An Ethics Feature in the May-June issue of the Journal of the American Board of Family Medicine describes the lessons learned as the Madras Medical Group transformed itself into a pharma-free clinic.  The small, private clinic of five physicians no longer has contact with detailers – representatives from the pharmaceutical industry who visit physicians to educate them about medications. The clinic also refuses drug samples, gifts and lunches from pharmaceutical companies.

Alice C. Gray

Pharma-free medical practices refuse gifts, lunches, educational programs and samples from pharmaceutical industries.

The corresponding author of the paper, David V. Evans, practiced at the clinic and is now an assistant professor of family medicine at the University of Washington. He and his colleagues at the Oregon State University College of Pharmacy and at University of Oregon Health & Sciences University  examined the clinic’s successful methods to change a culture ingrained in medicine.

“Detailing – selling drugs by educating physicians –  was first reported as a problem in the late 1950’s,” Evans said.  Since then, extensive research indicates that detailing can encourage physicians to prescribe medicines that may not be appropriate, necessary or cost-effective for patients, and that may pose safety concerns.

Academic medical centers, such as medical schools and teaching hospitals,  Evans noted, have critically looked at detailing,  have advocated against it nationally, and have set institutional policies prohibiting or limiting student, resident and faculty contact with detailers .

However, he added, three-fourths of the country’s physicians practice in the community, where interactions between physicians and pharmaceutical representatives are still commonplace.  Although some states have curbed contact between drug reps and physicians, most physicians in small, independent practices have little guidance on how to become pharma-free, the authors of the paper observed.

“Changing this situation is not easy, but with a deliberate and thoughtful approach it can occur,” Evans said.  Although his clinic’s personnel were not unanimous in wanting to go pharma-free, approaching it in smaller steps helped to decrease dissent.

First, those championing a pharma-free clinic quantified the presence of detailers and their marketing strategies.  This data helped convince the physicians and staff that a problem existed.  The staff and physicians then voiced their concerns. These included doing without prescription samples for patients.

The clinic then scheduled sessions for their health professionals to keep current about medications by reviewing rigorous scientific studies. To replace the pharma-sponsored lunches, the clinic held its own regular lunches for their clinicians and staff.  Clinic staff told patients about the change, and news media in the local area informed the nearby public.  The clinic also created a chart comparing average monthly costs of many heavily marketed drugs with first-line, less-expensive or generic drugs, if such alternatives were available.

“Becoming pharma-free at our clinic was not an overnight thing,” said Evans. “Cultural change takes time.  Eventually even the initial dissenters in the clinic came to feel good about the change, and it became a point of pride.”

Now, as a UW medical school faculty member who teaches medical students and residents, Evans, along with colleague Pam Pentin, educate future physicians on effectively managing drug detailers, including how to turn all of them away.

“One of the concerns,” Evans said, “is that medical students and residents may come up through their education without ever having interacted with a drug representative.  It’s important to teach medical students and residents how detailers operate in the real world. At the UW, family medicine residents learn about detailer strategies during their third-year practice management curriculum.  This year’s graduating residents will be the first to have taken the training.”

As of 2009, there was one drug sales representative for every eight physicians.  Despite increased scrutiny and regulation, Evans and his colleagues noted that the percentage of primary care physicians with industrial relationships remains high at 84 percent.  Evans explained that most drug reps are well trained and personable. They use marketing strategies time-tested in the social sciences.

“It’s a sophisticated operation. For example, before they go in to see physicians,” he said, “detailers sit in their cars data-mining on their electronic devices. They find out the physicians’ prescribing patterns from databases in which the patients’ names and other identifying information have been removed. They know how much a doctor has prescribed of drug A, and will either thank the doctor or encourage him or her to prescribe drug B instead.”

Beginning in August 2013, as part of the Affordable Care Act of 2013, a national web site will contain information for patients on the monetary value of what individual physicians accept from pharmaceutical firms.  The Physician Payment Sunshine Act will require manufacturers of drugs, devices and biologics to report all payments to physicians and teaching hospitals to a public web database.

What else can patients do to mitigate undesirable effects of drug marketing?  Evans advises asking their physicians about the issue. He suggests refusing drug samples if they are offered. Patients can also become aware of the effects of drug advertising on their own treatment choices.

The authors of the paper, “Breaking Up is Hard to Do: Lessons Learned from a Pharma-Free Practice Transformation,” wrote that they hope their description of how a clinic changed its practice “contributes to the ongoing discussion of the potential clinical influences and the ethics of the relationship between practicing physicians and pharmaceutical marketing.”

The other authors were Daniel M. Hartung and Denise Beasley of the Department of Pharmacy Practice, Oregon State University College of Pharmacy in Portland. The senior author was Lyle J. Fagnan, a physician in the Oregon Rural Practice-based Research Network in the Department of Family Practice, Oregon Health & Science University School of Medicine.

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The externally peer-reviewed analysis of the clinic transformation received no funding and the researchers declared no conflicts of interest.

Flickr user Eddie~S

Anti-bullying poster on the front door of a Berea, Ohio, school.

The research team analyzed responses collected in a 2010 Washington state survey of more than 24,000 public school students in grades eight through 12. The study found that 14 percent, 11 percent and 9 percent of male students in grades 8, 10, and 12 respectively reported being bullied because of perceived sexual orientation. For female students in those grades, the numbers were 11 percent, 10 percent and 6 percent respectively.

“These findings underscore the need for early prevention efforts before 10^th grade,” wrote the authors.

Being bullied because of perceived sexual orientation was linked to lower quality of life scores and increased the odds of depressed mood or consideration of suicide. Moreover, the size of these associations was greater than being bullied for other reasons

”Youth at this age group are extremely vulnerable to the effects of bullying when they are perceived rightly or wrongly to be gay, lesbian or bisexual. The effects are profound for many youth struggling with issues of identity and self-esteem,” said Patrick, principal investigator of the study.

“Bully-prevention or harm-reduction programs must address bullying because of perceived sexual orientation. All youths are entitled to safe school environments and support is essential for those who are most vulnerable to being bullied because of perceived sexual orientation,” the study concluded.

Read the article in the American Journal of Public Health.

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Getty Images

Illustration of the Bull-leaping Fresco from the Great Palace at Knossos, Crete

DNA analysis is unearthing the origins of the Minoans, who some 5,000 years ago established the first advanced Bronze Age civilization in present-day Crete. The findings suggest they arose from an ancestral Neolithic population that had arrived in the region about 4,000 years earlier.

The British archeologist Sir Arthur Evans in the early 1900’s named the Minoans after a legendary Greek king, Minos. Based on similarities between Minoan artifacts and those from Egypt and Libya, Evans proposed that the Minoan civilization founders migrated into the area from North Africa. Since then, other archaeologists have suggested that the Minoans may have come from other regions, possibly Turkey, the Balkans, or the Middle East.

Now, a team of researchers in the United States and Greece has used mitochondrial DNA analysis of Minoan skeletal remains to determine the likely ancestors of these ancient people.

Mitochondria, the energy powerhouses of cells, contain their own DNA, or genetic code. Because mitochondrial DNA is passed down from mothers to their children via the human egg, it contains information about maternal ancestry.

Getty Images

One of the buildings in Knossos restored by British archeologist Sir Arthur Evans. Knossos was the major civil center of the Minoans.

Results published May 14 in Nature Communications suggest that the Minoan civilization arose from the population already living in Bronze Age Crete. The findings indicate that these people probably were descendents of the first humans to reach Crete about 9,000 years ago, and that they have the greatest genetic similarity with modern European populations.

Read the scientific paper.

Dr. George Stamatoyannopoulos, University of Washington professor of medicine and genome sciences, is the paper’s senior author. He believes that the data highlight the importance of DNA analysis as a tool for understanding human history.

“About 9,000 years ago,” he noted, “there was an extensive migration of Neolithic humans from the regions of Anatolia that today comprise parts of Turkey and the Middle East. At the same time, the first Neolithic inhabitants reached Crete.”

“Our mitochondrial DNA analysis shows that the Minoan’s strongest genetic relationships are with these Neolithic humans, as well as with ancient and modern Europeans,” he explained.

“These results suggest the Minoan civilization arose 5,000 years ago in Crete from an ancestral Neolithic population that had arrived in the region about 4,000 years earlier,” he said. “Our data suggest that the Neolithic population that gave rise to the Minoans also migrated into Europe and gave rise to modern European peoples.”

Stamatoyannopoulos, who directs the UW Markey Molecular Medicine Center and who formerly headed the UW Division of Medical Genetics in the Department of Medicine, added, “Genetic analyses are playing in increasingly important role and predicting and protecting human health. Our study underscores the importance of DNA not only in helping us to have healthier futures, but also to understand our past.”

Stamatoyannopoulos and his research team analyzed samples from 37 skeletons found in a cave in Crete’s Lassithi plateau and compared them with mitochondrial DNA sequences from 135 modern and ancient human populations. The Minoan samples revealed 21 distinct mitochondrial DNA variations, of which six were unique to the Minoans and 15 were shared with modern and ancient populations. None of the Minoans carried mitochondrial DNA variations characteristic of African populations.

Further analysis showed that the Minoans were only distantly related to Egyptian, Libyan, and other North African populations. The Minoan shared the greatest percentage of their mitochondrial DNA variation with European populations, especially those in Northern and Western Europe.

When plotted geographically, shared Minoan mitochondrial DNA variation was lowest in North Africa and increased progressively across the Middle East, Caucasus, Mediterranean islands, Southern Europe, and mainland Europe. The highest percentage of shared Minoan mitochondrial DNA variation was found with Neolithic populations from Southern Europe.

The analysis also showed a high degree of sharing with the current population of the Lassithi plateau and Greece. In fact, the maternal genetic information passed down through many generations of mitochondria is still present in modern-day residents of the Lassithi plateau.

Co-authors of the study are Jeffery R. Hughey of Hartnell College; Peristera Paschou of Democritus University of Thrace; Petros Drineas of the Rensselaer Polytechnic Institute; Manolis Michalodimitrakis of the University of Crete; and Donald Mastropaolo, Dimitra M. Lotakis, Patrick A. Navas, and John A. Stamatoyannopoulos of the University of Washington. The study was partially supported by a grant from the National Institutes of Health (5T32 GM007454), as well as from private funding.

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Expensive, state-of-the-art medical devices and surgeries often are thwarted by the body’s natural response to attack something in the tissue that appears foreign. Now, University of Washington engineers have demonstrated in mice a way to prevent this sort of response. Their findings were published online this week in the journal Nature Biotechnology.

Lei Zhang, UW

These images show differences in collagen build-up in two tissue samples. Collagen is labeled in blue. The left image shows a thick collagen wall forming in the presence of a material that’s widely used for implantable devices. In contrast, collagen in the right image is more evenly dispersed in the tissue after the UW-engineered hydrogel has been implanted.

The UW researchers created a synthetic substance that fully resists the body’s natural attack response to foreign objects. Medical devices such as artificial heart valves, prostheses and breast implants could be coated with this polymer to prevent the body from rejecting an implanted object.

“It has applications for so many different medical implants, because we literally put hundreds of devices into the body,” said Buddy Ratner, co-author and a UW professor of bioengineering and of chemical engineering. “We couldn’t achieve this level of excellence in healing before we had this synthetic hydrogel.”

The body’s biological response to implanted devices – medical technologies that often cost millions to develop – has frustrated experts for years. After an implant, the body usually creates a protein wall around the medical device, cutting it off from the rest of the body. Scientists call this barrier a collagen capsule. Collagen is a protein that’s naturally found in our bodies, particularly in connective tissues such as tendons and ligaments.

If a device such as an artificial valve or an electrode sensor is blocked off from the rest of the body, it usually fails to work. Physicians and scientists have tried to minimize this, but they haven’t been able to eliminate it, Ratner said.

Ratner’s collaborator and co-author Shaoyi Jiang, a UW professor of chemical engineering, and his team implanted the polymer substance into the bodies of mice. The substance is known as a hydrogel, a flexible biomedical material swollen with water. It’s made from a polymer that has both a positive and negative charge, which serves to deflect all proteins from sticking to its surface. Scientists have found that proteins appearing on the surface of a medical implant are the first signs that a larger collagen wall will form.

After three months, Jiang and his team found that collagen was loosely and evenly distributed in the tissue around the polymer, suggesting that the mice bodies didn’t even detect the polymer’s presence.

For humans, the first three weeks after an implant are the most critical, because by then the body will show signs of isolating the implant by building a collagen wall. If this hasn’t happened in the first several weeks, it’s likely the body won’t default to an attack response toward the object.

“Scientists have tried many materials, and with no exception, this is the first non-porous, synthetic substance demonstrating that no collagen capsule forms, which could have positive implications for implantable materials, tissue scaffolds and medical devices,” Jiang said.

UW researchers and others have worked for nearly 20 years to find a way to help the body accept implants. In 1996, the National Science Foundation-funded UW Engineered Biomaterials (UWEB) research center opened at the UW, with Ratner serving as director. Since that time, researchers have been trying to make a material that is invisible to the body’s immune response and could eliminate the body’s negative reaction to medical implants.

Now, nearly two decades years later, engineers have found the “perfect” substance, Ratner said.

“This hydrogel is not just pretty good, it’s exceptional,” he said.

The UW researchers plan to test this in humans, likely by working with manufacturers to coat an implantable device with the polymer, then measure its ability to ward off protein build-up.

The research was funded by the U.S. Office of Naval Research, UWEB and the UW Department of Chemical Engineering.

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For more information, contact Ratner at ratner@uw.edu or 206-685-1005 and Jiang at sjiang@uw.edu. Jiang is traveling this week and is available by email.

Patrick Robinson

Boaters paddle on the Duwamish River while their dog wades in the mudflats.

In February, the Environmental Protection Agency proposed a plan to clean up the Duwamish. The new Health Impact Assessment details changes in health that may result from the cleanup. The report also makes recommendations about how to minimize health impacts, maximize health benefits, and reduce health disparities.

“Our findings demonstrate that EPA’s cleanup plan will significantly impact particular communities,” said Dr. William Daniell, an environmental and occupational epidemiologist and associate professor in the University of Washington School of Public Health.

More than a century of industrial and urban waste has contaminated the river with a mix of 41 toxic chemicals. In 2001, the EPA placed it on the Superfund National Priorities List.  Of the chemicals most concerning to human health, polychlorinated biphenyls, more commonly known as PCBs,  carcinogenic polycyclic aromatic hydrocarbons, arsenic, dioxins and furans top the list. Exposure to these toxins comes from eating resident fish or shellfish and coming into contact with contaminated sediment.

The Health Impact Assessment report was produced by researchers at the UW School of Public Health in collaboration with community health researchers from Just Health Action and the Duwamish River Cleanup Coalition/Technical Advisory Group.

In reference to prior assessments done by the agency, Daniell said: “EPA studies focused on disease outcomes and generally fail to identify and evaluate broader health implications. We hope that they will incorporate our findings and recommendations.”

EPA’s proposed plan will reduce health risks, but it will not succeed in meeting the levels obtained in Puget Sound. Nor will resident seafood be safe to eat for subsistence fishers or for Native American tribal members.

The UW report outlines recommendations to protect the health of the Duwamish, Muckleshoot and Suquamish Tribes, who are affected by the cleanup. In particular, the researchers suggest EPA collaborate with these tribes to address their health concerns and restore their safe access to natural resources and fish.

Sarah Fish

William Daniell, a UW environmental and occupation health epidemiologist, helped develop the report on the health impact of the Duwamish waterway cleanup.

In terms of the impact on local residents, construction-related activities and rail and truck traffic could increase air and noise pollution if not properly managed.  In addition, the cleanup may cause gentrification and displacement of local residents. If done correctly, cleanup may generate new jobs and revitalize the South Park and Georgetown neighborhoods.

“Disadvantaged people who have more life stress, such as poverty, exposure to crime, and less leisure time, are more vulnerable to contamination, which can explain some health disparities” said Linn Gould, executive director of Just Health Action. Gould  was the primary author of the Duwamish Valley Cumulative Health Impacts Analysis. It showed that, compared to King County residents, people who live in the Duwamish Valley have a shorter life expectancy, higher mortality from lung cancer, more hospitalizations for children with asthma, higher rates of diabetes and cardiovascular disease. In addition, more Duwamish Vally residents lack health insurance.

“Residents and other people who use the river have real and valid concerns about how to best protect their health during and after cleanup,” said BJ Cummings, community health projects manager for the Duwamish River Cleanup Coalition/Technical Advisory Group, which serves as EPA’s Community Advisory Group for the Superfund site cleanup.

“This study helps identify ways we can improve the result, especially for those who are most affected,” Cummings said

A final version of the report, with findings and recommendations for mitigation measures, will be provided to the EPA in June.

Support for the health impact assessment was provided by a grant from the Health Impact Project, a collaboration of the Robert Wood Johnson Foundation and The Pew Charitable Trusts.

Read the full report.

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Luc Viatour

All varieties of peppers are in the same botanical family as tobacco. A new study shows that eating peppers may reduce the risk of Parkinson’s disease.

Eating peppers — which are in the same botanical family as tobacco — may reduce the risk of Parkinson’s disease. The findings are reported in the May 9 edition of the Annals of Neurology, a journal of the American Neurological Association and Child Neurology Society.

Nearly one million people in the United States are living with Parkinson’s disease, a neurodegenerative disorder that results from the loss of dopamine-producing brain cells. In early stages, Parkinson’s is characterized by difficulties in controlling movement. Initial symptoms include hand tremors, limb rigidity, and problems walking. As the disease progresses, cognitive problems may develop and advance into dementia.

Dietary sources of nicotine may prove protective.

“Eating peppers twice or more per week was consistently associated with at least 30 percent reduced risk of developing Parkinson’s disease,” said the study’s lead author, Dr. Susan Searles Nielsen, a research scientist in the Department of Environmental and Occupational Health Sciences at the UW School of Public Health.

The investigation of dietary sources of nicotine stems from the puzzling epidemiologic findings that repeatedly show that people who have regularly used tobacco have about half the risk of developing Parkinson’s disease, explained Searles Nielsen. In 2012, she published a study that suggested that second-hand smoke also might reduce risk of the disease.

Sarah Fish

Dr. Susan Searles Nielsen, Department of Environmental and Occupational Health Sciences, researches the effects of dietary nicotine.

“It’s possible that people predisposed to Parkinson’s disease simply don’t respond well to tobacco smoke and therefore avoid it.  However, if tobacco is actually protective, and if the reason is nicotine as some experimental studies suggest,” said Searles Nielsen, “then our hypothesis was that other plants in the Solanaceae family that contain nicotine might also be protective.”

The subjects interviewed for the study included 490 Parkinson’s patients newly diagnosed at the UW Neurology Clinic or Group Health Cooperative between 1992-2008.  The control study subjects were 644 unrelated, neurologically normal people.

While she and the study co-authors investigated the association between Parkinson’s and the subjects’ dietary consumption of a variety of vegetables, including nicotine-containing peppers, tomatoes, and potatoes in the Solanaceae family, peppers showed the greatest protection.  The decreased risk of disease grew stronger with increasing pepper consumption and occurred mainly in people with little or no prior use of tobacco, which contains much more nicotine than the foods studied.

Searles Nielsen cautions that further studies are needed to confirm these findings and explore whether a similar but less toxic chemical shared by peppers and tobacco might be equally or more protective than nicotine.

Study co-authors included Dr. Harvey Checkoway and Dr. Gary Franklin from the UW Department of Environmental and Occupational Health Sciences and Dr. W.T. Longstreth and Dr. Phillip Swanson from the Department of Neurology in the UW School of Medicine.

Funding for the study was provided by the National Institute of Environmental Health Sciences, in part through the UW Superfund Research Program.

Northwestern University

Just as people take roads to gather in cities, some bacteria follow trails to congregate in colonies.

Bacteria may draw other bacteria to a site of infection by laying down trails of a “molecular glue” that lead free-swimming individuals to come together and organize into colonies.

In the study, researchers were looking at how a species of bacteria called Pseudomonas aeruginosa attach and move about on surfaces. P. aeruginosa is a common cause of serious, often difficult-to-treat infections.

One reason they are so difficult to treat is their ability to mass together and surround themselves with matrix of proteins, DNA and polysaccharides, called a biofilm, that protects them from antibiotics and the body’s immune attack.

The study was the result of a collaboration of researchers from the University of California, Los Angeles, the University of Washington in Seattle, and Northwestern University in Evanston, Illinois.

The findings were published May 8 in Nature in a paper titled, “Psl trails guide exploration and microcolony formation in Pseudomonas aeruginosa biofilms.”

Kun Zhao. from the UCLA Department of Bioengineering and Boo Shan Tseng from the UW Department of Microbiology are the paper’s lead authors. The senior authors are Gerald C. L. Wong, professor of bioengineering at the California Nanosystems Institute at UCLA;  Matthew R. Parsek,  UW  professor of microbiology, and Erik Luitjen, at Northwestern University.

In earlier studies, the researchers had noticed that when individual, free-swimming P. aeruginosa attached themselves to glass and began to crawl along the surface they left a trail of a polysaccharide called Psl.

“This was surprising because in the bacterial world this is somewhat unusual,” said Parsek,. “And it looked cool. But the question was whether it was biologically important.”

For this study, the researchers used a specially designed chamber that allowed them to watch how free-swimming P. aeruginosa attached to and moved about on a glass surface. They then used video microscopy to track and analyze the behavior the bacteria.

“Some of the bacteria remained fixed in position,” said Parsek. “But some moved around on the surface, apparently randomly but leaving a trail that influenced the surface behavior of other bacteria that encountered it.”

Once enough of the bacteria had gathered, about 50 or so, their behavior changed: they abandoned their wandering ways and began to organize into small structures called micro-colonies, the first step in biofilm formation.

If there are ways to inhibit the formation of these trails or block their effect, it may be possible to inhibit the formation of biofilms, Parsek said. This might help prevent infections or make them easier to treat.

The researchers are also interested to learn whether other bacterial species also take these polysaccharide trails as a signal to congregate. Pseudomonas infections often involve other bacterial species and this might explain how these polymicrobial infections get started.

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The UW portion of the study was supported by National Institutes of Health grants R01HL087920, R01AI077628, R01AI081983, R56AI061396 and National Science Foundation grant MCB0822405.

Clare McLean

Family physician Dr. Alisa Hideg is checked by a UW Medical Center nurse after receiving her shots in a UW tumor vaccine trial. Hideg was diagnosed with an aggressive form of breast cancer in 2011.

In June 2011 Dr. Alisa Hideg was a 42-year-old mother and family physician in the prime of her career practicing at Group Health in Spokane when she was diagnosed with estrogen and progesterone receptor negative/HER 2 positive breast cancer.

Breast cancer in young, premenopausal women is usually aggressive. So even after chemotherapy, a double mastectomy, and radiation, with her cancer in remission, Hideg wasn’t ready to take it easy. Both the type of breast cancer and the fact that it happened at a young age made her chances of relapse higher. This knowledge led her to experimental trials, and to the UW’s Tumor Vaccine Group.

Hideg found the UW Tumor Vaccine Group on the National Institutes of Health clinical trials website, ClinicalTrials.gov. She had heard about a trial at the University of Pennsylvania’s Perelmen School of Medicine, where the use of gene-transfer therapy converted the patients’ own immune cells into weapons aimed at cancerous tumors. All 12 patients had advanced stage leukemia; nine of the 12 responded positively to the treatment, and two of the first three patients treated have been in remission for two full years.  The Perlelmen results encouraged her to seek out a UW study to see if she qualified.

The UW Tumor Vaccine Group currently offers clinical trials for patients with breast, ovarian or colon cancer. Hideg is in a very desirable trial with very specific criteria, and being approved to participate wasn’t easy. The goal of the clinical trial is to allow the patient to make and keep enough antibodies to quash any future HER-2 expressing breast cancer.

Dr. Nora Disis, UW professor of medicine and principal investigator of the study, explains how the vaccine may work.

“The vaccine is designed to stimulate a particular cell of the immune system, the T cell, to recognize the HER2 protein (that causes cancer),” Disis said. “If effective immunity is generated, the T cell activated by the vaccine should be able to hunt out tumor cells wherever they may be and destroy them.  This particular study is testing the use of an immune stimulator, ampligen, which may be able to activate the T cells more effectively than other agents we have used before.“

Clare McLean

The injection site for the tumor vaccine being tested raises four small dots on Dr. Hideg’s forearm.

Last month, Hideg received a vaccine dose at UW Medical Center. The process is gentle — a series of four small injections that make a little grid of dots on the upper arm — but the body’s response can be angry. Hideg experienced flu-like symptoms after the first visit. The reaction  may actually be a promising sign that her body is responding to the vaccine.

She’s positive and funny in the face of serious medicine. She tweets pictures of her experience to a network of fans and writes about her cancer in Spokane’s daily newspaper, the Spokesman-Review. In addition to being a doctor, patient and full-time mother, Hideg recently went through a series of intense interviews to add “teacher” to her resume. She has become a clinical faculty member to teach second-year UW medical students at the Spokane WWAMI site.  WWAMI is a regionalized medical education program that covers Washington, Wyoming, Alaska, Montana and Idaho.

“Teaching has always been a part of my clinical practice,” Hideg said. “I have taught medical students, residents and others in my clinic since I finished my own training. This experience has reminded me how important teaching can be and how much I enjoy passing on what I have learned as a physician, a parent, and as a patient. Whether the vaccine is effective for me or not, I am grateful for the opportunity to participate in the trial and help move the science forward. I believe in the potential of vaccine therapy for cancer and perhaps for other diseases also and I want a future with more options for my daughter and for others.”

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University of Washington engineers and NanoFacture, a Bellevue, Wash., company, have created a device that can extract human DNA from fluid samples in a simpler, more efficient and environmentally friendly way than conventional methods.

UW/NanoFacture/KNR

Hand-held device for extracting DNA.

The device will give hospitals and research labs a much easier way to separate DNA from human fluid samples, which will help with genome sequencing, disease diagnosis and forensic investigations.

“It’s very complex to extract DNA,” said Jae-Hyun Chung, a UW associate professor of mechanical engineering who led the research. “When you think of the current procedure, the equivalent is like collecting human hairs using a construction crane.”

This technology aims to clear those hurdles. The small, box-shaped kit now is ready for manufacturing, then eventual distribution to hospitals and clinics. NanoFacture, a UW spinout company, signed a contract with Korean manufacturer KNR Systems last month at a ceremony in Olympia, Wash.

The UW, led by Chung, spearheaded the research and invention of the technology, and still manages the intellectual property.

Separating DNA from bodily fluids is a cumbersome process that’s become a bottleneck as scientists make advances in genome sequencing, particularly for disease prevention and treatment. The market for DNA preparation alone is about $3 billion each year.

Conventional methods use a centrifuge to spin and separate DNA molecules or strain them from a fluid sample with a micro-filter, but these processes take 20 to 30 minutes to complete and can require excessive toxic chemicals.

UW engineers designed microscopic probes that dip into a fluid sample – saliva, sputum or blood – and apply an electric field within the liquid. That draws particles to concentrate around the surface of the tiny probe. Larger particles hit the tip and swerve away, but DNA-sized molecules stick to the probe and are trapped on the surface. It takes two or three minutes to separate and purify DNA using this technology.

“This simple process removes all the steps of conventional methods,” Chung said.

The hand-held device can clean four separate human fluid samples at once, but the technology can be scaled up to prepare 96 samples at a time, which is standard for large-scale handling.

UW/NanoFacture/KNR

A close-up view of the portable device.

The tiny probes, called microtips and nanotips, were designed and built at the UW in a micro-fabrication facility where a technician can make up to 1 million tips in a year, which is key in proving that large-scale production is feasible, Chung said.

Engineers in Chung’s lab also have designed a pencil-sized device using the same probe technology that could be sent home with patients or distributed to those serving in the military overseas. Patients could swab their cheeks, collect a saliva sample, then process their DNA on the spot to send back to hospitals and labs for analysis.

This could be useful as efforts ramp up toward sequencing each person’s genome for disease prevention and treatment, Chung said.

The market for this device isn’t developed yet, but Chung’s team will be ready when it is. Meanwhile, the larger device is ready for commercialization, and its creators have started working with distributors.

A UW Center for Commercialization grant of $50,000 seeded initial research in 2008, and since then researchers have received about $2 million in funding from the National Science Foundation and the National Institutes of Health. Sang-gyeun Ahn, a UW assistant professor of industrial design, crafted the prototype.

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For more information, contact Chung at jae71@uw.edu or 206-543-4355.

The new, deadly Human Coronavirus-Erasmus Medical Center was named for the Dutch hospital that identified the virus in a patient specimen.

A new virus that causes severe breathing distress and kidney failure elicits a distinctive airway cell response to allow it to multiply.  Scientists studying the Human Coronavirus-Erasmus Medical Center, which first appeared April 2012 in the Middle East, have discovered helpful details about its stronghold tactics.

Their findings predict that certain currently available compounds might treat the infection.  These could act not by killing the virus directly but by keeping lung cells from being forced to create a hospitable environment for the virus to reproduce.  The researchers caution that their lab and computer predictions would need to be tested to see if the drugs work clinically.

The results appear in the April 30 issue of mBio, the Journal of the American Society for Microbiology. University of Washington virologist Laurence Josset is lead author of the paper, “Cell host-response to infection with novel human coronavirus-Erasmus Medical Center predicts potential antivirals and important differences with SARS-coronavirus.” She conducted the research in the laboratory of senior author Michael G. Katze, UW professor of microbiology noted for pioneering systems biology approaches to host and pathogen interactions.

Eleven of the 17 reported human coronavirus-Erasmus Medical Center cases worldwide were fatal. The virus is named for the Dutch hospital that identified the specimen from a Saudi Arabia patient. So far the illness has not easily passed person to person.  The new disease agent belongs to the betacoronavirus family, as does the severe acute respiratory syndrome virus, SARS.  Both viruses attack the lungs.  The new virus, however, is more closely related to bat coronaviruses than to SARS.  The two viruses latch onto different receptors to infect cells.

Rose Howard

Systems biologist Michael Katze (left) and virologist Laurence Josset are developing rapid computational analyses of host/pathogen interactions to quickly predict possible treatments for emerging infectious diseases.

Josset, Katze and their team learned that, shortly after human coronavirus-Erasmus Medical Center enters lung cells, it, like the SARS virus, induces changes in how the cells’ genes are regulated.  But the newer virus does so sooner.   Later, and throughout infection, the human coronavirus-EMC incites a massive sabotage – much greater than that of the SARS virus – of many genetic controls of protein production in lung cells grown in the laboratory.

“We found that a set of 207 genes in the lung cells was dysregulated early and permanently throughout infection with human coronavirus-EMC,” Josset said.  Various RNA levels were turned up or down.  The new virus appears to specifically hamper the work of several genes that enable the body to sense the presence of viruses.   The scientists believe such gene re-tuning by the virus could significantly lower the ability of lung cells to mount an appropriate antiviral reaction.

While SARS and coronavirus-Erasmus Medical Center activated a few similar lung cell responses for their own benefit, overall, not much overlap occurred.  Each bad actor had its own modus operandi for interfering with lung cell gene activities.

“These differences in host gene-expression responses in the lab-grown lung cells,” the researchers said, “might affect how each virus causes illness in an infected individual.”

At present no proven treatment exists for human coronavirus-Erasmus Medical Center.  Because the virus succeeds in multiplying by hijacking cellular processes initiated in response to infection, the scientists searched for drugs that might target these cellular responses, and in so doing stop the virus from reproducing.  The researchers mentioned that this same approach is already being tested in influenza treatment. Drugs that reduce the body’s excessive inflammatory reaction to the flu virus have therapeutic benefit.

The scientists obtained a rapid, comprehensive assessment of the new coronavirus’s infective strategies by creating a global profile of how it disrupts gene transcription, the process by which DNA is copied into RNA for subsequent translation into proteins.  They analyzed this extensive data with computer programs that predict which current drugs might be re-purposed to correct the body’s virus-co-opted immune response.

The method could have widespread applications in fighting future dangerous viruses.

“Such an approach has the advantage of accelerating treatment availability, which could be crucial in case of an outbreak of an emerging pathogen,” Josset said.

Katze concurred, “Laurence and others in our group are developing new computational approaches to efficiently exploit information about the gene expression profiles induced by existing drugs and small molecules. Our goal is to quickly identify drugs that can modify specific host responses to virus infection.”

In the case of human coronavirus-Erasmus Medical Center, the approach yielded two promising possibilities.  The analysis suggested that the early and sustained changes in lung cell gene regulation could be reverted by four types of kinase inhibitor and one kind of glucocorticoid.  Additional studies are necessary, the researcher said, to determine the safety, effectiveness and required dosages of these drugs in treating human coronavirus-EMC.

What this study highlights, Josset said, is the advantages of fast, automated analysis of the transcriptome (all the messenger RNAs transcribed from the genome) of the infected cells.

“This method globally and efficiently characterizes the host response to emerging pathogens,” Josset said.  Data on the basic properties of a new virus and its interactions with host cells can usually be collected speedily.  It takes, on average, between two weeks to a month after the virus has been identified and isolated.

The gene expression data obtained from the analysis of human coronavirus-Erasmus Medical Center infection, she said, was so robust that it “provides a plethora of data to mine for further understanding and ideas to test about the new virus.”

“Because,” she added, “host response profiles also can be used to quickly identify possible treatment strategies, we anticipate that generating such profiles will become a general strategy for rapid characterization of future emerging viruses.”

Katze noted, “The emergence of new viruses, such as the H7N9 influenza virus in China, will continue to be a threat to public health. Devising new strategies to rapidly identify effective antiviral drugs is a high priority.”

In addition to Josset and Katze, the other researchers on the project were Vineet D. Menachery, Lisa E. Gralinski, Sudhakar Agnihothram, Boyd L. Yount,  Rachel L. Graham,  and Ralph S. Baric, all of the University of North Carolina at Chapel Hill, and Pavel Sova and Victoria S. Carter, both of the UW.

The project was funded in part by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, contract HHSN272200800060C and grant U54AI081680.

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The researchers screened 35 veterans with blast injuries. They found that 42 percent had irregular hormone levels indicative of hypopituitarism, a condition that can often be controlled by replacing the deficient hormones.

“This could be a largely missed opportunity for successful treatment,” said Charles W. Wilkinson, study leader and a UW research associate professor in psychiatry and behavioral sciences.

John McCall/U.S. Marine Corps

Marines assigned to a route clearance platoon destroy IEDs discovered near Sangin, Afghanistan.

He said up to 20 percent of veterans returning from Afghanistan and Iraq have experienced at least one blast concussion. He said many of these veterans have a problem so under-recognized that even military physicians may fail to look for it.

Results from the study, “Prevalence of chronic hypopituitarism after blast concussion” by Wilkinson, Elizabeth A. Colasurdo, Kathleen F. Pagulayan, Jane B. Shofer, and Elaine R. Peskind, were presented at the Experimental Biology 2013 Meeting April 22 in Boston. The results were published in Frontiers in Neurotrauma last year, but the presentation included new data as well and the results be published again.

Wilkinson said studies in the past few years have suggested that 25 to 50 percent of people who suffer traumatic brain injuries later have low pituitary hormone levels — a decrease in the concentrations of at least one of eight hormones produced by the pituitary, a gland beneath the base of the brain.

Wilkinson said these studies focused on head injuries that civilians are more likely to receive, such as an automobile accident. He and his team decided to investigate whether veterans returning from Afghanistan and Iraq who suffer blast injuries show a similar frequency of hypopituitarism.

They collected blood samples from 35 veterans diagnosed with a blast concussion about a year prior — enough time for hormone changes to become evident. They then did a screen to compare blood concentrations of the eight hormones produced by the pituitary with the documented normal levels of these hormones.

The researchers found that about 42 percent of these veterans showed abnormally low levels of at least one of these hormones. The most common low hormone was human growth hormone, which can cause behavioral and cognitive symptoms similar to PTSD and depression. Low levels can also cause increases in blood lipids and changes in metabolism and blood pressure that can raise the risk of heart attack and stroke. The second most common problem was hypogonadism, changes in sexual hormones that can affect body composition and sexual function.

The tiny, pendulous gland shown in blue is the pituitary.

The researchers saw that some veterans had abnormal levels of vasopressin and oxytocin. Low levels of these hormones make it harder for people to bond with others and are linked to other mental health issues. Problems with these hormone levels, in addition to growth hormone, could contribute to difficulties with personal relationships, Wilkinson said.

He said the prevalence of hypopituitarism in the general population is estimated at 0.03 percent, a value far lower than that found in veterans with blast concussions. Therefore, more research is needed into victims of blast concussions.

“We’re screening hormone levels, not diagnosing definite disorders in this study,” he said. “These individuals would still need a clinical evaluation.” But, he said, if even 10 percent of these veterans have hypopituitarism, it’s a problem that physicians should be aware of.

The Departments of Defense and Veterans Affairs supported the study.

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Wash. Labor & Industries

The brass bell in the Workers Memorial Garden on the grounds of the Washington State Labor and Industries offices.

The Workers Memorial Day ceremony is being organized by the UW Department of Environmental and Occupational Health in the School of Public Health, UW Environmental Health and Safety, UW students, local union leaders, and the Harry Bridges Center for Labor Studies. The organizers are active in raising awareness and strengthening commitment to job safety and healthy work environments for Washington workers.

The Occupational Safety and Health Act of 1970 was signed into federal law to protect employees from workplace hazards. Yet, according to the event organizers, more effort is needed to keep American workers safe from preventable, job-related injuries, disease and death.

Workers Memorial Day recognizes fallen workers and calls attention to workplace safety issues

They note that in 2010, nationwide 4,547 workers were killed on the job, and another 5,000 lost their lives to occupation diseases.  For that same year, the Bureau of Labor Statistics estimates 3.1 million job injuries and illnesses among private-sector employees and 820,000 injuries and illnesses among public employees. The organizers added that, due to underreporting, these numbers might understate the problem.

Ten of those whose lives will be remembered April 24 were from King County, Wash. Among them were firefighters, home-care aides, laborers, longshoremen, park rangers, sales clerks, and taxi drivers. The names of the fallen workers will be read during the UW ceremony.

Nationally and internationally Workers Memorial Day is commemorated April 28, with events also held in the days leading up to the official date.  It was started by the Canadian Union of Public Employees in 1984, and recognized in the United States beginning in 1989.

The program for the April 24 UW ceremony:

Presentation of Colors
University of Washington Air Force ROTC Honor Guard
Karl Zapf, Bagpiper
Seattle Firefighters Pipes and Drums

Master of Ceremonies
David Freiboth, executive secretary, King County Labor Council

Keynote Address
The Importance of Workers’ Rights and Safety: A Call to Action
Michael Honey, professor of ethnic gender and labor studies, UW Tacoma

Memorial Recognition
Karen Hart, President SEIU 925
Our Fallen Workers – 2012
Names read by UW students, staff, and faculty, and community members
Our Fallen Workers Serving in the Armed Services – 2012
Names read by Cadet Justin Rees

A Message from Sen. Patty Murray

Moving Forward
Jeff Johnson, president, Washington State Labor Council
Marty Cohen, UW Field Research and Consultation Group
Megan Karalua, UAW Local 4121
Emily Garverick, UW United Students Against Sweatshops
Dow Constantine, King County Executive

Closing
Music by Michael Laslett and Mike Honey

]]> http://www.washington.edu/news/2013/04/23/workers-memorial-day-event-takes-place-april-24-at-hub-lyceum/feed/ 0 http://www.washington.edu/news/2013/04/15/high-glucose-levels-could-impair-ferroelectricity-in-bodys-connective-tissues/?utm_source=rss&utm_medium=rss&utm_campaign=high-glucose-levels-could-impair-ferroelectricity-in-bodys-connective-tissues http://www.washington.edu/news/2013/04/15/high-glucose-levels-could-impair-ferroelectricity-in-bodys-connective-tissues/#comments Mon, 15 Apr 2013 15:51:32 +0000 Michelle Ma http://www.washington.edu/news/?p=24161 High sugar levels in the body come at a cost to health. New research suggests that more sugar in the body could damage the elastic proteins that help us breathe and pump blood. The findings could have health implications for diabetics, who have high blood-glucose levels.

Researchers at the University of Washington and Boston University led by Jiangyu Li and Yanhang Zhang have discovered that a certain type of protein found in organs that repeatedly stretch and retract – such as the heart and lungs – is the source for a favorable electrical property that could help build and support healthy connective tissues. But when exposed to sugar, some of the proteins no longer could perform their function, according to findings published online April 15 in the journal Physical Review Letters.

Jiangyu Li, UW

The blue spots in this image show where glucose has halted ferroelectric switching in an elastin protein.

The property, called ferroelectricity, is a response to an electric field in which a molecule switches from having a positive to a negative charge. Only recently discovered in animal tissues, researchers have traced this property to elastin and found that when exposed to sugar, the elastin protein sometimes slows or stops its ferroelectric switching. This could lead to the hardening of those tissues and, ultimately, degrade an artery or ligament.

“This finding is important because it tells us the origin of the ferroelectric switching phenomenon and also suggests it’s not an isolated occurrence in one type of tissue as we thought,” said co-corresponding author Li, a UW associate professor of mechanical engineering. “This could be associated with aging and diabetes, which I think gives more importance to the phenomenon.”

About a year ago, Li and collaborators discovered ferroelectric switching in mammalian tissues, a surprising first for the field. Ferroelectricity is common in synthetic materials and is used for displays, memory storage and sensors. Li’s research team found that the wall of a pig’s aorta, the largest blood vessel carrying blood to the heart, exhibits ferroelectric switching properties.

Li said that discovery left researchers with a lot of questions, including whether this property is found in other soft tissues and the health implications of its presence. Observing differences in ferroelectric behavior at the protein level has helped to answer some of those questions.

The research team separated the aortic tissue into two types of proteins, collagen and elastin. Fibrous collagen is widespread in biological tissues, while elastin has only been found in animals with a backbone. Elastin, as its name suggests, is springy and helps the heart and lungs stretch and contract. Ferroelectric switching gives elastin the flexibility needed to perform repeated pulses as with an artery.

When researchers treated the elastin with sugar, they found that glucose suppressed ferroelectric switching by up to 50 percent. This interaction between sugar and protein mimics a natural process called glycation, in which sugar molecules attach to proteins, degrading their structure and function. Glycation happens naturally when we age and is associated with a number of diseases such as diabetes, high blood pressure and arteriosclerosis, a thickening and hardening of the arteries.

The research team has focused solely on the aortic tissues, but this finding likely applies to other biological tissues that have the protein elastin, such as the lungs and skin.

“I would expect the same phenomena will be observed in those tissues and organs as well,” Li said. “It will be more common than what we originally thought.”

Researchers next will drill down even more to look at the molecular mechanics of ferroelectric switching and further try to connect the process with disease onset.

Co-authors are Yuanming Liu, Nataly Q. Chen and Feiyue Ma at the UW, and Zhang, Yunjie Wang and Ming-Jay Chow at Boston University.

The research was funded by the National Science Foundation, the National Institutes of Health, the UW and a NASA Space Technology Research Fellowship.

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For more information, contact Li at 206-543-6226 or jjli@uw.edu.

A new procedure that thickens and thins fluid at the micron level could save consumers and manufacturers money, particularly for soap products that depend on certain molecules to effectively deal with grease and dirt. Researchers at the University of Washington published their findings online April 9 in the Proceedings of the National Academy of Sciences.

Read the back of most shampoos and dishwashing detergents and you’ll find the word “surfactant” in the list of active ingredients. Surfactant molecules are tiny, yet they are the reason dish soap can attack an oily spot and shampoo can rid the scalp of grease.

Surfactant molecules are made up of two main parts, a head and a tail. Heads are attracted to water, while the tails are oil-soluble. This unique structure helps them break down and penetrate grease and oil while immersed in water. It also makes the soaps, shampoos and detergents thicker, or more viscous.

Environmental Molecular Sciences Laboratory and UW

A web-like, gel structure is formed after fluid passes through the flow device. The unit of measurement is 1 micron.

Soap manufacturers add organic and synthetic surfactants – and often a slew of other ingredients – to their products to achieve a desired thickness and to help remove grease and dirt. These extra ingredients add volume to the soap products, which then cost more to manufacture, package and ship, ultimately shifting more costs to consumers, said Amy Shen, a UW associate professor of mechanical engineering and lead author of the paper.

The research team’s design could create the same thickening results without having to add extra ingredients.

“Our flow procedure can potentially help companies and consumers save a lot of money,” Shen said. “This way, companies don’t have to add too many surfactants to their products.”

Researchers found that when they manipulated the flow of a liquid through microscopic channels, the resulting substance became thicker. Now, scientists add a lot of salt, or alter the temperature and level of acidity to induce this change, but these methods can be expensive and more toxic, Shen said.

The team built a palm-sized tool called a microfluidics device that lets researchers pump water mixed with a little detergent and salt through a series of vertical posts. The distance between posts is about one-tenth the size of a single human hair. That micron-sized gap squeezes the liquid as it flows, causing it to quickly deform. The end result is a gel-like substance that’s more viscous and elastic.

University of Washington

A diagram showing how the microfluidics device works. Water mixed with salt and soap is injected into a spout (left back). The fluid travels through a series of posts (see enlarged segment) that cause the fluid to thicken.

When researchers looked at high-resolution images of the end product, they saw a series of wormlike rods attaching and intermingling with each other, creating an entangled web. This structure stayed intact after the procedure was complete, which suggests this process can create a permanent, scaffold-like network that could prove useful for biological applications, Shen said. She is collaborating with other UW researchers to try to create stable structures that could house enzymes and other biomarkers for detecting certain diseases.

Shen and her team also discovered that when they pumped a thicker, more elastic fluid through the device, the opposite effect happened – the gel became thinner and more porous. This could be useful in biomedical applications, Shen said, though it hasn’t yet been tested. In theory, a semi-solid gel could be injected into veins, then transform into a thinner liquid, delivering drugs throughout the body.

Researchers hope one eventual outcome will be a scaled-up industrial design of their microfluidics device that could help manufacturers churn out soap products that aren’t filled with an excess of added materials. Shen has presented her initial findings at Procter & Gamble Co.

“What we can provide are all of the important parameters for operating conditions so companies can have an industrial design to achieve their goals,” Shen said.

Research collaborators are Joshua Cardiel and Ya Zhao, UW doctoral students in mechanical engineering; Alice Dohnalkova, senior research scientist at Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory in Richland, Wash.; and Neville Dubash and Perry Cheung, former post-doctoral researchers in mechanical engineering.

The research was funded by the National Science Foundation.

###

For more information, contact Shen at amyshen@uw.edu or 206-708-3411.

Clare McLean

Airlift Northwest flight nurses and pilots disembark a patient from a turboprop at the Seattle base.

Beginning May 1, Airlift Northwest will station a Turbo Commander aircraft in Juneau to allow the medical transport service to reach more people living in outlying rural communities in Southeast Alaska.

Airlift has served Southeast Alaska for over 30 years transporting critically ill or injured patients to specialty care in Anchorage or Seattle, and will continue this service. Airlift currently operates a Learjet, which has limitations landing in smaller communities due to shorter airport runways.

The Turbo Commander is better suited to land on shorter runways allowing improved access to the smaller community airports based in Gustavas, Haines, Hoonah, Kake, Prince of Wales Island and Skagway.

“Airlift Northwest is dedicated to saving lives by providing pre-hospital emergency treatment on the ground and in the air,” said Chris Martin, executive director. “In response to requests for improved access to medical transport from providers in Southeast Alaska, we are pleased to offer this new service.”

“The turboprop will allow us to access patients who, in the past, have had to make their way to an area where we could get them in the Learjet. Now we won’t see that delay,” said Dr. Richard Utarnachitt, medical director for Airlift.

Patient care will be provided by two critical care nurses with current certifications in advanced skills for cardiac life support, pediatric life support, neonatal resuscitation and trauma care.

Airlift Northwest, an entity of UW Medicine, provides medical transport to critically ill and injured adults and children throughout the Pacific Northwest and beyond. It operates six bases in Washington and Alaska.

Airlift also announced recently that it will permanently base a Turbo Commander aircraft in Yakima to provide communities in Central Washington with improved access to urgent medical transport. Communities served by the Yakima-based crew include Wenatchee, Ellensburg, Omak, Moses Lake, the Tri-Cities, Sunnyside, Toppenish and other Central Washington locations.

Francisco Jose Roca Soler

Exuberant mycobacterial growth showing chains of fluorescent microbes in an infected zebrafish larva which had an excess of tumor necrosis factor.

Tumor necrosis factor – normally an infection-fighting substance produced by the body – can actually heighten susceptibility to tuberculosis if its levels are too high.

University of Washington TB researchers unravel this conundrum in a report this week in Cell.

Their study shows how excess production of this disease-cell destroyer at first acts as a TB germ killer. But later the opposite occurs: too much tumor necrosis factor encourages TB pathogens to multiply in the body.

In addition to figuring out some reasons behind this back-pedaling, the scientists learned that certain combinations of drugs already available for other conditions can curtail the shift from anti-TB to pro-TB.

The drug combination revealed in this study, the authors noted, “has the potential to revert some cases of hypersusceptibility to hyperresistance.”

The scientists were Francisco Jose Roca Soler, of the UW Department of Microbiology, and Lalita Ramakrishnan, UW professor of microbiology, medicine and immunology. A recipient of the National Institutes of Health Director’s Pioneer Award, Ramakrishnan is recognized for her work on how the TB pathogen and its hosts’ cells interact to cause disease.

These studies are conducted in zebrafish, an animal model for tuberculosis. The fish’s embryos and small fry are transparent. Researchers can see through their skin to observe their organs, tissues and cells and the internal appearance of some infections, for example, the bacterial cording of TB.

Roca and Ramakrishnan explained that TB had traditionally been thought of as a disease of failed immunity. However, more recent studies from their lab and other labs, both in zebrafish and in humans, have suggested that it also can result from too strong of a defensive inflammatory response.

“While tumor necrosis factor is a critical host defense against tuberculosis,” Roca and Ramakrishnan noted, “an excess of this factor is also implicated in the development of the disease in zebrafish and in humans.”

Variations in a specific location of the zebrafish genome can cause either too much or too little tumor necrosis factor to be produced, depending on the type of variation. In either case, deficiency or overabundance, zebrafish become prone to tuberculosis.

In both cases the scavenger cells, or macrophages, that are trying to clear away the TB pathogens by ingesting them, die and burst open. They are like torn vacuum cleaner bags spilling their dirty contents.

When the TB bacteria escape the confines of the scavenger cells, “they grow exuberantly in the extracellular environment,” Roca and Ramakrishnan said.

Researchers needed to work out the differences between TB susceptibility caused by too high or too low tumor necrosis factors because the distinction is vital to treatment decisions. Only patients whose genetics made them launch a pro-inflammatory response, benefited from steroid treatment, previous studies have shown. Steroids can increase the chance of death among TB patients with a weak inflammatory response.

In the present study, Roca and Ramakrishnan elucidated the molecular pathways by which too much tumor necrosis factor at first rapidly promotes macrophages to go after TB bacteria, and then turns around and forces the hard-working macrophages to die and expel their captives.

They found that both the microbiocidal activity, and the death of the macrophages, resulted from upping the production of reactive oxygen species by the mitochondria inside the macrophages. Mitochondria are the energy-generating power plants of living cells.

Tumor necrosis factor inside of infected macrophages induces reactive oxygen species from the mitochondria. These are the chemicals responsible for cell damage from oxidative stress.

Early on, reactive oxygen species can be beneficial. Initially their presence encourages the macrophages to destroy pathogens. As they accumulate, however, they promote self-harm.

Suddenly the macrophage is programmed to self-destruct. The reactive oxygen species carry out the death sentence by modulating a pathway for a substance called cyclophilin D, which sets the stage for the demolition of mitochondria.

Reactive oxygen species also play a role in acid sphingomyelinase-mediated ceramide production. This waxy substance occurs in cell membranes. One of its many roles is regulating signals for cell death.

The researchers were able to convert the high tumor necrosis factor state to become resistant to tuberculosis. They did so by genetically blockading both cyclophilin D and acid sphingomyelinase in previously susceptible zebrafish.

Similarly, they discovered that the drug combination of alisporivir, a cyclophilin D-inhibiting drug, and desipramine, an antidepressant that inactivates acid sphingomyelinase, also reverses susceptibility to TB in zebrafish prone to tumor necrosis factor excess.

Essentially, the experiments suggest that preventing cell death in TB infected macrophages can prolong their capacity to attack TB pathogens.

A longer-living army of macrophages, filled with the microbiocidal reactive oxygen species, will destroy the TB pathogens inside them and make the host highly resistant to tuberculosis.

Because excessive amounts of tumor necrosis factor are implicated in several inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, sarcoidosis, and Crohn’s, the authors noted, “The findings may be useful for understanding diseases in addition to tuberculosis.”

Grants from the National Institutes of Health and the Northwest Research Center of Excellence for Biodefense and Emerging Diseases, and a postdoctoral fellowship from the educational ministry of Spain, funded this research project.

The Cell paper is titled, “Tumor necrosis factor dually mediates resistance and susceptibility to mycobacteria through induction of mitochondrial reactive oxygen species.”

Dean Forbes

Brain surgeon and cancer researcher Eric Holland has been recruited to UW Medicine and Fred Hutchinson Cancer Research Institute. He will arrive this summer.

UW Medicine and the Fred Hutchinson Cancer Research Center have recruited world renowned neurosurgeon and brain cancer researcher Eric Holland to establish world-class research programs on brain and other solid-tumor cancers. He will leave Memorial Sloan-Kettering Cancer Center in New York City and arrive in Seattle this summer.

At UW Medicine, Holland will be a professor of neurological surgery, hold the Chap and Eve Alvord and Elias Alvord Chair in Neuro-oncology, and direct the Nancy and Buster Alvord Brain Tumor Center, established in 2009 to promote, develop and coordinate interdisciplinary brain tumor care and research among physicians and scientists in a variety of fields.

One of Holland’s priorities will be to recruit a team of internationally recognized brain cancer investigators to implement the vision of the late Ellsworth “Buster” Alvord, former head of neuropathology in the UW Department of Pathology and a Seattle philanthropist. Alvord and his family funded five endowed chairs in five different UW Medicine departments to create a multidisciplinary brain cancer research center.

“Eric Holland is exceptionally well qualified to lead the Alvord Brain Tumor Center, and I am confident that he will recruit outstanding researchers and clinicians to establish the Alvord Center as the best in the world,” said Paul G. Ramsey, CEO of UW Medicine and dean of the UW School of Medicine. “Under Dr. Holland’s leadership, we will be able to fulfill the vision for brain cancer research and clinical care established by Buster Alvord when he and his family made their extraordinarily generous commitment to establish the Alvord Center. I am delighted to welcome Eric Holland to UW Medicine.”

At Fred Hutch, where Holland’s research laboratory will be based, he will be senior vice president and director of the Human Biology Division, an interdisciplinary program that encourages collaboration among faculty with a broad range of expertise – from molecular and cellular biology to genetics and clinical research. The division’s structure fosters laboratory, computational and clinical research that yields discoveries which can be rapidly translated into cancer treatments. Holland will oversee the recruitment of new scientists who are at the forefront of solid-tumor translational research in such areas as breast, prostate, gastrointestinal and other cancers.

With advances in genomics increasingly playing an important role in solid-tumor oncology, Holland’s expertise in this area will provide strong leadership to strengthen Seattle’s reputation in translational, solid-tumor research.

“I am thrilled at the prospect of working with the world’s leading experts in genome sciences, computational biology and those involved in the development of novel platforms for delivering innovative therapies to cancer patients,” Holland said. “The highly collaborative, multidisciplinary nature of cancer research at Fred Hutch and UW Medicine provides a solid foundation to build on.”

Phil Borges

Tibet Portrait by photographer Phil Borges, whose work will be shown during UW Global Health Week.

A Community Cafe will take place from 6:30-8:30 p.m., Monday, April 15 in Parnassus Café. The event  will feature ACT Theatre performances, including a reading from “Middletown.” The play touches on themes of mental health and depression.

A visual arts exhibit will showcase work from several local artists. Among them are Ellen Garvens, a UW photography professor whose pictures capture the people who make and use prosthetics in Indonesia; John Blalock, a student in a masters of fine arts program and  an artist-in-residence at Seattle Children’s:  Phil Borges, a social documentary photographer;  and Consuelo Echeverria, a global health graduate student and artist.

A theater banner for the play “Middletown.”

Later in the week, the UW’s Global Health Resource Center will host a Global Health and the Arts Symposium with local artists. The symposium will be held from noon to 6 p.m., Saturday, April 20 in Foege Auditorium, located in the UW Foege Building

Kevin Shaw, a UW undergraduate minor in global health and one the event organizers, said beauty and aesthetics is important for human health, but is often lost in contemporary discourse.

Ellen Garven

Ellen Garven’s photo of a prosthetic leg being made in Indonesia.

“We need to explore what makes humans healthy and what makes them thrive in the absence of disease. That’s communities,” he said.  “Art builds communities and builds complete people. There is so much potential for people in the arts to make a difference in public health.”

The symposium will include three panels and several performances, including the Seattle Fandango Project, which brings people together through music, dance, and verse.

A dozen guest speakers are lined up. They include Borges, known for his work with indigenous communities; Jacque Larrainzar, policy director for the Seattle Office of Civil Rights, who helped organize a queer feminist collective in Mexico; Carlo Scandiuzzi, director of ACT Theatre in Seattle; and several students and faculty working at the intersection of the arts and global health, including Sutapu Basu, director of the UW Women’s Center, whose dramas address worldwide women’s health issues, particularly human trafficking.

The panels will explore existing partnerships and the possibilities of additional collaboration between art and global health. There also will be discussions on how art can advance women’s health.

The symposium will feature 10-minute live performances. Film clips from UCLA’s Art and Global Health Center also will be shown, including a project in which HIV-positive people document their lives.

Daren Wade, director of the Global Health Resource Center within the Department of Global Health, said reaching out to the arts community is long overdue.

“As a global health resource center, our charge is to intersect with all parts of campus and throughout the years, we have touched most of campus,” he said. “But we and the campus as a whole need to reach out more to the creative arts. This is how to connect best with the community.”

To find out more about Global Health Week and the Global Health and the Arts Symposium, please go to:
http://globalhealth.washington.edu/global-health-career-week-2013.

Dr. Debby W. Tsuang, professor of psychiatry and behavioral sciences, and Dr. Marshall S. Horwitz, professor of pathology, both at the University of Washington in Seattle, led the multi-institutional study.  Tsuang is also a staff physician at the Puget Sound Veterans Administration Health Care System.

The results are published in the April 3 online edition of the JAMA Psychiatry.

Loss of brain nerve cell integrity occurs in schizophrenia, but scientists have not worked out the details of when and how this happens. In all five families in the present study, the researchers found rare variants in genes tied to the networking of certain signal receptors on nerve cells distributed throughout the brain. These N-methyl-D-aspartate, or NMDA, receptors are widespread molecular control towers in the brain. They regulate the release of chemical messages that influence the strength of brain cell connections and the ongoing remodeling of the networks.

These receptors respond to glutamate, one of the most common nerve-signaling chemicals in the brain, and they are also found on brain circuits that manage dopamine release. Dopamine is a nerve signal associated with reward-seeking, movement and emotions.  Deficits in glutamate and dopamine function have both been implicated in schizophrenia but most of the medications that have been developed to treat schizophrenia have targeted dopamine receptors.

Tsuang and her groups’ discovery of gene variations that disturb N-methyl-D-aspartate receptor networking functions supports the hypothesis that decreased NMDA receptor-mediated nerve-signal transmissions contributes to some cases of schizophrenia.

Alice C. Gray

Gene variants that affect brain signal receptors may be one of several causes of schizophrenia symptoms, which can include terrifying hallucinations.

Tsuang pointed out that several hallucinogenic drugs, such as ketamine and phencyclidine (PCP, or angel dust), block N-methyl-D-aspartate receptors and can produce symptoms similar to schizophrenia. These are the strongest evidence implicating these receptors in schizophrenia. The drugs sometimes induce psychosis and terrifying sensory detachment. Reports of such effects in recreational drug users fingered faulty NMDA receptor networks as suspects in schizophrenia.

In all five of their study families, Tsuang’s team detected rare protein-altering variants in one of three genes involved with the N-methyl-D-aspartate receptor network.  One of the genes, GRM5, is directly linked with glutamate signaling. In the other two genes, the links are indirect and connected through other proteins synthesized in brain cells. One of these proteins, PPEF2, appears to affect the levels of certain brain nerve-cell signaling mediators, and the other altered protein, LRP1B, may compete with a normal protein for a binding spot on a subunit of the NMDA receptor.

These discoveries provide additional clues to the molecular disarray that might occur in the brain nerve cells of some patients with schizophrenia, and suggest new targets for therapy for certain patients. In a disease occurring in about 1 percent of the population, the picture of how and why schizophrenia arises in all these people is far from complete.

“Disorders like schizophrenia are likely to have many underlying causes,” Tsuang noted.  She added that it might eventually make sense to divide schizophrenia into categories based, for example, on which biochemical pathways in the brain are disrupted.  Treatments might be developed to correct the exact malfunctioning mechanisms underlying various forms of the disease.

Tsuang gave an example: Agents that stimulate N-methyl-D-aspartate receptor-mediated nerve-signal transmissions include glycine-site blockers and glycine-transport inhibitors have shown some encouraging results in pre-clinical drug trials, but mostly in adjunctive treatment in addition to standard antipsychotic therapy.

“But perhaps the data we have generated will help pharmaceutical companies target specific subunits of the NMDA receptors and pathways,” Tsuang said.  She added, however, that effective treatments may lag by many years after these kinds of discoveries.  Someday it may make sense to initiate such treatments in people at high genetic risk when early symptoms, such as apathy and lack of motivation, appear, and before brain dysfunction is severe.

Also, possessing the newly discovered gene mutations does not always mean that a person will become schizophrenic. In the recent family study, three of the five families had relatives with the protein-altering variants who did not have schizophrenia.

“This isn’t surprising,” Tsuang observed, “Given that schizophrenia is such a complex disorder, we would expect that not everyone who carries the variants would develop the disease.”  In the future, researchers will be seeking what triggers the gene variants into causing problems, other mutations within affected individuals’ genetic profile that might promote or protect against disease, as well as non-genetic factors in the onset of the illness in genetically susceptible people.

The researchers also utilized a strategy and selected more distant relatives of affected individuals for genetic sequencing.   Distant kin share, a smaller proportion of genes compared to closely related family members.  For example,siblings typically on the average share about 50 percent of their genes whereas cousins on the average share 12.5 percent of their genes. The researhers also hypothesized that the causative mutation within each family would be the same variant.

This strategy helped the researchers decrease the number of genetic variants that were detected by sequencing and thereby concentrate only on the remaining strongest candidates. The researchers also filtered their results against the many publicly available sequencing databases. This allowed them to pick out genetic variants not seen in individuals without psychiatric illness.

According to Tsuang, the research team was excited by recent advances in technology enabled them to uncover unknown, rare genetic variants not previously found in large populations without psychiatric condition. The ability to rapidly sequence only those portions of the genome that code for proteins made this experiment possible.

The next step for the researchers will be to screen for the newly discovered genetic variants in a large sample of unrelated cases of schizophrenia compared to controls. They want to determine if the variants are statistically associated with the disease.

The study was funded by the Brain and Behavior Research Foundation Independent Investigator Award, National Institute of Mental Health at the National Institutes of Health, and the United States Department of Veterans Affairs.

In addition to Tsuang and Horwitz, the first author on this publication is Andrew Timms, postdoctoral fellow in Horwitz’ laboratory and second author is Michael O. Dorschner of the UW Department of Psychiatry and Behavioral Sciences and the Puget Sound Veterans Administration Health Care System.

Other scientists on the study were Jeremy Wechsler and Robert Kirkwood, of the UW Department of Pathology;  Carl Baker and Evan Eichler of the UW Department of Genome Sciences; and Olena Korvatska of the UW Department of Medicine, Division of Medical Genetics; Kyu Yeong Choi and Katherine W. Roche, of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health;  Santhosh Girirajan of the Departments of Biochemistry and Molecular Biology and Anthropology at Pennsylvania State University.

The idea is to detect the conditions as early as possible, before symptoms begin to appear, so treatment can lessen the physical damage.

Now the University of Washington chemistry professors’ methodology is drawing interest from companies that could use it in tests distributed nationally and around the world.

U.S Air Force/Staff Sgt. Eric T. Sheler

The blood of a 2-week-old infant is collected for a routine newborn screening. Testing for lysosomal storage diseases uses a similar method to collect blood for screening.

“It’s the ultimate analytical device to find a needle in a haystack, when you know what you are looking for,” Gelb said.

Currently, the screening can detect six diseases — Krabbe, Pompe, Niemann-Pick, Gaucher, Fabry and Hurler syndromes — that are associated with enzyme deficiencies within lysosomes, structures that break down large molecules and eliminate waste in most cells. Three others are likely to be added to the screening soon, and more can be added as treatments for the conditions are developed.

One question – whether the UW-developed test, which uses a method called tandem mass spectrometry, could be integrated into routine newborn screening – was tested at the Washington State Newborn Screening laboratory.

A new research paper in press with the Journal of Pediatrics shows that not only can the lysosomal storage disease testing be integrated with other newborn screening, but that it is a better predictor than the methods currently used for non-lysosomal disorders, said Dr. Ronald Scott, the paper’s lead author and a UW professor of pediatrics.

There are more than 40 lysosomal storage diseases, but there are effective treatments for fewer than a dozen. “Those are the ones we focus on,” said Scott, who serves as an adviser to the Washington Health Department on newborn screening and has worked closely with Gelb and Tureček in their research (they are coauthors of the Journal of Pediatrics paper).

Newborns are routinely screened for a variety of disorders. In Washington state those range from maple syrup urine disorder to cystic fibrosis. But screening for lysosomal storage diseases is just now being added by a few states. New York, with efforts led by Hunter’s Hope Foundation, tests for Krabbe disease, the condition that claimed the life Hunter Kelly, son of former Buffalo Bills quarterback Jim Kelly.

New Jersey has passed legislation to screen for several disorders as soon as testing has passed federal approval and is readily available. Similar significant efforts, led by the Evanosky Foundation, are under way in Illinois and Missouri, and there have been inquiries from other states.

The screening developed by Gelb and Tureček is similar in some ways to newborn screening for other disorders – a spot of blood drawn from a baby’s heel is dried on a paper card, a small section of the blood spot is punched out and rehydrated, then target enzymes are incubated and measured using tandem mass spectrometry, a means of determining a substance’s chemical makeup and quantity.

“In the sense of making it to the real world, it’s very far along,” Gelb said of the technique. “But in terms of worldwide use, it’s still very early.”

Lysosomal disorders have a variety of effects and treatments. In Gaucher and Fabry disorders, for example, enzyme therapy can help to alleviate symptoms, Scott said. Enzyme therapy is not effective for Krabbe disease, an often-fatal disorder that affects the myelin sheath of nerves, and it is treated instead with a bone marrow transplant.

A condition called Mucopolysaccharidosis II – with symptoms ranging from a complete halt to development at an early age to learning disabilities, psychiatric problems or aortic valve disease at a later age – has not yet been added to the testing regimen. But testing can detect it early enough that an infant can be treated and kept stable until the age of 2, when a bone marrow transplant can be performed to treat symptoms that affect the central nervous system.

“Depending on the mutation, some affected individuals will develop a severe infantile form of the disease and be treated as soon as possible,” Tureček said. “Others will have milder forms that may cause associated health problems later in life, but there is no need for early treatment.”

Besides the growing U.S. interest, some in other countries – ranging from individual doctors to government officials – have expressed an interest in learning more. And there are concerns. Cost is an issue for some, Gelb said, while for others it’s that testing and early treatment aren’t necessarily a perfect answer.

“Many of these babies are not saved from illness,” he said. “They’re better, but they’re not perfect. Some are better than others.”

But Scott, who has spent his career leading research at UW and Seattle Children’s on a variety of pediatric genetic disorders, has been heartened by the advances in detection and treatment that have come in a relatively short time.

“I am absolutely enthralled with the changes that have been made for some of the lysosomal storage diseases in the last decade,” he said. “I have patients who in the past would have been seriously debilitated but who are now leading normal lives, going to college, raising families, and for the most part with no symptoms.”

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The partnership slate for UW Medicine Health.

UW Medicine will launch a multi-media initiative April 1 to provide consumers with health and wellness information. In partnership with Fisher Communications, UW Medicine also will increase awareness of the latest treatments and medical breakthroughs at UW Medicine.

“In support of our mission to improve the health of the public, UW Medicine recognizes the need to encourage each member of our community to take responsibility for their personal health,” said Dr. Paul G. Ramsey, CEO of UW Medicine. “With this initiative, our audiences will gain valuable knowledge and tools for engaging in preventive care and establishing rewarding personal health behaviors.”

KOMO broadcast reporter Molly Shen will introduce the UW Medicine Health series.

“The new initiative is part of UW Medicine’s overall strategy to provide comprehensive care for our community,” said Johnese Spisso, UW Medicine’s chief health system officer. “It will highlight UW Medicine’s expertise in a broad range of primary care and specialty fields while helping consumers make informed decisions about their treatment options in our health system.”

Look for:

• Regular television and radio spots featuring UW Medicine experts and patients.on Fisher Communication’s KOMO News, KOMO News Radio and STAR 101.5. Topics for the first three months include heart, vascular and brain health.

• A new dedicated website, UW Medicine Health, uwmedicinehealth.com. It will have timely news items, features and columns about health and wellness, medical research advances and patient stories.

KOMO news anchor Molly Shen will introduce the program to viewers and listeners of KOMO News, KOMO News Radio and Star 101.5. The first series of TV and radio spots on heart health will begin April 8. During these segments, UW Medicine experts and patients will share stories and insights about the care they received at UW Medicine.

This month’s articles on heart health include:

• UW Medicine Regional Heart Center leads in heart care.
• How to reduce your risk of coronary artery disease.
• New defibrillator for treating heart rhythm disorders.
• Multi-specialty care saves a triathlon runner with heart disease.

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For more information, contact UW Medicine Strategic Marketing & Communications at 206-543-3620.

Christopher Merrikh

Using bacteria as a model organism, Houra Merrikh, assistant professor of microbiology, and her student Samuel Million-Weaver, study DNA replication and transcription conflicts that can lead to genomic instability and mutations.

Bacteria appear to speed up their evolution by positioning specific genes along the route of expected traffic jams in DNA encoding. Certain genes are in prime collision paths for the moving molecular machineries that read the DNA code, as University of Washington scientists explain in this week’s edition of Nature. Read the article.

The spatial-organization tactics their model organism, Bacillus subtilis, takes to evolve and adapt might be imitated in other related Gram-positive bacteria, including harmful, ever-changing germs like staph, strep, and listeria, to strengthen their virulence or cause persistent infections. The researchers think that these mechanisms for accelerating evolution may be found in other living creatures as well.

Replication – the duplicating of the genetic code to create a new set of genes– and transcription – the copying of DNA code to produce a protein – are not separated by time or space in bacteria. Therefore, clashes between these machineries are inevitable. Replication traveling rapidly along a DNA strand can be stalled by a head-on encounter or same-direction brush with slower-moving transcription.

The senior authors of the study, Houra Merrikh, UW assistant professor of microbiology, and Evgeni Sokurenko, UW professor of microbiology, and their research teams are collaborating to understand the evolutionary consequences of these conflicts. The major focus of Merrikh and her research team is on understanding mechanistic and physiological aspects of conflicts in living cells – including why and how these collisions lead to mutations.

Impediments to replication, they noted, can cause instability within the genome, such as chromosome deletions or rearrangements, or incomplete separation of genetic material during cell division. When dangerous collisions take place, bacteria sometimes employ methods to repair, and then restart, the paused DNA replication, Merrikh discovered in her earlier work at the Massachusetts Institute of Technology.

Christopher Merrikh

The researchers on the Nature paper “Accelerated gene evolution through replication-transcription conflicts” pose before a microbiology history timeline. They are: Sandip Paul, Houra Merrikh, Evgeni Sokurenko, Sujay Chattopadhyay, and Samuel Million-Weaver, all of the UW Department of Microbiology

To avoid unwanted encounters, bacteria orient most of their genes along what is called the leading strand of DNA, rather than the lagging. The terms refer to the direction the encoding activities travel on different forks of the unwinding DNA. Head-on collisions between replication and transcription happen on the lagging strand.

Despite the heightened risk of gene-altering clashes, the study bacteria B. subtilis still orients 25 percent of all its genes, and 6 percent of its essential genes, on the lagging strand.

The scientist observed that genes under the greatest natural selection pressure for amino-acid mutations, a sign of their adaptive significance, were on the lagging strand. Amino acids are the building blocks for proteins. Based on their analysis of mutations on the leading and the lagging strands, the researchers found that the rate of accumulation of mutations was faster in the genes oriented to be subject to head-on replication-transcription conflicts, in contrast to co-directional conflicts.

According to the researchers, together the mutational analyses of the genomes and the experimental findings indicate that head-on conflicts were more likely than same-direction conflicts to cause mutations. They also found that longer genes provided more opportunities for replication-transcription conflicts to occur. Lengthy genes were more prone to mutate.

The researchers noted that head-on replication-transcription encounters, and the subsequent mutations, could significantly increase structural variations in the proteins coded by the affected genes. Some of these chance variations might give the bacteria new options for adapting to changes or stresses in their environment. Like savvy investors, the bacteria appear to protect most of their genetic assets, but offer a few up to the high-roll stakes of mutation.

The researchers pointed out, “A simple switch in gene orientation …could facilitate evolution in specific genes in a targeted way. Investigating the main targets of conflict-mediated formation of mutations is likely to show far-reaching insights into adaptation and evolution of organisms.”

The research project was supported with start-up funds from the UW Department of Microbiology and with grants from the National Institutes of Health (RC4AI092828 and RO1 GM084318.)

Scientists on this project, in addition to Merrikh and Sokurenko, were Sandip Paul, Samuel Million-Weaver, and Sujay Chattopadhyay, all of the UW Department of Microbiology.

Elizabeth Hunter

UW Medicine lung disease specialist Dr. Ganesh Raghu and pulmonary fibrosis patient support group leader Dave Sherry celebrate the establishment of the Center for Interstitial Lung Disease this week.

For 25 years, folks have traveled from all over the Pacific Northwest to meet for their pulmonary fibrosis support group at University of Washington Medical Center. This week, as they celebrated the support group’s quarter-century anniversary, the room buzzed with laughter, greetings, and smiles. Some members wore oxygen tanks, necessary after the disease began hardening and scarring their lung tissue and made breathing difficult.

Pulmonary fibrosis is a life-threatening disease in which excess fibrous tissue develops in the lungs. People with pulmonary fibrosis experience a hacking cough and shortness of breath that causes fatigue, weight loss, and weakness. No single cause of pulmonary fibrosis has been identified; it is often classified as a secondary effect of other interstitial lung diseases. The term “interstitial lung disease” refers to a large group of disorders involving both lungs, most of which cause progressive scarring of lung tissue (pulmonary fibrosis). There is no cure for pulmonary fibrosis, and almost no treatment. One can only hope to be a good candidate for a successful lung transplant.

A number support group members had already received lung transplants from UW Medical Center’s transplant services. One gentleman received news one month ago to the day, as he was walking out of the support group, that he was to have his transplant.

Dave Sherry, the group leader, beamed as he described the bond between fellow members. Each month, he and the team organize a speaker from UW Medical Center or an outside medical organization to give a talk about the disease. Members also spend time voicing their fears and successes with each other.

“We have a shared destiny that ties us together,” said Sherry. In fact, this support group has been so strong throughout the years that it became a model for other support groups. One prominent Italian surgeon was so impressed that he implemented a similar system of support groups in Europe.

Representatives from the Chicago-based Pulmonary Fibrosis Foundation, including CEO Dr. Daniel M. Rose, traveled to Seattle for the support group’s 25^th anniversary. Rose presented a short and fascinating lecture that compared the history of cystic fibrosis with pulmonary fibrosis. He emphasized the need for research and clinical trials, and showed how the Cystic Fibrosis Foundation’s aggressive approach to finding treatment for the disease ultimately improved the estimated lifespan of patients by more than 25 years. His goal is to approach pulmonary fibrosis with the same commitment to finding treatment and finding a cure.

Elizabeth Hunter

Some of the members of UW Medical Center’s pulmonary fibrosis support group gather for the 25th anniversary of the group this week.

Indeed, this month’s support group was particularly celebratory. In addition to the 25-year anniversary, this past week UW Medicine announced the formation of the Center for Interstitial Lung Disease. The Center’s founding director is Dr. Ganesh Raghu, UW professor of medicine in the Division of Pulmonary and Critical Care Medicine and co-director of UW Medical Center’s scleroderma clinic. Raghu is also the prescient doctor who had the foresight to start the long-running support group—the first of its kind in the world.

Said Raghu, ”The establishment of the Center for Interstitial Lung Diseases is an essential expansion of a long standing interstitial lung disease /sarcoidosis/pulmonary fibrosis program at UW Medical Center. The initiative will result in more accurate diagnoses and better outcomes for patients confronted with the challenges of interstitial lung diseases. This is the beginning of a new and exciting era of substantial progress for our patients, who will now receive care tailored to the individual patient’s preference and choice based on current and new evidence. It is my most sincere privilege and honor to serve our patients and to work with everyone at UW Medical Center. It is a superb clinical and research environment, committed to maintaining and restoring health for those in need.”

For UW Medicine, establishing the Center for Interstitial Lung Disease means more opportunities for research, collaboration, training, and technology. For these incredible patients, who have supported each other for so long, the Center could mean a new lease on life.

Barcelona Superconducting Center

Alya Red, an electromechanical computational model of the heart developed at the Barcelona Superconducting Center, shows cardiac muscle fibers. UW researchers are seeking ways to strengthen weakened heart muscles through gene therapy.

The potential of gene therapy to boost heart muscle function was explored in a recent University of Washington animal study. The findings suggest that it might be possible to use this approach to treat patients whose hearts have been weakened by heart attacks and other heart conditions.

Michael Regnier, UW professor and vice chair of bioengineering, Charles Murry, director of the Center for Cardiovascular Biology and co-director of the Institute for Stem Cell and Regenerative Medicine, and Sarah Nowakowski, a UW graduate student in bioengineering, led the study. The findings appeared online March 25 in the Proceedings of the National Academy of Sciences.

Normally, muscle contraction is powered by a molecule, the nucleotide called adenosine-5′-triphosphate, or ATP. Other naturally occurring nucleotides can also power muscle contraction, but in most cases they have proven to be less effective than ATP.

Dr. Charles Murry in his heart muscle cell research lab.

In an earlier study of isolated muscle, however, Regnier, Murry and their colleagues had found that one naturally occurring molecule, called 2 deoxy-ATP, or dATP, was actually more effective than ATP in powering muscle contraction.  dATP  increased both the speed and force of the contraction, at least over the short-term.

In the new study, the researchers wanted to see whether this effect could be sustained. To do this, they used genetic engineering to create a strain of mice whose cells produced higher-than-normal levels of an enzyme called ribonucleotide reductase. This enzyme converts the precursor of  ATP, adenosine-5’-diphosphate or ADP, to dADP, which, in turn, is rapidly converted to dATP.

Dr. Michael Regnier holds a model of a heart in one hand, and a hand weight in another.

“This fundamental discovery, that dATP can act as a ‘super-fuel’ for the contractile machinery of the heart, or myofilaments, opens up the possibility to treat a variety of heart failure conditions,” Regnier, an established investigator of the American Heart Association, said. “An exciting aspect of this study and our ongoing work is that a relatively small increase in dATP in the heart cells has a big effect on heart performance.”

The researchers found that increased production of the enzyme ribonucleotide reductase increased the concentration of dATP within heart cells approximately tenfold. Even though this level was still less than one to two percent of the cell’s total pool of ATP, the increase led to a sustained improvement in heart muscle function. The genetically engineered hearts contracted more quickly and with greater force.

“It looks as though we may have stumbled on an important pathway that nature uses to regulate heart contractility,” Murry added. “The same pathway that heart cells use to make the building blocks for DNA during embryonic growth makes dATP to supercharge contraction when the adult heart is mechanically stressed.”

Importantly, the elevated dATP effect was achieved without imposing additional metabolic demands on the cells. That observation suggests that the modification would not harm the cell’s functioning over the long-term.

The study’s findings, the authors write, suggest that treatments that elevate dATP levels in heart cells may prove to be an effective treatment for heart failure.

Read the PNAS scientific article, “Transgenic overexpression of ribonucleotide reductase improves cardiac performance.”

The work was supported by grants from the National Institutes of Health and the National Science Foundation Graduate Research Fellowship Program.

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BEAT BioTherapeutics, a private company spinout from the UW, has entered into an exclusive global license agreement covering  this technology and is moving forward with clinical development. For more information, visit www.BeatBioTherapeutics.com

Dr. King K. Holmes, noted for his work on sexually transmitted diseases, in a 2009 photo of a talk given at the Burke Museum.

Dr. King K. Holmes, professor and chair of the UW Department of Global Health, won the prestigious 2013 Canada Gairdner Global Health Award for his work in sexually transmitted diseases, the Gairdner Foundation announced March 20.

The award, valued at $100,000 Candian (about $97,300 U.S.) is one of the world’s most esteemed prizes for medical research. Since 1959, of the 312 individuals presented with a Canada Gairdner Award, 80 have gone on to receive a Nobel Prize. Holmes said he would contribute the money to the University of Washington.

Holmes was awarded the prize for his “global scientific contributions to the field of sexually transmitted disease and their effective treatment and prevention.” He becomes the 10th UW faculty member to win a Gairdner Award.

The Gairdner Foundation, in citing the award, said that today more than 35 sexually transmitted diseases have been discovered. Holmes and the scientists he mentored are working on approximately 20 of these.

“Dr. Holmes assisted in defining the causes of many major diseases and through leading numerous clinical trials, has paved the way for many standard-of-care therapies used to treat STDs today,” the foundation said in a release.

John Dirks, president and scientific director of the Gairdner Foundation, told The Lancet that Holmes “brought to medicine and public health the proper means of diagnosing, treating, and preventing STDs and of understanding their epidemiology. In addition, his amazing gift of mentorship launched so many trainees to the forefront of the global health scene, which, thanks in great measure to their achievements, is now a flourishing discipline in its own right. Holmes’ huge lifetime contribution has no parallel. Among the many mountains on the public health landscape he stands out as an Everest.”

Holmes holds the William H. Foege Endowed Chair in Global Health. He founded and directs the UW Center for AIDS and STD, which provides patient care, training and education, research and international technical assistance in the field of sexually transmitted diseases. Holmes is also head of Infectious Diseases at Harborview Medical Center.

Read The Lancet story.

Watch a brief video of Holmes on advances in AIDS survival.

A University of Washington team has developed a new method for color-coding cells that allows them to illuminate 100 biomarkers, a ten-time increase from the current research standard, to help analyze individual cells from cultures or tissue biopsies. The work is published this week (March 19) in Nature Communications.

Xiaohu Gao

A cell specimen used for two rounds of testing. In the top panel, two biomarkers are stained green and red, and in the bottom, after the sample has been regenerated, the same biomarkers are stained red and green. This shows that the same tissue can be used for multiple rounds of testing without degrading the tissue sample.

“Discovering this process is an unprecedented breakthrough for the field,” said corresponding author Xiaohu Gao, a UW associate professor of bioengineering. “This technology opens up exciting opportunities for single-cell analysis and clinical diagnosis.”

The research builds on current methods that use a smaller array of colors to point out a cell’s biomarkers – characteristics that indicate a special, and potentially abnormal or diseased, cell. Ideally, scientists would be able to test for a large number of biomarkers, then rely on the patterns that emerge from those tests to understand a cell’s properties.

The UW research team has created a cycle process that allows scientists to test for up to 100 biomarkers in a single cell. Before, researchers could only test for 10 at a time.

The analysis uses quantum dots, which are fluorescent balls of semiconductor material. Quantum dots are the smaller version of the material found in many electronics, including smartphones and radios. These quantum dots are between 2 and 6 nanometers in diameter, and they vary on the color they emit depending on their size.

Cyclical testing hasn’t been done before, though many quantum dot papers have tried to expand the number of biomarkers tested for in a single cell. This method essentially reuses the same tissue sample, testing for biomarkers in groups of 10 in each round.

Scott Manthey

Xiaohu Gao, left, and Pavel Zrazhevskiy in a UW bioengineering lab.

“Proteins are the building blocks for cell function and cell behavior, but their makeup in a cell is highly complex,” Gao said. “You need to look at a number of indicators (biomarkers) to know what’s going on.”

The new process works like this: Gao and his team purchase antibodies that are known to bind with the specific biomarkers they want to test for in a cell. They pair quantum dots with the antibodies in a fluid solution, injecting it onto a tissue sample. Then, they use a microscope to look for the presence of fluorescent colors in the cell. If they see particular quantum dot colors in the tissue sample, they know the corresponding biomarker is present in the cell.

After completing one cycle, Gao and co-author Pavel Zrazhevskiy, a UW postdoctoral associate in bioengineering, inject a low-pH fluid into the cell tissue that neutralizes the color fluorescence, essentially wiping the sample clean for the next round. Remarkably, the tissue sample doesn’t degrade at all even after 10 such cycles, Gao said.

Xiaohu Gao

This figure shows the cyclical process developed in the study. In step 1, the colored balls representing quantum dots of different colors are used to label biomarkers in cell and tissue samples. Step 2 shows how each biomarker can be isolated and separated into distinct images for analysis. Step 3 illustrates how the tissue sample is flushed clean between rounds to begin biomarker testing again.

For cancer research and treatment, in particular, it’s important to be able to look at a single cell at high resolution to examine its details. For example, if 99 percent of cancer cells in a person’s body respond to a treatment drug, but 1 percent doesn’t, it’s important to analyze and understand the molecular makeup of that 1 percent that responds differently.

“When you treat with promising drugs, there are still a few cells that usually don’t respond to treatment,” said Gao. “They look the same, but you don’t have a tool to look at their protein building blocks. This will really help us develop new drugs and treatment approaches.”

The process is relatively low-cost and simple, and Gao hopes the procedure can be automated. He envisions a chamber to hold the tissue sample, and wire-thin pumps to inject and vacuum out fluid between cycles. A microscope underneath the chamber would take photos during each stage. All of the images would be quantified on a computer, where scientists and physicians could look at the intensity and prevalence of colors.

Gao hopes to collaborate with companies and other researchers to move toward an automated process and clinical use.

“The technology is ready,” Gao said. “Now that it’s developed, we’re ready for clinical impacts, particularly in the fields of systems biology, oncology and pathology.”

The research was funded by the National Institutes of Health, the U.S. National Science Foundation, the U.S. Department of Defense, the Wallace H. Coulter Foundation and the UW’s Department of Bioengineering.

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For more information, contact Gao at 206-543-6562 or xgao@uw.edu. He will be unavailable for interviews by phone or email on Wednesday, March 20.

Mary Levin

Graduating medical student Anisa Ibrahim, at Match Day with her husband and baby daughter, will train as a pediatrician.

As the clock approaches 9 a.m, Friday, March 15, fourth-year University of Washington medical student Anisa Ibrahim awaits the sound of the gong with “a mixture of excitement and anxiety.” It’s the signal that will send her, along with fellow UW medical students gathered in the Health Sciences lobby, to the long tables of elegant purple-and-gold boxes containing their futures as beginning physicians.

Match Day, which takes place on the same day every year at medical schools across the nation, is when thousands of graduating medical students find out – at exactly the same time –  where they will train as residents via the National Resident Matching Program.

This year, 222 senior UW medical students learned of their 2013 residency positions at simultaneous gatherings across the UW School of Medicine’s five-state WWAMI region (Washington, Wyoming, Alaska, Montana and Idaho), including Match Day celebrations in Seattle, Billings, Missoula, Spokane, Boise and Anchorage.

Mary Levin

Seth Stratton learns he will be training in internal medicine at Northwestern.

For Ibrahim, the anticipation builds as she waits with her husband and young daughter to learn where she will begin the path to fulfilling her dream of becoming a pediatrician. Originally from Somalia, Ibrahim is the oldest of five children and the first in her family to attend college. She moved to Seattle as a young child, completed her undergraduate education at UW, and hopes to match at Seattle Children’s, her first choice for residency.

“But I think I’d be happy anywhere,” she said with a big smile.

Moments later Ibrahim, mom to two young daughters, is clearly elated when she learns she will be starting her residency at Seattle Children’s.

Mary Levin

Anisa Ibrahim is delighted with her residency match notification letter. First choice, Seattle Children’s!

“I am just thrilled,” she beamed.

UW medical student Seth Stratton said he’s quite happy with his second choice match at Northwestern University (his first choice was Vanderbilt). He’s the son of two UW faculty members: Dr. John Stratton, professor of medicine in the Division of  Cardiology, and Carolyn-Webster Stratton, a child psychologist and professor emeritus of family and child nursing. Seth said he plans to go into internal medicine with an eventual focus in cardiology and pulmonary/critical care medicine.

“It a unique opportunity to experience a different medical culture at a different place,” he said, adding with a smile, “though my parents probably would’ve been happier if I’d decided I wanted to stay here.”

Mary Levin

Medical student Ria Andrade and her husband share a toast. Ria plans to practice family medicine  in a medically underserved area.

Ria  Andrade, originally from Whittier, Calif., which she describes as “east of East L.A.,” applied only to family medicine community residency programs in southern California, because she’s eager to return to the region “where they’re doing the best at serving the populations I want to serve — the underserved and the undocumented.”

So Andrade and her husband of five years were delighted when she matched at her first choice for residency: Long Beach Memorial Medical Center.

Mary Levin

“I feel at peace today,” said Estell Williams, who learned she will train as a surgeon at the UW.

Estell Williams, the youngest of seven children and also the first in her family to go to college, also matched at her first choice: UW. She plans to become a surgeon and to continue her work to address the underrepresentation of minorities in medicine and healthcare disparities across populations.

Describing her emotions leading up to Match Day as “more excitement than anxiety,” Williams said she couldn’t be happier to have landed at UW.

“I feel at peace today,” she said. “I’ve worked hard for it – we all have.”

This year’s National Match is the largest in the history of the program. Read about some of the Match 2013 statistics nationwide.

Leila Gray

Window washers scale the new UW Medicine South Lake Union research building on Dexter Avenue North and Republican Street.

The newest research building at UW Medicine South Lake Union is completed, and is now undergoing commissioning and certification. Several UW biomedical research laboratories will be moving in from April through June.

Occupying the seven-story facility will be lab groups involved in kidney research, vision sciences, immunology, rheumatology, and infectious disease investigations.  These scientists are advancing the understanding of multiple sclerosis, blindness, malaria, lupus, renal failure and many other conditions.

Leila Gray

IT equipment is carted into the new facility

The construction is the third stage of development of UW Medicine’s facilities between Dexter Avenue North and Ninth Avenue North and between Mercer and Republican streets.  The Jeffrey and Susan Brotman Building (converted from the former Washington Energy “Blue Flame” building), an administration building and another laboratory building comprise the rest of the present complex.  A companion building, South Lake Union, 3.2, will be built west of South Lake Union 3.1 along the Dexter Avenue North.

The faculty, staff and students relocating to South Lake Union 3.1 will join a dynamic community of scholars. Already at UW Medicine South Lake Union are well-established programs in regenerative medicine and stem cell research, lung inflammation, cancer vaccine development, diabetes and obesity, mitochondrial medicine and several other fields. The move adds 300 to 325 more people to the workday population at UW Medicine South Lake Union, and raises the total to between 1,000 and 1,200.

Leila Gray

The west side of UW Medicine South Lake Union 3.1, seen from the corner of Dexter Avenue North and Republican Street.

“The people who will conduct their research in this building have been deeply involved in its design,” said Dr. John Slattery vice dean for research and graduate education in the UW School of Medicine and professor of pharmacology and of medicine. “As we get to the end of construction they have streamed to visit their new home.

“It is very rewarding to all of us,” he added, “to see how excited they are to move in and put the building to work. Through the process the researchers have come to know one another better, plan their community and interactions and initiate new projects made possible by this facility.  It is wonderful to see – just what we had hoped for.”

Jill K. Morelli, director of facilities for the Office of the Dean of Medicine, defined the purpose of the new building as “100 percent research.” She explained that the move will bring together scientists from different but related fields.

“The new building was designed to facilitate collaboration,” she said. The building has several gathering places for cross-disciplinary conversations. It also has a casual conference room with comfortable furnishings. Morelli called it “the living room of the building.” The building contains two large seminar rooms with videoconferencing capabilities, as well as a lobby and reception desk.“

Leila Gray

The reception area in the lobby of the new building awaits finishing touches.

Morelli described the design of the laboratories and their support areas as innovative and creative.

“They are models for the future and a great addition to the School of Medicine’s research portfolio,” she said.

The grounds for the new building will complement the existing inner plaza at UW Medicine South Lake Union.

“The landscaping,”  Morelli said, “will suggest the same sense of calm and quiet in the midst of busy city as does the plaza outside of South Lake Union I and II. “A water feature, crossed by a footbridge, will create the illusion of a stream flowing through the plaza and around a corner of the building . The setting will create an oasis from the intensity of the research endeavors occurring inside the building.”

Leila Gray

A construction worker at the front entrance to UW Medicine South Lake Union 3.1 on Eighth Avenue North.

There also are plans for a convenience store staffed by UW Housing and Food Services near the new building. Results of a contest to name the compact-size shop dubbed it Micro[scopic] Market.

The cavalcade of events and celebrations held at UW Medicine South Lake Union, and the free bus shuttles that carry people back and forth from Campus Parkway,  UW Medical Center and Harborview Medical Center a few times an hour, are dispelling the notion that UW Medicine South Lake Union is an island apart from the university. Many lectures take place in the large Orin Smith Auditorium, and several local researchers and national figures have attracted large audiences. Even an enterprising boat company has been ferrying people to and from South Lake Union to a Portage Bay dock on the UW west campus for a small fee.

“The additional videoconferencing in three rooms in the new building,” Morelli said, “will complement those elsewhere on the site and further UW Medicine South Lake Union’s connection to the UW Health Sciences and to the world.

A few building facts:

• Board of Regents approval April 2010
• Construction started July 2011
• Architect:  Perkins+Will
• Contractor: Sellen Construction
• Research and research support space:  188,000 gross square feel
• Total space: 330,000 gross square feet
• Parking: 266 spaces plus 2 bays in loading dock
• Cost of construction: $113 million
• Total project cost: $164 million
• Project is on time and on budget

UW global health expert Dr. Christopher Murray at an informal meeting in Tanzania.

These are some of the findings from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study, a collaborative project led by the Institute for Health Metrics and Evaluation at the UW. Country-specific findings, including those  for the United States, will be announced March 5 at the Bill & Melinda Gates Foundation in Seattle by Institute for Health Metrics and Evaluation Director Dr. Christopher Murray and Gates Foundation Co-chair and Trustee Bill Gates.

The findings detail the causes of death and disability – across age groups and sexes – for 187 countries around the world. The Global Burden of Diseases 2010 study encompasses researchers from 303 institutions and 50 countries, and the work, which generated 1 billion estimates for health challenges large and small, was funded by the Bill & Melinda Gates Foundation.

A full range of dynamic visualizations of the findings for the United States and other countries can be found at the Institute for Health Metrics and Evaluation website.These tools allow people everywhere to see the progress being made in health and the challenges that remain.

A global health researcher conducts an interview in Bangladesh.

“We know that the world’s health can only improve if we are measuring the right problems and evaluating the right solutions,” Murray said. “That’s why we are working hard to gather more and better data constantly and are challenging ourselves to improve our analytical methods. We also are expanding our network of collaborators. This extended network will improve the quality of the assessment but also provide a forum for ongoing reflection, learning, interpretation, and action based on the Globan Burden of Diseae results and future revisions.”

An image of a child jumping rope used in an NIH campaign to encourage American children and families to be more active.

Much of the illness and death in the United States is caused by a short list of ailments. The researchers found that just 17 distinct causes account for more than half of the American disease burden, measured as the number of years lost to disability and premature death. The top cause is ischemic heart disease, followed by chronic obstructive pulmonary disease, low back pain, lung cancer, and major depressive disorders.

In critical ways, the United States is lagging behind many wealthy and middle-income countries in terms of health. Americans live shorter lives, and shorter healthy lives, than do many other people. For example, men in 39 other countries – including Greece, Lebanon, and South Korea – live longer, and men in 30 other countries – such as Costa Rica, New Zealand, and Portugal – enjoy more years of good health.

Health is being largely eroded because Americans make poor lifestyle choices that cause lung ailments, musculoskeletal stress, and obesity-related illnesses such as heart disease and diabetes. Obesity’s impact is especially troubling. High body mass index as a risk factor rose by 45 percent between 1990 and 2010, and is now the third largest risk factor in the United States. Obesity accounts for more than one-tenth of total disease burden in 2010.

NIH

Obesity is a major contributor to the global burden of disease.

Like many countries in the world, the United States is struggling with a growing burden of disability. Almost all of the top causes of disability – back and neck pains, depression, anxiety, migraine headaches – grew as health threats from 1990 to 2010. These causes of disability are often not causes of death but their toll on health is dramatic.

The Washington Post wrote of the study, “The health of most of the planet’s population is rapidly coming to resemble that of the United States, where death in childhood is rare, too much food is a bigger problem than too little, and life is long and often darkened by disability.”

“We are in transition to a world where disability is the dominant concern as opposed to premature death,” Murray told the Post.

A public symposium on the study will be held on campus at 4 p.m., Monday,  March 11 to discuss the major findings and how the study provides a platform for collaboration across research centers on campus and worldwide. Murray will give a lecture “Findings of the Global Burden of Diseases, Injuries and Risk Factors 2010” in Hogness Auditorium at the UW Health Sciences Center. UW President Young, UW Provost Ana Mari Cauce, UW Medicine CEO Paul G. Ramsey, and UW School of Public Health Dean Howard Frumkin will discuss the implications of the study.

A Q&A session will follow and a reception will be held in the Health Sciences lobby. To register for the event, please go to  https://catalyst.uw.edu/webq/survey/alex27/192452.

Rhoda Baer

We may be exposed to endocrine-disrupting chemicals in our diet. Children are the most vulnerable to their effects.

While water bottles may tout BPA-free labels and personal care products declare phthalates not among their ingredients, these assurances may not be enough. According to a study published February 27 in the Nature Journal of Exposure Science and Environmental Epidemiology, we may be exposed to these chemicals in our diet, even if our diet is organic and we prepare, cook, and store foods in non-plastic containers.  Children may be most vulnerable.

“Current information we give families may not be enough to reduce exposures,” said Dr. Sheela Sathyanarayana, lead author on the study and an environmental health pediatrician in the UW School of Public Health and at Seattle Children’s Research Institute. She is a physician at Harborview Medical Center’s Pediatric Environmental Health Specialty Unit, and a UW assistant professor of pediatrics.

Phthalates and bisphenol A, better known as BPA, are synthetic endocrine-disrupting chemicals.  Previous studies have linked prenatal exposure to phthalates to abnormalities in the male reproductive system. Associations have also been shown between fetal exposure to BPA and hyperactivity, anxiety, and depression in girls.

The researchers compared the chemical exposures of 10 families, half of whom were given written instructions on how to reduce phthalate and BPA exposures. They received handouts prepared by the national Pediatric Environmental Health Specialty Units, a network of experts on environmentally related health effects in children. The other families received a five-day catered diet of local, fresh, organic food that was not prepared, cooked or stored in plastic containers.

Erik Stuhaug

Pediatrician Sheela Sathyanarayana studies the effects of environmental toxins on youngsters.

When the researchers tested the participants’ urinary concentrations of metabolites for phthalates and BPA, they got surprising results.  The researchers expected the levels of the metabolities to decrease in those adults and children eating the catered diet.

Instead, the opposite happened. The urinary concentration for phthalates were 100-fold higher than the those levels found in the majority of the general population. The comparison comes from a study conducted by the National Health and Nutrition Examination Survey. This is  a program of studies managed by the Centers for Disease Control and Prevention and designed to assess the health and nutritional status of adults and children in the United States.

The concentrations were also much higher for children as compared to the adults. The researchers then tested the phthalate concentrations in the food ingredients used in the dietary intervention. Dairy products—butter, cream, milk, and cheese—had concentrations above 440 nanograms/gram. Ground cinnamon and cayenne pepper had concentrations above 700 ng/g, and ground coriander had concentrations of 21,400 ng/g.

“We were extremely surprised to see these results.  We expected the concentrations to decrease significantly for the kids and parents in the catered diet group. Chemical contamination of foods can lead to concentrations higher than deemed safe by the US EPA,” said Dr. Sheela Sathyanarayana.

Using the study results, the researchers estimated that the average child aged three to six years old was exposed to 183 milligrams per kilogram of their body weight per day. The U.S. Environmental Protection Agency’s recommended limit is 20 mg/kg/day.

Wikimedia, Edgar181

This three-dimensional illustration shows the chemical structure of bisphenol A.

“It’s difficult to control your exposure to these chemicals, even when you try,” said Sathyanarayana. “We have very little control over what’s in our food, including contaminants. Families can focus on buying fresh fruits and vegetables, foods that are not canned and are low in fat, but it may take new federal regulations to reduce exposures to these chemicals.”

The other researchers in the study included Garry Alcedo (Seattle Children’s Research Institute), Brian E. Saelens and Chuan Zhou (UW Department of Pediatrics, Seattle Children’s Research Institute), Russell L. Dills and Jianbo Yu (UW Department of Environmental and Occupational Health Sciences) and Bruce Lanphear (BC Children’s Hospital and Simon Fraser University).

Their paper is titled, “Unexpected results in a randomized dietary trial to reduce phthalate and bisphenol A exposure.”

The study was supported through  by the Center for Ecogenetics and Environmental Health in the Department of Environmental and Occupational Health Sciences in the UW School of Public Health. A grant from the National Institute of Environmental Health provides major support for the center

Read about Sathyanarayana’s efforts to protect children from environmental exposure to toxic chemicals.