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Blog » Biology & Medicine

 
     
 

28th March 2017

New drug can dramatically cut bad cholesterol

A new drug, evolocumab, is shown to reduce bad cholesterol by 59%.

 

evolocumab

 

Coronary heart disease is the single biggest killer worldwide – causing over 7 million deaths each year – and "bad" LDL-cholesterol is a major cause. Statins can reduce the risk of heart disease, but they are not tolerated by everyone and only reduce cholesterol by a certain amount.

This month, the results of a major clinical trial have shown that a new cholesterol-lowering drug could further reduce the risk of heart attack or stroke for those already taking statins. The study of evolocumab (trade name Repatha) is published in the New England Journal of Medicine. This looked at over 27,500 patients in 49 countries living with heart disease and taking statins. The drug was found to lower cholesterol by an average of 59% and reduced the risk of a heart attack by 27% and stroke by 21% in the two years of follow-up.

Repatha is a human monoclonal antibody that inhibits PCSK9, an enzyme encoded by the PCSK9 gene. Repatha binds to PCSK9 and prevents it from binding to the Low-Density Lipoprotein Receptor (LDL-R), increasing the number of LDL-Rs available to clear bad cholesterol from the blood.

"It is much more effective than statins," said Prof. Peter Sever, from Imperial College London, a member of the study's executive committee. "It is probably the most important trial result of a cholesterol-lowering drug in over 20 years."

"This trial is a significant advance," said Prof. Sir Nilesh Samani, Medical Director at the British Heart Foundation. "Giving patients evolocumab, a PCSK9 inhibitor, on top of statins, not only helped to further reduce LDL-cholesterol, but also reduced the risk of cardiovascular events in people already affected by heart disease, without causing major side effects."

"We now have definitive data that by adding evolocumab to a background of statin therapy, we can significantly improve cardiovascular outcomes and do so safely," said Dr Marc Sabatine, of Harvard Medical School in Boston. "We need to treat LDL cholesterol more aggressively, and now we have a new validated means to do so."

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27th March 2017

Critical step found in DNA repair and cellular aging

A new study on mice has found a possible treatment for DNA damage from aging and radiation. This finding could be especially helpful for astronauts in space, who are at greater risk of DNA damage from cosmic radiation.

 

dna space
Credit: David Sinclair, Harvard Medical School

 

An international team – including researchers from Harvard and the University of New South Wales (UNSW) – has made a discovery that could lead to a revolutionary drug for reversing aspects of the aging process, improving DNA repair and ensuring the long-term survival of colonists on Mars.

In a paper published by the journal Science, they describe a critical step in the molecular process that allows cells to repair damaged DNA. Their tests on mice suggest a treatment is possible for humans exposed to radiation. It is so promising that it has attracted the attention of NASA, which believes the treatment can help its Mars mission during the 2030s.

While our cells have an innate capability to repair DNA damage − which happens every time we go out into the Sun, for example – their ability to do this declines as we age. The scientists identified that the metabolite NAD+, which is naturally present in every cell of our body, has a key role as a regulator in protein-to-protein interactions that control DNA repair. Treating mice with a NAD+ precursor, or "booster," called NMN improved their cells' ability to repair DNA damage caused by radiation exposure or old age.

"The cells of the old mice were indistinguishable from the young mice, after just one week of treatment," said the lead author, Professor David Sinclair of UNSW School of Medical Sciences and Harvard Medical School. Human trials of NMN therapy will begin within six months. "This is the closest we are to a safe and effective anti-aging drug that's perhaps only three to five years away from being on the market if the trials go well," says Sinclair.

 

 

 

The work has excited NASA, which faces the challenge of keeping its astronauts healthy during a four-year mission to Mars. Even on short missions, humans can experience accelerated aging from cosmic radiation, and suffer muscle weakness, memory loss and other symptoms when they return. On a trip to Mars the situation would be far worse: five per cent of the astronauts' cells would die and their chances of cancer would approach 100 per cent.

Cosmic radiation is not only an issue for astronauts. We're all exposed to it aboard aircraft, with a London-Singapore-Melbourne flight roughly equivalent in radiation to a chest x-ray. In theory, the same treatment could mitigate any effects of DNA damage for frequent flyers.

The other group that could benefit from this work is survivors of childhood cancers. 96 per cent of childhood cancer survivors suffer a chronic illness by age 45, including cardiovascular disease, Type 2 diabetes, Alzheimer's disease, and cancers unrelated to the original cancer.

"All of this adds up to the fact they have accelerated ageing, which is devastating," explains Sinclair's colleague, Dr Lindsay Wu. "It would be great to do something about that, and we believe we can with this molecule."

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24th March 2017

Aging partially reversed in mice by flushing out senescent cells

Dutch scientists have announced a new drug treatment able to reverse aspects of aging in old mice – restoring their stamina, coat of fur and even some organ function – by flushing out "senescent" cells in the body that have stopped dividing. Human trials are now planned.

 

aging cure mice future timeline

 

Researchers at the Erasmus University Medical Centre in Rotterdam, Netherlands, have found a way to turn back aging. By giving old mice a peptide that disrupts the binding between two proteins, the mice became fitter and more alert, their coat of fur became fuller again, and organ functions improved. This discovery was published yesterday in the leading scientific journal Cell.

Key player in the study is proxofim, a substance developed by the researchers themselves. It disrupts the binding between the proteins FOXO4 and p53. In contrast to existing substances used by researcher to intervene with aging, proxofim was found to have no adverse effects on the health of the mice. "The platelet count and the liver function, for example, remained normal," said Peter de Keizer, a researcher in Erasmus MC's department of Molecular Genetics and a lead author in this study.

Proxofim can deal with so-called "senescent" cells that play a significant role in aging. These are cells that have ceased to divide, but are not really dead: "In fact, their metabolism does continue, which means they continue to secrete all kinds of proteins, including inflammatory cytokines," says De Keizer. "These in turn cause more rapid aging of tissues and poorer organ function. They also play a role in cancer. The senescent cells make cancer less sensitive to chemotherapy and can accelerate the growth of tumours. In other words, we actually want to get rid of these cells."

Proxofim kills these senescent cells "and it stimulates the surrounding stem cells to create new tissue. It is a peptide, a small protein that can easily penetrate into cells."

When applied to mice, this had a major effect. After just three weeks, their running wheel activity nearly tripled, their organ function improved and after ten days their coat of fur became fuller again. The researchers would now like to start clinical trials on humans: "We first want to investigate the safety and efficacy further. We then hope to expand the study to patients with aggressive forms of cancer within one to two years, and then eventually to study geriatric ailments. We do not seek eternal life, but a longer life without ailments and in excellent health would be great."

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1st March 2017

Two-way communication in brain-machine interface achieved for the first time

Optical techniques for imaging and stimulating brain activity could lead to a new generation of more precise, bidirectional neural prostheses.

 

brain machine interface bmi future timeline
Credit: © Daniel Huber, UNIGE

 

Since the early 1970s, scientists have been developing brain-machine interfaces; the main application being the use of neural prosthesis in paralysed patients or amputees. A prosthetic limb directly controlled by brain activity can partially recover the lost motor function. This is achieved by decoding neuronal activity recorded with electrodes and translating it into robotic movements. However, such systems have limited precision, due to the absence of sensory feedback from the artificial limb.

Neuroscientists at the University of Geneva (UNIGE), Switzerland, looked at whether it was possible to transmit this missing sensation back to the brain by stimulating neural activity in the cortex. They discovered that not only was it possible to create an artificial sensation of neuroprosthetic movements, but that the underlying learning process occurs very rapidly. These findings, published in the scientific journal Neuron, were obtained by using modern imaging and optical stimulation tools, an alternative to the classical electrode approach.

Motor function is at the heart of all behaviour and allows us to interact with the world. Therefore, replacing a lost limb with a robotic prosthesis is the subject of much research, yet successful outcomes are rare. Why is that? Until now, brain-machine interfaces have been operated by relying largely on visual perception: the robotic arm is controlled by looking at it. The direct flow of information between the brain and machine thus remains unidirectional. However, movement perception is not only based on vision, but mostly on proprioception – the sensation of where the limb is located in space.

“We have therefore asked whether it was possible to establish a bidirectional communication in a brain-machine interface: to simultaneously read out neural activity, translate it into prosthetic movement and reinject sensory feedback of this movement back in the brain,” explains Daniel Huber, professor in the Department of Basic Neurosciences at UNIGE.

In contrast to traditional invasive approaches using electrodes, Huber’s team specialises in optical techniques for imaging and stimulating brain activity. Using a method called two-photon microscopy, they routinely measure the activity of hundreds of neurons with single cell resolution: “We wanted to test whether mice could learn to control a neural prosthesis by relying uniquely on an artificial sensory feedback signal”, explains Mario Prsa, researcher at UNIGE and the first author of the study. “We imaged neural activity in the motor cortex. When the mouse activated a specific neuron, the one chosen for neuroprosthetic control, we simultaneously applied stimulation proportional to this activity to the sensory cortex using blue light.”

Neurons of the sensory cortex were rendered photosensitive to this light, allowing them to be activated by a series of optical flashes and thus integrate the artificial sensory feedback signal. The mouse was rewarded upon every above-threshold activation, and just 20 minutes later, once the association was learned, the rodent was able to more frequently generate the correct neuronal activity.

This means that the artificial sensation was not only perceived, but that it was successfully integrated as a feedback of the prosthetic movement. So in this manner, the brain-machine interface functions bidirectionally. The Geneva researchers think that the reason why this fabricated sensation is so rapidly assimilated is because it most likely taps into very basic brain functions. Feeling the position of our limbs occurs automatically, without much thought and probably reflects fundamental neural circuit mechanisms. In the future, this type of bidirectional interface could allow more precisely displacing robotic arms, feeling touched objects or perceiving the necessary force to grasp them.

At present, the neuroscientists at UNIGE are examining how to produce a more efficient sensory feedback. They are currently capable of doing it for a single movement – but is it also possible to provide multiple feedback channels in parallel? This research sets the groundwork for developing a new generation of more precise, bidirectional neural prostheses.

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27th February 2017

Ultra-flexible brain probes demonstrated

Researchers from the University of Texas at Austin have developed ultra-flexible, nanoelectronic thread (NET) brain probes, designed to achieve more reliable long-term neural recording than existing probes and without causing scar formation when implanted.

 

ultra flexible brain probes
A rendering of the ultra-flexible probe in neural tissue gives viewers a sense of the device’s tiny size and footprint in the brain. Credit: Science Advances.

 

A team led by assistant professor Chong Xie and research scientist Lan Luan, from the University of Texas at Austin, have developed new probes that have mechanical compliances approaching that of brain tissue and are over 1,000 times more flexible than current neural probes. This ultra-flexibility leads to an improved ability to reliably record and track the electrical activity of individual neurons for long periods of time. There is a growing interest in developing long-term tracking of individual neurons for neural interface applications – such as high-performance prostheses for amputees, as well as new methods of following the progression of neurodegenerative and neurovascular diseases such as stroke, Parkinson's and Alzheimer's.

One of the problems with conventional probes is their size and mechanical stiffness; their larger dimensions and stiffer structures often cause damage around the tissue they encompass. Additionally, while it is possible for the conventional electrodes to record brain activity for months, they often provide recordings that are unreliable and degrade over time. It is also hard for conventional electrodes to track individual neurons for more than a few days.

In contrast, the UT Austin team's electrodes are flexible enough to comply with micro-scale movements of tissue and still stay in place. The probe's size also drastically reduces tissue displacement, so the brain interface is more stable, and the readings are more reliable for longer periods of time. To the researchers' knowledge, this new probe – which is as small as 10 microns at a thickness below 1 micron, and has a cross-section that is only a fraction of that of a neuron or blood capillary – is the smallest neural probe ever developed.

 

 

 

Following tests on mice, the researchers found that the probe's flexibility and size prevented the agitation of glial cells, which is the normal biological reaction to a foreign body and leads to scarring and neuronal loss.

"The most surprising part of our work is that the living brain tissue – the biological system – really doesn't mind having an artificial device around for months," Luan said.

The researchers also used advanced imaging techniques in collaboration with biomedical engineering professor Andrew Dunn and neuroscientists Raymond Chitwood and Jenni Siegel from the Institute for Neuroscience at UT Austin, to confirm that the neural interface did not degrade in the mouse model for over four months of experiments. The researchers plan to continue testing their probes in animal models and hope to eventually engage in clinical testing. Their latest research is published in the journal Science Advances.

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22nd February 2017

Life expectancy to reach 90 for the first time

A study published by The Lancet shows that in many countries, average life expectancy will increase significantly by 2030, exceeding 90 for the first time in South Korea. This trend will be slower in the USA, however – due to obesity, homicides and lack of equal access to healthcare.

 

future aging 2030 life expectancy 90

 

Life expectancies in developed countries are projected to continue increasing, with women's life expectancy surpassing 90 in South Korea by 2030, according to a study published in The Lancet.

The study predicts life expectancy is likely to be highest in South Korea (90.8), France (88.6) and Japan (88.4) for women, and in South Korea (84.1), Australia (84.0) and Switzerland (84.0) for men.

The researchers emphasise that people living longer will have major implications for health and social services. Countries will need to adapt and have policies to support healthy aging, increase investment in health and social care, and possibly change their retirement ages.

"As recently as the turn of the century, many researchers believed that life expectancy would never surpass 90 years," said Professor Majid Ezzati from Imperial College London, the study's lead author. "Our predictions of increasing lifespans highlight our public health and healthcare successes. However, it is important that policies to support the growing older population are in place. In particular, we will need to both strengthen our health and social care systems and to establish alternative models of care, such as technology-assisted home care."

 

home elderly care robot
"Care-O-bot". Credit: Kniff Projektagentur GbR / Fraunhofer IPA

 

Although life expectancy is predicted to increase for all 35 countries in the study, the extent of the increase varies from place to place. Comparing 2010 and 2030, female life expectancy will increase most in South Korea, Slovenia and Portugal (6.6, 4.7 and 4.4 years, respectively). For men, life expectancy will increase most in Hungary, South Korea and Slovenia (7.5, 7.0 and 6.4 years).

Life expectancy is predicted to increase least in Macedonia, Bulgaria, Japan and the USA (1.4, 1.5, 1.8 and 2.1 years) for women, and in Macedonia, Greece, Sweden and the USA (2.4, 2.7, 3.0 and 3.0 years) for men.

The USA is predicted to see relatively small improvements (from 81.2 in 2010, to 83.3 in 2030 for women; and 76.5 to 79.5 for men). Its life expectancy is already lower than most other high-income nations, and is expected to fall further behind in 2030 – mainly a result of its large inequalities, absence of universal health care and having the highest homicide rate, body mass index (BMI) and death rates for children and mothers of all high-income nations.

Conversely, South Korea's projected gains will be the result of continued improvements in economic status, improved nutrition for children, access to healthcare and medical technology across the whole population. This results in fewer deaths from infections and better prevention and treatment for chronic diseases, in a way that is more equitable than some Western countries.

The research also indicates that the gap in life expectancy between men and women is closing, as Professor Ezzati explains: "Men traditionally had unhealthier lifestyles, and so shorter life expectancies. They smoked and drank more, and had more road traffic accidents and homicides. However as lifestyles become more similar between men and women, so does their longevity."

"We repeatedly hear that improvements in human longevity are about to come to an end," he continues. "Many people used to believe that 90 years is the upper limit for life expectancy – but this research suggests we will break the 90 year barrier. I don't believe we're anywhere near the upper limit of life expectancy, if there even is one."

The researchers explain that the next step of their research will be to extend their model to specific diseases, as well as to all countries to provide more accurate predictions of life expectancy globally. They are careful to note that their study cannot take into account unprecedented events – such as revolutionary advances in medicine, the potentially disastrous effects of climate change, or political upheaval that may affect social and health systems.

 

future life expectancy 2030

 

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16th February 2017

Gene editing of human embryos receives backing from U.S. science committee

A committee from the US National Academy of Sciences (NAS) and National Academy of Medicine (NAM) has given cautious backing to gene editing of human embryos.

 

human embryo genetic future

 

Clinical trials for genome editing of the human germline – adding, removing, or replacing DNA base pairs in gametes or early embryos – could be permitted in the future, but only for serious conditions under stringent oversight, says a new report from the National Academy of Sciences and the National Academy of Medicine. The report outlines criteria that should be met before allowing germline editing clinical trials to go forward. Genome editing has already entered clinical trials for non-heritable applications, but should be allowed only for treating or preventing diseases or disabilities at this time, the report says.

Genome editing is not new. But the emergence of powerful, precise and less costly genome editing tools, such as CRISPR/Cas9, have led to an explosion of new research opportunities and potential clinical applications, both heritable and non-heritable, to address a wide range of human health issues. Recognising the promise and the concerns related to this technology, the NAS and NAM appointed a study committee of international experts to examine the scientific, ethical and governance issues surrounding human genome editing.

Human genome editing is already widely used in basic research and is in the early stages of development and trials for clinical applications that involve somatic (non-heritable) cells. These therapies affect only the patient – not any offspring – and should continue for treatment and prevention of disease and disability, using the existing ethical norms and regulatory framework, the committee says.

However, there is significant public concern about the prospect of using these same techniques for so-called “enhancement” of human traits and capacities such as physical strength, or even for uses that are not possible, such as improving intelligence. The report recommends that genome editing for enhancement should not be allowed at this time, and that broad public input and discussion should be solicited before allowing clinical trials for somatic genome editing for any purpose other than treating or preventing disease or disability.

“Human genome editing holds tremendous promise for understanding, treating, or preventing many devastating genetic diseases, and for improving treatment of many other illnesses,” said Alta Charo, committee co-chair and a Professor of Law and Bioethics at the University of Wisconsin-Madison. “However, genome editing to enhance traits or abilities beyond ordinary health raises concerns about whether the benefits can outweigh the risks, and about fairness if available only to some people.”

 

genetic enhancement

 

Germline genome editing, in contrast, is contentious because genetic changes would be inherited by the next generation. Many view germline editing as crossing an “ethically inviolable” line, the report says. Concerns raised include spiritual objections to interfering with human reproduction to speculation about effects on social attitudes toward people with disabilities to possible risks to the health and safety of future children. But germline genome editing could provide some parents who are carriers of genetic diseases with their best or most acceptable option for having genetically related children who are born free of these diseases.

Heritable germline editing is not ready to be tried in humans. Much more research is needed before it could meet the appropriate risk and benefit standards for clinical trials. The technology is advancing very rapidly, though – making heritable genome editing of early embryos, eggs, sperm, or precursor cells in the foreseeable future “a realistic possibility that deserves serious consideration,” the report says. Although heritable germline genome editing trials must be approached with caution, the committee said, caution does not mean prohibition.

At present, heritable germline editing is not permissible in the United States, due to an ongoing prohibition on the U.S. Food and Drug Administration’s ability to use federal funds to review “research in which a human embryo is intentionally created or modified to include a heritable genetic modification.” Various other countries have signed an international convention that prohibits germline modification.

If current restrictions are removed, and for countries where germline editing would already be permitted, the committee recommended stringent criteria that would need to be met before going forward with clinical trials. They include:

(1) absence of reasonable alternatives;
(2) restriction to editing genes that have been convincingly demonstrated to cause or strongly predispose to a serious disease or condition;
(3) credible pre-clinical and/or clinical data on risks and potential health benefits;
(4) ongoing, rigorous oversight during clinical trials;
(5) comprehensive plans for long-term multigenerational follow-up; and
(6) continued reassessment of both health and societal benefits and risks, with wide-ranging, ongoing input from the public.

"Previously, it was easy for people to say, 'This isn't possible, so we don't have to think about it much,'" said MIT researcher Richard Hynes, who helped lead the committee. "Now we can see a path whereby we might be able to do it, so we have to think about how to make sure it's used only for the right things and not for the wrong things."

"These kinds of scenarios used to be science fiction; they used to be seen as far-off hypotheticals," said biotechnologist Marcy Darnovsky from the Centre for Genetics and Society. "But actually, right now, I think they're urgent social justice questions ... [W]e're going to be creating a world in which the already privileged and affluent can use these high-tech procedures to make children [with] biological advantages. And the scenario that plays out is not a pretty one."

 

designer babies future timeline

 

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30th January 2017

First 3-D observation of protein complexes working inside cells

Researchers have combined genetic engineering, super-resolution microscopy and biocomputation to witness in 3-D the protein machinery inside living cells. Their method unveils key functional features of protein assemblies that are vital for life, and will make it possible to study cellular protein machinery in health and in disease.

 

nanomachines future timeline nanotechnology
Left: in vivo image of nanomachines using current microscopy techniques. Right: the new method allows 3-D observation of nanomachines in vivo and provides a 25-fold improvement in resolution. Credit: O. Gallego, IRB Barcelona

 

Scientists at the Institute for Research in Biomedicine (IRB Barcelona) have published a study in which they observed protein nanomachines (also called protein complexes) – the structures responsible for performing cell functions – for the first time in living cells and in 3-D. This work was done in collaboration with researchers at the University of Geneva in Switzerland and the Centro Andaluz de Biología del Desarrollo in Seville.

Currently, biologists who study the function of protein nanomachines isolate these complexes in test tubes, divorced from the cell, and then apply in vitro techniques that allow them to observe their structure up to the atomic level. Alternatively, they use techniques that allow the analysis of these complexes within the living cell, but that give little structural information. In this latest study, however, the scientists have managed to directly observe the structure of the protein machinery in living cells while it is executing its function.

"In vitro techniques allow us to make observations at the atomic level, but the information provided is limited," explains Oriol Gallego, IRB Barcelona researcher and study coordinator. "We will not know how an engine works if we disassemble it and only look at the individual parts. We need to see the engine assembled in the car and running. In biology, we still do not have the tools to observe the inner workings of a living cell, but the technique that we have developed is a step in the right direction. We can now see, in 3-D, how the protein complexes carry out their functions."

The new technique combines super-resolution microscopy – a discovery that was recognised with the 2014 Nobel Prize in Chemistry – cell engineering, and computational modelling. This enables the observation of protein complexes with a precision of 5 nanometres (nm), a resolution "four times better than that offered by super-resolution and that allows us to perform cell biology studies that were previously unfeasible," explains Gallego (*a nm is a millionth of a mm. Human hairs have a width of 100,000 nm).

 

 

 

Cells were genetically modified by the researchers to build artificial supports inside, onto which they could anchor protein complexes. The supports were designed in such a way as to allow them to regulate the angle from which the immobilised nanomachinery was viewed. The 3-D structure of protein complexes was then determined by using super-resolution techniques to measure distances between the different components, then integrating them in a process similar to that used by GPS.

Gallego used this method to study exocytosis, a mechanism that the cell uses to communicate with the cell exterior. For instance, neurons communicate with each other by releasing neurotransmitters via exocytosis. Their study allowed the scientists to reveal the entire structure of a key nanomachine in exocytosis that until now was an enigma: "We now know how this machinery, which is formed by eight proteins, works and what each protein is important for," said Gallego. "This knowledge will help us to better understand the involvement of exocytosis in cancer and metastasis – processes in which this nanomachinery is altered."

The study is published in the journal Cell.

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30th January 2017

3-D printer can make human skin

Researchers in Madrid have demonstrated a prototype 3-D printer that can print fully functional human skin.

 

3d printer human skin bioprinter future timeline
Credit: Image courtesy of Universidad Carlos III de Madrid – Oficina de Información Científica

 

Scientists from the Universidad Carlos III de Madrid (UC3M), Centre for Energy, Environmental and Technological Research (CIEMAT), Hospital General Universitario Gregorio Marañón, in collaboration with BioDan Group, have announced a prototype 3-D bioprinter that creates fully functional human skin. The skin is adequate for transplanting to patients, or for use in research or the testing of cosmetic, chemical, and pharmaceutical products.

This breakthrough is described in the scientific journal Biofabrication. It replicates the natural structure of the skin, with an external layer, the epidermis with its stratum corneum, which acts as protection against the external environment, together with a thicker, deeper layer, the dermis. This last layer consists of fibroblasts that produce collagen, the protein that gives elasticity and mechanical strength to the skin.

Bioinks are key to 3-D bioprinting, according to the experts. When creating skin, instead of cartridges and coloured inks, injectors with biological components are used. In the words of Juan Francisco del Cañizo, of the Hospital General Universitario: “Knowing how to mix the biological components, in what conditions to work with them so that the cells don’t deteriorate, and how to correctly deposit the product is critical to the system.” The act of depositing these bioinks, which are patented by CIEMAT and licensed by the BioDan Group, is controlled by a computer, which deposits them on a print bed in a precise and orderly manner.

The process for making these tissues can be carried out in two ways: to produce allogeneic skin, from a stock of cells, done on a large scale, for industrial processes; and to create autologous skin, which is made case by case from the patient’s own cells, for therapeutic use, such as in the treatment of severe burns.

“We use only human cells and components to produce skin that is bioactive and can generate its own human collagen, thereby avoiding the use of the animal collagen that is found in other methods,” they note.

There are several advantages to this new technology: “This method of bioprinting allows skin to be generated in a standardised, automated way, and the process is less expensive than manual production,” points out Alfredo Brisac, CEO of BioDan Group, the Spanish bioengineering firm specialising in regenerative medicine that is collaborating on this research and commercialising the printer.

Currently, this development is in the phase of being approved by different European regulatory agencies to guarantee that the skin being produced is adequate for use in transplants on burn patients and those with other skin problems. In addition, these tissues can be used to test pharmaceutical products, as well as cosmetics and consumer chemical products where current regulations require testing that does not use animals.

 

 

 

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26th January 2017

The first stable semi-synthetic organism

Scientists at the Scripps Research Institute have created the first stable semi-synthetic organism. This can hold two artificial bases, x and y, in its genetic code indefinitely. It could lead to entirely new forms of life with synthetic DNA, the team says, with many potential uses in medicine.

 

first stable semi synthetic organism 2017

 

Life’s genetic code has only ever contained four natural bases: G, A, C and T. These pair up to form two “base pairs” – rungs of the DNA ladder – and they have simply been rearranged to create bacteria and butterflies, penguins and people. Four bases make up all life as we know it.

Until now. Scientists at the Scripps Research Institute (TSRI) have announced the development of the first stable semisynthetic organism. Building on their 2014 study in which they synthesised a DNA base pair, the researchers created a new bacterium that uses the four natural bases (A, T, C and G), which every living organism possesses, but that also holds two synthetic bases called X and Y in its genetic code.

Prof. Floyd Romesberg and his team have now shown that their single-celled organism can hold on, indefinitely, to the synthetic base pair as it divides. Their work is published this week in the journal Proceedings of the National Academy of Sciences.

“We’ve made this semi-synthetic organism more life-like,” comments Romesberg, senior author of the study.

While applications are still far in the future, the researchers say the work could be used to create new functions for single-celled organisms that play important roles in drug discovery and much more.

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13th January 2017

Scientists discover master regulator of cellular aging

Scientists at the Scripps Research Institute report the discovery of TZAP, a protein that binds the ends of chromosomes and determines how long telomeres can be.

 

telomeres and chromosomes

 

Scientists at the Scripps Research Institute (TSRI) in the U.S. have identified a protein that fine-tunes the cellular clock involved in aging. This novel protein, named TZAP, binds the ends of chromosomes and determines how long telomeres, the segments of DNA that protect chromosome ends, can be. Understanding telomere length is crucial, because telomeres set the lifespan of cells in the body – dictating critical processes such as aging and the incidence of cancer.

“Telomeres represent the clock of a cell,” said TSRI Associate Professor Eros Lazzerini Denchi, corresponding author of the study, published yesterday in the journal Science. “You are born with telomeres of a certain length, and every time a cell divides, it loses a little bit of the telomere. Once the telomere is too short, the cell cannot divide anymore.”

Naturally, researchers are curious whether lengthening telomeres could slow aging, and many scientists have looked into using a specialised enzyme called telomerase to “fine-tune” the biological clock. One drawback they’ve found, however, is that unnaturally long telomeres are a risk factor in developing cancer.

“This cellular clock needs to be finely tuned to allow sufficient cell divisions to develop differentiated tissues and maintain renewable tissues in our body and, at the same time, to limit the proliferation of cancerous cells,” said Denchi.

In this new study, the researcher found that TZAP controls a process called “telomere trimming”, ensuring that telomeres do not become too long.

“This protein sets the upper limit of telomere length,” explained Lazzerini Denchi. “This allows cells to proliferate – but not too much.”

For the last few decades, the only proteins known to specifically bind telomeres were the telomerase enzyme and a protein complex known as the Shelterin complex. The discovery of TZAP is a surprise, since many scientists in the field believed there were no additional proteins binding to telomeres.

“There is a protein complex that was found to localise specifically at chromosome ends, but since its discovery, no protein has been shown to specifically localise to telomeres,” said study first author Julia Su Zhou Li, a graduate student in the Lazzerini Denchi lab.

“This study opens up a lot of new and exciting questions,” said Denchi.

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12th January 2017

New drug stops spread of melanoma by 90%

Researchers have discovered that a new chemical compound, and potential drug, reduces the spread of melanoma cells by up to 90%.

 

melanoma

 

The human-made, small-molecule drug compound targets a gene's ability to make RNA molecules and proteins in melanoma tumours. This gene activity causes the disease to spread, but the compound can shut it down. Until now, few other compounds of this kind have been able to accomplish this.

"It's been a challenge developing small-molecule drugs that can block this gene activity that works as a signalling mechanism known to be important in melanoma progression," says Richard Neubig, pharmacology professor at Michigan State University and co-author of the study. "Our chemical compound is actually the same one that we've been working on to potentially treat the disease scleroderma, which now we've found works effectively on this type of cancer."

Scleroderma is a rare and often fatal autoimmune disease that causes hardening of skin tissue, as well as organs such as the lungs, heart and kidneys. The same mechanisms that produce fibrosis, or skin thickening, in scleroderma also contribute to the spread of cancer.

Small-molecule drugs make up over 90% of drugs on the market today and Neubig's co-author Kate Appleton, a postdoctoral student, said the findings are an early discovery that could be highly effective in battling the deadly skin cancer. About 10,000 people die each year from the disease in the US.

"Melanoma is the most dangerous form of skin cancer," Appleton said. "One reason the disease is so fatal is that it can spread throughout the body very quickly and attack distant organs such as the brain and lungs."

Through their research, Neubig and Appleton, along with their collaborators, found that the compounds were able to stop proteins, known as Myocardin-related transcription factors, or MRTFs, from initiating the gene transcription process in melanoma cells. These triggering proteins are initially turned on by another protein called RhoC, or Ras homology C, which is found in a signalling pathway that can cause the disease to aggressively spread in the body.

Their compound reduced the migration of melanoma cells by 85 to 90 percent. The team also discovered that the potential drug greatly reduced tumours specifically in the lungs of mice that had been injected with human melanoma cells.

"We used intact melanoma cells to screen for our chemical inhibitors," Neubig said. "This allowed us to find compounds that could block anywhere along this RhoC pathway."

Figuring out which patients have this pathway turned on is an important next step in the development of their compound, because it would help them determine which patients would benefit the most. "The effect of our compounds on turning off this melanoma cell growth and progression is much stronger when the pathway is activated," explained Appleton. "We could look for the activation of the MRTF proteins as a biomarker to determine risk, especially for those in early-stage melanoma."

If the disease is caught early, the chance of death is only 2 percent. But if caught late, that figure rises to 84 percent.

"The majority of people die from melanoma because of the disease spreading," said Neubig. "Our compounds can block cancer migration and potentially increase patient survival."

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12th January 2017

New tooth repair method could revolutionise dental treatments

Researchers at Kings College London report a way of using an Alzheimer's drug to stimulate the renewal of living stem cells in tooth pulp.

 

tooth regeneration transforming dental care 2017

 

Following trauma or an infection, the soft inner pulp of a tooth can become exposed and infected. To protect the tooth from infection, a thin band of dentine is naturally produced and this seals the tooth pulp, but is insufficient to effectively repair large cavities. Currently, dentists use human-made cements or fillings – such as calcium and silicon-based products – to treat these larger cavities and fill holes in teeth. This cement remains in the tooth and fails to disintegrate, meaning that the normal mineral level of the tooth is never completely restored.

However, in a study published this week by Scientific Reports, scientists from the Dental Institute at King's College London have proven a way to activate the stem cells contained in the pulp of the tooth and generate new dentine – the mineralised material that protects the tooth – in large cavities, potentially reducing the need for fillings or cements.

This novel, biological approach could allow teeth to use their natural ability to fully repair large cavities, rather than using cements or fillings, which are prone to infections and often need replacing a number of times. Indeed, when fillings fail or infection occurs, dentists have to remove and fill an area that is larger than what is affected, and after multiple treatments the tooth may eventually need to be extracted.

Significantly, one of the small molecules used by the team to stimulate the renewal of stem cells included Tideglusib, previously used in clinical trials to treat neurological disorders including Alzheimer's disease. This presents a real opportunity to fast-track the treatment into practice.

Using biodegradable collagen sponges, the team applied low doses of small molecule glycogen synthase kinase (GSK-3) to the tooth. They found that the sponge degraded over time and that new dentine replaced it, leading to complete and natural repair. Collagen sponges are commercially-available and clinically approved, again adding to the potential of the treatment's swift pick-up and use in dental clinics.

"The simplicity of our approach makes it ideal as a clinical dental product for the natural treatment of large cavities – by providing both pulp protection and restoring dentine," says lead author of the study, Professor Paul Sharpe from King's College London. "In addition, using a drug that has already been tested in clinical trials for Alzheimer's disease provides a real opportunity to get this dental treatment quickly into clinics."

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17th December 2016

Aging partially reversed in mice

Scientists have used a new form of gene therapy to partially reverse aging in mice. After six weeks of treatment, the animals appeared younger, had straighter spines and better cardiovascular health, healed quicker when injured, and lived 30% longer. Trials on humans could follow within the next decade.

 

aging reversal mice future timeline
Left: muscle tissue from an aged mouse. Right: muscle tissue from an aged mouse subjected to cell reprogramming. Credit: Salk Institute

 

Researchers at the Salk Institute in California have found that intermittent expression of genes normally associated with an embryonic state can reverse the hallmarks of old age.

This approach was tested on human skin cells in a dish, causing them to begin looking and behaving young again. But not only that – it also resulted in the rejuvenation of mice with a premature aging disease, countering signs of aging and extending the animals' lifespans by 30%. This early-stage work provides insights into the cellular drivers of aging, as well as possible therapeutic approaches for improving human health and longevity.

"Our study shows that aging may not have to proceed in one single direction," says Juan Belmonte, a professor in Salk's Gene Expression Laboratory and the senior author of a paper appearing this week in the journal Cell. "It has plasticity and, with careful modulation, aging might be reversed."

As people in modern societies live longer, their risk of developing age-related diseases goes up. In fact, the data shows that the biggest risk factor for heart disease, cancer and neurodegenerative disorders is simply age. One clue to stopping or reversing aging lies in the study of cellular reprogramming – a process in which scientists can convert any cell type into induced pluripotent stem cells (iPSCs), based on the expression of four genes known as the Yamanaka factors. These iPSCs, like embryonic stem cells, are capable of dividing indefinitely and becoming any cell type present in our bodies.

"What we and other stem cell labs have observed is that when you induce cellular reprogramming, cells look younger," says Alejandro Ocampo, researcher and a co-author of the paper. "The next question was whether we could induce this rejuvenation process in a live animal."

While cellular rejuvenation sounds desirable, a process that works in laboratory cells is not necessarily good for an entire organism. For one thing, although rapid cell division is critical in growing embryos, in adults such growth can be an indication of cancer. For another, having large numbers of cells revert back to embryonic status in an adult can result in organ failure, ultimately leading to death. For these reasons, the Salk team wondered whether they could avoid cancer and improve aging characteristics by inducing the Yamanaka factors for just a short period of time.

Sure enough, their "partial" cellular reprogramming approach did not cause tumours or death. This was the first study in which cellular reprogramming extended lifespan in a live animal. Previous efforts resulted in mice that either died immediately, or developed extensive tumours: "We were surprised and excited to see that we were able to prolong the lifespan by in vivo reprogramming," explains co-first author Pradeep Reddy. "In other studies, scientists have completely reprogrammed cells, all the way back to a stem-cell-like state. But we show, for the first time, that by expressing these factors for a short duration, you can maintain the cell's identity while reversing age-associated hallmarks."

The Salk team used their short reprogramming method during cyclic periods in live mice with progeria. The results were striking: compared to the untreated mice, the reprogrammed mice looked younger; their cardiovascular and other organ function improved, and they lived 30% longer, yet did not develop cancer. On a cellular level, the animals showed the recovery of molecular aging hallmarks that are affected not only in progeria, but also in normal aging.

The Salk researchers believe that induction of epigenetic changes, via chemicals administrated in creams or injections, may be the most promising approach to achieve rejuvenation in humans. However, due to the complexity of aging, these therapies may take up to 10 years to reach clinical trials.

"Obviously, mice are not humans and we know it will be much more complex to rejuvenate a person," says Prof. Belmonte. "But this study shows that aging is a very dynamic and plastic process – and therefore, will be more amenable to therapeutic interventions than what we previously thought."

 

 

 

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21st November 2016

Gut tissue grown from stem cells

Researchers have used human pluripotent stem cells to grow human intestinal tissues with functioning nerves, and then used these to recreate and study a severe intestinal nerve disorder.

 

gut tissue grown from stem cells

 

Gut tissue is highly complex, so is difficult to create in the lab. It has an inner layer that absorbs nutrients and secretes digestive enzymes, muscles that push food along its length, and nerves that coordinate muscle contractions.

However, researchers at Cincinnati Children's Hospital Medical Center have achieved a breakthrough in creating lab-grown gut tissue. They report using human pluripotent stem cells to grow human intestinal tissues with functioning nerves and pulses like the real thing. They later used this tissue to recreate and study a severe intestinal nerve disorder called Hirschsprung's disease.

Published in the journal Nature Medicine, their findings describe an unprecedented approach to engineer and study tissues in the intestine – the body's largest immune organ, its food processor and main interface with the outside world. The study authors believe that medical science is now a step closer to using human pluripotent stem cells (which can become any cell type in the body) for regenerative medicine and growing patient-specific human intestines for transplant.

"One day, this technology will allow us to grow a section of healthy intestine for transplant into a patient – but the ability to use it now, to test and ask countless new questions, will help human health to the greatest extent," said Michael Helmrath, MD, co-lead study investigator.

This ability starts with being able to model and study intestinal disorders in functioning human organ tissue with genetically-specific patient cells. It will also allow researchers to test new therapeutics in functioning lab-grown human intestine before clinical trials in patients.

 

gut tissue stem cells future timeline
Human intestinal organoids with nerves. Credit: Cincinnati Children's Hospital Medical Center

 

"Many oral medications give you diarrhoea, cramps and impair intestinal motility. A fairly immediate goal for this technology that would help the largest number of people is as a first-pass screen for new drugs to look for off-target toxicities and prevent side effects in the intestine," explained Jim Wells, PhD, co-lead investigator and director of the Pluripotent Stem Cell Facility at Cincinnati Children's.

"We tried a few different approaches largely based on the hypothesis that, if you put the right cells together at the right time in the petri dish, they'll know what to do. It was a longshot, but it worked," said Wells.

The appropriate mix caused enteric nerve precursor cells and intestines to grow together in a manner resembling developing fetal intestine. The result was the first evidence for generating complex and functional three-dimensional intestinal organoids in a petri dish, and fully derived from human pluripotent stem cells.

"This is one of the most complex tissues to have been engineered," said Wells, who explained that the gastrointestinal tract contains the second largest number of nerves in the human body. He and colleagues used their tissue to study a rare form of Hirschsprung's disease – a condition in which the rectum and colon fail to develop a normal nervous system. A severe form of Hirschsprung's is caused by a fault in the gene PHOX2B. Tests in a petri dish and mice demonstrated that mutating PHOX2B causes profound detrimental changes to innervated intestinal tissues.

Helmrath is now making and testing hollow tubes of the lab-grown tissue. These are 2 centimetres long, but if extended to 10 centimetres, they could make good transplants for short bowel syndrome, a condition that can affect premature babies.

As science continues to learn more about how important intestinal health is to overall health, using functioning lab-generated human intestine creates an array of new research opportunities, Wells and Helmrath said. This will include the ability to conduct deeper studies into nutritional health, diabetes, severe intestinal diseases like inflammatory bowel disease and Crohn's disease, and other biochemical changes in the body.

Their work is described today in the paper, Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system.

 

 

 

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20th November 2016

Researchers discover new antibiotics by sifting through the human microbiome

Scientists at Rockefeller University have identified which genes in a microbe's genome ought to produce antibiotic compounds and then synthesised those compounds to discover two promising new antibiotics.

 

new antibiotics 2016
Credit: Sean Brady

 

Most antibiotics in use today are based on natural molecules produced by bacteria, and given the rise of antibiotic resistance, there's an urgent need to find more of them. Yet coaxing bacteria to produce new antibiotics is a tricky proposition. Most bacteria won't grow in the lab. And even when they do, most of the genes that cause them to churn out molecules with antibiotic properties never get switched on.

Researchers at the Rockefeller University in New York have found a way around these problems, however. By using computational methods to identify which genes in a microbe's genome ought to produce antibiotic compounds and then synthesising those compounds themselves, they were able to discover two promising new antibiotics without having to culture a single bacterium.

The team, led by Sean Brady, head of the Laboratory of Genetically Encoded Small Molecules, began by trawling publicly available databases for the genomes of bacteria that reside in the human body. They then used specialised computer software to scan hundreds of those genomes for clusters of genes that were likely to produce molecules known as non-ribosomal peptides, which form the basis of many antibiotics. They also used the software to predict the chemical structures of the molecules that the gene clusters ought to produce.

The software initially identified 57 potentially useful gene clusters, which the researchers winnowed down to 30. Brady and his colleagues then used a method called solid-phase peptide synthesis to manufacture 25 different chemical compounds. By testing those compounds against human pathogens, the researchers successfully identified two closely related antibiotics, which they dubbed humimycin A and humimycin B. Both are found in a family of bacteria called Rhodococcus – microbes that had never yielded anything resembling the humimycins when cultured via traditional laboratory techniques.

 

Rhodococcus
Rhodococcus. Credit: Jerry Sims

 

The humimycins proved especially effective against Staphylococcus and Streptococcus bacteria, which can cause dangerous infections in humans and tend to grow resistant to various antibiotics. Further experiments suggested that the humimycins work by inhibiting an enzyme that bacteria use to build their cell walls – and once that cell wall-building pathway is interrupted, the bacteria die.

A similar mode of action is employed by beta-lactams, a broad class of commonly prescribed antibiotics whose effect often wanes as bacteria develop ways to resist them. Yet the scientists found that one of the humimycins could be used to re-sensitise bacteria to beta-lactams that they had previously outsmarted.

In one experiment, they exposed beta-lactam resistant Staphylococcus microbes to humimycin A in combination with a beta-lactam antibiotic, and the bugs once again succumbed. Remarkably, that held true even when humimycin A had little effect by itself – a result that Brady attributes to the fact that both compounds work by interrupting different steps in the same biological pathway.

"It's like taking a hose and pinching it in two spots," explains Prof. Brady. Even if neither kink halts the flow altogether on its own, "eventually, no more water comes through."

To further test that proposition, Brady and his colleagues infected mice with a beta-lactam resistant strain of Staphylococcus aureus, a microbe that often causes antibiotic-resistant infections in hospital patients. Mice that were subsequently treated with a mixture containing both humimycin A and a beta-lactam antibiotic fared far better than those treated with only one drug or the other – a finding that could point towards a new treatment regimen for humans infected with beta-lactam resistant S. aureus.

Brady hopes that this discovery will inspire scientists to mine the genomes of bacteria for more molecules that could yield similarly useful results. And he looks forward to applying his methods to the many bacterial species beyond the human microbiome, which might harbour their own molecular treasures – not to mention the even greater number of bacteria whose genomes have not yet been sequenced, but that undoubtedly will be over time.

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13th November 2016

Lab-grown mini lungs successfully transplanted into mice

Scientists can now grow 3-D models of lungs from stem cells, creating new ways to study respiratory diseases.

 

lungs

Credit: Briana R Dye, Priya H Dedhia, Alyssa J Miller, Melinda S Nagy, Eric S White, Lonnie D Shea, Jason R Spence

 

Researchers at the University of Michigan have transplanted lab-grown mini lungs into immunosuppressed mice where the structures were able to survive, grow and mature.

"In many ways, the transplanted mini lungs were indistinguishable from human adult tissue," says senior study author Jason Spence, Ph.D., associate professor in the Department of Internal Medicine and the Department of Cell and Developmental Biology at U-M Medical School.

The findings were published in eLife and described by authors as a potential new tool to study lung disease.

Respiratory diseases account for nearly 1 in 5 deaths worldwide, and lung cancer survival rates remain poor despite numerous therapeutic advances during the past 30 years. The numbers highlight the need for new, physiologically relevant models for translational lung research.

Lab-grown lungs can help because they provide a human model to screen drugs, understand gene function, generate transplantable tissue and study complex human diseases, such as asthma.

Lead study author Briana Dye, a graduate student in the U-M Department of Cell and Developmental Biology, used numerous signalling pathways involved with cell growth and organ formation to coax stem cells – the body's master cells – to make the miniature lungs.

The researchers' previous study showed mini lungs grown in a dish consisted of structures that exemplified both the airways that move air in and out of the body, known as bronchi, and the small lung sacs called alveoli, which are critical to gas exchange during breathing.

But to overcome the immature and disorganised structure, the researchers attempted to transplant the miniature lungs into mice, an approach that has been widely adopted in the stem cell field. Several initial strategies to transplant the mini lungs into mice were unsuccessful.

Working with Lonnie Shea, Ph.D., professor of biomedical engineering at the University of Michigan, the team used a biodegradable scaffold, which had been developed for transplanting tissue into animals, to achieve successful transplantation of the mini lungs into mice. The scaffold provided a stiff structure to help the airway reach maturity.

"In just eight weeks, the resulting transplanted tissue had impressive tube-shaped airway structures similar to the adult lung airways," says Dye.

They characterised the transplanted mini lungs as well-developed tissue, possessing a highly organised epithelial layer lining the lungs. One drawback was that the alveolar cell types did not grow in the transplants. Still, several specialised lung cell types were present, including mucus-producing cells, multiciliated cells and stem cells found in the adult lung.

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13th November 2016

Machine learning can identify a suicidal person

Using a person's spoken or written words, a new computer algorithm identifies with high accuracy whether that person is suicidal, mentally ill but not suicidal, or neither.

 

brain words algorithm

 

A new study shows that technology known as machine learning is up to 93% accurate in correctly classifying a suicidal person and 85% accurate in identifying a person who has a mental illness but is not suicidal, or neither. These results provide strong evidence for using intelligent software as a decision-support tool to help clinicians and caregivers identify and prevent suicidal behaviour.

"These computational approaches provide novel opportunities to apply technological innovations in suicide care and prevention, and it surely is needed," explains John Pestian, PhD, professor in Biomedical Informatics & Psychiatry at Cincinnati Children's Hospital Medical Centre and the study's lead author. "When you look around healthcare facilities, you see tremendous support from technology, but not so much for those who care for mental illness. Only now are our algorithms capable of supporting those caregivers. This methodology can easily be extended to schools, shelters, youth clubs, juvenile justice centres, and community centres, where earlier identification may help to reduce suicide attempts and deaths."

Pestian and his team enrolled 379 patients over the study's 18 month period – from emergency departments as well as inpatient and outpatient centres across three sites. Those enrolled included patients who were suicidal, diagnosed as mentally ill but not suicidal, or neither (serving as a control group).

Each patient completed standardised behavioural rating scales and participated in a semi-structured interview, answering five open-ended questions to stimulate conversation such as "Do you have hope?" "Are you angry?" and "Does it hurt emotionally?"

The researchers extracted and analysed both verbal and non-verbal language from the data. They then used machine learning algorithms to classify the patients into one of the three groups. Their results showed that machine learning algorithms could tell the difference between the groups with an accuracy of up to 93%. The scientists also noticed that the control patients tended to laugh more during interviews, sigh less, and express less anger, less emotional pain and more hope.

This software could become more and more useful in the future, as depression is expected to become the number one global disease burden by 2030. However, such intelligent algorithms may raise concerns over privacy and civil liberties, with potential for information to be abused. For example, authorities might use the software to spy on citizens as they communicate via email or social media, perhaps deciding from the data and wording style that a certain individual is dangerous and must be imprisoned, even if that person is actually innocent.

The study is published in the journal Suicide and Life-Threatening Behavior.

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12th November 2016

Graphic cigarette warnings could prevent 652,000 deaths over next 50 years

A study published in the journal Tobacco Control finds that graphic warnings on cigarette packs could prevent 652,000 deaths in the U.S. over the next 50 years.

 

cigarettes future timeline

 

Using prominent, graphic images on cigarette packs warning against the dangers of smoking could avert more than 652,000 deaths, up to 92,000 low birth weight infants, up to 145,000 preterm births, and about 1,000 cases of sudden infant deaths in the U.S. over the next 50 years, say researchers from Georgetown Lombardi Comprehensive Cancer Center.

Their study, published online in the journal Tobacco Control, is the first to estimate the effects of pictorial warnings on cigarette packs on the health of both adults and infants in the U.S.

Although more than 70 nations have adopted or are considering adopting the World Health Organisation's Framework Convention for Tobacco Control to use such front and back of-the-pack warnings, they have not been implemented in the U.S. These pictorial warnings have been required by law, but an industry lawsuit has stalled implementation. Currently, a text-only warning appears on the side of cigarette packs in the U.S.

 

cigarettes text warning

 

The study used a tobacco control policy model, known as "SimSmoke", developed by Georgetown Lombardi's David T. Levy, PhD, which looks at the effects of past smoking policies, as well as future policies. SimSmoke is peer-reviewed, and has been used and validated in more than 20 countries.

In this study, Levy and his colleagues looked at changes in smoking rates in Australia, Canada and the UK, which have already implemented prominent pictorial warning labels (PWLs). Eight years after PWLs were implemented in Canada, there was an estimated 12 to 20 percent relative reduction in smoking prevalence. After PWLs began to be used in Australia in 2006, adult smoking prevalence fell from 21.3 percent in 2007 to 19 percent in 2008. After implementation in the UK during 2008, smoking prevalence fell 10 percent in the following year.

The researchers used these and other studies and, employing the SimSmoke model, estimated that implementing PWLs in the U.S. would directly reduce smoking prevalence in relative terms by 5 percent in the near term, increasing to 10 percent over the long-term. If implemented in 2016, PWLs are estimated to reduce the number of smoking attributable deaths (heart disease, lung cancer and COPD) by an estimated 652,800 by 2065.

"The bottom line is that requiring large pictorial warnings would help protect the public health of people in the United States," says Prof. Levy. "There is a direct association between these warnings and increased smoking cessation and reduced smoking initiation and prevalence. That would lead to significant reduction of death and morbidity, as well as medical cost."

As of today, 40 percent of cancers diagnosed in the U.S. may have a link to tobacco use, according to the Centres for Disease Control and Prevention (CDC). It is the leading preventable cause of cancer and cancer deaths. Tobacco causes more than just lung cancer – based on current evidence, it can cause cancers of the mouth and throat, voice box, oesophagus, stomach, kidney, pancreas, liver, bladder, cervix, colon, rectum and a type of leukaemia. At least 70 chemicals found in tobacco smoke are known to cause cancer, with exposure to second-hand smoke (aka passive smoking) also causing it. Cigarette smoking is estimated to result in $289 billion a year in medical costs and productivity loss. About 70% of all smokers want to quit – and if they do so before the age of 40, they can gain almost all of the 10 years of life expectancy they would otherwise have lost.

"There are more than 36 million smokers in the U.S.," says Tom Frieden, CDC Director. "Sadly, nearly half could die prematurely from tobacco-related illnesses, including 6 million from cancer, unless we implement the programs that will help smokers quit."

New data released from the National Health Interview Survey shows that cigarette smoking among U.S. adults declined from 20.9 percent (45.1 million) in 2005 to 15.1 percent (36.5 million) in 2015. During 2014-2015 alone, there was a 1.7 percentage point decline, resulting in the lowest prevalence of adult cigarette smoking since the CDC's NHIS began collecting such data in 1965.

"When states invest in comprehensive cancer control programs – including tobacco control – we see greater benefits for everyone, and fewer deaths from tobacco-related cancers," said Lisa Richardson, director of CDC's Division of Cancer Prevention and Control. "We have made progress, but our work is not done."

 

cigarettes historical trend


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11th November 2016

Mouse neurons seen firing in real-time in 3-D

Scientists at Rockefeller University have used a technique called "light sculpting" to see the neurons of a mouse brain firing in real-time in 3-D.

 

3d mouse neurons

 

No single neuron produces a thought or a behaviour – anything the brain accomplishes is a vast collaborative effort between cells. When at work, neurons talk rapidly to each other, forming networks as they communicate. Researchers at Rockefeller University in New York are developing technology that would make it possible to record brain activity as it plays out across these networks. In research published by Nature Methods, they recorded the activity of mouse neurons layered in 3-D sections of brain as they signalled to each other in real time.

"The ultimate goal of our work is to investigate how large numbers of interconnected neurons throughout the brain interact in real time and how their dynamics lead to behaviour," says Alipasha Vaziri, Ph.D., head of the Laboratory of Neurotechnology and Biophysics. "By developing a new method based on 'light sculpting' and using it to capture the activity of the majority of the neurons within a large portion of the cortex, a layered brain structure involved amongst others in higher brain function, we have taken a significant step in this direction."

This type of recording presents a considerable technical challenge because it requires tools capable of capturing short-lived events within individual cells, all while observing large volumes of brain tissue. Vaziri began working toward this goal about six years ago. His group first succeeded in developing a light-microscope–based approach to observing the activity in a 302-neuron roundworm brain, before moving on to the 100,000-neuron larval zebrafish. Their next target was the mouse brain, which is more challenging for two reasons: not only is it more complex, with 70 million neurons, but the rodent brain is also opaque, unlike the more transparent worm and larval fish brains.

To make the activity of neurons visible, they had to be altered. The researchers engineered the mice so their neurons could emit fluorescent light when they signalled to one another. The stronger the signal, the brighter the cells would shine. The system they developed had to meet competing demands – it needed to generate a spherically-shaped area, slightly smaller than the neurons and capable of exciting fluorescence from them. Meanwhile, it also had to move quickly enough to scan thousands of these cells in three dimensions as they fired in real time.

The team accomplished this using a technique called "light sculpting," in which short pulses of laser light – each lasting only a quadrillionth of a second – are dispersed into their coloured components. These are then brought back together to generate the "sculpted" excitation sphere. This sphere is scanned to illuminate the neurons within a plane, then refocused on another layer of neurons above or below, allowing neural signals to be recorded in three dimensions.

In this way, Vaziri and his colleagues recorded the activity in one-eighth of a cubic millimetre of the animal's brain cortex, a volume that represents the majority of a unit known as a cortical column. By simultaneously capturing and analysing the dynamic activity of the neurons within a cortical column, researchers think they might be able to understand brain computation as a whole. In this case, the section of cortex they studied is responsible for planning movement. They are currently working to capture the activity of an entire such unit.

"Progress in neuroscience, and many other areas of biology, is limited by the available tools," Vaziri says. "By developing increasingly faster, higher-resolution imaging techniques, we hope to be able to push the study of the brain into new frontiers."

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20th October 2016

Depression's physical source discovered

Researchers have discovered the physical source of depression in the human brain, which is found to affect the lateral orbitofrontal cortex, implicated in non-reward.

 

physical location of depression in the human brain

 

Understanding of the physical root of depression has been advanced, thanks to research by the University of Warwick, UK, and Fudan University, China. The study shows that depression affects the part of the brain which is implicated in non-reward – the lateral orbitofrontal cortex – so that sufferers of the condition feel a sense of loss and disappointment associated with not receiving rewards.

This area of the brain, which becomes active when rewards are not received, is also connected with the part of the brain involved in one's sense of self, thus potentially leading to thoughts of personal loss and low self-esteem. Depression is also associated with reduced connectivity between the reward brain area in the medial orbitofrontal cortex and memory systems in the brain, which may account for sufferers having less focus on happy memories.

These new discoveries could herald a breakthrough in treating depression, by going to the root cause of the illness, and helping depressed people to stop focussing on negative thoughts.

In this particularly large study, almost 1,000 people in China had their brains scanned using a high precision MRI, which analysed the connections between the medial and lateral orbitofrontal cortex – the different parts of the human brain affected by depression. The study was carried out by Professor Edmund Rolls from Warwick, Professor Jianfeng Feng from Warwick and from Fudan University in Shanghai, Dr Wei Cheng from Fudan, and by other centres in China.

Depression is expected to overtake heart disease to become the leading global disease burden by 2030. Professor Jianfeng Feng comments on how it has become increasingly prevalent: "More than one in ten people in their lifetime suffer from depression, a disease which is so common in modern society and we can even find the remains of Prozac (a depression drug) in the tap water in London."

"Our finding, with the combination of big data we collected around the world and our novel methods, enables us to locate the roots of depression which should open up new avenues for better therapeutic treatments in the near future for this horrible disease," says Feng.

Professor Edmund Rolls looks forward to the new treatments the research could lead to: "The new findings on how depression is related to different functional connectivities of the orbitofrontal cortex have implications for treatments in the light of a recent non-reward attractor theory of depression."

The research, 'Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression', is published in the peer-reviewed journal Brain.

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17th October 2016

Biotech firm to develop 3D bioprinted liver tissue for direct transplantation to patients

Organovo, a company focused on delivering scientific and medical breakthroughs using 3D bioprinting technology, has announced its plan to develop 3D bioprinted human liver tissue for direct transplantation to patients.

 

liver highlighted
© Yodiyim | Dreamstime.com

 

Organovo is announcing its program to develop 3D bioprinted human liver tissue based on the achievement of strong results in preclinical studies that used animal models. These demonstrated engraftment, vascularisation and sustained functionality of bioprinted liver tissue, including stable detection of liver-specific proteins and metabolic enzymes. The company expects to pursue this opportunity with a formal preclinical development program.

For patients in need of a liver transplant, no robust alternatives exist today. Approximately 17,000 patients are on the U.S. liver transplant waiting list, but only 6,000 liver transplants are performed each year.

Organovo plans to develop clinical solutions in two initial areas. First, acute-on-chronic liver failure (ACLF) is a recognised and distinct orphan disease entity encompassing an acute deterioration of liver function in patients with liver disease, which affects 150,000 patients annually in the United States. Second, paediatric metabolic liver diseases are another orphan disease indication where a bioprinted liver tissue patch may show therapeutic benefits.

The total addressable market opportunity for these initial indication areas exceeds $3 billion. Assuming development progresses according to its plan, Organovo intends to submit an Investigational New Drug application to the U.S. Food and Drug Administration (FDA) for its therapeutic liver tissue in three to five years. Organovo will seek breakthrough therapy designation, clinical development outside the United States, and other opportunities to help accelerate time to market. The company will also present more detailed preclinical results at upcoming scientific conferences.

 

liver bioprinting
Credit: Organovo

 

"We're excited to introduce an implantable bioprinted liver tissue as the first preclinical candidate in our therapeutic tissue portfolio, and see the early results as extremely promising," said Keith Murphy, CEO of Organovo. "The scientific and commercial progress we have already made with ExVive Human Liver Tissue in drug toxicity testing has given us a firm foundation upon which to build a larger tissue for transplant. Advancing our first therapeutic tissue into preclinical development is an important milestone for Organovo, and it speaks to the power of our technology platform in addressing multiple applications, including preclinical safety, disease modelling and tissue replacement products for surgical implantation. We believe that 3D bioprinted tissues have an opportunity to provide options for patients who suffer from liver disorders."

"Organovo's approach is designed to overcome many challenges that cell therapies and conventional tissue engineering have struggled to address – including limited engraftment and significant migration of cells away from the liver," said Eric Michael David, M.D., J.D., chief strategy officer and executive vice president of preclinical development. "In our preclinical studies, we deliver a patch of functional tissue directly to the liver, which integrates well, remains on the liver and maintains functionality. We believe our tissues have the potential to extend the lives of patients on liver transplant lists, or those who do not qualify for transplants due to other factors."

"Supply issues are a constant and growing challenge in transplant medicine and liver has the second highest transplant need among all organs," commented David A. Gerber, M.D., FACS, Professor of Surgery and Chief of Transplant Surgery, UNC School of Medicine. "New solutions in development, such as 3D bioprinted human tissues, have the potential to create tissues that could augment and extend organ function to give more time to those patients on transplant waiting lists. Moreover, we are continuing to push the boundaries and understand how to scale 3D bioprinting and tissue engineering to develop larger tissues."

"There are many conditions in areas such as liver, kidney, gastrointestinal, vascular, and lung disease where supplying a tissue patch may be curative, or bridge a patient a few more years before they need a transplant," said Dr. John Geibel, at Yale University. "The promise of 3D bioprinting human tissues to address these unmet needs is significant."

 

 

 

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13th October 2016

Playing golf can add five years to your life expectancy

Playing golf is likely to increase life expectancy, help prevent chronic diseases and improve mental health, a new study suggests.

 

golf life expectancy

 

Researchers from the University of Edinburgh reviewed 5,000 studies into golf to build a comprehensive picture of the sport’s health benefits, as well as its potential drawbacks. They found it can significantly improve both physical and mental health for people of all ages, genders and backgrounds. Furthermore, it was shown that these improvements are of particular help to seniors, as the benefits of playing golf increase with age. Balance and muscle endurance, for example, can be enhanced in older people.

Golfers playing a regular round of 18 holes can walk four to eight miles, typically burning a minimum of 500 calories – easily enough to reach and exceed the minimum government recommendations for exercise. Even those using an electric cart were found to average four miles of walking. In addition to the obvious physical benefits, golf can significantly improve mental health and well-being – increasing exposure to sunshine and fresh air, while reducing the risk of anxiety, depression and dementia.

In one of the studies they analysed, the researchers noted a 40% reduction in mortality rates among 300,000 members of the Swedish Golf Federation, corresponding to an increase in life expectancy of about five years.

"The moderate physical activity that golf provides increases life expectancy, has mental health benefits, and can help prevent and treat more than 40 major chronic diseases, such as heart attacks, stroke, diabetes, breast and colon cancer," says Dr Andrew Murray, lead author and researcher for the Golf & Health Project at the University of Edinburgh. "Evidence suggests golfers live longer than non-golfers, enjoying improvements in cholesterol levels, body composition, wellness, self-esteem and self-worth. Given that the sport can be played by the very young to the very old, this demonstrates a wide variety of health benefits for people of all ages."

However, there were also a number of risks found to be associated with playing golf – such as lightning strikes, and accidents involving carts. Golf was found to be the sport with the highest incidence of lightning strikes in the US, while more than 15,000 golf cart-related injuries were reported a year.

Their study is published online this month in the British Journal of Sports Medicine.

 

 

 

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6th October 2016

Scientists calculate the upper limit of human lifespan

Gains in the maximum human lifespan reached a plateau in the 1990s, according to researchers. They report that the absolute physical limit of human lifespan is 125 years.

 

human aging lifespan

 

A study published yesterday in Nature by the Albert Einstein College of Medicine suggests that it may not be possible to extend the human lifespan beyond the ages already attained by the oldest people on record.

Since the 19th century, average life expectancy has risen almost continuously – thanks to improvements in public health, diet, living standards and other areas. On average, for example, U.S. babies born today can expect to live to nearly 79, compared with only 47 for those born in 1900. Since the 1970s, the maximum duration of life – the age to which the oldest people live – has also risen. But according to the Einstein College researchers, this upward arc for maximal lifespan has a ceiling: and we've already touched it.

"Demographers, as well as biologists, have contended there is no reason to think that the ongoing increase in maximum lifespan will end soon," said senior author Jan Vijg, Ph.D., professor and chair of genetics. "But our data strongly suggest that it has already been attained and that this happened in the 1990s."

Dr. Vijg and his colleagues analysed data from the Human Mortality Database, which compiles mortality and population data from more than 40 nations. Since 1900, those countries generally show a decline in late-life mortality: the fraction of each birth cohort (i.e. people born in a particular year) who survive to old age (defined as 70 and up) increased with their calendar year of birth, pointing toward a continuing increase in average life expectancy.

But when the researchers looked at survival improvements since 1900 for people aged 100 and above, they found that gains in survival peaked at around 100 and then declined rapidly, regardless of the year people were born. "This finding indicates diminishing gains in reducing late-life mortality and a possible limit to human lifespan," said Dr. Vijg.

He and his colleagues then looked at "maximum reported age at death" data from the International Database on Longevity. They focused on people verified as living to age 110 or older between 1968 and 2006 in the four countries (the U.S., France, Japan and the U.K.) with the largest number of long-lived individuals. Age at death for these supercentenarians increased rapidly between the 1970s and early 1990s, but reached a plateau around 1995 – further evidence for a lifespan limit. This plateau, the researchers note, occurred close to 1997 – the year of death for 122-year-old French woman, Jeanne Calment, who achieved the maximum documented lifespan of any person in history.

Using maximum-reported-age-at-death data, the Einstein researchers put the average maximum human lifespan at 115 years – a calculation allowing for record-oldest individuals occasionally living longer or shorter than 115 years (Jeanne Calment, they conclude, was a statistical outlier). Finally, they calculate 125 years as the absolute limit of human lifespan. Expressed another way, this means the probability in any given year of seeing a person live to 125 anywhere in the world is less than 1 in 10,000.

"Further progress against infectious and chronic diseases may continue boosting average life expectancy – but not maximum lifespan," says Dr. Vijg. "While it's conceivable that therapeutic breakthroughs might extend human longevity beyond the limits we've calculated, such advances would need to overwhelm the many genetic variants that appear to collectively determine the human lifespan. Perhaps resources now being spent to increase lifespan should instead go to lengthening healthspan – the duration of old age spent in good health."

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6th October 2016

Caffeine may reduce the risk of dementia

A study by the University of Wisconsin-Milwaukee shows that caffeine consumption may cut the risk of dementia in older women by 36%.

 

coffee

 

Among a group of older women, self-reported caffeine consumption of more than 261 mg per day was associated with a 36 percent reduction in the risk of incident dementia over 10 years of follow-up. This level is equivalent to two to three 8-oz cups of coffee per day, five to six 8-oz cups of black tea, or seven to eight 12-ounce cans of cola.

"The mounting evidence of caffeine consumption as a potentially protective factor against cognitive impairment is exciting given that caffeine is also an easily modifiable dietary factor with very few contraindications," said Ira Driscoll, PhD, the study's lead author and a professor of psychology at the University of Wisconsin-Milwaukee. "What is unique about this study is that we had an unprecedented opportunity to examine the relationships between caffeine intake and dementia incidence in a large and well-defined, prospectively-studied cohort of women."

The findings come from participants in the Women's Health Initiative Memory Study, which is funded by the National Heart, Lung, and Blood Institute. Driscoll and her research colleagues used data from 6,500 community-dwelling, postmenopausal women aged 65 and older who reported some level of caffeine consumption. Intake was estimated from questions about coffee, tea, and cola beverage intake, including frequency and serving size.

In 10 years or less of follow-up with annual assessments of cognitive function, 388 of these women received a diagnosis of probable dementia or some form of global cognitive impairment. Those who consumed above the median amount of caffeine for this group (with average intake of 261 mg per day) were diagnosed at a lower rate than those who fell below the median (with an average intake of 64 mg per day). The researchers adjusted for risk factors such as hormone therapy, age, race, education, body mass index, sleep quality, depression, hypertension, prior cardiovascular disease, diabetes, smoking, and alcohol consumption.

The paper "Relationships Between Caffeine Intake and Risk for Probable Dementia or Global Cognitive Impairment: The Women's Health Initiative Memory Study" is available at: http://biomedgerontology.oxfordjournals.org/content/early/2016/09/20/gerona.glw078

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3rd October 2016

Measles has officially been eradicated from the Americas

The Region of the Americas is the first in the world to have officially eliminated measles, a viral disease that can cause severe health problems including pneumonia, brain swelling and even death. This achievement culminates a 22-year effort involving mass vaccination against measles, mumps and rubella throughout the Americas.

 

 

 

The declaration of measles' elimination was made by the International Expert Committee for Documenting and Verifying Measles, Rubella, and Congenital Rubella Syndrome Elimination in the Americas. The announcement came during the 55th Directing Council of the Pan American Health Organisation/World Health Organisation (PAHO/WHO), attended by ministers of health from throughout the region.

Measles is the fifth vaccine-preventable disease to be eliminated from the Americas, after the regional eradication of smallpox in 1971, polio in 1994, and rubella and congenital rubella syndrome in 2015.

"This is a historic day for our region and indeed the world," said Carissa Etienne, PAHO/WHO Director. "It is proof of the remarkable success that can be achieved when countries work together in solidarity towards a common goal. It is the result of a commitment made more than two decades ago, in 1994, when the countries of the Americas pledged to end measles circulation by the turn of the 21st century."

Before mass vaccination was initiated in 1980, measles caused nearly 2.6 million annual deaths worldwide. In the Americas, 101,800 deaths were attributed to the disease between 1971 and 1979. A cost-effectiveness study on measles elimination in Latin America and the Caribbean has estimated that with vaccination, 3.2 million measles cases will have been prevented in the region and 16,000 deaths between 2000 and 2020.

"This historic milestone would never have been possible without the strong political commitment of our Member States in ensuring that all children have access to life-saving vaccines," Etienne continued. "It would not have been possible without the generosity and commitment of health workers and volunteers who have worked so hard to take the benefits of vaccines to all people – including those in vulnerable and hard-to-reach communities."

 

measles vaccination
Credit: Pan American Health Organisation

 

Measles transmission had been considered interrupted in the region since 2002, when the last endemic case was reported in Venezuela. However, as it continued to circulate in other parts of the world, some countries in the Americas experienced imported cases, with over 5,000 reported infections between 2003 and 2014. The Expert Committee reviewed evidence presented by all the countries of the region between 2015 and August 2016 and decided that it met the established criteria for elimination. This process included six years of work with countries to document evidence of the elimination.

As a result of worldwide measles elimination efforts, only 245,000 measles cases were reported globally in 2015, a substantial decline from earlier years. More than a half of these reported cases were in Africa and Asia. To maintain measles elimination, the Expert Committee have recommended that all countries of the Americas strengthen active surveillance and maintain their populations' immunity through routine vaccination.

"I would like to emphasise that our work on this front is not yet done," warned Etienne. "We cannot become complacent with this achievement but must rather protect it carefully. Measles still circulates widely in other parts of the world, and so we must be prepared to respond to imported cases. It is critical that we continue to maintain high vaccination coverage rates, and it is crucial that any suspected measles cases be immediately reported to the authorities for rapid follow-up."

Under the WHO's Global Vaccine Action Plan, measles will be wiped out by 2020 everywhere except Southeast Asia. Humanity is clearly winning the fight against this particular virus.

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