Posts Tagged ‘health’

1-alzheimersdi
Diagram of the brain of a person with Alzheimer’s Disease.

In recent years, researchers have largely converged on the role of inflammation in the development and progression of Alzheimer’s disease (AD). Studies over the past decade have revealed unexpected interactions between the brain and the immune system, and metabolic conditions such as obesity and diabetes may activate inflammatory responses that contribute to the development and progression of AD.

The activation of the inflammatory response is controlled by the inflammasome, a multi-protein oligomer that promotes the release of several pro-inflammatory cytokines including interleukin 1β (IL-1β) and interleukin 18 (IL-18). In an earlier study, a group of researchers with the University of Massachusetts Medical School, the University of Tokyo and the University of Bonn reported that mice with a cognate of Alzheimer’s disease that were additionally bred to knock out the NLRP3 gene encoding the inflammasome were completely protected from neurodegenerative effects of the disease. The researchers presumed that this was the result of their inability to produce IL-1β and IL-18.

This finding was quite promising, suggesting that targeting components of the inflammasome might be a path to Alzheimer’s treatments. In their new study, they sought to determine the effect of IL-18 by breeding IL-18 knockout mice. The researchers considered IL-18 to be a promising target, because levels are elevated in the cerebrospinal fluid of AD patients with mild cognitive impairment. Additionally, it is known to increase the production of amyloid peptide.

But the result of the new mouse study was startling, and completely unprecedented in Alzheimer’s research. The IL-18 knockout mice developed a lethal seizure disorder that the researchers attribute to an increase in neuronal network transmission. The authors write, “… the effects of IL-18 deletion were so dramatic that we were unable to identify previous evidence to help understand the phenomena.”

The finding that a proinflammatory cytokine might in some way ameliorate seizure-inducing neural activity seems counterintuitive, since inflammation is theorized to promote neurodegenerative symptoms in AD. The researchers believe that epilepsy is understudied in AD patients, even though it is a common complication; they point out that two-thirds of AD patients experience both motor and non-motor seizures. Additionally, AD patients with epilepsy are more likely to develop memory loss and other cognitive symptoms, and experience a more widespread loss of brain cells than AD patients without epilepsy, according to the researchers.

They theorize that IL-18 may be counteracting seizure-promoting effects of IL-1β, and suppressing IL-18 thus induced seizures in the test mice. “In fact,” they write, “the countereffect of IL-18 and IL-1β has been documented in a mouse model of cerebellar ataxia. Importantly, we found that the acute application of IL-18 protein reduced excitatory synaptic transmission in the hippocampus, providing evidence that IL-18 has a protective function in neuronal excitability. Thus, we speculate that IL-18 directly suppresses these proepileptogenic effects of IL-1β in APP/PS1 mice.”

However, the most important implication of the study may be that, while the inflammasome is a promising therapeutic target for Alzheimer’s, inhibiting specific cytokines could negatively affect people with the disease.

More information: Inflammasome-derived cytokine IL18 suppresses amyloid-induced seizures in Alzheimer-prone mice. Proceedings of the National Academy of Sciences (2018). doi.org/10.1073/pnas.1801802115

Abstract
Alzheimer’s disease (AD) is characterized by the progressive destruction and dysfunction of central neurons. AD patients commonly have unprovoked seizures compared with age-matched controls. Amyloid peptide-related inflammation is thought to be an important aspect of AD pathogenesis. We previously reported that NLRP3 inflammasome KO mice, when bred into APPswe/PS1ΔE9 (APP/PS1) mice, are completely protected from amyloid-induced AD-like disease, presumably because they cannot produce mature IL1β or IL18. To test the role of IL18, we bred IL18KO mice with APP/PS1 mice. Surprisingly, IL18KO/APP/PS1 mice developed a lethal seizure disorder that was completely reversed by the anticonvulsant levetiracetam. IL18-deficient AD mice showed a lower threshold in chemically induced seizures and a selective increase in gene expression related to increased neuronal activity. IL18-deficient AD mice exhibited increased excitatory synaptic proteins, spine density, and basal excitatory synaptic transmission that contributed to seizure activity. This study identifies a role for IL18 in suppressing aberrant neuronal transmission in AD.
Journal reference: Proceedings of the National Academy of Sciences

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Researchers have identified a brand new ‘micro-organ’ inside the immune system of mice and humans – the first discovery of its kind for decades – and it could put scientists on the path to developing more effective vaccines in the future.

Vaccines are based on centuries of research showing that once the body has encountered a specific type of infection, it’s better able to defend against it next time. And this new research suggests this new micro-organ could be key to how our body ‘remembers’ immunity.

The researchers from the Garvan Institute of Medical Research in Australia spotted thin, flat structures on top of the immune system’s lymph nodes in mice, which they’ve dubbed “subcapsular proliferative foci” (or SPFs for short).

These SPFs appear to work like biological headquarters for planning a counter-attack to infection.

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Immune cells gathering at the SPF, with the purple band showing the SPF surface.

These SPFs only appear when the mice immune systems are fighting off infections that have been encountered before.

What’s more, the researchers detected SPFs in human lymph nodes too, suggesting our bodies react in the same way.

“When you’re fighting bacteria that can double in number every 20 to 30 minutes, every moment matters,” says senior researcher Tri Phan. “To put it bluntly, if your immune system takes too long to assemble the tools to fight the infection, you die.”

“This is why vaccines are so important. Vaccination trains the immune system, so that it can make antibodies very rapidly when an infection reappears. Until now we didn’t know how and where this happened.”

Traditional microscopy approaches analyse thin 2D slices of tissue, and the researchers think that’s why SPFs haven’t been spotted before – they themselves are very thin, and they only appear temporarily.

In this case the team made the equivalent of a 3D movie of the immune system in action, which revealed the collection of many different types of immune cell in these SPFs. The researchers describe them as a “one-stop shop” for fighting off remembered infections, and fighting them quickly.

Crucially, the collection of immune cells spotted by the researchers included Memory B type cells – cells which tell the immune system how to fight off a particular infection. Memory B cells then turn into plasma cells to produce antibodies and do the actual work of tackling the threat.

“It was exciting to see the memory B cells being activated and clustering in this new structure that had never been seen before,” says one of the team, Imogen Moran.

“We could see them moving around, interacting with all these other immune cells and turning into plasma cells before our eyes.”

According to the researchers, the positioning of the SPF structures on top of lymph nodes makes them perfectly positioned for fighting off infections – and fast.

They’re strategically placed at points where bacteria would invade, and contain all the ingredients required to keep the infection at bay.

Now we know how the body does it, we might be able to improve vaccine techniques – vaccines currently focus on making memory B cells, but this study suggests the process could be made more efficient by also looking at how they transform into plasma cells through the inner workings of an SPF.

“So this is a structure that’s been there all along, but no one’s actually seen it yet, because they haven’t had the right tools,” says Phan.

“It’s a remarkable reminder that there are still mysteries hidden within the body – even though we scientists have been looking at the body’s tissues through the microscope for over 300 years.”

The research has been published in Nature Communications.

https://www.sciencealert.com/researchers-identify-new-lymph-node-structures-powering-immunity

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1. In a nationally representative survey of American adolescents, there was a fivefold increase in prevalence of lifetime abstinence from substance use among high school seniors.

2. Prevalence of lifetime abstinence from cigarettes and alcohol increased most drastically, whereas rates of marijuana and other substance use have remained more steady.

Substance use is an important modifiable health behavior, and previous studies have focused on use of individual substances. In this cross-sectional study, researchers sought to characterize trends in substance nonuse among adolescents by analyzing responses to the Monitoring the Future Project (MTF), a survey of nationally representative samples of 8th-, 10th-, and 12th-grade students between 1976 and 2014. Prevalence of lifetime abstinence from substance use among high school seniors has risen from 5% in 1976 to 26% in 2014, with similar trends among 8th- and 10th-grade students. Abstinence from cigarettes and alcohol increased dramatically during the study period, while abstinence of marijuana and other illicit substances increased only slightly and, in the case of marijuana, have fallen from peak levels in the 1990s. Students who were male, African American, or reported higher levels of religious involvement were significantly more likely to report lifetime abstinence. Lower odds of reporting lifetime abstinence were noted among students with low grade point average, past-month truancy, employment during the school year, and living in a single-parent household.

These findings are limited by self report bias. True prevalence may be underestimated because adolescents who were not in school to take the survey and those who were missing data for any substance were excluded from analysis. Nonetheless, the study is strengthened by its large, nationally representative sample of high school students. For physicians, these results highlight the importance of identifying and discussing the use of marijuana and other substances with adolescents and parents.

https://www.psychiatryadvisor.com/addiction/abstinence-from-substance-use-among-adolescents-is-increasing/article/787208/?utm_source=newsletter&utm_medium=email&utm_campaign=pa-update-dmd-20180825&cpn=psych_md%2cpsych_all&hmSubId=2yAHMYaJqF41&NID=1710903786

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Even the occasional drink is harmful to health, according to the largest and most detailed research carried out on the effects of alcohol, which suggests governments should think of advising people to abstain completely.

The uncompromising message comes from the authors of the Global Burden of Diseases study, a rolling project based at the University of Washington, in Seattle, which produces the most comprehensive data on the causes of illness and death in the world.

Alcohol, says their report published in the Lancet medical journal, led to 2.8 million deaths in 2016. It was the leading risk factor for premature mortality and disability in the 15 to 49 age group, accounting for 20% of deaths.

Current alcohol drinking habits pose “dire ramifications for future population health in the absence of policy action today”, says the paper. “Alcohol use contributes to health loss from many causes and exacts its toll across the lifespan, particularly among men.”

Most national guidelines suggest there are health benefits to one or two glasses of wine or beer a day, they say. “Our results show that the safest level of drinking is none.”

The study was carried out by researchers at the Institute of Health Metrics and Evaluation (IHME), who investigated levels of alcohol consumption and health effects in 195 countries between 1990 to 2016. They used data from 694 studies to work out how common drinking was and from 592 studies including 28 million people worldwide to work out the health risks.

Moderate drinking has been condoned for years on the assumption that there are some health benefits. A glass of red wine a day has long been said to be good for the heart. But although the researchers did find low levels of drinking offered some protection from heart disease, and possibly from diabetes and stroke, the benefits were far outweighed by alcohol’s harmful effects, they said.

Drinking alcohol was a big cause of cancer in the over-50s, particularly in women. Previous research has shown that one in 13 breast cancers in the UK were alcohol-related. The study found that globally, 27.1% of cancer deaths in women and 18.9% in men over 50 were linked to their drinking habits.

In younger people globally the biggest causes of death linked to alcohol were tuberculosis (1.4% of deaths), road injuries (1.2%), and self-harm (1.1%).

In the UK, the chief medical officer Sally Davies has said there is no safe level of drinking, but the guidance suggests that drinkers consume no more than 14 units a week to keep the risks low. Half a pint of average-strength lager contains one unit and a 125ml glass of wine contains around 1.5 units.

While the study shows that the increased risk of alcohol-related harm in younger people who have one drink a day is small (0.5%), it goes up incrementally with heavier drinking: to 7% among those who have two drinks a day (in line with UK guidance) and 37% for those who have five.

One in three, or 2.4 billion people around the world, drink alcohol, the study shows. A quarter of women and 39% of men drink. Denmark has the most drinkers (95.3% of women, and 97.1% of men). Pakistan has the fewest male drinkers (0.8%) and Bangladesh the fewest women (0.3%). Men in Romania and women in Ukraine drink the most (8.2 and 4.2 drinks a day respectively), while women in the UK take the eighth highest place in the female drinking league, with an average of three drinks a day.

“Alcohol poses dire ramifications for future population health in the absence of policy action today. Our results indicate that alcohol use and its harmful effects on health could become a growing challenge as countries become more developed, and enacting or maintaining strong alcohol control policies will be vital,” said the report’s senior author, Prof Emmanuela Gakidou.

“Worldwide we need to revisit alcohol control policies and health programmes, and to consider recommendations for abstaining from alcohol. These include excise taxes on alcohol, controlling the physical availability of alcohol and the hours of sale, and controlling alcohol advertising. Any of these policy actions would contribute to reductions in population-level consumption, a vital step toward decreasing the health loss associated with alcohol use.”

Dr Robyn Burton, of King’s College London, said in a commentary in the Lancet that the conclusions of the study were clear and unambiguous. “Alcohol is a colossal global health issue and small reductions in health-related harms at low levels of alcohol intake are outweighed by the increased risk of other health-related harms, including cancer,” she wrote.

“There is strong support here for the guideline published by the Chief Medical Officer of the UK who found that there is ‘no safe level of alcohol consumption’.”

Public health policy should be to prioritise measures to reduce the numbers who drink through price increases, taxation, or setting the price according to the strength of the drink (minimum unit pricing), followed by curbs on marketing and restricting the places where people can buy alcohol.

“These approaches should come as no surprise because these are also the most effective measures for curbing tobacco-related harms, another commercially mediated disease, with an increasing body of evidence showing that controlling obesity will require the same measures,” she wrote.

Ben Butler, a Drinkaware spokesperson, said: “This new study supports existing evidence about the harms associated with alcohol. Our research shows that over a quarter of UK adults typically exceed the low risk drinking guidelines and are running the risk of serious long term illnesses.”

But David Spiegelhalter, Winton professor for the public understanding of risk at the University of Cambridge, said the data showed only a very low level of harm in moderate drinkers and suggested UK guidelines were very low risk.

“Given the pleasure presumably associated with moderate drinking, claiming there is no ‘safe’ level does not seem an argument for abstention,” he said. “There is no safe level of driving, but government do not recommend that people avoid driving. Come to think of it, there is no safe level of living, but nobody would recommend abstention.”

https://www.theguardian.com/society/2018/aug/23/no-healthy-level-of-alcohol-consumption-says-major-study

20120917-restriction

Instead of survival of the fittest, evolution might actually be about survival of the laziest.

That’s according to a new study published Tuesday in the journal The Royal Society. Researchers from the University of Kansas studied fossils of ancient mollusks and gastropods, and found that organisms with higher metabolic rates were more likely to go extinct.

Animals that required less energy to power their daily lives and maintain their bodily functions were more likely to win in the long run, the results showed.

While metabolism isn’t the only factor that determines whether a species goes extinct, the researchers suggest that it’s a very important component of long-term survival.

That new finding adds to a growing body of evidence that links lower metabolism with longevity. (Naked mole rats, for example, are the longest living rodents thanks to a quirk in their metabolism.)

Rozalyn Anderson, an associate professor at the University of Wisconsin’s School of Medicine and Public Health, told Business Insider that her work in monkeys also suggests metabolism is at the center of the aging process.

“I think it’s all about energy: energy use, energy storage and the type of pathways that are being engaged to derive energy,” she said.

Restricting calories in monkeys
Anderson’s most recent research has been on the impacts of restricting caloric intake in Rhesus monkeys.

In a study of 76 monkeys published in the journal Science in 2009, Anderson and her colleagues found that restricting how many calories the animals consumed by 25% over a span of 20 years made them age differently, compared to a group of control monkeys that ate however much they wanted.

The monkeys who ate less were 2.5 times less likely to have an age-related disease like cancer or heart disease.

“The calorically restricted animals age differently,” Anderson said. “They don’t age slower, they age differently, and the way they age is associated with less disease risk. And that difference is in terms of their metabolism.”

She added that restricting a body’s caloric intake — the fuel it takes in — alters how the body produces and consumes energy, making it more energetically efficient.

Anderson also noted that the monkeys that underwent caloric restriction maintained their level of physical activity as they aged, whereas the control animals’ physical activity levels decreased. She explained at a conference in 2014 that for calorically restricted animals, there’s a lower metabolic cost associated with movement — more “bang for your buck” when it comes to trading nutrients for usable energy units.

When humans restrict their calories, researchers have seen similar outcomes. A two-year-long, NIH-supported study published in The Journals of Gerontology in 2015 found that participants who restricted their calories by 12% on average saw decreases in risk factors that contribute to age-related heart disease and diabetes. The experiment did not significantly alter their metabolism, though.

Connecting the dots between factors in the aging process
Anderson said that in her various studies of different facets of aging, she’s most fascinated when her research uncovers pathways that converge and overlap. This is happening more and more in the field of aging, and it’s helping her piece together why caloric restriction seems to alter parts of the aging process.

“I think it’s all completely connected, and these are just different ways of looking at the same phenomenon, which is the things that change with age that makes older people more vulnerable to disease than young people,” Anderson said. “How could you imagine a machine as complicated as a person or a monkey or a mouse, and not have it massively interconnected?”

For example, she found that a specific group of microRNAs — molecules that control gene expression — that she studied in relation to aging a while back plays an active role in the body’s response to caloric restriction. Anderson also found links between caloric restriction and her previous studies on NAD, a molecule that’s tied to energy metabolism and mitochondria. Putting these cellular-level studies into a bigger picture allows Anderson to gauge how all the moving parts come together when calories are limited.

“There’s this idea that the constellation of cells in a tissue are performing different tasks and different ones are creating vulnerability in different ways,” Anderson said. “It’s becoming more nuanced, for sure, it’s becoming more complicated. But it’s also making more sense. Which is why I think it’s kind of cool.”

Aging is inevitable, Anderson said, but her work is suggesting that how you age is flexible and manipulatable.

Understanding the relationship between metabolism and aging will allow scientists to better design studies on longevity. And as more research reveals how and why animals with lower metabolisms live longer and survive better, scientists may be able to figure out ways to mimic those effects in humans.

https://www.thisisinsider.com/restricting-calories-could-protect-against-aging-2018-8

Good Grip, Good Health

Posted: August 15, 2018 in Uncategorized
Tags: , , , ,

Measuring hand grip can help identify youths who could benefit from lifestyle changes, Baylor University researcher says. While other studies have shown that muscle weakness as measured by grip strength is a predictor of unhealthy outcomes — including cardiovascular and metabolic diseases, disability and even early mortality — this is the first to do so for adolescent health over time, a Baylor University researcher said.

“What we know about today’s kids is that because of the prevalence of obesity, they are more at risk for developing pre-diabetes and cardiovascular disease than previous generations,” said senior author Paul M. Gordon, Ph.D., professor and chair of health, human performance and recreation in Baylor’s Robbins College of Health and Human Sciences.

“This study gives multiple snapshots over time that provide more insight about grip strength and future risks for developing diabetes and cardiovascular disease,” he said. “Low grip strength could be used to predict cardiometabolic risk and to identify adolescents who would benefit from lifestyle changes to improve muscular fitness.”

Students tracked in the study were assessed in the fall of their fourth-grade year and at the end of the fifth grade. Using the norms for grip strengths in boys and girls, researchers measured the students’ grips in their dominant and non-dominant hands with an instrument called a handgrip dynamometer.

Researchers found that initially, 27.9 percent of the boys and 20.1 percent of the girls were classified as weak. Over the course of the study, boys and girls with weak grips were more than three times as likely to decline in health or maintain poor health as those who were strong.

Researchers also screened for and analyzed other metabolic risk factor indicators, including physical activity, cardiorespiratory fitness, body composition (the proportion of fat and fat-free mass), blood pressure, family history, fasting blood lipids and glucose levels.

“Even after taking into account other factors like cardiorespiratory fitness, physical activity and lean body mass, we continue to see an independent association between grip strength and both cardiometabolic health maintenance and health improvements,” Gordon said.

While much emphasis has been placed on the benefits of a nutritious diet and aerobic activity, this study suggests that greater emphasis needs to be placed on improving and maintaining muscular strength during adolescence.

If someone with a strong grip develops an even stronger grip, “we don’t necessarily see a drastic improvement in that individual’s health,” Gordon noted. “It’s the low strength that puts you at risk.

“Given that grip strength is a simple indicator for all-cause death, cardiovascular death and cardiovascular disease in adults, future research is certainly warranted to better understand how weakness during childhood tracks into and throughout adulthood,” he said. “Testing grip strength is simple, non-invasive and can easily be done in a health care professional’s office. It has value for adults and children.”

An estimated 17.2 percent of U.S. children and adolescents aged 2 to 19 years are obese and another 16.2 percent are overweight, according to the National Center for Health Statistics. Excess weight carries a greater lifetime risk of diabetes and premature heart disease. While the World Health Organization and the U.S. Department of Health and Human Services recommend that youths perform at least 60 minutes of moderate to vigorous physical activity daily — including vigorous activity at least three days a week — fewer than a quarter of U.S. children do so, according to a report by the nonprofit National Physical Activity Plan Alliance.

Reference: Peterson, M. D., Gordon, P. M., Smeding, S., & Visich, P. (2018). Grip Strength Is Associated with Longitudinal Health Maintenance and Improvement in Adolescents. The Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2018.07.020

https://www.technologynetworks.com/proteomics/news/good-grip-good-health-307585?utm_campaign=Newsletter_TN_BreakingScienceNews&utm_source=hs_email&utm_medium=email&utm_content=65175478&_hsenc=p2ANqtz-887HvGM-iiCBXuYuQ-OC_o-JSzmK_HOnCxRga2M8gAVZDF4SejOFma20Bb04GZ9F3uhKOjczHVcuNF-Htnak8rN-Hfow&_hsmi=65175479


Age-related macular degeneration, diabetic retinopathy and glaucoma were all associated with a higher risk of developing Alzheimer’s disease in a new study.

by Rich Haridy

A new study has found an interesting correlation between several degenerative eye diseases and the onset of Alzheimer’s disease. No mechanism explaining the connection has been proposed at this stage but it is thought these eye conditions may help physicians identify patients at risk of developing Alzheimer’s at a stage before major symptoms appear.

The five-year study followed almost 4,000 patients over the age of 65, all without clinically diagnosed Alzheimer’s disease at the time of enrolment. After five years, 792 subjects were officially diagnosed with Alzheimer’s. The study found that those subjects with age-related macular degeneration, diabetic retinopathy or glaucoma, were 40 to 50 percent more likely to develop Alzheimer’s compared to patients without those specific conditions. No correlation between cataracts and an increased risk of Alzheimer’s were found.

“We don’t mean people with these eye conditions will get Alzheimer’s disease,” cautions Cecilia Lee, lead researcher on the study. “The main message from this study is that ophthalmologists should be more aware of the risks of developing dementia for people with these eye conditions and primary care doctors seeing patients with these eye conditions might be more careful on checking on possible dementia or memory loss.”

The researchers are clear that there are no definable causal connections between these eye conditions and Alzheimer’s at this stage, but the study does highlight the potential of using the eye as a way to better understand what is going on in the brain. Intriguingly, this isn’t the first bit of research that has found correlations between signs detected in the eye and the onset of Alzheimer’s disease.

Last year, a team from Cedars-Sinai Medical Center revealed that the same type of amyloid protein deposits found in the brain, and hypothesized as a major pathogenic cause of Alzheimer’s, can also be detected on the retina. That research suggested a possible investigational eye scan could become an effective early screening device for the disease.

While this new study does not at all cross over with last year’s research, and there is no implication that amyloid proteins play a part in these degenerative eye diseases, it does add to a fascinating growing body of work that highlights the eye’s role in helping offer a deeper insight into the cognitive health of our brain.

The research was published in the journal Alzheimer’s & Dementia.

https://newatlas.com/eye-disease-alzheimers-connection/55823/