Protein being studied to fight cancer; may cause toxicity in cardiac cells.

Asa Gustafsson, UC San Diego

A study by researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences and the Department of Pharmacology at UC San Diego, shows that a protein called MCL-1, which promotes cell survival, is essential for normal heart function.

Their study, published in the June 15 online issue of the journal Genes & Development, found that deletion of the gene encoding MCL-1 in adult mouse hearts led to rapid heart failure within two weeks, and death within a month.

MCL-1 (myeloid cell leukemia-1) is an anti-apoptotic protein, meaning that it prevents or delays the death of a cell. It is also a member of the BCL-2 family of proteins that regulate mitochondria – the cell’s power producers – and cell death. Aberrant expression of anti-apoptotic BCL-2 family members is one of the defining features of cancer cells, and is strongly associated with resistance to current therapies. Thus, these proteins are currently major targets in the development of new therapies for patients with cancer.

But, while MCL-1 is up regulated in a number of human cancers, contributing to the overgrowth of cancer cells, it is found at high levels in normal heart tissue. Additionally, the researchers found that autophagy – a process which deals with mitochondrial maintenance and is normally induced by myocardial stress – was impaired in mice with MCL-1 deficient hearts.

In summary, the study demonstrated that the loss of MCL-1 led to rapid dysfunction of mitochondria, impaired autophagy and heart failure, even in the absence of cardiac stress.

“Cardiac injury, such as a heart attack, causes levels of MCL-1 to drop in the heart, and this process may increase cardiac cell death,” said Åsa B. Gustafsson, Ph.D., an associate professor at UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences. “Therefore, preserving normal levels of this protein in cardiac tissue could reduce damage after a heart attack and prevent progression to heart failure.”

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Poor sleep may be most harmful to women with heart disease, UCSF study finds.

Aric Prather, UC San Francisco

Many women get too little sleep, despite considerable evidence showing the importance of sleep to overall health. Now a new UC San Francisco study has discovered another reason inadequate sleep may be harmful, especially to women and their hearts.

The study found that poor sleep – particularly waking too early – appears to play a significant role in raising unhealthy levels of inflammation among women with coronary heart disease. The elevated inflammation affected only women, not men, even when adjusted for medical, lifestyle and socio-demographic differences, the authors said.

The findings highlight potentially important gender differences and provide evidence that inflammation may serve as a key biological pathway through which poor sleep contributes to the progression of heart disease in women, the researchers reported.

The study will be published online today (June 5) in the Journal of Psychiatric Research.

“Inflammation is a well-known predictor of cardiovascular health,” said lead author Aric Prather, Ph.D., a clinical health psychologist and assistant professor of psychiatry at UCSF. “Now we have evidence that poor sleep appears to play a bigger role than we had previously thought in driving long-term increases in inflammation levels and may contribute to the negative consequences often associated with poor sleep.”

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UC Davis takes team approach to improve cardiac arrest training.

Working to improve cardiac arrest training — training for what are called “Code Blue” events — a multidisciplinary UC Davis Health System team has created a novel initiative that takes advantage of the university’s high-tech simulation facilities and equipment and its highly regarded emergency and trauma care expertise.

“Few formalized training programs exist in the country for interprofessional, multidisciplinary Code Blue teams,” said Aaron Bair, associate professor of emergency medicine and medical director for the UC Davis Center for Health and Technology, where much of the simulation training and expertise are based. “The lack of team training can result in confused or poor communication during a code event. We’ve designed a program that identifies specific processes and measures for improvement and is able to provide educational opportunities throughout the health system to address deficiencies.”

Known as the Code Blue Team Training Initiative, Bair and his colleagues are working their way through various units at UC Davis Medical Center, where they have been scheduling short but intense cardiopulmonary arrest scenarios using high-fidelity human patient simulators. The exercises involve the full range of clinical care personnel, including residents, pharmacists, respiratory therapists, nurses, physicians and others.

“What’s unique about this initiative is that not only do we use portable simulation mannequins to create a very realistic Code Blue scenario,” said Bair, “but we have a team of observers taking detailed notes. The exercises are also videotaped, and we provide immediate feedback as well as a follow-up debriefing so that every participant learns about their strengths and knows the areas where there is room for improvement.”

Data gathered during the exercises assess both technical and non-technical skills, such as measuring the compression fraction during CPR (the fraction of time during a pulseless arrest when chest compressions are actually being performed, which can correspond to survival outcomes), CPR interruptions, the timing of medications, leadership and communication. Video from the training exercise is available to participants so they can better understand the key training principles. In addition, the Code Blue team is producing new online educational modules at the Center for Health and Technology to help enhance code response skills and performance. A number of these modules are already available through iTunes U.

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Pulse oximetry test, already used at UCLA, will be mandatory statewide July 1.

Baby Gaël

Before he was discharged from UCLA Medical Center, Santa Monica, baby Gaël Villegas received the standard panel of newborn screenings to check for genetic and metabolic diseases and hearing. The results showed a healthy baby.

Then, one more screening — a non-mandatory test that the UCLA Health System routinely offers — was performed to check for critical congenital heart disease, or CCHD.

The test, known as a pulse oximetry screening, detected a problem. Baby Gaël was soon diagnosed with a condition that prevented his blood from flowing properly, and he was transferred to Mattel Children’s Hospital UCLA in Westwood. At 7 days old, he underwent a six-hour open-heart surgery with Dr. Hillel Laks, a professor of cardiothoracic surgery at UCLA, to repair the defect. Had it been left undetected and untreated, Gaël would have eventually ended up back in the hospital in serious condition.

“Without the screening, we would have taken him home thinking that he was perfectly healthy,” said Gaël’s father, Davis Villegas. “When they did the test and told us about his heart condition it was hard news to get, but now we see that it was a blessing in disguise. It was better to know about the problem from the beginning so they could fix it.”

While UCLA has been performing pulse oximetry tests voluntarily for the past year as part of its overall program to provide the best methods for early detection and the prompt initiation of appropriate therapies for CCHD, recently passed legislation mandates that all babies born in California hospitals be screened for CCHD starting July 1.

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Patients in “medical homes” more likely to get flu shots, receive regular care.

Too many cooks may spoil a recipe, and too many doctors may give you the flu.

That’s the takeaway from a new study by the UCLA Center for Health Policy Research that found that Californians who jump from provider to provider rather than seeing a regular doctor who coordinates their care may be less likely to get the kind of preventive treatment that protects against the flu and flare ups in their chronic conditions.

Specifically, the study used data from the 2009 California Health Interview Survey (CHIS) to estimate whether the approximately 4.76 million California adults with chronic conditions such as diabetes, asthma and heart disease had three key characteristics of “medical home” care. Those three characteristics are:

• The patient saw a regular doctor over time rather than switching from provider to provider.
• This regular doctor developed an individual treatment plan for the patient.
• The doctor coordinated the patient’s care.

The result? Californians who had all three of these characteristics were the most likely to get a regular flu shot, compared with those without a usual source of care. They were also more likely to have seen their doctor five or more times in the past year and to have called their doctor with a question about their care. Additionally, they were the most confident about their ability to manage their health.

“Seeing the same doctor over time builds familiarity, trust and confidence for both provider and patient,” said Nadereh Pourat, the UCLA center’s director of research and lead author of the study. “And if that doctor takes a coordinated approach to their patients’ care, there seems to be a big payoff in terms of better health for their patients.”

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UCLA study looks in detail at more than 2,500 patients treated over last 20 years.
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Tamara Horwich, UCLA

UCLA researchers examining outcomes for advanced heart-failure patients over the past two decades have found that, coinciding with the increased availability and use of new therapies, overall mortality has decreased and sudden cardiac death, caused by the rapid onset of severe abnormal heart rhythms, has declined.

However, the team found that even today, with these significant improvements, one-third of patients don’t survive more than three years after being diagnosed with advanced disease. Heart failure is increasingly common, affecting close to 6 million individuals in the United States alone.

“We are doing a good job of ensuring that patients receive the latest therapies for heart failure, but we still have a lot more work to do,” said senior author Dr. Tamara Horwich, an assistant professor of cardiology at the David Geffen School of Medicine at UCLA. “It is very sobering that despite recent improvements, a third of advanced heart-failure patients aren’t surviving past three years.”

The findings are published in the May issue of the journal Circulation–Heart Failure.

The study focused on heart failure patients referred to UCLA, a major center for advanced heart failure management and heart transplants. The researchers examined outcomes in 2,507 adults who had “heart failure with reduced ejection fraction,” which is characterized by a weak heart muscle.

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ViVita Technologies includes UC Davis vet, three biomedical engineering doctoral students.

The winning team for both first place and People's Choice: (from left) Maelene Wong, biomedical engineering graduate student; Leigh Griffiths, assistant professor of veterinary medicine and epidemiology; Jeni Lee, biomedical engineering graduate student; and Gina MacBarb, biomedical engineering graduate student.

A new approach to tissue preparation that makes heart valve replacements less likely to be rejected by the body’s immune system — potentially giving transplant patients longer, healthier lives — was the clear favorite in this year’s UC Davis business plan competition — sweeping both the first prize and the People’s Choice award.

ViVita Technologies, a team comprising a UC Davis veterinarian and three biomedical engineering doctoral students, took home a total of $12,000 in the 13th annual Big Bang! Business Plan Competition, run by MBA students in the UC Davis Graduate School of Management: $10,000 for first place, decided by a team of judges, and $2,000 for the People’s Choice award, decided by a vote of the approximately 150 people who attended the awards ceremony Thursday evening (May 16) at the UC Davis Conference Center.

Second prize of $5,000 went to Davis Chem, a team that is working to commercialize a sustainable method of producing isobutryaldehyde, a common base chemical used in everything from paint to cosmetics, with genetically modified E. coli bacteria rather than with the petroleum products currently used in production.

ViVita Technologies was driven to create its product to address the current shortage of organs. “But unlike with current heart valve transplants, the patient would be free from a lifetime of drugs,” said Maelene Wong, chief executive officer of the nascent company.

The ViVita process removes substances that trigger patients’ immune response while preserving the structural integrity and functional properties of the replacement valve tissue. The method has been successfully tested on small animals, they said.

The proprietary process allows the patient’s own cells to join and grow with the transplant tissue — a process that the team says could eventually be used for any organ transplant. Such an organ transplant would allow the person to lead a normal, healthy life without fear of organ rejection and the need to spend a lifetime on anti-rejection medication. It would also allow for better transplant methods for children, who often need new transplants, and additional surgeries, when their bodies grow, Wong said.

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Inhalation of emissions can contribute to clogged arteries.

Jesus Araujo, UCLA

Academic researchers have found that breathing motor vehicle emissions triggers a change in high-density lipoprotein (HDL) cholesterol, altering its cardiovascular protective qualities so that it actually contributes to clogged arteries.

In addition to changing HDL from “good” to “bad,” the inhalation of emissions activates other components of oxidation, the early cell and tissue damage that causes inflammation, leading to hardening of the arteries, according to the research team, which included scientists from UCLA and other institutions.

The findings of this early study, done in mice, are available in the online edition of the journal Arteriosclerosis, Thrombosis and Vascular Biology, a publication of the American Heart Association, and will appear in the journal’s June print edition.

Emission particles such as those from vehicles are major pollutants in urban settings. These particles are coated in chemicals that are sensitive to free radicals, which have been known to cause oxidation. The mechanism behind how this leads to atherosclerosis, however, has not been well understood.

In the study, the researchers found that after two weeks of exposure to vehicle emissions, mice showed oxidative damage in the blood and liver — damage that was not reversed after a subsequent week of receiving filtered air. Altered HDL cholesterol may play a key role in this damaging process, they said.

“This is the first study showing that air pollutants promote the development of dysfunctional, pro-oxidative HDL cholesterol and the activation of an internal oxidation pathway, which may be one of the mechanisms in how air pollution can exacerbate clogged arteries that lead to heart disease and stroke,” said senior author Dr. Jesus Araujo, an associate professor of medicine and director of environmental cardiology at the David Geffen School of Medicine at UCLA.

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UCLA nursing hosting event April 11-13.

New findings on the role gender plays in the diagnosis, treatment and prevention of heart disease will be among the research topics highlighted by faculty members and students from the UCLA School of Nursing at the annual Western Institute of Nursing Conference, which runs from April 11 to 13 in Anaheim.

At a special state-of-the-science panel on Saturday, April 13, UCLA professor Lynn V. Doering will present a review of gender differences in identification, treatment and outcomes for cardiovascular disease, with a focus on coronary atherosclerosis, heart failure and stroke. During the same panel, UCLA professor JoAnn Eastwood will introduce her novel study in which she is partnering with a community organization and using mobile health technologies to reduce cardiac risk factors among young minority women.

“Cardiovascular disease is the No. 1 killer of women and accounts for more female deaths than all cancers and lung disease combined,” Doering said. “Heart disease — particularly its symptoms — presents differently in women, and it is not so obvious in current testing, so it is harder to diagnose. The cutting-edge work that is being presented will provide critical information on diagnosis, treatment and prevention of cardiovascular disease in women.”

Also during the three-day conference, UCLA School of Nursing faculty and doctoral students will present symposia on health care and nursing education for vulnerable populations and on the behavioral symptoms of dementia.

During the symposium “Cultivating Nurse Leaders: A Framework for Nursing Education in Vulnerable Populations” on Friday, April 12, three UCLA nursing researchers will discuss their work on finding ways to eliminate the cultural, financial and language barriers that impact health care delivery. Health disparities continue to exist among vulnerable populations, the researchers stress, and addressing inequities requires mentoring and guiding new nurse–scientists to conduct research in this important area.

On Saturday, April 13, “Promoting the Health of Vulnerable Populations” will take a look at the challenges of meeting the health care needs of four vulnerable populations: homeless men on parole, homeless men and women who suffer from frailty, methamphetamine users who are mothers, and American Indians suffering effects of abuse.

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Blocking inflammation pathway prevents cardiac fibrosis following heart attack, study shows.

Bruce Hammock and Nipavan Chiamvimonvat, UC Davis

New research from UC Davis published in the Proceedings of the National Academy of Sciences shows that blocking an enzyme that promotes inflammation can prevent the tissue damage following a heart attack that often leads to heart failure.

Led by Nipavan Chiamvimonvat, cardiologist and professor of internal medicine, a team of researchers tested a compound that inhibits the enzyme soluble epoxide hydrolase — or sEH — one of the key players in the robust immune-system response that heals tissue following an injury. The enzyme, however, can become counterproductive after a cardiac event.

Chiamvimonvat explained that sEH increases proinflammatory lipid mediators, leading to long-term, heightened inflammatory conditions. It also causes cells, which typically link together and provide the foundation for heart tissue, to overwork. The outcome is scar tissue, or fibrosis, that results in an abnormal relaxation of the heart after each beat, taxing remaining heart muscle as it performs double duty and eventually leading to a decline in the heart’s pumping action.

“We often see patients following a heart attack in clinic who initially respond well to current treatments, which address the initial causes of the cardiac event and try to preserve heart function,” said Chiamvimonvat, whose research focuses on the biological mechanisms of heart disease. “Over time, though, heart function in some patients continues to worsen and can lead to heart failure. It would be ideal to have new approaches that target the cellular overproduction that leads to heart muscle stiffening and cardiac fibrosis.”

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Ambitious UCSF project highlights promise of precision medicine.

Heidi Dohse has spent much of her adulthood monitoring a pacemaker implanted into her chest at the age of 19 to repair arrhythmias, or rapid irregular heartbeats.

For years, that’s meant that Dohse, 49, has had to fly several times a year from her New York home to California for check-ups with the medical team at UC San Francisco that performed the life-saving procedure to correct her heart rhythms when she was a teenager.

Those time-consuming trips are no longer as necessary since she’s enrolled in an ambitious UCSF-developed online cardiovascular study that harnesses the power of mobile technology to monitor patients using their smartphones and send the information to doctors who can analyze the data and provide instant feedback.

“Because I live in New York and my UCSF doctors are here in San Francisco, I can use all these mobile devices and tools to feel like I’m still a patient of theirs,” Dohse said. “It’s one of the reasons my staying with UCSF makes sense.”

Through the Health eHeart Study, which launched today (March 19), physicians hope to better understand how the heart functions and to develop new ways to predict and prevent cardiovascular disease. The study – funded by the Salesforce.com Foundation – aims to enroll 1 million people from around the world.

“We hope to be able to collect copious amounts of data on a large segment of the population so we can develop very robust and accurate models to predict the occurrence of heart disease in people who don’t yet have heart disease, or slow the progression in people who already have heart disease,” said cardiac electrophysiologist Jeffrey Olgin, M.D., chief of the UCSF Division of Cardiology.

A major goal of the Health eHeart Study is to make health care delivery more precise.

The study allows participants to submit data via a secure online survey and uses smartphone technology to measure a participant’s heart rate, blood pressure and pulse rate. The information is sent back to researchers, who can make recommendations to help prevent or treat heart disease.

The concept of precision medicine – which emerged from a 2010 National Academy of Sciences report co-authored by UCSF Chancellor Susan Desmond-Hellmann, M.D., M.P.H., and Charles Sawyers, M.D., of Memorial Sloan-Kettering Cancer Center – is to transform medical care worldwide by integrating the wealth of data emerging from both the human genome and research on the molecular basis of disease, with information from patients’ health records and environmental data. It has become a driving vision for UCSF, which is convening a summit in May to create a roadmap for precision medicine nationwide.

“With this platform, we hope to be able to diagnose and treat heart patients more rapidly than is currently done with traditional research, since we’ll have a large patient population,” Olgin said. “And because these patients are connected to us electronically and through their smartphones, we can deploy the study very quickly.”

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UCLA nursing professor co-authors World Health Organization report.

Linda Sarna, UCLA

Nurses and midwives can play a critical role in lessening people’s risk of cardiovascular diseases, cancers, chronic respiratory disease and diabetes, according to a groundbreaking new report issued by the World Health Organization and co-authored by a UCLA nursing professor.

These four non-communicable disease types account for a combined 60 percent of all deaths worldwide.

“The global burden of non-communicable diseases is already high and continues to grow in all regions of the world,” said Linda Sarna, a professor at the UCLA School of Nursing and co-author of the report. “Nurses and midwives have the expertise to help individuals and communities improve health outcomes.”

Sarna points out that since nurses and midwives make up more than 50 percent of all health care providers in most countries, they are the logical candidates to affect lifestyle changes among patients and increase health awareness. Worldwide, there are more than 19 million nurses and midwives, she said.

The 38-page report issued by the WHO highlights evidence-based, value-added nursing interventions that have been shown to reduce such risk factors as tobacco use, alcohol dependence, physical inactivity and unhealthy diets.

“The examples contained in the report are proven activities that nurses can start doing today to make a meaningful impact with their patients and in their community,” Sarna said. “Many of the interventions have been proven to reduce costs and improve the quality of care.”

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