Life Extension Magazine®

Issue: Jan 2014

Outwitting Our Aging Brain

We are zeroing in on a prime culprit behind Alzheimer’s, stroke, and cognitive impairment. The term for this disorder is “hypoperfusion.” It means an inadequate supply of blood to a body part. Hypoperfusion causes a series of harmful changes that severely diminish neurological function. Life Extension® members will find comfort that their healthy life­style choices have been proven to help protect against hypoper­fusion. This article will profoundly change how neurodegenerative disease is viewed. It provides a rational basis to prevent and reverse circulatory deficits that cripple and destroy our aging brains.

By William Faloon

William Faloon
William Faloon

We are zeroing in on a prime culprit behind Alzheimer’s, stroke, and age-related cognitive impairment.

The term for this reversible disorder is “hypoperfusion.” It means an inadequate supply of blood to a body part.

Hypoperfusion of the brain occurs in response to reduced blood flow. The result of hypoperfusion is a series of harmful changes that severely diminish neurological function.

We have long known about structural changes that adversely impact the aging brain. Preceding this structural deterioration, however, is a decline in microvascular blood flow.

What researchers are increasingly recognizing is that most aging humans suffer from obstructions to cerebral blood flow that result in chronic hypoperfusion.1 This sets in motion a cascade of neuronal injuries that can manifest as memory loss,2 depression,3-6 and cognitive dysfunction.7-9 The long-term impact of hypoperfusion is a higher risk of stroke,10,11 vascular dementia,12,13 and Alzheimer’s disease.14-16

Life Extension® members will find comfort that their healthy lifestyle choices have been proven to help protect against hypoperfusion. We must never underestimate, however, the fragile nature of our aging circulatory systems.

This article represents a compilation of new findings that will profoundly change how neurodegenerative disease is viewed. It provides a rational basis to prevent and reverse the circulatory deficits that cripple and destroy our aging brains.

Don’t Let Your Brain Shrink!

Don’t Let Your Brain Shrink!  

Normal aging is associated with diminished blood flow to the brain. This pathology is known as hypoperfusion and causes cell injury and death.17

Hypertension (high blood pressure) accelerates brain atrophy in humans.18 It does this by damaging the cerebral circulatory system to the point that it cannot adequately transport blood.19,20

Blood vessels damaged by hypertension (and other factors) lose their ability to nourish cells, which can result in chronic hypoperfusion and loss of brain function.20

The combination of hypertension and hypoperfusion is associated with smaller brain volume.18

Once the cerebral vasculature is damaged, lowering blood pressure will not reverse brain shrinkage, and shrinkage may continue despite successful blood pressure control.20 The reason is that deformed and dysfunctional cerebral arteries may require higher blood pressure to avoid hypoperfusion.19 In other words, in some people with cerebrovascular damage, higher blood pressure may be needed to “squeeze” blood into their brain. This “squeezing” process results in additional blood vessel damage and increased stroke risk.19

While hypertension is a significant cause of arterial damage and hypoperfusion, aging humans have to do more than lower their blood pressure to reverse hypoperfusion.

Role Of Hypoperfusion In Alzheimer’s Disease

Role Of Hypoperfusion In Alzheimer’s Disease  

Hypoperfusion is no longer a controversial aspect of Alzheimer’s disease.15,21

Disrupted blood flow (hypoperfusion) is evident when Alzheimer’s manifests in its initial stage as mild cognitive impairment all the way to full-blown dementia.7,14-16,21

Hypoperfusion is also evident in cognitively healthy persons at high-risk for developing Alzheimer’s due to family history or genetic factors.21

Through the advent of advanced imaging technologies, it is now known that Alzheimer’s disease is associated with both global and regional cerebral hypoperfusion.21,22 Scientists have discovered that perfusion deficits in regions of the brain observed in Alzheimer’s disease patients are also present in people at increased risk for Alzheimer’s.21

While there is still debate as to whether decreased blood flow in Alzheimer’s is a cause or consequence of the disease, hypoperfusion is definitively associated with both structural and functional changes in the Alzheimer’s brain.21

Aging humans now have documented opportunities to aggressively explore treatments to prevent, or at least slow the progression of diseases like Alzheimer’s and stroke by guarding against hypoperfusion,also known as cerebrovascular insufficiency.

Hypoperfusion Associated With Reduced Memory Function

Metabolic syndrome is a cluster of cardiovascular risk factors that is also associated with cognitive decline and dementia.2

Common characteristics of metabolic syndrome include elevated glucose,23 high triglycerides,23 insulin resistance,24 abdominal obesity,23,24 low testosterone (in men),25,26 and hypertension.24

A study of late middle-aged adults showed that mean cerebral blood flow was 15% lower in those with metabolic syndrome compared to age-matched controls. The metabolic syndrome group also had lower immediate memory function. In this study,abdominal obesity and elevated triglycerides were most strongly associated with lower cerebral blood flow (hypoperfusion).2

Our “Tiny” Capillaries
Our 'Tiny' Capillaries

With each heartbeat, blood is thrust into arteries that branch into smaller arterioles that branch further into capillaries where they deliver oxygen and nutrients to cells.27 Even medically-educated individuals forget just how tiny capillaries that oxygenate our neurons really are.

A typical red blood cell is 6-10 micrometers, but capillary diameter is only 8-10 micrometers on average.27,28 Capillaries are so narrow that red blood cells often have to bend their shape to squeeze through them.29

Platelets are usually 2-4 micrometers,30 but anything that causes abnormal platelet clumping (thrombosis) creates a mass that cannot fit through thread-like capillaries.31 This helps explain how precarious our aging cerebral vascular system is and how readily hypoperfusion develops via disrupted capillary beds.

Not only are capillaries tiny, but they are also extremely delicate. Instead of the tough layers that make up arteries, capillaries consist only of a single layer of endothelial cells lying on a basement membrane.29,32 Hypertension destroys fragile capillaries leaving in its wake hypoperfused regions of the brain, often described as cerebral perfusion deficits .33

Capillaries surround neurons and diffuse oxygen and nutrients into them.33 Any interruption to capillary blood flow has the potential to injure or kill neurons.33 This is why hypoperfusion must be prevented or reversed if we are to preserve our cognitive integrity.

Abnormal platelet aggregation increases as humans age, which explains why thrombosis is an increasing threat with aging.34,35 Any blood particle larger than 5-10 micrometers can clog capillaries, and if enough capillaries become occluded in the brain, an ischemic stroke can occur.33

Risk factors in the blood that cause brain vasculature to become blocked include excess homocysteine,36 fibrinogen,37 C-reactive protein,38 and triglycerides.39 Homocysteine creates more havoc at the capillary level than it does in large blood vessels.40 Fibrinogen promotes occlusive thrombosis.41 Inflammation42 damages the delicate endothelium, and triglycerides clog capillary beds.43

Maintaining capillary integrity is essential to prevent hypoperfusion and the neurodegeneration that invariably accompanies it. Most Life Extension members already take steps to guard their overall health, which confers tremendous benefits in sustaining capillary blood flow, thus protecting against hypoperfusion.

Hypoperfusion Associated With Weakened Heart Function

A group of 211 men aged 68 went through a battery of tests to assess cognitive and cardiac function. These same men were tested 14 years later.44 Those with weakened hearts as measured on an echocardiogram and abnormal EKG patterns at baseline scored lower on verbal and speed-performance neurological tests. The doctors who conducted this study concluded that heart deficiencies in the study subjects were “associated with lower cognitive test results and may predict cognitive decline and silent cerebral perfusion abnormalities 14 years later.44

Another study found reduced cerebral perfusion in elderly men with abnormal EKGs and nighttime blood pressure dipping. The doctors who conducted this study concluded:

Silent myocardial ischemia may contribute to cerebrovascular disease in non-demented elderly men. Cerebral perfusion seems to be most vulnerable to myocardial ischemia in elderly with nocturnal blood pressure dipping.”45

These and other studies show that circulatory interruptions caused by even relatively mild cardiac disturbances deprive the brain of blood flow and result in cognitive impairments. So taking supplements like coenzyme Q10,46 lipoic acid,47 carnitine48,49 and PQQ50-53 not only help boost cardiac output to the brain, but also protect the brain and enhance mitochondrial energy production within brain cells (neurons).

Visualizing The Aging Brain

Don’t Let Your Brain Shrink!  

Advanced neuroimaging methods are enabling doctors to observe structural, functional, and biochemical changes in the brain, thus allowing earlier diagnosis of neurodegenerative diseases.54

A review of studies using enhanced neuroimaging techniques showed significant individual differences in the rate of cerebral aging (such as a decay of brain volume and reduction of blood flow) that accompanies loss of cognitive function.54

One neuroimaging study looked at degeneration in regions of the brain (frontal and temporal lobes) and their relationship with hypoperfusion. The researchers found worsening of frontal-temporal degeneration in response to lower cerebral blood flow. More severe hypoperfusion related to greater functional deficit.55

Preventing Progression To Senility

Mild cognitive impairment is considered an early stage of dementia. A group of researchers conducted a 3-year test and found the conversion rate from mild cognitive impairment to dementia was 11.65% each year.56

They found that cognitive decline and hypoperfusion were related to diabetes, carotid stenosis, and changes in the white matter area of the brain. The researchers conducting this study concluded:

“… our findings could imply that controlling blood glucose, removing carotid stenosis, and improving cerebral perfusion could be effective measures to delay cognitive decline in patients with mild cognitive impairment and prevent conversion from mild cognitive impairment to dementia.”56

Another study looked at structural alterations (such as amyloid beta deposition) and vascular organization in brains of aged monkeys and human Alzheimer’s brain tissue. The findings suggest that amyloid plaque brain formation relates to multiple underlying pathologies that occur in partnership with vascular or metabolic deficit.57 This data provides a mechanistic explanation for why senile plaques (as seen in Alzheimer’s) are present preferentially near the cerebral vasculature, and the importance of guarding against hypoperfusion.

Reversing Brain Damage In Former NFL Players

Brain injuries are common in professional football players and severe cases sometimes make headline news stories.59-62

A clinical trial was conducted on 30 retired NFL players who demonstrated brain damage and cognitive impairment. They underwent baseline testing of cognitive function and brain perfusion as measured by SPECT imaging.63

Participants were encouraged to lose weight (if appropriate) and take the following supplements for six months:

Reversing Brain Damage In Former NFL Players

Fish oil 64-66

1,720 mg EPA
1,160 mg DHA

Vinpocetine 67-72

15 mg

Ginkgo extract 73-78

120 mg

Alpha Lipoic Acid 79-82

300 mg

Acetyl L-Carnitine 80,83-85

1,000 mg

Huperzine A 86-88

150 mcg

N-acetyl-cysteine 89-93

600 mg

High-potency multivitamin 94,95

The rationale behind using these nutrients was that they were individually shown to enhance blood flow, protect against free radicals, enhance brain cell membrane structure, boost acetylcholine, enhance neuronal metabolic activity, and reduce chronic inflammatory markers.

After six months, the tests were repeated. There were statistically significant increases in scores of attention, memory, reasoning, information processing speed, and accuracy in these retired NFL players. The SPECT scan showed increased perfusion in areas throughout much of the brain. The researchers who conducted this trial concluded:

“This study demonstrates that cognitive and cerebral blood flow improvements are possible in this group with multiple interventions.”63

Neurological trauma during football events accelerates brain aging. Life Extension members should be gratified to know that they have been taking most, if not all of the nutrients shown in this study to reverse brain damage in retired NFL players. This brain damage clearly linked hypoperfusion with cognitive impairment.

Tying This All Together

A review published in 2011 titled “Cerebral microvascular pathology and neurodegeneration” provided a meticulous description as to how cerebro- vascular dysfunction precedes and accompanies cognitive impairment and senility.58 What made this report stand out was that it utilized a novel micro-pathology technique to permit viewing the cerebral vasculature in a 3-diminsional setting.

This 2011 review detailed how perilous our cerebral blood supply becomes with aging, describing tortuous arterioles that barely transport blood, obliterated capillary beds that no longer nourish neurons, and thickened veins that impede blood flow. It went on to describe how hypoperfusion occurs early in Alzheimer’s and other degenerative brain disorders.58

Of interest was the demonstration of a decline in cerebral angiogenesis that precludes natural repair of vascular deficits—and the dangers of particles in the blood (such as circulating clots) that destroy capillary beds, all of which contribute to the hypoperfusion and other vascular deficits that underlie neurodegenerative disease.58

An enormous volume of accumulated research reveals why virtually all aging humans suffer cognitive impairment, and why there are so many cases of crippling stroke and dementia.58

Aggressive intervention is clearly needed to protect our memories and very identities against the microvascular pathologies that have been accepted far too long as a hallmark of “normal” aging.

The encouraging news is that nutrients, hormones, and certain drugs that Life Extension members already take are proving more than ever to protect against cerebral circulatory deficits that occur in the aging brain.

Vinpocetine Reverses Cerebral Hypoperfusion

European doctors prescribe a periwinkle-originated drug called vinpocetine to patients suffering from cognitive problems ranging from short-term memory loss to Alzheimer’s dementia.

Vinpocetine exerts several anti-aging mechanisms, but its most profound effect may be its ability to interfere with processes associated with chronic cerebral hypoperfusion.103 The diverse mechanisms of vinpocetine explain its beneficial effects on clinical signs and symptoms of cerebrovascular insufficiency.

Life Extension has long been familiar with vinpocetine and has recommended it since the 1980s. The FDA tried to shut down our organization and incarcerate me for doing this. The FDA’s rationale was that vinpocetine was not an approved medicinal in the United States, even though it was safely and effectively being prescribed in Europe.

Fortunately, vinpocetine is now sold as a dietary supplement at a fraction of the price it would cost as an FDA-approved prescription drug. Life Extension members have obtained optimal daily doses of vinpocetine for the past three decades in a popular brain boosting formula they take.

Hypoperfusion Facilitates Alzheimer’s Disease

For years, neuroscientists have attributed Alzheimer’s disease to structural malformations observed in the brains of Alzheimer’s patients.96 Terms used to describe these Alzheimer’s alterations include beta-amyloid plaque and neurofibrillary tangles.

Newer findings, however, link hypoperfusion to the formation and progression of these Alzheimer’s malformations. One recent human study found cerebral blood flow to be 20% lower in Alzheimer’s patients compared to a similar aged group with normal cognitive function.97This correlates with other research showing that cerebral blood flow is decreased in Alzheimer’s patients.14-16

Mild cognitive impairment is the transitional clinical stage between loss of cognition in normal aging and severe dementia. Both Alzheimer’s disease and mild cognitive impairment have been linked to abnormalities in brain perfusion.98

A study evaluated brain perfusion in patients with mild Alzheimer’s dementia and patients with mild cognitive impairment, and compared them to cognitively healthy elderly controls. The researchers found lower cerebral perfusion throughout many regions of the brain in patients with mild cognitive impairment and Alzheimer’s and suggested that evaluating cerebral perfusion might better diagnose those with serious neurological impairment.99

In an intriguing study that shatters conventional wisdom, researchers identified elderly people that had significant amounts of beta-amyloid plaque and neurofibrillary tangles, but were not demented. The researchers compared these non-demented individuals to Alzheimer’s patients. The difference was the amount of amyloid plaque found in the vasculature was almost 2-fold higher in the Alzheimer’s patients. This led the scientists to conclude that in addition to Alzheimer’s structural abnormalities, “vascular integrity must play an important role in cognitive failure.”100

Another study performed mental tests and brain perfusion tests (SPECT scans) on normal elderly individuals, those with mild cognitive impairment, and those with Alzheimer’s patients. Over a two-year period, there was a worsening of the mental test scores in the two cognitively dysfunctional groups. In the mild cognitive impairment and Alzheimer’s groups, cerebral perfusion fell in the left postsubicular area of the brain.101 The postsubicular region is necessary for the recognition of familiar environments, and is required for the formation of new object–place associations that support recognition memory.102

This study showed that Alzheimer’s patients had extensive cerebral perfusion reductions. Worsening of mental test scores was related to decreased perfusion in multiple regions of the brain (bilateral middle, posterior cingulate, left frontal, temporal and parietal areas, and postsubicular area).101

This corroborates other studies that correlate cerebral hypoperfusion with diagnosis of Alzheimer’s disease.

Exercise Reverses Brain Decay

Several human studies show that aerobic exercise increases the size of the cognitive centers of the brain and improves memory.104,105

One study showed that 1-2 years of aerobic exercise increased hippocampal volume by 2%, which was accompanied by improved memory function.104 Considering hippocampal volume often shrinks with aging, this improvement in size should be viewed as substantial.

A review of several studies showed better physical fitness to be associated with improved cognitive functioning. This review showed that beneficial mechanisms behind the effect of exercise on cognitive health were “increases in brain perfusion and the ability of cerebral blood vessels to respond to demand.”105

Green Tea Inhibits Hypoperfusion Damage

Green Tea Inhibits Hypoperfusion Damage  

Cerebral hypoperfusion results in oxidative stress that leads to neurodegenerative disease.

Health conscious people today take antioxidant supplements to protect against free radicals and the oxidative damage they inflict.

A study was done on rats where experimental cerebral hypoperfusion was induced and the effects of green tea extract evaluated.106 The scientists wanted to see if two different doses of green tea polyphenols over a 4-8 week time period could prevent cognitive deficits and the oxidative brain cell damage that occurs in response to hypoperfusion.

High-dose green tea extract was found to scavenge oxygen free radicals, enhance antioxidant potential, decrease lipid peroxide production, and reduce oxidative DNA damage. The high-dose group had better spatial learning and memory than saline-treated rats. These beneficial effects, however, were not found in the lower-dose group.106

The human equivalent amount of green tea extract in the high-dose group would be about 4,800 mg/day. The low dose human equivalent amount would be 1,200 mg of green tea extract daily.

The first supplement I take upon wakening is a 725 mg green tea extract capsule. There’s no particular reason for this, but since I don’t drink coffee or tea regularly, it seems to make sense to swallow a tea extract capsule when my day starts. To emulate this rat study, I would have to swallow six of these green tea extract capsules.

I do not believe, however, that I or most of our members need to take anywhere near this high dose of green tea. That’s because we take so many other antioxidants like gamma tocopherol,107 astaxanthin,108,109 benfotiamine,110 PQQ,53,111 lipoic acid,112,113 and carnosine114,115 that are proven to guard against oxidative stress in the brain.

So I will continue my one green tea extract capsule each morning and rely on the many other antioxidants I take to suppress the free radicals that are inevitably generated in my 59-year-old brain.

New Way To Protect Against Brain Aging

Proven methods exist to help reverse hypoperfusion and better oxygenate our brain.63 That alone, however, will not fully restore youthful cerebral functions. Additional pathologic mechanisms underlie age-associated mental impairment.54 These damaging factors should all be corrected if we are to achieve meaningful improvement in our thinking ability.

It is refreshing to know that studies are documenting the brain benefits of fish oil,116 carnitine,80 lipoic acid,80,84 vinpocetine,70,103,117-119 and other nutrients Life Extension members have long used.

What’s needed now is something to fill “missing gaps” that enable degenerative aging processes to destroy our precious neurons.

A solution has been found in an extract from an Oriental orchid called Gastrodia elata, which is used in China to treat neurological disorders,120 just as vinpocetine is prescribed in Europe for conditions relating to hypoperfusion.121

Gastrodia acts as a “brain shield,” calming neurons and protecting them from oxidant,122,123 inflammatory,120,124-127 and excitatory damage122,128-137 associated with hypoperfusion and stroke.122,136-142 As a result, Gastrodia helps prevent cognitive decline and memory loss.123,125,143-147

As you’ll read, Gastrodia has even been shown to protect against cognitive impairment inflicted during heart bypass surgery.

Surgery-Induced Hypoperfusion

Surgery-Induced Hypoperfusion  

Each year, hundreds of thousands of Americans undergo heart surgery that requires that they be placed on a heart-lung machine.148 A tragic side effect to this procedure is that it can cause capillary blockage in the brain that leads to hypoperfusion and severe cognitive deficits.149

Scientists have recently uncovered a unique reason why this occurs. During heart surgery, blood bleeding from surgical wounds is suctioned up into the cardio-pulmonary circuit of the heart-lung machine and then reintroduced into the patient.58

This suctioned blood is laden with lipids (fats), especially from the sternal bone marrow in the chest that has to be cut through to gain access to the heart. These lipid globules slip by the normal filters of the heart-lung machine and travel to the brain where they become lodged in capillaries as microemboli.58

While some of these microemboli pass through the brain in a few hours or days, some remain impacted for weeks or longer.58 These microemboli block capillary blood flow, causing hypoperfusion and eventual death to affected brain cells.

A novel method of protecting the brain against this type of hypoperfusion is to run suctioned blood through a special device called a “cell saver” that cleanses blood of lipids as it separates out red cells. This technique has been documented in experimental models to improve surgical outcomes.58

Some surgical patients undergo accelerated cognitive declines that can continue 3-5 years after heart surgeries and can lead to dementia.58,150 It is thus well worth implementing multiple strategies to protect against the hypoperfusion that results when lipid globules rapidly release into the bloodstream.

Gastrodia Extract Proven Under Toughest Conditions

A study of 200 cardiac surgery patients was done where prior to surgery, half the group was administered Gastrodia extract intravenously and the other half a placebo.151 Five different areas of cognitive function were measured before surgery began.

After the surgery and just prior to being discharged from the hospital, 42% of the placebo patients had a deficit in at least one area of cognitive measurement, which is about the standard number expected. In the group given Gastrodia extract, however, only 9% showed any evidence of cognitive impairment.151

A three-month follow-up evaluation showed that 31% of the placebo arm still had at least one cognitive deficit, as opposed to only 6% of patients given Gastrodia.151This follow-up reveals how long cognitive deficits persist in patients undergoing heart surgery and the statistically and clinically significant protection conferred by Gastrodia extract.

The kind of brain injury suffered during cardiac surgery is analogous to accelerated aging, though much worse in some ways. That’s because the sudden release of lipid globules is not a natural event that your body has a defense against. The most common natural type of emboli comes from blood clots that break lose inside blood vessels. Your body has enzymes that may dissolve these tiny blood clots, but not necessarily the lipid globules released during certain surgeries. While surgery-induced capillary impaction occurs acutely, its effects may persist indefinitely as chronically hypoperfused areas of the brain slowly die.58

The ability of Gastrodia to protect humans undergoing this massive attack of lipid (fat) globules signifies a tremendous ability of this orchid extract to protect against “normal” pathologies in the aging brain. These include inflammation, excitotoxicity, oxidation, hypoperfusion, and structural changes in neurons.120,122-137 The science, in fact, shows that Gastrodia provides a virtual “shield” against the most common causes of brain aging.

Gastrodia extract has been added to the most popular formula Life Extension members take to protect and enhance their neurological functions. It’s also available as a stand-alone supplement.

Our “Fragile” Aging Brains

Our “Fragile” Aging Brains  

The most important organ in our body is also the most fragile.

Stroke is a leading cause of death in the United States.152 Alzheimer’s incidence is spiraling upwards.153 Both are related to hypoperfusion, as is the mental slowdown that aging people encounter.

We will soon be publishing an article on a disease that virtually none of you knew existed. This disease (leukoaraiosis) involves deleterious changes in the brain’s vital white matter where transmission of nerve impulses enables one part of the brain to communicate with other parts of the brain.154 Enhanced imaging technologies are enabling doctors to identify this cognitive-robbing disorder in huge numbers of aging individuals.154,155 It shouldn’t surprise you to learn that an underlying culprit behind this white matter disorder is hypoperfusion.154 This means all the good steps you are taking to protect against known brain disorders may also shield you against this new one.

We’re also going to discuss the science behind keeping one’s overall neurological function in the most youthful condition possible, such as exercising your brain by reading articles like this that inundate you with new information.

An achievable New Year’s resolution is to take assertive steps to improve your cognitive function while slashing your risk of neurodegenerative disease. This article has provided practical steps that can be initiated immediately, including adding Gastrodia to one’s daily supplement program.

Time Of Year To Stock Up On Life-Saving Supplements

Once a year, we discount all of our cutting-edge formulas so that our members can stock up at extra-low prices.

We hope you’ll take advantage of this year’s Super Sale to obtain premium-grade supplements to protect your health today, while helping to support biomedical research aimed at achieving unprecedented life span extensions.

In 2012, Life Extension spent a record $14.6 million on some of the world’s most ambitious projects to halt aging and eliminate premature death. In this issue, we describe recent grants made to pioneering young scientists. These aggressive research programs are only made possible through the generous support of our many members.

I cannot tell you how much your support through product purchases is needed and appreciated to battle inept bureaucrats who would prefer our non-profit research foundation cease to exist.

Until February 3, 2014, members take advantage of Super Sale discounts to stock up on cutting-edge formulas designed to circumvent aging processes (including loss of neurological function) that used to be considered inevitable consequences of living too long!

For longer life,

For Longer Life

William Faloon

References

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