies of Parkinson’s, showed that those neurons remained active.

“The scans enabled us to see where the protein went – and just as hoped, it had been taken up by neurons and transported along nerve fibers to where it was needed, the substantia nigra.” Bankiewicz said. Parkinson’s disease attacks the substantia nigra, which is a part of the brain that controls movement.

A clinical trial is planned to test the safety of the method, according to the National Institutes of Neurological Disorders and Stroke, which funded this research. In a workup for the trial, the National Institutes of Health Rapid Access to Interventional Development (NIH RAID) program is supporting additional toxicity studies, as well as the production of clinical grade virus.

Reference: Kells AP et al. “Regeneration of the MPTP-Lesioned Dopaminergic System after Convection-Enhanced Delivery of AAV2-GDNF.” Journal of Neuroscience, Vol. 30 (no. 28), July 14, 2010.)

First Stages of Tissue Production Isolated from human ES Cells

Scientists at the UCLA Broad Stem Cell Research Center have described a population of cells that mark the very first stage of differentiation of human embryonic stem cells as they enter a developmental pathway that leads to the production of blood, heart muscle, blood vessels and bone. 

Researchers hope that these cells could one day be used for clinical treatments for a wide range of medical conditions, as the discovery may help scientists create better and safer tissues for use in regenerative medicine. The finding also will allow scientists to better understand the differences between pluripotent stem cells, which can become every cell in the body, and cells that have lost their pluripotency and are on their way to becoming specific types of tissue cells.
 
The study was published July 20 in the early online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences.
 
"Scientists are very interested in understanding how cells that are pluripotent are directed to become specific tissues," said Dr. Gay Crooks, a UCLA professor of pathology and laboratory medicine and senior author of the study. "We want to know what it is that switches on and off to make a pluripotent cell no longer be pluripotent. In this study, we found a cell population that can help us understand these processes, as it is such a close relative to embryonic stem cells but has lost the ability to be pluripotent."
 
During early development, human embryonic stem cells can follow three distinct developmental pathways to form the primary germ cell layers: the mesoderm, the ectoderm and the endoderm. These three germ cell layers then become all the tissues in the human body. In this study, Crooks and her team studied human embryonic stem cells that followed the mesoderm pathway, which gives rise to blood cells, blood vessels, cardiac cells, muscle, cartilage, bone and fat.
 
Dr. Denis Evseenko, lead investigator on the study and an assistant researcher in the UCLA  Department of Pathology and Laboratory Medicine, placed human embryonic stem cells into culture and, after three or four days, found a small subset of the cells that had lost a key cell-surface marker characteristic of the pluripotent state and had gained a new marker that is a hallmark of mesodermal cells. Because the markers are displayed on the cell surface, Crooks said, specific antibodies can be used to isolate the human embryonic mesodermal progenitors (hEMP cells) from the other cells in culture.
 
"The hEMP cells are the earliest stage of cells that are transitioning from human embryonic stem cells into the cells of the mesoderm," she said. "While these hEMP cells appear to be committed to forming mesoderm, they have not yet determined what type of mesodermal tissue they will become. Because of this, we hope they may serve as a source to produce large numbers of blood, bone or muscle cells, once we learn how to drive them further along the correct pathway."
 
Crooks' research program focuses on making blood stem cells from human embryonic stem cells. Studies have shown that the blood stem cells created from human embryonic stem cells in the lab lack some of the functions possessed by the blood stem cells found in bone marrow or umbilical cord blood. As a result, the blood from embryonic stem cells does not develop into an optimal immune system. Crooks hopes that hEMP cells could be used to create blood stem cells as powerful and potent as those found in bone marrow and cord blood, cells that would be safe to use in humans to treat such diseases as leukemia and sickle cell anemia.
 
The hEMP cells were tested extensively to ensure they had lost the ability to form teratomas, encapsulated tumors with tissue or organ components. The ability to create teratomas is a hallmark of embryonic stem cells.
 
"Researchers agree that it is not a good idea to use pluripotent stem cells in people because of the risk that they might form teratomas," Crooks said. "The hEMP cells we isolated did not have the ability to make teratomas, so they should be a safer choice when thinking about developing therapies for use in humans."
 
Crooks and Evseenko are now studying how to best direct the hEMP cells into all the mesoderm cell lineages, including blood cells, and how to manipulate the cells so they become functional cells as they proliferate and differentiate.
 
The study was funded by the California Institute of Regenerative Medicine and the UCLA Broad Stem Cell Research Center.

Vaccine Reduces Infant Pneumonia and Complications

A pneumococcal conjugate vaccine introduced in the U.S. 10 years ago appears to reduce pneumonia and serious associated complications, such as blood infections, in the vaccine’s target range, children less than a year old, according to new research.

However, pneumonia and associated complications, including a lung infection called empyema, increased in older children, the study found. The results also show a narrowing of racial disparities in the rates of pneumonia and associated severe complications.

The study by researchers at The Children’s Hospital of Philadelphia is called “National Hospitalization Trends for Pediatric Pneumonia and Associated Complications.” It appears in the online version of the journal Pediatrics. The study looked at 619,102 patients younger than 18 years old who were hospitalized for “community-acquired pneumonia” in the years 1997, 2000, 2003 or 2006 and recorded in the national Kids’ Inpatient Database.

“The rate of hospitalizations for pneumonia declined among infants less than 1 year of age. This is the primary target population for pneumococcal vaccination, suggesting that the vaccine may contribute to reductions in infant pneumonia,” said Samir Shah, MD, MSCE, senior author of the study and a pediatric infectious diseases physician at the Children’s Hospital of Philadelphia. “While we aren’t sure why we are seeing higher rates of pneumonia hospitalizations in older children, we think the decrease in infection rates in younger children is due to the vaccine.”

The vaccine, known as PCV7, is administered to infants to prevent infection with the Streptococcus pneumoniae bacteria, the leading bacterial cause of pneumonia. Streptococcus pneumoniae, or pneumococcus, also causes ear infections, sinusitis, blood infections, and meningitis. There are more than 90 types of pneumococcal bacteria and PCV7 protects against seven of the most common strains. A recently licensed pneumococcal vaccine now protects against the 13 most common strains.

Before routine use of pneumococcal conjugate vaccine, infections caused more than 700 cases of meningitis, 13,000 blood infections and about 5 million ear infections each year in the U.S. The infection also contributed to about 200 deaths each year, according to the Centers for Disease Control and Prevention. After PCV7 was licensed, the rate of invasive pneumococcal disease such as meningitis and blood infections decreased by 76 percent among children 5 years and younger, according to the CDC.  “The impact of PCV7 on pneumonia has been more difficult to evaluate,” said Dr. Shah, “because of the specific cause of pneumonia is sometimes difficult to determine.”

The rate of hospitalizations for community-acquired pneumonia in the first year of life declined by 22 percent from 1997 to 2006, according to the study. Conversely, the rate of hospitalizations for pneumonia in children 6 to 12 increased 22 percent, and for children over 13 the rate increased by more than 40 percent. Lung complications related to pneumonia, such as empyema, were highest in children ages 1 to 5 years, the study found.

“This is the first national study to comprehensively examine rates of pneumonia-related complications before and after the introduction of the PCV7 vaccine,” said Grace E. Lee, MD, a lead researcher in the study and pediatric infectious diseases fellow at Children’s Hospital. “Rates of systemic complications such as sepsis and respiratory failure decreased by 9 percent overall and approximately 35 percent for infants less than one year of age. The overall 9 percent decrease in systemic complication rates for the entire population in the study was largely attributable to the decrease in rates for infants and might be explained in part by the fact that infants have been the primary recipient of the vaccine.”

“In contrast, rates of hospitalization for lung complications such as empyema increased by more than 70 percent for children between one and 18 years of age,” said Dr. Lee. The reasons for such increases are not yet known.

The vaccine may also disproportionately benefit black children, shown in past studies to have a higher frequency of pneumococcal infections, including pneumonia. While rates of pneumonia were higher for black children compared to white children in all years of this study, the difference narrowed from a ratio of 1.98 in 1997 to a ratio of 1.59 in 2006.

Additional studies are needed to determine the underlying factors associated with these changes, the study authors noted.

Other authors include Scott A. Lorch, MD, MSCE; Seth Sheffler-Collins, MPH, and Matthew P. Kronman, MD, of Children’s Hospital. The study was funded with support from the Academic Pediatric Association Young Investigator Award, National Institute of Allergy and Infectious Diseases, and the Robert Wood Johnson Foundation.