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International collaboration led by Keck School of Medicine of USC researchers identifies new genetic variants indicating susceptibility to prostate cancer



prostate cancer.

The data study, analyzing more than 87,000 individuals of European, African, Japanese and Latino ancestry, is the largest of its kind and is the first that combines multiple studies across different ethnic populations.

“The goal of this research is to identify regions of the genome that contribute susceptibility to prostate cancer that could be used for understanding a man’s future risk of developing this disease,” said principal investigator Christopher Haiman, Sc.D., professor of preventive medicine, Keck School of Medicine of USC. “This research also emphasizes the importance of common genetic variation in the etiology of prostate cancer, and the importance of large-scale international genetics consortia.”

According to the American Cancer Society, prostate cancer is the second most common cancer among American men, behind skin cancer. It is estimated that nearly 30,000 men will die of prostate cancer and more than 233,000 new cases will be diagnosed in 2014.

Past genome-wide association studies identified 77 variants associated with prostate cancer risk. The additional 23 variants found in the new study “give us another piece in the puzzle,” Haiman said, and new targets for researchers looking into the causes of prostate cancer.

The combined studies that are part of this research have been conducted around the world over the past seven years. The research is chiefly funded by the NCI GAME-ON Consortium, formed to encourage interdisciplinary international collaborations.

The study, “A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer,” was published Sept. 14, 2014 in Nature Genetics.

Amin Al Olama, A., Kote-Jarai, Z., Berndt, S.I., Conti, D.V., Schumacher, F. ... Haiman, C.A. (2014). A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nature Genetics. Published online Sept. 14, 2014; doi: 10.1038/ng.3094

ABOUT KECK MEDICINE OF USC: Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology (No. 9), and among the Top 25 hospitals in the United States for urology (No. 20) and cancer care (No. 23). The medical center was also awarded an “A” grade from The Leapfrog Group in March, representing outstanding patient safety practices and overall patient outcomes.

For more information, go to www.keckmedicine.org/beyond
An international study co-led by Keck School of Medicine of the University of Southern California (USC) scientists and researchers in the United Kingdom has revealed 23 new genetic susceptibility locations indicating risk for
Preeminent USC surgeon and emergency medicine pioneer dies at 88
Gail Victor Anderson, M.D., was the first professor and chairman of an academic department of emergency medicine in the nation









A memorial service is planned for Friday, Sept. 19, from 11 a.m. to 1 p.m. at the Aresty Auditorium of the USC Health Sciences Campus.

Best known as the “father of emergency medicine,” Dr. Anderson became the first professor and chairman of an academic department of emergency medicine in the United States when the dean of USC's medical school and the medical director of the county hospital asked him to take the position in 1971. Upon his retirement as chairman of the department in 2002, his faculty at the Los Angeles County (LAC) + USC Medical Center had trained more emergency physicians than any other residency program in the country.

“Not many people can say that they launched a new medical specialty, but Gail was one of the few individuals who launched a highly successful specialty in emergency medicine,” said Ed Newton, M.D., interim chair of the USC Department of Emergency Medicine. “In fact, people now can hardly imagine a hospital without emergency medicine. Gail was not only an astute politician and leader, but he was also highly concerned with the welfare of the individual patients. He set that tone for the entire department for many years to come.”

Born on Oct. 3, 1925, in Pensacola, Florida, Dr. Anderson served in the United States Navy during World War II before attending college and graduating from medical school at Loma Linda University. Following residency training in obstetrics and gynecology in Washington, D.C., he became the director of the ob-gyn service at Los Angeles County General Hospital in 1958. Recognized as an extremely accomplished gynecological surgeon and teacher of gynecological surgery, Dr. Anderson became a noted researcher of diabetic pregnancy and rose to become professor and acting chair of the obstetrics and gynecology department at USC.

After the USC emergency medicine training program began in 1971, Dr. Anderson and others continued to push for formal recognition of the specialty during the next two decades. He travelled internationally to meet with physicians also interested in the advancement of emergency medicine. In the early 1970s, he founded the first physician assistant emergency medicine program at LAC+USC. In 1976, he and 11 other representatives formed the American Board of Emergency Medicine and served as its president from 1987 to 1988. Emergency medicine was designated as an independent freestanding specialty the following year.

In 1996, the American College of Emergency Physicians presented the James D. Mills Award for Outstanding Contribution to Emergency Medicine to Dr. Anderson. On the occasion of his retirement, the Board of Supervisors of the County of Los Angeles renamed the emergency department at LAC+USC “The Gail Anderson, M.D. Department of Emergency Medicine.”

Dr. Anderson was active in civic organizations and served the South Pasadena community as school board president, high school team physician, and instructor in school health classes. He was an accomplished athlete, including being a champion Navy boxer, a standout college baseball player, an avid golfer, a skillful tennis player, an enthusiastic skier, and an adventurous sailor.

While his motto was "the patient comes first” during his professional career, he was a loving and caring husband and father known affectionately to his sons as "Doc" and later, to his grandchildren as "Grampa Doc." Dr. Anderson is survived by his wife, Alice; his five sons, Gail Jr., David, Jerrold, Walter, and Mark, and their wives and children; his brother, Donald; and many nieces and nephews.

In lieu of flowers, the family requests donations to Gail V. Anderson, Sr., M.D. Memorial Fund at the Keck School of Medicine of USC, 1975 Zonal Avenue, KAM 300, Los Angeles, CA 90033-9034.  Please contact Stephanie Cypert at (323) 442-2352 for information about donations.

ABOUT KECK MEDICINE OF USC: Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology (No. 9), and among the Top 25 hospitals in the United States for urology (No. 20) and cancer care (No. 23). The medical center was also awarded an “A” grade from The Leapfrog Group in March, representing outstanding patient safety practices and overall patient outcomes.

For more information, go to www.keckmedicine.org/beyond
Gail Victor Anderson, M.D., founding faculty member of the Department of Emergency Medicine at the University of Southern California (USC) and a pioneer in the field, died of complications from pneumonia on Sept. 6, 2014, in Pasadena, California. He was 88.

“The world of medicine has suffered a great loss,” said Carmen A. Puliafito, M.D., MBA, dean of the Keck School of Medicine of USC. “The USC Department of Emergency Medicine residency program is one of the country’s most highly regarded, and that was very much due to Gail’s stewardship.”
Treating insomnia in elderly reduces inflammation, lowers risk for chronic diseases
UCLA study finds a common form of psychotherapy is most effective at alleviating sleeplessness




United States — that sleep loss can increase the risk for cardiovascular disease, hypertension, weight gain, type 2 diabetes, and even lead to an earlier death.

The reason for the increased risk of health problems is thought to be an association between insomnia and an increase in inflammation throughout the body that becomes chronic. Though inflammation can be a good thing — part of a robust immune response that heals injury and fights infection, chronic inflammation can damage and kill healthy cells, leading to disease.

What hasn’t been known is whether treating insomnia could reduce inflammation, thereby lowering the risk for chronic disease in older adults. Nor has it been known what the most effective therapy is to treat insomnia.

Now UCLA researchers have answered both these questions. In a new study, they demonstrate that reducing insomnia can indeed lead to decreases in inflammation, and second, that a form of psychotherapy called cognitive behavioral therapy proved superior to other forms of treatment.

The study appears in the September issue of the journal Sleep.

The results were obtained from a randomized clinical trial of 123 adults older than 55, and showed that treating insomnia led to decreases in a known marker of inflammation called C-reactive protein (CRP). The protein is found in blood plasma, and its levels rise in response to an acute inflammatory stimulus. The CRP levels were measured at the beginning of the study, again after treatment, and again in a follow-up 16 months later.

“What we found particularly intriguing was that the levels of the CRP inflammatory marker remained low even 16 months after treating the insomnia,” said Michael Irwin, first author, and a professor of psychiatry and director of the Cousins Center for Psychoneuroimmunology at the UCLA Semel Institute for Neuroscience and Human Behavior.

The researchers also compared three treatments for insomnia:

Cognitive behavioral treatment (CBT), a form of therapy that helps people learn how to identify and change destructive or disturbing thought patterns that have a negative influence on behavior;

Tai chi chih (TCC), the westernized version of the Chinese martial art characterized by slow movement and meditation;

And sleep seminar education, which provided educational information related to the physical, medical, and psychosocial factors of aging and their contribution to sleep problems.

They found that, “by far” noted Irwin, cognitive behavioral therapy performed better than tai chi chih and sleep seminar education in reducing insomnia, and also showed greater and more sustained improvements in sleep quality, the ability to maintain continuous sleep throughout the night, and study participants’ reports of fatigue, and depressive symptoms.

“This is the first randomized, controlled trial that has evaluated the comparative efficacy of TCC versus CBT, a standardized behavioral intervention for insomnia,” Irwin said. The research team found that those who got cognitive behavioral treatment showed a reduced rate of diagnostic insomnia that was nearly double either of the other two treatments.

The benefit of treating insomnia to reduce inflammation is comparable to the benefit reported with vigorous physical activity or weight loss, he noted. “To advance public health, these findings prominently emphasize the position of sleep among the three pillars of health — diet, exercise and sleep.

“Finally, if insomnia is untreated and sleep disturbance persists, we found that CRP levels progressively increase,” Irwin said. “Together, these findings indicate that it is even more critical to treat insomnia in this population who are already at elevated risk for aging-related inflammatory disease.”

Other authors on the study included Richard Olmstead, Carmen Carrillo, Nina Sadeghi, Elizabeth Breen, Tuff Witarama, Megumi Yokomizo; Helen Lavretsky, Jude Carroll, Sarosh Motivala, and Perry Nicassio, all of UCLA; and Richard Bootzin, of the University of Arizona. Funding was provided by the National Institute of Aging. The authors have indicated no financial conflicts of interest.
Lack of sleep can make you sick. And while everybody has the occasional restless night, for those who suffer from chronic insomnia — some 15 percent of older adults in the
Keck Medical Center of USC surgeon becomes first in world to use FDA cleared advanced robotic technology to remove kidney tumor in outpatient procedure




Urologic surgeons at the USC Institute of Urology, part of Keck Medicine of USC, used a Food and Drug Administration (FDA)-cleared laparoscopic device, the high intensity focused ultrasound (HIFU) surgical ablation system for ablating intra-abdominal tumors. The system enables surgeons to penetrate the abdominal cavity with keyhole cuts to eliminate tumors of four centimeters or less.

Inderbir Gill, M.D., founding executive director, USC Institute of Urology, and chairman and professor, Catherine and Joseph Aresty Department of Urology at the Keck School of Medicine of USC, performed the surgery on patient Gary Fradkin, a 62-year-old Van Nuys resident, who went home the same day, three to four days less than patients typically experience with kidney cancer surgery.

“Using a focused beam of ultrasound directly on the tumor and minimally invasive surgery, we destroyed the tumor without surgically removing it from the body,” Gill said. “The most important aspects of this technology are the reduced trauma to the patient and the ability to save the kidney, without the tumor, for a healthier lifestyle post-surgery. This surgery offers fewer chances for infection and post-operative complications. Our goal is to save as much of the good kidney as possible and help patients return to a normal lifestyle quickly.”

According to the American Cancer Society, nearly 64,000 new cases of kidney cancer will occur in 2014, of which nearly 14,000 Americans will die from the disease. Kidney cancer is one of the 10 most common cancers in men and women and has been on the increase since the 1990s with a typical patient at an average age of 65. Some research indicates the possible increase may be because of improved imaging tests. Yet, while diagnoses are increasing, survival rates are also increasing, especially among expert surgeons using advanced technology.

HIFU surgery is an option for patients whose tumors are four centimeters or smaller, which accounts for about 10 percent of all kidney tumors, Gill said. Although this surgery was on a kidney, HIFU surgery can also be an option for cancer of the prostate, liver, pancreas and other organs.

For Fradkin, a post-production engineer who builds screening rooms and performs other software and hardware installation work as part of the film industry, the faster recovery time of the HIFU procedure is advantageous to his busy work life and active, healthy lifestyle. Fradkin previously had two cancerous kidney tumors removed by Gill at Keck Medical Center of USC, whom he credits with saving his kidney after another urologist recommended removing it. Fradkin’s kidneys continue to have functioning problems, leaving limited options for removing one kidney, said Gill, who is recognized internationally for his work in robotic surgery and expertise in complicated procedures. Gill pioneered and perfected the procedure to maintain uninterrupted blood flow to the kidney during surgery, making the kidney more viable after the tumor is removed.

For Fradkin, the prospect of being inactive bothered him more than cancer surgery. An avid cross-fit athlete and windsurfer, getting back to his day-to-day life as quickly as possible was the key to saying yes to the new procedure.

“The cancer part didn’t scare me,” Fradkin said. “But at 62 years old it’s hard to keep in shape, and I was worried about starting all over again, especially with my cross-fit class. The silver lining this time is that this is an outpatient procedure. It didn’t surprise me a bit that Dr. Gill would suggest this new technology. He’s always on the cutting edge of surgery.”

Most kidney tumors are discovered when they are small and the patient is not experiencing symptoms, which was the case with Fradkin. Although traditional surgery is an effective remedy, the risk of complications from such surgery can be daunting.

Of 12 patients in the United Kingdom who participated in a 2011 proof-of-concept study of HIFU for kidney tumors, seven were cancer-free after 24 months.

ABOUT THE USC INSTITUTE OF UROLOGY: The USC Institute of Urology leads the way in robotic and open surgery for urologic cancers, including minimally invasive focal therapy. Faculty researchers are also studying genetic and other causes of bladder, prostate and kidney cancer. Their innovations build on USC’s prior accomplishments over three decades in pioneering groundbreaking treatments, including bladder reconstruction techniques that have changed patients’ lives for the better. The Institute provides a complete range of treatments for various urologic conditions through several specialized centers, including the Center for Robotic Surgery, Center of Comprehensive Urologic Oncology, Center for Female Pelvic Medicine and Reconstructive Surgery, Center for Endourology & Stone Disease, Center for Genito-urinary Reconstruction and Prosthetics, Center for Targeted Therapies and a new Center for Male Infertility. The institute has clinical locations in Los Angeles, Bakersfield, Beverly Hills, Glendale, Glendora, Lancaster, Pasadena, Thousand Oaks, Tulare and Tustin.

ABOUT KECK MEDICINE OF USC: Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology (No. 9), and among the Top 25 hospitals in the United States for urology (No. 20) and cancer care (No. 23). The medical center was also awarded an “A” grade from The Leapfrog Group in March, representing outstanding patient safety practices and overall patient outcomes.
Keck Medical Center of the University of Southern California (USC) is the first medical center in the world to use new robotic technology in an outpatient procedure for a kidney cancer patient.
Providence Little Company of Mary Foundation Awarded Grant in Statewide Drive to Insure More Californians
Funding to Educate Public about Covered California Insurance Options






         Covered California’s Navigator Grant Program will provide education and in-person enrollment assistance to consumers who joined the statewide insurance exchange this year and for those who plan to enroll in 2015. It targets under-served populations, including those who never have had health insurance, do not speak English well, who lost health insurance coverage when they lost their jobs and those who work at jobs that don’t provide insurance.

         “Our core strategy is to create healthier communities together by partnering to improve access to top quality, affordable care,” said Patricia Modrzejewski, is chief development officer and president, Providence Health & Services Foundations/Southern California. “We’re proud to be a part of this campaign to help more Californians obtain health care insurance, which is sure to improve the health of our communities.”

         Providence health care promoters – or promotoras – will reach out in the South Bay and Westside communities to the uninsured and educate them on accessing health coverage through Covered California, which launched this year. The promotoras, speak both English and Spanish, and are certified by the state to educate and enroll the public in health insurance options. 

         Under the terms of the grant, supported by the federal funding provided under the Affordable Care Act, the Providence team will reach out to the community for an eight-month period, starting Oct. 1. Open enrollment for consumers to choose health care plans begins Nov. 15, and continues through Feb. 15, but Covered California will begin reaching out in October to those with insurance to prepare them for renewing their coverage.

         Providence promotoras will draw upon their successes learned earlier this year in helping vulnerable populations find health care coverage. Justin Joe, manager for Providence’s navigator grant program, acknowledged Providence’s commitment to collaborate in the community in this effort.

         “We are excited to continue developing partnerships with local churches, schools and other neighborhood groups to get more people in our communities covered,” he said.

         Educating the uninsured on health care will include explaining terminology and concepts such as copays, premiums and deductibles, and how those out-of-pocket costs should be weighed in choosing the appropriate insurance plans for clients and their families.

About Providence Health & Services: Providence Health & Services, Southern California, is a Catholic not-for-profit, mission-driven healthcare system. Providence Southern California operates six award-winning hospitals and a comprehensive, fully-integrated network of primary care clinics, urgent care centers, home care, TrinityCare and TrinityKids Care hospice as well as Providence High School. Providence is anchored locally by Providence Holy Cross Medical Center in Mission Hills, Providence Saint Joseph Medical Center in Burbank, Providence Saint John’s Health Center in Santa Monica, Providence Tarzana Medical Center and Providence Little Company of Mary Medical Centers in Torrance and San Pedro. With more than 3,400 physicians, Providence provides coordinated primary and specialty care through an array of physician groups and individual providers including Providence Medical Institute and physician groups in the South Bay, the West Valley and Santa Clarita. Providence affiliate, Facey Medical Group, provides primary and specialized care in the San Fernando, Santa Clarita and San Gabriel valleys. For more information, visit California.providence.org.

About Covered California: Covered California is the state’s marketplace for the federal Patient Protection and Affordable Care Act. Covered California, in partnership with the California Department of Health Care Services, was charged with creating a new health insurance marketplace in which individuals and small businesses can get access to affordable health insurance plans. Covered California helps individuals determine whether they are eligible for premium assistance that is available on a sliding-scale basis to reduce insurance costs or whether they are eligible for low-cost or no-cost Medi-Cal. Consumers can then compare health insurance plans and choose the plan that works best for their health needs and budget. Small businesses can purchase competitively priced health insurance plans and offer their employees the ability to choose from an array of plans and may qualify for federal tax credits.

Covered California is an independent part of the state government whose job is to make the new market work for California’s consumers. It is overseen by a five-member board appointed by the governor and the Legislature. For more information about Covered California, please visit www.CoveredCA.com.
The Providence Little Company of  Mary Foundation was awarded a $183,342 grant this week by Covered California as part of  a statewide outreach campaign to attract consumers to the insurance exchange made possible through the federal Affordable Care Act.
Keck Medicine of USC’s USC Institute of Urology appoints highly regarded resident as new assistant professor of clinical urology










He is also associate residency program director and director of Surgical Simulation and Education at the USC Institute of Urology.

After completing his urology residency at Los Angeles County + USC Medical Center, Hung completed a fellowship in advanced laparoscopy and robotics under Inderbir Gill, M.D., a world leader in minimally invasive urological surgery.

Hung is an expert in robotic, laparoscopic and traditional open surgery for diseases of the adrenal, kidney, ureter, bladder and prostate. He is a recognized leader in the validation and development of innovative surgical simulation technologies. To train the next generation of urologic surgeons, he developed the first-ever procedure-specific simulation for robotic surgery.

He has written several first-author and senior-author papers in leading urologic journals on surgical simulation and image-guided therapies for urologic diseases. He is a regular peer-reviewer for leading urologic journals, including European Urology, Journal of Urology and the British Journal of Urology International. He has presented at several international and national meetings, and has received distinct honors, including speaking at the 2014 American Urological Association annual meeting to present his work on robotic surgical simulation and mentoring.

ABOUT THE USC INSTITUTE OF UROLOGY: The USC Institute of Urology leads the way in robotic and open surgery for urologic cancers, including minimally invasive focal therapy. Faculty researchers are also studying genetic and other causes of bladder, prostate and kidney cancer. Their innovations build on USC’s prior accomplishments over three decades in pioneering groundbreaking treatments, including bladder reconstruction techniques that have changed patients’ lives for the better. The Institute provides a complete range of treatments for various urologic conditions through several specialized centers, including the Center for Robotic Surgery, Center of Comprehensive Urologic Oncology, Center for Female Pelvic Medicine and Reconstructive Surgery, Center for Endourology & Stone Disease, Center for Genito-urinary Reconstruction and Prosthetics, Center for Targeted Therapies and a new Center for Male Infertility. The institute has clinical locations in Los Angeles, Bakersfield, Beverly Hills, Glendale, Glendora, Lancaster, Pasadena, Thousand Oaks, Tulare and Tustin.

ABOUT KECK MEDICINE OF USC: Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology (No. 9), and among the Top 25 hospitals in the United States for urology (No. 20) and cancer care (No. 23). The medical center was also awarded an “A” grade from The Leapfrog Group in March, representing outstanding patient safety practices and overall patient outcomes.

For more information, go to www.keckmedicine.org/beyond
Keck Medicine of the University of Southern California (USC)’s USC Institute of Urology announces the addition of a top resident, Andrew J. Hung, M.D., an expert in surgery for a variety of urological conditions and an innovator in surgical skills, to its urologic surgical team.

Hung, assistant professor of clinical urology at the Keck School of Medicine of USC, part of Keck Medicine of USC, began practicing July 1 at the Keck Medicine of USC – Pasadena and Keck Medicine of USC – Downtown Los Angeles satellite clinics. He also practices at Keck Hospital of USC and the USC Norris Comprehensive Cancer Center and Hospital, both part of Keck Medicine of USC.
UCLA Spark campaign raising funds to treat low sexual desire in female cancer survivors




consciousness about changes to their bodies, such as scaring, or simply from the stress of battling a life-threatening disease.

These sexual aftereffects are often ignored or described as the “price of survival.” Currently, no treatments have been approved by the Food and Drug Administration (FDA) to treat low sexual desire. Pro-sexual research studies are not supported by federal government grants, and the technology expenses associated with this research are larger than philanthropic foundations typically support.

For this reason, researchers at UCLA, led by Nicole Prause, an associate research scientist at the UCLA Semel Institute for Neuroscience and Human Behavior, are turning to UCLA Spark, an online crowdfunding platform aimed at providing fundraising support for innovative projects at UCLA. For this effort, the Accelerating Desire in Survivors (ADIS) Project, the fundraising goal is beginning with $7,000. That will allow the researchers to help fulfill a need expressed by the community of cancer survivors, recruit volunteers, document the experiences that women report, and finally, to establish a basis for future clinical trials.

Prause and her colleagues want to test a brain stimulation device that may improve a women’s own sexual responsiveness. They believe they finally have the science to know that such devices can target the brain areas that are impaired in women who report problems with low sex drive..

For the study, they will use Transcranial Magnetic Stimulation (TMS), a non-invasive procedure already approved by the FDA to treat depression that has not responded to traditional treatments. TMS uses magnetic fields to alter activity in the brain. Brain stimulation has demonstrated long-term, positive effects; only one series of treatments may be needed, and it is very safe without long-term side effects. 

Women who survive cancer often have long-term effects from the disease or its treatments. Sexual wellness concerns are very common, yet women often feel guilty for even asking about their sexual loss, and doctors are surprisingly shy to ask. The aim of this study is to provide alternative treatment options for women cancer survivors who struggle with their sexual wellness.

The loss of sexual desire is not merely a lifestyle adjustment. It affects intimacy with partners who supported these women through treatment, may impede their ability to have a family, and can contribute to the development of depression. Supporting this research provides a voice to women who want intimacy back in their lives after defeating cancer.

UCLA Spark will host the crowdfunding campaign for 30 days from September 23, 2014 through October 23, 2014. Throughout the month, updates on the project's progress will be provided.

For the study, women who report a loss of pleasure following cancer treatments are invited to attend three TMS treatments on the UCLA campus. Their brain's response to pleasure and their feelings of pleasure will be recorded beginning and after each treatment; patients will also receive an assessment of brain wave response both before and after treatment to show that the TMS treatment successfully improved their sexual response; the data are recorded anonymously and analyzed, and can be used to support larger clinical trials.

The majority of the funding will be used to pay for the cost of the brain stimulation. TMS itself is $350 per stimulation and requires a qualified technician and physician (for safety oversight) to be present, an additional cost. The women who volunteer are compensated for their time and effort in support of this feasibility study. 

This would be the very first demonstration of brain stimulation used to increase sexual response in these women.

Importantly, the ADIS project will provide evidence in cancer survivors that would support a larger clinical trial in 2015. Long term, the goal is to develop TMS as an intervention for all women who have low sexual desire and have lost pleasure in their lives. 

The study will be led by one of the few research teams in the world with the expertise to conduct such a project:

Nicole Prause (Ph.D.), is a scientist championing neuroscience research into women's sexual behaviors. She is an associate research scientist at the UCLA Semel Institute for Neuroscience and Human Behavior, and one of the few sexual psychophysiologists (psycho=psychology, physiology=body response) in the United States.

Marco Iacoboni (MD, Ph.D.), is fascinated by human connections and develops cutting edge transcranial brain stimulation with his team (TMS fellow Choi Deblieck, safety oversight physician Allan Wu) at the UCLA Brain Mapping Center. He headlined early research into mirror neurons and has written about them for the public: "Mirroring People: The New Science of How We Connect with Others."

Donations of any size and scope will make a dramatic impact on the ability of the scientists to research a neglected area of women's health. 

In addition to any donations, the researchers ask that individuals champion women's health by sharing the ADIS message on Facebook, and on Twitter using the hashtag #ReclaimRecovery. Please see http://ucla.in/ZHuGds for more information.

The Semel Institute for Neuroscience and Human Behavior is an interdisciplinary research and education institute devoted to the understanding of complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior, and the causes and consequences of neuropsychiatric disorders. In addition to conducting fundamental research, the institute faculty seeks to develop effective strategies for prevention and treatment of neurological, psychiatric and behavioral disorder, including improvement in access to mental health services and the shaping of national health policy. 
Women who survive cancer face a number of long-term challenges after treatment; for many, this can include a loss of their sex drive. The reasons are varied, ranging from self-
Keck Medicine of USC researchers discover dual purpose of cancer drug in regulating expression of genes




The team investigated whether demethylation of gene bodies induced by the drug 5-Aza-CdR (decitabine), which is used to treat pre-leukemia, could alter gene expression and possibly be a therapeutic target in cancer.

“When we put the drug in cancer cells, we found it not only reactivated some tumor suppressor genes, but it down-regulated the overexpressed oncogene (cancer gene),” said Gangning Liang, Ph.D., associate professor of research, Keck School of Medicine of USC Department of Urology, who is corresponding author on the research. “Overexpression is what turns cancer ‘on.’ The mechanism by which the drug accomplishes this dual action is by removing DNA methylation in the gene body, which we didn’t expect.”

DNA methylation is an epigenetic signaling tool used by cells use to turn genes off. DNA methylation is an important component in many cellular processes, including embryonic development. Mistakes in methylation are linked to several human diseases, including cancer.

The research builds upon past research by Peter Jones, Ph.D., D.Sc., former director of the USC Norris Comprehensive Cancer Center, Distinguished Professor of Urology and Biochemistry & Molecular Biology, and now director of research at the Van Andel Institute.

"The beginnings of epigenetic therapy, which is now the standard of care for myelodysplastic syndrome, can be traced back to the discovery of the DNA demethylating effects of 5-Azacytidine at (USC-affiliated) Children’s Hospital Los Angeles in 1980,” Jones said. “Since that time we have always assumed that the drugs act by switching genes on, thus reapplying the ‘brakes’ to cancer cells. In this paper we show that they may also work by turning down the levels of genes, which have become overexpressed in cancer. In other words, they may also decrease the ‘gasoline’ and this two pronged mechanism, which was entirely unexpected, may help explain why patients respond to epigenetic therapy."

The research, “Gene body methylation can alter gene expression and is a therapeutic target in cancer,” was published online Sept. 25, 2014 in Cancer Cell.

The research is funded by National Institutes of Health grants R37 CA-082422 and RO1 CA-124518.

Yang, X., Han, H., DeCarvalho, D.D., Lay, F.D., Jones, P.A., & Liang, G. (2014). Gene body methylation can alter gene expression and is a therapeutic target in cancer.
Cancer Cell, Published online Sept. 25, 2014 http://dx.doi.org/10.1016/j.ccr.2014.07.028

ABOUT USC NORRIS COMPREHENSIVE CANCER CENTER: USC Norris Comprehensive Cancer Center has been leading the fight to make cancer a disease of the past. As one of the eight original comprehensive cancer centers in the United States, its mission is to treat and prevent cancer by advancing and integrating education, research, and personalized patient care. For 40 years, USC Norris has been revolutionizing cancer research with innovative surgical techniques and novel cancer treatments. The cancer center's breakthroughs and discoveries in the field of epigenetics have led the way to a greater understanding of the underlying causes of cancer and new methods of prevention, detection, and treatment. With a multidisciplinary team of more than 250 dedicated scientists and physicians, USC Norris Comprehensive Cancer Center offers patients hope in the battle against cancer.

ABOUT KECK MEDICINE OF USC: Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology (No. 9), and among the Top 25 hospitals in the United States for urology (No. 20) and cancer care (No. 23). The medical center was also awarded an “A” grade from The Leapfrog Group in March, representing outstanding patient safety practices and overall patient outcomes.

For more information, go to www.keckmedicine.org/beyond
Keck Medicine of USC scientists have discovered new clues about a drug instrumental in treating a certain blood cancer that may provide important targets for researchers searching for cures.
Keck School of Medicine of USC receives federal Administration on Aging grant to become the National Center on Elder Abuse
NCEA provides assistance, training, education and tools to states and community-based organizations addressing elder abuse that affects 1 in 10 seniors each year




part of the Administration on Community Living (ACL) in the U.S. Department of Health and Human Services (HHS).

The $2.2 million three-year grant funds NCEA’s programs which includes technical assistance and training to states and community-based organizations to develop effective prevention, intervention and response efforts addressing elder abuse. The NCEA will also conduct research and advocate for policy changes on behalf of older adults.

“One in 10 Americans over age 60 suffer some form of elder abuse – that is 5 million seniors each year,” said Laura Mosqueda, M.D., chair of the department of Family Medicine and Geriatrics at the Keck School of Medicine of USC and director for the National Center on Elder Abuse. “We see elder abuse, neglect and exploitation as one of the most pressing civil rights issues facing our aging society, and we’re proud to be named the National Center on Elder Abuse to help educate, inform and address the injustices inflicted on our nation’s seniors.”

Elder abuse is a growing problem as Americans are living longer. In fact, 10,000 of baby boomers turn 65 every day and people over the age of 85 represent the fastest growing segment of our society.  With this growing senior population at the same time the number of people who will care for our frail elders is decreasing, the problem of elder abuse will only grow. Elder abuse is manifest in many forms: physical abuse, emotional abuse, sexual abuse, exploitation, neglect and abandonment. Perpetrators can be family members or spouses, health-care workers and others preying upon the vulnerabilities of aged people.

The National Center on Elder Abuse (NCEA) will be spearheaded by Dr. Mosqueda and the team at the Keck School of Medicine of USC in collaboration with the USC School of Gerontology, the American Bar Association and other organizations dedicated to supporting an aging America. The NCEA will be dedicated to increasing identification and reporting of elder abuse; improving the aging community’s ability to detect, intervene and prevent elder abuse; and stimulating sustainable and innovative systems.

“This prestigious designation underscores Keck Medicine of USC’s commitment to the health, safety and wellness of our growing population of older Americans,” said Tom Jackiewicz, senior vice president and CEO of USC Health which oversees Keck Medicine of USC, the university-based medical system. “As a health system dedicated to education, research and clinical care, we are perfectly matched to administrate the National Center on Elder Abuse.”

“With the leadership of Dr. Mosqueda, the National Center on Elder Abuse at Keck School of Medicine of USC becomes a beacon to all of us as we age and face the potential darker issues of getting older,” said Carmen A. Puliafito, M.D., M.B.A., dean of the Keck School of Medicine of USC. “We will be the entity others look to when they need state-of-the-art information and we will be the leaders that push the field forward through education, research, advocacy and other programs to end elder abuse.”

A top-ranked medical system in several specialty areas, Keck Medicine of USC was ranked No. 33 in this year’s U.S. News and World Report “Best Hospitals” issue.

ABOUT KECK MEDICINE OF USC:Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology (No. 9), and among the Top 25 hospitals in the United States for urology (No. 20), cancer care (No. 23) and Top 50 in geriatrics (No. 33). The medical center was also awarded an “A” grade from The Leapfrog Group in March, representing outstanding patient safety practices and overall patient outcomes.

For more information, go to www.keckmedicine.org/beyond
Keck School of Medicine of the University of Southern California (USC) was named the sole grant recipient to become the National Center on Elder Abuse (NCEA), a vital clearinghouse created by the Administration on Aging (AoA),
Memory loss associated with Alzheimer’s reversed for first time
Small trial from UCLA and Buck Institute succeeds using systems approach to memory disorders




mixed up the names of her pets. Patient two kept forgetting once familiar faces at work, forgot his gym locker combination, and had to have his assistants constantly remind him of his work schedule. Patient three’s memory was so bad she used an iPad to record everything, then forgot her password. Her children noticed she commonly lost her train of thought in mid-sentence, and often asked them if they had carried out the tasks that she mistakenly thought she had asked them to do.

Since its first description over 100 years ago, Alzheimer’s disease has been without effective treatment. That may finally be about to change: in the first, small study of a novel, personalized and comprehensive program to reverse memory loss, nine of 10 participants, including the ones above, displayed subjective or objective improvement in their memories beginning within 3-to-6 months after the program’s start. Of the six patients who had to discontinue working or were struggling with their jobs at the time they joined the study, all were able to return to work or continue working with improved performance. Improvements have been sustained, and as of this writing the longest patient follow-up is two and one-half years from initial treatment. These first ten included patients with memory loss associated with Alzheimer’s disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI; when a patient reports cognitive problems). One patient, diagnosed with late stage Alzheimer’s, did not improve. 

The study, which comes jointly from the UCLA Mary S. Easton Center for Alzheimer’s Disease Research and the Buck Institute for Research on Aging, is the first to suggest that memory loss in patients may be reversed, and improvement sustained, using a complex, 36-point therapeutic program that involves comprehensive changes in diet, brain stimulation, exercise, optimization of sleep, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry.  

The findings, published in the current online edition of the journal Aging, “are very encouraging. However, at the current time the results are anecdotal, and therefore a more extensive, controlled clinical trial is warranted,” said Dale Bredesen, the Augustus Rose Professor of Neurology and Director of the Easton Center at UCLA, a professor at the Buck Institute, and the author of the paper. 

In the case of Alzheimer’s disease, Bredesen notes, there is not one drug that has been developed that stops or even slows the disease’s progression, and drugs have only had modest effects on symptoms. “In the past decade alone, hundreds of clinical trials have been conducted for Alzheimer’s at an aggregate cost of over a billion dollars, without success,” he said.

Other chronic illnesses such as cardiovascular disease, cancer, and HIV, have been improved through the use of combination therapies, he noted. Yet in the case of Alzheimer’s and other memory disorders, comprehensive combination therapies have not been explored. Yet over the past few decades, genetic and biochemical research has revealed an extensive network of molecular interactions involved in AD pathogenesis. “That suggested that a broader-based therapeutics approach, rather than a single drug that aims at a single target, may be feasible and potentially more effective for the treatment of cognitive decline due to Alzheimer’s,” said Bredesen.

While extensive preclinical studies from numerous laboratories have identified single pathogenetic targets for potential intervention, in human studies, such single target therapeutic approaches have not borne out. But, said Bredesen, it’s possible addressing multiple targets within the network underlying AD may be successful even when each target is affected in a relatively modest way. “In other words,” he said, “the effects of the various targets may be additive, or even synergistic.”

The uniform failure of drug trials in Alzheimer’s influenced Bredesen’s research to get a better understanding of the fundamental nature of the disease. His laboratory has found evidence that Alzheimer’s disease stems from an imbalance in nerve cell signaling: in the normal brain, specific signals foster nerve connections and memory making, while balancing signals support memory loss, allowing irrelevant information to be forgotten. But in Alzheimer’s disease, the balance of these opposing signals is disturbed, nerve connections are suppressed, and memories are lost. 

The model of multiple targets and an imbalance in signaling runs contrary to the popular dogma that Alzheimer’s is a disease of toxicity, caused by the accumulation of sticky plaques in the brain. Bredesen believes the amyloid beta peptide, the source of the plaques, has a normal function in the brain – as part of a larger set of molecules that promotes signals that cause nerve connections to lapse. Thus the increase in the peptide that occurs in Alzheimer’s disease shifts the memory-making vs. memory-breaking balance in favor of memory loss. 

Given all this, Bredesen thought that rather than a single targeted agent, the solution might be a systems type approach, the kind that is in line with the approach taken with other chronic illnesses—a multiple-component system.  

“The existing Alzheimer’s drugs affect a single target, but Alzheimer’s disease is more complex. Imagine having a roof with 36 holes in it, and your drug patched one hole very well—the drug may have worked, a single “hole” may have been fixed, but you still have 35 other leaks, and so the underlying process may not be affected much.”

Bredesen’s approach is personalized to the patient, based on extensive testing to determine what is affecting the plasticity signaling network of the brain. As one example, in the case of the patient with the demanding job who was forgetting her way home, her therapeutic program consisted of some, but not all of the components involved with Bredesen’s therapeutic program, and included:

(1) eliminating all simple carbohydrates, leading to a weight loss of 20 pounds; (2) eliminating gluten and processed food from her diet, with increased vegetables, fruits, and non-farmed fish; (3) to reduce stress, she began yoga; (4) as a second measure to reduce the stress of her job, she began to meditate for 20 minutes twice per day; (5) she took melatonin each night; (6) she increased her sleep from 4-5 hours per night to 7-8 hours per night; (7) she took methylcobalamin each day; (8) she took vitamin D3  each day; (9) fish oil each day; (10) CoQ10 each day; (11) she optimized her oral hygiene using an electric flosser and electric toothbrush; (12) following discussion with her primary care provider, she reinstated hormone replacement therapy that had been discontinued; (13) she fasted for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime; (14) she exercised for a minimum of 30 minutes, 4-6 days per week.  

The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results are anecdotal, and therefore a more extensive, controlled clinical trial is needed.

The downside to this program is its complexity. It is not easy to follow, with the burden falling on the patients and caregivers, and none of the patients were able to stick to the entire protocol. The significant diet and lifestyle changes, and multiple pills required each day, were the two most common complaints. The good news, though, said Bredesen, are the side effects: “It is noteworthy that the major side effect of this therapeutic system is improved health and an optimal body mass index, a stark contrast to the side effects of many drugs.”

The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results need to be replicated. “The current, anecdotal results require a larger trial, not only to confirm or refute the results reported here, but also to address key questions raised, such as the degree of improvement that can be achieved routinely, how late in the course of cognitive decline reversal can be effected, whether such an approach may be effective in patients with familial Alzheimer’s disease, and last, how long improvement can be sustained,” he said.  

Cognitive decline is a major concern of the aging population. Already, Alzheimer’s disease affects approximately 5.4 million Americans and 30 million people globally. Without effective prevention and treatment, the prospects for the future are bleak. By 2050, it’s estimated that 160 million people globally will have the disease, including 13 million Americans, leading to potential bankruptcy of the Medicare system. Unlike several other chronic illnesses, Alzheimer’s disease is on the rise--recent estimates suggest that AD has become the third leading cause of death in the United States behind cardiovascular disease and cancer.

Multiple entities provided support for the study including the National Institutes of Health (AG16570, AG034427 and AG036975). Please see paper for the complete list.

The Mary S. Easton Center for Alzheimer's Disease Research is part of the UCLA Department of Neurology which encompasses more than 26 disease-related research programs. This includes all of the major categories of neurological diseases and methods, encompassing neurogenetics and neuroimaging as well as health services research. The 140 faculty members of the Department are distinguished scientists and clinicians who have been ranked #1 in NIH funding for 9 consecutive years beginning in 2002. The Department is dedicated to understanding the human nervous system and improving the lives of people with neurological diseases, focusing on three key areas: patient/clinical care, research, and education. For more information, see http://www.neurology.ucla.edu/

The Buck Institute is the U.S.’s first independent research organization devoted to Geroscience – focused on the connection between normal aging and chronic disease. Based in Novato, CA, The Buck is dedicated to extending “Healthspan”, the healthy years of human life and does so utilizing a unique interdisciplinary approach involving laboratories studying the mechanisms of aging and those focused on specific diseases. Buck scientists strive to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer’s and Parkinson’s, cancer, cardiovascular disease, macular degeneration, osteoporosis, diabetes and stroke.  In their collaborative research, they are supported by the most recent developments in genomics, proteomics, bioinformatics and stem cell technologies. For more information: www.thebuck.org
Patient one had two years of progressive memory loss. She was considering quitting her job, which involved analyzing data and writing reports, she got disoriented driving, and
Antioxidant Found in Grapes Uncorks New Targets for Acne Treatment
UCLA study points to resveratrol as key to possible combination therapy




The team also found that combining resveratrol with a common acne medication, benzoyl peroxide, may enhance the drug’s ability to kill the bacteria and could translate into new treatments.

Published in the current online edition of the journal Dermatology and Therapy, the early lab findings demonstrated that resveratrol and benzoyl peroxide attack the acne bacteria, called Propionibacterium acnes, in different ways.

Resveratrol is the same substance that has prompted some doctors to recommend that adults drink red wine for its heart-health properties. The antioxidant stops the formation of free radicals, which cause cell and tissue damage. Benzoyl peroxide is an oxidant that works by creating free radicals that kill the acne bacteria.

“We initially thought that since actions of the two compounds are opposing, the combination should cancel the other out, but they didn’t,” said Dr. Emma Taylor, the study’s first author and an assistant clinical professor of medicine in the division of dermatology at the David Geffen School of Medicine at UCLA. “This study demonstrates that combining an oxidant and an antioxidant may enhance each other and help sustain bacteria-fighting activity over a longer period of time.”

The team grew colonies of the bacteria that causes acne and then added various concentrations of resveratrol and benzoyl peroxide both alone and together. The researchers monitored the cultures for bacterial growth or killing for 10 days.

They found that benzoyl peroxide was able to initially kill the bacteria at all concentration levels, but the effect was short lived and didn’t last beyond the first 24 hours.

Resveratrol didn’t have a strong killing capability, but it inhibited bacterial growth for a longer period of time. Surprisingly, the two compounds together proved the most effective in reducing bacteria counts.

“It was like combining the best of both worlds and offering a two-pronged attack on the bacteria,” said senior author Dr. Jenny Kim, professor of clinical medicine in the division of dermatology at the Geffen School.

Scientists have understood for years how benzoyl peroxide works to treat acne, but less has been known about what makes resveratrol effective — even though it has been the subject of previous studies. Using a high-powered microscope, the UCLA researchers observed that bacteria cells lost some of the structure and definition of their outer membranes, which indicated that resveratrol may work by altering and possibly weakening the structure of the bacteria.

The researchers also cultured human skin cells and blood cells with the two compounds to test their toxicity. They found that benzoyl peroxide was much more toxic than resveratrol, which could help explain what causes skin to become red and irritated when it’s used as a topical treatment in high dose or concentration.

Taylor noted that combining the two compounds allowed for prolonged antibacterial effects on the acne bacteria while minimizing its toxicity to other skin cells. The finding could lead to a more effective and less irritating topical acne therapy.

“We hope that our findings lead to a new class of acne therapies that center on antioxidants such as resveratrol,” Taylor said.

The next stage of research will involve further laboratory testing to better understand the mechanism of the two compounds. Additional research will be needed to validate the findings in patients.

Millions suffer from acne, and it has a significant psychosocial effect on patients, but limited progress has been made in developing new strategies for treating it. According to researchers, antibiotic resistance and side effects limit the efficacy of the current treatments, which include benzoyl peroxide, retinoids, antibiotics and Accutane (isotretinonin).

The study was funded in part by a Women’s Dermatologic Society Academic Research Grant and the National Institutes of Health (RO1 AR053542).

A patent application has been filed for the combination treatment of benzoyl peroxide and resveratrol, which is owned by the University of Calfironia Regents and managed by the UCLA Office of Intellectual Property and Industry Sponsored Research. Other disclosures are available in the manuscript.
Got grapes? UCLA researchers have demonstrated how resveratrol, an antioxidant derived from grapes and found in wine, works to inhibit growth of the bacteria that causes acne.
Two UCLA scientists receive NIH grants to further BRAIN Initiative research




new ways to treat, cure and prevent traumatic brain injuries and brain disorders such as Alzheimer’s disease and epilepsy. 

Today, two UCLA faculty members, Dr. X. William Yang, a professor of psychiatry, and Dr. Daniel Geschwind, a professor of psychiatry, neurology and genetics, were among more than 100 investigators who received funding through the National Institutes of Health’s first wave of investments in research supporting the initiative. 

In all, the NIH awarded $46 million to researchers in 15 states and several countries to develop new tools and technologies to understand the brain’s basic neural circuit function and to capture a dynamic view of the brain in action. 

With more than 500 neuroscientists throughout campus, UCLA is well positioned to play a significant role in the effort. The campus boasts strength not only in neuroscience but also in genetics, nanotechnology, psychology, psychiatry and other academic fields, and researchers from those disciplines work closely together. Even before the national initiative was announced last year, efforts were already underway at UCLA to encourage more cross-disciplinary cooperation. That effort, called UCLA Neuroscience, is chaired by Professor Kelsey Martin, who also chairs UCLA’s biological chemistry department.

“UCLA benefits from a long-standing culture of interdisciplinary research,” Martin said. “Engineers collaborate with neurologists; psychiatrists work with biochemists. The close proximity of UCLA’s medical enterprise to engineering, basic sciences, nanoscience and social sciences — an asset that few other research universities can claim — is a major boon when it comes to encouraging faculty to work together.”

That type of collaboration is a key facet of the research being conducted by Geschwind and Yang, who put together interdisciplinary teams to develop tools that will help scientists better understand the human brain.

X. William Yang

A team led by Yang received a three-year, $1.9 million BRAIN Initiative Award. 

Yang, a member of the Center for Neurobehavioral Genetics at the UCLA Semel Institute for Neuroscience and Human Behavior and the Department of Psychiatry and Biobehavioral Sciences at the David Geffen School of Medicine at UCLA, is collaborating with Dr. Larry Zipursky, a professor of biological chemistry and a Howard Hughes Medical Institute investigator; Dr. Peyman Golshani, a UCLA assistant professor of neurology; and Dr. Hongwei Dong of the USC Keck School of Medicine’s Laboratory of Neuro Imaging.

Their project will develop novel but simple genetic tools that allow visualization of the elaborate morphology, activity and synaptic connections of many different types of neurons in the intact mouse brain. They will also develop new brain mapping computer programs that accelerate reconstruction of neuronal structures and map the neurons onto a standardized reference brain atlas. The tools could allow researchers to link changes within fine structures of specific neurons to the more global function of the brain, and they could enable scientists to model brain disorders, making it easier to discover new disease mechanisms and test new therapies.

“Although mice are obviously different from humans, they are one of the best mammalian models to study brain function and dysfunction,” Yang said. “There are many similarities in terms of neuronal cell types and neural circuits between mouse and human, and there is much to be learned about the mysteries of how the mammalian brain works. We are grateful for this funding.” 

Daniel Geschwind

Geschwind’s research team received a three-year, $2 million grant. 

“After almost 100 years of brain research, we still do not have a complete parts list for the cerebral cortex, which is the pinnacle of human brain evolution,” he said. “We will need to drill down. By using remarkable genomic technologies that allow us to measure all of the genes expressed in a single human brain cell, we can approach defining and identifying the major cell types in the developing human brain.”

In collaboration with Dr. Michael Wigler’s laboratory at Cold Spring Harbor Laboratory in Maine, Geschwind and his team will work toward completing that “parts list” by measuring up to 10,000 individual cells to obtain a representative sample of the types of cells in the brain. Then, using mathematical methods, they will group cells into categories based on the similarities in the patterns of gene expression. 

Ultimately, the team will develop a three-dimensional map of each cell type in the circuits in living mice by applying another new technique that makes the brain transparent, enabling researchers to see all of its cells. The process will rely on new microscopy that is being developed in the laboratory of Dr. Katsushi Arisaka, a UCLA professor of physics and astronomy. The technique will permit rapid image acquisition at high resolution, making parts of individual cells and their connections visible.

Because the project will generate a huge amount of data — more than 1 terabyte — the team is also working with the lab of David Shattuck, an associate professor of neurology at UCLA’s Ahmanson-Lovelace Brain Mapping Center, to develop new techniques for automated image analysis.

“Once we have this parts list, we can use it to understand how cells develop and form the circuits that comprise in the adult brain,” said Geschwind, director of the neurogenetics program and the Center for Autism Research and Treatment at the UCLA Semel Institute. “This is an important step, as many developmental disorders such as autism and schizophrenia arise during the process of brain development.

“Understanding how brain cells develop will serve as a foundation for understanding how disease-causing mutations lead to brain disorders, as well as understanding human brain evolution.”
In April 2013, UCLA scientists led by Chancellor Gene Block were among the guests at President Obama’s announcement of the BRAIN Initiative. The program is aimed at discovering
New digital health solutions unveiled at top influencer conference hosted by USC Center for Body Computing




designers and funders. Speakers will focus on a broad range of topics that showcase the latest innovations in digital health to potentially transform medicine: Music and virtual patient consult apps, wearable tech and industrial design, patient advocacy, Big Data experts, leading investors as well as an Academy Award winner and others talking about patient empowerment and creating your personal health story.

Additional themes explored at this year’s conference include patient privacy issues, 24/7 streams of biometric data that potentially allow diagnosis and treatment to happen in real-time for patients, soldiers or athletes, and the fact that multibillion-dollar companies are turning their focus on digital health to help patients.

The USC CBC, founded in 2007, has been instrumental in leading the narrative on digital health and shaping the body computing movement. Over the years, CBC collaborations with startups and now major companies, combined with interdisciplinary research and development, have resulted in innovative solutions that use digital health to make the world a healthier place. So far 2014 has seen 23 digital health-related FDA clearances for smartphone-connected medical devices and apps.

“Patients can and should be the heroes of their own health stories,” said Leslie A. Saxon, M.D., a Keck Medicine of USC cardiologist and founder/executive director of USC CBC, and internationally recognized for synthesizing business, engineering, entertainment arts and medicine into new paradigms.  “Historically, medical apps have been under-represented, but new apps and innovations, like those we are unveiling today, equip patients to take control over their personal health. Our chief goal is to develop the next-generation digital health solutions and put those in the hands of patients – which can potentially transform medicine.”

The business community agrees. Funding for digital health solutions is expected to nearly double in the next three years – from $3.5 billion in start-ups in 2014 to $6.5 billion in 2017.  The demand is met with equal force on the patient side, with 75 percent of patients expecting digital solutions in the near future, according to a recent report from McKinsey & Company.

At the summit, more than 20 international experts will cover topics from biometrics, design, virtual office visits, patient consent, Big Data and privacy to elite athletic training and venture capital funding.  Some of the day’s highlights include:

Leslie Saxon, M.D. announces results of collaborative study between CBC and AliveCor Heart Monitor that collected and analyzed data collected from 1,000 patients through its FDA-approved mobile electrocardiogram (ECG) device the past year.  She will unveil the Biogram app, a collaboration between USC Viterbi School of Engineering, AliveCor and Medable, and the first app that allows heart rate to be shared with a photo.

Stuart Karten, founder of Karten Design, and Sonny Wu, founder of MisFit Wearables, will explore the future of design and digital health solutions where wearable technology will be replaced by new invisible solutions and implantable microscopic sensors.

Ed Saxon, keynote speaker and multiple Academy Award winning producer, talks about the role storytelling plays in delivering digital medical care so patients can engage in a truly durable and impactful way.

Michelle Longmire, M.D. and founder of Medable, unveils VADable app for iOS created in collaboration with CBC for artificial heart pump patients (ventricular assist devices/VADs) to connect the entire team of caregivers, primary physicians, cardiologists and others through the app for “virtual visits.”

Deborah Peel, M.D. and founder of Patient Privacy Rights and Matt Hogan of Datacoup will look at the issues of personal health data and how to use data to our benefit and what that means in the post-Snowden era.

Dave Albert, M.D. and founder of AliveCor, will explain over-the-counter approval this year and how automated analysis of ECGs provide a groundbreaking example for computerized decision support tools.

Hoby Darling, CEO of Skullcandy, Inc. and Andy Walshe of Red Bull, look at how entertainment, technology and data enhance human performance.

Leaders in venture capital and digital health offer the latest industry perspectives, including Jack Young of Qualcomm Ventures, Dana Mead of Kleiner Perkins and Casper De Clerq of Norwest Ventures.

Ryan Capretta of Proactive Sports shows how sensor data collected from NFL players demonstrate the value of biometric data in training elite athletes, in a joint project with CBC and Zephyr.

Rachel Francine and Andy Tubman, 2014 Body Computing SLAM Contest Winners will present their innovative concept SingFit that garnered a $10,000 prize last night from CBC and Skullcandy Inc., to use the power of music to improve health. The SingFit app finds new solutions by digitizing the evidence-based music therapy technique of lyric prompting, which enables practically everyone, including those with dementia, autism, Parkinson’s and traumatic brain injuries to sing on a regular basis in order to achieve therapeutic goals.

About the USC Center for Body Computing Conference: The 8th Annual USC Center for Body Computing Conference is an event designed to bring digital and life sciences executives, sensor and mobile app inventors, strategists, designers, investors and visionaries from health care, entertainment and technology together for one day to showcase an international array of digital and mobile health ideas.

Founded by Leslie Saxon, an international digital health guru and trained USC cardiologist who has spoken at TEDMED, SXSW and WIRED international conferences, the USC CBC conference is her promise to make consumers “the heroes of their own health stories.” The conference will be held on the USC campus in downtown Los Angeles on October 3. For more information or to register for the conference, visit: uscbodycomputing.org

ABOUT KECK MEDICINE OF USC: Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology (No. 9), and among the Top 25 hospitals in the United States for urology (No. 20) and cancer care (No. 23). The medical center was also awarded an “A” grade from The Leapfrog Group in March, representing outstanding patient safety practices and overall patient outcomes.

For more information, go to http://www.keckmedicine.org/beyond
The University of Southern California (USC) Center for Body Computing (CBC), part of Keck Medicine of USC, today hosts the 8th Annual USC CBC Conference, the leading digital health revolution event of international creators,
Keck Medicine of USC’s USC Institute of Urology appoints highly regarded male fertility expert











She is skilled in surgical techniques for the treatment of these conditions, including minimally invasive vasectomy and microsurgical vasectomy reversals, advanced sperm retrieval techniques, and other procedures. For erectile dysfunction she also specializes in correction of penile curvature and penile prostheses for erectile dysfunction.

Her research goals include discovering the causes of male factor infertility, 60 percent of which is unknown. She presents research at major national and international meetings and is a reviewer for several scientific journals.

Samplaski recently completed her fellowship in male infertility and andrology at Mount Sinai Hospital at the University of Toronto after finishing her urology residency at the Cleveland Clinic Foundation at the Glickman Urological and Kidney Institute in Cleveland, Ohio. Samplaski completed medical school at George Washington University School of Medicine in Washington, D.C.

She has presented at several international and national meetings and has received distinct honors including being awarded the Society for Male Reproduction and Urology Traveling 2013 Scholar at the American Society for Reproductive Medicine, the Arnold Belker Traveling Fellow 2013 at Society for the Study of Male Reproduction at the AUA, Fellow Award for Basic Science and Clinical Research at Robson Research Day, 2013 Outstanding Trainee Investigator Award at the American Society of Andrology Annual Conference, and the NIH Trainee Travel Award at the American Society of Andrology Annual Conference.

ABOUT THE USC INSTITUTE OF UROLOGY: The USC Institute of Urology leads the way in robotic and open surgery for urologic cancers, including minimally invasive focal therapy. Faculty researchers are also studying genetic and other causes of bladder, prostate and kidney cancer. Their innovations build on USC’s prior accomplishments over three decades in pioneering groundbreaking treatments, including bladder reconstruction techniques that have changed patients’ lives for the better. The Institute provides a complete range of treatments for various urologic conditions through several specialized centers, including the Center for Robotic Surgery, Center of Comprehensive Urologic Oncology, Center for Female Pelvic Medicine and Reconstructive Surgery, Center for Endourology & Stone Disease, Center for Genito-urinary Reconstruction and Prosthetics, Center for Targeted Therapies and a new Center for Male Infertility. The institute has clinical locations in Los Angeles, Bakersfield, Beverly Hills, Glendale, Glendora, Lancaster, Pasadena, Thousand Oaks, Tulare and Tustin.

ABOUT KECK MEDICINE OF USC: Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-based medical systems in the Los Angeles area. Encompassing academic, research and clinical excellence, the medical system attracts internationally renowned experts who teach and practice at the Keck School of Medicine of USC, the region’s first medical school; includes the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established by the National Institutes of Health (NIH) in the United States; has a medical faculty practice, the USC Care Medical Group; operates the Keck Medical Center of USC, which includes two acute care hospitals: 401-licensed bed Keck Hospital of USC and 60-licensed bed USC Norris Cancer Hospital; and owns USC Verdugo Hills Hospital, a 158-licensed bed community hospital. It also includes more than 40 outpatient facilities, some at affiliated hospitals, in Los Angeles, Orange, Kern, Tulare and Ventura counties.

U.S. News & World Report ranked Keck Medical Center of USC among the Top 10 in ophthalmology (No. 9), and among the Top 25 hospitals in the United States for urology (No. 20) and cancer care (No. 23). The medical center was also awarded an “A” grade from The Leapfrog Group in March, representing outstanding patient safety practices and overall patient outcomes.

For more information, go to www.keckmedicine.org/beyond
Highly regarded male fertility expert Mary Katherine Samplaski, M.D., has been recruited to the Keck Medicine of the University of Southern California (USC)’s USC Institute of Urology.

Samplaski is an expert in male reproductive health, including fertility preservation counseling and treatment, vasectomies and vasectomy reversals, low testosterone, erectile dysfunction, sexual dysfunction, Peyronie’s disease and testicular pain. She specializes in the management of male infertility with the aim of improving natural conception or improved outcomes from assisted reproduction. She also specializes in fertility for spinal cord injury patients.
UCLA study finds link between neural stem cell overgrowth and autism-like behavior in mice



Among the most commonly observed physical changes seen in individuals with Autism Spectrum Disorder (ASD) is a period of accelerated brain growth after birth. No one knows why, or whether an enlarged brain is linked with any specific behavioral changes. 

Now a new study by researchers at UCLA demonstrates how, in pregnant mice, inflammation, a first line of defense of the immune system, can cause brain overgrowth by triggering an excessive division of neural stem cells.

The paper appears October 9 in the online edition of the journal Stem Cell Reports.  

“Previous studies in mice have suggested that mild maternal inflammation can produce offspring with enlarged brains and autistic features,” said senior author Harley Kornblum, director of the Neural Stem Cell Research Center at UCLA’s Semel Institute for Neuroscience and Human Behavior, and a professor of psychiatry, pharmacology, and pediatrics at the Geffen School of Medicine. “We have now shown that one way maternal inflammation could result in larger brains and, ultimately, autistic behavior, is through the activation of the neural stem cells that reside in the brain of all developing and adult mammals,” he said. 

To mimic an environmental factor—ranging from pollution, bacteria, or the flu--that could activate the immune system, in their study the researchers injected a pregnant mouse early in gestation with a single, very low dose of lipopolysaccharide, a molecule that is an endotoxin--a toxin inside bacteria that is released when the cell disintegrates—that’s found in E. Coli bacteria. The researchers discovered the toxin caused an excessive production of neural stem cells and enlarged brains in the offspring. Neural stem cells differentiate into the major types of cells in the brain, including the neurons that process and transmit information and the glial cells that support and protect those neurons.

Notably, the researchers found that mice with enlarged brains also displayed abnormal behaviors associated with mice-like autism. For example, they were less likely to vocalize when separated from their mother as pups, less likely to be interested in interacting with other mice, showed signs of increased levels of anxiety, and were more likely to engage in repetitive behaviors like excessive grooming.

There are many environmental factors that can cause the activation of a pregnant woman’s immune system, said Kornblum. “Although it’s known that maternal inflammation is a risk factor for some neurodevelopmental disorders such as autism, it’s not thought to directly cause them,” he said. Autism, for example, is clearly a highly heritable (genetic) disorder, he noted, but other, non-genetic factors clearly play a role. 

The researchers also found evidence that the brain-growth stimulating effect of the immune reaction was even greater in mice with a specific genetic mutation—a lack of one copy of a tumor suppressor gene called PTEN (“phosphatase and tensin homolog”). The PTEN protein normally helps to prevent cells from growing and dividing too rapidly. In humans, having an abnormal version of the PTEN gene leads to very large head size or macrocephaly, a condition that also is associated with a high risk of ASD. 

“Autism is a complex group of disorders, with a variety of causes. Our study shows a potential way that maternal inflammation could be one of those contributing factors, even if it is not solely responsible, through interactions with known risk factors,” Kornblum said.

In addition, the team found that the increased neural stem cell proliferation and brain overgrowth was stimulated by the activation of a specific molecular pathway; that is, a series of actions among molecules within a cell that leads to a certain cell function. This pathway involved the enzyme NADPH oxidase, which the UCLA researchers previously found to be associated with neural stem cell growth. “The discovery of these mechanisms has identified new therapeutic targets for common autism-associated risk factors,” says Janel Le Belle, an associate researcher in Kornblum’s lab and the lead author on the paper. “The molecular pathways that are involved in these processes are ones that can be manipulated and possibly even reversed pharmacologically. Furthermore, in agreement with past clinical findings, these data add to the significant evidence that autism-associated brain alterations begin prenatally and continue to evolve after birth,” she said.

“While it was not surprising to us, it may be surprising to others that neural stem cell hyper-proliferation can contribute to autism-associated features like brain overgrowth and behaviors,” Kornblum added. “Autism neuropathology is primarily thought of as a dysregulation of neuronal connectivity, although the molecular and cellular means by which this occurs is not known. Therefore, our hypothesis—that one potential means by which autism may develop is through an overproduction of cells in the brain, which then results in altered connectivity—is a new way of thinking about autism etiology.”

The next step, the researchers say, is to determine if and how the changes that were observed lead to changes in the connections between brain cells, and if those effects can be altered after they have happened. To do so, they are using a type of stem cell known as an induced pluripotent stem cell—which is generated directly from adult cells—to produce neural stem cells from the blood samples of individuals with both autism and brain overgrowth. “We will use these cells to determine the genetic and environmental factors that interact to overstimulate neural stem cell function,” Le Belle said. 

In addition to Kornblum and Le Belle, other authors on the study were Jantzen Sperry, Amy Ngo, Yasmin Ghochani, Dan Laks, Manuel López Aranda, and Alcino J. Silva, all of UCLA. Support was provided by several entities, including the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Autism Speaks, and the National Institutes of Health (grants P50-HD-055784 and MH65756). Please see study for complete list.

The Semel Institute for Neuroscience and Human Behavior is an interdisciplinary research and education institute devoted to the understanding of complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior, and the causes and consequences of neuropsychiatric disorders. In addition to conducting fundamental research, the institute faculty seeks to develop effective strategies for prevention and treatment of neurological, psychiatric and behavioral disorder, including improvement in access to mental health services and the shaping of national health policy. 
Maternal inflammation may be a contributing risk factor to autism through activation of brain cell division, study says
Using a Novel Biological Aging Clock, UCLA Researchers Find that Obesity Accelerates Aging of the Liver
Finding may Explain Why Obese People Suffer from Early Onset of many Age-related Diseases, Including Liver Cancer




obesity greatly accelerates aging of the liver. This finding could explain the early onset of many age-related diseases, including liver cancer, in obese subjects.

Although it had long been suspected that obesity ages a person faster, it hadn’t been possible to prove the theory, said study first author Steve Horvath, a professor of human genetics at the David Geffen School of Medicine at UCLA and a professor of biostatistics at the UCLA Fielding School of Public Health. Using the epigenetic clock Horvath developed last year, he and Jochen Hampe from the University Hospital Dresden showed that carrying excessive weight can negatively impact select human tissues.

“This is the first study that evaluated the effect of body weight on the biological ages of a variety of human tissues,” Horvath said. “Given the obesity epidemic in the Western world, the results of this study are highly relevant for public health.”

The findings appear Oct. 13, 2014, in the early online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences.

Horvath’s aging clock uses a previously unknown time-keeping mechanism in the body to accurately gauge the age of diverse human organs, tissues and cell types. He and his collaborators focused on a naturally occurring process called methylation, a chemical modification of the DNA molecule.

Horvath used this epigenetic clock to measure the biological age of several tissues. The aging clock proved accurate in matching biological to chronological age in lean subjects. But liver tissues from obese subjects tended to have a higher biological age than expected. 

In this study, Horvath looked at almost 1200human tissue samples, including 140 liver samples, to study the relationship between epigenetic age acceleration and body weight. While obesity doesn’t affect the epigenetic age of fat, muscle or blood tissue, he and his collaborators found that, on average, the epigenetic age of the liver increased by 3.3 years for every 10 Body Mass Index (BMI) units.

For example, a woman who is 5 feet 5 and weighs 140 pounds has a BMI of 23.3. A woman the same height but weighing 200 pounds would have a body mass index of 33.3. Her liver would be about three years older than the woman who weighed 140 pounds, the study found.

“This does not sound like a lot, but it is actually a very strong effect,” Horvath said. “For some people, the age acceleration due to obesity will be much more severe, even up to 10 years older.”

Horvath also found that rapid weight loss induced by bariatric surgery did not reverse the accelerated aging, at least in the short term. 

Going forward, Horvath and his team want to determine if the premature epigenetic aging of liver tissue in obese people can be prevented to possibly reduce their risk of diabetes and liver cancer. They plan to work on models that allow them to dissect the exact molecular mechanisms behind this aging process - which is not known at this point - in order to find the right targets for therapy and prevention.

“The increased epigenetic age of liver tissue in obese individuals should provide insights into common liver-related comorbidities of obesity, such as insulin resistance and liver cancer,” the study states. “These findings support the hypothesis that obesity is associated with accelerated aging effects and stresses once more the importance of maintaining a healthy weight.”

The study was funded by the National Institutes of Health (NIA/HIH 5RO1AG04511-02), the Virtual Liver Network, the Christian-Albrechts-University Kiel and the University Hospitals Schleswig-Holstein and Dresden in Germany.
Using a recently developed biomarker of aging known as an epigenetic clock, UCLA researchers working closely with a German team of investigators have found for the first time that