Health Care: 05/29/14

Thursday, 29 May 2014

Cholesterol plays a key role in cell migration

University of Barcelona's researchers led by Professor Carles Enrich, from the Department of Cell Biology, Immunology and Neurosciences of the Faculty of Medicine at the University of Barcelona (UB) and CELLEX Biomedical Research Centre of IDIBAPS, have found that cholesterol plays a key role in cell mobility and tissue invasion. The results of the study prove that the accumulation of LDL cholesterol cells - the one carried by low-density lipoproteins - may play a crucial role in promoting cell mobility. On the contrary, high levels of HDL cholesterol - the one carried by high-density lipoproteins - may avoid cell propagation. This is a key study to better understand cancer metastasis, the process in which cancer cells invade healthy tissues, and foster the discussion on the relationship between cholesterol levels and cancer incidence.

Daniel Grinberg and Lluïsa Vilageliu, from the Department of Genetics of the Faculty of Biology, and Joan Blasi, from the Department of Pathology and Experimental Therapy of the Faculty of Medicine, participated in the paper, published on the journal Cell Reports. Researchers from the Garvan Institute of Medical Research, the University of Sidney (Australia), Queensland University of Technology (Brisbane, Australia) and the University of Hamburg (Germany) also collaborated in the study.

The study was developed by means of experiments carried out with cell cultures of patients with Niemann-Pick disease. These people present a genetic anomaly that causes cholesterol accumulation in the cell; that produces different motor and neurological disorders. "It is generally thought that cholesterol, one of the most important lipids in our body, is in the blood; but few people ask themselves what cholesterol does in the cell", points out Carles Enrich. "Cholesterol -adds the researcher - plays different functions in the cell. Besides being crucial to produce membranes, it also regulates vesicular trafficking. Now, it has been proved that cholesterol plays a key role in the regulation of other mechanisms, for instance cell mobility and propagation and, therefore, it is a crucial factor in metastasis".

Most cells in our body bind other cells by means of integrins, molecules that act as bridges located at the cell surface. UB researchers explored how integrins move in the cells and discovered cholesterol's key role. Enrich points out that "in the cell, cholesterol controls the trafficking of vesicles, which are responsible for transporting integrins to cell surface. Cholesterol depletion in the trans-Golgi network interferes integrin trafficking which has direct repercussions on cell migration".

New knowledge about the mechanisms of cancer metastasis

The study provides new therapeutic options to control metastasis and points out a strategy to be applied to cancer patients who also have cholesterol disorders. "It must be considered that the drugs prescribed to regulate cholesterol may modify cell migration ability. Therefore, progress in personalized therapy is absolutely important", highlights Enrich.

Now, researchers' challenge is to understand why cholesterol stays in the cell. "We want to study what endosome membrane mechanisms block intracellular traffic and hold cholesterol and their negative consequences for our health", concludes Carles Enrich.

Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries. Reverter M, Rentero C, Garcia-Melero A, Hoque M, Vilà de Muga S, Alvarez-Guaita A, Conway JR, Wood P, Cairns R, Lykopoulou L, Grinberg D, Vilageliu L, Bosch M, Heeren J, Blasi J, Timpson P, Pol A, Tebar F, Murray RZ, Grewal T, Enrich C., Cell Rep. doi: 10.1016/j.celrep.2014.03.043, published online 17 April 2014.

University of Barcelona

Misguided DNA-repair proteins caught in the act

Accumulation of DNA damage can cause aggressive forms of cancer and accelerated aging, so the body's DNA repair mechanisms are normally key to good health. However, in some diseases the DNA repair machinery can become harmful. Scientists led by a group of researchers at The Scripps Research Institute (TSRI) in La Jolla, CA, have discovered some of the key proteins involved in one type of DNA repair gone awry.

The focus of the new study, published in the journal Cell Reports, is a protein called Ring1b. The TSRI researchers found that Ring1b promotes fusion between telomeres - repetitive sequences of DNA that act as bumpers on the ends of chromosomes and protect important genetic information. The scientists also showed inhibiting this protein can significantly reduce the burden on cells affected by such telomere dysfunction.

"We are very far from therapy, but I think a lot of the factors we've identified could play key roles in processing dysfunctional telomeres, a key event in tumorigenesis [cancer initiation]," said Eros Lazzerini Denchi, assistant professor at TSRI who led the study.

The Trouble with Telomeres

Humans are born with long telomeres, but these become shorter every time a cell in the body divides. With age, telomeres become very short, especially in tissues that have high proliferation rate.

That's when the problems start. When telomeres become too short, they lose their telomere protective cap and become recognized by the DNA repair machinery proteins. This can lead to the fusion of chromosomes "end-to-end" into a string-like formation.

Joined chromosomes represent an abnormal genomic arrangement that is extremely unstable in dividing cells. Upon cell division, joined chromosomes can rupture, creating new break points that can further re-engage aberrant DNA repair. These cycles of fusion and breakage cause a rampant level of mutations that are fertile ground for cancer.

"You basically scramble the genome, and then you have lots of chances to select very nasty mutations," said Lazzerini Denchi.

Setting a DNA Trap

To understand how to prevent these deleterious fusions, Lazzerini Denchi and his colleagues wanted to identify all the repair factors involved.

The researchers decided to set a trap. Using genetically engineered cells, the researchers were able to remove a telomere binding protein called TRF2. Without TRF2, telomeres are unprotected and DNA repair proteins are recruited to chromosome ends, where they promote chromosome fusions.

The researchers then trapped and isolated all the proteins they found bound to the telomeres. "It was like a fishing expedition, and the bait in our case was the telomeric DNA sequence," said Lazzerini Denchi.

Cristina Bartocci, a postdoctoral fellow in Lazzerini Denchi's lab at the time and first author of the new study, spent more than two years perfecting a technique to identify proteins that flocked to the telomeres. "It was a pretty challenging experiment to perform," she said.

The researchers then separated the proteins from the DNA sequences and sent the proteins to TSRI Professor John Yates's laboratory for mass spectrometry analysis. This analysis revealed 24 known repair proteins and 100 additional proteins whose role in dysfunctional telomeres had not been previously described.

The team then refined their search and took a closer look at the role of the repair factor protein called Ring1b. For the first time, the scientists were able to link Ring1b to the chromosome fusion process. Bartocci said the role of Ring1b in dysfunctional telomere repair was "pretty striking."

"If you don't have Ring1b, the process of fusing the chromosomes is not very efficient," said Lazzerini Denchi.

In addition to Ring1b, the team has found nearly 100 factors that might be related to errors in DNA damage repair. The next step in this research is to further refine the long list of DNA repair factors and study other proteins that could affect human health.

In addition to Lazzerini Denchi, Bartocci and Yates, other contributors to the paper, "Isolation of Chromatin from Dysfunctional Telomeres Reveals an Important Role for Ring1b in NHEJ-Mediated Chromosome Fusions," were Jolene K. Diedrich, Iliana Ouzounov and Julia Li of TSRI, and Andrea Piunti and Diego Pasini of the European Institute of Oncology. DOI: 10.1016/j.celrep.2014.04.002

The research was supported by a Pew Scholars Award, the Novartis Advanced Discovery Institute, National Institutes of Health Grants AG038677 and P41 GM103533, the Italian Association for Cancer Research, the Italian Ministry of Health and a fellowship from FIRC.

Scripps Research Institute

Tumor modeling predicts most effective drugs targeting brain cancer

Researchers at University of California, San Diego School of Medicine and Moores Cancer Center have used computer simulations of cancer cells - cancer avatars - to identify drugs most likely to kill cancer cells isolated from patients' brain tumors.

The findings, published in the online issue of the Journal of Translational Medicine, may help researchers stratify cancer patients for clinical trials according to their cancers' genomic signatures and predicted sensitivities to different cancer drugs.

Such an approach would allow scientists to selectively test cancer drugs on those who would be most likely to respond to them, while simultaneously reducing patients' exposures to toxic drugs that would likely be ineffective.

"Genomics tells us that cancers are a lot like snowflakes. No two cancers are alike so it does not make sense to give all patients the same drugs. This is the idea behind personalizing therapies for cancer," said lead author Sandeep Pingle, MD, PhD, a project scientist in the laboratory of Santosh Kesari, MD, PhD, chief of the division of Neuro-Oncology, professor in the department of neurosciences, director of Neuro-Oncology at UC San Diego Moores Cancer Center and the study's senior author.

"With the virtual cell model, we can take into account all the complexity of cellular processes to predict which drugs will be the most effective against a particular tumor based on its genomic profile," Pingle said. "This is a first step toward personalized medicine."

Researchers developed a virtual cell that represents the internal workings of a normal, healthy cell, depicting them as a complex collection of signaling pathways and metabolic networks. The virtual healthy cell can be made cancerous. Indeed, it can be turned into any kind of cancer cell by distorting specific points and pathways in the system. These cellular distortions represent a person's so-called cancer avatar. Once the avatar is generated, a computer model predicts which drugs, based upon their known functions, are most likely to kill a real cancer cell.

For the study, researchers generated cancer avatars for cells obtained from patients with glioblastoma, a highly aggressive cancer of the brain's glial cells. The condition has a five-year survival rate of about 10 percent. The computer generated predictions were then "truth-checked" against standard, cultured cells in drug-sensitivity experiments.

"The advantage of computational modeling is the ability to incorporate the wealth of genomic and proteomic information on cancer cells and to screen drugs and combinations of drugs much faster and cost effectively," said Kesari. "Our ultimate goal is to take this technology to the clinic to identify the best drugs for treating each individual cancer patient."

Co-authors include Zeba Sultana, Shweta Kapoor, Ansu Kumar, Shahabuddin Usmani and Ashish Agrawal, Cellworks Research India Ltd.; Sandra Pastorino, Pengfei Jiang, Rajesh Mukthavaram,Ying Chao, Ila Sri Bharati, Natsuko Nomura and Milan Makale, UC San Diego Moores Cancer Center; Taher Abbasi, Cellworks Group Inc.; and Shireen Vali, Cellworks Research India Ltd. and Cellworks Group Inc.

The study was funded, in part, by the National Brain Tumor Society, Barbara and Joseph Ajello Trust Fund, Tuttleman Family Foundation, MCJ Amelior Foundation and Boston Fire Department/Kenney Foundation.

University of California - San Diego

New test to diagnose cancer- and infertility-causing parasite

Scientists in Portugal and Angola have discovered a fast, non-invasive way to test for a cancer-causing parasite that kills hundreds of thousands of people every year. The two teams have also made important discoveries on hormonal changes and mutations caused by this infection.

The parasite Schistosoma haematobium is contracted through contaminated waters when parasite larvae released by infected snails enter the blood vessels via the skin, where they can live for up to 5 years. During that period, the larvae release eggs, which - when excreted to the outside - again infect snails and initiate a new life cycle of parasites.

However, rather than being excreted out, many eggs get stuck on tissues and organs, resulting in schistosomiasis. This triggers immune attacks that also destroy the surrounding tissue. Most often, the urogenital system is affected, where the disease can cause bladder cancer.

In terms of public health, experts consider only malaria to have a more devastating impact in developing countries. Schistosomiasis is endemic in 76 of the poorest countries in the world.

About 243 million people are infected with the disease, which kills about 200,000 people every year. Following infection, women often contract female genital schistosomiasis, which affects the cervix and uterus. Female genital schistosomiasis results in bleeding and pain during sex and infertility.

Screening the urine of women at risk of infection for catechols is a quick, non-invasive test that will improve public health in endemic regions.

Until recently, experts thought that infertility and bladder cancer arising from this infection were byproducts of the immune system attacking the parasite eggs trapped inside the body. The team responsible for the new research has now shown that estrogen-like molecules are produced by the parasite, which they say could be responsible for encouraging cancer development.

The researchers wondered if these molecules, called catechols, may also be responsible for infertility in women with schistosomiasis. Enlisting the help of fertility specialists, they analyzed the urine from 93 women in a region of Angola where the S. haematobium parasite is endemic.

They discovered catechols in the urine of women who tested positively for parasite eggs, but not in the urine of uninfected women. The researchers also found an association between catechols and infertility.

Studying the mechanisms involved, the team found that the catechols "down-regulate" estrogen receptors and trigger DNA mutations. Either or both of these actions could be responsible for the bladder cancer and infertility common to schistosomiasis patients.

Explaining their findings, recently published in the journal PLOS ONE, team leader Monica Botelho says:

"Estrogen metabolism/degradation is a normal body process - estrogens are degraded into catechols and these into quinones. But if there are too many quinones (due to an excessive estrogen production or altered metabolism) this can cause DNA damage, because they tend to bind to DNA disturbing it. Now we detect these molecules not only in the serum, but also the urine of patients infected with Schistosoma, while uninfected patients do not have them.

They have been linked before to cancer (thyroid, breast and prostate) and auto-immunity (when the immune system attacks the own body). Now we see them in infertility associated with schistosomiasis infection."

However, Botelho's team have yet to answer the question of why the parasite produces estrogenic molecules at all. Current theories suggest that the molecules may reduce the density of the bladder wall in order to facilitate the escape of the eggs from the body, or that the manipulated hormonal environment better suits the living conditions of the parasite.

While further research will be needed to answer this, more immediate benefits to vulnerable groups are offered by the discovery of the catechols. It is now possible to diagnose infection quickly and easily by screening urine for presence of these molecules, which, the team notes, "should improve the public health in under-resourced and under-served populations."

A hint of the role of RaDAR in a kind of melanoma

A Ludwig Cancer Research study has identified a novel pathway by which proteins are actively and specifically shuttled into the nucleus of a cell. Published online in Cell, the finding captures a precise molecular barcode that flags proteins for such import and describes the biochemical interaction that drives this critically important process. The discovery could help illuminate the molecular dysfunction that underpins a broad array of ailments, ranging from autoimmune diseases to cancers.

Although small proteins can diffuse passively through pores built into the nuclear membrane, most nuclear proteins have to be actively driven into the nucleus through specialized pores to ensure that the cell functions normally. Proteins targeted to specific compartments in cells often carry a sequence of amino acids that, like a barcode, tells components of the cell's transport machinery where they should be located in order to perform their biochemical duties.

"Until now, only one nuclear import pathway for active transport has been extensively characterized," says Xin Lu, Ludwig director at the University of Oxford whose laboratory led the study. "It targets proteins that encode what's known as the nuclear localization signal (NLS). Yet about half of the proteins that get into the nucleus do not bear an NLS, and how they get there has long puzzled researchers. Now we have discovered an alternative signal by which proteins devoid of NLS are tagged for nuclear import." The finding will help scientists better understand the roles many hitherto poorly characterized proteins play in cellular life, and identify many others that work within the nucleus on such tasks as gene regulation and expression.

The researchers were led to their discovery while investigating how an important tumor suppressor protein known as ASPP, which Lu's laboratory has been studying for many years, gets into the nucleus. Their experiments revealed that a widely shared element of protein structure found in ASPP, known as the ankyrin repeat (AR), plays a central role in the protein's nuclear localization.

Lu's team shows in the study that the import signal that flags proteins for the new pathway consists of two consecutive ARs that share one feature: each has a hydrophobic amino acid (one with chemical properties that repel water) that is located 13 amino acids into the repeat. This structural signature, they find, is bound by a small protein named RanGDP. Lu and her colleagues have named this new pathway the RaDAR (RanGDP-Ankyrin Repeat) nuclear import pathway. They have so far identified more than 46 proteins encoded by the human genome that carry this barcode for nuclear delivery.

In decoding this new nuclear import signal, Lu and her team also uncover a possible molecular mechanism underlying human familial melanomas, which are often linked to mutations in a protein known as p16. "We show that the p16 mutation most frequently associated with such cancers," Lu explains, "confers the RaDAR barcode to the protein, resulting in its aberrant accumulation in the nucleus." The RaDAR signature is also associated with a number of regulators of cell proliferation and gene regulation, including the NF-kB family of proteins, which shuttle between the cytoplasm and nucleus, and have been implicated in several human cancers, and autoimmune and inflammatory diseases.

Lu's team is now investigating the spectrum of proteins that use the RaDAR pathway and exploring methods by which the ankyrin repeat that bears that barcode might be exploited to develop entirely novel diagnostics and therapies. That includes incorporating the new nuclear import barcode into synthetic molecules named DARPins to target biologics and other kinds of drugs specifically to the nucleus.

Pandemic emergency response considered by AAAS panel

When a pandemic spreads, health officials must quickly formulate a strategy to limit infections and deaths. This requires sifting through huge amounts of data in a short amount of time and organize medical staff who may have little information on the pandemic.

If you would like to help coordinate a rapid reaction to pandemics, a professor at the Georgia Institute of Technology in Atlanta designed software that biological data on the pandemic with demographics of the endangered population combines so that health officials can develop a game plan to limit the pandemic expansion. The software also combing social media sites for real-time information about the pandemic and the activities of the population.

Eva Lee, Director of the Center for Operations Research in medicine and health care on the h. Milton Stewart School of industrial and Systems Engineering at the Georgia Institute of Technology in Atlanta, talked about her emergency response software on the 2014 AAAS annual meeting in Chicago.

"We have developed a real-time system that the demographics of the area that is affected, and also pick up on-the-ground data about who's available and does what, and will gather on the movement of the affected population," Lee said. "Our work is the first to include demographic information and real-time population behavior and interlace with the biological information to come up with a decision that health officials can actually use."

Lee was the Chairman of the panel entitled "Emergency Response and community resilience through Engineering and computational advances."

Lee shareed its experience in helping federal officials respond to the H1N1 flu in 2009, as well as her experience plans an emergency response to a possible outbreak of anthrax. Lee was also involved in the coordination of a response to the 2010 Haiti earthquake, and the decontamination and health screening effort in Japan after the 2011 Fukushima radiological disaster.

Other speakers on the Panel are Ronald Eguchi ImageCat's Inc. in Long Beach, Calif., who talked about inventory data capture tools to assess risk of natural disasters. Yasuaki Sakamoto, of Stevens Institute of Technology in Hoboken, NJ, spoke about improving social media for disaster relief.

Emergency responders should a pandemic quickly collect information on the biological agent to assess the characteristics of the pandemic and decide what treatment would be most effective. They also collect information about the risk factors of the individuals in the pandemic, such as the severity of the disease of the patient, and if children or pregnant women are infected.

"The big challenge in a pandemic is how do you use all this information to determine the best strategy gets you the minimum number of total infections and death rate," Lee said.

Information of Lee's official health systems approach to determine where to allocate medical resources and staff in the best way so that most operations will be successful. By the software developed in her lab at Georgia Tech, officials may provide, such as how much vaccine to give at-risk populations and how much to give to the general population to limit the spread of the infection and mortality. Officials can also where medical sites to prevent traffic crashes and deterioration of the pandemic as infected patients on treatment sites converge.

"We can do a real time optimization to tell you exactly what the sites you need to set up and which should go where," said Lee.

"Emergency Response and community resilience through Engineering and computational advances" 14 February 2014 2014 on the AAAS annual meeting in Chicago.

Georgia Institute of Technology

Hurricanes Katrina and Rita may have caused up to half of recorded stillbirths in worst hit areas

Hurricanes Katrina and Rita may have been responsible for up to half of all recorded stillbirths in the worst hit areas, suggests research published online in the Journal of Epidemiology & Community Health.

And the true fetal death toll may even be higher, because of the displacement of people whose homes and way of life were destroyed, suggest the authors.

Hurricane Katrina struck the state of Louisiana, USA, on August 29 2005, followed by Hurricane Rita a month later on September 24. Katrina was the costliest natural disaster in American history, while Rita was the fourth most intense hurricane ever recorded.

Both hurricanes caused widespread damage to property and infrastructure and left a trail of injury, death, and trauma in their wake.

The researchers used composite figures from several government agencies, showing that the hurricanes caused damage in 38 out of 64 areas (parishes) in the state, with almost 205,000 housing units affected.

In four parishes, more than half of the local housing stock was damaged; in three others, between 10% and 50% was damaged. Elsewhere, the level of damage to housing stock was categorised as 1%-10%, or less than 1%.

The researchers then calculated the odds of a pregnancy resulting in a stillbirth in damaged and undamaged areas (less than 1% damage) in the 20 months before, and the 28 months after, Katrina struck.

But they also looked at all birth data between 1999 and 2009 in Louisiana to gauge usual patterns: during this period, 5194 stillbirths were recorded.

They then used space-time models to assess whether the extent of damage wrought by the hurricanes was linked to the risk of stillbirths in a given area.

Their calculations indicated that the risk of a pregnancy ending in a stillbirth was 40% higher in parishes where 10-50% of housing stock had been damaged, and more than twice as high in areas where over 50% of the housing stock had taken a hit.

After taking account of known risk factors, every 1% increase in the extent of damage to housing stock was associated with a corresponding 7% rise in the number of stillbirths.

Based on these figures, the researchers calculated that of the 410 stillbirths officially recorded in extensively damaged parishes, up to half (117-205) may have been directly caused by the hurricanes and the subsequent devastation.

Their estimates suggest that stillbirths made up around 17.5% to 30.5% of the total death toll in the wake of the hurricanes.

But the risk of stillbirth may have been even higher, suggest the researchers. In the hardest hit areas, the number of live births was more than 40% lower in 2007 than it was in 2004. And in parishes with more half of the housing stock damaged, the live birth rate fell by 79% in the three months following Katrina.

This "precipitous decline" is likely to reflect the well documented exodus of residents from the coastal parishes of Louisiana into other areas, they suggest.

They point to previously published research, showing a link between maternal stress, depression, and trauma and birth complications, including stillbirths.

And they warn that climate change scientists have predicted an increase in the frequency, intensity, and duration of North Atlantic tropical cyclones like Hurricanes Katrina and Rita.

"Insofar as our empirical findings meaningfully generalise in time, the health risks to the unborn and their perinatal development will likely increase with more frequent and intense hurricanes," they write.

WHO officials respond to criticisms of polio vaccination campaign in Syria

In a Comment published in The Lancet, Ala Alwan and Bruce Aylward from the World Health Organisation (WHO) respond to recent allegations that UN agencies including WHO have blocked vaccination campaigns and obstructed the testing of polio samples. Outlining the actions which have been taken by WHO and other agencies to address the rising threat of polio in the Middle East, Alwan and Aylward state that, "Fully implementing this response plan has required overcoming immense hurdles to reach every child amid the wreckage of Syria's public infrastructure and health system, the active conflict and insecurity, the dearth of trust, and one of the largest refugee crises since the second World War. These challenges have been compounded by erroneous allegations that - rather than doing everything possible to protect all Syrian children and the huge international investment in global polio eradication - United Nations agencies, and the World Health Organization (WHO) in particular, had 'blocked a vaccination campaign', were 'obstructing the testing of polio samples', and by extension disregarding fundamental humanitarian principles."

"Every day, thousands of local and international public health workers, community members and volunteers on all sides of this conflict risk their lives to deliver basic services - including and especially immunization - to all Syrians. It is essential that the complexities of the environment in which they are working is properly understood and that where information is incomplete, or is not shared for security reasons, it is not replaced with speculation or accusation...Halfway through the Syrian polio outbreak response, many critical programme indicators are improving, particularly in terms of access to vaccine, coverage and surveillance performance. Addressing the remaining gaps in programme implementation in Syria is a deadly serious issue; compounding this challenge with inaccurate information significantly and unnecessarily complicates an already very difficult and dangerous operating environment."

Work increases resilience among survivors in a town where half the people have PTSD symptoms

Though just two of Hirono's 5,418 residents lost their lives in Japan's mega-earthquake and tsunami, a new study shows that the survivors are struggling to keep their sanity.

One year after the quake, Brigham Young University professor Niwako Yamawaki and scholars from Saga University evaluated the mental health of 241 Hirono citizens. More than half of the people evaluated experienced "clinically concerning" symptoms of post-traumatic stress disorder. Two-thirds of the sample reported symptoms of depression.

Those rates exceed levels seen in the aftermath of other natural disasters, but what happened in Japan wasn't just a natural disaster. Leaked radiation from nuclear power plants forced residents of Hirono to relocate to temporary housing far from home.

"This was the world's fourth-biggest recorded earthquake, and also the tsunami and nuclear plant and losing their homes - boom boom boom boom within such a short time," said Yamawaki, a psychology professor at BYU. "The prevalence one year after is still much higher than other studies of disasters that we found even though some time had passed."

Yamawaki got the idea for this study while shoveling mud from a damaged Japanese home one month after the tsunami flooded coastal towns. She had just arrived for a previously scheduled fellowship at Saga University. During her off-time, she traveled to the affected area and volunteered in the clean-up effort. One seemingly stoic homeowner broke down in tears when Yamawaki and her husband thanked her for the chance to help.

"She said 'This is the first time I have cried since the disaster happened,'" Yamawaki said. "She just said 'Thank you. Thank you for letting me cry.'"

Back at Saga University, Yamawaki collaborated with Hiroko Kukihara to conduct a study on the mental health and resilience of survivors. Their report appears in the journal Psychiatry and Clinical Neurosciences.

Participants in the study lived in temporary housing provided by the Japanese government when Hirono was evacuated. With an average age of 58, the people are noticeably older than the populations of normal Japanese towns. Yamawaki suspects that young people were more likely to permanently relocate elsewhere in Japan following the disaster.

The researchers didn't just measure the rates of mental illness; they also performed a statistical analysis to learn what fostered resilience among the survivors. Eating right, exercising regularly and going to work all promoted resilience and served as a buffer against mental illness.

"Having something to do after a disaster really gives a sense of normalcy, even volunteer work," Yamawaki said.

As the researchers got to know survivors, they heard from so many that they missed seeing their former neighbors. The mass relocation outside the radiation zone broke up many neighborhood ties.

"Japanese are very collectivistic people and their identity is so intertwined with neighbors," Yamawaki said. "Breaking up the community has so much impact on them."

While it's hard to fathom the scope of the devastation in the coastal region of Fukushima, most survivors believe something like this will happen again. If so, this new study provides a blueprint for how to help them put their lives back together again.

Mental health care model reduced symptoms in those most affected by BP oil spill

A model of care developed by the Department of Psychiatry at LSU Health Sciences Center New Orleans School of Medicine to provide mental health services after the Deepwater Horizon Gulf Oil Spill reduced both mental health and general medical symptoms. The novel approach embedded psychiatrists, psychologists, social workers and telemedicine resources into primary care clinics in the most affected areas. This new model can be used in communities at risk for disasters and rural communities with limited mental health resources. The initiative is featured in the March 2014 issue of the journal, Psychiatric Services, now available online.

"After researching existing models of care nationally, we found none fully adaptable to the postdisaster needs of close-knit, rural communities with inadequate availability of mental health resources," notes Dr. Howard Osofsky, Professor and Chair of Psychiatry at LSU Health Sciences Center New Orleans School of Medicine. "So, we integrated behavioral health with primary care to build sustainable services along with community resilience. This was especially important given the limited resources and the increase in mental disorders the Gulf Oil Spill compounded in communities still recovering from Hurricane Katrina."

The mental health surveillance conducted by the LSUHSC Department of Psychiatry in communities highly affected by the oil spill from the fall of 2010 through 2012 found even greater increases in psychiatric symptoms than indicated by the Centers for Disease Control and Prevention. Symptoms included those of posttraumatic stress disorder (PTSD), depression and generalized anxiety disorder. Additionally, residents reported increases in physical symptoms.

Part of the Gulf Region Health Outreach Program funded by the Deepwater Horizon Medical Benefits Class Action Settlement, LSUHSC, with input from stakeholders, provides services in clinics, schools and communities. The model of integrative behavioral health in primary care clinics is based upon a team approach with centralized care management to coordinate the field efforts of the mental health specialists, extended by the use of telemedicine. A network of care tailored to the individual needs of each clinic and provider supports behavioral health screening, acute and emergency care, as well as ongoing treatment. Real-time emergency evaluations of patients are conducted during clinic hours, and telemedicine consultations are conducted 24 hours a day, seven days a week.

"It's an interprofessional stepped-care collaborative where primary care providers can treat behavioral health issues in regular consultation with mental health professionals and clinical decision support," says Dr. Osofsky. "However, if the behavioral health problem is outside of the comfort level of the primary care provider, treatment is managed by direct assessment by the mental health professional along with on-site and telemedicine care."

The five primary care clinics currently being served refer a total of 50 to 75 new patients a week to the team; the numbers will increase in 2014 with the addition of clinics in affected areas that are being rebuilt.

Significant decreases in psychiatric symptoms were found at the one-month follow-up with further declines at the three-month follow-up. General medical symptoms have also shown significant improvement.

In addition to Dr. Osofsky, coauthors at LSU Health Sciences Center New Orleans include Dr. Joy Osofsky, Professor or Pediatrics and Psychiatry, and Dr. John Wells, Assistant Professor of Psychiatry, along with Dr. Carl Weems at the University of New Orleans.

"These efforts have resulted in fewer hospitalizations and barriers to care, and they provide the highest-quality mental health care, with continuity between primary care providers and specialist mental health clinicians" concludes Dr. Osofsky.

Link discovered between clusters of 'broken hearts' and massive natural disasters

Dramatic spikes in cases of Takotsubo cardiomyopathy, also called broken heart syndrome, were found in two states after major natural disasters, suggesting the stress of disasters as a likely trigger, according to research to be presented at the American College of Cardiology's 63rd Annual Scientific Session. Authors call for greater awareness among emergency department physicians and other first responders.

Takotsubo cardiomyopathy, or broken heart syndrome, is a disorder characterized by a temporary enlargement and weakening of the heart muscle, which is often triggered by extreme physical or emotional stress - for example, being in a car accident or losing a child or spouse. Previous international studies have also linked broken heart syndrome to natural disasters, including the 2004 earthquake in Japan. This is the first U.S. study to examine the geographic distribution of the condition in relation to such catastrophes.

Researchers at the University of Arkansas identified 21,748 patients diagnosed with primary cases of broken heart syndrome in 2011 using a nationwide hospital discharge database. After mapping the cases by state, Vermont and Missouri emerged as having the highest rate of cases, with 380 cases per million residents in Vermont and 169 per million in Missouri. Most states had fewer than 150 cases per million residents. New Hampshire and Hawaii had the lowest rate of the disease that year.

The rate of broken heart cases in Vermont in 2011 was more than double most other states. This was the same year that Tropical Storm Irene pummeled the state with heavy rain and wind, causing the most devastation Vermont has experienced since the Great Flood of 1927. Similarly, researchers found broken heart syndrome at a rate of 169 cases per million in Missouri in 2011, the same year a massive tornado ripped through Joplin, Mo., demolishing neighborhoods and killing at least 158 people.

"Despite the seemingly increasing number of natural disasters we have, there is limited data about how it might affect the heart," said Sadip Pant, M.D., internist at the University of Arkansas for Medical Sciences, and lead investigator of the study. "Our findings suggest two disasters, one in Vermont and one in Missouri, might have been possible triggers for the clustering of Takotsubo cardiomyopathy cases in these regions."

Patients with broken heart syndrome often complain of chest pain and shortness of breath, symptoms that mimic those of a heart attack, which can delay diagnosis. In addition, biomarkers in the blood and changes on electrocardiogram can raise suspicions of possible heart attack. While broken heart syndrome typically resolves within a month or two, in the acute scenario it can result in serious complications such as heart failure, life-threatening arrhythmias and stroke. Previous studies by the same group found that as many as one in four patients with broken heart syndrome have some form of arrhythmia and 1 to 7 percent suffer cardiac arrest. Many patients are diagnosed in the cath lab when doctors see there are no blockages in the artery, or imaging reveals changes in the shape of the heart that are characteristic of broken heart syndrome.

"By and large, it is a very reversible form of cardiomyopathy, but in the acute phase these patients need to be monitored closely to be sure they are stable and to prevent and manage problems," Pant said, adding that the impetus for the study was the increasing number of cases and a desire to find out what might trigger clusters of broken heart syndrome. "It's also something that emergency doctors and medical personnel need to be aware of as they are often on the frontlines seeing patients after disaster strikes."

Episodes are thought to be driven by the sympathetic response and surges of adrenaline in the body, similar to the well-known fight-or-flight reaction. This leads to depressed function of the apex and middle segment of the heart and increased contractility of the base producing a balloon-like appearance.

"It's a perfect example of our brain-heart connection," Pant said. "The emotional stress we have in our brain can lead to responses in the heart, and not much is known about this condition."

Of course everyone's threshold for stress is different. There were other natural disasters in 2011. Pant said that because these events occur more frequently in some parts of the country, residents in these regions may have adapted to and experienced less stress during such occurrences; whereas in places like Vermont, where natural disasters are relatively rare, people may be more susceptible to extreme stress when a disaster hits particularly hard.

Hospital admissions for broken heart syndrome have been on the rise, but it is unknown whether the growing numbers are due to clinicians being more aware of the condition, especially since a reimbursement billing code was established for it in 2006, or if there is a true increase in its incidence. Either way, Pant says it is important to identify potential triggers.

Takotsubo cardiomyopathy got its name because the abnormal shape of the heart resembles a Japanese octopus fishing pot (tako=octopus, tsubo=pot). Pant says more research is needed to further explore the pathophysiological basis and management of this disease.

Guidance for evacuees in disaster zones inspired by ant colonies

An escape route mapping system based on the behavior of ant colonies could give evacuees a better chance of reaching safe harbor after a natural disaster or terrorist attack by building a map of showing the shortest routes to shelters and providing regular updates of current situations such as fires, blocked roads or other damage via the smart phones of emergency workers and those caught up in the disaster.

Koichi Asakura of Daido University in Nagoya and Toyohide Watanabe of the Nagoya Industrial Science Research Institute in Japan have carried out successful simulations of the construction of navigational maps using this approach and report details in the International Journal of Knowledge and Web Intelligence. Following a major earthquake, tsunami, typhoon or other disaster it is crucial for those affected, including emergency workers, to obtain and share accurate and timely information about the situation as it unfolds. Lives can only be saved if evacuation to safe areas and shelters is not stymied by blocked roads, fires and other problems.

The team's new system has two key features: First it utilizes the smart phones that are now ubiquitous across cities as networked, mobile sensors that can feed information back to emergency centers. The second feature exploits our understanding of the behavior of an ant colony. This provides a way to determine whether or not particular problems are recent or not, just as individual ants use pheromone trails, and the concentration changes in those pheromones to assess how recently a colony member left a particular signal and so find the optimal routes to and from the nest via food supplies. By using this approach to analyze the data from myriad smart phones as evacuees head for shelter, it is possible to build an active navigational map using the phones' GPS and other tools.

The system circumvents the problem that would be almost inevitable during a disaster that closed circuit television (CCTV) cameras would be unreliable whereas sufficient numbers of wireless communication devices might remain active for sufficient time given a large enough number of service providers and communication towers spread widely across the disaster area. The next step will be to develop an ad hoc mobile networking system so that evacuees can themselves access these active maps rather than the present system that provides advice to emergency services for guiding evacuees. Such a network might also circumvent the problem of service provider outages by allowing individual smart phones to create a local network.

"Construction of navigational maps for evacuees in disaster areas based on ant colony systems" in Int. J. Knowledge and Web Intelligence, 2014, 4, 300-313

Inderscience Publishers

Civilians trained by American mental health professionals bring healing to trauma victims of Libya's civil war, Baylor study finds

Civilians traumatized by Libya's civil war in 2011 - which left many homeless, poor and grieving for loved ones - have virtually no access to mental health professionals, but many have found healing through small groups led by Libyan volunteers who were trained by American professionals, according to a Baylor University study.

The finding has implications for traumatized people elsewhere, including in Somalia and Ethiopia, where similar efforts have begun; and in Egypt and Uganda, where such training is to begin soon, said Matthew Stanford, Ph.D., a professor of psychology and neuroscience in Baylor's College of Arts & Sciences, who led the research. The study is published online in the South African Journal of Psychology.

"The American Psychological Association over the past few years has called for psychologists to develop new ways to deliver mental health services, because there simply aren't enough providers in the United States - and it's even worse elsewhere," Stanford said. "Taking basic therapeutic principles and putting them into a format peers can deliver has been very effective."

In November 2012, shortly after the eight-month war's end, Stanford and a team from Acts of Mercy International a Christian relief organization, traveled to Libya and found an inadequate mental health system - fewer than 30 psychiatrists and no licensed psychologists or social workers in a country of more than 6 million people.

Libyans are struggling to cope with the aftermath of the war as well as 42 years under the brutal rule of dictator Moammar Gadhafi, a regime in which many were tortured or systematically raped. As many as 15,000 Libyans were killed and more than 50,000 injured in the war, and thousands live as "internally displaced persons (IDPs)" in camps throughout the country, Stanford said.

Team members focused on a camp for about 2,500 people near Benghazi. They recruited 10 volunteer civilians, who completed an intensive four-hour training - including lectures and role-playing - translated into Arabic and led by Acts of Mercy International staff. The peer-led "Hope Groups" met regularly for 10 weeks with 149 participants in 17 groups of friends and relatives in the camp. The average group size was eight people.

After 10 weeks, members anonymously completed the Posttraumatic Stress Disorder Checklist, a 17-item self-report broadly used within the mental health community. The report showed that the groups were helpful, with interaction among members, and most of the civilian leaders said they felt they could successfully train someone else to be a leader.

While prior research has shown that outcomes through mutual help groups - such as Alcoholics Anonymous - are comparable to much more costly professional treatments, use of peer-led groups for war-related trauma in civilians had not been investigated until the Baylor study.

"A lot of times, people think, 'I'm just going to tough it out.' But sometimes, that's just not possible," Stanford said.

While the program's content was simplified, it was challenging for translators unfamiliar with mental health concepts.

But "despite cultural and language differences, there are a lot of universal things that cut across cultures," Stanford said. "In an ideal world, the people would be seeing licensed therapies and getting medications, but this is different. It's simplified, but they do get a dramatic reduction in symptoms."

In the sessions, participants learned about such common symptoms of trauma as depression, sleep problems, anger and guilt. They learned ways to cope with crises and rebuild emotional closeness that had been disrupted by trauma.

For leaders, overseeing groups has "really given them a purpose," Stanford said. "They want to be trained as leaders in towns that have been destroyed and go to other camps and begin training others. That's what you hope for - that they'll take ownership of it."

Stanford is executive director and co-founder of the Mental Health Grace Alliance, with bases in Waco and Los Angeles. Other researchers were Jose Padilla, co-founder of Mental Health Grace Alliance, who has lived and worked for more than 10 years in Arabic-speaking Muslim countries and who edited the material; Timothy M. Elverson of Acts of Mercy International's United Kingdom office; and Edward B. Rogers, a doctoral candidate at Baylor.

Baylor University

PMS, menopause and hot flashes

Having premenstrual syndrome (PMS) before menopause does not mean women will be troubled by hot flashes afterward. But they may face more menopause complaints other than hot flashes, such as trouble with memory and concentration, finds a new study published online in Menopause, the journal of The North American Menopause Society (NAMS).

The research team at the Helsinki University Central Hospital and Folkhälsan Research Institute in Helsinki, Finland, are the first to show a link between PMS and a worse quality of life after menopause. They uncovered the link by asking 120 healthy postmenopausal women who had not taken hormones to answer standard questionnaires about the premenstrual symptoms they had had and about their current health. The investigators also had the volunteers keep a diary of their hot flashes, recording how many they had and the severity of each.

Nearly 90% of the women recalled having PMS. For half of these women, the symptoms interfered with work, home or social life, and about 40% of these women rated their PMS as moderate or severe. But the analysis showed that hot flashes and their severity had no significant relationship to PMS. The symptoms were, however, linked with depression, poor sleep, feeling less attractive, and especially with memory and concentration problems after menopause.

Whether these results mean that PMS and menopause complaints other than hot flashes have a common cause, such as a similar change in regulation of the autonomic nervous system or genes that predispose to both, are topics for future research.

Meanwhile, says NAMS Executive Director Margery Gass, MD, "Women who are troubled by PMS can be reassured that it doesn't mean bothersome hot flashes are inevitable later."

Favorable outcomes emerge from integrating mental health into obstetics/gynecology services

Women who received collaborative care for depression at two UW Medicine obstetrics and gynecology clinics showed fewer symptoms after treatment than women receiving usual depression care in the same setting, according to recent University of Washington research.

The study, published in the journal Obstetrics & Gynecology, is the first to bring collaborative depression care to an obstetrics/gynecology or women's health care setting. Approximately one-third of American women list an obstetrician/gynecologist as their primary physician.

In the study, led by UW professors Wayne Katon and Susan Reed, women were randomly assigned to receive the collaborative care intervention or typical care. Collaborative care helped decrease depression symptoms for most women by at least 50 percent after one year of treatment. Women who received collaborative care also were more likely to return for follow-up care and reported greater satisfaction with the care they received.

"More women than men experience depression, and underserved poor and minority women have a greater chance of experiencing this disorder," said Katon, a UW professor of psychiatry and behavioral sciences. "Since many of these women seek depression care with a primary or specialty care provider, we wanted to offer more thorough care in a setting that's easier for these women to access."

The collaborative approach comprises counseling and greater patient engagement than is typical of mental health care at specialty clinics. It involves psychiatrists, clinicians, specialists and depression care managers. The team meets weekly to review patient progress and provide treatment recommendations. The care manager follows up with patients.

"Collaborative care benefits the community not only by helping women with depression regain function in their lives, but also by lowering healthcare costs," said Reed. She is a professor of obstetrics and gynecology and director of women's health at Harborview Medical Center.

"We anticipate fewer women will go to emergency rooms for acute care problems related to mental health, and more women will be able to rejoin the workforce."

The approach, called "Depression Attention for Women Now," or DAWN, was tested at Harborview Medical Center and UW Medical Center's Roosevelt Clinic. Of the 205 participants, more than half were managing post-traumatic stress disorder as well as depression symptoms and many had low incomes and little or no health insurance. Nearly half were women of color.

Women in each group received treatment for up to 12 months; follow-up continued for an additional six months. Women who received collaborative care could opt for follow-ups in person or by phone, and choose whether they wanted counseling, medication or a combination of both.

Many participants, Reed said, expressed that it was the first time they felt anyone cared about their mental health. One participant wrote that the approach gave her tools to manage her depression on her own.

Though the study ended last year, the researchers have begun implementing the collaborative-care model at Harborview Medical Center's Women's Clinic. They are also looking to provide that approach to the large Latina population in Eastern Washington, who often have problems accessing mental health services.

"The collaborative-care model could be adapted for other types of specialty care," Reed said. "As we saw, the model was especially beneficial for women who faced barriers to healthcare, as collaborative care addressed multiple health concerns - not just obstetric and gynecologic health but also mental health - in one place."

Three of the study’s other authors are from the UW: Joan Russo, associate professor of psychiatry and behavioral sciences; Carmen Croicu, attending physician for the Department of Psychiatry and Behavioral Sciences; and Anna LaRocco-Cockburn, depression manager for the same department. Jennifer Melville, a UW professor of obstetrics and gynecology, was the primary author of the grant that funded the study.

The project was funded by the National Institute of Mental Health grant R01-MH085668.

Improving Care for Depression in Obstetrics and Gynecology

University of Washington