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Brain Ketones Vs Glucose

Can Ketones Help Rescue Brain Fuel Supply In Later Life? Implications For Cognitive Health During Aging And The Treatment Of Alzheimer’s Disease

Can Ketones Help Rescue Brain Fuel Supply In Later Life? Implications For Cognitive Health During Aging And The Treatment Of Alzheimer’s Disease

1Research Center on Aging, Sherbrooke, QC, Canada 2Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada 3Department of Pharmacology and Physiology, Université de Sherbrooke, Sherbrooke, QC, Canada We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer’s disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults <40 years-old who have genetic or lifestyle risk factors for AD but in whom cognitive decline has not yet started. Examples include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of AD. (iii) Regional brain glucose uptake is impaired in AD and mild cognitive impairment (MCI), but brain uptake of ketones (beta-hydroxybutyrate and acetoacetate), remains the same in AD and MCI as in cognitively healthy age-matched controls. These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD. Since glucose is the brain’s main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD. (iv) Interventions that raise ketone availability to the brain improve cognitive outcomes in both MCI and AD as well as in acute experimental hypoglycemia. Ketones are the brain’s main alternative fuel to glucose and brain ketone uptake is still normal in MCI and in early AD, which would help explain why ketogenic i Continue reading >>

Fueling Up: Glucose, Ketones & Your Brain

Fueling Up: Glucose, Ketones & Your Brain

Last week, Accera, Inc. reported that its drug AC-1204 failed in a phase 3 clinical trial for Alzheimer's disease. Unlike recent high-profile drug failures from Lilly and Merck, Accera's drug was not targeting beta-amyloid plaques. Instead, it attempted to slow the progression of Alzheimer's by affecting how neurons get and use energy. The failure of Accera's drug is raising questions about whether targeting the energy system in neurons makes sense as an approach for treating Alzheimer's disease. Glucose (sugar) supplies most of the energy to the brain. But as we age, our brains can become less efficient at converting glucose into energy. In Alzheimer's patients, glucose utilization is even more compromised. However, when there is insufficient glucose, the brain can use a backup fuel source—ketones [1]. Accera's AC-1204 attempted to harness this backup system. AC-1204 is a formulation of caprylic acid, which is a type of medium chain triglyceride (MCT) commonly found in foods such as coconut oil. The body can convert MCTs into ketones, the brain's alternative energy source. Some evidence suggests that in early Alzheimer's patients, the brain can still use ketones, even if it is less able to use glucose [2]. Accera reported that its trial may have failed because AC-1204 failed to increase the concentration of ketones in the blood, which affects the ability of the brain to use them as energy. The Alzheimer's Drug Discovery Foundation (ADDF), the nonprofit behind Cognitive Vitality, is funding several Alzheimer's treatments that target the brain's energy system in more direct ways. At Imperial College London, Dr. Paul Edison is conducting a clinical trial to test liraglutide, a diabetes drug that appears to increase the brain's ability to use glucose. Dr. Christian Holsc Continue reading >>

Ketones Suppress Brain Glucose Consumption

Ketones Suppress Brain Glucose Consumption

Go to: 1. INTRODUCTION Neurodegeneration after oxidative stress limits the recovery of tissue response and appears to be caused by impaired glycolysis. If indeed there is a defect in glucose metabolism it might be beneficial to supplement energy metabolism with an alternate substrate. It was suggested that brain can supplement glucose as the principal energy substrate with ketone bodies1–3 without altering oxygen consumption4,5. Classic studies of ketosis induced by fasting or starvation in humans showed that brain function was maintained which was attributed to the utilization (oxidation) of ketone bodies as alternate energy substrates to glucose by the brain6. Rats that have been fasted for 2–3 days showed no difference in cerebral blood flow (CBF) or CMRO27. One mechanism by which ketosis might be beneficial is through the metabolic step where ketones enter the TCA cycle at the level of citrate bypassing glycolysis, the step after pyruvate dehydrogenase complex where the enzyme activity is often impaired. Through feed-back regulation, ketones are known to down regulate glycolytic rates at various levels such as citrate, phosphofructokinase and/or hexokinase. In addition, particularly in brain, ketones are a carbon source for glutamate (anaplerosis) and thus help to balance glutamate/glutamine homeostasis through stabilization of energy metabolism in astrocyte following recovery from a hypoxic/ischemic event. Based on our experiments and evidence in the literature, we have developed the hypothesis that ketones are effective against pathology associated with altered glucose metabolism, the rationale being that ketosis helps to regulate glucose metabolism. In this study, the effects of ketosis on the local cerebral metabolic rate of glucose consumption (CMRglu) were Continue reading >>

Does The Brain Function Better On Ketones (ketone Fuel) Or Glucose?

Does The Brain Function Better On Ketones (ketone Fuel) Or Glucose?

In some cases yes, and in others no. Li Xinran mentions epilepsy, but that may not be a good example for overall brain function, rather only an improvement of a tiny epileptogenic trigger locus. Let me also mention that membrane stabilization from fatty acids and cholesterol would not take place from direct supplementation of beta-hydroxybutyrate and beta-ketobutyrate. Those are carb substances delivered to the brain by the blood and used to generate energy. The brain's use of ketone fuels (sans acetone) can certainly augment the brain's energy. But this is not particularly significant in magnitude. The brain's use of glucose is not impaired by insulin resistance like other tissues. Bypassing glucose does not give the energy windfall to the brain that it does for heart, liver, kidney, lung and muscles, except for the brain's neuroendocrine glands that stick through the blood-brain barrier and do use the GLUT-4 glucose receptors that are impaired by insulin resistance. There is another potential brain-energy impairment when ketone fuels are derived from ketosis (wholesale beta-oxidation of fat) and not from some kind of IV or dietary supplementation. That is impairment of gluconeogenesis by inadequate substrate. When in ketosis, the body converts the glycerol (glycerine) from the triglyceride backbone into glucose. But the amount of glycerol from catabolized fat is relatively low, especially when measured by energy content. So the body also makes glucose from amino acids, which may not be in good supply. Catabolism of muscle protein to make glucose works, but only for a limited time, and with serious long-term consequences. One could eat more protein, and supplement amino acids, glycerine, fatty alcohols and small amounts of glucose/carb to offset this liability, but eve Continue reading >>

Keto Diet: Ketones Vs Glucose For Brain Function | Advanced Nutrition

Keto Diet: Ketones Vs Glucose For Brain Function | Advanced Nutrition

Ketosis is a metabolic state where the liver takes proteins and fat and produces molecules to use for energy. Ketosis allows a starving person to survive for days (or even months). Some athletes see improvements while others feel miserable whenever they are in a condition that is ketogenic. Is a ketogenic diet right for you? Ketogenic Diet and the Brain Your brain is about 2 percent of your body mass, even though it requires approximately 20 percent of your basal metabolic rate, more if you are a thinker. Various parts of your brain use different amounts of glucose, and almost twice as much in the morning. You will need to fuel your mind more if you are using your mind working hard through the day and solving problems. If you’re working more on engine control, (state a skill involving precision or equilibrium), then you will use less glucose. Many people can attest to how much energy is used by the brain when challenged. Although sugar is run off by our brains rather than fat, they are also able to run off of ketones as an alternate fuel source. People who market diets tend to be aware the simple fact that an increase in ketones improves repair and the healing of neurons and increases the neurotransmitter GABA. (GABA makes it possible to sleep. It’s also the main neurotransmitter that sleep drugs and antipsychotic drugs influence.) Due to the impact of ketones on the brain, a ketogenic diet can really help those with seizures. Of course, ketosis means you’re burning far more fat, (in the form of ketones), for energy compared to glucose, and also, for the most part, that’s usually great thing. You won’t venture to some harmful diabetic ketosis amount as long as you are generating even only a tiny amount of insulin. So as long as you are not Type 2 or a Type 1, Continue reading >>

Brain, Livin' On Ketones - A Molecular Neuroscience Look At The Ketogenic Diet

Brain, Livin' On Ketones - A Molecular Neuroscience Look At The Ketogenic Diet

Edited October 3, 2013: A 2.0 version of this post can be found at Scientific American MIND Guest blogs, here. And here's me talking about it. Feel free to check it out! Remember when your high school biology teacher said that the brain absolutely NEEDS glucose to function? Well, that’s not entirely true. Under severe carbohydrate restriction, the brain can adapt and start burning ketones as fuel. Originally devised as a therapy for drug-resistant epilepsy in children, the ketogenic diet (keto) has been gaining popularity lately. It’s a high fat, moderate protein and low carbohydrate diet (LCHF) designed to force the body to go into a state called metabolic ketosis. With the advent of books like “Good Calories, Bad Calories” and “Why we get fat”, LCHF diets are increasingly touted as the magic bullet to weight loss. While there is considerable interest in the medical community in using the ketogenic diet to manage metabolic syndrome or prevent cardiovascular disease, more attention has focused on its role in drug-resistant seizure management and (potentially) neuroprotective effects in brain damage. In the last decade, keto has been shown to improve memory in patients at risk for Alzheimer’s disease, stabilize mood in type II bipolar disorder, reduce symptoms in Parkinson’s disease and even ameliorate some behavioral and social deficits in autism. Keto also seems to decrease brain cancer progression. ALL without observable side effects. Although most of these studies were unblinded (hence placebo can’t be ruled out), the effect is still amazing. What is going on in the brain? And why aren’t pharmaceutical companies racing to package keto into a convenient treat-all 3-a-day pill? How does the body go into ketosis? Source: Simple speaking, strict carbo Continue reading >>

Ketone Bodies

Ketone Bodies

Ketone bodies Acetone Acetoacetic acid (R)-beta-Hydroxybutyric acid Ketone bodies are three water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone) that are produced by the liver from fatty acids[1] during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise,[2], alcoholism or in untreated (or inadequately treated) type 1 diabetes mellitus. These ketone bodies are readily picked up by the extra-hepatic tissues, and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy.[3] In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids. Ketone bodies are produced by the liver under the circumstances listed above (i.e. fasting, starving, low carbohydrate diets, prolonged exercise and untreated type 1 diabetes mellitus) as a result of intense gluconeogenesis, which is the production of glucose from non-carbohydrate sources (not including fatty acids).[1] They are therefore always released into the blood by the liver together with newly produced glucose, after the liver glycogen stores have been depleted (these glycogen stores are depleted after only 24 hours of fasting)[1]. When two acetyl-CoA molecules lose their -CoAs, (or Co-enzyme A groups) they can form a (covalent) dimer called acetoacetate. Beta-hydroxybutyrate is a reduced form of acetoacetate, in which the ketone group is converted into an alcohol (or hydroxyl) group (see illustration on the right). Both are 4-carbon molecules, that can readily be converted back into acetyl-CoA by most tissues of the body, with the notable exception of the liver. Acetone is the decarboxylated form of acetoacetate which cannot be converted Continue reading >>

Ketones: Your Brain’s Preferred Fuel Source

Ketones: Your Brain’s Preferred Fuel Source

Ketones have long been touted as a superior fuel source for the brain that possesses a wide array of cognitive benefits. Our brains are made up of two types of cells, neurons, and glial cells, and both are imperative for our brains to function properly (1). Under normal physiological conditions, the principle energy source utilized by the brain cells is glucose (2). Glucose transporters saturate brain capillaries to allow glucose to cross the blood-brain barrier. Once in the brain, glucose is metabolized to pyruvate which enters the mitochondria of the brain cells to ultimately generate energy through aerobic metabolism (3). However, ketone bodies may also provide energy to the brain through different mechanisms. Brain Fuel In addition to glucose, brain cells can derive energy from monocarboxylates which include lactate and the ketone bodies beta-hydroxybutyrate (β-HB) and acetoacetate (AcAc) (2). It is controversial whether or not lactate can be used as a fuel source in the brain; however, many laboratories have reported that BHB is a major fuel supplier for the brain, especially under specific physiological conditions (3,4). BHB and glucose do not nourish the brain uniformly but rather have specific areas of localization. BHB accumulates primarily in the pituitary and pineal glands, as well as in portions of the hypothalamus, and the lower cortical layers (4). Physiological conditions that elevate BHB and consequently provide increased energy to the aforementioned areas of the brain include starvation, fasting, pregnancy, prolonged exercise, uremia, during the prenatal period, infancy, during the chronic consumption of a high fat/low carbohydrate ketogenic diet, and possibly even ketone supplementation (4). Ketones: Brain’s Utilization Capacity Low circulating gluc Continue reading >>

Burn Your Own Fat For Fuel Using Ketones

Burn Your Own Fat For Fuel Using Ketones

Have you ever heard of a ketogenic diet? A ketogenic diet means your body is using ketones for energy production rather than sugar. Ketones are an alternative fuel source for the body, and are produced when eating a high fat and low carbohydrate diet. This type of diet is called "ketogenic" because your body is in a state of "ketosis" meaning fueled by ketones rather than sugar (aka glucose). Here are 9 reasons why you want your body to be fueled by ketones instead of sugar: 1. You literally burn your own fat for energy Your body can run on either glucose or ketones. Which would you choose? Well, when you look at what this actually means: Glucose is produced from the breakdown of glycogen (strings of glucose), this means you are burning glycogen to produce fuel for your body. Ketones on the other hand are produced from the breakdown of fat (fatty acids), this means you are literally burning your own fat stores to produce energy. You can make ketones from eating very low carb (sub 50 net carbs), fasting, or consuming a product that can induce or supply the production of ketones (such as MCT oil). 2. No more “Hangry” You know that feeling when are so starving that every little thing is irritating, and you need to eat right. NOW? Terrible feeling right? Blame the carbs! After a blood sugar spike from eating carbs, this will trigger insulin whose job is to get that sugar out of your blood as fast as it can (because sugar in your blood is toxic and inflammatory), resulting in an even lower blood sugar than you started with. Low blood sugar (aka hypoglycemia) is that terrible anxiousness you are feeling. No bueno! And how do you make that feeling go away the fastest? Eating sugar. And the vicious cycle continues. Fat is the only macronutrient that won't raise blood sugar, Continue reading >>

Are Carbs Helping Or Destroying Your Brain?

Are Carbs Helping Or Destroying Your Brain?

Your brain is a complicated organ. Extremely complicated. In fact, the human brain is complicated enough that the human brain can’t even understand the human brain. Modern science has discovered many interesting factoids about how our brains function, including things like the location of our memory center, the location of our speech center, where long term memories are formed, and how sleep restores neurological function. Yet despite a very deep understanding of this mysterious organ, scientists routinely debate the answer to an incredibly basic question: Are carbohydrates good or bad for your brain? It’s a simple question, really. But the answer is complicated. Very complicated. Attempting to understand how to fuel your brain optimally is a challenging task indeed. Read 10 articles on the internet and you’re presented with 10 different answers. Read 10 more articles and you’re bound to get extremely confused. In the quest for understanding what foods fuel your brain optimally, there seem to be two main reoccurring themes, shown below. In order to get to the bottom of this debate, let’s dig into basic brain physiology. Theme #1: Your brain loves carbohydrates Your Brain Is A Glucose Hog Make no mistake, your brain is the most selfish organ in your body. Think of your brain as a metabolic pig – constantly taking energy from the bloodstream and storing none of it for itself. It’s no wonder that your brain is one of the hungriest organs in your body – more than 80 billion neurons are sending and receiving electrical signals 24 hours a day, creating complex thoughts and emotions. Even when you are asleep, neurons in your brain are busy sending a flurry of electrical signals from one region to the next, consolidating memories and information from the previou Continue reading >>

Ketone Bodies Provide An Alternative Fuel Source For Neurons1

Ketone Bodies Provide An Alternative Fuel Source For Neurons1

Ketone bodies are the brain’s natural back-up fuel2 When glucose levels are low, for example during periods of starvation or from a ketogenic diet, the liver is triggered to produce ketone bodies as a back-up fuel source.2 In adults, significantly elevated ketone body levels are usually encountered only when insulin signaling is disrupted (eg, in diabetes). Therefore, ketosis is often viewed as an abnormal condition. However, ketosis serves as an important survival function during mammalian development and when food is scarce.3 Properties of ketone bodies Ketone body metabolism may have a number of advantages over glucose metabolism: Is able to readily cross blood-brain barrier1 Improves metabolic efficiency4 Reduces production of reactive oxygen species4 Increases antioxidant capacity4 May assist brain cells in clearing away debris from disease or injury3 Can supply up to 60% of the brain’s energy needs2 Metabolism of glucose and ketone bodies in neuronal mitochondria4 Ketone bodies do not undergo glycolysis and are able to enter the TCA cycle in fewer steps than glucose. Acetyl CoA, acetyl coenzyme A; ATP, adenosine triphosphate; TCA cycle, tricarboxylic acid cycle (also known as the citric acid cycle or Krebs cycle). Elevating ketone body levels has a long clinical history5 1970 Modifications made to ketogenic diet to include medium-chain triglycerides. All variations approximately equal in reducing seizures7,8 2004 Phase IIa trial demonstrates correlation between ketosis and improved Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS–Cog) scores in APOE4(-) patients with mild to moderate Alzheimer’s disease11 2009 Medium-chain triglycerides (MCTs) as a source of ketone bodies2 MCTs contain medium-chain fatty acids (octanoic [8:0] and decanoic Continue reading >>

Why The Brain Is Key To Your Keto-adaption

Why The Brain Is Key To Your Keto-adaption

Your brain only represents 2% of your bodyweight, yet uses 20-25% of your total resting energy expenditure. Roughly 500 calories per day are needed just for the brain. If you have always eaten a high carb based diet your brain runs on 100% glucose (carbohydrates). And you only have a very small reservoir of glucose available to you. I will try and show you why your brain is really the key piece of the puzzle in keto-adaption. First I need to explain a few things. Our body`s cells can use 2 sources of fuel for energy, glucose (carbohydrate), or fat. There are a few cells that can only use glucose for energy. It is because of these cells, that the human body must maintain a certain level of glucose, at all times. This is called glucose homeostasis. Glucose homeostasis simply means this. The human body is required to maintain tight control of your blood sugar levels 70-110. It is required to maintain this level of blood sugar for the few cells, that can only use glucose for energy. These cells are found in the brain (if not keto-adapted), the red blood cells, a few in the kidneys, and your retinas. Also if your blood sugar goes much over 110, this becomes toxic to your cells, and if your blood sugar goes to low, you will not have the necessary glucose needed, to maintain fuel, to these cells. So this is glucose homeostasis. Why is this important? The brain, being the main control center of the body, must be keep going every second, of every day. The red blood cells carry the oxygen in the bloodstream, You must be able to breath, to remain alive. Your kidneys filter your blood, No more blood, and you are no longer alive, And I would say your eyesight is pretty important also. Here are the amounts of glucose needed daily, for the cells that can only run on glucose. 1- The br Continue reading >>

How Low-carb And Ketogenic Diets Boost Brain Health

How Low-carb And Ketogenic Diets Boost Brain Health

Low-carb and ketogenic diets have many health benefits. For example, it is well known that they can cause weight loss and help fight diabetes. However, they are also beneficial for certain brain disorders. This article explores how low-carb and ketogenic diets affect the brain. Although there is a lot of overlap between low-carb and ketogenic diets, there are also a few important differences. Ketogenic diet: Carbs are limited to 50 grams or less per day. A major goal is to increase blood levels of ketones, molecules that can partly replace carbs as an energy source for the brain. Low-carb diet: Protein is usually not restricted. Ketones may or may not rise to high levels in the blood. On a ketogenic diet, the brain is mainly fueled by ketones. These are produced in the liver when carb intake is very low. On a standard low-carb diet, the brain will still be largely dependent on glucose, although it may burn more ketones than on a regular diet. Low-carb and ketogenic diets are similar in many ways. However, a ketogenic diets contains even fewer carbs, and will lead to a significant rise in blood levels of ketones. You may have heard that your brain needs 130 grams of carbs per day to function properly. This is one of the most common myths about low-carb diets. In fact, a report by the US Institute of Medicine's Food and Nutrition Board states: "The lower limit of dietary carbohydrates compatible with life apparently is zero, provided that adequate amounts of protein and fat are consumed." Although a zero-carb diet isn't recommended because it eliminates many healthy foods, you can definitely eat much less than 130 grams per day and maintain good brain function. It is a common myth that you need to eat 130 grams of carbs per day to provide the brain with energy. Low-carb d Continue reading >>

Inverse Relationship Between Brain Glucose And Ketone Metabolism In Adults During Short-term Moderate Dietary Ketosis: A Dual Tracer Quantitative Positron Emission Tomography Study

Inverse Relationship Between Brain Glucose And Ketone Metabolism In Adults During Short-term Moderate Dietary Ketosis: A Dual Tracer Quantitative Positron Emission Tomography Study

Ketones (principally β-hydroxybutyrate and acetoacetate (AcAc)) are an important alternative fuel to glucose for the human brain, but their utilisation by the brain remains poorly understood. Our objective was to use positron emission tomography (PET) to assess the impact of diet-induced moderate ketosis on cerebral metabolic rate of acetoacetate (CMRa) and glucose (CMRglc) in healthy adults. Ten participants (35 ± 15 y) received a very high fat ketogenic diet (KD) (4.5:1; lipid:protein plus carbohydrates) for four days. CMRa and CMRglc were quantified by PET before and after the KD with the tracers, 11C-AcAc and 18F-fluorodeoxyglucose (18F-FDG), respectively. During the KD, plasma ketones increased 8-fold (p = 0.005) while plasma glucose decreased by 24% (p = 0.005). CMRa increased 6-fold (p = 0.005), whereas CMRglc decreased by 20% (p = 0.014) on the KD. Plasma ketones were positively correlated with CMRa (r = 0.93; p < 0.0001). After four days on the KD, CMRa represented 17% of whole brain energy requirements in healthy adults with a 2-fold difference across brain regions (12–24%). The CMR of ketones (AcAc and β-hydroxybutyrate combined) while on the KD was estimated to represent about 33% of brain energy requirements or approximately double the CMRa. Whether increased ketone availability raises CMR of ketones to the same extent in older people as observed here or in conditions in which chronic brain glucose hypometabolism is present remains to be determined. Continue reading >>

Exogenous Ketones For Fat Burn

Exogenous Ketones For Fat Burn

OVERVIEW Exogenous ketones are the newest scientific breakthrough in the world of health and wellness, making the job of achieving ketosis, the state in which the body is burning fat/ketones as fuel rather than glucose, much easier. They come in powder form and are ingested exogenously (a fancy word for outside the body). Exogenous ketones are comprised of beta-hydroxybutyrate salts, which flood your bloodstream with ketones and put the body in ketosis within 30-60 minutes. This means that you can reap all the amazing health benefits of being in ketosis in a simple and effective way (just mix the exogenous ketones with water & drink!). Research is now linking exogenous ketones to a multitude of benefits, including more efficient weight loss, athletic performance enhancement, cancer prevention, cognitive improvement, neuroprotection and anti-inflammatory properties. (See research links below.) In addition, exogenous ketones are an extremely useful tool to easily transition to the ketogenic diet. When taken daily, they can reduce carb/sugar cravings, turn on your fat burners, give you more energy, and keep "low-carb flu" at bay. So bottom line, exogenous ketones are perfect for anyone looking to improve their health and wellbeing. WHY USE THEM Reason #1 - Fat Burning Exogenous ketones for fat burn. Taking exogenous ketones will get you into ketosis quickly. Once your body is done using the exogenous ketones you ingested as fuel, then it will start looking for other places to get ketones from. And lucky for you, ketones are made from the fat stored in your body! So as your body produces more of these ketones as fuel, you end up burning fat. Reason #2 - Energy Our bodies use ketones via our mitochondria to generate energy. They are an alternative fuel source to glucose and Continue reading >>

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