Researchers report initial success in promising approach to prevent tooth decay



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Analysis: Condition could predict life or death in heart patients

A growing health problem affecting older Americans puts them at higher risk for dying after heart surgery and other interventional procedures, such as heart catheterizations, according to findings published in the current edition of the Journal of the American College of Cardiology and co-authored by two leading University of Kentucky cardiologists.

The study analyzed the results of eight major research trials involving nearly 20,000 patients who underwent interventional heart procedures, such as balloon angioplasty or stent placement. Patients with peripheral arterial disease (PAD), which mainly includes blockages in leg arteries, were found to be more than twice as likely to die within a week after interventional heart procedures compared with patients free of PAD. This doubling in mortality rates persisted at 30-day and later follow-up. At one year following the heart procedure, 5 percent of patients with PAD had died versus 2.1 percent of patients without PAD. However, while nearly half of Americans 65 or older are expected to have the condition by 2050, only a quarter of PAD patients presently receive treatment. Further, patients with PAD undergoing heart interventions were also more at risk for other complications, including blood clots and bleeding requiring a transfusion.

The study was authored by 13 internationally recognized cardiology researchers, including Dr. David J. Moliterno, Gill Heart Institute medical director and professor and chief of cardiovascular medicine in the UK College of Medicine Department of Internal Medicine, and Dr. Steven R. Steinhubl, associate professor and director of cardiovascular education and clinical research at UK.

"Peripheral arterial disease is prevalent in Kentucky and throughout much of the United States, yet it is strikingly under diagnosed and certainly under treated. It is undeniably easy to ask patients if their legs cramp when they walk, and if so to take a blood pressure recording in not only their arms but also their legs. These steps could be life-saving," Moliterno said.

While the study does not indicate that patients with PAD should avoid interventional procedures, it is a strong reminder that extra precaution should be taken when treating these patients.


Bargain or waste of money? Consumers don't always agree

CONTACT: Nancy Gardner nancylou@u.washington.edu 206-543-2580

Once consumers buy an item, it is often difficult for them to get rid of it, even if it makes rational sense to do so. This is even the case if those purchases might include shoes that cause blisters or clothes that no longer fit, said Erica Okada, an assistant professor of marketing at the University of Washington Business School. In their minds, she said, it would be a "waste" of good money to throw a purchased item away, even if the money has already been spent and further use of the item isn't going to bring the money back.

In a study published in this month's Journal of Marketing, Okada found that in markets where there are frequent, successive introductions of new and enhanced products, consumers who have bought an older model have a similarly difficult time upgrading to a new version.

"Consumers don't always seek value in a consistent or rational way as economists assume they do," she said. "For example, in upgrading from a portable MP3 player purchased a few years ago to a newer one with more enhanced capabilities, the consumer wouldn't necessarily have to get rid of the old one, but the old one would presumably no longer be used once a new model is purchased. In effect, the old one would become redundant and be taken out of commission, which would again, be a 'waste' of good money."

According to Okada, it's the psychological cost of upgrading that hinders the purchase of newer models by consumers who have an older model. But for consumers who are first-time buyers, she found there are no psychological barriers preventing them from buying the newest model.

"People keep a mental account of the costs and benefits over time," she said. "As the cumulative enjoyment from consumption increases, the consumer gets his or her money's worth from the purchase. The account is closed once the consumer finishes using the product. If an upgrader purchases an enhanced product, he or she will no longer use the existing product, which triggers the closing of that mental account. There is a psychological cost associated with closing the existing account before consumers have gotten their money's worth out of the existing product."

For the paper, Okada did a number of studies to test her theory, including what consumers would be willing to pay for new cell phones in different situations. She asked 179 cell phone users how much they would pay for a new phone, either as an upgraded model or as a replacement purchase. On average, the users perceived the new phones to be superior to the phones they already owned. In the replacement scenario, participants were asked to imagine they had lost their existing phones. This created a situation in which there would be no existing phone to become obsolete as a result of the new purchase, and would resemble a new purchase because there would be no mental cost. Ninety people were assigned the replacement condition; 89 to the upgrade condition.

People in the replacement purchase group were willing to pay considerably more for the phone than were people who would purchase the phone as an upgrade. That makes sense, said Okada, since people in the replacement condition effectively had no working phone and the new phone's marginal benefit would presumably be greater. Replacement buyers were also willing to pay more for the new phone when they thought the features of their existing phones were made better. However, in the upgrade group people were willing to pay more for a phone with new features than they were for phones offering improved features. For example, a new cell phone with a camera feature would be more appealing than one with improved sound quality to a consumer who already has a phone without a camera.

These findings demonstrate how the decision-making process is different when there is a mental cost vs. when there is not, and they apply to the comparative preferences of upgraders vs. first-time buyers, she said. First-time buyers do not incur any mental cost in purchasing a new model, and upgraders do.

Okada theorizes that marketers can introduce an enhanced product to consumers by adding new features or improving existing features, and because the decision-making is different for those who upgrade vs. first-time buyers there is a difference in the relative preference for the two types of product enhancements. Adding new features would be more attractive to upgraders, and improving existing features would be more attractive to first-time buyers.

"There are intrinsic differences between a consumer who already has a product and is considering an upgrade, and a consumer who is purchasing for the first time," she said. "The existing assumption is that they would be the same, but in actuality the first-time buyer may have more to gain marginally because he or she starts out with nothing and may be less knowledgeable about the product category."


Popular ADHD drug safe and effective for pre-schoolers

Monitor youngsters closely for side effects, researchers caution

A new study by researchers from the Johns Hopkins Children's Center and five other medical centers concludes that carefully measured, low doses of methylphenidate (Ritalin) are safe and effective for attention-deficit and hyperactivity disorder (ADHD) in preschoolers. Investigators warn, however, that 3- to 5-year-olds appear more sensitive to the drug's side effects, which include irritability, insomnia and weight loss, than are older children with ADHD and require closer monitoring.

Children who took the drug also experienced somewhat slower growth rates. On average, children on the drug grew half an inch per year less than expected and gained 2.9 pounds less than expected. Researchers recommend that pediatricians weigh the risks of slowed growth rates against the benefits of treatment. Children on long-term treatment with methylphenidate should be monitored carefully several times a year to assess growth changes over time.

Methylphenidate is the most widely prescribed drug for the treatment of ADHD in children but is not approved by the Food and Drug Administration (FDA) for use in children younger than 6.

Results of the federally funded research, the first large-scale, long-term study of the safety and value of the drug in younger children, appear in a special section of the November issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

"These results give us the missing links in the decision to prescribe a drug that's been widely used off-label in preschool-age children," says Mark Riddle, M.D., director of Child and Adolescent Psychiatry at the Children's Center and a co-author on the study, which followed 303 children between 3 and 5 over 70 weeks. "We were able to confirm what many already suspected-that even lower doses in preschoolers can safely achieve the desired therapeutic effect and indeed that low doses are often optimal."

Children in the study were started on a low-dose regimen of medication ranging from 3.75 mg total daily to 22.5 mg total daily. By comparison, the cumulative daily dose for older children ranges from 15 mg per day to 50 mg per day. The optimal dose needed to reduce symptoms ranged widely in preschool-age children, but on average, 14 mg daily was effective in reining in symptoms.

"One of the surprises was that in some cases, doses as low as even 3 to 4 mg a day were helpful to some preschoolers, which goes to show that lower doses need to be given a chance before higher doses are tried," Riddle explains.

About 11 percent of those enrolled in the study experienced side effects severe enough to drop out. These included weight loss, anxiety, skin picking, mood disturbances and insomnia.

"We want parents to know that trained professionals can make an accurate diagnosis and prescribe helpful and safe treatment in preschoolers with ADHD," Riddle says. "But do expect your prescribing physician to monitor side effects closely and regularly and to tweak the dose if necessary."

ADHD is characterized by a wide range of symptoms, including inability to concentrate, being easily distracted, fidgeting and restlessness, among others. Left untreated, ADHD can interfere with academic progress and social and emotional development. More than 4.4 million children in the United States have ADHD, according to estimates by the Centers for Disease Control and Prevention. About 2 percent of preschool-age children are believed to have ADHD.

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Johns Hopkins Medicine Media Relations and Public Affairs October 23, 2006

Other Hopkins researchers included Elizabeth Kastelic, M.D., Golda Ginsburg, Ph.D., Margaret Schlossberg, Ph.D.., Alexander Scharko, M.D., now at the University of Wisconsin, and Jaswinder Ghuman, M.D., now at the University of Arizona. The study was led by Laurence Greenhill, M.D., of Columbia University and the New York State Psychiatric Institute. Other study sites included Duke University, New York University, the University of California-Los Angeles, and the University of California-Irvine.


Far more than a meteor killed dinos

There's growing evidence that the dinosaurs and most their contemporaries were not wiped out by the famed Chicxulub meteor impact, according to a paleontologist who says multiple meteor impacts, massive volcanism in India, and climate changes culminated in the end of the Cretaceous Period.

The Chicxulub impact may, in fact, have been the lesser and earlier of a series of meteors and volcanic eruptions that pounded life on Earth for more than 500,000 years, say Princeton University paleontologist Gerta Keller and her collaborators Thierry Adatte from the University of Neuchatel, Switzerland, and Zsolt Berner and Doris Stueben from Karlsruhe University in Germany. A final, much larger and still unidentified impact 65.5 million years ago appears to have been the last straw, exterminating two thirds of all species in one of the largest mass extinction events in the history of life. It's that impact – not Chicxulub – which left the famous extraterrestrial iridium layer found in rocks worldwide that marks the impact that finally ended the Age of Reptiles.

"The Chicxulub impact could not have caused the mass extinction," says Princeton University paleontologist Gerta Keller, "because this impact predates the mass extinction and apparently didn't cause any extinctions."

Keller is scheduled to present that evidence at the Annual Meeting of the Geological Society of America in Philadelphia, 22-25 October. The results of her research, which was funded by the National Science Foundation, will be discussed in two technical sessions and a public lecture sponsored by the Philadelphia Geological Survey.

Marine sediments drilled from the Chicxulub crater itself, as well as from a site in Texas along the Brazos River, and from outcrops in northeastern Mexico reveal that Chicxulub hit Earth 300,000 years before the mass extinction. Small marine animal microfossils were left virtually unscathed, says Keller.

"In all these localities we can analyze the marine microfossils in the sediments directly above and below the Chicxulub impact layer and cannot find any significant biotic effect," said Keller. "We cannot attribute any specific extinctions to this impact." No one has ever published this critical survival story before, she said. Keller's research was funded by the National Science Foundation.

The story that seems to be taking shape is that Chicxulub, though violent, actually conspired with the prolonged and gigantic eruptions of the Deccan Flood Basalts in India, as well as with climate change, to nudge species towards the brink. They were then shoved over with a second large impact.

The Deccan volcanism did the nudging by releasing vast amount of greenhouse gases into the atmosphere over a period of more than a million years leading up tothe mass extinction. By the time Chicxulub struck, the oceans were already 3-4 degrees warmer, even at the bottom, she says.

"On land it must have been 7-8 degrees warmer," says Keller. "This greenhouse warming is well documented. The temperature rise was rapid, over about 20,000 years, and it stayed warm for about100,000 years, then cooled back to normal well before the mass extinction."

Marine species at the time suffered from the heat. Most adapted to the stress conditions by dwarfing, growing less than half their normal size and reproducing rapidly with many offspring to increase the chances for survival. The Chicxulub impact coincided with this time. By the time climate cooled back to normal, most tropical species were on the brink of extinction. Then the second large impact hit and pushed them over the brink – many straight to extinction.

As for how the dinosaurs were affected, that's a bit harder to say specifically, since dinosaurs did not leave a lot of fossils behind to tell the tale.

"Dinosaur fossils are few and far between," Keller said. "People love the dinosaurs but we can only really study what happened to them by looking at microfossils because these little critters are everywhere at all times. In just a pinch of sediment we can tell you the age, the prevailing climate, the environment in which it was deposited and what happened. It's remarkable."

What the microfossils are saying is that Chicxulub probably aided the demise of the dinosaurs, but so did Deccan trap volcanism's greenhouse warming effect and finally a second huge impact that finished them off. So where's the crater?

"I wish I knew," said Keller. "There is some evidence that it may have hit in India, where a crater of about 500 kilometers in diameter is estimated and named Shiva by paleontologist Sankar Chatterjee from the Museum of Texas Tech University in Lubbock. The evidence for it, however, is not very compelling at this time."
Mineral discovery explains Mars’ landscape

A Queen’s University researcher has discovered a mineral that could explain the mountainous landscape of Mars, and have implications for NASA’s next mission to the planet.

“Satellites orbiting Mars show us images of canyons and gullies that appear to have been created by a flood or rapid out-washing,” says Ron Peterson, Queen’s geologist. “Exploration rovers, currently moving about on the planet’s surface, also show us that there is no visible water on the surface of Mars, but that there was in the past.”

Dr. Peterson suggests that Mars was likely wetter in the past. All of the images that are coming back from the rovers show layering in the rock which is indicative of sediment manipulated by water. This kind of out-wash would require a fair amount of water on the planet at some point.

The study, published this week in GEOLOGY, a publication of the Geological Society of America, suggests that these findings may provide insight into how to retrieve a sample of Mars' surface and return it to earth.

Dr. Peterson will share his findings with NASA at the Johnson Space Centre in Houston next week to provide insight into designing the next Mars exploration rover and planning its mission.

The discovery was made in Dr. Peterson’s unheated garage using epsomite, also known as Epsom salts. The solution was left to crystallize for several days at temperatures below freezing, which formed crystals that have unusual properties. The crystals were then rapidly melted, which created mould-like channels and gullies – similar to what we see on the surface of Mars.

Martian terrain may have been created in a similar fashion. Dr. Peterson suggests that many years ago, water interacted with rocks on the surface of the planet to create an acidic cocktail, which created layers of material. When the surface layer melted, it created the topography that exploration rovers show us today.

“These findings may help us better understand the surface of Mars,” says Dr. Peterson, expert in geological science and engineering. “These possible new minerals that may be found on Earth help us see that although there are many differences between Earth and Mars, such as atmosphere and gravity, there are many things that are the same – it is another world, but there are certainly similarities.”

PLEASE NOTE: A PDF copy of the study is available upon request. To learn more about Research at Queen's ... Contact: Molly Kehoe, (613) 533-2877, molly.kehoe@queensu.ca Lorinda Peterson, (613) 533-3234, lorinda.peterson@queensu.ca
Cell wall of pneumonia bacteria can cause brain and heart damage

Investigators at St. Jude Children's Research Hospital have discovered in mouse models how cell walls from certain pneumonia-causing bacteria can cause fatal heart damage; researchers have also shown how antibiotic therapy can contribute to this damage by increasing the number of cell wall pieces shed by dying bacteria. The team also demonstrated in a mouse model how to prevent this from happening.

The study shows that pieces of cell walls from Streptococcus pneumoniae bacteria "hijack" a protein on the lining of the blood vessel wall and use it to slip out of the bloodstream and into the brain and heart. A report on this study appears in the November 1 issue of the Journal of Immunology. These findings explain why blood stream infection with S. pneumoniae commonly leads to temporary impairment of heart function, and they suggest a way to prevent that from occurring, according to Elaine Tuomanen, M.D., chair of the St. Jude Department of Infectious Diseases. S. pneumoniae is a leading cause of pneumonia, sepsis (a potentially life-threatening bloodstream infection) and meningitis (inflammation of the membranes surrounding the brain and spinal cord).

The St. Jude team found that pieces of cell wall from S. pneumoniae that escape from the bloodstream enter neurons (brain cells). In a previous report published in the July issue of Infection and Immunity, St. Jude researchers reported that in the mouse model, cell wall fragments damaged neurons in the part of the brain called the hippocampus. Tuomanen is senior author of both reports.

In the current study, the researchers showed how the cell wall fragments escape the bloodstream and enter cells. Specifically, they demonstrated that pieces of the bacterial cell wall bind to the vascular endothelium (inner surface of the blood vessel) by hooking onto a protein called platelet activating factor receptor (PAFr). Platelet activating factor (PAF) is an immune system signaling molecule that activates certain white blood cells. It normally binds to PAFr on the cell lining. The St. Jude team demonstrated that phosphorylcholine, a molecule on the bacteria's cell wall, resembles PAF and exploits this similarity to bind to PAFr.

The researchers demonstrated the role of PAFr by injecting fragments of S. pneumoniae cell wall into normal mice as well as mice that lacked the gene for PAFr (Pafr-/- mice). None of the regular mice survived after eight hours, and cell wall was found in their hearts and brains. However, all of the Pafr-/- mice survived and almost no cell wall was found outside the blood stream. This suggests that PAFr is required for cell walls to escape the bloodstream and enter cardiomyocytes (heart muscle cells) and neurons. Moreover, cell wall fragments lacking phosphorylcholine did not bind to the inner lining of the blood vessels of the animal models, a finding that demonstrates S. pneumoniae cell walls use this molecule to latch onto PAFr.

"S. pneumoniae have learned how to exploit PAFr and use it as a ferry to cross the endothelium of the blood vessels and escape from the bloodstream," Tuomanen said. "From there they enter the cardiomyocytes or neurons in the brain by binding to PAFr on those cells as well."

The investigators used laboratory culture studies to show that while neurons and endothelial cells remained healthy after cell wall uptake, a rapid decline occurred in cardiomyocytes' ability to contract as they do in the heart. The researchers were able to block this effect by first treating the cardiomyocytes with a molecule called CV-6209, which blocked PAFr, preventing the cell wall from binding to it. In fact, mice pretreated for 16 hours with CV-6209 survived, while mice treated after inoculation of cell wall did not.

"Our success in preserving cardiomyocyte function even in the presence of cell wall suggests that it might be possible to safely pre-treat people infected with S. pneumoniae with a drug that blocks PAF before we administer antibiotics," Tuomanen said. "This might protect the heart from the build-up of cell wall fragments released from bacteria killed by the antibiotic."

Tuomanen's team has also developed evidence that explains how the S. pneumoniae cell wall binds to PAFr on the surface of endothelial cells, neurons and cardiomyocytes and triggers a cascade of biochemical signals called the PAFr-beta-arrestin 1 pathway. The St. Jude researchers reported that this pathway is responsible for bacterial uptake into these cells. Furthermore, the researchers succeeded in blocking a key enzyme of this pathway in cardiomyoctyes using a molecule called PLC inhibitor U73122. The treatment prevented the cell from taking up the fragments but did not appear to interfere with the cell's normal functions. This suggests that a drug that blocks the pathway responsible for pulling cell fragments into the cell might not have serious side effects on the cell.

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Other authors of this paper include co-first authors Sophie Fillon, Konstantinos Soulis and Surender Rajasekaran, Heath Benedict-Hamilton, Jana N. Radin, Carlos J. Orihuela, Karim C. El Kasmi, Gopal Murti, Deepak Kaushai and Peter Murray (all of St. Jude); Waleed Gaber (University of Tennessee, Memphis); and Joerg Weber (Charite-Universitaetsmedizin, Berlin, Germany). This work was supported in part by ALSAC.




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