Alzheimer’s neuronal death process not triggered by amyloid-beta, but by tau

WASHINGTON — New research points to tau, not amyloid-beta (Abeta) plaque, as the seminal event that spurs neuron death in disorders such as Alzheimer’s disease. The finding, which dramatically alters the prevailing theory of Alzheimer’s development, also explains why some people with plaque build-up in their brains don’t have dementia.

The study is published online today in the journal Molecular Neurodegeneration.

Neuronal death happens when tau, found inside neurons, fails to function. Tau’s role is to provide a structure — like a train track —inside brain neurons that allows the cells to clear accumulation of unwanted and toxic proteins.

“When tau is abnormal, these proteins, which include Abeta, accumulate inside the neurons,” explains the study’s senior investigator, Charbel E-H Moussa, MB, PhD, assistant professor of neuroscience at Georgetown University Medical Center. “The cells start to spit the proteins out, as best they can, into the extracellular space so that they cannot exert their toxic effects inside the cell. Because Abeta is ‘sticky,’ it clumps together into plaque,” Moussa says.

He says his study suggests the remaining Abeta inside the neuron (that isn’t pushed out) destroys the cells, not the plaques that build up outside. “When tau does not function, the cell cannot remove the garbage, which at that point includes Abeta as well as tangles of nonfunctioning tau, and the cell dies. The Abeta released from the dead neuron then sticks to the plaque that had been forming.”

Moussa’s experiments in animal models also show less plaques accumulate outside the cell when tau is functioning; when tau was reintroduced into neurons that did not have it, plaques did not grow.

Malfunctioning tau can occur due to errant genes or through aging. As individuals grow older, some tau can malfunction while enough normal tau remains to help clear the garbage. In these cases, the neurons don’t die, he says. “That explains the confusing clinical observations of older people who have plaque build-up, but no dementia,” Moussa says.

Moussa has long sought a way to force neurons to clean up their garbage. In this study, he shows that nilotinib, a drug approved to treat cancer, can aid in that process. Nilotinib helps the neuron clear garbage, but requires some functional tau, he says.

“This drug can work if there is a higher percentage of good to bad tau in the cell,” Moussa says. “There are many diseases of dementia that have malfunctioning tau and no plaque accumulation, such as frontal temporal dementia linked to Parkinsonism,” Moussa says. “The common culprit is tau, so a drug that helps tau do its job may help protect against progression of these diseases.”

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Co-authors include researchers from Capital Medical University in Beijing, China, and Merck Research Laboratories.

Funding for these studies was provided by Georgetown University grants and by Merck & Co.

Moussa is an inventor on a Georgetown University patent application for use of nilotinib as a therapeutic approach in neurodegenerative diseases. Source

Posted in Alzheimer's, Dementia | Leave a comment

Resveratrol could REVERSE benefits of being active

Contrary to popular belief, use of the supplement resveratrol (RSV) may not actually enhance the effects of high-intensity interval training (HIIT).

Many news outlets and health blogs have long recommended RSV as a complement to exercise and to enhance performance. However, results from a study by Queen’s researcher Brendon Gurd suggest that RSV may actually impede the body’s response to training.

“The easiest way to experience the benefits of physical activity is to be physically active,” says Dr. Gurd, a professor in the School of Kinesiology and Health Studies. “The efficacy of RSV at improving metabolic and cardiovascular functions is not as profound as was once thought.”

Resveratrol occurs naturally in the skin of red grapes and has long been associated with the health benefits connected to a Mediterranean-style diet. Recently, it’s become possible to purchase RSV supplements, which are often marketed as “exercise mimics.”

Sixteen participants who engaged in less than three hours of aerobic exercise per week at the time of enrolment were asked to perform HIIT three times per week for four weeks. During this time, participants were administered daily doses of either RSV or a placebo.

Results after the four-week study showed that RSV supplementation may actually oppose the effects of exercise alone. In fact, the placebo group showed an increase in some of the benefits associated with physical activity as opposed to the group taking RSV whose physical fitness didn’t improve.

“The results we saw suggest that concurrent exercise training and RSV supplementation may alter the body’s normal training response induced by low-volume HIIT,” says Dr. Gurd. “The data set we recorded during this study clearly demonstrates that RSV supplementation doesn’t augment training, but may impair the affect it has on the body.”

Results observed by the team question the ability of RSV to act as an exercise-enhancing supplement and highlight the need for further research. This research was published in Applied Physiology, Nutrition and Metabolism. More

Posted in Exercise: Benefits, Nutrition: Information: Confusion, Nutrition: Resveratrol, Nutrition: Wine | Leave a comment

9 Horrible Things You Need to Stop Doing Right Now

The article below was originally published at Inc.com.

Perhaps you’ve heard of a “not-to-do list.” CEOs and productivity experts recommend the idea highly as a huge productivity booster that will help you free up time and headspace for all the things that really matter.

Sounds great. But what should go on it? Best-selling author Tim Ferriss has some ideas. In a recent short podcast he offered nine suggestions of bad work habits that many entrepreneurs and others desperately need to eliminate (chances are you are doing at least a couple of these–I’m personally massively guilty of two and five), so there is almost certainly something here that can boost your output.

Don’t overwhelm yourself, Ferriss says. Just tackle one or two at a time, eliminating counterproductive habits step by step, and eventually you’ll reclaim impressive amounts of time and energy.

Do Not Answer Calls from Unrecognized Numbers

Ferriss gives a couple of rationales for this one. First, the interruption will throw your concentration, costing you far more in time and brain power than just the conversation itself, and second, if it’s important, you’ll find yourself in a poor negotiating position, scrambling to formulate your thoughts when the caller is already well prepared. Instead, use Google Voice to check your messages or a service like PhoneTag to have them sent to you as email. More

 

Posted in Heart Health: Cardiac Rehab | Leave a comment

Vitamin D Deficiency Across the Board in Neuromuscular Disease

Newswise — A study presented at the annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) adds more credence to a growing awareness of the high prevalence of vitamin D deficiency in neuromuscular disease.

“Previous work has shown vitamin D deficiency to be quite common in other neurological disorders such as multiple sclerosis, myasthenia gravis, and Parkinson’s disease. This study suggests this concern may be more prevalent in other neuromuscular conditions as well,” said Ileana Howard, MD, AANEM News Science Editorial Board member.

Vitamin D supplementation has been suggested to improve function in frail elderly patients at risk for falls, as well as individuals with myasthenia gravis and Parkinson’s. The impact of vitamin D deficiency and supplementation on function in other neurologic conditions has yet to be explored.

“While the connection between vitamin D deficiency and neurologic disease is likely complex and not yet fully understood, this study may prompt physicians to consider checking vitamin D levels in their patients with neurologic conditions and supplementing when necessary,” said Dr. Howard.

The study, entitled Surprising Prevalence of Significant Vitamin D Deficiency in Neuro-muscular Disease Clinic in Central Pennsylvania, was conducted by Sankar Bandyopadhyay, MD, and Sol Dejesus, MD, from Hershey, PA.

Posted in Nutrition: Vitamin D, Science Updates | Leave a comment

Elderly may fall because they cannot see where they are going

(Reuters Health) – Older people with strabismus, where one eye points slightly inward or outward affecting vision, are about 27 percent more likely than people without the condition to be injured by a fall, according to a new study.

The disorder, often called “wandering eye,” becomes more common with age and can cause double vision or depth perception problems because the two eyes are not pointing in the same direction.

Previous studies have shown that having other eye disorders like cataracts, glaucoma or age-related macular degeneration increases the risk of injuries, fractures or falls, the study team writes in JAMA Opthalmology. But this is the first to examine whether so-called binocular vision problems have the same effect.

“Strabismus in adults is becoming more prevalent as the aging population increases and we do not know the impact of strabismus on patient quality of life and morbidity,” lead author Dr. Stacy Pineles told Reuters Health in an email.

“We hypothesized that strabismus could cause double vision or diminished depth perception, and we wanted to see whether this was associated with injuries such as falls, fractures, and musculoskeletal injuries,” said Pineles, an ophthalmologist with the Jules Stein Eye Institute at the University of California, Los Angeles. More

 

 

Posted in Elder Care: Falls, Eye Disease: Strabismus | Leave a comment

Sandwiches may be a source of too much dietary salt

(Reuters Health) – Americans consume too much sodium, according to current guidelines, and much of the excess may be hidden in our sandwiches, researchers say.

Based on national survey data depicting American eating habits over the course of a single day, the study found that half of all adults had a sandwich. And those who did took in more calories and sodium overall than those who didn’t.

The study team calculates that sandwiches, on average, contribute about a fifth of the entire day’s sodium intake for people who eat them.

“Excessive sodium intake is a health risk because of the relationship between sodium and blood pressure,” said the study’s lead author, Rhonda Sebastian, a nutritionist in the Food Surveys Research Group of the U.S. Department of Agriculture (USDA).

High sodium intake has been linked to worsening high blood pressure, a condition that can, in turn, increase the risk of heart disease, congestive heart failure and kidney disease, according to the USDA’s 2010 Dietary Guidelines for Americans.

The USDA recommends that everyone, including children, should limit their sodium intake to no more than 2,300 milligrams per day, or about one teaspoon of salt. More

 

Posted in Nutrition is Medicine, Nutrition: Salt | Leave a comment

CDC issues ‘Essentials’ to ‘interact positively with children’

Essentials for Parenting Toddlers and Preschoolers helps parents interact positively with children. It provides proven answers to common challenges so moms, dads, and caregivers can help two- to four-year-olds grow up happy and healthy.

  • Communicating with Children: Learn skills like praise and active listening
  • Creating Structure: Set expectations using family rules, reward charts, and daily schedules
  • Giving Directions: Encourage listening by giving simple directions
  • Using Discipline & Consequences: Get behaviors you want to happen more
  • Using Time-Out: Know when, where, and how to implement time-out

Read free articles, watch videos, and practice exercises for building positive relationships with kids. These techniques can reduce stress while developing a bond that’s safe, stable, and nurturing.

“All parents want the best for their children. CDC’s Essentials for Parenting Toddlers and Preschoolers provides answers to common challenges so parents can be more confident and enjoy helping kids grow up.”

Ileana Arias, PhD – Principal Deputy Director of the Centers for Disease Control and Prevention

Posted in Health Care: Costs, Parenting | Leave a comment

Controlling parents may affect later relationships

(Reuters Health) – – Teens whose parents use guilt or withholding have trouble working out disagreements well into adulthood, according to a new study.

“To maintain healthy relationships, it is important to be able to assert one’s own beliefs during a disagreement while also continuing to be warm toward the person,” said lead author Barbara Oudekerk, a psychologist at the University of Virginia in Charlottesville.

Previous studies have found that teens who struggle with confidently expressing their opinions during a disagreement are at risk for using hostile methods in their own relationships and experiencing depression and loneliness in close relationships in adulthood.

Experiences with parents do seem to “cascade” into future friendships, the authors found.

For the study, 184 teens were interviewed at age 13 and again at age 18, answering questions about how often their mother or father exerted psychological control, such as using guilt, withdrawing love, fostering anxiety or employing other manipulative techniques.

Some parents used psychological control by saying, for example, “If you really cared for me, you wouldn’t do things to worry me,” or by becoming distant when their teens didn’t see eye to eye with them.

Researchers also assessed the teens’ ability to reason, to “be their own people” and to express confidence, as well as their ability to show warmth and connection at ages 13, 18 and 21… . More

 

Posted in Human Behavior: Relationships, Parenting, Science Updates | Leave a comment

High milk intake linked with HIGHER fracture and mortality risk: British Medical Journal

A high milk intake in women and men is not accompanied by a lower risk of fracture and instead may be associated with a higher rate of death, suggests observational research published in The BMJ this week.

This may be explained by the high levels of lactose and galactose (types of sugar) in milk, that have been shown to increase oxidative stress and chronic inflammation in animal studies, say the researchers.

However, they point out that their study can only show an association and cannot prove cause and effect. They say the results “should be interpreted cautiously” and further studies are needed before any firm conclusions or dietary recommendations can be made.

A diet rich in milk products is promoted to reduce the likelihood of osteoporotic fractures, but previous research looking at the importance of milk for the prevention of fractures and the influence on mortality rates show conflicting results.

So a research team in Sweden, led by Professor Karl Michaëlsson, set out to examine whether high milk intake may increase oxidative stress, which, in turn, affects the risk of mortality and fracture.

Two large groups of 61,433 women (aged 39-74 years in 1987-1990) and 45,339 men (aged 45-79 years in 1997) in Sweden completed food frequency questionnaires for 96 common foods including milk, yoghurt and cheese.

Lifestyle information, weight and height were collated and factors such as education level and marital status were also taken into account. National registers were used to track fracture and mortality rates.

Women were tracked for an average of 20 years, during which time 15,541 died and 17,252 had a fracture, of whom 4,259 had a hip fracture.

In women, no reduction in fracture risk with higher milk consumption was observed. Furthermore, women who drank more than three glasses of milk a day (average 680 ml) had a higher risk of death than women who drank less than one glass of milk a day (average 60 ml).

Men were tracked for an average of 11 years, during which time 10,112 died and 5,066 had a fracture, with 1,166 hip fracture cases. Men also had a higher risk of death with higher milk consumption, although this was less pronounced than in women.

Further analysis showed a positive association between milk intake and biomarkers of oxidative stress and inflammation.

In contrast, a high intake of fermented milk products with a low lactose content (including yoghurt and cheese) was associated with reduced rates of mortality and fracture, particularly in women.

They conclude that a higher consumption of milk in women and men is not accompanied by a lower risk of fracture and instead may be associated with a higher rate of death. Consequently, there may be a link between the lactose and galactose content of milk and risk, although causality needs be tested.

“Our results may question the validity of recommendations to consume high amounts of milk to prevent fragility fractures,” they write. “The results should, however, be interpreted cautiously given the observational design of our study. The findings merit independent replication before they can be used for dietary recommendations.”

Michaëlsson and colleagues raise a fascinating possibility about the potential harms of milk, says Professor Mary Schooling at City University of New York in an accompanying editorial. However, she stresses that diet is difficult to assess precisely and she reinforces the message that these findings should be interpreted cautiously.

“As milk consumption may rise globally with economic development and increasing consumption of animal source foods, the role of milk and mortality needs to be established definitively now,” she concludes.  Source

Posted in Health Care: Medical Errors, Nutrition: Food: Milk, Osteoporosis | 3 Comments

Tumor growth finding may be huge breakthrough

Newswise — New research at The University of Texas MD Anderson Cancer Center has unearthed a previously unknown phenomenon: Key regulatory molecules are decreased when deprived of oxygen which leads to increased cancer progression in vitro and in vivo.

As tumors grow, they can outgrow their blood supply, leaving some of the tumor with areas where the tissue is oxygen starved, a condition known as tumor hypoxia. Conventional wisdom would suggest the lack of oxygen would slow growth. However, new information about hypoxia has been come to light in the MD Anderson study which looked at how certain enzymes were impacted. Surprisingly, hypoxia led to tumor progression. In short, cancer cells are wily and able to adapt in order to maintain continued growth.

“We showed that that hypoxia causes a downregulation of, or decrease in, quantities of Drosha and Dicer, enzymes that are necessary for producing microRNAs (miRNAs). MiRNAs are molecules naturally expressed by the cell that regulate a variety of genes,” said Anil Sood, M.D., professor of gynecologic oncology and reproductive medicine and cancer biology. “At a functional level, this process results in increased cancer progression when studied at the cellular level.”

Sood’s findings are published in this month’s issue of Nature Communications. Sood also was part of a study led by the Ontario Cancer Institute in Toronto, which reported in the same issue on hypoxia and regulation of DICER in breast cancer.

The investigation discovered that hypoxia-altered miRNA’s ability to mature in cells. Given that approximately one-third of the body’s genes are regulated by miRNA, Sood said that it was not surprising that cancer cells have altered miRNA levels and that miRNAs are extensively involved in cancer progression.

“Although global miRNA downregulation in cancer has been reported, the mechanism behind it has not been fully understood,” he said. “We already knew that downregulation of the enzymes Drosha and Dicer in ovarian, lung and breast cancer is associated with poor patient outcomes. In this study, we identified new methods for downregulation of miRNA.”

This chain of events stalled development of miRNA in its tracks, due to hypoxia leading to reduced levels of Drosha and Dicer. Rajesha Rupaimoole, a graduate student in the cancer biology program and first author of the study demonstrated that the disruption of molecular machinery depends on the transcription factors, ETS1 and ELK1 in order to successfully decrease one of the enzymes, Drosha, which consequently spur continued tumor growth. Transcription factors are proteins that turn genetic instructions on and off.

Sood’s team, however, demonstrated that ETS1 and ELK1 could be “silenced” when deprived of oxygen in vivo when they were targeted by specific RNA molecules known as small interfering RNA (siRNA).

“The rescue of Drosha by siRNAs targeting ETS1 and ELK1 led to significant tumor regression,” said Rupaimoole.

With a better understanding of how hypoxia regulates critical enzymes, Sood believes that there is potential for a new approach to halting tumor progression.

“Use of Drosha- and Dicer-independent siRNA-based gene targeting is an emerging strategy to develop therapies that target undruggable genes,” said Rupaimoole. “A comprehensive understanding of Drosha and Dicer downregulation under hypoxic conditions is an important leap towards comprehending how miRNA can go awry during cancer progression.”

MD Anderson participants in the study included Rajesha Rupaimoole, Sherry Wu, Ph.D., Sunila Pradeep, Ph.D., Cristina Ivan, Kshipra Gharpure, Archana Nagaraja, Guillermo Armaiz-Pena, Ph.D., Michael McGuire, Ph.D., Behrouz Zand, M.D., Heather Dalton, M.D., Justyna Filant, Ph.D., Justin Bottsford-Miller, M.D., Chunhua Lu, M.D., Ph.D., Nouara Sadaoui, Lingegowda Mangala, Ph.D., and Morgan Taylor, Ph.D., all of the department of gynecologic oncology and reproductive medicine; Cristian Rodriguez-Aguayo, Ph.D. , Gabriel Lopez-Berestein, M.D., and George Calin, M.D., Ph.D., all of the department of experimental therapeutics; Menashe Bar-Eli, Ph.D. and Li Huang, department of cancer biology; and Wei Zhang, Ph.D., department of pathology. Other participating institutions included the University of North Carolina, Chapel Hill, N.C., University Health Network, Toronto, and Indiana University, Indianapolis.

The study was funded by the National Institutes of Health (CA016672, CA109298, UH2TR000943-04, P50 CA083639, P50 CA098259, U54 CA151668, U24 CA143835, and CA155332), the National Cancer Institute (CA009666, T32 CA101642), the Cancer Prevention and Research Institute of Texas (RP110595, RP10152, and RP101489), the Ovarian Research Fund, Inc., and the Department of Defense (OC073399), the Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer, The RGK Foundation, The Gilder Foundation, The Judi A. Rees Ovarian Cancer Research Fund, Mr. and Mrs. Daniel P., Gordon, the H.A. and Mary K. Chapman Charitable Foundation, The Blanton-Davis Ovarian Cancer Research Program, the Russell and the Diana Hawkins Family Foundation , and the Foundation for Women’s Cancer.

Posted in Cancer: Breast, Cancer: Lung, Cancer: Ovarian, Health Care: Medical Errors, microRNA | Leave a comment

Not sleeping: the price we all pay

COLUMBUS, Ohio – Most Americans who spend part of the year on daylight saving time look forward to the extra hour of sleep when it’s time to “fall back” to standard time. We are a nation of sleep-deprived people, and experts at The Ohio State University Wexner Medical Center say all ages suffer in various, unhealthy ways.

“For children, sleep deprivation can lead to behavior problems, trouble focusing and learning in school and it can affect their immune systems,” said Dr. Aneesa Das, a sleep medicine specialist at Ohio State’s Wexner Medical Center. “Chronic tiredness makes it harder to cope and process what’s going on around you.”

When children enter the teen years, sleep becomes a bigger issue. Das says a teen’s circadian rhythm, or internal body clock, tells them to stay awake later and sleep later than children and adults do. She says only 15 percent of teenagers get the recommended sleep they need.

“Sleep is time the body uses to restore itself. Muscles and other tissues repair themselves, hormones that control growth, development and appetite are released. Energy is restored and memories are solidified, so we need to try to get regular sleep on a regular basis,” Das said.

For adults, sleep loss is even more serious. It accumulates over the years and has been shown to contribute to several chronic diseases including heart disease, diabetes, high blood pressure, depression and obesity. Adulthood is also when sleep-related disorders, such as insomnia or sleep apnea, are more likely. During menopause, women often experience night sweats and insomnia due to changing levels of hormones. As men age, an enlarged prostate can lead to more frequent trips to the bathroom overnight. Certain medications can also disrupt sleep, such as those for heart arrhythmia, high blood pressure and asthma.

“Adult sleep gets more fragmented, or interrupted during the night,” Das said. “This could be caused by a medical condition, caring for young children, light and noise disturbance, pets or just the stress of the day.”

Here are the recommended hours of sleep we should get throughout our lifetime, according to the National Sleep Foundation:

– Infants: up to 16 hours total, including naps
– Toddlers (1-3 yrs): 12-14 hours, including naps
– Preschool (3-5 yrs): 11-13 hours, most do not nap after age 5
– School-age (5-12 yrs): 10-11 hours
– Teens: 8.5-9.5 hours
– Adults: 7-9 hours

To improve the chances of getting a good night’s sleep, Das offers a few tips: don’t perform vigorous exercise within four hours of bedtime; have a wind down routine that includes dim light; avoid using tablets, phones and laptops before bed because they emit blue light that interferes with sleep; try a warm bath two hours before bedtime and beware of sleep aid medications because they can have side effects.

Posted in Pediatric Health: Sleep, Sleep | Leave a comment

Teen drinking lower when there are social host laws

(Reuters Health) – When laws hold adults responsible when kids drink on their property, kids are less likely to spend their weekends drinking at parties, according to a new study.

States or local governments can enact ‘social host’ laws, which penalize adults hosting underage drinking parties with fines or imprisonment, potentially even if the adults do not furnish the alcohol.

Past research on the effectiveness of such laws has been limited, the authors of the new study write.

Social host laws may not be well enforced in many communities, and it is also likely that many parents and adults are not aware of the laws, which makes the new results somewhat surprising, said lead author Mallie J. Paschall of the Prevention Research Center in Oakland, California.

California has no statewide social host laws, but at least 75 cities and a number of counties have enacted them, he told Reuters Health by email.

For the new study, Paschall and his coauthors examined drinking patterns in 50 California cities with populations between 50,000 and 500,000 people, using city ordinances to rate the presence and strictness of social host laws. More

 

 

Posted in Alcohol, Parenting, Pediatric Health: Teenagers | Leave a comment

Diabetes is fueling TB globally

(Reuters) – Cases of tuberculosis are set accelerate worldwide unless action is taken to curb diabetes, a chronic condition that weakens the immune system and triples the risk a person will develop the lung disease, health experts warned on Wednesday.

Tuberculosis (TB), which killed an estimated 1.5 million people last year according to the World Health Organization (WHO), is caused by bacteria that lie dormant in many people.

However, diabetics TB become sick from latent TB infection far more often than other people because their immune systems are compromised — a fact that could unleash an epidemic of co-infection as diabetes rates soar along with growing obesity.

It is not the first time that the world has been confronted with such co-infection. The HIV/AIDS pandemic, which destroyed the immune systems of millions, lead to a quadrupling of TB rates in many countries in Africa.

Now doctors fear a re-run of that scenario as diabetes takes hold around the world, including in many poorer countries.

The big worry is that six of the top 10 countries projected to have the greatest numbers of diabetics by 2035 — China, India, Brazil, Indonesia, Pakistan, and Russia — are classified as high TB burden countries by the WHO.  More

Posted in Diabetes, Infectious Diseases: Tuberculosis, World Health: Africa, World Health: Obesity, World Health: Pakistan, World Health: Tuberculosis | Leave a comment