OREGON STATE UNIVERSITY

scientific research and advances

Breakthrough in study of aluminum should yield new technological advances

CORVALLIS, Ore. – Researchers at Oregon State University and the University of Oregon today announced a scientific advance that has eluded researchers for more than 100 years – a platform to study and fully understand the aqueous chemistry of aluminum, one of the world’s most important metals.

The findings, reported in Proceedings of the National Academy of Sciences, should open the door to significant advances in electronics and many other fields, ranging from manufacturing to construction, agriculture and drinking water treatment.

Aluminum, in solution with water, affects the biosphere, hydrosphere, geosphere and anthrosphere, the scientists said in their report. It may be second only to iron in its importance to human civilization. But for a century or more, and despite the multitude of products based on it, there has been no effective way to explore the enormous variety and complexity of compounds that aluminum forms in water.

Now there is.

“This integrated platform to study aqueous aluminum is a major scientific advance,” said Douglas Keszler, a distinguished professor of chemistry in the OSU College of Science, and director of the Center for Sustainable Materials Chemistry.

“Research that can be done with the new platform should have important technological implications,” Keszler said. “Now we can understand aqueous aluminum clusters, see what’s there, how the atomic structure is arranged.”

Chong Fang, an assistant professor of chemistry in the OSU College of Science, called the platform “a powerful new toolset.” It’s a way to synthesize aqueous aluminum clusters in a controlled way; analyze them with new laser techniques; and use computational chemistry to interpret the results. It’s simple and easy to use, and may be expanded to do research on other metal atoms.

“A diverse team of scientists came together to solve an important problem and open new research opportunities,” said Paul Cheong, also an OSU assistant professor of chemistry.

The fundamental importance of aluminum to life and modern civilization helps explain the significance of the advance, researchers say. It’s the most abundant metal in the Earth’s crust, but almost never is found in its natural state. The deposition and migration of aluminum as a mineral ore is controlled by its aqueous chemistry. It’s found in all drinking water and used worldwide for water treatment. Aqueous aluminum plays significant roles in soil chemistry and plant growth.

Aluminum is ubiquitous in cooking, eating utensils, food packaging, construction, and the automotive and aircraft industries. It’s almost 100 percent recyclable, but in commercial use is a fairly modern metal. Before electrolytic processes were developed in the late 1800s to produce it inexpensively, it was once as costly as silver.

Now, aluminum is increasingly important in electronics, particularly as a “green” component that’s cheap, widely available and environmentally benign.

Besides developing the new platform, this study also discovered one behavior for aluminum in water that had not been previously observed. This is a “flat cluster” of one form of aluminum oxide that’s relevant to large scale productions of thin films and nanoparticles, and may find applications in transistors, solar energy cells, corrosion protection, catalytic converters and other uses.

Ultimately, researchers say they expect new technologies, “green” products, lowered equipment costs, and aluminum applications that work better, cost less and have high performance.

The research was made possible, in part, by collaboration between chemists at OSU and the University of Oregon, through the Center for Sustainable Materials Chemistry. This is a collaboration of six research universities, which is sponsored and funded by the National Science Foundation.

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Douglas Keszler, 541-737-6736

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Aluminum in manufacturing

Aluminum manufacturing

Nanotech system, cellular heating may improve treatment of ovarian cancer

The study this story is based on is available online: http://bit.ly/18PLoY4

 

CORVALLIS, Ore. – The combination of heat, chemotherapeutic drugs and an innovative delivery system based on nanotechnology may significantly improve the treatment of ovarian cancer while reducing side effects from toxic drugs, researchers at Oregon State University report in a new study.

The findings, so far done only in a laboratory setting, show that this one-two punch of mild hyperthermia and chemotherapy can kill 95 percent of ovarian cancer cells, and scientists say they expect to improve on those results in continued research.

The work is important, they say, because ovarian cancer – one of the leading causes of cancer-related deaths in women – often develops resistance to chemotherapeutic drugs if it returns after an initial remission. It kills more than 150,000 women around the world every year.

“Ovarian cancer is rarely detected early, and because of that chemotherapy is often needed in addition to surgery,” said Oleh Taratula, an assistant professor in the OSU College of Pharmacy. “It’s essential for the chemotherapy to be as effective as possible the first time it’s used, and we believe this new approach should help with that.”

It’s known that elevated temperatures can help kill cancer cells, but heating just the cancer cells is problematic. The new system incorporates the use of iron oxide nanoparticles that can be coated with a cancer-killing drug and then heated once they are imbedded in the cancer cell.

Other features have also been developed to optimize the new system, in an unusual collaboration between engineers, material science experts and pharmaceutical researchers.

A peptide is used that helps guide the nanoparticle specifically to cancer cells, and the nanoparticle is just the right size – neither too big nor too small – so the immune system will not reject it. A special polyethylene glycol coating further adds to the “stealth” effect of the nanoparticles and keeps them from clumping up. And the interaction between the cancer drug and a polymer on the nanoparticles gets weaker in the acidic environment of cancer cells, aiding release of the drug at the right place.

“The hyperthermia, or heating of cells, is done by subjecting the magnetic nanoparticles to an oscillating, or alternating magnetic field,” said Pallavi Dhagat, an associate professor in the OSU School of Electrical Engineering and Computer Science, and co-author on the study. “The nanoparticles absorb energy from the oscillating field and heat up.”

The result, in laboratory tests with ovarian cancer cells, was that a modest dose of the chemotherapeutic drug, combined with heating the cells to about 104 degrees, killed almost all the cells and was far more effective than either the drug or heat treatment would have been by itself.

Doxorubicin, the cancer drug, by itself at the level used in these experiments would leave about 70 percent of the cancer cells alive. With the new approach, only 5 percent were still viable.

The work was published in the International Journal of Pharmaceutics, as a collaboration of researchers in the OSU College of Pharmacy, College of Engineering, and Ocean NanoTech of Springdale, Ark. It was supported by the Medical Research Foundation of Oregon, the PhRMA Foundation and the OSU College of Pharmacy.

“I’m very excited about this delivery system,” Taratula said. “Cancer is always difficult to treat, and this should allow us to use lower levels of the toxic chemotherapeutic drugs, minimize side effects and the development of drug resistance, and still improve the efficacy of the treatment. We’re not trying to kill the cell with heat, but using it to improve the function of the drug.”

Iron oxide particles had been used before in some medical treatments, researchers said, but not with the complete system developed at OSU. Animal tests, and ultimately human trials, will be necessary before the new system is available for use.

Drug delivery systems such as this may later be applied to other forms of cancer, such as prostate or pancreatic cancer, to help improve the efficacy of chemotherapy in those conditions, Taratula said.

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Cancer treatment

Beyond antibiotics: “PPMOs” offer new approach to bacterial infection

CORVALLIS, Ore. – Researchers at Oregon State University and other institutions today announced the successful use of a new type of antibacterial agent called a PPMO, which appears to function as well or better than an antibiotic, but may be more precise and also solve problems with antibiotic resistance.

In animal studies, one form of PPMO showed significant control of two strains of Acinetobacter, a group of bacteria of global concern that has caused significant mortality among military personnel serving in Middle East combat.

The new PPMOs offer a fundamentally different attack on bacterial infection, researchers say.

They specifically target the underlying genes of a bacterium, whereas conventional antibiotics just disrupt its cellular function and often have broader, unwanted impacts. As they are further developed, PPMOs should offer a completely different and more precise approach to managing bacterial infection, or conceptually almost any disease that has an underlying genetic component.

The findings were published today in the Journal of Infectious Diseases, by researchers from OSU, the University of Texas Southwestern Medical Center, and Sarepta, Inc., a Corvallis, Ore., firm.

“The mechanism that PPMOs use to kill bacteria is revolutionary,” said Bruce Geller, a professor of microbiology in the OSU College of Science and lead author on the study. “They can be synthesized to target almost any gene, and in that way avoid the development of antibiotic resistance and the negative impacts sometimes associated with broad-spectrum antibiotics.

“Molecular medicine,” Geller said, “is the way of the future.”

PPMO stands for a peptide-conjugated phosphorodiamidate morpholino oligomer – a synthetic analog of DNA or RNA that has the ability to silence the expression of specific genes. Compared to conventional antibiotics, which are often found in nature, PPMOs are completely synthesized in the laboratory with a specific genetic target in mind.

In animal laboratory tests against A. baumannii, one of the most dangerous Acinetobacter strains, PPMOs were far more powerful than some conventional antibiotics like ampicillin, and comparable to the strongest antibiotics available today. They were also effective in cases where the bacteria were resistant to antibiotics.

PPMOs have not yet been tested in humans. However, their basic chemical structure, the PMO, has been extensively tested in humans and found safe. Although the addition of the peptide to the PPMO poses an uncertain risk of toxicity, the potency of PPMOs reduces the risk while greatly improving delivery of the PMOs into bacterial cells, Geller said.

Geller said research is being done with Acinetobacter in part because this pathogen has become a huge global problem, and is often spread in hospitals. It can cause respiratory infection, sepsis, and is a special concern to anyone whose immune system is compromised. Wounds in military battle conditions have led to numerous cases in veterans, and A. baumannii is now resistant to many antibiotics. “Urgent new approaches to therapeutics are needed,” the scientists said in their report.

Continued research and eventually human clinical trials will be required before the new compounds are available for health care, the researchers said. This and continued studies have been supported by the National Institutes of Health, the other collaborators and the N.L. Tartar fund.

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Editor’s Note: A scanning electron microscope image of A. baumannii is available online (please provide image credit as indicated at web site): http://bit.ly/GztejR

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Innovative approach could ultimately end deadly disease of sleeping sickness

CORVALLIS, Ore. – A tag team of two bacteria, one of them genetically modified, has a good chance to reduce or even eliminate the deadly disease African trypanosomiasis, or sleeping sickness, researchers at Oregon State University conclude in a recent mathematical modeling study.

African trypanosomiasis, caused by a parasite carried by the tsetse fly, infects 30,000 people in sub-Saharan Africa each year and is almost always fatal without treatment. In a 2008 epidemic, 48,000 people died.

In this research, scientists evaluated the potential for success of a new approach to combat the disease – creating a genetically modified version of the Sodalis bacteria commonly found in the gut of the flies that carry the disease, and using different bacteria called Wolbachia to drive the GMO version of Sodalis into fly populations.

When that’s done, the GMO version of Sodalis would kill the disease-causing trypanosome parasite. According to the analysis published in PLOS Neglected Tropical Diseases, researchers say this should work – and could offer a model system for other tropical, insect-carried diseases of even greater importance, including dengue fever and malaria.

“There are a few ‘ifs’ necessary for this to succeed, but none of them look like an obstacle that could not be overcome,” said Jan Medlock, an assistant professor in the OSU Department of Biomedical Sciences, and lead author on the new report.

“If everything goes right, and we are optimistic that it will, this could be enormously important,” Medlock said. “There’s a potential here to completely solve this disease that has killed many thousands of people, and open new approaches to dealing with even more serious diseases such as malaria.”

Some of the “ifs” include: the transgenic Sodalis has to be reasonably effective at blocking the parasite, at or above a level of about 85 percent; the Wolbachia bacteria, which has some effect on the health of flies affected with it, must not kill too many of them; and the target species of fly has to be a majority of the tsetse flies in the areas being treated.

The research shows that dealing with all of those obstacles should be possible. If so, this might spell the end of a tropical disease that has plagued humans for hundreds, possibly thousands of years. African trypanosomiasis causes serious mental and physical deterioration – including the altered sleep patterns that give the disease its name – and is fatal without treatment. It’s still difficult to treat, and neurologic damage is permanent.

Past efforts to control the disease, including insect traps, insecticide spraying, and use of sterile insects have been of some value, but only in limited areas and the effects were not permanent.

The strength of the new approach, researchers say, is that once the process begins it should spread and be self-sustaining - it should not be necessary to repeatedly take action in the huge geographic areas of Africa. Due to some genetic manipulation, the flies carrying the Wolbachia bacteria should naturally increase their populations and have an inherent survival advantage over conventional tsetse flies.

As the flies carrying transgenic bacteria continue to dominate and their populations spread, trypanosomiasis should fairly rapidly disappear. Whether the mechanism of control could wane in effectiveness over time is an issue that requires further study, scientists said.

Work has begun on the GMO version of Sodalis that has the capability to resist trypanosomes . It’s not yet finalized, Medlock said, but it should be possible, and when complete, the bacteria will be very specific to tsetse flies.

Medlock, an expert in modeling the transmission of various diseases – including human influenza – says the analysis is clear that this approach has significant promise of success. Because of the relatively low infectiousness of the parasite and the ability of Wolbachia to drive the resistance genes, no part of the system has to be 100 percent perfect in order to ultimately achieve near eradication of this disease, he said.

Accomplishing a similar goal with diseases such as malaria may be more difficult, he said, because that disease historically has shown a remarkable ability to mutate and overcome many of the approaches used to attack it. However, at least some near-term gains may be possible, he said.

Collaborators on this study included scientists from the OSU College of Veterinary Medicine and the Yale School of Public Health. It was supported by the National Institutes of Health and the Miriam Weston Trust.

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Tsetse fly

Tsetse fly

California’s new mental health system helps people live independently

CORVALLIS, Ore. – A new analysis by Oregon State University researchers of California’s mental health system finds that comprehensive, community-based mental health programs are helping people with serious mental illness transition to independent living.

Published in the October issue of the American Journal of Public Health, this study has important implications for the way that states finance and deliver mental health programs, and speaks to the effectiveness of well-funded, comprehensive community programs.

In November of 2004, California voters passed the Mental Health Services Act, which allocated more than $3 billion for comprehensive community mental health programs, known as Full Service Partnerships (FSP). While community-based, these programs are different from usual mental health services programs in most states because they provides a more intensive level of care and a broader range of mental health services and supports, such as medication management, crisis intervention, case management and peer support.

It also provides services such as food, housing, respite care and treatment for co-occurring disorders, such as substance abuse.

“We found that these programs promoted independent living in the community among people who had serious mental illness but had not been served or underserved previously,” said Jangho Yoon, an assistant professor of health policy and health economist in OSU’s College of Public Health and Human Sciences and lead author of the study. “Overall, it reduced their chance of living on the street or being incarcerated in jails and prisons.”

The researchers looked at data from 43 of California’s 53 counties, resulting in a sample of 9,208 adults over the course of four years. They found that participants who stayed enrolled in the program continuously, without interruption, were 13.5 percent more likely to successfully transition to independent living.

However, they found that non-white patients were less likely to live independently, and more likely to end up in jail or homeless.

“Although FSPs represent the most well-funded comprehensive community-based programs in the country, they are still community programs and therefore program participation is voluntary,” Yoon said.  “My guess is that minorities may not benefit fully from these programs in their communities possibly due to greater stigma, and less family/social supports. But it needs further investigation.”

Patients with schizophrenia and bipolar disorders were also less likely to benefit from the community programs, because of the nature and severity of their mental health issues.

Yoon is an expert on health management policy, specifically policy around the area of mental health. He said other states haven’t followed California’s lead, in part because of the cost of such extensive programming. Yoon said some of the funding made possible by the federal Patient Protection and Affordable Care Act, which includes $460 million for community mental health services for states to use, may help other states to create similar programs.

“Nobody would disagree that the public mental health system has historically been under-funded in the U.S.,” he said. “The message for other states is clear: investment in well-funded, recovery-oriented, comprehensive community mental health programs clearly improves lives of people with serious mental illness, and may also save money from reduced dependency and incarcerations in this population.”

Tim Bruckner of the University of California, Irvine, and Timothy Brown of the University of California, Berkeley, contributed to this study, which was jointly funded by the California Department of Mental Health and the California Health Care Foundation.

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Jangho Yoon, 541-737-3839

Red grapes, blueberries may enhance immune function

CORVALLIS, Ore. – In an analysis of 446 compounds for their the ability to boost the innate immune system in humans, researchers in the Linus Pauling Institute at Oregon State University discovered just two that stood out from the crowd – the resveratrol found in red grapes and a compound called pterostilbene from blueberries.

Both of these compounds, which are called stilbenoids, worked in synergy with vitamin D and had a significant impact in raising the expression of the human cathelicidin antimicrobial peptide, or CAMP gene, that is involved in immune function.

The findings were made in laboratory cell cultures and do not prove that similar results would occur as a result of dietary intake, the scientists said, but do add more interest to the potential of some foods to improve the immune response.

The research was published today in Molecular Nutrition and Food Research, in studies supported by the National Institutes of Health.

“Out of a study of hundreds of compounds, just these two popped right out,” said Adrian Gombart, an LPI principal investigator and associate professor in the OSU College of Science. “Their synergy with vitamin D to increase CAMP gene expression was significant and intriguing. It’s a pretty interesting interaction.”

Resveratrol has been the subject of dozens of studies for a range of possible benefits, from improving cardiovascular health to fighting cancer and reducing inflammation. This research is the first to show a clear synergy with vitamin D that increased CAMP expression by several times, scientists said.

The CAMP gene itself is also the subject of much study, as it has been shown to play a key role in the “innate” immune system, or the body’s first line of defense and ability to combat bacterial infection. The innate immune response is especially important as many antibiotics increasingly lose their effectiveness.

A strong link has been established between adequate vitamin D levels and the function of the CAMP gene, and the new research suggests that certain other compounds may play a role as well.

Stilbenoids are compounds produced by plants to fight infections, and in human biology appear to affect some of the signaling pathways that allow vitamin D to do its job, researchers said. It appears that combining these compounds with vitamin D has considerably more biological impact than any of them would separately.

Continued research could lead to a better understanding of how diet and nutrition affect immune function, and possibly lead to the development of therapeutically useful natural compounds that could boost the innate immune response, the researchers said in their report.

Despite the interest in compounds such as resveratrol and pterostilbene, their bioavailability remains a question, the researchers said. Some applications that may evolve could be with topical use to improve barrier defense in wounds or infections, they said.

The regulation of the CAMP gene by vitamin D was discovered by Gombart, and researchers are still learning more about how it and other compounds affect immune function. The unique biological pathways involved are found in only two groups of animals – humans and non-human primates. Their importance in the immune response could be one reason those pathways have survived through millions of years of separate evolution of these species.

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Blueberries

Blueberries


Grapes

Red grapes

Gut microbes closely linked to range of health issues

CORVALLIS, Ore. –A new understanding of the essential role of gut microbes in the immune system may hold the key to dealing with some of the more significant health problems facing people in the world today, Oregon State University researchers say in a new analysis.

Problems ranging from autoimmune disease to clinical depression and simple obesity may in fact be linked to immune dysfunction that begins with a “failure to communicate” in the human gut, the scientists say. Health care of the future may include personalized diagnosis of an individual’s “microbiome” to determine what prebiotics or probiotics are needed to provide balance.

Appropriate sanitation such as clean water and sewers are good. But some erroneous lessons in health care may need to be unlearned – leaving behind the fear of dirt, the love of antimicrobial cleansers, and the outdated notion that an antibiotic is always a good idea. We live in a world of “germs” and many of them are good for us.

“Asked about their immune system, most people might think of white blood cells, lymph glands or vaccines,” said Dr. Natalia Shulzhenko, author of a new report in Clinical Reviews in Allergy and Immunology, and assistant professor and physician in the OSU Department of Biomedical Sciences. “They would be surprised that’s not where most of the action is. Our intestines contain more immune cells than the entire rest of our body.

“The human gut plays a huge role in immune function,” Shulzhenko said. “This is little appreciated by people who think its only role is digestion. The combined number of genes in the microbiota genome is 150 times larger than the person in which they reside. They do help us digest food, but they do a lot more than that.”

An emerging theory of disease, Shulzhenko said, is a disruption in the “crosstalk” between the microbes in the human gut and other cells involved in the immune system and metabolic processes.

“In a healthy person, these microbes in the gut stimulate the immune system as needed, and it in turn talks back,” Shulzhenko said. “There’s an increasing disruption of these microbes from modern lifestyle, diet, overuse of antibiotics and other issues. With that disruption, the conversation is breaking down.”

An explosion of research in the field of genomic sequencing is for the first time allowing researchers to understand some of this conversation and appreciate its significance, Shulzhenko said. The results are surprising, with links that lead to a range of diseases, including celiac disease and inflammatory bowel disease. Obesity may be related. And some studies have found relevance to depression, late-onset autism, allergies, asthma and cancer.

In the new review, researchers analyzed how microbe dysfunction can sometimes result in malabsorption and diarrhea, which affects tens of millions of children worldwide and is often not cured merely by better nutrition. In contrast, a high-fat diet may cause the gut microbes to quickly adapt to and prefer these foods, leading to increased lipid absorption and weight gain.

The chronic inflammation linked to most of the diseases that kill people in the developed world today – heart disease, cancer, diabetes – may begin with dysfunctional gut microbiota.

Understanding these processes is a first step to addressing them, Shulzhenko said. Once researchers have a better idea of what constitutes healthy microbiota in the gut, they may be able to personalize therapies to restore that balance. It should also be possible to identify and use new types of probiotics to mitigate the impact of antibiotics, when such drugs are necessary and must be used.

Such approaches are “an exciting target for therapeutic interventions” to treat health problems in the future, the researchers concluded.

The study, supported by OSU, included researchers from both the College of Veterinary Medicine and the College of Pharmacy.

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Dr. Natalia Shulzhenko, 541-737-1051

Viruses associated with coral epidemic of “white plague”

CORVALLIS, Ore. – They call it the “white plague,” and like its black counterpart from the Middle Ages, it conjures up visions of catastrophic death, with a cause that was at first uncertain even as it led to widespread destruction – on marine corals in the Caribbean Sea.

Now one of the possible causes of this growing disease epidemic has been identified – a group of viruses that are known as small, circular, single-strand DNA (or SCSD) viruses. Researchers in the College of Science at Oregon State University say these SCSD viruses are associated with a dramatic increase in the white plague that has erupted in recent decades.

Prior to this, it had been believed that the white plague was caused primarily by bacterial pathogens. Researchers are anxious to learn more about this disease and possible ways to prevent it, because its impact on coral reef health has exploded.

“Twenty years ago you had to look pretty hard to find any occurrences of this disease, and now it’s everywhere,” said Nitzan Soffer, a doctoral student in the Department of Microbiology at OSU and lead author on a new study just published in the International Society for Microbial Ecology. “It moves fast and can wipe out a small coral colony in a few days.

“In recent years the white plague has killed 70-80 percent of some coral reefs,” Soffer said. “There are 20 or more unknown pathogens that affect corals and in the past we’ve too-often overlooked the role of viruses, which sometimes can spread very fast.”

This is one of the first studies to show viral association with a severe disease epidemic, scientists said. It was supported by the National Science Foundation.

Marine wildlife diseases are increasing in prevalence, the researchers pointed out. Reports of non-bleaching coral disease have increased more than 50 times since 1965, and are contributing to declines in coral abundance and cover.

White plague is one of the worst. It causes rapid tissue loss, affects many species of coral, and can cause partial or total colony mortality. Some, but not all types are associated with bacteria. Now it appears that viruses also play a role. Corals with white plague disease have higher viral diversity than their healthy counterparts, the study concluded.

Increasing temperatures that stress corals and make them more vulnerable may be part of the equation, because the disease often appears to be at its worst by the end of summer. Overfishing that allows more algae to grow on corals may help spread pathogens, researchers said, as can pollution caused by sewage outflows in some marine habitats.

Viral infection, by itself, does not necessarily cause major problems, the researchers noted. Many healthy corals are infected with herpes-like viruses that are persistent but not fatal, as in many other vertebrate hosts, including humans.

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Coral with white plague


Marine research

Taking samples

Autistic children with better motor skills more adept at socializing

CORVALLIS, Ore. – In a new study looking at toddlers and preschoolers with autism, researchers found that children with better motor skills were more adept at socializing and communicating.

Published online today in the journal Research in Autism Spectrum Disorders, this study adds to the growing evidence of the important link between autism and motor skill deficits.

Lead author Megan MacDonald is an assistant professor in the College of Public Health and Human Sciences at Oregon State University. She is an expert on the movement skills of children with autism spectrum disorder.

Researchers tested 233 children ages 14 to 49 months diagnosed with autism.

“Even at this early age, we are already seeing motor skills mapping on to their social and communicative skills,” MacDonald said. “Motor skills are embedded in everything we do, and for too long they have been studied separately from social and communication skills in children with autism.”

Developing motor skills is crucial for children and can also help develop better social skills. MacDonald said in one study, 12-year-olds with autism were performing physically at the same level as a 6-year-old.

“So they do have some motor skills, and they kind of sneak through the system,” she said. “But we have to wonder about the social implications of a 12-year-old who is running like a much younger child. So that quality piece is missing, and the motor skill deficit gets bigger as they age.”

In MacDonald’s study, children who tested higher for motor skills were also better at “daily living skills,” such as talking, playing, walking, and requesting things from their parents.

“We can teach motor skills and intervene at young ages,” MacDonald said. “Motor skills and autism have been separated for too long. This gives us another avenue to consider for early interventions.”

MacDonald said some programs run by experts in adaptive physical education focus on both the motor skill development and communicative side. She said because autism spectrum disorder is a disability that impacts social skills so dramatically, the motor skill deficit tends to be pushed aside.

“We don’t quite understand how this link works, but we know it’s there,” she said. “We know that those children can sit up, walk, play and run seem to also have better communication skills.

This study was coauthored by Catherine Lord of Weill Cornell Medical College and Dale Ulrich of the University of Michigan. It was supported by the National Institutes of Health, the Simons Foundation, First Words and Blue Cross Blue Shield Foundation of Michigan.

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Megan MacDonald
Researcher Megan MacDonald practices important motor skills, like throwing a ball, with a child. (photo courtesy of OSU College of Public Health and Human Sciences)

Statins being overprescribed for growing number of kidney disease patients

PORTLAND, Ore. – A new analysis concludes that large numbers of patients in advanced stages of kidney disease are inappropriately being prescribed statins to lower their cholesterol – drugs that offer them no benefit and may increase other health risks such as diabetes, dementia or muscle pain.

The findings, which were published in the American Journal of Cardiovascular Drugs as a review of multiple studies, raise serious questions about the value of cholesterol-lowering therapies in kidney disease.

The issue is important, the researchers say, because the incidence of chronic kidney disease is rising in the United States at what they called “an alarming rate.” Also, kidney disease patients are 23 times more likely to get cardiovascular disease, and for them it’s the leading cause of death.

But for these patients, the frequent decision to prescribe statin drugs to lower cholesterol in order to reduce the risk of cardiovascular disease is not supported by the wider body of research, experts say.

“There is very little benefit to statin drugs for patients in the early stages of kidney disease, and no benefit or possible toxicity for patients in later stages,” said Ali Olyaei, a professor of pharmacotherapy in the College of Pharmacy at Oregon State University, and lead author on the new report.

“I believe the evidence shows that the majority of people with chronic kidney disease are taking statins inappropriately,” Olyaei said. “They may help a little in early-stage disease, but those people are not the ones who generally die from cardiovascular diseases. And by the end stages the risks outweigh any benefit. More drugs are not always better.”

Some of the particular risks posed by statin use, especially at higher doses, include severe muscle pain known as rhabdomyolysis, an increase in dementia and a significant increase in the risk of developing diabetes. The body of research also shows that statins do nothing to slow the progression of kidney disease, contrary to some reports that it might.

The impetus to use statin drugs – some of the most widely prescribed medications in the world to lower cholesterol – is obvious in end-stage kidney disease, because those patients have a mortality rate from coronary heart disease 15 times that of the general population. Unfortunately, evidence shows the drugs do not help prevent mortality in that situation. There is also no proven efficacy of the value of statins in patients using dialysis, researchers said.

If statins are prescribed in early-stage kidney disease, the study concluded that low dosages are more appropriate.

Collaborators on this report, which was supported by OSU, included researchers from the Oregon Health and Science University and the University of Illinois at Chicago.

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Ali Olyaei, 503-494-1308