Gene mapping for everyone? Study says not so fast

Gene scans for everyone? Not so fast. New research suggests that for the average person, decoding your own DNA may not turn out to be a really useful crystal ball for future health.

3 april 2012--Today, scientists map entire genomes mostly for research, as they study which genetic mutations play a role in different diseases. Or they use it to try to diagnose mystery illnesses that plague families. It's different from getting a genetic test to see if you carry, say, a particular cancer-causing gene.

But as genome mapping gets faster and cheaper, scientists and consumers have wondered about possible broader use: Would finding all the glitches hidden in your DNA predict which diseases you'll face decades later?

Johns Hopkins University developed a model using registries of thousands of identical twins, who despite their shared genes can develop different diseases. They examined 24 ailments, including different types of cancer, heart disease, diabetes and Alzheimer's.

Under best-case scenarios, most people would be told they had a somewhat increased risk of at least one disease, said Dr. Bert Vogelstein, a Hopkins cancer geneticist and the study's senior author.

But a negative test for most of the rest of the diseases doesn't mean you won't get them. It just means that you're at no more risk than the general population. Those are the findings Vogelstein's team reported Monday in the journal Science Translational Medicine. Why? Cancer, for example, typically doesn't result from inherited genes but from mutations that can form anytime, Vogelstein explained. Many other common diseases are influenced by lifestyle and environment - so you'd still have to eat well, exercise and take the other usual precautions.

The study examined just one possible future use of genome mapping. It doesn't mean there aren't other benefits from the effort.

Make no mistake: This technology does have huge promise for customizing care for certain people, especially children with otherwise undiagnosed illnesses, said Dr. James Lupski of Baylor College of Medicine, who wasn't involved in Monday's study.

Last year, Baylor researchers reported one of the first examples of genome mapping directly benefiting a patient. It found a mutation that pointed to the right treatment for a 14-year-old girl's baffling trouble breathing.

But even if finding a genetic explanation doesn't lead to treatment, knowing whether it was inherited can help parents decide whether to chance having another baby, Lupski added.

"There are families where this can be transformative," said Lupski. He had his own genome mapped to identify the cause of a rare nerve disorder.

Treating cancer as a chronic disease

New research from the Technion-Israel Institute of Technology Rappaport Faculty of Medicine and Research Institute and the Rambam Medical Center may lead to the development of new methods for controlling the growth of cancer, and perhaps lead to treatments that will transform cancer from a lethal disease to a chronic, manageable one, similar to AIDS.

02 april 2012--By placing cancer cells in and near a growth developed from a population of human stem cells, scientists have demonstrated that the cancer cells grow and proliferate more robustly when exposed to human cells than they do in a typical petri dish or mouse model. The cancer cell population is also more diverse than had previously been understood. The research was published in the current advanced online issue of the journal Stem Cells. Maty Tzukerman, Rambam senior research scientist and the project leader and senior co-author on the report, says that this model will facilitate targeted drug discovery aimed at blocking the cancer cell self-renewal process.

Previous studies have determined that some tumor cells appear to be differentiated, while others retain the self-renewal property that makes cancer so deadly. According to Technion Professor Karl Skorecki, director of Medical Research and Development at Rambam Health Care Campus and senior co-author on the report, this new research attempts to understand how cancer grows, and to find ways to halt the runaway replication.

In order to mimic the human cancer environment as closely as possible, the research team developed a teratoma - a tumor made of a heterogenous mix of cells and tissues - by enabling the differentiation of human embryonic stem cells into a variety of normally occuring human cell lines on a carrier mouse. The human cellular teratoma constitutes a new platform of healthy human cells for monitoring the behavior and proliferation of human cancer cells.

For this study, the team took cells from one woman's ovarian clear cell carcinoma and injected them either into or alongside the human stem cell-derived environment. "We noticed very early on, rather strikingly, that the human cancer cells grow more robustly when they are in the teratoma environment compared to any other means in which we grew them, such as in a mouse muscle or under the skin of a mouse," says Skorecki.

The scientists were able to tease out six different kinds of self-renewing cells, based on behavior - how quickly they grow, how aggressive they are, how they differentiate - and on their molecular profile. This was a previously unknown finding, that one tumor might have such a diversity of cells with crucial fundamental growth properties. Tzukerman explains that the growth of the cancer cell subpopulations can now be explained by their proximity to the human cell environment.

The researchers cloned and expanded the six distinct cell populations and injected them into the human stem cell teratomas. One key observation is that some cells, which were not self-replicating in any other model, became self-replicating when exposed to the human cells.

Skorecki said that while he wasn't surprised that the human environment affected the growth, he was in fact surprised by the magnitude of the effect: "We've known for years now that cancers are complex organs, but I didn't think the power of the human stem cell environment would be so robust, that it would make such a big difference in how the cells were grown."

The researchers point out that they do not yet know the cues that particularly enhance the cancer's proliferation, and the team is now working on isolating the factors from human cells that promote such plasticity and self-renewing properties. The scientists explain that this may eventually allow physicians to manage cancer as a chronic disease: instead of one therapy against the entire tumor, researchers may develop a method to tease out the variety of self-renewing cell lines of a particular tumor and determine what allows each to thrive, then attack that mechanism.

Skorecki and Tzukerman say that an important next step in this line of cancer research will be to identify and develop ways of blocking the factor or factors that promote this essential self-renewing property of cancer, thus relegating many forms of cancer to controllable, chronic diseases.

This research was supported with grants from the Daniel M. Soref Charitable Trust, the Skirball Foundation, the Richard D. Satell Foundation, the Sohnis and For man families, and the Israel Science Foundation.

Provided by American Technion Society

MRI and neuropsychological tests best predict Alzheimer's disease in old patients

Investigators from the University of Amsterdam, Netherlands, have shown that in most elderly patients invasive and expensive techniques, i.e. lumbar puncture and PET scan, are not useful to establish the diagnosis of Alzheimer's disease. They arrived at this conclusion after analysis of data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a large collaborative research project of medical centers in the USA and Canada.

01 april 2012--The Dutch researchers divided the ADNI sample into two halves, a younger (<75 y) and an older half (>74 y). They showed that the CSF biomarkers (amyloid and tau), and FDG- PET, are informative in the younger but not in the older patients.

In the older patients MRI scans and neuropsychological tests appeared to convey useful information, but CSF biomarkers and FDG-PET did not. The latter two techniques are informative only in younger patients. MRI scans and cognitive tests are not only helpful in distinguishing patients who are already demented from those who are not, but also in predicting who among older MCI patients will progress to dementia within a few years. Predictions based on CSF biomarkers may turn out to be right on the longer term, say five or ten years, in patients who live that long and become demented.

"But this long-term prediction is not what doctors, patients and families really need", says Willem A. van Gool, professor of neurology at the University of Amsterdam. "They want to know the causes of the symptoms, which made them seek help at a memory clinic, and they want to know what the prognosis is in a shorter time frame."

From a theoretical point of view these results underscore that dementia in the older elderly is not exactly the same as Alzheimer's disease in younger patients. It is probably a mix of disease mechanisms. At older ages vascular brain damage and degenerative processes other than amyloid accumulation, such as sclerosis of the hippocampus, are probably important contributors to the dementia syndrome. "At any rate", according to Van Gool, "research findings stemming from relatively young patient samples cannot readily be extrapolated to the vast majority of older dementia patients. In older persons with dementia the causes are more complex than mere amyloid-beta accumulation, and researchers have to address this complexity."

Ben Schmand, professor of clinical neuropsychology at the University of Amsterdam, stresses a practical implication for clinicians. "In MCI patients", he says, "particularly in older patients, it is not sufficient to base a diagnosis solely on a brief memory test, a MRI scan, and a lumbar puncture. Generally, a more thorough clinical evaluation will be necessary Cerebrospinal fluid biomarkers and PET scanning remain informative in relatively young patients."

Provided by IOS Press

People with multiple chronic illnesses have trouble coordinating care

People with chronic illnesses often see up to 5 specialists a year. One major challenge for these patients and their doctors is coordinating care among multiple health care providers. Younger patients and those with several chronic illnesses are more likely to report difficulties with care coordination than older patients with just one chronic illness, finds a new study in Health Services Research.

31 march 2012--“Physicians will tell you there is only so much they can do in coordinating care, especially for patients with complex conditions who see multiple specialists across different care settings like hospitals, rehab centers, and skilled nursing facilities,” said the study’s lead author Daniel Maeng, Ph.D., of the Geisinger Center for Health Research.

To investigate care coordination from the patient’s perspective, Maeng and colleagues surveyed over 9,200 adults with at least one of the following chronic illnesses: high blood pressure, asthma, diabetes, heart disease and depression. About 42 percent reported having more than two of these chronic conditions, with diabetes, high blood pressure and heart disease being the most common combination.

Twenty-seven percent of survey respondents reported that care coordination was a major or minor problem.

Researchers also measured engagement in health care, using the Patient Activation Measure (PAM) developed by Judith Hibbard Ph.D. and colleagues at the University of Oregon. The PAM measures how much a patient feels in charge of their health and confidence in their ability to take steps to manage their health. Those who had higher PAM scores were the least likely to report care coordination problems. In addition, older patients reported fewer issues with care coordination, presumably due to their increased experience with the health care system and more time spent communicating with their physicians.

Researchers were surprised, however, by other patient characteristics that didn’t appear to be associated with care coordination problems. “If you were to conjecture who might be less likely to report adequate coordination—you would think that education might matter, or maybe income level, or insurance coverage, or gender,” Maeng said. “But none of those things seemed to make any difference.”

Ann O’Malley, M.D., of the Center for Studying Health System Change, a nonpartisan health policy research organization, said the findings mesh with results from her own research. “Ironically, coordination efforts often happen to be focused on lower income populations because that is where hospitals really stand to lose money if they don’t coordinate that care well,” she said. For example, hospitals face financial penalties from Medicaid if patients with certain illnesses, such as congestive heart failure, are readmitted soon after discharge.

The study’s findings indicate that health care providers should place special emphasis on coordinating care for those patients who have multiple chronic conditions, Maeng said.

“That makes sense because those are the people who are sickest and have the most doctors involved in their care,” said O’Malley, who was not associated with the study.

More information: Maeng DD, MArtsolf GR, Scanlon DP, et al. (2012). Care coordination for the chronically ill: understanding the patient’s perspective Health Services Research.

Provided by Health Behavior News Service

Parkinson's disease patients can become more creative when they take dopamine

Some Parkinson's Disease patients can suddenly become creative when they take dopamine therapy, producing pictures, sculptures, novels and poetry. But their new-found interests can become so overwhelming that they ignore other aspects of their everyday life, such as daily chores and social activities, according to research published in the March issue of the European Journal of Neurology.

30 march 2012--Italian researchers studied 36 patients with Parkinson's Disease - 18 with increased artistic production and 18 without - and compared them with 36 healthy controls without Parkinson's. None of the patients had engaged in artistic hobbies before they took dopamine.

"Patients were included in the artistic group if they started working on creative projects for two or more hours a day after starting taking dopamine" explains lead author Dr Margherita Canesi, a neurological specialist at the Centro Parkinson e Disordini del Movimento in Milan.

"Our findings suggest that the patients' newly acquired artistic skills were probably there all along, but did not start to emerge until they took the dopamine therapy. They did not appear to be connected with abnormal repetitive behaviours, such as impulse control disorders or punding - stereotyped behavior characterised by an intense fascination with a complex, excessive, non-goal oriented, repetitive activity.

"Other researchers have noted that altered creative drive has been observed in patients who have neurodegenerative diseases or have had a stroke. However the anatomical and physiological understanding of creativity is difficult to establish and quantify."

Dopamine is a neurotransmitter that helps control the brain's reward and pleasure centres. It helps to regulate movement and emotional responses and enables people to see rewards and work towards them. Parkinson's Disease is caused by dopamine deficiency and using medication to increase dopamine levels in the brain is one of the most popular kinds of therapy.

Key findings of the study included:

• The artwork presented by the patients was mainly drawings/paintings (83%), poetry/novels (50%) and sculpture (28%). In 78% of cases, the patients showed more than one skill, normally writing plus painting or drawing.
• Some of the patients produced art that was sold and books that were published, but, at the other end of the scale, some of the creative work was of a very poor quality.
• By using the Torrence Test of Creative Thinking to compare the three groups, the researchers showed that the artistic Parkinson's Disease patients had similar overall and individual scores to the healthy controls. However the non-artistic patients had significantly lower overall scores than the healthy controls and significantly lower scores than the artistic patients when it came to the elaboration sub-score.
• There was no correlation between the Torrence Test of Creative Thinking scores and the scores obtained using the Barratt Impulsivity Scale, one of the oldest and most widely used measures of impulsive personality traits.
• The researchers also used the Minnesota Impulsive Disorders Interview. This showed that one creative patient was positive for compulsive sexual behaviour, one creative patient for compulsive buying and two creative and three non-creative patients for pathological gambling. However, there was little difference in the Torrence scores for patients who tested positive or negative on the Minnesota scale.
• None of the patients or healthy controls displayed the stereotyped behaviour measured by the Punding Rating Scale.

"In conclusion, we found that newly acquired creative drive in patients with Parkinson's Disease, after the introduction of dopaminergic therapy, is not related to impulsivity or impulse control disorders as measured by the Barratt Impulsivity Scale or the Minnesota Impulsive Disorders Interview" says Dr Canesi.

"We believe that their desire to be creative could represent emerging innate skills, possibly linked to repetitive and reward-seeking behaviours. Further studies are needed to support our preliminary observations."

More information: Artistic productivity and creative thinking in Parkinson's disease. Canesi et al. European Journal of Neurology. 19, pp468-472. (March 2012) doi:10.1111/j.1468-1331.2011.03546.x

Provided by Wiley

Elderly are almost 10 times more likely to die of malaria than younger tourists

Tourists who have visited a malaria-infected country and are over the age of 65 are almost 10 times more likely to die from the disease than those who are aged 18-35, reveals a study published in the British Medical Journal today. The death rate among tourists is particularly high when returning from a 'winter sun' holiday in the Gambia, West Africa.

29 march 2012--Authors from the London School of Hygiene and Tropical Medicine and the University of Oxford carried out an observational study based on 20 years of UK data involving over 25,000 patients. They looked at the comparison between fatal and non-fatal cases of malaria and found that tourists are over 9 times more likely to die from the disease than those who are of African heritage travelling to meet friends or family. Most cases of travellers' malaria in the UK do affect people of African heritage, but their risks of dying from the disease are relatively low. This may be due to early exposure to malaria, or to greater awareness of the symptoms and a tendency to seek medical help earlier.

The risk of dying from malaria increased steadily with age, with 25/548 (4.6%) of cases being fatal in people aged over 65. There were no deaths in children under 5 years. Overall, case fatality was 3.0% (81 deaths in 2740 cases) in tourists compared with 0.32% (26/8077) in travellers visiting friends and relatives. Those born in African countries with endemic malaria had a case fatality of 0.4% (36/8937) compared with 2.4%. Case fatality was particularly high in people visiting the Gambia (3.9%, (28/726)) compared with any other west African country (0.4% (58/13,448). Looking only at tourists increased this difference, with a case fatality of 6.0% (20/333) for cases from the Gambia compared with 1.4% (8/565) for tourists visiting the rest of west Africa.

There are reported to be 250 million cases of malaria in the world each year with over 800,000 associated deaths. Travel to infected countries such as Africa is increasing and the UK has one of the highest rates of imported malaria in the world, half of which comes from migrants travelling from infected countries.

For tourists, low drug prophylaxis rates and low awareness of the dangers of malaria may well be factors for death from malaria. There is also a higher death rate in December with over a quarter of deaths occurring then, which may be due to travellers mistaking symptoms for common winter viruses, or getting less rapid diagnosis over the holiday period. The more commonly malaria is seen in an NHS region, the lower the death rate suggesting familiarity with treating the disease may lead to better outcomes. Delay in seeking care may well be a major factor; treated early the outcome for malaria should be good.

The authors conclude that those of African heritage who are visiting friends and family are far more likely to get malaria due to low prophylaxis uptake, but tourists travelling from Europe, especially on winter sun holidays in Africa are far more likely to die from the disease once acquired, a risk that further increases in older tourists. They stress the importance of interventions from doctors who should give pre-travel advice encouraging prompt presentation when returning travellers have a fever and the need for taking anti-malaria drugs. They say doctors must make holidaymakers aware that malaria is common, fatal and needs early diagnosis, but they should also be targeting those of African heritage.

Provided by British Medical Journal

New research characterizes glaucoma as neurologic disorder rather than eye disease

A new paradigm to explain glaucoma is rapidly emerging, and it is generating brain-based treatment advances that may ultimately vanquish the disease known as the "sneak thief of sight." A review now available in Ophthalmology, the journal of the American Academy of Ophthalmology, reports that some top researchers no longer think of glaucoma solely as an eye disease. Instead, they view it as a neurologic disorder that causes nerve cells in the brain to degenerate and die, similar to what occurs in Parkinson disease and in Alzheimer's. The review, led by Jeffrey L Goldberg, M.D., Ph.D., assistant professor of ophthalmology at the Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, describes treatment advances that are either being tested in patients or are scheduled to begin clinical trials soon.

28 march 2012--Glaucoma is the most common cause of irreversible blindness worldwide. For many years, the prevailing theory was that vision damage in glaucoma patients was caused by abnormally high pressure inside the eye, known as intraocular pressure (IOP). As a result, lowering IOP was the only goal of those who developed surgical techniques and medications to treat glaucoma. Creating tests and instruments to measure and track IOP was crucial to that effort. Today, a patient's IOP is no longer the only measurement an ophthalmologist uses to diagnose glaucoma, although it is still a key part of deciding how to care for the patient. IOP-lowering medications and surgical techniques continue to be effective ways to protect glaucoma patients' eyes and vision. Tracking changes in IOP over time informs the doctor whether the treatment plan is working.

But even when surgery or medication successfully lowers IOP, vision loss continues in some glaucoma patients. Also, some patients find it difficult to use eye drop medications as prescribed by their physicians. These significant shortcomings spurred researchers to look beyond IOP as a cause of glaucoma and focus of treatment.

The new research paradigm focuses on the damage that occurs in a type of nerve cell called retinal ganglion cells (RGCs), which are vital to the ability to see. These cells connect the eye to the brain through the optic nerve.

RGC-targeted glaucoma treatments now in clinical trials include: medications injected into the eye that deliver survival and growth factors to RGCs; medications known to be useful for stroke and Alzheimer's, such as cytidine-5-diphosphocholine; and electrical stimulation of RGCs, delivered via tiny electrodes implanted in contact lenses or other external devices. Human trials of stem cell therapies are in the planning stages.

"As researchers turn their attention to the mechanisms that cause retinal ganglion cells to degenerate and die, they are discovering ways to protect, enhance and even regenerate these vital cells," said Dr. Goldberg. "Understanding how to prevent damage and improve healthy function in these neurons may ultimately lead to sight-saving treatments for glaucoma and other degenerative eye diseases."

If this neurologically-based research succeeds, future glaucoma treatments may not only prevent glaucoma from stealing patients' eyesight, but may actually restore vision. Scientists also hope that their in-depth exploration of RGCs will help them determine what factors, such as genetics, make some people more vulnerable to glaucoma.

Provided by American Academy of Ophthalmology

Antipsychotic medication associated with modest heart attack risk in older patients with dementia

Antipsychotic medication was associated with a modest and time-limited increased risk of myocardial infarction (heart attack) among older patients treated with cholinesterase inhibitors for dementia, according to a study published Online First by Archives of Internal Medicine.

27 march 2012--Antipsychotic medications are commonly prescribed for older patients to manage the symptoms of dementia, which can include physical aggression, agitation and hallucinations. For this indication, previous studies have suggested the use of antipsychotic agents (APs) was linked to an increased risk of stroke and safety warnings were issued in several countries. Studies focusing on the risk of death from all causes led to similar conclusions. However, the effect of AP use on the risk of acute myocardial infarction (MI) in patients with treated dementia "remains poorly examined," the authors write in their study background. .

Antoine Pariente, M.D., Ph.D., then of the Université de Montreal, Canada, now of Université Bordeaux Ségalen, France, and colleagues investigated the risk of MI associated with the use of APs in patients with dementia treated with cholinesterase inhibitors (ChIs). Using the Quebec, Canada, prescription claims database, the authors identified 37,138 patients during the study period (January 2000 through December 2009) who were 66 years or older and had ChI treatment. Of them, 10,969 (29.5 percent) started AP treatment during the study period. They were matched with 10,969 non-AP users.

"Our study results indicate that the use of APs is associated with a modest increase in the risk of MI among community-dwelling older patients with treated dementia," the authors note. "The increased risk seems to be highest at the beginning of treatment and seems to decrease thereafter, with the first month of treatment accounting for the highest period of risk."

The results indicate that within one year of starting AP treatment, 1.3 percent of the patients had an incident MI. Hazard ratios for the risk of MI after initiating AP treatment were 2.19 for the first 30 days; 1.62 for the first 60 days; 1.36 for the first 90 days and 1.15 for the first 365 days.

Researchers also performed a self-controlled case series (SCCS) study among 804 new AP users who had an incident MI. The results indicate incidence rate ratios of 1.78 for the one- to 30-day period; 1.67 for the 31- to 60-day period; 1.37 for the 61-to 90-day period; 1.18 for the remaining exposure period; and 0.80 for the withdrawal period.

"Because AP use is frequent in patients with dementia (29.5 percent in our study population), the increased risk of MI may have a major public health effect, which highlights the need for communicating such risk and for close monitoring of patients during the first weeks of treatment," the authors conclude.

In an invited commentary, Sudeep S. Gill, M.D., M.Sc., and Dallas P. Seitz, M.D., of Queen's University, Kingston, Ontario, Canada, write: "The increased risk for death associated with antipsychotic use has raised several important questions, and among them is the question of how exposure to these drugs leads to death."

"Important lessons about the pathogenesis of cardiovascular disease may underlie the observed association between antipsychotic drug use and AMI (acute myocardial infarction) that is described by Pariente et al, but we must await further research to clarify the mechanisms contributing to this association," they comment.

"Meanwhile, physicians should limit prescribing of antipsychotic drugs to patients with dementia and instead use other techniques when available, such as environmental and behavioral strategies, to keep these patients safe and engaged."

More information: Arch Intern Med. Published online March 26, 2012. doi:10.1001/archinternmend.2012.28
Arch Intern Med. Published online March 26, 2012. doi:10.1001/archinternmed.2012.682

Curcumin shows promise in attacking Parkinson's disease

Curcumin, a compound found in the spice turmeric, is proving effective at preventing clumping of a protein involved in Parkinson's disease, says a Michigan State University researcher.

26 march 2012--A team of researchers led by Basir Ahmad, an MSU postdoctoral researcher, demonstrated earlier this year that slow-wriggling alpha-synuclein proteins are the cause of clumping, or aggregation, which is the first step of diseases such as Parkinson's. A new study led by Ahmad, which appears in the current issue of the Journal of Biological Chemistry, shows that curcumin can help prevent clumping.

"Our research shows that curcumin can rescue proteins from aggregation, the first steps of many debilitating diseases," said Lisa Lapidus, MSU associate professor of physics and astronomy who co-authored the paper with Ahmad. "More specifically, curcumin binds strongly to alpha-synuclein and prevents aggregation at body temperatures."

Lapidus' lab uses lasers to study protein folding. Proteins are chains of amino acids that do most of the work in cells. Scientists understand protein structure, but they don't know how they are built – a process known as folding. Lapidus' team is shedding light on the process by correlating the speed at which protein folds with its tendency to clump or bind with other proteins.

When curcumin attaches to alpha-synuclein it not only stops clumping, but it also raises the protein's folding or reconfiguration rate. By bumping up the speed, curcumin moves the protein out of a dangerous speed zone allowing it to avoid clumping with other proteins.

Finding a compound that can fix a protein when it first begins to misfold can lead scientists to identify drugs that can treat certain diseases. Doctors won't be prescribing curcumin pills any time soon, though, Lapidus said.

"Curcumin's usefulness as an actual drug may be pretty limited since it doesn't go into the brain easily where this misfolding is taking place," she said. "But this kind of study showcases the technique of measuring reconfiguration and opens the door for developing drug treatments."

Provided by Michigan State University

New hope for treating Alzheimer's Disease: A role for the FKBP52 protein

New research in humans published today reveals that the so-called FKBP52 protein may prevent the Tau protein from turning pathogenic. This may prove significant for the development of new Alzheimer's drugs and for detecting the disease before the onset of clinical symptoms.

25 march 2012--A study published online today in the Journal of Alzheimer's Disease, for the first time demonstrates that the FKBP52 protein, discovered by Prof. Etienne BAULIEU twenty years ago, may prevent hyperphosphorylation of Tau protein, which has been shown to characterise a number of cerebral neurodegenerative diseases, including Alzheimer's Disease (AD).

This work has been carried out by Professor Etienne Baulieu and his research team at Inserm (National Institute for medical research in France) with the support of philanthropists who help the Institut Baulieu, based in France.

Limited research exists on Tau and its role in the development of AD, but it is known that many neurodegenerative diseases are characterised by the deposition of pathological hyperphosphorylated forms of Tau protein, into structures known as 'Tau tangles'. The mechanism of Tau toxicity is unclear and there are currently no drug treatments targeting Tau, nor any biomarkers that predict the risk of a future "Tauopathy". Professor Baulieu decided to focus on Tau abnormalities and was the first to discover in 2010, an interaction between Tau, and the FKBP52 protein.

The new research takes his previous research to the next level. It demonstrates a direct correlation between high levels of hyperphosphorylated Tau protein and reduced levels of FKBP52, in brain cells from patients who have died following Alzheimer's Disease, compared with normal brain cells. This suggests that FKBP52 could control the aberrant production of pathogenic Tau. When FKBP52 is reduced in the nerve cells of AD patients, pathogenic Tau is free to accumulate and contribute to the degeneration of brain cells.

In conclusion, early measurement of FKBP52 levels could form the basis of a predictive test for Alzheimer's Disease before the onset of clinical symptoms, and new compounds modulating FKBP52's activity could become the next generation of treatments for the disease.

Commenting on this new research, Professor Baulieu said: "There is still a worrying lack of research into the causes of age-related brain disorders such as Alzheimer's Disease and dementia. I founded the Institut Baulieu, with the aim of being able to treat and even prevent these diseases.

Research on Tau has been very limited, and until recently, I was among the few scientists focusing on Tau pathology. The discovery of the FKBP52 protein is the only 'anti-Tau' perspective so far. Its reduced production in the brains of Alzheimer's patients marks a turning point in understanding this complex disease.

I believe it takes us one step closer to developing an effective treatment and possible predictive tests for the increasing number of people who may develop Alzheimer's Disease in our ageing societies."

Provided by IOS Press

Learning best when you rest: Sleeping after processing new info most effective, new study shows

Nodding off in class may not be such a bad idea after all. New research from the University of Notre Dame shows that going to sleep shortly after learning new material is most beneficial for recall.

24 march 2012--Titled "Memory for Semantically Related and Unrelated Declarative Information: The Benefit of Sleep, the Cost of Wake," the study was published March 22 in PLOS One.

Notre Dame Psychologist Jessica Payne and colleagues studied 207 students who habitually slept for at least six hours per night. Participants were randomly assigned to study declarative, semantically related or unrelated word pairs at 9:00 a.m. or 9:00 p.m., and returned for testing 30 minutes, 12 hours or 24 hours later. Declarative memory refers to the ability to consciously remember facts and events, and can be broken down into episodic memory (memory for events) and semantic memory (memory for facts about the world). People routinely use both types of memory every day – recalling where we parked today or learning how a colleague prefers to be addressed.

At the 12-hour retest, memory overall was superior following a night of sleep compared to a day of wakefulness. However, this performance difference was a result of a pronounced deterioration in memory for unrelated word pairs; there was no sleep-wake difference for related word pairs. At the 24-hour retest, with all subjects having received both a full night of sleep and a full day of wakefulness, subjects' memories were superior when sleep occurred shortly after learning, rather than following a full day of wakefulness.

"Our study confirms that sleeping directly after learning something new is beneficial for memory. What's novel about this study is that we tried to shine light on sleep's influence on both types of declarative memory by studying semantically unrelated and related word pairs," Payne says.

"Since we found that sleeping soon after learning benefited both types of memory, this means that it would be a good thing to rehearse any information you need to remember just prior to going to bed. In some sense, you may be 'telling' the sleeping brain what to consolidate."

Provided by University of Notre Dame

Alzheimer's disease spreads through linked nerve cells, brain imaging studies suggest

Alzheimer's disease and other forms of dementia may spread within nerve networks in the brain by moving directly between connected neurons, instead of in other ways proposed by scientists, such as by propagating in all directions, according to researchers who report the finding in the March 22 edition of the journal Neuron.

23 march 2012--Led by neurologist and MacArthur Foundation "genius award" recipient William Seeley, MD, from the UCSF Memory and Aging Center, and post-doctoral fellow Helen Juan Zhou, PhD, now a faculty member at Duke-NUS Graduate Medical School in Singapore, the researchers concluded that a nerve region's connectedness to a disease hot spot trumps overall connectedness, spatial proximity and loss of growth-factor support in predicting its vulnerability to the spread of disease in some of the most common forms of dementia, including Alzheimer's disease.

The finding, based on new magnetic resonance imaging research (MRI), raises hopes that physicians may be able to use MRI to predict the course of dementias – depending on where within an affected network degenerative damage is first discovered – and that researchers may use these predicted outcomes to determine whether a new treatment is working. Network modeling combined with functional MRI might serve as an intermediate biomarker to gauge drug efficacy in clinical trials before behavioral changes become measurable, according to Seeley.

"Our next goal is to further develop methods to predict disease progression, using these models to create a template for how disease will progress in the brain of an affected individual," Seeley said. "Already this work suggests that if we know the wiring diagram in a healthy brain, we can predict where the disease is going to go next. Once we can predict how the network will change over time we can predict how the patient's behavior will change over time and we can monitor whether a potential therapy is working."

The new evidence suggests that different kinds of dementias spread from neuron to neuron in similar ways, even though they act on different brain networks, according to Seeley. Seeley's previous work and earlier clinical and anatomical studies showed that the patterns of damage in the dementias are linked to particular networks of nerve cells, but until now scientists have found it difficult to evaluate in humans their ideas about how this neurodegeneration occurs.

In the current study, the researchers modeled not only the normal nerve network that can be affected by Alzheimer's disease, but also those networks affected by frontotemporal dementia (FTD) and related disorders, a class of degenerative brain diseases identified by their devastating impact on social behaviors or language skills.

The scientists mapped brain connectedness in 12 healthy people. Then they used data from patients with the five different diseases to map and compare specific regions within the networks that are damaged by the different dementias.

"For each dementia, we looked at four ideas that scientists often bring up to explain how dementia might target brain networks," Seeley said. "The different proposed mechanisms lead to different predictions about how a region's place in the healthy network affects its vulnerability to disease."

In the "nodal stress" hypothesis, small regions within the brain that serve as hubs to carry heavy signaling traffic would undergo wear and tear that gives rise to or worsens disease. In the "trophic failure" mechanism, breakdowns in connectivity would disrupt transport through the network of growth factors needed to maintain neurons. In the "shared vulnerability" mechanism, specific genes or proteins common to neurons in a network would make them more susceptible to disease. But predictions from the "trans-neuronal spread" mechanism model best fit the network connectivity maps constructed by the researchers.

"The trans-neuronal spread model predicts that the more closely connected a region is to the node of disease onset – which we call the epicenter – then the more vulnerable that region will be once the disease begins to spread," Seeley said. "It's as if the disease is emanating from a point of origin, but it can reach any given target faster if there is a stronger connection."

The scientists tracked and analyzed linkages within nerve networks that the dementias target. They used a technique called functional connectivity MRI to measure and spatially represent activity in specific regions of key networks in the brains of the healthy subjects. The MRI readout allowed the researchers to model each region within the network as a distinct but interconnected node. They ranked the nodes that most consistently fired together as being the most closely connected.

Across the five diseases investigated in the study, trans-neuronal spread was the proposed mechanism for which the data best matched the predictions. Previous studies of animals and cells in the laboratory also support the idea that disease-related proteins can spread from an affected neuron to other neurons via intercellular connections.

For more than three decades researchers have been noticing that regions affected by Alzheimer's disease are connected by axons that branch between and connect neurons, Seeley said. Trans-neuronal spread is a proven hallmark of certain rare neurodegenerative diseases – such as Creutzfeldt-Jakob disease – that are propagated by misfolded cell-surface proteins called prions, which induce neighboring proteins to change shape, aggregate and wreak havoc.

While Alzheimer's disease and FTD are not considered infectious, abnormal protein structures also are implicated in these common dementias. Recent experiments in which researchers transplanted post-mortem, human brain extracts from dementia patients into genetically modified mice have resulted in disease, Seeley said, "But it is difficult to explore these ideas in humans, and we wanted to begin to bridge this knowledge gap."

The findings of the UCSF researchers are reinforced by a study conducted independently and published in the same edition of the journal by a research team led by Ashish Raj, PhD, from Weill Medical College of Cornell University. The Cornell scientists used another MRI technique, called diffusion tensor imaging, to examine connectedness in affected nerve networks, obtaining similar results.

Provided by University of California - San Francisco

Aspirin to prevent and treat cancer: The evidence continues to build

A collection of three papers (two published in The Lancet and one in The Lancet Oncology) add to the growing evidence base suggesting that daily aspirin can be used to help prevent and possibly treat cancer. All three papers are by Professor Peter M Rothwell, University of Oxford and John Radcliffe Hospital, Oxford, and colleagues.

22 march 2012--Previous studies by Rothwell and colleagues have established that daily aspirin reduces the long-term risk of death due to cancer (Lancet 2007, 2010, 2011). However the short-term effects are less certain, especially in women, as is how the risk/benefit of aspirin changes over time. In the first paper (The Lancet), the authors studied individual patient data from 51 randomised trials of daily aspirin versus no aspirin to prevent vascular events such as heart attacks.

They found that aspirin reduced the risk of a cancer death by 15% compared with controls. This improved to a 37% reduced risk of a cancer death for those on aspirin from 5 years and onwards. The reduction in cancer deaths on aspirin resulted in a 12% reduction in non-vascular deaths overall during the trials. In these trials of primary prevention, the reduction in non-vascular deaths accounted for almost all (91%) of the deaths prevented. Daily low-dose aspirin reduced cancer incidence by around a quarter from 3 years and onwards, with similar reductions in men (23%) and women (25%).

Although the reduced risk of major vascular events in these trials was initially offset by an increased risk of major bleeding, both these effects diminished over time, leaving only the reduced risk of cancer from 3 years and onwards (an absolute reduction of 3 cases per 1000 patients per year, 12 per 1000 control versus 9 per 1000 in aspirin groups). The authors also found that case-fatality from major extracranial bleeds was also two thirds lower on aspirin than on control.

The authors say: "Alongside the previously reported reduction by aspirin of the long-term risk of cancer death, the short-term reductions in cancer incidence and mortality and the decrease in risk of major extracranial bleeds with extended use, and their low case-fatality, add to the case for daily aspirin in prevention of cancer."

They add: "In view of the very low rates of vascular events in recent and ongoing trials of aspirin in primary prevention, prevention of cancer could become the main justification for aspirin use in this setting."

A second Article in The Lancet reports the effect of aspirin on cancer metastasis (or how cancer grows/spreads). In this study, the authors collected new data on metastases of cancers that were diagnosed during all five large randomised trials of daily aspirin (75mg or more daily) versus control for the prevention of vascular events in the UK.

They found that, with a mean follow-up of 6.5 years, allocation to aspirin reduced risk of cancer with distant metastasis by 36%, risk of adencarcioma (common solid cancers including colon, lung, and prostate cancers) by 46%, and of other solid cancers (eg bladder, kidney) by 18%. These reductions were due mainly to a reduction by almost half in the proportion of adenocarcinomas that had metastatic disease.

The researchers also found that aspirin reduced the risk of adenocarcinoma with metastasis at initial diagnosis by almost a third (31%), and risk of metastasis on subsequent follow-up in patients without metastasis initially (by 55%), particularly in patients with colorectal cancer(by 74%), and in patients who remained on trial treatment up to or after diagnosis (by 69%).

Aspirin reduced death due to cancer in patients who developed adenocarcinoma (especially those without metastasis at diagnosis, by around half). Aspirin reduced the overall risk of fatal adenocarcinoma in the trial populations (by 35%) but not the risk of other fatal cancers (eg blood cancers). The effects of aspirin were independent of age, and sex, and were also seen with a low-dose, slow-release formulation of aspirin designed to inhibit platelets but to have little systemic bioavailability.

"These findings provide the first proof in man that aspirin prevents distant cancer metastasis. Previous animal studies had shown that platelets play a part in metastasis of cancer via the bloodstream to distant tissues and that such metastasis might be prevented by aspirin," say the authors. "That aspirin prevents metastasis at least partly accounts for the reduced cancer mortality recently reported in trials of aspirin versus control in prevention of vascular events and suggests that aspirin will also be effective in treatment of some cancers. The lack of dependence of this effect of aspirin on its systemic bioavailability suggests that it is platelet-mediated. Other antiplatelet drugs might therefore have a similar effect on risk of metastasis and combining different drugs might increase benefit."

The third study, published in The Lancet Oncology, also looked at aspirin's effect on metastases, this time using a systematic review of observational versus randomised trials. The authors did this comparison because while randomised trials of aspirin could clearly establish the risk of colorectal cancer, several other solid cancers, and of metastasis, these trials lacked the statistical power to establish effects on less common cancers and on cancers in women. The potential advantage of observational studies, particularly case control studies, is that if they can be shown to produce reliable results they can be done very quickly, rather than waiting 10-20 years for the results of prospective trials.

They found that observational studies showed a 38% reduced risk of colorectal cancer, matching well to the 42% reduction shown by randomised trials. Similar matches in risk were found for oesophageal, gastric, biliary, and breast cancer.

The authors conclude: "Observational studies show that regular use of aspirin reduces the long-term risk of several cancers and the risk of distant metastasis. Results of methodologically rigorous studies are consistent with those obtained from randomised controlled trials, but sensitivity is particularly dependent on appropriately detailed recording and analysis of aspirin use."

In a linked Comment, Dr Andrew T Chan and Dr Nancy R Cook, Brigham and Women's Hospital, Harvard Medical School, Boston, say: "Despite a convincing case that the vascular and anticancer benefits of aspirin outweigh the harms of major extracranial bleeding, these analyses do not account for less serious adverse effects on quality of life, such as less severe bleeding."

They conclude: "Rothwell and colleagues' impressive collection of data moves us another step closer to broadening recommendations for aspirin use. Moreover, future evidence-based guidelines for aspirin prophylaxis can no longer consider the use of aspirin for the prevention of vascular disease in isolation from cancer prevention."

More information: http://www.thelanc … /article/PII S0140-6736(11)61720-0/abstract
http://www.thelanc … 0140-6736(12)60209-8/abstract
http://www.thelanc … 1470-2045(12)70112-2/abstract
http://www.thelanc … 0140-6736(11)61654-1/abstract

New evidence links Alzheimer's disease and diabetes

An emerging body of research suggests that Alzheimer's disease may be linked to insulin resistance, constituting a third type of diabetes. This model is based on several observations including an increased risk of developing Alzheimer's disease for diabetic patients, and reduced insulin levels in the brain tissue of Alzheimer's disease patients.

21 march 2012--Though intriguing, the existing evidence does not reveal if defective insulin signaling is causative of Alzheimer's or how insulin resistance impacts cognitive function. Two back-to-back research articles in the Journal of Clinical Investigation – led by Konrad Talbot, Steve Arnold and colleagues at the University of Pennsylvania and by Fernanda De Felice, Sergio Ferreria and colleagues at the University of Rio de Janeiro - address the connection between insulin resistance and Alzheimer's disease.

The University of Pennsylvania team examined insulin signaling in human brain tissue postmortem, and concluded that the activation state of many insulin signaling molecules were highly related to memory and cognitive function. They further suggest that insulin resistance is a common and early feature of Alzheimer's disease.

The De Felice group further observed impaired insulin signaling in Alzheimer's brain tissue in rodent and non-human primate model systems as well as from tissue from human patients. They went on to show in a mouse model system of Alzheimer's disease that treatment with a new anti-diabetic drug normalized insulin signaling and remarkably improved cognitive function.

Cumulatively, these two new studies strongly support a connection between insulin resistance and Alzheimer's disease and provide hope for new therapeutics in Alzheimer's disease treatment.

More information: An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease–associated Aß oligomers - http://www.jci.org … 1f2106f5edc4

Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline - http://www.jci.org … 73792af09d60

Provided by Journal of Clinical Investigation

Hepatitis C, a leading killer, is frequently undiagnosed but often curable

20 march 2012-- Hepatitis C virus — not AIDS-causing HIV — is the leading chronic virus infection leading to death in the United States, and its victims most often are baby boomers. More than half who are infected do not know it.

Researchers from the U.S. Centers for Disease Control and Prevention (CDC) found in a study published in the February 21 issue of the Annals of Internal Medicine that hepatitis C had overtaken HIV as a cause of death in the United States by 2007.

Deaths in the United States due to HIV infection have been steadily decreasing, and dropped below 13,000 in 2007, while deaths from hepatitis C infection have been steadily increasing, first surpassing 15,000 per year in 2007.

The good news, according to UCSF liver specialist Alex Monto, MD, is that there has been progress in fighting both diseases, and the kinds of drug combination strategies that have done so much to transform HIV infection from a death sentence to a manageable disease are poised to further boost cure rates for those infected with hepatitis C.

“We know that not enough people with risk factors get tested,” Monto says. “There are a lot of people walking around with hepatitis C who don’t know it.”

Monto directs the liver clinic at the UCSF-affiliated San Francisco Veteran’s Affairs Medical Center, one of four hepatitis C centers nationally within the VA system. Like boomers, veterans are disproportionately affected by hepatitis C. The VA cares for 165,000 patients who are chronically infected with the virus.

Three Million in U.S. Diagnosed with Hep C

Chronic Hepatitis C has been diagnosed in about three million people in the United States. It often causes no symptoms, and many who have been infected for years or even decades may remain unaware of it until symptoms finally appear. The ultimate cause of death attributable to chronic infection is cirrhosis or liver cancer, although the disease progresses to cirrhosis in fewer than half of cases. There is no vaccine.

“The main risk factor in the United States is past injection-drug use,” Monto says. “The others most at risk are those who received blood transfusions before 1992,” Monto says, referring to the year when high-quality screening of the blood supply was implemented.

Compared to HIV or hepatitis B, the risk of hepatitis C being transmitted by sex is low, Monto says, but among men who have sex with men there has been an increase in reports of the virus being sexually transmitted, more so among those who are infected with HIV.

“Anybody with a history of ever being exposed to injection drugs or who received a transfusion before the blood supply was screened should be tested,” Monto says. “That’s not controversial at all. What has been controversial is whether or not all baby boomers should be screened.”

Another study in this week’s edition of the journal suggests that a one-time blood test ordered by primary care providers to screen for antibodies to hepatitis C in those born between 1945 and 1965 would be cost effective — costing $2,874 for each chronically infected patient identified — and would lead to the identification of more than 800,000 previously undiagnosed cases.

Those who are chronically infected may be able to reduce the likelihood of disease progression by avoiding alcohol, by maintaining a healthy weight, and by being vaccinated against hepatitis A and hepatitis B, Monto says.

Treatment Often Cures Hepatitis C

About four out of five who are infected do not rid themselves of the virus without treatment. For about a decade the standard treatment was a combination of two drugs — pegylated interferon given once per week by subcutaneous injection, and daily ribavirin pills, with treatment lasting from six to 11 months. This treatment represented a vast improvement — offering cure rates of 40 percent to 50 percent in most patients, according to Monto.

Within the past year two new drugs of a type known as protease inhibitors have become available. These are valuable for the 75 percent of U.S. hepatitis C patients infected with a form of the virus called genotype 1. With the protease inhibitors added to the mix, the duration of treatment may be shorter, and the cure rate has increased to about 70 percent in patients who have not previously been treated, Monto says. A cure may be less likely for those who have been previously treated, depending on how they responded to earlier treatment.

“New therapies are clearly getting better, and there are probably 25 to 30 new drugs in the pipeline, with many coming out in the next few years,” Monto says. “There are going to be drugs that are better than the ones we have so far.” Several UCSF researchers, including Monto, are helping to evaluate new drugs in clinical trials. UCSF researchers also are investigating the role of the immune system in hepatitis C and hepatitis B infection.

Not to Be Confused with Hepatitis B

Hepatitis B chronically infects about half as many as hepatitis C in the United States, and hits those of Asian descent especially hard — they account for half of hepatitis B infections. Hepatitis B is responsible for about 1,800 deaths yearly in the United States.

Despite the similar names, the two viruses are not closely related. Hepatitis B is spread much more easily through sexual intercourse, and passes from mother to newborn child much more easily. In most adults who become infected the immune system successfully controls infection. Only about five percent of adults exposed to hepatitis B become chronically infected, according to Monto.

There are vaccines for hepatitis B. A UCSF laboratory team led by William Rutter, PhD, now professor emeritus, first demonstrated that an uncontaminated source of material for a hepatitis B vaccine could be obtained by mass-producing viral proteins in genetically engineered, laboratory-grown yeast. This was the groundwork leading to the first marketed genetically engineered vaccine, made by Chiron, a company co-founded by Rutter.

Provided by University of California, San Francisco

Poor literacy skills linked to increased mortality risk among older people

One in three older people who have difficulty reading and understanding basic health related information may be at increased risk of death, concludes a study published in the British Medical Journal today.

19 march 2012--The findings have important implications given rising levels of long term conditions and the UK government's plans for patients to become responsible and active partners in their care.

Poor literacy skills are already associated with a wide range of adverse health outcomes. Much of the existing research into health literacy (being able to apply reading skills and basic knowledge in a health context) has been conducted in the US. Low health literacy is associated with less knowledge of chronic diseases, poorer mental and physical health, limited use of preventive services, and higher rates of admissions to hospital.

However, the scale of literacy problems in older adults in England is not known.

So a team of researchers at University College London set out to investigate the relationship between health literacy and mortality in older adults in England, irrespective of known risk factors like age, socioeconomic position and pre-existing illness.

The study involved 7,857 adults aged 52 years and over who took part in the second wave (2004-5) of the English Longitudinal Study of Ageing (ELSA). Participants completed a test of functional health literacy, which assessed understanding of written instructions for taking an aspirin tablet. Deaths were monitored until October 2009.

A total of 621 deaths occurred during follow up: 321 (6%) in the high test score group, 143 (9%) in the medium group and 157 (16%) in the low group.

One in three adults was unable to completely understand the medicine label instructions, indicating limited health literacy.

Adults with the lowest health literacy scores were more than twice as likely to die within five years as those with the highest scores. Differences in age, socioeconomic position, and general health at the start of the study accounted for less than half of the increased risk.

Even after adjusting for measures of cognitive (mental) function, low health literacy was still a significant predictor of mortality.

This study suggests that a third of older adults in England have difficulties reading and understanding basic health related written information. Those with the poorest understanding are at greatest risk of mortality, say the authors.

The findings should remind all healthcare professionals to adopt effective communication techniques for patients with low health literacy, they conclude. At a broader level, the design and delivery of health related services for older adults in England "should be sensitive to the limited health literacy capabilities within this population."

Provided by British Medical Journal

Study finds PSA testing cuts prostate cancer death risk, but does it save lives?

Countering other reports, researchers found the screen reduced mortality rate by 30 percent.

18 march 2012-- Adding another perspective to one of the most controversial and confounding issues in medicine, a new European study reports that men who received routine prostate-specific antigen (PSA) tests to check for signs of prostate cancer were 30 percent less likely to die from the disease.

But the big picture isn't simple enough for the new research to solve once and for all the question of whether PSA testing helps men.

"There is little doubt that a man who undergoes testing will have about a 30 percent less chance of dying from prostate cancer," said the study's lead author, Dr. Fritz Schroder, professor of urology at Erasmus University in Rotterdam, Netherlands. "On the other side, there's a 30 percent chance that a cancer found is insignificant and the patient may be confronted with the side effects of treatment unnecessarily."

Schroder is referring to the major issue in the PSA debate: Do the PSA tests do more harm than good?

In some cases, the tests detect cancer that would be deadly, giving men an opportunity to treat it and potentially survive. In other cases, men are unnecessarily treated for cancer that actually would develop so slowly that it wouldn't threaten their lives.

There's also the matter of cost -- PSA screenings cost an estimated $3 billion in the United States each year -- and the potentially severe side effects of treatment, including incontinence and impotence. In addition, the new study found that only about 0.5 percent of men developed the cancer and died from it in the period reviewed.

For the new study, the scientists examined the medical records of more than 160,000 men in eight European countries, who ranged in age from 55 to 69 when the study began. Some were randomly assigned to receive PSA screening tests.

After an average of 11 years, the men in the study who got screened were 21 percent less likely to have died from prostate cancer.

The study findings appear in the March 15 issue of the New England Journal of Medicine.

A physician who wrote an accompanying journal commentary said the new findings "add more confusion" to the issue. But one thing is clear: They don't convince him that routine PSA tests are a good idea.

The problem is that "you can have prostate cancer sitting there, doing nothing," said Dr. Anthony Miller, professor emeritus of epidemiology at the University of Toronto's Dalla Lana School of Public Health. "It's not going to kill them; it's not going to grow."

But a PSA test can still discover prostate cancer, leading to unnecessary tests and treatment.

"You'll always find people who are convinced that no matter what is done, the evidence doesn't matter and what they really want to find out is if they have any cancer," Miller said. "They will assume that the mere fact of finding a cancer will mean that good has been done."

Miller recommends the PSA test only for men who have certain symptoms or if it's used to monitor treatment in men who have prostate cancer. "As a general screening for healthy men, I do not recommend it at all," he said.

Miller also doesn't recommend the prostate examination done by hand that physicians commonly give to middle-aged and older men, unless symptoms are present.

More information: For more about prostate cancer, try the U.S. National Library of Medicine.

Lack of sleep may increase calorie consumption

If you don't get enough sleep, you may also eat too much — and thus be more likely to become obese.

17 march 2012--That is the findings of researchers who presented their study at the American Heart Association's Epidemiology and Prevention/Nutrition, Physical Activity and Metabolism 2012 Scientific Sessions.

"We tested whether lack of sleep altered the levels of the hormones leptin and ghrelin, increased the amount of food people ate, and affected energy burned through activity," said Virend Somers, M.D., Ph.D., study author and professor of medicine and cardiovascular disease at the Mayo Clinic, Rochester, Minn.. Leptin and ghrelin are associated with appetite.

The researchers studied 17 normal, healthy young men and women for eight nights, with half of the participants sleeping normally and half sleeping only two-thirds their normal time.

Participants ate as much as they wanted during the study.

Researchers found:

• The sleep deprived group, who slept one hour and 20 minutes less than the control group each day consumed an average 549 additional calories each day.
• The amount of energy used for activity didn't significantly change between groups, suggesting that those who slept less didn't burn additional calories.
• Lack of sleep was associated with increased leptin levels and decreasing ghrelin — changes that were more likely a consequence, rather than a cause, of over-eating.

"Sleep deprivation is a growing problem, with 28 percent of adults now reporting that they get six or fewer hours of sleep per night," said Andrew D. Calvin, M.D., M.P.H., co-investigator, cardiology fellow and assistant professor of medicine at the Mayo Clinic.

The researchers noted that while this study suggests sleep deprivation may be an important part and one preventable cause of weight gain and obesity, it was a small study conducted in a hospital's clinical research unit.

"Larger studies of people in their home environments would help confirm our findings," Calvin said.

Provided by American Heart Association

REM sleep disorder doubles risk of mild cognitive impairment, Parkinson's

People with symptoms suggesting rapid eye movement sleep behavior disorder, or RBD, have twice the risk of developing mild cognitive impairment (MCI) or Parkinson's disease within four years of diagnosis with the sleep problem, compared with people without the disorder, a Mayo Clinic study has found. The researchers published their findings recently in the Annals of Neurology.

16 march 2012--One of the hallmarks of rapid eye movement (REM) sleep is a state of paralysis. In contrast, people with rapid eye movement sleep behavior disorder, appear to act out their dreams when they are in REM sleep. Researchers used the Mayo Sleep Questionnaire to diagnose probable RBD in people who were otherwise neurologically normal. Approximately 34 percent of people diagnosed with probable RBD developed MCI or Parkinson's disease within four years of entering the study, a rate 2.2 times greater than those with normal rapid eye movement sleep.

"Understanding that certain patients are at greater risk for MCI or Parkinson's disease will allow for early intervention, which is vital in the case of such disorders that destroy brain cells. Although we are still searching for effective treatments, our best chance of success is to identify and treat these disorders early, before cell death," says co-author Brad Boeve, M.D., a Mayo Clinic neurologist.

Previous studies of Mayo Clinic patients have shown that an estimated 45 percent of people who suffer from RBD will develop a neurodegenerative syndrome such as mild cognitive impairment or Parkinson's disease within five years of diagnosis.

"This study is the first to quantify the risk associated with probable RBD in average people, not clinical patients, and it shows that we can predict the onset of some neurodegenerative disorders simply by asking a few critical questions," says lead author Brendon P. Boot, M.D., a behavioral neurologist. Dr. Boot was at Mayo Clinic when the study was conducted. He is now at Harvard University.

MCI is an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. It involves problems with memory, language, thinking and judgment that are greater than typical age-related changes.

An estimated 500,000 Americans suffer from Parkinson's disease, which is characterized by tremor or shakiness, stiffness of the limbs and trunk, slowness of movement, and impaired balance and coordination.

Provided by Mayo Clinic

Scientists identify cofilin, a protein linked to Alzheimer's, as key to molecular motors

Microscope image showing balloon-like membrane protrusions or blisters (green) and abnormal F-actin (red) in cells where cofilin was depleted.These defects result from excessive myosin II

15 march 2012--A protein that has been linked to Alzheimer’s disease and cancer is at the center of groundbreaking research by a team of Colorado State University scientists. The team found that the protein, called cofilin, regulates the forces that are essential, for example, for cells to migrate around the body.

The research appears this week in Developmental Cell journal.

Scientists have known that mutations to cofilin in mice create defects that lead to disease similar to those that affect humans; for example, where the nervous system doesn’t develop properly. They’ve also known that cofilin is responsible for assembling and dissembling F-actin, a polymer that provides the scaffolding that gives cells their shape.

But Colorado State scientists have now discovered a new behavior of cofilin that helps them understand more about how defects are created when cofilin is lost from cells: The protein helps regulate the forces generated by a class of molecular motors known as Myosin II, said O’Neil Wiggan, a research scientist and lead author on the paper. Other authors include biochemistry professors Jim Bamburg and Jennifer DeLuca and research associate Alisa Shaw.

Myosin II is part of healthy cells, too, but they must have the proper propulsion behind them. Excessive force can cause deviation in cells and propagate unhealthy cells. Wiggan compared it to the force required to hammer a small nail vs. hitting a pole in the ground – different forces are required.

The revelation ultimately could help scientists design treatments for cancer and disease.

“Cofilin controls forces that direct not just the morphology but many different aspects of cell function – such as migration and division,” Wiggan said. “Understanding how cofilin plays a role in controlling these forces means we might be able to develop therapeutic targets for treating diseases such as cancer where these forces become deregulated.

“These contractile forces power cell migration, and cell migration is what is required for metastases, which is the deadly part of cancer,” Wiggan said.

“We’ve shown in this paper that when you reduce the levels of cofilin in human cells, the cells develop blister-like membrane protrusions and have cell division defects, which are typical of what’s in cancer cells. A feature of cancer cells is that they accumulate imbalance in the division of chromosomes.”

Another feature of cancer tissues is that they stiffen, as in breast cancer. By controlling the forces that cause that stiffness, the cofilin pathway may contribute to tumor development, Wiggan said.

Scientists generally have linked cofilin function to such diseases as Alzheimer’s, spina bifida and Hirschsprung’s disease. While the new CSU paper sheds light on cofilin behavior, more research is needed.

“We don’t understand the basis of the defects in disease – perhaps, for instance, they’re related to extra forces in these cells which might inhibit their ability to migrate properly,” Wiggan said. “Before you can translate what cofilin’s doing in these specific contexts, you have to understand what cofilin does in cells in general.”

Provided by Colorado State University