Alzheimer's-like symptoms reversed in mice

Green tea.

A diet containing compounds found in green tea and carrots reversed Alzheimer's-like symptoms in mice genetically programmed to develop the disease, USC researchers say.

Researchers emphasize that the study, recently published in the Journal of Biological Chemistry, was in mice, and many mouse discoveries never translate into human treatments. Nevertheless, the findings lend credence to the idea that certain readily available, plant-based supplements might offer protection against dementia in humans.

"You don't have to wait 10 to 12 years for a designer drug to make it to market; you can make these dietary changes today," said senior author Terrence Town, a professor of physiology and neuroscience at the Keck School of Medicine of USC's Zilkha Neurogenetic Institute. "I find that very encouraging."

What's more, the study supports the idea that combination therapy, rather than a single magic bullet, may offer the best approach to treating the 5.7 million Americans living with Alzheimer's. Combination treatment is already the standard of care for diseases such as cancer, HIV infection and rheumatoid arthritis.

For this study, the researchers took a look at two compounds: EGCG, or epigallocatechin-3-gallate, a key ingredient in green tea, and FA, or ferulic acid, which is found in carrots, tomatoes, rice, wheat and oats.

The researchers randomly assigned 32 mice with Alzheimer's-like symptoms to one of four groups with an equal number of males and females. For comparison, each group also contained an equal number of healthy mice. For three months, the mice consumed a combination of EGCG and FA, or EGCG or FA only, or a placebo. The dosage was 30 mg per kilogram of body weight -- a dosage well-tolerated by humans and easily consumed as part of a healthy, plant-based diet or in the form supplements.

Before and after the three-month special diet, scientists ran the mice through a battery of neuropsychological tests that are roughly analogous to the thinking and memory tests that assess dementia in humans. Of particular note was a maze in the shape of a Y, which tests a mouse's spatial working memory -- a skill that humans use to find their way out of a building.

Healthy mice instinctively explore each arm of the Y maze, looking for food or a route to escape and entering the three arms in sequence more often than by chance alone. Impaired mice can't do this as well as their mentally healthy counterparts.

"After three months, combination treatment completely restored working memory and the Alzheimer's mice performed just as well as the healthy comparison mice," Town said.

How did it work? Town says one mechanism appeared to be the substances' ability to prevent amyloid precursor proteins from breaking up into the smaller proteins called amyloid beta that gum up Alzheimer patients' brains. In addition, the compounds appeared to reduce neuroinflammation and oxidative stress in the brain -- key aspects of Alzheimer's pathology in humans.

Town said he and his lab will continue exploring combination treatment, with a focus on plant-derived substances that inhibit production of the sticky amyloid beta plaques.

A nap a day keeps high blood pressure at bay

New research shows that people who took advantage of a midday snooze were more likely to have a noticeable drop in blood pressure compared with those who didn't nap.

t seems that napping may do more than just reboot our energy level and improve our mood. New research being presented at the American College of Cardiology's 68th Annual Scientific Session found that people who took advantage of a midday snooze were more likely to have a noticeable drop in blood pressure compared with those who didn't nap.

"Midday sleep appears to lower blood pressure levels at the same magnitude as other lifestyle changes. For example, salt and alcohol reduction can bring blood pressure levels down by 3 to 5 mm Hg," said Manolis Kallistratos, MD, cardiologist at the Asklepieion General Hospital in Voula, Greece, and one of the study's co-authors, adding that a low-dose antihypertensive medication usually lowers blood pressure levels by 5 to 7 mm Hg, on average.

Overall, taking a nap during the day was associated with an average 5 mm Hg drop in blood pressure, which researchers said is on par with what would be expected from other known blood pressure-lowering interventions. In addition, for every 60 minutes of midday sleep, 24-hour average systolic blood pressure decreased by 3 mm Hg.

"These findings are important because a drop in blood pressure as small as 2 mm Hg can reduce the risk of cardiovascular events such as heart attack by up to 10 percent," Kallistratos said. "Based on our findings, if someone has the luxury to take a nap during the day, it may also have benefits for high blood pressure. Napping can be easily adopted and typically doesn't cost anything."

This is the first study to prospectively assess midday sleep's affect on blood pressure levels among people whose blood pressure is reasonably controlled, according to the researchers. The same research team previously found midday naps to be associated with reduced blood pressure levels and fewer antihypertensive medications being prescribed among people with very high blood pressure readings.

"The higher the blood pressure levels, the more pronounced any effort to lower it will appear. By including people with relatively well-controlled blood pressure, we can feel more confident that any significant differences in blood pressure readings are likely due to napping," Kallistratos said.

The study included 212 people with a mean blood pressure of 129.9 mm Hg. They were 62 years old on average and just over half were female. About 1 out of 4 participants were smokers and/or had Type 2 diabetes. The groups were similar in terms of risk factors for heart disease except there were more smokers in the napping group. Researchers assessed and recorded blood pressure for 24 hours consecutively, midday sleep time (the average duration was 49 minutes), lifestyle habits (for example, alcohol, coffee and salt consumption, physical activity levels), and pulse wave velocity, a measure of stiffness in the arteries. Participants wore an ambulatory blood pressure monitor to measure and track blood pressure at regular intervals during routine daily living, rather than just one time in the clinic. At study recruitment, participants also underwent an echocardiogram, an ultrasound of the heart that shows its structure and function.

In their analyses, researchers adjusted for factors known to influence blood pressure levels, including age, gender, lifestyle and medications. There were no differences in terms of the number of antihypertensive medications taken between the two groups, and pulse wave velocity tests and echocardiograms were also similar.

Overall, average 24-hour systolic blood pressure was 5.3 mm Hg lower among those who napped compared with those who didn't (127.6 mm Hg vs 132.9 mm Hg). When looking at both blood pressure numbers, people who slept during the day had more favorable readings (128.7/76.2 vs 134.5/79.5 mm Hg). There also appeared to be a direct linear relationship between time asleep and blood pressure; as reported, for each hour of napping, the average 24-hour systolic blood pressure lowered by 3 mm Hg.

"We obviously don't want to encourage people to sleep for hours on end during the day, but on the other hand, they shouldn't feel guilty if they can take a short nap, given the potential health benefits," Kallistratos said. "Even though both groups were receiving the same number of medications and blood pressure was well controlled, there was still a significant decrease in blood pressure among those who slept during midday."

Researchers said the findings are further bolstered because patients had similar dipping blood pressure rates at night (natural drops during nighttime sleep), meaning that any reductions in ambulatory blood pressure were separate from this phenomenon and give greater confidence that reductions in ambulatory blood pressure could be due to daytime napping.

Further research is needed to validate these findings. Although it falls outside the scope of this study, researchers said one could speculate that along with the heart-healthy Mediterranean diet endemic to this region, the cultural acceptance of midday napping may also play a role in the healthier profile seen in these populations.

Nearly half of American adults have high blood pressure. Many don't know they have it because there are often no signs or symptoms; over time, high blood pressure increases the risk of both heart attack and stroke.

Kallistratos will present the study, "Mid-day Sleep Effects as Potent as Recommended Lifestyle Changes in Patients With Arterial Hypertension," on Monday, March 18.

Wide variations in how well or poorly people age

Researchers found 76-year-olds in Japan and 46-year-olds in Papua New Guinea have the same level of age-related health problems as an "average" person aged 65.

At what age do you feel 65?

A 30-year gap separates countries with the highest and lowest ages at which people experience the health problems of a 65-year-old, according to a new scientific study.

Researchers found 76-year-olds in Japan and 46-year-olds in Papua New Guinea have the same level of age-related health problems as an "average" person aged 65.

"These disparate findings show that increased life expectancy at older ages can either be an opportunity or a threat to the overall welfare of populations, depending on the aging-related health problems the population experiences regardless of chronological age." said Dr. Angela Y. Chang, lead author and postdoctoral fellow at the Center for Health Trends and Forecasts at the University of Washington. "Age-related health problems can lead to early retirement, a smaller workforce, and higher health spending. Government leaders and other stakeholders influencing health systems need to consider when people begin suffering the negative effects of aging."

These negative effects include impaired functions and loss of physical, mental, and cognitive abilities resulting from the 92 conditions analyzed, five of which are communicable and 81 non-communicable, along with six injuries.

The studies and additional information are available at http://www.healthdata.org

The study, published yesterday in the international medical journal The Lancet Public Health, is the first of its kind, according to Chang, whose center is housed at the UW's Institute for Health Metrics and Evaluation. Where traditional metrics of aging examine increased longevity, this study explores both chronological age and the pace at which aging contributes to health deterioration. The study uses estimates from the Global Burden of Disease study (GBD).

Researchers measured "age-related disease burden" by aggregating all disability-adjusted life years (DALYs), a measurement of loss of healthy life, related to the 92 diseases. The findings cover 1990 to 2017 in 195 countries and territories. For example, in 2017, people in Papua New Guinea had the world's highest rate of age-related health problems with more than 500 DALYs per 1,000 adults, four times that of people in Switzerland with just over 100 DALYs per 1,000 adults.

The rate in the United States was 161.5 DALYs per 1,000, giving it a ranking of 53rd, between Algeria at 52nd with 161.0 DALYs per 1,000 and Iran at 54th with 164.8 DALYs per 1,000.

Using global average 65-year-olds as a reference group, Chang and other researchers also estimated the ages at which the population in each country experienced the same related burden rate. They found wide variation in how well or poorly people age. Ranked first, Japanese 76-year-olds experience the same aging burden as 46-year-olds in Papua New Guinea, which ranked last across 195 countries and territories. At 68.5 years, the United States ranked 54th, between Iran (69.0 years) and Antigua and Barbuda (68.4 years).

The study is entitled "Measuring population ageing: an analysis of the Global Burden of Disease Study 2017."

Additional findings include:

• Age-related disease burden rates decreased over time across all regions between 1990 and 2017, representing reductions in deaths and disease severity of age-related problems.
• In 2017, people in 108 countries experienced earlier accumulation of problems associated with aging, whereas those in 87 countries experienced slower onset of aging.
• Globally, the age-related diseases with the most deaths and DALYs were ischemic heart disease, brain hemorrhage, and chronic obstructive pulmonary disease (COPD).

Countries with highest equivalent age to global 65-year-olds in 2017:

1. Japan: 76.1 years
2. Switzerland: 76.1
3. France: 76.0
4. Singapore: 76.0
5. Kuwait: 75.3
6. South Korea: 75.1
7. Spain: 75.1
8. Italy: 74.8
9. Puerto Rico: 74.6
10. Peru: 74.3

Countries with lowest equivalent age to global 65-year-olds in 2017:

1. Papua New Guinea: 45.6 years
2. Marshall Islands: 51.0
3. Afghanistan: 51.6
4. Vanuatu: 52.2
5. Solomon Islands: 53.4
6. Central African Republic: 53.6
7. Lesotho: 53.6
8. Kiribati: 54.2
9. Guinea-Bissau: 54.5
10. Federated States of Micronesia: 55.0

Countries with lowest age-related burden rate in 2017:

1. Switzerland: 104.9 DALYs per 1,000 adults aged 25 or older
2. Singapore: 108.3
3. South Korea: 110.1
4. Japan: 110.6
5. Italy: 115.2
6. Kuwait: 118.2
7. Spain: 119.2
8. France: 119.3
9. Israel: 120.2
10. Sweden: 122.1

Countries with highest age-related burden rate in 2017:

1. Papua New Guinea: 506.6 DALYs per 1,000 adults aged 25 or older
2. Marshall Islands: 396.6
3. Vanuatu: 392.1
4. Afghanistan: 380.2
5. Solomon Islands: 368.0
6. Central African Republic: 364.6
7. Lesotho: 360.5
8. Kiribati: 347.5
9. Guinea-Bissau: 343.4
10. Eritrea: 325.7

Capturing bacteria that eat and breathe electricity

Pools of hot water like this are the home to bacteria that can eat and breathe electricity.

Last August, Abdelrhman Mohamed found himself hiking deep into the wilderness of Yellowstone National Park.

Unlike thousands of tourists who trek to admire the park's iconic geysers and hot springs every year, the WSU graduate student was traveling with a team of scientists to hunt for life within them.

After a strenuous seven mile walk through scenic, isolated paths in the Heart Lake Geyser Basin area, the team found four pristine pools of hot water. They carefully left a few electrodes inserted into the edge of the water, hoping to coax little-known creatures out of hiding -- bacteria that can eat and breathe electricity.

After 32 days, the team returned to the hot springs to collect the submerged electrodes. Working under the supervision of Haluk Beyenal, Paul Hohenschuh Distinguished Professor in the Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Mohamed and postdoctoral researcher Phuc Ha analyzed the electrodes.

Voila! They had succeeded in capturing their prey -- heat-loving bacteria that "breathe" electricity through the solid carbon surface of the electrodes.

The WSU team, in collaboration with colleagues from Montana State University, published their research detailing the multiple bacterial communities they found in the Journal of Power Sources.

"This was the first time such bacteria were collected in situ in an extreme environment like an alkaline hot spring," said Mohamed, adding that temperatures in the springs ranged from about 110 to nearly 200 degrees Fahrenheit.

These tiny creatures are not merely of academic interest.

They may hold a key to solving some of the biggest challenges facing humanity -- environmental pollution and sustainable energy. Such bacteria can "eat" pollution by converting toxic pollutants into less harmful substances and generating electricity in the process.

"As these bacteria pass their electrons into metals or other solid surfaces, they can produce a stream of electricity that can be used for low-power applications," said Beyenal.

Most living organisms -- including humans -- use electrons, which are tiny negatively-charged particles, in a complex chain of chemical reactions to power their bodies. Every organism needs a source of electrons and a place to dump the electrons to live. While we humans get our electrons from sugars in the food we eat and pass them into the oxygen we breathe through our lungs, several types of bacteria dump their electrons to outside metals or minerals, using protruding hair-like wires.

To collect bacteria in such an extreme environment over 32 days, Mohamed invented a cheap portable potentiostat, an electronic device that could control the electrodes submerged in the hot springs for long periods of time.

"The natural conditions found in geothermal features such as hot springs are difficult to replicate in laboratory settings," said Beyenal. "So, we developed a new strategy to enrich heat-loving bacteria in their natural environment."

HIV remission achieved in second patient

Scanning electron microscopic (SEM) image revealing the presence of numerous human immunodeficiency virus-1 (HIV-1) virions budding from a cultured lymphocyte.

A second person has experienced sustained remission from HIV-1 after ceasing treatment, reports a paper led by researchers at UCL and Imperial College London.

The case report, published in Nature and carried out with partners at the University of Cambridge and the University of Oxford, comes ten years after the first such case, known as the 'Berlin Patient.'

Both patients were treated with stem cell transplants from donors carrying a genetic mutation that prevents expression of an HIV receptor CCR5.

The subject of the new study has been in remission for 18 months after his antiretroviral therapy (ARV) was discontinued. The authors say it is too early to say with certainty that he has been cured of HIV, and will continue to monitor his condition.

"At the moment the only way to treat HIV is with medications that suppress the virus, which people need to take for their entire lives, posing a particular challenge in developing countries," said the study's lead author, Professor Ravindra Gupta (UCL, UCLH and University of Cambridge).

"Finding a way to eliminate the virus entirely is an urgent global priority, but is particularly difficult because the virus integrates into the white blood cells of its host."

Close to 37 million people are living with HIV worldwide, but only 59% are receiving ARV, and drug-resistant HIV is a growing concern. Almost one million people die annually from HIV-related causes.

The report describes a male patient in the UK, who prefers to remain anonymous, and was diagnosed with HIV infection in 2003 and on antiretroviral therapy since 2012.

Later in 2012, he was diagnosed with advanced Hodgkin's Lymphoma. In addition to chemotherapy, he underwent a haematopoietic stem cell transplant from a donor with two copies of the CCR5Δ32 allele in 2016.

CCR5 is the most commonly used receptor by HIV-1. People who have two mutated copies of the CCR5 allele are resistant to the HIV-1 virus strain that uses this receptor, as the virus cannot enter host cells.

Chemotherapy can be effective against HIV as it kills cells that are dividing. Replacing immune cells with those that don't have the CCR5 receptor appears to be key in preventing HIV from rebounding after the treatment.

The transplant was relatively uncomplicated, but with some side effects including mild graft-versus-host disease, a complication of transplants wherein the donor immune cells attack the recipient's immune cells.

The patient remained on ARV for 16 months after the transplant, at which point the clinical team and the patient decided to interrupt ARV therapy to test if the patient was truly in HIV-1 remission.

Regular testing confirmed that the patient's viral load remained undetectable, and he has been in remission for 18 months since ceasing ARV therapy (35 months post-transplant). The patient's immune cells remain unable to express the CCR5 receptor.

He is only the second person documented to be in sustained remission without ARV. The first, the Berlin Patient, also received a stem cell transplant from a donor with two CCR5Δ32 alleles, but to treat leukaemia. Notable differences were that the Berlin Patient was given two transplants, and underwent total body irradiation, while the UK patient received just one transplant and less intensive chemotherapy.

Both patients experienced mild graft-versus-host disease, which may also have played a role in the loss of HIV-infected cells.

"By achieving remission in a second patient using a similar approach, we have shown that the Berlin Patient was not an anomaly, and that it really was the treatment approaches that eliminated HIV in these two people," said Professor Gupta.

The researchers caution that the approach is not appropriate as a standard HIV treatment due to the toxicity of chemotherapy, but it offers hope for new treatment strategies that might eliminate HIV altogether.

"Continuing our research, we need to understand if we could knock out this receptor in people with HIV, which may be possible with gene therapy," said Professor Gupta.

"The treatment we used was different from that used on the Berlin Patient, because it did not involve radiotherapy. Its effectiveness underlines the importance of developing new strategies based on preventing CCR5 expression," said co-author Dr Ian Gabriel (Imperial College Healthcare NHS Trust).

"While it is too early to say with certainty that our patient is now cured of HIV, and doctors will continue to monitor his condition, the apparent success of haematopoietic stem cell transplantation offers hope in the search for a long-awaited cure for HIV/AIDS," said Professor Eduardo Olavarria (Imperial College Healthcare NHS Trust and Imperial College London).

The research was funded by Wellcome, the Medical Research Council, the Foundation for AIDS Research, and National Institute for Health Research (NIHR) Biomedical Research Centres at University College London Hospitals, Oxford, Cambridge and Imperial.

The research team is presenting the findings today (March 5) at the annual Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.