Of the mice that received the treatment, 75 percent got their memory functions back.
Australian researchers have come up with a non-invasive ultrasound technology that clears the brain of neurotoxic amyloid plaques – structures that are responsible for memory loss and a decline in cognitive function in Alzheimer’s patients.
If a person has Alzheimer’s disease, it’s usually the result of a build-up of two types of lesions – amyloid plaques, and neurofibrillary tangles. Amyloid plaques sit between the neurons and end up as dense clusters of beta-amyloid molecules, a sticky type of protein that clumps together and forms plaques.
Neurofibrillary tangles are found inside the neurons of the brain, and they’re caused by defective tau proteins that clump up into a thick, insoluble mass. This causes tiny filaments called microtubules to get all twisted, which disrupts the transportation of essential materials such as nutrients and organelles along them, just like when you twist up the vacuum cleaner tube.
As we don’t have any kind of vaccine or preventative measure for Alzheimer’s – a disease that affects 343,000 people in Australia, and 50 million worldwide – it’s been a race to figure out how best to treat it, starting with how to clear the build-up of defective beta-amyloid and tau proteins from a patient’s brain. Now a team from the Queensland Brain Institute (QBI) at the University of Queensland have come up with a pretty promising solution for removing the former.
Publishing in Science Translational Medicine, the team describes the technique as using a particular type of ultrasound called a focused therapeutic ultrasound, which non-invasively beams sound waves into the brain tissue. By oscillating super-fast, these sound waves are able to gently open up the blood-brain barrier, which is a layer that protects the brain against bacteria, and stimulate the brain’s microglial cells to activate. Microglila cells are basically waste-removal cells, so they’re able to clear out the toxic beta-amyloid clumps that are responsible for the worst symptoms of Alzheimer’s.
The team reports fully restoring the memory function of 75 percent of the mice they tested it on, with zero damage to the surrounding brain tissue. They found that the treated mice displayed improved performance in three memory tasks – a maze, a test to get them to recognise new objects, and one to get them to remember the places they should avoid.
“We’re extremely excited by this innovation of treating Alzheimer’s without using drug therapeutics,” one of the team, Jürgen Götz, said in a press release. “The word ‘breakthrough’ is often misused, but in this case I think this really does fundamentally change our understanding of how to treat this disease, and I foresee a great future for this approach.”
The team says they’re planning on starting trials with higher animal models, such as sheep, and hope to get their human trials underway in 2017.
You can hear an ABC radio interview with the team here.
Surgeons in Cambridgeshire have performed the first heart transplant in Europe using a non-beating heart.
Donor hearts are usually from people who are brain-stem dead, but whose hearts are still beating. In this case, the organ came from a donor after their heart and lungs had stopped functioning, so-called circulatory death. Papworth hospital says the technique could increase the number of hearts available by at least 25%. The recipient Huseyin Ulucan, 60, from London, had a heart attack in 2008. He said: “Before the surgery, I could barely walk and I got out of breath very easily, I really had no quality of life.” He said he was “delighted” with the improvement in health since the transplant. “Now I’m feeling stronger every day, and I walked into the hospital this morning without any problem,” he said.
There have been 171 heart transplant in the past 12 months in the UK. But demand exceeds supply, and some patients have to wait up to three years for a suitable organ. Many patients die before an organ becomes available. Non-beating-heart donors provide kidneys, livers and other organs, but until now it has not been possible to use the heart because of concerns it would suffer damage. The new procedure involved re-starting the heart in the donor five minutes after death and perfusing it and other vital organs with blood and nutrients at body temperature. The lead transplant surgeon, Stephen Large, said: “We had the heart beating for about 50 minutes, and by monitoring its function were able to tell that it was in very good condition.”
The organ was then removed and transferred to a heart-in-a-box machine, where it was kept nourished and beating for a further three hours before the transplant surgery at Papworth. The organ care system is also used for maintaining lung, liver and kidneys outside the body. The standard method for transporting hearts and other organs for transplant is to pack them in ice, but some organs can be damaged by this process. The Papworth team said that restoring the heartbeat after death and keeping the organ nourished had helped reduce damage in the heart muscle. Last year surgeons in Australia performed the world’s first transplant using a non-beating heart, also using the heart-in-a-box technology.
TransMedics, the US company that makes the organ care machine, said each unit cost £150,000 plus £25,000 per patient transplanted. Papworth and Harefield hospitals are the only two heart transplant units in the UK who use the device. Prof James Neuberger, associate medical director for organ donation and transplantation at NHS Blood and Transplant, said: “Sadly, there is a shortage of organs for transplant across the UK and patients die in need of an organ. “We hope Papworth’s work and similar work being developed elsewhere will result in more hearts being donated and more patients benefiting from a transplant in the future. “We are immensely grateful to the donor’s family, and we hope they are taking great comfort in knowing that their relative’s organs have saved lives and have also made an important contribution to heart transplantation in the UK.”
Dr. S is a young surgeon who graduated shortly after the outbreak of the crisis in Syria. He now works in a makeshift hospital in a semi-rural neighbourhood located to the east of Damascus. This is a facility that received dedicated MSF support and supplies throughout the period of siege, support that continues on a regular monthly basis to this day. He tells the story of his medical journey – an experience that parallels the war in the country.
A temporary truce that death could not penetrate
There was a pregnant woman who was trapped during the time we were under full siege. She was due to deliver soon. All negotiation attempts to get her out failed. She needed a cesarean operation, but there was no maternity hospital we could get her to, and I had never done this operation before.
A few days before the expected delivery date, I was trying to get a working internet connection to read up information on doing a C-section. The clock was ticking and my fear and stress started to peak. I wished I could stop time, but the woman’s labour started. The atmosphere was tense already, with mad shelling hammering the area. The bombardments had reached a deafening level. We brought the woman into the operating theatre and I did the operation. Joy overwhelmed me when we knew the baby girl was healthy, and her mother too.
In this madness, our work as surgeons is to save as many lives as we can. Sometimes we succeed, and sometimes we fail. It is as if we repair the damage that the war left. But this operation was not the usual damage repair; it helped bring new life to this earth. It was a magical moment; a temporary truce that death could not penetrate.
I chose a deserted school as my hospital
I graduated as a surgeon shortly after the crisis started in Syria. In the Summer of 2011, with the acceleration of events and medical needs increasing, I started working in small private hospitals. A few months later, I was arrested, as were many of my colleagues. At the beginning of 2012 I was out, and I returned to treat people and carry on my general surgery specialization. I was working in improvised field hospitals, operating in conditions that were largely unsuitable for medical work. We worked in the east of Damascus and then in the Ghouta area, where the medical need was urgent.
At the end of 2012, a semi-rural neighbourhood located to the east of Damascus witnessed violent clashes. The area was packed with displaced people at the time, without any medical centre to treat wounded people. I went there and decided to set up a field hospital. Following a search, I chose a deserted school that had previously been hit. The upper floors were damaged, but the ground floor, as well as the basement, were in a good shape. Despite the daily, continuous shelling on the area, and the constant fear and stress, the medical team with which I worked managed to provide tremendous medical care to those who needed it the most.
One day in July 2013, around 10:00 am, the hospital was hit by a rocket. The massive explosion turned the place upside down and its pressure tore out the wooden walls. Medical tools and people were thrown in all directions. Soon a dust cloud settled over the building and made it impossible to see. The explosion was like nothing before. I thought that worse could follow and this explosion might be only the beginning of something very bad. Indeed, shells rained on the area and we could hear the clashes getting worse.
As we were getting over the shock, one of the hospital workers collapsed. She lived near the hospital. Her young boy was at home and the area was coming under heavy shelling. She could not keep it together and she wanted to save her child. A medic offered to go out and look for the child. I did not like the idea because we did not know what was going on outside. As soon as the medic was out of the hospital door, he saw a tank with its gun facing towards him. A healthy man walked out, and few moments later, he came back with shards of metal in his body. It was only then that we realized the severity of the situation outside. We decided to evacuate the hospital – two medics per patient to carry them – and we got out of the back door.
It was apocalyptic! We tried to walk fast towards a small medical centre not far from there. Shelling was hammering the fields around us. I was expecting the worst with every shell we heard. We managed to arrive at our destination unharmed. It was like a miracle. We had left our equipment in the evacuated hospital, but we did not dare to go back there. Over the next days, we heard that the fighting was moving away from the area around the hospital. Under heavy bombardment, we decided to go back and bring our equipment. We had to do that to be able to treat people. Taking turns to do the trip, we managed to retrieve as much as possible after ten days.
From then, we were under siege – impossible to get in and out of there. This was also true for medical supplies. We received a flow of injured people since the first day of the siege. I often operated on two people at once. We worked around the clock. Sleeping and resting were an impossible luxury. We managed to stop for few moments before dawn to eat some food and drink some water, before getting back to work. Most days heavy shelling and raging fighting brought us more injured people, leaving us no chance to rest. The numbers of injured people were way beyond what we could handle, and that forced us to make painful clinical decisions.
After the siege
We were under siege for eight months, up until February 2014. Eight months of suffering and stress, followed by a ceasefire, during which many people managed to go back to their homes. It became easier to get hold of supplies, and that helped us to continue providing medical care to people in need. Nevertheless, the humanitarian situation remained bad. There were still often clashes at the edges of the this area and the shelling was still frequent. This formal ceasefire did not change the nature of our work, but we finally found enough time to expand the hospital. People returning to the neighbourhood meant an increase in the needs, thus more pressure on us. We setup an obstetrics department and clinics to provide basic medical care and chronic diseases management. We could start doing bone, internal and urinary surgeries; all operations we could not perform before because we had suffered critical shortages of supplies and we had been prioritizing life-saving operations.
MSF continued to provide us with much of what we needed. We even received laboratory kit, which allowed us to carry out diagnostic tests. And we received an incubator for the obstetrics unit. Little by little, we could start to respond to all the basic general medical needs for the people in the area.
It has to stop, one day
Three years of non-stop surgery under tough circumstances – I have maxed out. I’ve had enough of scenes of misery. I was on the phone recently with my surgery professor and he said: “regardless of the operating conditions, your work during these three years matches my whole 30 years’ experience as a doctor. You have reached retirement in just three years.” And indeed, every moment of every day I feel I have had enough, but we have no other choice. People here need us. They are in desperate need of all kinds of medical care, from the most simple to the most complicated. We cannot add another reason for the deterioration of this already disastrous situation.
Today, I am almost certain that, when the war is over, I will quit medicine. Any human being would make that decision after living what I have lived through. I look forward to the end of this war. It has to stop, one day. Then, I can choose what to do. Only then, will we be truly alive again.
Think of it as interval training for the dinner table.University of Florida Health researchers have found that putting people on a feast-or-famine diet may mimic some of the benefits of fasting, and that adding antioxidant supplements may counteract those benefits.
Fasting has been shown in mice to extend lifespan and to improve age-related diseases. But fasting every day, which could entail skipping meals or simply reducing overall caloric intake, can be hard to maintain.
“People don’t want to just under-eat for their whole lives,” said Martin Wegman, an M.D.-Ph.D. student at the UF College of Medicine and co-author of the paper recently published in the journal Rejuvenation Research. “We started thinking about the concept of intermittent fasting.”
Michael Guo, a UF M.D.-Ph.D. student who is pursuing the Ph.D. portion of the program in genetics at Harvard Medical School, said the group measured the participants’ changes in weight, blood pressure, heart rate, glucose levels, cholesterol, markers of inflammation and genes involved in protective cell responses over 10 weeks.
“We found that intermittent fasting caused a slight increase to SIRT 3, a well-known gene that promotes longevity and is involved in protective cell responses,” Guo said.
The SIRT3 gene encodes a protein also called SIRT3. The protein SIRT3 belongs to a class of proteins called sirtuins. Sirtuins, if increased in mice, can extend their lifespans, Guo said. Researchers think proteins such as SIRT3 are activated by oxidative stress, which is triggered when there are more free radicals produced in the body than the body can neutralize with antioxidants. However, small levels of free radicals can be beneficial: When the body undergoes stress — which happens during fasting — small levels of oxidative stress can trigger protective pathways, Guo said.
“The hypothesis is that if the body is intermittently exposed to low levels of oxidative stress, it can build a better response to it,” Wegman said.
The researchers found that the intermittent fasting decreased insulin levels in the participants, which means the diet could have an anti-diabetic effect as well.
The group recruited 24 study participants in the double-blinded, randomized clinical trial. During a three-week period, the participants alternated one day of eating 25 percent of their daily caloric intake with one day of eating 175 percent of their daily caloric intake. For the average man’s diet, a male participant would have eaten 650 calories on the fasting days and 4,550 calories on the feasting days. To test antioxidant supplements, the participants repeated the diet but also included vitamin C and vitamin E.
At the end of the three weeks, the researchers tested the same health parameters. They found that the beneficial sirtuin proteins such as SIRT 3 and another, SIRT1, tended to increase as a result of the diet. However, when antioxidants were supplemented on top of the diet, some of these increases disappeared. This is in line with some research that indicates flooding the system with supplemental antioxidants may counteract the effects of fasting or exercise, said Christiaan Leeuwenburgh, Ph.D., co-author of the paper and chief of the division of biology of aging in the department of aging and geriatric research.
“You need some pain, some inflammation, some oxidative stress for some regeneration or repair,” Leeuwenburgh said. “These young investigators were intrigued by the question of whether some antioxidants could blunt the healthy effects of normal fasting.”
On the study participants’ fasting days, they ate foods such as roast beef and gravy, mashed potatoes, Oreo cookies and orange sherbet — but they ate only one meal. On the feasting days, the participants ate bagels with cream cheese, oatmeal sweetened with honey and raisins, turkey sandwiches, apple sauce, spaghetti with chicken, yogurt and soda — and lemon pound cake, Snickers bars and vanilla ice cream.
“Most of the participants found that fasting was easier than the feasting day, which was a little bit surprising to me,” Guo said. “On the feasting days, we had some trouble giving them enough calories.”
Leeuwenburgh said future studies should examine a larger cohort of participants and should include studying a larger number of genes in the participants as well as examining muscle and fat tissue.
- Martin P Wegman, Michael Guo, Douglas M Bennion, Meena N Shankar, Stephen M Chrzanowski, Leslie A Goldberg, Jinze Xu, Tiffany A Williams, Xiaomin Lu, Stephen I Hsu, Stephen D Anton, Christiaan Leeuwenburgh, Mark L Brantly.Practicality of Intermittent Fasting in Humans and its Effect on Oxidative Stress and Genes Related to Aging and Metabolism.Rejuvenation Research, 2014; 141229080855001 DOI: 1089/rej.2014.1624
Seventeen years after losing the use of his hand in a motorcycle crash, Marcus Kemeter volunteered to have it amputated and replaced with a bionic version.
“It wasn’t hard for me to decide to do the operation,” said Kemeter, 35, a used-car dealer in Austria. “I couldn’t do anything with my hand. The prosthesis doesn’t replace a full hand, but I can do a lot of stuff.”
Kemeter’s artificial hand was made possible by a new medical procedure developed at the Medical University of Vienna, which combines reconstructive surgery with advances in prosthetics and months of training and rehabilitation, according to an article published Wednesday in the Lancet, a U.K. medical journal. The researchers performed the procedure on three Austrian men from 2011 to 2014.
The technique, called bionic reconstruction, offers hope for patients like Kemeter who have brachial plexus injuries, which can result in severe nerve damage and the loss of function in the arms.
The nerves of the brachial plexus start in the neck and branch out to control shoulder, arms and hands. They can be damaged in collisions from car and motorcycle accidents, and in sports like football and rugby. In the past, surgical reconstruction for brachial plexus patients could restore some function in their arms but not hands.
The injuries result in an “inner amputation,” permanently separating the hands from neural control, said Oskar Aszmann, a professor of plastic and reconstructive surgery at the Vienna university who is the lead author of the Lancet study.
The damaged limbs “are a biologic wasteland,” Aszmann said in a telephone interview. The solution is transplanting nerves and muscles from the legs into the arm, creating new avenues for signals from the brain.
“We can establish a new signal and we can use these signals to drive a prosthetic hand,” he said.
The process represents a significant step for patients with brachial plexus injuries, said Levi Hargrove, a researcher in prosthetics at the Rehabilitation Institute of Chicago.
“It provides them with an option,” he said. “As mechanical prosthesis become more advanced and more functional, this should only improve.”
The ultimate success of the procedure won’t be known for years and will depend on how often patients use their new hands, said Simon Kay and Daniel Wilks in a Lancet article accompanying the study. Kay is a hand surgeon at the Leeds Teaching Hospital, while Wilks is at The Royal Children’s Hospital in Melbourne.
“Compliance declines with time for all prostheses, and motorized prostheses are heavy, need power and are often noisy,” they wrote.
Kemeter, who lives in the Lower Austrian town of Hollabrunn, damaged his shoulder in a 1996 motorcycle accident. That year, he had surgery that grafted new nerves to his arm, which restored some function to his shoulder and elbow. Over the next decade and a half, his arm withered and atrophied, with his fingers permanently clenched.
“I could feel everything but I couldn’t do anything with the hand,” he said.
In 2011, Aszmann transplanted Kemeter’s nerves from his lower leg and muscle from his thigh to his injured forearm. After waiting three months for the nerves to grow back, Kemeter’s arm was connected to a computer, where he could practice manipulating a virtual hand.
“The brain has forgotten to use the hand,” Aszmann said. “We have to retrain them.”
The next step was connecting the prosthesis to the new nerves, with Kemeter’s biological hand still in place, to train him to use the device. That helps patients with the decision to amputate, Aszmann said.
“When it’s obvious this mechatronic hand can be of great use to them, then the decision to have the hand amputated is a very easy one,” he said. “If I have to convince someone, they’re not a good patient.”
Finally, after the amputation wounds healed and the prosthesis was fitted, the adjustment to the new appendage took only a few days.
“I can do much more than before,” Kemeter said. “Carrying big things, for example, wasn’t possible with only one hand. Now I can do it.”
Related News and Information: Bionic Hands Move Close to Human Control With Sensation of Touch Innovative Prosthetic Arm From Segway Inventor Cleared by U.S. First Bionic Leg to Harness Nerves Allows Mind Control Movement.
»Anyone who knows me also knows that I have a huge sweet tooth. I always have. My friend and fellow graduate student Andrew is equally afflicted, and living in Hershey, Pennsylvania – the “Chocolate Capital of the World” – doesn’t help either of us.
But Andrew is braver than I am. Last year, he gave up sweets for Lent. I can’t say that I’m following in his footsteps this year, but if you are abstaining from sweets for Lent this year, here’s what you can expect over the next 40 days.
Sugar: natural reward, unnatural fix
In neuroscience, food is something we call a “natural reward.” In order for us to survive as a species, things like eating, having sex and nurturing others must be pleasurable to the brain so that these behaviours are reinforced and repeated.
Evolution has resulted in the mesolimbic pathway, a brain system that deciphers these natural rewards for us. When we do something pleasurable, a bundle of neurons called the ventral tegmental area uses the neurotransmitter dopamine to signal to a part of the brain called the nucleus accumbens. The connection between the nucleus accumbens and our prefrontal cortex dictates our motor movement, such as deciding whether or not to taking another bite of that delicious chocolate cake. The prefrontal cortex also activates hormones that tell our body: “Hey, this cake is really good. And I’m going to remember that for the future.”
Not all foods are equally rewarding, of course. Most of us prefer sweets over sour and bitter foods because, evolutionarily, our mesolimbic pathway reinforces that sweet things provide a healthy source of carbohydrates for our bodies. When our ancestors went scavenging for berries, for example, sour meant “not yet ripe,” while bitter meant “alert – poison!”
Fruit is one thing, but modern diets have taken on a life of their own. A decade ago, it was estimated that the average American consumed 22 teaspoons of added sugar per day, amounting to an extra 350 calories; it may well have risen since then. A few months ago, one expert suggested that the average Briton consumes 238 teaspoons of sugar each week.
Today, with convenience more important than ever in our food selections, it’s almost impossible to come across processed and prepared foods that don’t have added sugars for flavour, preservation, or both.
These added sugars are sneaky – and unbeknown to many of us, we’ve become hooked. In ways that drugs of abuse – such as nicotine, cocaine and heroin – hijack the brain’s reward pathway and make users dependent, increasing neuro-chemical and behavioural evidence suggests that sugar is addictive in the same way, too.
Sugar addiction is real
“The first few days are a little rough,” Andrew told me about his sugar-free adventure last year. “It almost feels like you’re detoxing from drugs. I found myself eating a lot of carbs to compensate for the lack of sugar.”
There are four major components of addiction: bingeing, withdrawal, craving, and cross-sensitisation (the notion that one addictive substance predisposes someone to becoming addicted to another). All of these components have been observed in animal models of addiction – for sugar, as well as drugs of abuse.
A typical experiment goes like this: rats are deprived of food for 12 hours each day, then given 12 hours of access to a sugary solution and regular chow. After a month of following this daily pattern, rats display behaviours similar to those on drugs of abuse. They’ll binge on the sugar solution in a short period of time, much more than their regular food. They also show signs of anxiety and depression during the food deprivation period. Many sugar-treated rats who are later exposed to drugs, such as cocaine and opiates, demonstrate dependent behaviours towards the drugs compared to rats who did not consume sugar beforehand.
Like drugs, sugar spikes dopamine release in the nucleus accumbens. Over the long term, regular sugar consumption actually changes the gene expression and availability of dopamine receptors in both the midbrain and frontal cortex. Specifically, sugar increases the concentration of a type of excitatory receptor called D1, but decreases another receptor type called D2, which is inhibitory. Regular sugar consumption also inhibits the action of the dopamine transporter, a protein which pumps dopamine out of the synapse and back into the neuron after firing.
In short, this means that repeated access to sugar over time leads to prolonged dopamine signalling, greater excitation of the brain’s reward pathways and a need for even more sugar to activate all of the midbrain dopamine receptors like before. The brain becomes tolerant to sugar – and more is needed to attain the same “sugar high.”
Sugar withdrawal is also real
Although these studies were conducted in rodents, it’s not far-fetched to say that the same primitive processes are occurring in the human brain, too. “The cravings never stopped, [but that was] probably psychological,” Andrew told me. “But it got easier after the first week or so.”
In a 2002 study by Carlo Colantuoni and colleagues of Princeton University, rats who had undergone a typical sugar dependence protocol then underwent “sugar withdrawal.” This was facilitated by either food deprivation or treatment with naloxone, a drug used for treating opiate addiction which binds to receptors in the brain’s reward system. Both withdrawal methods led to physical problems, including teeth chattering, paw tremors, and head shaking. Naloxone treatment also appeared to make the rats more anxious, as they spent less time on an elevated apparatus that lacked walls on either side.
Similar withdrawal experiments by others also report behaviour similar to depression in tasks such as the forced swim test. Rats in sugar withdrawal are more likely to show passive behaviours (like floating) than active behaviours (like trying to escape) when placed in water, suggesting feelings of helplessness.
A new study published by Victor Mangabeira and colleagues in this month’s Physiology & Behavior reports that sugar withdrawal is also linked to impulsive behaviour. Initially, rats were trained to receive water by pushing a lever. After training, the animals returned to their home cages and had access to a sugar solution and water, or just water alone. After 30 days, when rats were again given the opportunity to press a lever for water, those who had become dependent on sugar pressed the lever significantly more times than control animals, suggesting impulsive behaviour.
These are extreme experiments, of course. We humans aren’t depriving ourselves of food for 12 hours and then allowing ourselves to binge on soda and doughnuts at the end of the day. But these rodent studies certainly give us insight into the neuro-chemical underpinnings of sugar dependence, withdrawal, and behaviour.
Through decades of diet programmes and best-selling books, we’ve toyed with the notion of “sugar addiction” for a long time. There are accounts of those in “sugar withdrawal” describing food cravings, which can trigger relapse and impulsive eating. There are also countless articles and books about the boundless energy and new-found happiness in those who have sworn off sugar for good. But despite the ubiquity of sugar in our diets, the notion of sugar addiction is still a rather taboo topic.
Are you still motivated to give up sugar for Lent? You might wonder how long it will take until you’re free of cravings and side-effects, but there’s no answer – everyone is different and no human studies have been done on this. But after 40 days, it’s clear that Andrew had overcome the worst, likely even reversing some of his altered dopamine signalling. “I remember eating my first sweet and thinking it was too sweet,” he said. “I had to rebuild my tolerance.”
And as regulars of a local bakery in Hershey – I can assure you, readers, that he has done just that.«