Blood clots

Every year, millions of people come into emergency rooms complaining of chest pains, yet those pains are only sometimes due to heart attacks. Unfortunately in many of those cases, the only way to be sure of what’s going on is to admit the patient for an overnight stay, and administer time-consuming and costly tests. Now, however, a new procedure could reveal the presence and location of a blood clot within hours. It’s made possible by the injection of nanoparticles, each containing a million atoms of bismuth – a toxic heavy metal.

The particles were developed by Dr. Dipanjan Pan, at the Washington University School of Medicine in St. Louis, Missouri.

He used bismuth because it shows up on a spectral CT scanner, which is itself a new type of technology. Whereas regular CT scanners only provide black and white images, spectral scanners use the entire spectrum of the X-ray beam to differentiate objects, and display metals (such as bismuth) in color.

Injecting a straight-up shot of toxic heavy metals into a patient’s bloodstream would have dire consequences. To keep the nanoparticles harmless, they were created from a compound in which bismuth atoms were attached to fatty acid chains that won’t come apart in the body. This compound was dissolved in a detergent, which was then combined with phospholipids – a key component of cell membranes. Like oil droplets in vinegar, the nanoparticles proceeded to self-assemble, with the bismuth compound at the core and a phospholipid membrane on the outside. Trials on mice showed that the body was able to release the bismuth from within the membrane, in a safe form.

Pan also added a molecule to the nanoparticles’ surface that is attracted to fibrin, a protein that is found in blood clots but not elsewhere in the vascular system. That molecule draws the particles to blood clots, where the bismuth shows up as a color such as green or yellow on a spectral CT scan image.

Not only could the technology be used to locate blood clots, but it could possibly even treat their cause – ruptures in artery walls. If the nanoparticles contained some sort of healing agent, then once they attached to the fibrin in a blood clot, they could set about sealing any weak spots.

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Blood Clots

Firefly proteins could provide an agent for the generation of near-infrared light, which in turn could help to improve the detection of blood clots.

Researchers from Connecticut College have been studying luciferase, the enzyme that makes fireflies glow, hoping to develop a new medical imaging agent to improve the monitoring of treatment with heparin, a blood thinner taken to prevent blood clots. Combining a protein from firefly luciferase with a dye that allows the protein to emit near-infrared light enabled the new material to detect tiny amounts of factor Xa, which is a blood protein used to monitor the effectiveness of heparin treatment.

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Fake Skin

Ink-jet printing technology has inspired scientists to look for ways to build sheets of skin that could one day be used for grafts in burn victims, experts said Sunday.

One technique involves a portable bioprinter that could be carried to wounded soldiers on the battlefield where it would scan the injury, take cells from the patient and print a section of compatible skin.

Another uses a three-dimensional printer combining donor cells, biofriendly gel and other materials to build cartilage.

The 3-D printer was shown at work, building a prototype of an ear during a half-hour demonstration at a Washington science conference.

Hod Lipson of Cornell University in New York said it worked much like an ink-jet printer.

“It spits out plastic to gradually build an object layer by layer… after a couple of hours you end up with a real physical object that you can hold in your hand,” he said.

“Just imagine — if you could take cells from a donor, culture them, put them into an ink and recreate an implant that is alive and made of the original cells from the donor — how useful that would be in terms of avoiding rejection,” said Lipson.

“That is where we are going. Let’s see how far we can go.”

Studies using the technology in animals have shown promise, particularly with printed cartilage, which is relatively simple in its construction and is tough so it can withstand the rigors of printing.

“There are very severe limitations,” Lipson said. “We are right now limited to cells… that can handle being printed.”

Scientist James Yoo of Wake Forest University in North Carolina said his team’s approach to printing skin has shown positive results in repairing skin in mouse and pig models.

“One approach is to directly deploy cells to the wound site and the other approach is to build a tissue construct outside the body and transfer it into the body,” said Yoo.

The technology works in part via a scanner that takes a measure of the affected area and identifies the depth and extent of the injury, informing the bioprinter of how many layers of cells need to be made.

Both scientists said the advances were still in their early stages and required more research and refinement before they are ready for human patients.

“One of the challenges that we will eventually face is like anything else, when you are trying to transfer the technology into the body, how can we create and connect those tissues?” said Yoo.

“Whatever you put in the body has to be connected with the body’s blood vessels, blood supply and oxygen.”

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Asthma Attacks

Engineers at Siemens have developed a mobile phone sized device that is capable of detecting nitric oxide (NO), an oncoming asthma attack marker, at parts per billion scale. Once the device makes it to the consumer market, asthma patients will be able to take preemptive action and raise their drug dosage levels when an attack looks impending.

The new sensor can detect increases in NO one day before an acute asthma attack occurs. Over the past few years, medical researchers and health insurance companies have recognized that NO levels are an effective indication of an impending asthma attack. In the analysis of a patient’s breath, the system first converts nitrogen monoxide into nitrogen dioxide, after which the air flows across the actual sensor. Only the particles signaling the attack adhere to the sensor’s surface. This generates a voltage that is measured by a field-effect transistor. The intensity of the voltage is directly dependent on the amount of nitrogen monoxide in the patient’s breath. On the basis of this value, the patient can decide what dose of anti-inflammatory medication he or she should take.

Another type of breath sensor under consideration would allow athletes to check whether they are exercising enough to burn fat. The detection principle is the same, except that the system measures the level of acetone. The latter is generated in the body when fat is burned and is also detectable in a person’s breath.

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A team of mathematicians from The University of Queensland has helped design a prototype for a new generation of bone implants that could potentially reduce surgery and rehabilitation times, as well as provide a solution for patients for whom current orthopaedic implants are not suitable.

Using a mathematical approach called “topology optimisation” – a method that optimises the layout of a material within a particular design space – the team has come up with a prototype of a three-dimensional scaffold that closely matches the stiffness of human bone, while at the same time has an open pore structure for transporting essential nutrients through the implant.

Such scaffolds can form the building blocks of bone implants that will be fully customisable to patients’ needs.

Conventional implants are manufactured out of fully dense (and non-porous) titanium, which can be too stiff for the surrounding bone.

This mismatch in stiffness has been identified as a major causal factor in implant loosening. Further, conventional implants can be unsuitable for patients who have suffered from severe trauma, tumours, infection or deformities.

“Customised, porous implants may be able to alleviate these issues by matching both the geometry and the properties of the surrounding bone,” said Dr Vivien Challis, of UQ’s School of Mathematics and Physics, and co-author of the study that was recently published in Advanced Engineering Materials.

“Our project is a great example of the way in which mathematics can drive interdisciplinary, cutting-edge research,” she said.

“A feature of our research is the constant interaction between theory, experiment and numerical simulation.”

Other researchers in the study are Associate Professors Anthony Roberts and Joseph Grotowski (both from The University of Queensland), as well as Professor Timothy Sercombe and Dr Lai-Chang Zhang (both from The University of Western Australia).

The team has succeeded in manufacturing these complex bone implant designs using an advanced manufacturing technique called “selective laser melting” – a process in which a high-powered laser is used to melt metal powder into the required shape, layer by layer.

The multi-disciplinary team’s research will help develop better-performing orthopaedic implants for Australia’s aging population.

The team has been working on this project since 2008 and is funded by the Australian Research Council (ARC). Their research will continue under the recently-announced ARC funding for 2011-2013.

More information: The paper, “Prototypes for Bone Implant Scaffolds Designed via
Topology Optimization and Manufactured by Solid Freeform Fabrication,” was published in the November 2010 issue of Advanced Engineering Materials and can be found online.

A computationally generated image of the three-dimensional bone implant prototype was featured on the cover of the same issue.

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PneumoniaCheck

A team of mechanical engineering and bioengineering graduate students at Georgia Tech has developed an innovative device for capturing aerosols originating in the lungs. The common problem in diagnosing pneumonia is that during collection, the sample often gets contaminated by oral bacteria. The PneumoniaCheck takes advantage of air currents to separate particles coming from the lungs from those originating in the mouth so that pulmonary phlegm hits the filter and everything else goes into the balloon below. David Ku, the engineering professor who oversaw the project, says that the PneumoniaCheck “has the potential to save more lives than any other medical device.” To be available for sale later this month, via a spinoff firm MD Innovate, we hope the professor’s comments come true.

The device contains a plastic tube with a mouthpiece. A patient coughs into the device to fill up a balloon-like upper airway reservoir before the lung aerosols go into a filter. Using fluid mechanics, PneumoniaCheck separates the upper airway particles of the mouth from the lower airway particles coming from the lungs.

The FDA has cleared PneumoniaCheck for sale in the U.S. The device is licensed but its patent is pending.

Researchers in Sydney have come up with a fix for chronic pain that’s not really a fix at all: a smart chip that, when embedded in the spine, intercepts and blocks pain messages en route to the brain.

The smart chip is embedded in the spine or somewhere else between the brain and the source of chronic pain. The chip itself is housed in a biocompatible casing that is smaller than the head of a match. That in turn is wired to a larger implanted device containing a battery – which charges wirelessly from an outside source – and a computer processor.

According to its designers at National ICT Australia (NICTA), the chip can measure the properties of signals and pick out the ones that are carrying pain to the nerve center. When it sees a pain signal headed brainward, it can send out a 10-volt electric pulse that blocks the pain signal; no signal, no pain.

The device is designed for those with serious chronic back pain or leg pain, though it could ostensibly be used to block all kinds of pains in the body. That in turn could increase productivity in workers suffering from chronic pain and save patients and health care systems fair sums of money.

It also seems like it could fool the brain into ignoring something potentially important. After all, pain exists to let us know something is wrong, and it’s not difficult to picture scenarios where interfering with that natural signal pathway could lead to larger, more pronounced problems. That being said, the potential to help Brett Favre play through three more seasons can’t be bad.

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Daily Aspirin Can Reduce Your Chances of Dying From Cancer Up to 60%

Researchers have found a drug that’s unexpectedly effective at reducing one’s chances of dying from many common forms of cancer, in some cases lessening fatalities up to 60%. It’s a small, long term daily dose of aspirin.

In a new report, stemming from eight long term studies including some 25,000 patients, British researchers found that a small, 75 milligram dose of aspirin taken daily for at least five years reduces risk of dying from common cancers roughly 10 to 60 percent. Here are some of the findings, published today on the website of medical journal The Lancet:

• After 5 years of daily aspirin, death due to gastrointestinal cancers decreased by 54%.
• After 20 years, death due to prostate cancer decreased by 10%
• After 20 years, death due to lung cancer decreased by 30% (among those with adenocarcinomas, typically seen in nonsmokers)
• After 20 years, death due to colorectal cancer decreased by 40%
• After 20 years, death due to esophageal cancer decreased by 60%

The author of the study, Professor Peter Rothwell of the University of Oxford and John Radcliffe Hospital, says that the findings don’t necessarily mean you should start a daily aspirin regimen—it can still be responsible for some complications, like bleeding, that have historically kept it from being recommended for daily consumption—though Rothwell suggests the new data could lead people to reevaluate aspirin’s risks:

They do demonstrate major new benefits that have not previously been factored into guideline recommendations…previous guidelines have rightly cautioned that in healthy middle-aged people, the small risk of bleeding on aspirin partly offsets the benefit from prevention of strokes and heart attacks…But the reductions in deaths due to several common cancers will now alter this balance for many people.

While the study didn’t find any difference in the results between men and women, the age of the patients affected the findings significantly; older patients benefited drastically more from daily aspirin than younger ones, and doctors say that the ideal candidate for a daily dose of aspirin are probably those nearing their 50s. Researchers will continue testing to explore these promising initial results, but in the meantime it’s cool to know that we might already have an effective cancer-battling drug on hand in our medicine cabinets.

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Future stitches could be made out of your own muscle cells, ensuring proper re-growth of injured muscle tissues.

Researchers in Massachusetts are implanting injured mice with microthreads coated with human muscle cells, reports Technology Review. The threads are made of the same proteins the human body uses to heal wounds, and when seeded with muscle cells, they act as a scaffold for the construction of healthy tissue.

In a study presented earlier this month, George Pins, associate professor of bioengineering at Worcester Polytechnic Institute, and his colleagues sliced out 30 percent of the lower leg muscle in some mice. They took microthreads made of the protein fibrin and coated them with human muscle cells that had been discarded during surgery, Tech Review says. Then they implanted the microthreads into the mouse muscle wounds.

Within a couple days, the cells integrated into the mouse tissue; after a week, the microthreads started to degrade. After 10 weeks, the wound was full of human cells, according to Pins.

Traumatic muscle injuries often don’t heal well because scar tissue can prevent them from functioning properly. And for muscle regeneration techniques to work, the tissue must align properly, or the muscles won’t contract.

The wounded mice had less scar tissue, suggesting the microthread technique could solve that problem, Tech Review reports. And the microthreads seemed to simulate native wound healing, signaling other cells to migrate to the wound area and grow new tissue in the right alignment. The researchers believe the microthreads even stimulated the mice to regrow their own tissue, not just human cells, but they need confirmation.

The next step is to determine whether the new human tissue behaves like real muscle.

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LONDON – Scientists have released genetically modified mosquitoes in an experiment to fight dengue fever in the Cayman Islands, British experts said Thursday.

It is the first time genetically altered mosquitoes have been set loose in the wild, after years of laboratory experiments and hypothetical calculations. But while scientists believe the trial could lead to a breakthrough in stopping the disease, critics argue the mutant mosquitoes might wreak havoc on the environment.

“This test in the Cayman Islands could be a big step forward,” said Andrew Read, a professor of biology and entomology at Pennsylvania State University, who was not involved in the project. “Anything that could selectively remove insects transmitting really nasty diseases would be very helpful,” he said.

Dengue is a potentially fatal mosquito-borne disease that can cause fever, muscle and joint pain, and hemorrhagic bleeding. More than 2.5 billion people are at risk and the World Health Organization estimates there are at least 50 million cases every year. There is no treatment or vaccine.

Unlike malaria, which is also spread by mosquitoes, dengue outbreaks are unpredictable and bed nets are of limited use because dengue-spreading mosquitoes also bite during the day.

Researchers at Oxitec Limited, an Oxford-based company, created sterile male mosquitoes by manipulating the insects’ DNA. Scientists in the Cayman Islands released 3 million mutant male mosquitoes to mate with wild female mosquitoes of the same species. That meant they wouldn’t be able to produce any offspring, which would lower the population. Only female mosquitoes bite humans and spread diseases.

From May to October, scientists released batches of genetically mutated male mosquitoes in cages three times a week in a 40-acre (16-hectare) area. By August, mosquito numbers in that region dropped by 80 percent compared with a neighboring area where no sterile male mosquitoes were released.

Luke Alphey, Oxitec’s chief scientific officer, said with such a small area, it would have been very difficult to detect a drop in dengue cases. But their modeling estimates suggested an 80 percent reduction in mosquitoes should result in fewer dengue infections.

For years, scientists have been working to create mutant mosquitoes to fight diseases like malaria and dengue, which they say could stop outbreaks before they start. But, others suspect it could be an environmental nightmare.

“If we remove an insect like the mosquito from the ecosystem, we don’t know what the impact will be,” said Pete Riley, campaign director of GM Freeze, a British non-profit group that opposes genetic modification.

He said mosquito larvae might be food for other species, which could starve if the larvae disappear. Or taking out adult mosquito predators might open up a slot for other insect species to slide in, potentially introducing new diseases.

Humans have a patchy track record of interfering with natural ecosystems, Riley said. In the past, such interventions have led to the overpopulation of species including rabbits and deer. “Nature often does just fine controlling its problems until we come along and blunder into it.”

Oxitec’s Alphey said their genetically modified mosquitoes can’t permanently change the ecosystem because they only last for a generation. But to stamp out dengue in endemic areas like Asia and South America, billions of the special-order mosquitoes would likely be needed to stifle their wild counterparts.

Yeya Toure, who leads the World Health Organization’s team on Innovative Vector Control Interventions, called the Cayman Islands trial promising and said it’s worth continuing the genetic modification experiments.

He said genetically altered mosquitoes aren’t meant to replace existing tools like insecticides, but to compensate for their limitations, like when mosquitoes develop resistance.

Read said creating mutated mosquitoes might actually be the least invasive way to control dengue. By keeping a lid on the mosquito population via genetic modification, Read said entire ecosystems would be spared the toxic effects of indiscriminately spraying pesticides.

He said the bigger problem would be selling the idea of genetically altered mosquitoes to the public. In the Cayman Islands, officials said they worked closely with the local community and encountered surprisingly little resistance.

“We still have people who don’t believe in vaccines,” Read said. “How are we going to convince them it’s OK to let scientists release genetically altered mosquitoes into the wild?”

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