Gene Clue to Post-Traumatic Stress Disorder Risk

Susceptibility to post-traumatic stress disorder could be partially determined by gene variants, says a study.

A US team looked at the DNA from 200 members of 12 families who survived the 1988 Armenian earthquake. It found those who carried two gene variants which affect the production of serotonin – which affects mood and behaviour – were more likely to display symptoms of PTSD.

Gene Clue to Post-Traumatic Stress Disorder Risk

The research is published in Journal of Affective Disorders.

PTSD can arise after any kind of experience that causes trauma, whether that be in war, after a natural disaster or because of child abuse or sexual assault.

Symptoms can include flashbacks, feeling emotionally numb or hyper-alert to danger, and avoiding situations that act as reminders of the original trauma.

It is estimated that up to 3% of the general population is likely to be affected by PTSD at some point.

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Screening Hope

The Armenian earthquake, which had a magnitude of 7.1, occurred on 7 December 1988. It hit the northern part of Armenia, which was then part of the Soviet Union. It killed at least 25,000 people.

All those who took part in the study had experienced the earthquake, 90% saw dead bodies and 92% saw people who had been seriously injured.

They also undertook a recognised assessment to evaluate what, if any, PTSD symptoms they had experienced.

When the University of California, Los Angeles (UCLA) researchers analysed the Armenian families’ DNA, they saw that those who had experienced more PTSD symptoms were more likely to have two specific gene variants – TPH1 and TPH2.

Dr Armen Goenjian, a research professor of psychiatry who led the work, said: “We suspect that the gene variants produce less serotonin, predisposing these family members to PTSD after exposure to violence or disaster. Our next step will be to try and replicate the findings in a larger, more heterogeneous population.”

But he said that, if larger studies did confirm the finding, they could eventually lead to new ways to screen people at risk of PTSD, and target specific medicines for preventing and treating the disorder.

Dr Goenjian added: “A diagnostic tool based upon TPH1 and TPH2 could enable military leaders to identify soldiers who are at higher risk of developing PTSD, and reassign their combat duties accordingly. Our findings may also help scientists uncover alternative treatments for the disorder, such as gene therapy or new drugs that regulate the chemicals responsible for PTSD symptoms.”

Depression Link

Psychologist Dr Jennifer Wild, who is an expert in PTSD, said the finding was significant, but it would be “premature” to give it too much emphasis.

She added: “The link between the gene variant and PTSD is strong, which is promising in terms of guiding future research and possibly leading to a genetic screening test. But the gene variant discovered in the study only accounted for a small proportion of PTSD symptoms in sufferers. Psychological factors, such as past history of trauma or a trait called neuroticism, tend to predict PTSD with much greater precision and they are less costly to assess.”

And she said that the fact people were asked to think back to their experiences – rather than studied while they were experiencing them – was also problematic.

The commonly used antidepressants SSRIs (selective serotonin re-uptake inhibitors) improve mood by prolonging the effect of serotonin in the brain by slowing its absorption by brain cells.

But Dr Wild said the recommended treatment for PTSD was psychological therapy, and that SSRIs were not recommended in the UK for PTSD treatment.

Source: BBC News

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UK Biobank Opens to Researchers

The UK Biobank, the most comprehensive health study in the UK, is opening its doors to researchers.

It has collated about 20TB (terabytes) of securely stored data, the equivalent of 30,000 CDs-worth, on 500,000 people.

The aim of the biobank is to improve the prevention, diagnosis and treatment of a wide range of conditions such as heart disease, cancer and diabetes.

England’s chief medical officer, Dame Sally Davies, said the UK Biobank would be a “globally unique resource”.

The biobank began recruiting participants three years ago, and was open to people aged 40 to 69.

Each answered questions on their health, lifestyle, diet, memory, work and family history.

They also had a range of measurements taken, including blood pressure, pulse rate, height, weight, body fat and lung function, and provided blood, saliva and urine samples.

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Very exciting day

About 26,000 people with diabetes, 50,000 with joint disorders, 41,000 teetotallers and 11,000 heart attack patients are taking part.

Participants’ health will be followed over many years.

It is about to undertake repeat measures of 20,000 participants from the Manchester area, and later this year it will ask participants to wear an activity monitor for one week.

It has also been overseeing a diet questionnaire, which has been filled in by 400,000 participants.

The hope is that the UK Biobank will allow scientists to investigate why some people develop particular diseases in middle age while others do not, with the hope of developing new treatments and prevention strategies.

It will be open to researchers from the UK and abroad, who will be able to use the – anonymised – data in their work.

Professor Sir Rory Collins, principal investigator at the biobank, said: “This is without doubt a very exciting day for medical research, not just in the UK but around the world. We are grateful to participants for their trust and support so far. But they have not joined the project to see it remain idle; we all want to see the resource used extensively to bring about benefits to health and wellbeing.”

Prof Dame Sally Davies, chief medical officer and chief scientific adviser at the Department of Health, said: “UK Biobank is a globally unique resource which places the UK at the forefront of the quest to understand why some people develop life-threatening diseases or debilitating conditions.

“It has huge potential for future generations and will help us understand how our children and our children’s children can live longer, healthier lives.”

The biobank is funded by the Wellcome Trust, Medical Research Council, Department of Health, Scottish Government, Welsh Government and the British Heart Foundation.

Source: BBC News UK

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US Face Transplant gives Man new Jaw, Teeth and Tongue

US doctors have carried out what they say is the most extensive face transplant ever performed.

The operation at the University of Maryland gave Richard Norris a new face, including jaw, teeth and tongue.

US Face Transplant gives Man new Jaw, Teeth and Tongue

The 37-year-old has lived as a recluse for 15 years after being severely injured in a gun accident, and wore a mask whenever he went outside.

The surgery was funded by the US Navy, which hopes the techniques will help casualties from Iraq and Afghanistan.

Surgeons who carried out the 36-hour operation say it was part of a series of transplant operations lasting 72 hours, using organs from one donor in five patients including Mr Norris.

He lost his lips and nose in the accident, and only had limited movement of his mouth.

The lead surgeon says Mr Norris will now get his life back.

“Our goal is to restore function as well as have aesthetically pleasing results,” said Eduardo Rodriguez.

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The team at the University of Maryland say Mr Norris is now brushing his teeth and shaving, and has regained his sense of smell.

The US government estimates that 200 wounded troops might be eligible for face transplants.

The first face transplant was performed in France in 2005, on a woman who was mauled by her dog.

In 2010 surgeons in Spain carried out the world’s first full face transplant.

Source: BBC News UK

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Gene Flaw Linked to Serious Flu Risk

Scientists have identified a genetic flaw that may explain why some people get more ill with flu than others.

Writing in Nature, the researchers said the variant of the IFITM3 gene was much more common in people hospitalised for flu than in the general population. It controls a malformed protein, which makes cells more susceptible to viral infection.

Gene flaw linked to serious flu risk

Experts said those with the flaw could be given the flu jab, like other at-risk groups.

Researchers removed the gene from mice. They found that when they developed flu, their symptoms were much worse than those seen in mice with the gene.

Evidence from genetic databases covering thousands of people showed the flawed version of the gene is present in around one in 400 people.

The scientists, who came from the UK and US, then sequenced the IFITM3 genes of 53 patients who were in hospital with flu.

Three were found to have the variant – a rate of one in 20. The researchers say these findings now need to be replicated in bigger studies. And they add it is probably only part of the genetic jigsaw that determines a person’s response to flu.

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First Clue

Professor Paul Kellam of the Wellcome Trust Sanger Institute, who co-led the research, said: “At the moment, if someone is in a more vulnerable group because of co-morbidity [another health problem], they would be offered the flu vaccine.

“This is the idea here.” But he said having this variant would not make any difference to how people were treated.

Prof Kellam added: “Our research is important for people who have this variant as we predict their immune defences could be weakened to some virus infections.  “Ultimately as we learn more about the genetics of susceptibility to viruses, then people can take informed precautions, such as vaccination to prevent infection.”

Professor Peter Openshaw, director of the Centre for Respiratory Infection at Imperial College London, said: “This new discovery is the first clue from our detailed study of the devastating effects of flu in hospitalised patients. “It vindicates our conviction that there is something unusual about these patients.”

Sir Mark Walport, director of the Wellcome Trust, said: “During the recent swine flu pandemic, many people found it remarkable that the same virus could provoke only mild symptoms in most people, while, more rarely, threatening the lives of others.

“This discovery points to a piece of the explanation: genetic variations affect the way in which different people respond to infection. This important research adds to a growing scientific understanding that genetic factors affect the course of disease in more than one way. Genetic variations in a virus can increase its virulence, but genetic variations in that virus’s host – us – matter greatly as well.”

Source: BBC News UK

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Will we ever Grow Replacement Hands?

It might seem unbelievable, but researchers can grow organs in the laboratory. There are patients walking around with body parts which have been designed and built by doctors out of a patient’s own cells.

Over the past few weeks on the BBC News website we have looked at the potential for bionic body parts and artificial organs to repair the human body. Now we take a look at “growing-your-own”.

There is a pressing need. A shortage of available organs means many die on waiting lists and those that get an organ must spend a lifetime on immunosuppressant drugs to avoid rejection.

Is the idea of growing hands a myth or a far-off reality

The idea is that using a patient’s own stem cells to grow new body parts avoids the whole issue of rejection as well as waiting for a donor.

Dr Anthony Atala, director of the Institute for Regenerative Medicine at the Wake Forest Baptist Medical Center in North Carolina, US, has made breakthroughs in building bladders and urethras.

He breaks tissue-building into four levels of complexity. Flat structures, such as the skin, are the simplest to engineer as they are generally made up of just the one type of cell.

Tubes, such as blood vessels and urethras, which have two types of cells and act as a conduit. Hollow non-tubular organs like the bladder and the stomach, which have more complex structures and functions.

Solid organs, such as the kidney, heart and liver, are the most complex to engineer. They are exponentially more complex, have many different cell types, and more challenges in the blood supply.

“We’ve been able to implant the first three in humans. We don’t have any examples yet of solid organs in humans because its much more complex,” Dr Atala told the BBC.

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Bladder builders

His technique for growing bladders starts with taking a tissue sample, about half the size of a postage stamp, from the bladder that is being repaired.

Over about a month, the cells are grown in the laboratory in large quantities. Meanwhile a scaffold in the shape of the organ, or part of the organ, being replaced is built.

“We coat the scaffold, basically like creating a layer cake. We place the cells on the structure one layer at a time with the cells in the correct positions,” Dr Atala said.

The cake is then “baked” for a two weeks in an oven, which has the same conditions as the inside of the human body. The new bladder is then ready to be implanted back into the body.

Eventually the scaffold is absorbed by the body, leaving the cells in place. Building a scaffold for the bladder is one thing, building one for the heart is far more complicated. One of the problems when you move to larger organs is the getting the blood supply to work, connecting arteries, capillaries and veins to keep the organ alive.

A bladder scaffold is used to hold together the new structure

It is why some researchers are investigating “decellularisation” – taking an existing donated organ, stripping out the original cells and replacing them with new cells from the patient who will receive the organ.

Prof Martin Birchall, a surgeon at University College London, has been involved in a number of windpipe transplants performed in this way.

The technique starts with a donor windpipe which is then effectively put through a washing machine. Repeated cycles of enzymes and detergents break down and wash away the host cells.

What is left behind is a web of proteins, mostly collagens and elastins, which give the windpipe its structure. It would look and feel like a windpipe, just without cells – a natural scaffold.

The next steps are very similar to those for making the bladder. Stem cells are taken, this time from bone marrow, and grown in a lab before being layered onto the scaffold.

The first patient was fitted with one of these windpipes in Spain in 2008.

Prof Birchall said: “We’ve made some inroads by starting with the windpipe. We’re looking at some other tissues now like the oesophagus and diaphragm and overseas the big breakthroughs have been in building the bladder and urethra.

“Those are the areas in which immediate breakthroughs have occurred, but I see a raft of further first-in-man studies in other organs happening in the next five years.”

Heartbeat

There are already strong hints of what the next steps could be. Dr Doris Taylor, who is about to move to the Texas Heart Institute, has used the decellurisation technique on rats’ hearts and produced beating organs.

The cells were stripped away leaving a “ghost heart” and were then injected with heart cells. Eight days later the heart was beating, albeit at just 2% of normal heart function.

She said the technique could “absolutely” be used on any organ that had a blood supply. She told the BBC: “It’s not science fiction any more, but moving that to more complex organs is the challenge ahead of us.”

Other groups have also produced miniature organs or “organoids”. They are not the full-blown thing, but they perform the same functions at a smaller scale.

Wake Forest researchers have produced liver organoids which can break down drugs.

Dr Atala said: “The challenge for us is – how do we scale up?” Bioprinting, just like an office printer except it “prints” cells layer by layer, has been used to “print” a kidney.

While these findings are a very long way from making it into hospitals, if indeed they ever do, the scientists involved are convinced these techniques will come good.

“The vision has to be tempered by the past and the number of false dawns that have occurred,” Prof Birchall said. But I genuinely do believe stem-cell technologies and tissue engineering is going to completely transform healthcare delivery in the future. I see it incrementally reaching out to replace transplantation. The writing is on the wall for it to do wonderful things.”

Dr Atala said: “The strategies are out there to someday be able to target every organ in the body we are not there yet. We are nowhere near there yet. But the goal of the field is to keep on advancing the number of tissues that we can target.”

Of course growing a hand is even more challenging than anything being tried in laboratories so far. Will it ever be possible?

“You never say never, but certainly it’s something I will most likely not see in my lifetime,” Dr Atala concluded.

Source: BBC News UK

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Human Stem Cells Help Blind Rats

Stem cells taken from the back of a human eye have restored some vision to blind rats, according to researchers.

They say the findings could help treat blindness, caused by glaucoma, if similar results can be repeated in humans.

The study, published in the journal Stem Cells Translational Medicine, used the cells to form new nerves in the eye. These hooked up with the existing nerves, restoring sight.

Human Stem Cells Help Blind Rats

Glaucoma can lead to blindness and is caused by a build-up of pressure within the eye. This kills retinal ganglion cells, the nerves which take information from the retina and pass it onto the brain.

Researchers at University College London and Moorfields Eye Hospital believe they have regenerated the retinal ganglion cells using human stem cells.

With permission from families, cell samples were taken from eyes which had been donated for cornea transplants.

Very rare cells in the eye, Muller glia stem cells, were collected. These were grown in the laboratory and converted into retinal ganglion cells.

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These cells were then transplanted into the eyes of rats without retinal ganglion cells. Before the transplant the rats were blind. Afterwards, electrodes attached to the rats’ heads showed that their brains were responding to low levels of light.

One of the researchers Dr Astrid Limb said the new cells were not joining up with the optic nerve as they would normally. Instead they appeared to be “bridging” with other nerves in the retina, which could pass the message on.

She said: “Although this research is still a long way from the clinic, it is a significant step towards our ultimate goal of finding a cure for glaucoma and other related conditions.”

Prof Peng Khaw, the director of the National Institute for Health Research centre at Moorfields, said: “These results are very exciting.  We see patients with glaucoma whose lives would be transformed with an improvement of only a small percentage of nerve cell function.  The results of these experiments suggest that this may be possible in the future using cells we all have in our own eyes to achieve this.”

The study was funded by the Medical Research Council. Its head of regenerative medicine, Dr Rob Buckle, said: “Repair of the eye is an area that is now at the forefront of this field, and this study highlights a new route for delivering the promise of regenerative medicine to treat disabling conditions such as glaucoma.”

Source: BBC News UK

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Watermelon Found to be Source of Salmonella Outbreak

A salmonella outbreak linked to watermelons has affected 35 people in the UK, health experts have revealed.

One person has died, although they had serious underlying health issues.

The Health Protection Agency (HPA) said three times the usual number of cases of Salmonella Newport infection for this time of year had been seen. Cases of illness caused by the same strain have been seen in Ireland and Germany.

Over 200 cases of Salmonella Newport are reported in the UK each year. Infection causes a similar illness to other forms of salmonella infection and symptoms include diarrhoea, vomiting, abdominal pain and fever.

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The people affected in this outbreak, which began in early December, ranged in age from six months to 85 years.  Around 70% of cases were in women, and the East of England has had more cases than other regions.

Experts say there are two possible ways watermelons could have caused infection.

One is that the surface of the melons could have been contaminated with Salmonella bacteria which may have transferred on to the flesh of the melon during the cutting process.

The second is if the melons were stored or washed in contaminated water, the salmonella bacteria could have got into the flesh of the melon through the cut stem.

Wash Fruit and Veg

Dr Bob Adak, head of the gastrointestinal diseases department at the HPA, which has been monitoring the outbreak in England, Wales and Northern Ireland said, “Although it’s too soon to say with certainty what the likely cause of infection is, early indications suggest that a number of people became unwell after eating watermelon. This has also been noted in the cases in Scotland and Germany although further investigation is ongoing.”

He added: “It’s important to remember the risk of becoming unwell after eating watermelon is very low. These cases only represent a very small proportion of total consumption.  It is always advisable to wash fruits and vegetables – including watermelon – before consumption to reduce the risk of possible illness.”

Dr Paul Wigley, at the University of Liverpool said: “Salmonella Newport is not an particularly unusual form. “Fruit and vegetables are not the main source of infection which is usually meat or unpasteurised dairy products, but they can be contaminated with Salmonella in production or processing. There are examples of fruit and salad vegetables causing major salmonella outbreaks including salad onions, lettuce and peanuts. As Salmonella Newport is often associated with cattle or horses, contamination from animal manure used as fertiliser is a potential source. ”

The HPA and the Food Standards Agency are currently investigating the source of this outbreak.

Salmonella Newport has been found in many different foods in previous UK outbreaks – the largest one was in 2004 and was associated with eating lettuce at restaurants and takeaways.

Source: BBC News UK

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Transplant Jaw made by 3D Printer Claimed as First

A 3D printer-created lower jaw has been fitted to an 83-year-old woman’s face in what doctors say is the first operation of its kind.

The transplant was carried out in June in the Netherlands, but is only now being publicised. The implant was made out of titanium powder – heated and fused together by a laser, one layer at a time.

A high-temperature plasma spray was used to cover the jaw part with a bioceramic coating

Technicians say the operation’s success paves the way for the use of more 3D-printed patient-specific parts.

The surgery follows research carried out at the Biomedical Research Institute at Hasselt University in Belgium, and the implant was built by LayerWise – a specialised metal-parts manufacturer based in the same country.

Articulated joints

The patient involved had developed a chronic bone infection. Doctors believed reconstructive surgery would have been risky because of her age and so opted for the new technology.

The implant is a complex part – involving articulated joints, cavities to promote muscle attachment and grooves to direct the regrowth of nerves and veins.

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However, once designed, it only took a few hours to print.

“Once we received the 3D digital design, the part was split up automatically into 2D layers and then we sent those cross sections to the printing machine,” Ruben Wauthle, LayerWise’s medical applications engineer, told the BBC. It used a laser beam to melt successive thin layers of titanium powder together to build the part. This was repeated with each cross section melted to the previous layer. It took 33 layers to build 1mm of height, so you can imagine there were many thousand layers necessary to build this jawbone.”

Once completed, the part was given a bioceramic coating. The team said the operation to attach it to the woman’s face took four hours, a fifth of the time required for traditional reconstructive surgery.

“Shortly after waking up from the anaesthetics the patient spoke a few words, and the day after the patient was able to swallow again,” said Dr Jules Poukens from Hasselt University, who led the surgical team. The new treatment is a world premiere because it concerns the first patient-specific implant in replacement of the entire lower jaw.”

Screw-in teeth

The woman was able to go home after four days.

Her new jaw weighs 107g, just over a third heavier than before, but the doctors said that she should find it easy to get used to the extra weight.

Follow-up surgery is scheduled later this month when the team will remove healing implants inserted into holes built into the implant’s surface.

A specially made dental bridge will then be attached to the part, following which false teeth will be screwed into the holes to provide a set of dentures.

Printed organs

The team said that it expected similar techniques to become more common over the coming years.

“The advantages are that the surgery time decreases because the implants perfectly fit the patients and hospitalisation time also lowers – all reducing medical costs,” said Mr Wauthle. “You can build parts that you can’t create using any other technique. For example you can print porous titanium structures which allow bone in-growth and allow a better fixation of the implant, giving it a longer lifetime.”

The research follows a separate project at Washington State University last year in which engineers demonstrated how 3D-printer-created ceramic scaffolds could be used to promote the growth of new bone tissue.

They said experiments on animals suggested the technique could be used in humans within the next couple of decades. LayerWise believes the two projects only hint at the scope of the potential medical uses for 3D printing.

Mr Wauthle said that the ultimate goal was to print body organs ready for transplant, but cautioned that such advances might be beyond their lifetimes.

He said “There are still big biological and chemical issues to be solved. At the moment we use metal powder for printing. To print organic tissue and bone you would need organic material as your ‘ink’. Technically it could be possible – but there is still a long way to go before we’re there.”

Source: BBC News UK

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