A published July 19 in the journal eLife brings new hope for HIV treatments. The research by scientists at the 天美影视传媒, the Max Planck Institute for Dynamics and Self-Organization and the University of Cologne indicates that carefully designed cocktails of broadly neutralizing antibodies, or bNAbs, could help treat HIV while minimizing the risk of the virus evolving to 鈥渆scape鈥� treatment.

The study shows that computational approaches to selecting combinations of bNAbs based on viral genetics could help prevent viral escape, making HIV treatment more effective.

鈥淥ur study shows that leveraging genetic data can help us design more effective HIV therapies,鈥� said senior author , a UW assistant professor of physics. 鈥淥ur approach may also be useful for designing therapies against other rapidly evolving agents that cause disease, such as the Hepatitis C virus, drug-resistant bacteria or cancer tumor cells.鈥�

Antibodies are a class of proteins made by the immune system to recognize and fight pathogens. In HIV infections, bNAbs are a specific subset of antibodies that recognize multiple strains of HIV.

Broadly neutralizing antibodies offer a promising new tool to treat or potentially cure infections with rapidly evolving viruses such as HIV. But clinical trials using a single bNAb to treat HIV have shown that some viral strains may survive the treatment and lead to a rebound of viruses in the blood. Combinations of bNAbs may therefore be a more effective approach, but finding the best combinations is a challenge.

鈥淔or our study, we proposed using a computational approach to predict the effectiveness of bNAb combinations based on the HIV genetics,鈥� said lead author Colin LaMont, a researcher at the Max Planck Institute for Dynamics and Self-Organization in Germany.

The team used high-throughput DNA sequencing to analyze the genomes of HIV viruses collected over 10 years from 11 untreated patients with HIV. They used these data to predict which viral strains might be able to escape treatment with different bNAbs and whether evolving to dodge bNAbs was associated with a survival cost. Next, using computational methods, they applied the knowledge gained to predict viral rebounds in three real-life trials using bNAbs. Finally, the team used their computational approach to develop a combination of bNAbs that is least likely to allow any virus to escape.

In the process, they discovered reasons why some bNAbs target broader populations of HIV than others. For example, some bNAbs, such as one called 10-1074, perform better against diverse populations of viruses because mutations that allow viruses to escape from 10-1074 also make those viruses less likely to survive. Others bNAbs, including one called PGT121, are more effective against viral populations with lower genetic diversity because mutations that enable escape are rare. Overall, the results suggested that the optimal combination includes three bNAbs: PG9, PGT151 and VRC01.

鈥淲e鈥檝e shown the combination of PG9, PGT151 and VRC01 reduces the chance of viral rebound to less than 1%,鈥� said LaMont. 鈥淚t does this by targeting three different regions of the virus鈥� protective outer wrapping, or envelope.鈥�

鈥淐ombining bNAbs, administered via intravenous infusion every few months, with current antiretroviral therapies that require daily doses could further improve long-term HIV treatment success,鈥� said Nourmohammad.

Antiretroviral therapy reduces the ability of HIV to multiply and create new variants, limiting the genetic diversity of the viral population and lowering the likelihood for emergence of bNAb escape variants. The authors say that future studies are needed to confirm the potential benefits of combining antiretroviral therapy and broadly neutralizing antibodies.

Co-authors on the study are Jakub Otwinowski at the Max Planck Institute for Dynamics and Self-Organization and Kanika Vanshylla, Henning Gruell and Florian Klein at the University of Cologne in Germany. The research was funded by the National Science Foundation, the German Research Foundation and the Max Planck Institute for Dynamics and Self-Organization.

For more information, contact Nourmohammad at armita@uw.edu.

Adapted from a by eLife.

Although modern roundworms, fruit flies and humans are separated by hundreds of millions of years of evolution, all three species use many similar molecular strategies to control cell growth, development and function, according to research conducted by a collaboration of scientists from around the world, including several from the UW.

鈥淚f features of the genomes of these disparate organisms are the same, it is likely those features are important and fundamental to cell function,鈥� said , UW professor and chair of genome sciences, and a co-author on several papers on this research in the Aug. 28 Nature. The work is part of a federally funded effort to understand the genomes of two organisms common in biomedical research, Drosophila melanogaster, the fruit fly, and Caenorhabditis elegans, a 1 millimeter-long, soil-dwelling roundworm, and to correlate findings with those of the human genome.

Read about the research at:

UW Medicine outpatients will be able to see doctor鈥檚 notes in their medical records

Patients become more involved in their medical care when they can read their doctors鈥� full clinical notes in their online medical record. So says research accumulated over the past several years at three U.S. clinical sites, one of them Harborview Medical Center.

That finding, and the realization among most participating doctors that their initial misgivings about the open notes concept were unfounded, is leading UW Medicine to make that same access available in late October to outpatients at all of its clinics and hospitals.

See how open notes work:

Teaching about rapidly changing health topics like Ebola

Dr. Doug Black, an infectious-disease specialist and UW associate professor of pharmacy practice, describes how he teaches students about Ebola, a fast-changing health topic, by appealing to their curiosity, sense of discovery, and desire for accurate, up-to-date information.

Follow the Q & A:

Insight into successful depression care for women

In America, about a fourth of women will experience a major depressive episode in their lifetimes. UW research has shown that collaborative care from a primary-care provider and a mental health professional is an effective model for treating women’s depression. The聽 newest report, Aug. 26 in the online American Journal of Psychiatry, found that women with publicly funded health insurance or without insurance coverage experienced greater improvement in depression symptoms, with collaborative care, than did women with commercial insurance. The method the researchers used, called DAWN for Depression Attention for Women Now, will be offered at Harborview Medical Center in Seattle.

Learn more:

What price for a cure? The economics of drug pricing

The uproar against the $1,000-a-pill hepatitis C drug Sovaldi, generic name sofosbuvir, may signal a turning point in drug pricing in the United States.聽 Purchasers appear to be pushing back and saying, 鈥淣o.鈥� 聽In a Q & A in HSNewsbeat, Sean Sullivan, professor of pharmacy and health services, explains how drug prices are set and changing attitudes on what purchasers are willing to pay. 聽Read what he has to say:

Selenium, Vitamin E heighten prostate cancer risk

Some men who take high doses of selenium and vitamin E supplements could increase their risk of aggressive prostate cancer, according to a recent study led by Alan Kristal, professor of epidemiology. Learn more about the potential downside of 聽taking these antioxidants:

A class of drugs used to treat anxiety and epileptic seizure reduces some autistic behaviors in mice, when given in low, non-sedating doses.聽 These findings point to the possibility of testing a new therapeutic approach to managing autism in people. The findings are reported in the March 19 issue of the CELL journal Neuron.

William Catterall, UW chair and professor聽 of pharmacology, is senior author of聽 the research paper.

鈥淭hese are very exciting results because they suggest that existing drugs, called benzodiazepines, might be useful in treatment of the core deficits in autism,鈥� he said

These deficits include repetitive behaviors and difficulty relating to others.聽The condition is often聽accompanied by specific聽learning problems.聽Catterall explained that a particular, well-studied聽strain of mice聽acts in聽ways that聽resemble these聽autistic traits.聽 Scientists are interested in their brain chemistry.

Normally, inhibitory nerve cells in the brain聽send chemical signals that put the brake on excitatory nerve cells. Research indicates that the strain of mice with autistic behaviors have lower activity of inhibitory neurons and higher activity of excitatory neurons in the brain.聽In the study, scientists restored the balance with low, nonsedating聽doses of benzodiazipine.

鈥淥ur results provide strong evidence that increasing inhibitory neurotransmission is an effective approach to improvement of social interactions, repetitive behaviors, and cognitive deficits in a well-established autism animal model that has some similar behavioral features as human autism,鈥� Catterall said.

Read at the new site for the UW Health Sciences and UW Medicine news.

on the research.

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.聽 The small, private clinic of five physicians no longer has contact with detailers 鈥� 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.

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

鈥淒etailing 鈥� selling drugs by educating physicians 鈥� 聽was first reported as a problem in the late 1950鈥檚,鈥� Evans said. 聽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,聽 Evans noted, have critically looked at detailing,聽 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鈥檚 physicians practice in the community, where interactions between physicians and pharmaceutical representatives are still commonplace.聽 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.

鈥淐hanging this situation is not easy, but with a deliberate and thoughtful approach it can occur,鈥� Evans said. 聽Although his clinic鈥檚 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.聽 This data helped convince the physicians and staff that a problem existed.聽 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.聽 Clinic staff told patients about the change, and news media in the local area informed the nearby public. 聽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.

鈥淏ecoming pharma-free at our clinic was not an overnight thing,鈥� said Evans. 鈥淐ultural change takes time.聽 Eventually even the initial dissenters in the clinic came to feel good about the change, and it became a point of pride.鈥�

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.

鈥淥ne of the concerns,鈥� Evans said, 鈥渋s that medical students and residents may come up through their education without ever having interacted with a drug representative.聽 It鈥檚 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.聽 This year鈥檚 graduating residents will be the first to have taken the training.鈥�

As of 2009, there was one drug sales representative for every eight physicians. 聽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.聽 Evans explained that most drug reps are well trained and personable. They use marketing strategies time-tested in the social sciences.

鈥淚t鈥檚 a sophisticated operation. For example, before they go in to see physicians,鈥� he said, 鈥渄etailers sit in their cars data-mining on their electronic devices. They find out the physicians鈥� prescribing patterns from databases in which the patients鈥� 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.鈥�

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.聽 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?聽 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,鈥� wrote that they hope their description of how a clinic changed its practice 鈥渃ontributes to the ongoing discussion of the potential clinical influences and the ethics of the relationship between practicing physicians and pharmaceutical marketing.鈥�

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.

That might not sound like a big deal to the average brewmaster, but the findings overturn results reported in scientific literature in the last 40 years and could lead to new pharmaceuticals to treat diabetes, some types of cancer and other maladies.

“Now that we have the right results, what happens to the bitter hops in the beer-brewing process makes a lot more sense,” said Werner Kaminsky, a 天美影视传媒 research associate professor of chemistry.

Kaminsky is the lead author of a describing the findings, published this month in the journal .

There is documentation that beer and its bittering acids, in moderation, have beneficial effects on diabetes, some forms of cancer, inflammation and perhaps even weight loss.

Kaminsky used a process called X-ray crystallography to figure out the exact structure of those acids, humulone molecules and some of their derivatives, produced from hops in the brewing process. That structure is important to researchers looking for ways to incorporate those substances, and their health effects, into new pharmaceuticals.

Humulone molecules are rearranged during the brewing process to contain a ring with five carbon atoms instead of six. At the end of the process two side groups are formed that can be configured in four different ways 鈥� both groups can be above the ring or below, or they can be on opposite sides.

Which of the forms the molecule takes determines its “handedness,” Kaminsky said, and that is important for understanding how a particular humulone will react with another substance. If they are paired correctly, they will fit together like a nut and bolt.

If paired incorrectly, they might not fit together at all or it could be like placing a right hand into a left-handed glove. That could produce disastrous results in pharmaceuticals.

Kaminsky cited thalidomide, which has a number of safe uses but was famously used to treat morning sickness in pregnant women in the late 1950s and early 1960s before it was discovered to cause birth defects. Molecule “handedness” in one form of the drug was responsible for the birth defects, while the orientation of molecules in another form did not appear to have the negative effects.

To determine the configuration of humulones formed in the brewing process, coauthors Jan Urban, Clinton Dahlberg and Brian Carroll of , a Seattle pharmaceutical firm that funded the research, recovered acids from the brewing process and purified them.

They converted the humulones to salt crystals and sent them to Kaminsky, who used X-ray crystallography 鈥� a technique developed in the early 20^th century 鈥� to determine the exact configuration of the molecules.

“Now that we know which hand belongs to which molecule, we can determine which molecule goes to which bitterness taste in beer,” Kaminsky said.

The authors point out that while “excessive beer consumption cannot be recommended to propagate good health, isolated humulones and their derivatives can be prescribed with documented health benefits.”

Some of the compounds have been shown to affect specific illnesses, Kaminsky said, while some with a slight difference in the arrangement of carbon atoms have been ineffective.

The new research sets the stage for finding which of those humulones might be useful in new compounds to be used as medical treatments.

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For more information, contact Kaminsky at 206-543-7585 or wernerka@uw.edu.