Smog Might Cloud Your Memory

Serena Gordon wrote . . . . . . . . .

The very air you breathe may make you vulnerable to developing dementia, a new study suggests.

British researchers found that people exposed to higher levels of air pollution had 40 percent higher odds of developing dementia.

“We found that older patients across greater London who were living in areas with higher air pollution were more likely to be diagnosed with dementia in subsequent years,” said study author Iain Carey. He’s a senior lecturer in epidemiology at the University of London.

Carey said the increased risk persisted even after his team accounted for other factors that might increase dementia, such as smoking and diabetes.

However, the researchers aren’t suggesting that people need to abandon cities.

“Since this is an observational study, any findings need to be treated with caution. It only tells us there may be a possible link between air pollution and dementia, and more research is needed to confirm and understand this,” Carey said.

Dementia is a catch-all term for a number of brain disorders that cause trouble with memory and thinking. The most common form of dementia is Alzheimer’s disease, according to the U.S.-based Alzheimer’s Association.

The second most common form of dementia is called vascular dementia. This occurs when the brain is deprived of blood flow and oxygen due to other conditions, such as a stroke or a number of small strokes, the Alzheimer’s Association explained.

The study focused on people who were eventually diagnosed with these two forms of dementia.

The researchers began by reviewing the records of nearly 131,000 adults registered with 75 general physician practices in the London area. Carey said all of the locations were in urban areas.

At the start of the study, all of the participants were between the ages of 50 and 79. None had been diagnosed with dementia.

The researchers then estimated each person’s annual exposure to air pollution, such as nitrogen dioxide, particulate matter and ozone. They also estimated the participants’ proximity to heavy traffic.

After an average follow-up of seven years, almost 2,200 people — or nearly 2 percent of the total group — had been diagnosed with dementia.

Those living in the areas with the highest levels of nitrogen dioxide compared to those living with the lowest exposure had a 40 percent increased risk of developing dementia, the study found. The odds of an Alzheimer’s disease diagnosis was 50 percent higher for people living with the highest exposure to nitrogen dioxide.

Similar increases in risk were also seen for high levels of particulate matter. For other measures, such as ozone and distance to heavy traffic, the researchers said there was less evidence of any links.

Carey said it’s not clear why air pollution appears to be linked to dementia. He noted that other research has suggested that children’s brain development may be affected by pollution.

Heather Snyder, senior director of medical and scientific operations for the Alzheimer’s Association, said this study “raises a lot of interesting questions.” But she also said it’s too soon to speculate how pollution might play a role in dementia.

“Dementia is complex and there are lots of things that may contribute to dementia risk. I don’t think you can draw any conclusions from this study,” Snyder said.

Dr. Bruce Silverman, a neurologist at Ascension Providence Hospital in Southfield, Mich., also thought it was too early to make any recommendations based on this study. He also noted that dementia occurs in people living all over — in urban, suburban and rural areas.

But he said if you start looking at factors that might cause premature death of nerve cells in the brain, “living in an environment that is toxic to those cells from pollution is probably not healthy.”

Both Snyder and Silverman recommended that if people are concerned about dementia, there are steps they can take to help prevent the disorder, or to potentially help slow the progress of dementia if you already have it.

Steps that both experts recommended included getting regular exercise, eating a healthy diet low in saturated fat with plenty of vegetables and fruits, getting adequate sleep, and keeping your brain engaged with things like puzzles, new learning and social activities.

The study was published in the BMJ.

Source: HealthDay


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What Time Is It in Your Body?

Marla Paul wrote . . . . . . . . .

The first simple blood test to identify your body’s precise internal time clock as compared to the external time has been developed by Northwestern Medicine scientists.

The test, TimeSignature – which requires only two blood draws – can tell physicians and researchers the time in your body despite the time in the external world. For instance, even if it’s 8 a.m. in the external world, it might be 6 a.m. in your body.

“This is a much more precise and sophisticated measurement than identifying whether you are a morning lark or an night owl,” said lead author Rosemary Braun, assistant professor of preventive medicine (biostatistics) at Northwestern University Feinberg School of Medicine. “We can assess a person’s biological clock to within 1.5 hours.

“Various groups have tried to get at internal circadian time from a blood test, but nothing has been as accurate or as easy to use as TimeSignature,” Braun said.

Previously, measurements this precise could only be achieved through a costly and laborious process of taking samples every hour over a span of multiple hours.

The paper was published in the journal PNAS.

Processes in nearly every tissue and organ system in the body are orchestrated by an internal biological clock, which directs circadian rhythm, such as the sleep-wake cycle. Some individuals’ internal clocks are in sync with external time but and others are out of sync and considered misaligned.

The new test for the first time will offer researchers the opportunity to easily examine the impact of misaligned circadian clocks in a range of diseases from heart disease to diabetes and Alzheimer’s disease. When the blood test eventually becomes clinically available, it also will provide doctors with a measurement of an individual’s internal biological clock to guide medication dosing at the most effective time for his or her body.

The software and algorithm are available for free to other researchers so they can assess physiological time in a person’s body. Northwestern has filed for a patent on the blood test.

“This is really an integral part of personalized medicine,” said coauthor Dr. Phyllis Zee, chief of sleep medicine in neurology at Feinberg and a Northwestern Medicine neurologist. “So many drugs have optimal times for dosing. Knowing what time it is in your body is critical to getting the most effective benefits. The best time for you to take the blood pressure drug or the chemotherapy or radiation may be different from somebody else.”

Zee also is the Benjamin and Virginia T. Boshes Professor of Neurology.

The test measures 40 different gene expression markers in the blood and can be taken any time of day, regardless of whether the patient had a good night’s sleep or was up all night with a baby. It is based on an algorithm developed by Braun and colleagues by drawing subjects’ blood every two hours and examining which genes were higher or lower at certain times of day. Scientists also used gene expression data from studies conducted at four other centers.

The scientists then developed a novel machine-learning method that was used to train a computer to predict the time of day based on patterns in these gene expression measurements. Out of about 20,000 genes measured, these 40 emerged with the strongest signal.

“Timing is everything,” said study coauthor Ravi Allada, a professor of neurobiology at Northwestern’s Weinberg College of Arts and Sciences. “We know if you have disruption of your internal clock, it can predispose you to a range of diseases. Virtually every tissue and organ system are governed by circadian rhythm.

“Before we didn’t have a clinically feasible way of assessing the clock in healthy people and people with disease. Now we can see if a disrupted clock correlates with various diseases and, more importantly, if it can predict who is going to get sick.?”

A link between circadian misalignment and diabetes, obesity, depression, heart disease and asthma has been identified in preclinical research by scientist Joe Bass, chief of endocrinology, metabolism and molecular medicine at Feinberg.

Down the road, Zee envisions improving health and treating disease by aligning people’s circadian clocks that are out of sync with external time.

“Circadian timing is a modifiable risk factor for improving cognitive health, but if we can’t measure it, it’s difficult to know if we’ve made the right diagnosis,” Zee said. “Now we can measure it just like a lipid level.”

The paper is titled “A Universal Method for Robust Detection of Circadian State from Gene Expression.” Other Northwestern coauthors include William L. Kath of the McCormick School of Engineering and Sabra M. Abbott and Kathryn J. Reid of Feinberg.

Source : Northweatern University

Scientists Identify Hormone Link Between Diabetes and Hypertension

Physician researchers with The Ohio State University College of Medicine at the Wexner Medical Center say increased levels of the hormone aldosterone, already associated with hypertension, can play a significant role in the development of diabetes, particularly among certain racial groups.

“This research is an important step toward finding new ways to prevent a major chronic disease,” said Dr. K. Craig Kent, dean of the College of Medicine. “This shows how our diabetes and metabolism scientists are focused on creating a world without diabetes.”

Results of this study were published online today by the Journal of the American Heart Association.

“Aldosterone is produced by the adrenal gland. We’ve known for some time that it increases blood pressure. We’ve recently learned it also increases insulin resistance in muscle and impairs insulin secretion from the pancreas. Both actions increase a person’s risk of developing type 2 diabetes, but the question was – how much,” said Dr. Joshua J. Joseph, lead investigator and an endocrinologist at Ohio State Wexner Medical Center.

Joseph and his team followed 1,600 people across diverse populations for 10 years as part of the Multi-Ethnic Study of Atherosclerosis. They found, overall, the risk of developing type 2 diabetes more than doubled for people who had higher levels of aldosterone, compared to participants with lower levels of the hormone. In certain ethnicities, the effect was even greater. African Americans with high aldosterone levels have almost a three-fold increased risk. Chinese Americans with high aldosterone are 10 times more likely to develop diabetes.

“I looked into this as a promise to my father. He had high levels of aldosterone that contributed to his hypertension, and he thought it also might be linked to his diabetes. As my career progressed, I had the opportunity to research it, and we did find a link to diabetes,” Joseph said.

One question that remains is why there are wide differences in risk among various ethnic groups. Joseph said it could be genetics or differences in salt sensitivity or something else, and it needs further study.

Just over 30 million Americans have diabetes and nearly a fourth of them don’t know it, according to the Centers for Disease Control and Prevention. Another one in three Americans has prediabetes. Despite current preventive efforts, the numbers continue to climb among various racial/ethnic groups.

Next, Joseph will lead a federally funded clinical trial at Ohio State Wexner Medical Center to evaluate the role of aldosterone in glucose metabolism. African American participants who have prediabetes will take medication to lower their aldosterone levels. Researchers will study the impact on blood glucose and insulin in those individuals.

“We know there’s a relationship between aldosterone and type 2 diabetes. Now we need to determine thresholds that will guide clinical care and the best medication for treatment,” Joseph said.

He expects to start enrolling patients in that trial later this year.

Source: The Ohio State University


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New Cancer Treatment Uses Enzymes to Boost Immune System and Fight Back

Researchers at The University of Texas at Austin have developed a new approach to treating cancer using enzyme therapy.

The enzyme, PEG-KYNase, does not directly kill cancer cells but instead empowers the immune system to eradicate unwanted cells on its own. PEG-KYNase is designed to degrade kynurenine, a metabolite produced by numerous tumors that suppresses the immune system. The UT team’s findings were published in a recent issue of Nature Biotechnology.

A healthy, fully functioning immune system can combat the spread of cancer cells and eliminate tumors by itself. However, tumors have evolved in multiple ways to suppress the immune system, leading to the growth and metastasis of cancer cells.

“Our immune system constantly polices the body and normally recognizes and eliminates cancerous cells,” said Everett Stone, research assistant professor in the College of Natural Sciences’ Department of Molecular Biosciences and co-author of the study. “Kynurenine acts as a roadblock to immune cells that impedes normal surveillance; our drug removes this obstacle.”

Enzymes have been used in specific treatments before, to treat cancers such as leukemia for example, but this is the first time one has been designed to take on the role of immune checkpoint inhibitor. The researchers are confident this approach could prove effective in treating a variety of different cancers.

The team, led by Stone and professor George Georgiou in the Cockrell School of Engineering, developed an enzyme therapy that stimulates a human immune system abnormally suppressed by cancer cells, unleashing the body’s power to fight back against the disease.

Their next step is to initiate clinical trials to test the safety and efficacy of the enzyme.

“Our work presents a new therapeutic approach to overcoming the suppression of the immune system by cancer cells,” said Georgiou, who is a professor in the Cockrell School’s chemical and biomedical engineering departments, the College of Natural Sciences’ molecular biosciences department and Dell Medical School’s oncology department. “By relieving immune suppression, the immune system becomes primed to kill cancer cells and eradicate tumors.”

The research was funded by the Cancer Prevention and Research Institute of Texas, the American Cancer Society and Kyn Therapeutics, the company that is pursuing the clinical development of this approach.

Source: University of Texas at Austin

Study Links Widely-used Drug Azathioprine to Skin Cancers

Roddy Isles wrote . . . . . . . . .

A drug used to treat inflammatory bowel disease, arthritis and vasculitis as well as to prevent organ rejection in transplant patients has been identified as an important contributor to skin cancer development, in a research study carried out at the University of Dundee, Queen Mary University of London and the Wellcome Sanger Institute.

The research, published in Nature Communications, identified a `strong case for an association’ between the drug azathioprine and the mutational signature found in cases of cutaneous squamous cell carcinoma (cSCC), a common form of skin cancer.

It was already known that use of azathioprine leads to increased photosensitivity to UVA light, probably contributing to development of skin cancers. This new study finds that use of azathioprine leaves a molecular fingerprint in skin cancers, further implicating it in cSCC development.

Charlotte Proby, Professor of Dermatology in the School of Medicine at Dundee, said, “We recommend all physicians give appropriate advice on UVA avoidance including year-round sun protection for their patients on azathioprine.”

Professor Proby and colleagues said they were not necessarily advocating withdrawal of azathioprine.

“As with all medications the risks must be balanced against the benefits, particularly with the need to treat potentially life-threatening diseases with an effective drug,” she said.

“It is important that sun protection, skin surveillance and early diagnosis/lesion removal are part of the routine management of patients on azathioprine.”

cSCC is a common skin cancer with more than 40,000 new cases diagnosed annually in the UK, with significant health economic implications.

Sophia Lowes, from Cancer Research UK, said, “It’s important to protect your skin from the sun when it’s strong, especially if you burn easily or are taking medications which make you more sun-sensitive. The most effective protection is to spend time in the shade and cover up with a hat, long-sleeved top and sunglasses. For the bits you can’t cover, use sunscreen with at least 4 stars and SPF 15 or higher for protection against both UVA and UVB rays.”

Importantly, this new study also reveals the molecular landscape of cSCC and highlights potential targets that may be developed for future therapeutic approaches to manage cSCC.

Different carcinogens leave a different `mutational signature’ in a cancer. By studying these signatures, researchers can start to determine what the causes of a cancer are.

The researchers in the School of Medicine at Dundee, in collaboration with the Wellcome Sanger Institute and Queen Mary University of London, were able to carry out mutational signature analysis of cSCC tumours from 37 patients, many of whom had been on azathioprine. They found a new mutational signature, Signature 32, which correlated with time on azathioprine therapy.

Source: University of Dundee


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