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Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells

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Very interesting finding reported by the Salk Institute:

Salk Institute scientists have found preliminary evidence that tetrahydrocannabinol (THC) and other compounds found in marijuana can promote the cellular removal of amyloid beta, a toxic protein associated with Alzheimer’s disease.

While these exploratory studies were conducted in neurons grown in the laboratory, they may offer insight into the role of inflammation in Alzheimer’s disease and could provide clues to developing novel therapeutics for the disorder.

“Although other studies have offered evidence that cannabinoids might be neuroprotective against the symptoms of Alzheimer’s, we believe our study is the first to demonstrate that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells,” says Salk Professor David Schubert, the senior author of the paper.

Alzheimer’s disease is a progressive brain disorder that leads to memory loss and can seriously impair a person’s ability to carry out daily tasks. It affects more than five million Americans according to the National Institutes of Health, and is a leading cause of death. It is also the most common cause of dementia and its incidence is expected to triple during the next 50 years.

It has long been known that amyloid beta accumulates within the nerve cells of the aging brain well before the appearance of Alzheimer’s disease symptoms and plaques. Amyloid beta is a major component of the plaque deposits that are a hallmark of the disease. But the precise role of amyloid beta and the plaques it forms in the disease process remains unclear.

In a manuscript published in June 2016’s Aging and Mechanisms of Disease, the Salk team studied nerve cells altered to produce high levels of amyloid beta to mimic aspects of Alzheimer’s disease.

The researchers found that high levels of amyloid beta were associated with cellular inflammation and higher rates of neuron death. They demonstrated that exposing the cells to THC reduced amyloid beta protein levels and eliminated the inflammatory response from the nerve cells caused by the protein, thereby allowing the nerve cells to survive. . .

Continue reading.

This means, were the DEA and the Obama Administration rational, that marijuana would no longer be a Schedule I drug, since Schedule I drugs, which are drugs that satisfy three conditions:

  1. The drug or other substance has a high potential for abuse.
  2. The drug or other substance has no currently accepted medical use in treatment in the United States.
  3. There is a lack of accepted safety for use of the drug or other substance under medical supervision.

Since marijuana does not satisfy any of these (marijuana’s potential for abuse is much less that that for alcohol, which is not a Schedule I drug), marijuana is being used to treat pain and PTSD (and the use of addictive opioids for pain relief is significantly lower in states in which medical marijuana is legal), and the use of marijuana is much safer than, for example, the use of alcohol. The CDC reports: “There are more than 2,200 alcohol poisoning deaths in the U.S. each year – an average of 6 alcohol poisoning deaths every day.” Alcohol is not a Schedule I drug, but it does meet all the criteria. Marijuana is a Schedule I drug, but it meets none of the criteria.

This seems extremely stupid to me.

Written by LeisureGuy

27 August 2016 at 11:04 am

Gut reaction: the surprising power of microbes

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Ed Yong reports in the Guardian:

‘So, what’s in the thermos?” I asked.

I was standing in a lift at Washington University in St Louis, with Professor Jeff Gordon and two of his students, one of whom was holding a metal canister.

“Just some faecal pellets in tubes,” she said.

“They’re microbes from healthy children, and also from some who are malnourished. We transplanted them into mice,” explained Gordon, as if this was the most normal thing in the world.

The lift doors opened, and I followed Gordon, his students, and the thermos of frozen pellets into a large room. It was filled with rows of sealed chambers made of transparent plastic. Peering inside one of these chambers, I met the eyes of one of the strangest animals on the planet. It looked like just a mouse, and that is precisely why it was so weird. It was just a mouse, and nothing more.

Almost every other animal on Earth, whether centipede or crocodile, flatworm or flamingo, hippo or human, is a teeming mass of bacteria and other microbes. Each of these miniature communities is known as a microbiome. Every human hosts a microbiome consisting of some 39 trillion microbes, roughly one for each of their own cells. Every ant in a colony is a colony itself. Every resident in a zoo is a zoo in its own right. Even the simplest of animals such as sponges, whose static bodies are never more than a few cells thick, are home to thriving microbiomes.

But not the mice in Gordon’s lab. They spend their entire lives separated from the outside world, and from microbes. Their isolators contain everything they need: drinking water, brown nuggets of chow, straw chips for bedding, and a white styrofoam hutch for mating in privacy. Gordon’s team irradiates all of these items to sterilise them before piling them into loading cylinders. They sterilise the cylinders by steaming them at a high temperature and pressure, before hooking them to portholes in the back of the isolators, using connecting sleeves that they also sterilise.

It is laborious work, but it ensures that the mice are born into a world without microbes, and grow up without microbial contact. The term for this is “gnotobiosis”, from the Greek for “known life”. We know exactly what lives in these animals – which is nothing. Unlike every other mouse on the planet, each of these rodents is a mouse and nothing more. An empty vessel. A silhouette, unfilled. An ecosystem of one.

Each isolator had a pair of black rubber gloves affixed to two portholes, through which the researchers could manipulate what was inside. The gloves were thick. When I stuck my hands in, I quickly started sweating.

I awkwardly picked up one of the mice. It sat snugly on my palm, white-furred and pink-eyed. It was a strange feeling: I was holding this animal but only via two black protrusions into its hermetically sealed world. It was sitting on me and yet completely separated from me. When I had shaken hands with Gordon earlier, we had exchanged microbes. When I stroked this mouse, we exchanged nothing.

The mouse seemed normal, but it was not. Growing up without microbes, its gut had not developed properly – it had less surface area for absorbing nutrients, its walls were leakier, it renewed itself at a slower pace, and the blood vessels that supplied it with nutrients were sparse. The rest of its body hadn’t fared much better. Compared with its normal microbe-laden peers, its bones were weaker, its immune system was compromised, and it probably behaved differently too. It was, as microbiologist Theodor Rosebury once wrote, “a miserable creature, seeming at nearly every point to require an artificial substitute for the germs [it] lacks”.

The woes of the germ-free mouse vividly show just how invaluable the microbiome is. Most of us still see microbes as germs: unwanted bringers of pestilence that we must avoid at all costs. This stereotype is grossly unfair. Most microbes do not make us sick. At worst, they are passengers or hitchhikers. At best, they are invaluable parts of our bodies: not takers of life but its guardians. They help to digest our food, educate our immune systems, protect us from disease, sculpt our organs, guide our behaviour, and maintain our health. This wide-ranging influence explains why the microbiome has, over the last decade, become one of the hottest areas of biology, and why Gordon – arguably the most influential scientist in the field – is so fascinated by it.

By studying our microbial companions, he is trying to unpick exactly how the microbiome is connected to obesity and its polar opposite – malnutrition. He is studying which species of microbes influence these conditions, and how they in turn are influenced by our diets, our immune systems, and other aspects of our lives. Ultimately, he wants to use that knowledge to manipulate the microbial worlds within us to improve our health.


Jeff Gordon may be one of the most respected scholars of the human microbiome, but he is also one of the hardest to get in touch with. It took me six years of writing about his work to get him to answer my emails, so visiting his lab was a hard-won privilege. I arrived expecting someone gruff and remote. Instead, I found an endearing and affable man with crinkly eyes, a kindly smile, and a whimsical demeanour. As he walked around the lab, he called people “professor” – including his students. His aversion to the media comes not from aloofness, but from a distaste for self-promotion. He even refrains from attending scientific conferences, preferring to stay out of the limelight and in his laboratory.

Ensconced there, Gordon has done more than most to address how microbes affect our health. But whenever I asked Gordon about his influence, he tended to deflect credit on to students and collaborators past and present – a roster that includes many of the field’s biggest stars. Their status testifies to Gordon’s – he’s not just a king, but a king-maker, too. And his figurehead status is all the more remarkable because long before the microbiome crossed his mind, he was already a well-established scientist who had published hundreds of studies on how the gut develops in a growing human body.

In the 1990s, he started to suspect that bacteria influence this process, but he was also struck by how difficult it would be to test that idea. The gut contains thousands of species of microbes. Gordon aimed to isolate parts of this daunting whole and examine it under controlled conditions. He needed that critical resource that scientists demand but biology withholds: control. In short, he needed germ-free mice – and lots of them – so he bred them himself. He could load these rodents with specific microbes, feed them with pre-defined diets, and do so again and again in controlled and repeatable conditions. He could treat them as living bioreactors, in which he could strip down the baffling complexity of the microbiome into manageable components that he could systematically study.

In 2004, Fredrik Bäckhed, a member of Gordon’s team, used the sterile rodents to run an experiment that would set the entire lab on a focused path – one devoted to understanding the connections between the microbiome, nutrition, and health. They inoculated germ-free mice with microbes harvested from the guts of conventionally raised rodents. Normally, the sterile rodents can eat as much as they like without putting on weight, but this ability disappeared once their guts were colonised. They didn’t start eating any more food – if anything, they ate slightly less – but they converted more of that food into fat and so put on more pounds.

Mouse biology is similar enough to that of human beings for scientists to use them as stand-ins in everything from drug testing to brain research; the same applies to their microbes. Gordon reasoned that if those early results apply to humans, our microbes must surely influence the nutrients that we extract from our food, and thus our body weight. That was a powerful insight. We typically think of weight as a simple balance between the calories we take in through food and those we burn through physical activity. By contrast, the idea that multitudes of organisms in our bodies could influence that balance was outlandish at the time. “People weren’t talking about it,” says Gordon.

And yet, in 2004, team member Ruth Ley found another connection between microbes and weight, when she showed that obese people (and mice) have different communities of microbes in their guts. The most obvious difference lay in the ratio of the two major groups of gut bacteria – the firmicutes and the bacteroidetes. Obese people had more firmicutes and fewer bacteroidetes than their leaner counterparts. This raised an obvious question: does extra body fat cause a relative increase in firmicutes – or, more tantalisingly, does the tilt make individuals fatter? Is the connection, as Gordon likes to put it, causal or casual? The team couldn’t answer that question by relying on simple comparisons. They needed experiments.

That’s where Peter Turnbaugh came in. Then a graduate student in the lab, he harvested microbes from fat and lean mice, and then fed them to germ-free rodents. Those that got microbes from lean donors put on 27% more fat, while those with obese donors packed on 47% more fat. It was a stunning result: Turnbaugh had effectively transferred obesity from one animal to another, simply by moving their microbes across. “It was an ‘Oh my God’ moment,” said Gordon. “We were thrilled and inspired.”

These results showed that the guts of obese individuals contain altered microbiomes that can indeed contribute to obesity, at least in some contexts. The microbes were perhaps harvesting more calories from the rodents’ food, or affecting how they stored fat. Either way, it was clear that microbes don’t just go along for the ride; sometimes, they grab the wheel. . .

Continue reading.

Written by LeisureGuy

27 August 2016 at 9:11 am

Posted in Daily life, Health, Science

Glycemic effects of various foods on a teaspoons-of-sugar scale

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Sugar equivalents

The interesting graph above is from this post at DietDoctor.com. The post begins:

For people with diabetes, it’s not the carb count of a food that matters most, but how much it affects blood sugar levels. So how bad are different foods compared to, say, spoonfuls of sugar?

That’s something that Dr. David Unwin has focused on teaching his patients, with great results, according to this new paper.

Take a look at the picture above. A serving of potatoes has a similar effect as 8 teaspoons of sugar, and rice is even worse. Meanwhile eggs (a low-carb staple) was like 0 tea spoons.

So what happens to Dr. Unwin’s patients on a low-carb diet? . . .

Continue reading.

Written by LeisureGuy

24 August 2016 at 11:30 am

US prisons are poorly run and do not even give inmates sufficient drinking water

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Alice Speri reports in The Intercept:

In the summer months, 84 inmates at the Price Daniel Unit, a medium-security prison four hours west of Dallas, share a 10-gallon cooler of water that’s kept locked in a common area. An inmate there can expect to receive one 8 oz. cup every four hours, according to Benny Hernandez, a man serving a 10-year sentence at the prison. The National Academy of Medicine recommends that adults drink about twice that amount under normal conditions and even more in hot climates. According to Hernandez, in the summer the temperature in his prison’s housing areas can reach an astonishing 140 degrees.

The prison provides ice for the cooler twice a day, but the ice has long melted before the hottest part of the day, he wrote in a post on Prison Writers, a website where inmates share their experiences behind bars. “Prisoners look upon the summer months in the Texas Department of Criminal Justice (TDCJ) with dread and trepidation,” he wrote. “For one is acutely aware that one may not survive another summer. Many do not.”

The TDCJ, which runs Texas prisons and houses more than 146,000 inmates, is currently in the middle of litigation over what inmates and advocates have said is deadly heat in its facilities. But Texas is not the only state facing such lawsuits. Louisiana is defending its refusal to install air conditioning on death row, while prisons and jails across the country have been ordered by courts to address their sweltering temperatures and extend protections to inmates, particularly the ill and elderly.

A spokesperson for TDCJ wrote in a statement to The Intercept that “the well-being of staff and offenders is a top priority for the agency and we remain committed to making sure that both are safe during the extreme heat.” He said that only 30 of the state’s 109 prisons have air conditioning in all inmate housing areas, because many were built before that became a common feature and retrofitting them would be “extremely expensive.” Instead, he said, the agency has taken measures like offering water and ice, restricting inmate activities, and training staff to recognize heat-related illness. The spokesperson said that inmates have “the ability to access water throughout the day” and that ice and water coolers are refilled continuously — contradicting the accounts of inmates who said that ice rations are often reduced and sometimes outright denied, that in some facilities they are given no ice or cold water for days at a time, that ice is so scarce that inmates will buy it off each other, and that inmates residing in a given cell block are given ice water to pass down the row of cells, which often leads to violence and hoarding of the vital resource.

Hernandez, the Price Daniel Unit inmate, acknowledged that prison officials there took some “precautionary measures,” like the water cooler and placing fans in common areas of the prison, but said that was hardly enough. Inmates have fans in their cells only if they can afford to buy them from the prison commissary, and “once the temperature exceeds 95 degrees Fahrenheit, the fans simply circulate hot air,” he wrote.

“It routinely feels as if one’s sitting in a convection oven being slowly cooked alive.”

In a 2014 report documenting the “deadly heat” inside Texas prisons, researchers with the University of Texas School of Law’s Human Rights Clinic found that since 2007, at least 14 inmates had died from extreme heat exposure in prisons across the state. The report documented at length the . . .

Continue reading.

Read the whole thing. There’s a lot more and it’s disgusting, describing callous (and even criminal) neglect of human rights and the health of prisoners. Texas, of course, is a particular example of a state government that fails to address the needs of its citizens, but other states also fail to meet minimal human-rights standards.

Later in the article:

. . . “Part of the reason why you see this kind of irrational behavior — spending far more to fight the lawsuit than it would cost to just air-condition the prison — is because AC is seen as a luxury and prison officials don’t want to be seen as running luxurious prisons,” said Fathi. “Climate control is not a matter of comfort and luxury — it’s a matter of life or death.”

So far, the ACLU and other rights groups have been making that case one facility at a time. In Wisconsin, they won a court order to air-condition a prison where temperatures were reaching “potentially lethal levels.” In Mississippi, they won an order to provide fans, iced water, and daily showers when the heat index exceeds 90 degrees. They also secured protections for inmates more susceptible to heat-related injury at the Baltimore City Jail. In the Maricopa County jail in Arizona, run by Sheriff Joe Arpaio, the ACLU won an order that inmates on certain kinds of medication that make them more vulnerable to heat be housed in temperatures of 85 degrees or below.

“Unfortunately, because we have this very decentralized criminal justice system, you have to fight it out state by state and facility by facility” said Fathi. . .

Written by LeisureGuy

24 August 2016 at 11:02 am

Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model

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Very interesting article in Science Translational Medicine from the AAAS. The abstract:

Amyloid-β (Aβ) peptide has been implicated in the pathogenesis of Alzheimer’s disease (AD). We present a nonpharmacological approach for removing Aβ and restoring memory function in a mouse model of AD in which Aβ is deposited in the brain. We used repeated scanning ultrasound (SUS) treatments of the mouse brain to remove Aβ, without the need for any additional therapeutic agent such as anti-Aβ antibody. Spinning disk confocal microscopy and high-resolution three-dimensional reconstruction revealed extensive internalization of Aβ into the lysosomes of activated microglia in mouse brains subjected to SUS, with no concomitant increase observed in the number of microglia. Plaque burden was reduced in SUS-treated AD mice compared to sham-treated animals, and cleared plaques were observed in 75% of SUS-treated mice. Treated AD mice also displayed improved performance on three memory tasks: the Y-maze, the novel object recognition test, and the active place avoidance task. Our findings suggest that repeated SUS is useful for removing Aβ in the mouse brain without causing overt damage, and should be explored further as a noninvasive method with therapeutic potential in AD.

Written by LeisureGuy

24 August 2016 at 9:54 am

US is No. 1! — in calories/day. Ties for No. 2 in obesity.

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This chart shows the macronutrient consumption, and the table that accompanies the chart can be sorted on any column. US average per capita calorie consumption per day is 3770; number 2 is Austria (3760) and then Greece at 3700. Egypt is relatively low (3160 calories/person/day), but Egypt has a higher obesity rate than the U.S.: 33.1% for Egypt, 33% for the US.

One explanation might be that Egyptians get 73% of their calories from carbohydrates, the US gets 49% from carbs. (These figures are from the first chart.) Of course, Ethiopia has a 1.1% obesity rate while getting 79% of calories from carbs, but Ethiopians on average consume only 1950 calories per person per day: not enough spare calories to contribute to obesity.

Saudi Arabia also presents a puzzle: 3130 calories/person/day, 64% of calories from carbs, obesity rate 33%. That’s the same obesity rate as the US (and Egypt, the US, and Saudi Arabia have the highest obesity rates in the world), but the US calorie consumption is higher (3770 calories/person/day, 49% of calories from carbs.

But take a look at the chart show prevalence of diabetes: Saudi Arabia is No. 1 here with 23.4%, Egypt has 16.6%, and the US is 9.4%.

Mexico has a diabetes rate of 15.6%, with calories consumption at 3250/person/day, 62% from carbs. Mexico’s obesity rate is 32.1%, which is close to the US.

You can spend a fair amount of time looking at the differences among nations. The first chart, which allows sorting, is quite useful.

Carb consumption as a percentage of daily calories tends to be high in nations where daily calorie consumption is low because carbohydrates are a relatively inexpensive source of calories.

Thanks to Quebec Steve for pointing out the charts.

Written by LeisureGuy

24 August 2016 at 9:49 am

Posted in Daily life, Food, Health, Science

To encourage good choices, put more healthful foods on the left

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Who would have guessed?

Maybe people follow the rules the odd psychologist recommends to the protagonist (who became frozen in trying to make a choice) in John Barth’s The End of the Road:

At the end of my last session — it had been decided that I was to return to Baltimore experimentally, to see whether and how soon my immobility might recur — the Doctor gave me some parting instructions.

“It would not be well in your particular case to believe in God,” he said, “Religion will only make you despondent. But until we work out something for you it will be useful to subscribe to some philosophy. Why don’t you read Sartre and become an existentialist? It will keep you moving until we find something more suitable for you. Study the World Almanac: it is to be your breviary for a while. Take a day job, preferably factory work, but not so simple that you are able to think coherently while working. Something involving sequential operations would be nice. Go out in the evenings; play cards with people. I don’t recommend buying a television set just yet. If you read anything outside the Almanac, read nothing but plays — no novels or non-fiction. Exercise frequently. Take long walks, but always to a previously determined destination, and when you get there, walk right home again, briskly. And move out of your present quarters; the association is unhealthy for you. Don’t get married or have love affairs yet: if you aren’t courageous enough to hire prostitutes, then take up masturbation temporarily. Above all, act impulsively: don’t let yourself get stuck between alternatives, or you’re lost. You’re not that strong. If the alternatives are side by side, choose the one on the left; if they’re consecutive in time, choose the earlier. If neither of these applies, choose the alternative whose name begins with the earlier letter of the alphabet. These are the principles of Sinistrality, Antecedence, and Alphabetical Priority — there are others, and they’re arbitrary, but useful. Good-by.”

Written by LeisureGuy

22 August 2016 at 7:44 am

Posted in Books, Food, Health, Science

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