Brazilian researchers identify RNA that regulates cell death

Researchers from the University of São Paulo (USP) have identified an RNA known as INXS that, although containing no instructions for the production of a protein, modulates the action of an important gene in the process of apoptosis, or programmed cell death.

31 july 2014--According to Sergio Verjovski-Almeida, professor at the USP Chemistry Institute and coordinator of a research funded by São Paulo Research Foundation (FAPESP), INXS expression is generally diminished in cancer cells, and methods that are capable of stimulating the production of this non-coding RNA can be used to treat tumors.

In experiments on mice, the USP scientists were able to effect a 10-fold reduction in the volume of subcutaneous malignant tumors by administering local injections of a plasmid – a circular DNA molecule – containing INXS. The findings were published in the most recent issue of the journal Nucleic Acids Research.

The group headed by Verjovski-Almeida at USP has devoted the past five years to investigating the regulatory role of so-called intronic non-protein-coding genes – those found in the same region of the genome as a coding gene but on the opposite DNA strand. INXS, for example, is an RNA expressed on the opposite strand of a gene coding for a protein known as BCL-X.

"We were studying several protein-coding genes involved in cell death in search of evidence that one of them was regulated by intronic non-coding RNA. That was when we found the gene for BCL-X, which is located on chromosome 20," he explained.

The researcher explained that BCL-X is present in cells in two different forms: one that inhibits apoptosis (BCL-XL) and one that induces the process of cell death (BCL-XS). The two isoforms act on the mitochondria but in opposite ways. The BCL-XS isoform is considered a tumor suppressor because it activates protein complexes known as caspases, which are required for the activation of other genes that cause cell death.

"In a healthy cell, there is a balance between the two BCL-X isoforms. Normally, there is already a smaller number of the pro-apoptotic form (BCL-XS). However, in comparing tumor cells to non-tumor cells, we observed that tumor cells contain even fewer of the pro-apoptotic form, as well as reduced levels of INXS. We suspect that one thing affects the other," the researcher said.

To confirm the hypothesis, the group silenced INXS expression in a normal cell lineage and the result, as expected, was an increase in the BCL-XL (anti-apoptotic) isoform. "The rate between the two – which was 0.25 – decreased to 0.15; in other words, the pro-apoptotic form that previously represented one fourth of the total began to represent only one sixth," Verjovski-Almeida explained.

The opposite occurred when the researchers artificially increased the amount of INXS using plasmid expression in a kidney cancer cell line, with the non-coding RNA being reduced. "The pro-apoptotic form increased, and the anti-apoptotic form decreased," the researcher noted.

The next step was to subject the cancer cell lineages to agents known to induce cell death, such as ultraviolet light and chemotherapy drugs, to see whether INXS expression increased.

The researchers repeated the experiment, but his time silenced the INXS gene. They then observed that, even in the presence of ultraviolet light, the pro-apoptotic isoform did not increase and the cells did not die.

The final stage of the study was to verify whether the increase in INXS expression is related to the death of cancer cells in vivo. To do this, the researchers subcutaneously implanted human kidney cancer cells in mice and waited 40 and 60 days for the tumor to reach a volume of 300 cubic millimeters (mm3) and become palpable.

The animals were then divided into two groups: one half began to receive injections of the plasmid containing INXS at the site of the tumor; the other half, which served as the control, received only the empty plasmid.

After 15 days of treatment, the tumors in the control group animals had grown to an average volume of 600 mm3. However, in the group treated with INXS, the average tumor volume measured 70 mm3 – nearly 10 times smaller.

According to the assessment of Verjovski-Almeida, it is possible to develop therapies to fight cancer that are able to increase the quantity of INXS in only the tumor cells, and the USP group plans to test some of these strategies in the future.

In a new thematic project, titled "Characterization of the mechanisms of action of long non-coding RNA involved in the programs of gene activation in human cells," recently approved by FAPESP, the group plans to further study the mechanisms through which INXS modulates the BCL-X gene to understand why this non-coding RNA is reduced in cancer cells.

Provided by Fundação de Amparo à Pesquisa do Estado de São Paulo

Elderly can get fit in 60 seconds

The health of OAPs can be dramatically improved with high-intensity training (HIT), a new study has shown.

30 july 2014--Scientists here at Abertay University, who specialise in exercise and the ageing process, put a group of pensioners through the exercise regime - a population group on which HIT had never been tested before.

They found that - in just six weeks - doing one minute of exercise twice a week not only significantly increased physical fitness and functional ability (the ability to get up out of a chair or carry shopping), but also significantly reduced blood pressure - a risk factor for cardiovascular disease (CVD).

These discoveries have important implications.

Currently, more than 10 million people in the UK are aged over 65, with this figure set to double in the next 30 years.

As people get older, muscles get weaker and smaller, and poor muscle function is a major health concern in the elderly.

The older population is also at greater risk of developing heart disease and type 2 diabetes and - together with frailty - these health issues cost the NHS in the region of £30 billion a year.

Although it is well-known that exercise can help reduce the effects of these age-related declines and can improve quality of life, the majority of older people find it difficult to meet the current exercise guidelines.

These consist of performing moderate to vigorous intensity physical activity - such as fast walking or running - several days per week.

Lack of time is reported as the most common barrier to meeting these guidelines, and the research team at Abertay believes that HIT offers an alternative to the current, unrealistic, recommendations.

Dr John Babraj explains:

"The ageing process is generally looked on quite negatively by society, with everyone knowing that you find it more difficult to carry out day-to-day activities like standing up from your chair, or carrying your shopping, as you get older.

"What we found with this study - which involves doing just one minute of exercise twice week - is that it not only improved the participants' physical health and ability to do these things, but also their perceptions of their own ability to engage inphysical activity. They enjoyed it, were delighted with the effects it had on their health and, on top of that, felt they could fit it into their lives, which is something they aren't able to do with current exercise recommendations.

"If people aren't meeting the targets, we need to find ways to work with them when it comes to exercise, rather than just persisting with something that isn't working. High-intensity training is an achievable alternative that could make a real difference to people's health and their quality of life.

"With the current increase in the number of retired people, it is important that we find new ways to keep them active that have a positive impact on their health and wellbeing.

"There is eight years of evidence which shows that HIT has a significant impact on obesity, diabetes and heart disease, and this study adds to that, showing that it is something that older people can benefit from too."

In the study participants were divided into two groups, with one acting as a control and the other required to take part in two sessions of high-intensity training per week.

Each session consisted of 6-second all-out sprints on an exercise bike, with each participant fitted with a heart rate monitor throughout.

The number of sprints in each session was progressively increased over the course of the trial from 6 x 6-second sprints to 10 x 6-second sprints.

A minimum of one minute recovery time was allowed between each sprint, and participants were not allowed to start sprinting again until their heart rate had gone back down to below 120bpm.

Dr Babraj concludes:

"When it comes to the sprints, you don't have to go at the speed of someone like Usain Bolt. As long as you are putting in your maximal effort - whatever speed that happens to be - it will improve your health.

"However, as with any type of exercise, it is important to consult with your doctor before you begin doing HIT, in case there are any underlying health issues."

More information: Adamson, S. B., Lorimer, R., Cobley, J. N. and Babraj, J. A. (2014), "Extremely Short–Duration High-Intensity Training Substantially Improves the Physical Function and Self-Reported Health Status of Elderly Adults." Journal of the American Geriatrics Society, 62: 1380–1381. DOI: 10.1111/jgs.12916

Provided by University of Abertay Dundee

5 things to know about Ebola outbreak in W. Africa

In this photo taken on Sunday, July 27, 2014, a boy, center, selling soft drinks walk past a clinic taking care of Ebola patients in the Kenema District on the outskirts of Kenema, Sierra Leone. Liberia President Ellen Johnson Sirleaf has closed some border crossings and ordered strict quarantines of communities affected by the Ebola outbreak. The announcement late Sunday came a day after Sirleaf formed a new taskforce charged with containing the disease, which has killed 129 people in the country and more than 670 across the region.(AP Photo/ Youssouf Bah)

29 july 2014—There has been panic and fear about the deadly Ebola disease spreading ever since Nigerian health officials reported Friday that a Liberian man sick with the disease had traveled to Togo and then Nigeria before dying. Here are five things to know about Ebola and how it is spread:

1. THE WEST AFRICA EBOLA OUTBREAK IS NOW THE LARGEST IN HISTORY. The World Health Organization says more than 672 people have died from Ebola. A total of 1,201 cases had been reported as of last week in Guinea, Liberia and Sierra Leone. In addition, one Liberian man has died in Nigeria.

2. BUT SOME PEOPLE HAVE SURVIVED EBOLA. While the fatality rate for Ebola can be as high as 90 percent, health officials in the three countries say people have recovered from the virus and the current death rate is about 70 percent. Those who fared best sought immediate medical attention and got supportive care to prevent dehydration even though there is no specific treatment for Ebola itself.

3. EBOLA CAN LOOK A LOT LIKE OTHER DISEASES. The early symptoms of an Ebola infection include fever, headache, muscle aches and sore throat, according to the World Health Organization. It can be difficult to distinguish between Ebola and the symptoms of malaria, typhoid fever or cholera. Only in later stages do people with Ebola begin bleeding both internally and externally, often through the nose and ears.

4. EBOLA IS ONLY SPREAD THROUGH BODILY FLUIDS. The Ebola virus is not airborne, so people would have to come into contact with the bodily fluids of an infected person. These include blood, sweat, vomit, feces, urine, saliva or semen—making transmission through casual contact in a public setting unlikely.

5. FEAR AND MISINFORMATION THOUGH IS MAKING THINGS WORSE. In each of the affected countries, health workers and clinics have come under attack from panicked residents who mistakenly blame foreign doctors and nurses for bringing the virus to remote communities. Family members also have removed sick Ebola patients from hospitals, including one woman in Sierra Leone's capital who later died. Police had to use tear gas to disperse others who attacked a hospital in the country.

Heart attack patients could be treated more quickly

Clinical judgement, combined with an electrocardiogram (ECG) and blood test on arrival, is effective in reducing unnecessary hospital admissions for chest pain, a new study shows.

28 july 2014--The findings of a research group in Manchester, published in the Emergency Medicine Journal, could potentially make a huge difference to a large number of patients.

Chest pain is the most common reason for emergency hospital admission. In Manchester, the incidence of premature death due to heart disease and stroke is amongst the highest in England.

Previous research has shown that typical symptoms in patients presenting to emergency departments have not been useful in differentiating between heart conditions requiring immediate hospital admission (acute coronary syndromes; ACS), and non-cardiac conditions. This is because the symptoms of patients with heart disease can be similar to those experienced by patients with non-cardiac conditions, such as indigestion. However, the role of overall clinical judgement has not been extensively studied.

The latest research, led by Dr Richard Body, Consultant in Emergency Medicine at Manchester Royal Infirmary, assessed the diagnostic accuracy of emergency doctors' clinical judgement for acute coronary syndromes – both alone and in combination with the tests available on arrival – ECG and a blood test which detects a protein called troponin.

The study was undertaken at Stockport NHS Foundation Trust, where doctors in the emergency department recorded their overall clinical judgement for ACS using a five-point Likert scale (from 'definitely ACS' to 'definitely not' ACS). This data was then compared with patients' outcomes, including heart attack or the occurrence of major adverse cardiac events within 30 days.

The results showed that for patients who are suspected to have an ACS, clinical judgement cannot be relied upon by itself to rule out or rule in that diagnosis. However, when combined with an ECG and troponin test clinical judgement appeared to be an effective tool and the results suggest that at least 25 per cent of patient admissions could have avoided. The study also suggested that this was the case regardless of whether the clinician was a consultant or junior doctor.

Dr Rick Body, who is also National Institute for Health Research Postdoctoral Research Fellow and Honorary Lecturer in Cardiovascular Medicine at The University of Manchester, said: "I think the beauty of this technique is its simplicity. For years we've been working hard to improve our technology and our tests for heart attacks. This research suggests that, if the initial tests are normal and the doctor thinks that the diagnosis of a heart attack is unlikely, it may be perfectly safe to reassure patients that they do not have a heart attack without relying on further tests and observation in hospital.

"It is still early days but the study, which was funded through an NIHR Clinical Lecturer grant and a College of Emergency Medicine Research Grant, could potentially make a huge difference to large numbers of patients.

"In order to ensure the safety of patients, further research is still vital to ensure that our findings can be repeated with different groups of doctors and patients. We will also need to know if doctors would be confident enough in their judgement to use the technique in practice."

Provided by University of Manchester

Study shows epigenetic changes can drive cancer

Cancer has long been thought to be primarily a genetic disease, but in recent decades scientists have come to believe that epigenetic changes – which don't change the DNA sequence but how it is 'read' – also play a role in cancer. In particular DNA methylation, the addition of a methyl group (or molecule), is an epigenetic switch that can stably turn off genes, suggesting the potential to cause cancer just as a genetic mutation can. Until now, however, direct evidence that DNA methylation drives cancer formation was lacking.

27 july 2014--Researchers at the USDA/ARS Children's Nutrition Research Center at Baylor College of Medicine and Texas Children's Hospital have now created a mouse model providing the first in vivo evidence that epigenetic alterations alone can cause cancer. Their report appears today in the Journal of Clinical Investigation.

"We knew that epigenetic changes are associated with cancer, but didn't know whether these were a cause or consequence of cancer. Developing this new approach for 'epigenetic engineering' allowed us to test whether DNA methylation changes alone can drive cancer," said Dr. Lanlan Shen, associate professor of pediatrics at Baylor and senior author of the study.

Shen and colleagues focused on p16, a gene that normally functions to prevent cancer but is commonly methylated in a broad spectrum of human cancers. They devised an approach to engineer DNA methylation specifically to the mouse p16 regulatory region (promoter). As intended, the engineered p16 promoter acted as a 'methylation magnet'. As the mice reached adulthood, gradually increasing p16 methylation led to a higher incidence of spontaneous cancers, and reduced survival.

"This is not only the first in vivo evidence that epigenetic alteration alone can cause cancer," said Shen. "This also has profound implications for future studies, because epigenetic changes are potentially reversible. Our findings therefore both provide hope for new epigenetic therapies and validate a novel approach for testing them."

Shen, who is also with the NCI-designated Dan L. Duncan Cancer Center at Baylor, predicts that this new approach will be widely useful because in addition to p16, there are many other genes and diseases other than cancer that are connected to epigenetics (such as neurodevelopmental diseases, obesity and diabetes). Just as genetic engineering has become a standard approach for studying how genetic mutations cause disease, epigenetic engineering will now enable functional studies of epigenetics.

"This opens up the door for a whole new paradigm of how to understand tumorigenesis. If we can identify epigenetic changes that predispose people to cancer, these may actually be treatable or preventable, so this opens up a lot of optimism in new ways to deal with cancer," said Dr. Robert Waterland, associate professor of pediatrics at Baylor, who was also involved in the study.

Provided by Baylor College of Medicine

Slow walking speed and memory complaints can predict dementia 

A study involving nearly 27,000 older adults on five continents found that nearly 1 in 10 met criteria for pre-dementia based on a simple test that measures how fast people walk and whether they have cognitive complaints. People who tested positive for pre-dementia were twice as likely as others to develop dementia within 12 years. The study, led by scientists at Albert Einstein College of Medicine of Yeshiva University and Montefiore Medical Center, was published online on July 16, 2014 in Neurology, the medical journal of the American Academy of Neurology.

26 july 2014--The new test diagnoses motoric cognitive risk syndrome (MCR). Testing for the newly described syndrome relies on measuring gait speed (our manner of walking) and asking a few simple questions about a patient's cognitive abilities, both of which take just seconds. The test is not reliant on the latest medical technology and can be done in a clinical setting, diagnosing people in the early stages of the dementia process. Early diagnosis is critical because it allows time to identify and possibly treat the underlying causes of the disease, which may delay or even prevent the onset of dementia in some cases.

"In many clinical and community settings, people don't have access to the sophisticated tests—biomarker assays, cognitive tests or neuroimaging studies—used to diagnose people at risk for developing dementia," said Joe Verghese, M.B.B.S., professor in the Saul R. Korey Department of Neurology and of medicine at Einstein, chief of geriatrics at Einstein and Montefiore, and senior author of the Neurology paper. "Our assessment method could enable many more people to learn if they're at risk for dementia, since it avoids the need for complex testing and doesn't require that the test be administered by a neurologist. The potential payoff could be tremendous—not only for individuals and their families, but also in terms of healthcare savings for society. All that's needed to assess MCR is a stopwatch and a few questions, so primary care physicians could easily incorporate it into examinations of their older patients."

The U.S. Centers for Disease Control and Prevention estimates that up to 5.3 million Americans—about 1 in 9 people age 65 and over—have Alzheimer's disease, the most common type of dementia. That number is expected to more than double by 2050 due to population aging Neurology paper reported on the prevalence of MCR among 26,802 adults without dementia or disability aged 60 years and older enrolled in 22 studies in 17 countries. A significant number of adults—9.7 percent—met the criteria for MCR (i.e., abnormally slow gait and cognitive complaints). While the syndrome was equally common in men and women, highly educated people were less likely to test positive for MCR compared with less-educated individuals. A slow gait, said Dr. Verghese, is a walking speed slower than about one meter per second, which is about 2.2 miles per hour (m.p.h.). Less than 0.6 meters per second (or 1.3 m.p.h.) is "clearly abnormal."

To test whether MCR predicts future dementia, the researchers focused on four of the 22 studies that tested a total of 4,812 people for MCR and then evaluated them annually over an average follow-up period of 12 years to see which ones developed dementia. Those who met the criteria for MCR were nearly twice as likely to develop dementia over the following 12 years compared with people who did not.

Dr. Verghese emphasized that a slow gait alone is not sufficient for a diagnosis of MCR. "Walking slowly could be due to conditions such as arthritis or an inner ear problem that affects balance, which would not increase risk for dementia. To meet the criteria for MCR requires having a slow gait and cognitive problems. An example would be answering 'yes' to the question, 'Do you think you have more memory problems than other people?'"

For patients meeting MCR criteria, said Dr. Verghese, the next step is to look for the causes of their slow gait and cognitive complaints. The search may reveal underlying—and controllable—problems. "Evidence increasingly suggests that brain health is closely tied to cardiovascular health—meaning that treatable conditions such as hypertension, smoking, high cholesterol, obesity and diabetes can interfere with blood flow to the brain and thereby increase a person's risk for developing Alzheimer's and other dementias," said Dr. Verghese.

What about people who meet MCR criteria but no treatable underlying problems can be found?

"Even in the absence of a specific cause, we know that most healthy lifestyle factors, such as exercising and eating healthier, have been shown to reduce the rate of cognitive decline," said Dr. Verghese. "In addition, our group has shown that cognitively stimulating activities—playing board games, card games, reading, writing and also dancing—can delay dementia's onset. Knowing they're at high risk for dementia can also help people and their families make arrangements for the future, which is an aspect of MCR testing that I've found is very important in my own clinical practice."

More information: "Motoric cognitive risk syndrome: Multi-country prevalence and dementia risk." Other Einstein authors were Emmeline Ayers, M.P.H., Nir Barzilai, M.D., Roee Holtzer, Ph.D., and Cuiling Wang, Ph.D.

Provided by Albert Einstein College of Medicine

Researcher shows how stress hormones promote brain's building of negative memories

The ASU study's findings about stress hormones, such as cortisol (3-D rendering seen above), are important as they pertain to women, since women are twice as likely to develop disorders from stress and trauma that affect memory, such as Post Traumatic Stress Disorder. Credit: Wikimedia Commons

When a person experiences a devastating loss or tragic event, why does every detail seem burned into memory whereas a host of positive experiences simply fade away?

25 july 2014--It's a bit more complicated than scientists originally thought, according to a study recently published in the journal Neuroscience by ASU researcher Sabrina Segal.

When people experience a traumatic event, the body releases two major stress hormones: norepinephrine and cortisol. Norepinephrine boosts heart rate and controls the fight-or-flight response, commonly rising when individuals feel threatened or experience highly emotional reactions. It is chemically similar to the hormone epinephrine – better known as adrenaline.

In the brain, norepinephrine in turn functions as a powerful neurotransmitter or chemical messenger that can enhance memory.

Research on cortisol has demonstrated that this hormone can also have a powerful effect on strengthening memories. However, studies in humans up until now have been inconclusive – with cortisol sometimes enhancing memory, while at other times having no effect.

A key factor in whether cortisol has an effect on strengthening certain memories may rely on activation of norepinephrine during learning, a finding previously reported in studies with rats.

In her study, Segal, an assistant research professor at the Institute for Interdisciplinary Salivary Bioscience Research at ASU, and her colleagues at the University of California-Irvine showed that human memory enhancement functions in a similar way.

Conducted in the laboratory of Larry Cahill at U.C. Irvine, Segal's study included 39 women who viewed 144 images from the International Affective Picture Set. This set is a standardized picture set used by researchers to elicit a range of responses, from neutral to strong emotional reactions, upon view.

Segal and her colleagues gave each of the study's subjects either a dose of hydrocortisone – to simulate stress – or a placebo just prior to viewing the picture set. Each woman then rated her feelings at the time she was viewing the image, in addition to giving saliva samples before and after. One week later, a surprise recall test was administered.

What Segal's team found was that "negative experiences are more readily remembered when an event is traumatic enough to release cortisol after the event, and only if norepinephrine is released during or shortly after the event."

"This study provides a key component to better understanding how traumatic memories may be strengthened in women," Segal added, "because it suggests that if we can lower norepinephrine levels immediately following a traumatic event, we may be able to prevent this memory enhancing mechanism from occurring, regardless of how much cortisol is released following a traumatic event."

Further studies are needed to explore to what extent the relationship between these two stress hormones differ depending on whether you are male or female, particularly because women are twice as likely to develop disorders from stress and trauma that affect memory, such as in Posttraumatic Stress Disorder (PTSD). In the meantime, the team's findings are a first step toward a better understanding of neurobiological mechanisms that underlie traumatic disorders, such as PTSD.

Provided by Arizona State University

Study examines postoperative pneumonia prevention program in surgical ward

A postoperative pneumonia prevention program for patients in the surgical ward at a California Veterans Affairs hospital lowered the case rate for the condition, which can cause significant complications and increase the cost of care.

24 july 2014--Pneumonia is a common infection that accounts for about 15 percent of all hospital-acquired infections and as much as 3.4 percent of complications among surgical patients.

The study outlines the results (2008-2012) for a postoperative pneumonia prevention program for patients who were not on a mechanical ventilator in the hospital's surgical ward. The prevention program had several components, including ongoing education for surgical ward nursing staff on pneumonia prevention, coughing and deep-breathing exercises with incentive spirometer, twice daily oral hygiene with chlorhexidine, walking, sitting up to eat and elevated head-of-bed.

Between 2008 and 2012, there were 18 cases of postoperative pneumonia among 4,099 at-risk hospitalized patients for a case rate of 0.44 percent. That is a 43.6 percent decrease from the hospital's preintervention rate of 0.78 percent. Pneumonia rates in all years were lower than the preintervention rate (0.25 percent, 0.50 percent, 0.58 percent, 0.68 percent and 0.13 percent in 2008-2012, respectively).

"Despite the limitations listed earlier, our study supports the concept that successful and sustained reduction of pneumonia among postoperative patients requires multiple performance measures and unrelenting standardized quality improvement efforts."

More information: JAMA Surgery. Published online July 23, 2014. DOI: 10.1001/jamasurg.2014.1216

Provided by The JAMA Network Journals

Life expectancy gains threatened as more older Americans suffer from multiple conditions

With nearly four in five older Americans living with multiple chronic medical conditions, a new study by researchers at Johns Hopkins Bloomberg School of Public Health finds that the more ailments you have after retirement age, the shorter your life expectancy. The analysis, one of the first to examine the burden of multiple chronic conditions on life expectancy among the elderly, may help explain why increases in life expectancy among older Americans are slowing.

24 july 2014--A report on the findings, based on an analysis of 1.4 million Medicare enrollees, appears in the August issue of the journal Medical Care.

"Living with multiple chronic diseases such as diabetes, kidney disease and heart failure is now the norm and not the exception in the United States," says Eva H. DuGoff, a recent PhD recipient at the Johns Hopkins Bloomberg School of Public Health and lead author of the report. "The medical advances that have allowed sick people to live longer may not be able to keep up with the growing burden of chronic disease. It is becoming very clear that preventing the development of additional chronic conditions in the elderly could be the only way to continue to improve life expectancy."

For their analysis, researchers used the Medicare 5% sample, a nationally representative sample of Medicare beneficiaries, enrolled as of January 1, 2008, which included 21 defined chronic conditions and the records of nearly 1.4 million people 67 and older.

Life expectancy in the U.S. is rising more slowly than in other parts of the developed world and many blame the obesity epidemic and its related health conditions for the worsening health of the American population.

The analysis found that, on average, a 75-year-old American woman with no chronic conditions will live 17.3 additional years (that's to more than 92 years old). But a 75-year-old woman with five chronic conditions will only live, on average, to the age of 87, and a 75-year-old woman with 10 or more chronic conditions will only live to the age of 80. Women continue to live longer than men, while white people live longer than black people.

It's not just how many diseases you have, but also what disease that matters. At 67, an individual with heart disease is estimated to live an additional 21.2 years on average, while someone diagnosed with Alzheimer's disease is only expected to live 12 additional years.

On average, life expectancy is reduced by 1.8 years with each additional chronic condition, the researchers found. But while the first disease shaves off just a fraction of a year off life expectancy for older people, the impact grows as the diseases add up.

"We tend to think about diseases in isolation. You have diabetes or you have heart failure. But many people have both, and then some," says senior author Gerard F. Anderson, PhD, a professor in the Department of Health Policy and Management at the Johns Hopkins Bloomberg School of Public Health. "The balancing act needed to care for all of those conditions is complicated, more organ systems become involved as do more physicians prescribing more medications. Our system is not set up to care for people with so many different illnesses. Each one adds up and makes the burden of disease greater than the sum of its parts."

The researchers say their findings could be useful to Social Security and Medicare planners as they make population and cost predictions for the future. Policymakers are facing a different landscape as so many more people are living with multiple chronic conditions than before: 60 percent of those 67 and older in the U.S. have three or more of these diseases, the researchers found. Eventually, there may be a tipping point, when the medical advances that have boosted life expectancy for so long can no longer keep pace with the many illnesses people are collecting as they age.

"We already knew that living with multiple chronic conditions affects an individual's quality of life, now we know the impact on quantity of life," DuGoff says. "The growing burden of chronic disease could erase decades of progress. We don't want to turn around and see that life expectancy gains have stopped or reversed."

More information: Medical Care: August 2014 - Volume 52 - Issue 8 - p 688-694. DOI: 10.1097/MLR.0000000000000166

Provided by Johns Hopkins University Bloomberg School of Public Health

Weight loss over two years predicts reduced diabetes risk

23 july 2014—Weight loss over two years is associated with reduced diabetes incidence and improvement in cardiometabolic risk factors, according to a study published online July 14 in Diabetes Care.

Linda M. Delahanty, R.D., from Massachusetts General Hospital in Boston, and colleagues examined measures of weight loss in relation to incident diabetes and cardiometabolic risk factors. Data were collected for 1,000 participants in the Diabetes Prevention Program lifestyle intervention arm. They analyzed nine weight measures, characterizing baseline weight, short- versus long-term weight loss, short- versus long-term weight regain, and weight cycling. The authors sought to examine predictors of incident diabetes and improvement in cardiometabolic risk factors.

The researchers found that weight loss in the first six months was protective of diabetes (hazard ratio, 0.94 per kg; P < 0.01) and cardiometabolic risk factors (P < 0.01); however, long-term weight loss (from zero to two years) was the strongest predictor of decreased incidence of diabetes (hazard ratio, 0.90 per kg; P < 0.01) and cardiometabolic risk factor improvement (for example, fasting glucose; P < 0.01). Per participant, weight cycling ranged from zero to six times and correlated positively with incident diabetes (hazard ratio, 1.33; P < 0.01), fasting glucose (P = 0.02), homeostatic model assessment insulin resistance (P = 0.04), and systolic blood pressure (P = 0.01). The effect of weight cycling was significant for diabetes risk (hazard ratio, 1.22; P = 0.03), but not for cardiometabolic traits, after adjustment for baseline weight.

"Two-year weight loss was the strongest predictor of reduced diabetes risk and improvements in cardiometabolic traits," the authors write.

Pharmaceutical, nutrition, and exercise industries donated materials, equipment, or medicines and/or supported the study.

More information: Abstract 

Researchers discover new link between obesity, inflammation, and insulin resistance

Obesity-linked inflammation can lead to type 2 diabetes. Credit: Andy Dean Photography

22 july 2014--A new study by researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) has identified a new signal that triggers the events leading to insulin resistance in obesity. The signal causes inflammation in adipose tissue and leads to metabolic disease. The study, published July 17 in Cell Metabolism, suggests that blocking this signal may protect against the development of metabolic disease, type 2 diabetes, and other disorders caused by obesity-linked inflammation.

"We have uncovered a precise mechanism that explains how inflammation occurs in obesity," said Jorge Moscat, Ph.D., professor and director of the Cell Death and Survival Networks Program at Sanford-Burnham. "The results are important because we know that inflammation of the fat tissue causes insulin resistance, a risk factor for metabolic syndrome and a primary feature of type 2 diabetes. If we can inhibit obesity-linked inflammation, we may be able to prevent the metabolic abnormalities, including type 2 diabetes, associated with obesity," said Maria Diaz-Meco, Ph.D., from the same Program at Sanford-Burnham and co-director of this study.

NBR1 protein triggers inflammation

The researchers initiated their study by comparing levels of the NBR1 protein in healthy men and women with a wide range of body mass index (BMI) and fatness, to levels in men with metabolic syndrome. NBR1 is an inflammatory signaling molecule originally discovered in the labs of Moscat and Maria Diaz-Meco. Metabolic syndrome is a clinical classification of a combination of health problems—including insulin resistance—that are linked to an increased risk of diabetes and early heart disease.

The analysis found that men with metabolic syndrome had higher levels of NBR1 that correlated with metabolic alterations and markers of inflammation, providing the initial clue that NBR1 plays a role in obesity-linked inflammation and metabolic syndrome.

How NBR1 works

To understand how NRB1 works, the research team fed mice in which NBR1 was genetically inactivated a high-fat diet. Compared to normal mice, the mice without NBR1 had less inflammation and better glucose tolerance, suggesting that the protein was promoting inflammation and glucose intolerance.

The researchers went on to show that NBR1 mediates its effects by binding to a protein called MEKK3, and when NBR1 and MEKK3 interact, they cause adipose tissue inflammation.

"MEKK3 is a very attractive protein because it can be therapeutically targeted with small molecules that can lead to the generation of new drugs for insulin resistance, and potentially type 2 diabetes," said Diaz-Meco.

"It's estimated that over 35 percent of American adults are insulin resistant, and without an intervention, many of these cases will progress into type 2 diabetes. An important next step is to look for MEKK3-NBR1 inhibitors to reverse insulin resistance with the promise of new therapies for the treatment of type 2 diabetes," added Steven R. Smith, M.D., professor in the Metabolic Disease Program at Sanford-Burnham, scientific director of the Translational Research Institute for Metabolism and Diabetes, chief scientific officer of Florida Hospital, and co-author of the study.

Provided by Sanford-Burnham Medical Research Institute

Scientists map one of most important proteins in life—and cancer

Scientists reveal the structure of one of the most important and complicated proteins in cell division – a fundamental process in life and the development of cancer – in research published in Nature today.

21 july 2014--Images of the gigantic protein in unprecedented detail will transform scientists' understanding of exactly how cells copy their chromosomes and divide, and could reveal binding sites for future cancer drugs.

A team from The Institute of Cancer Research, London, and the Medical Research Council Laboratory of Molecular Biology in Cambridge produced the first detailed images of the anaphase-promoting complex (APC/C).

The APC/C performs a wide range of vital tasks associated with mitosis, the process during which a cell copies its chromosomes and pulls them apart into two separate cells. Mitosis is used in cell division by all animals and plants.

Discovering its structure could ultimately lead to new treatments for cancer, which hijacks the normal process of cell division to make thousands of copies of harmful cancer cells.

In the study, which was funded by Cancer Research UK, the researchers reconstituted human APC/C and used a combination of electron microscopy and imaging software to visualise it at a resolution of less than a billionth of a metre.

The resolution was so fine that it allowed the researchers to see the secondary structure – the set of basic building blocks which combine to form every protein. Alpha-helix rods and folded beta-sheet constructions were clearly visible within the 20 subunits of the APC/C, defining the overall architecture of the complex.

Previous studies led by the same research team had shown a globular structure for APC/C in much lower resolution, but the secondary structure had not previously been mapped. The new study could identify binding sites for potential cancer drugs.

Each of the APC/C's subunits bond and mesh with other units at different points in the cell cycle, allowing it to control a range of mitotic processes including the initiation of DNA replication, the segregation of chromosomes along protein 'rails' called spindles, and the ultimate splitting of one cell into two, called cytokinesis. Disrupting each of these processes could selectively kill cancer cells or prevent them from dividing.

Dr David Barford, who led the study as Professor of Molecular Biology at The Institute of Cancer Research, London, before taking up a new position at the Medical Research Council Laboratory of Molecular Biology in Cambridge, said:

"It's very rewarding to finally tie down the detailed structure of this important protein, which is both one of the most important and most complicated found in all of nature. We hope our discovery will open up whole new avenues of research that increase our understanding of the process of mitosis, and ultimately lead to the discovery of new cancer drugs."

Professor Paul Workman, Interim Chief Executive of The Institute of Cancer Research, London, said: "The fantastic insights into molecular structure provided by this study are a vivid illustration of the critical role played by fundamental cell biology in cancer research.

"The new study is a major step forward in our understanding of cell division. When this process goes awry it is a critical difference that separates cancer cells from their healthy counterparts. Understanding exactly how cancer cells divide inappropriately is crucial to the discovery of innovative cancer treatments to improve outcomes for cancer patients."

Dr Kat Arney, Science Information Manager at Cancer Research UK, said "Figuring out how the fundamental molecular 'nuts and bolts' of cells work is vital if we're to make progress understanding what goes wrong in cancer cells and how to tackle them more effectively. Revealing the intricate details of biological shapes is a hugely important step towards identifying targets for future cancer drugs."

More information: Molecular architecture and mechanism of the anaphase-promoting complex, Nature, DOI: 10.1038/nature13543

Provided by Cancer Research UK

The 'obesity paradox': Cardiovascular mortality lowest among overweight patients

Credit: Peter Häger/Public Domain

20 july 2014--High body mass index (BMI) is associated with multiple cardiovascular diseases. However, emerging data suggest that there is an "obesity paradox," that being overweight may actually protect patients from cardiovascular mortality. Investigators have now confirmed that the risk of total mortality, cardiovascular mortality, and myocardial infarction is highest among underweight patients, while cardiovascular mortality is lowest among overweight patients, according to two reports published today in Mayo Clinic Proceedings.

Currently more than two-thirds of adult Americans are classified as overweight or obese. Because of the high prevalence of coronary heart disease (CAD), overweight and obese patients more frequently undergo revascularization procedures such as percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). Obesity has been considered a risk factor for worst clinical outcomes following cardiovascular procedures like these, however, emerging data suggest that higher BMI protects against adverse outcomes in many acute and chronic disease states. This prompted experts to reexamine assumptions about body fat and explore the counterintuitive phenomenon known as the "obesity paradox."

In a landmark meta-analysis of 36 studies, Abhishek Sharma, MD, Cardiology Fellow at the State University of New York Downstate Medical Center in Brooklyn, New York, and colleagues determined that low BMI (less than 20 kg/m2) in tens of thousands of patients with coronary artery disease who underwent coronary revascularization procedures was associated with a 1.8- to 2.7-fold higher risk of myocardial infarction and all-cause and cardiovascular mortality over a mean follow up period of 1.7 years. Conversely overweight and obese patients had more favorable outcomes. Cardiovascular mortality risk was lowest among overweight patients with a high BMI (25-30 kg/m2) compared to people with a normal BMI (20-25 kg/m2). Indeed, in obese and severely obese patients with a BMI in the 30-35 and over 35 kg/m2 range, all-cause mortality was 27% and 22% lower than people with normal BMI.

Dr. Sharma observes, "At this stage we can only speculate on the reasons for this paradox. One explanation may be that overweight patients are more likely to be prescribed cardioprotective medications such as beta blockers and statins and in higher doses than the normal weight population. Further, obese and overweight patients have been found to have large coronary vessel damage, which might contribute to more favorable outcomes. This population may have a higher metabolic reserve, which might act protectively in chronic conditions like CAD. Also, there could be a difference in the pathophysiology of cardiovascular disease in over- and underweight patients. A non-modifiable genetic predisposition may also play a role in underweight patients."

He concludes, "However, this is still speculation. Further prospective studies are needed to investigate this association and explore potential underlying mechanisms."

In a second study published in the same issue, investigators examined the "obesity paradox" from another perspective by evaluating the effects of body composition as a function of lean mass index (LMI) and body fat (BF) on the correlation between increasing BMI and decreasing mortality. They estimated BF and LMI in nearly 48,000 people with a preserved left ventricular ejection fraction of more than 50% and examined the survival advantages of obesity across strata of these body compositions.

This large observational study showed that higher lean body mass was associated with 29% lower mortality, and while higher fat mass also exhibited survival benefits, this advantage disappeared after adjustment for lean body mass, suggesting that non-fat tissue bears the primary role in conferring greater survival.

"Body composition plays a critical role in the obesity paradox," says senior investigator Carl Lavie, MD, FACC, FACP, FCCP, Medical Director of Cardiac Rehabilitation and Preventative Cardiology at the John Ochsner Heart & Vascular Institute, Ochsner Clinical School, the University of Queensland School of Medicine, New Orleans. "Whenever examining a potential protective effect of body fat, lean mass index – which likely represents larger skeletal muscle mass – should be considered. At higher BMI, body fat is associated with an increase in mortality."

Noted expert Kamyar Kalantar-Zadeh, MD, MPH, PhD, of the Department of Medicine, University of California Irvine Medical Center, Orange, CA, observes that "although the underlying mechanisms of the obesity paradox and reverse epidemiology remain unclear, the consistency of the data is remarkable, leaving little doubt that these observational data are beyond statistical constellations and bear biologic plausibility.

"The findings in these studies should not be considered as an attempt to undermine the legitimacy of the anti-obesity campaign in the best interest of public health. Nonetheless, given the preponderance and consistency of epidemiologic data, there should be little doubt that in certain populations higher BMI, which is associated with higher risk of metabolic syndrome and poor cardiovascular outcomes in the long-term, confers short-term survival and cardiovascular advantages. Metaphorically we can liken cardiovascular risk factors to a friend who is a negative influence, causing you to misbehave and be sentenced to jail, but once imprisoned the friend remains loyal and protects you against poor prison conditions and other inmates."

More information: "Relationship of Body Mass Index With Total Mortality, Cardiovascular Mortality, and Myocardial Infarction After Coronary Revascularization: Evidence From a Meta-analysis," by Abhishek Sharma, MD; Ajay Vallakati, MD; Andrew J. Einstein, MD, PhD, FACC; Carl J. Lavie, MD, FACC, FACP, FCCP; Armin Arbab-Zadeh, MD, PhD, FACC; Francisco Lopez-Jimenez, MD, MSc, FAHA, FACC; Debabrata Mukherjee, MD, MS, FACC; and Edgar Lichstein, MD, FACC:dx.doi.org/10.1016/j.mayocp.2014.04.020

"Body Composition and Mortality in a Large Cohort With Preserved Ejection Fraction: Untangling the Obesity Paradox," by Alban De Schutter, MD; Carl J. Lavie, MD, FACC, FACP, FCCP; Sergey Kachur, MD; Dharmendrakumar A. Patel, MD; and Richard V. Milani, MD: dx.doi.org/10.1016/j.mayocp.2014.04.025

Provided by Elsevier

Incidence of stroke in the elderly has dropped by 40 percent over the last 20 years

A new analysis of data from 1988-2008 has revealed a 40% decrease in the incidence of stroke in Medicare patients 65 years of age and older. This decline is greater than anticipated considering this population's risk factors for stroke, and applies to both ischemic and hemorrhagic strokes. Investigators also found death resulting from stroke declined during the same period. Their findings are published in the July issue of The American Journal of Medicine.

18 july 2014--Preventable but deadly, stroke is the fourth leading cause of mortality in the United States, with approximately 795,000 strokes occurring each year. Beyond the impact on patients, treatment and after care place high demands on doctors and health care facilities. With an aging population reaching Medicare age, deconstructing and studying stroke statistics are important for understanding the causes underlying this downward trend, benefiting both patients and providers.

"Shedding light on trends in the burden of stroke among Medicare beneficiaries may provide important information for policy purposes, including describing the past and current scope of the condition, assessing the potential effect of stroke prevention interventions on a national level, and identifying areas where resources can be targeted more specifically and effectively," says lead investigator Margaret C. Fang, MD, MPH, an Associate Professor of Medicine at the University of California San Francisco School of Medicine, who also serves as the Medical Director of the UCSF Anticoagulation Clinic.

The study was constructed to analyze stroke cases over the past two decades, not to investigate causation; however, researchers did find evolving patterns in the risk factors associated with strokes. Although the prevalence of diabetes mellitus increased over time, other risk factors, such as cigarette smoking, measured systolic blood pressure, and total cholesterol values, decreased.

The decline in stroke rates paralleled increasing use of antihypertensive and statin medications and might explain the reduction in stroke rates. "Antihypertensive medications reduce the risk of stroke by approximately 32% and statins by approximately 21%. Stroke rates seem to decrease most sharply after year 1998, approximately when statin use became more prevalent," explains Dr. Fang. "If true, then this illustrates how medical interventions have resulted in significant improvements in health on a population level."

Investigators analyzed occurrence data from a sample of Medicare patients diagnosed as having suffered a stroke. Risk factors such as high blood pressure, diabetes, smoking status, and high lipid levels were gathered from the National Health and Nutrition Examination Survey (NHANES). The Medicare Current Beneficiary Survey was used to determine medication use.

The team identified more than one million stroke events from 1988 to 2008, of which 87.3% were ischemic and 12.7% hemorrhagic strokes. The analysis showed a reduction in ischemic strokes from 927 per 100,000 in 1988 to just 545 per 100,000 in 2008. Hemorrhagic strokes decreased from 112 per 100,000 to 94 per 100,000 over the same time period, primarily among men.

Data indicated that stroke mortality also declined. The risk-adjusted 30-day mortality rate for ischemic strokes fell from 15.9% in 1988 to 12.7% in 2008. For hemorrhagic stroke, the mortality rates declined slightly from 44.7% in 1988 to 39.3% in 2008.

Dr. Fang notes that "Our analysis confirms the continuing and devastating effect of hemorrhagic stroke, but was unable to assess for casual factors influencing mortality rates; relatively few interventions have been shown to reduce stroke-related mortality. Timely administration of intravenous thrombolytics is associated with more favorable outcomes from ischemic stroke, but has not been shown to have significant effects on mortality. In addition, the rate of thrombolytic administration continues to be low in the United States."

More information: "Trends in Stroke Rates, Risk, and Outcomes in the United States, 1988 to 2008," by Margaret C. Fang, MD, MPH, Marcelo Coca Perraillon, MA, Kaushik Ghosh, PhD, David M. Cutler, PhD, Allison B. Rosen, MD, MPH, ScD (DOI: dx.doi.org/10.1016/j.amjmed.2014.03.017) appears in The American Journal of Medicine, Volume 127/Issue 7 (July 2014)

Provided by Elsevier

Fundamental research is paving the way for development of first vaccine for heart disease

Researchers at Wayne State University have made a fundamental discovery and, in subsequent collaboration with scientists at La Jolla Institute for Allergy and Immunology (LIAI), are one step closer to the goal of developing the world's first T-cell peptide-based vaccine for heart disease—the number one killer in the nation.

17 july 2014--Atherosclerosis is a chronic inflammatory disease of the arterial walls, which thicken due to accumulation of fatty materials such as cholesterols and triglycerides. Blocking of arteries supplying blood to the heart is the underlying cause of many heart diseases. Nearly 600,000 Americans die of heart disease every year. Although cholesterol is believed to be a major factor in creating the plaque that leads to heart disease, immune inflammation is another important contributor in arterialplaque buildup. The goal of the vaccine is to reduce immune-based inflammation in the arteries, leading to decreased plaque buildup.

The scientists published their findings in the December 2013 issue of Frontiers in Immunology, entitled "Atheroprotective vaccination with MHC-II restricted peptides from ApoB-100." These experiments show proof of concept for the development of an autoantigen-specific vaccine for reducing the amount of atherosclerotic plaques in mice. If successful, the vaccine could aid in preventing heart disease and stop or reduce disease progression. In addition to heart disease, the vaccine could target strokes, which are also a product of plaque buildup in arteries.

The published work, performed in the laboratory of Klaus Ley, M.D., a prominent vascular biologist of LIAI, was based on the fundamental discovery made by Harley Tse, Ph.D., professor of immunology and microbiology in Wayne State's School of Medicine, and professor in Wayne State's Cardiovascular Research Institute, and Michael Shaw, Ph.D., adjunct assistant professor of immunology and microbiology at Wayne State. Shaw and Tse are the first to demonstrate that two T cell epitopes of the autoantigen apoB100 are deeply involved in the development of the disease. Their novel discovery is reported in the article, "Identification of two Immunogenic T cell Epitopes of ApoB-100 and their Autoimmune Implications," published in the April – June 2014 issue (volume 2) of Journal of Immunology and Clinical Research.

"ApoB100 is an apolipoprotein of the LDL (low-density lipoprotein) particle which is the notorious 'bad cholesterol' that contributes to the formation of plaques in the vessel wall," said Tse. "Although T cells of the immune system are known to participate in the development of heart disease, by what and how these T cells are directed to act have not been elucidated. The lack of this knowledge has greatly hampered the development of immune peptide-based therapeutics to control the disease. With the discovery of the disease-causing T cell epitopes, we can now manipulate the activities of the T cells responding to these epitopes to control the disease."

Since immune T cells are normally activated by a short sequence (called an epitope), and not by the whole molecule of an antigen, Shaw and Tse conceptualized that finding the apoB100 epitopes capable of stimulating the disease causing (atherogenic) T cells is a prerequisite for understanding how these T cells are involved in heart disease development and for finding ways to control their adverse effects.

Based on this idea, they identified two short sequences (3501–3515 and 978–992) of ApoB100 (ApoB3501-3515 and ApoB978-992, also designated peptides P3 and P6, respectively) that were able to direct specific T cells to proliferate as well as to cause worsening atherosclerosis. This discovery is significant because it identifies the target T cells and makes it possible to manipulate this population of pathologic T cells away from their harmful activities.

The subsequent collaboration with Ley's laboratory bears the first fruits of this effort.

Provided by Wayne State University

One in three cases of Alzheimer's worldwide potentially preventable, new estimate suggests

A third of Alzheimer's disease cases worldwide can be attributed to risk facts that can be potentially modified, such as lack of education and physical inactivity, according to NIHR-funded research published in The Lancet Neurology today.

16 july 2014--The estimate is lower than the previous estimate of one in two cases as it takes into account the fact some of the risk factors used in previous studies are related. For example, three of the risk factors (diabetes, hypertension and obesity) are linked with physical inactivity and all of these are related to educational level.

Current estimates suggest that by 2050, more than 106 million people will be living with Alzheimer's disease, a huge increase on the 30 million people affected by the disease in 2010. Alzheimer's disease is caused by a complex interplay of genetic and lifestyle factors. Amongst the greatest lifestyle factors are lack of exercise, smoking, poor educational attainment and depression, all of which can be targeted to reduce the risk.

A study published in 2011 suggested that as many as one in two cases of Alzheimer's could potentially be prevented by modifying lifestyle factors. However, this study treated the risk factors as being independent of one another. In today's study, led by Professor Carol Brayne from the Cambridge Institute of Public Health at the University of Cambridge and involving co-authors from the 2011 study, this estimate has been lowered to one in three cases.

The seven key risk factors for which there is consistent evidence of an association with the disease are diabetes, midlife hypertension, midlife obesity, physical inactivity, depression, smoking, and low educational attainment. The researchers estimate that by reducing the relative risk from each of these risk factors by 10%, it will be possible to reduce the prevalence of Alzheimer's in 2050 by 8.5%, preventing 9 million cases.

Dr Deborah Barnes from the University of California, San Francisco and the San Francisco VA Medical Center, who led the 2011 study and is a co-author on this new study, says: "It's important that we have as accurate an estimate of the projected prevalence of Alzheimer's as possible, as well as accurate estimates of the potential impact of lifestyle changes at a societal level. Alzheimer's disease is placing an ever increasing burden on health services worldwide as well as on both patients and their carers. Our hope is that these estimates will help public health professionals and health policy makers design effective strategies to prevent and manage this disease."

Professor Brayne adds: "Although there is no single way to prevent dementia, we may be able to take steps to reduce our risk of developing dementia at older ages. We know what many of these factors are, and that they are often linked. Simply tackling physical inactivity, for example, will reduce levels of obesity, hypertension and diabetes, and prevent some people from developing dementia as well as allowing a healthier old age in general – it's a win-win situation."

More information: "Potential for primary prevention of Alzheimer's disease: an analysis of population-based data." Sam Norton PhD,Fiona E Matthews PhD,Deborah E Barnes PhD,Prof Kristine Yaffe MD,Prof Carol Brayne MD. The Lancet Neurology - 1 August 2014 ( Vol. 13, Issue 8, Pages 788-794 ) DOI: 10.1016/S1474-4422(14)70136-X

Provided by University of Cambridge

This story is republished courtesy of MIT News (web.mit.edu/newsoffice/), a popular site that covers news about MIT research, innovation and teaching.

Living with attitude

The quest for the elixir of life has led us down many paths. Everything from a diet of only fruit and nuts to indulging in a little bit of everything has been charged with the power to extend our lives.

But a new book by academic and clinician Dr Timothy Sharp suggests psychological health could be the key. Live happily and you will probably live longer, posits Dr Sharp, who describes the extra years many of us are now living as the gift of a "third age".

"Properly enjoyed, this phase of life need not be one of illness or decline but rather, for the vast majority of us, one of growth, wisdom, maturity and more," he says in the introduction to Live Happier, Live Longer.

The founder of the Happiness Institute and an Adjunct Professor in positive psychology at the University of Technology, Sydney, Dr Sharp has for many years been studying what makes us happy. But it was only when he was invited to talk about positive psychology at a financial planning conference a couple of years ago that he turned his attention to what happiness means for older people.

"A lot of the financial planners came up to me to chat and it became clear their goals in looking after their clients were similar to mine as a psychologist and life coach: advising people how to best live their lives," says Dr Sharp.

"Their strategies were mostly making sure people had enough money to look after themselves but they realised more than money was at stake."

Live Happier, Live Longer was not directly influenced by the debate about increasing the pension eligibility age to 70, but Dr Sharp says it is important to talk about the implications of working longer.

"What does work really mean now and what does retirement mean? The definitions are changing."

There are many positives about working later in life such as greater financial security and social connections, "which all help to lead a healthy life", says Dr Sharp.

"But I am not suggesting people should be forced to work longer because of financial necessity," he says, adding that many jobs would be too physically demanding for someone in their late 60s.

Live Happier, Live Longer examines scientific research that provides practical strategies to improve the quality and length of our lives.

Not surprisingly, exercise, diet and sleep are important, as are mental health, interpersonal relationships, a sense of belonging and purpose, and spirituality. The list is pretty much the same across the generations.

But Dr Sharp points out that some things come naturally to older people – such as worrying less about what others think of them, taking life at a more relaxed pace, feeling less angry. Others need to be worked at – mixing with younger people, having a strong purpose in life.

"Having a purpose in life is a core construct for leading a meaningful life rather than just a pleasurable life," he says. "But it becomes more important as you get older. It is about giving back to your children, your grandchildren, or mentoring younger people, sharing your knowledge and experience. When you are lying on your death bed you will not be wishing you had spent an extra hour at the office.

"One of my hopes with this book is that it will bust the myths about older people and that we start valuing and cherishing them, and bring back some of the respect we had for them in the past."

Provided by University of Technology, Sydney

Early palliative care cuts costs for critically ill patients

Palliative care delivered early during hospitalization can help cut costs for critically ill patients, finds a new study in Health Services Research.

15 july 2014--"Palliative care programs are increasingly prevalent in U.S. hospitals but the financial incentives for hospitals to deploy them are not well-understood," explains lead author Ian McCarthy, Ph.D., an assistant professor of economics at Emory. Today, 88 percent of large hospitals have palliative care teams and, said McCarthy, palliative care programs have proven "highly effective at addressing a wide range of needs felt by…patients and their families."

Palliative care aims to relieve suffering, be it physical, emotional, social or spiritual. Unlike hospice, palliative care is not limited to the last six months of life. Nor must palliative care patients be considered terminally ill: they often continue to receive disease-modifying treatments along with palliative care services.

Palliative care is a "fairly new medical specialty that has proven to substantially improve patient outcomes when it's delivered alongside routine treatments," says Sean Morrison, M.D., director of the National Palliative Care Research Center and a professor at Mount Sinai's School of Medicine. With palliative care, said Morrison, "symptoms are better managed, families are better cared for, and patients have better quality of life" with reduced pain and suffering.

The new study had two objectives: (1) to quantify potential savings from in-hospital palliative care teams; and (2) to provide guidance to hospital systems on structuring appropriate care teams and the best ways to use palliative care teams for maximal savings.

The researchers analyzed data gathered between January 2009-to-June 2012 at five hospitals within one Dallas-Fort Worth area hospital system. The sample comprised data from 38,475 inpatient stays for people 18 or older hospitalized for 7 to 30 days; and noted whether patients did or did not receive a palliative care consult.

The results, the authors wrote, revealed that "among patients who died in the hospital, there was a significant cost savings from palliative care of $3,426 per inpatient stay." Contrary to previous research, however, they found no cost savings difference for patients discharged alive. This finding, however, can be explained by difference in timing of palliative care, the patient's diagnosis and make-up of the palliative care team, noted the researchers.

They found that savings associated with palliative care were highest for patients who had a consult with a palliative care team within the first 10 days of their hospital stay and for patients diagnosed with cancer. Savings also reached their highest levels when a palliative care team included more involvement of physicians and registered nurses.

The findings showed potential savings for palliative care teams even in facilities with high hospice utilization. Hospitals can achieve the highest quality of care and greatest savings by implementing both hospice and palliative care when appropriate.

Morrison called the work "a well designed study with robust findings." Society today is seeking improved health care quality and costs savings, he said, and palliative care has demonstrated that it can contribute on both fronts. He called for requirements to be put in place for hospitals to routinely use palliative care, and to make the regular use of palliative care a condition for participation in Medicare.

Provided by Health Behavior News Service