Ultrasound technology is taking to the skies with the Essex & Herts Air Ambulance Trust, a charity that provides a free, life-saving Helicopter Emergency Medical Service for the critically ill and injured of Essex, Hertfordshire and the surrounding areas. Stuart Elms, Clinical Director of the Trust, explained: ‘We operate two helicopters crewed by full-time pre-hospital care doctors and critical care paramedics who can be rushed to the scene of an incident with highly specialized and advanced life-saving equipment and pharmacy. As part of our practice, we are moving towards using ultrasound for management of cardiac arrest and advanced life support. Working with expert sites such as the Essex Cardiothoracic Centre at Basildon, Harefield Hospital and SonoSite, our aim is to train our critical care paramedics to use point-of-care ultrasound, allowing us to tailor our cardiac care even more accurately.’ ‘SonoSite is a world leader in point-of-care ultrasound, and its hand-carried iViz instrument lends itself perfectly to pre-hospital use, both in the aircraft and at the scene. The system is small and portable with a good screen that gives a brilliant view, and can be used one handed. The preset views allow rapid set-up and scanning, and are supported by a training mode that allows comparison of normal and abnormal pathology. Ultimately, we also hope to take advantage of the system’s mobile computing capacity to automatically upload data to electronic patient report forms prior to arrival at the hospital. Our aim is to make as much use of ultrasound as we currently do of stethoscopes – whether they are cardiac, medical or trauma patients – helping to improve outcomes.’

www.sonosite.com

For medics on the battlefield and doctors in remote or developing parts of the world, getting rapid access to the drugs needed to treat patients can be challenging. Biopharmaceutical drugs, which are used in a wide range of therapies including vaccines and treatments for diabetes and cancer, are typically produced in large, centralized fermentation plants. This means they must be transported to the treatment site, which can be expensive, time-consuming, and challenging to execute in areas with poor supply chains.
Now a portable production system, designed to manufacture a range of biopharmaceuticals on demand, has been developed by researchers at MIT, with funding from the Defense Advanced Research Projects Agency (DARPA).
In a paper the researchers demonstrate that the system can be used to produce a single dose of treatment from a compact device containing a small droplet of cells in a liquid.

In this way, the system could ultimately be carried onto the battlefield and used to produce treatments at the point of care. It could also be used to manufacture a vaccine to prevent a disease outbreak in a remote village, according to senior author Tim Lu, an associate professor of biological engineering and electrical engineering and computer science, and head of the Synthetic Biology Group at MIT’s Research Laboratory of Electronics.
‘Imagine you were on Mars or in a remote desert, without access to a full formulary, you could program the yeast to produce drugs on demand locally,’ Lu says.

The system is based on a programmable strain of yeast, Pichia pastoris, which can be induced to express one of two therapeutic proteins when exposed to a particular chemical trigger. The researchers chose P. pastoris because it can grow to very high densities on simple and inexpensive carbon sources, and is able to express large amounts of protein.

‘We altered the yeast so it could be more easily genetically modified, and could include more than one therapeutic in its repertoire,’ Lu says.
When the researchers exposed the modified yeast to estrogen β-estradiol, the cells expressed recombinant human growth hormone (rHGH). In contrast, when they exposed the cells to methanol, the yeast expressed the protein interferon.
The cells are held within a millimeter-scale table-top microbioreactor, containing a microfluidic chip, which was originally developed by Rajeev Ram, a professor of electrical engineering at MIT, and his team, and then commercialized by Kevin Lee – an MIT graduate and co-author – through a spin-off company.
A liquid containing the desired chemical trigger is first fed into the reactor, to mix with the cells.

Inside the reactor, the cell-and-chemical mixture is surrounded on three sides by polycarbonate; on the fourth side is a flexible and gas-permeable silicone rubber membrane. By pressurizing the gas above this membrane, the researchers are able to gently massage the liquid droplet to ensure its contents are fully mixed together.
‘This makes sure that the one milliliter (of liquid) is homogenous, and that is important because diffusion at these small scales, where there is no turbulence, takes a surprisingly long time,’ says Ram, who was also a senior author of the paper.
Because the membrane is gas permeable, it allows oxygen to flow through to the cells, while any carbon dioxide they produce can be easily extracted.
The device continuously monitors conditions within the microfluidic chip, including oxygen levels, temperature, and pH, to ensure the optimum environment for cell growth. It also monitors cell density.
If the yeast is required to produce a different protein, the liquid is simply flushed through a filter, leaving the cells behind. Fresh liquid containing a new chemical trigger can then be added, to stimulate production of the next protein.
Although other research teams have previously attempted to build microbioreactors, these have not have not had the ability to retain the protein-producing cells while flushing out the liquid they are mixed with, Ram says. ‘You want to keep the cells because they are your factory,’ he says. ‘But you also want to rapidly change their chemical environment, in order to change the trigger for protein production.’

The researchers are now investigating the use of the system in combinatorial treatments, in which multiple therapeutics, such as antibodies, are used together.
Combining multiple therapeutics in this way can be expensive if each requires its own production line, Lu says.
‘But if you could engineer a single strain, or maybe even a consortia of strains that grow together, to manufacture combinations of biologics or antibodies, that could be a very powerful way of producing these drugs at a reasonable cost,’ he says.

MIT news.mit.edu/2016/portable-device-produces-biopharmaceuticals-on-demand-0729

Many people who experience chest pain, but don’t have a heart attack, breathe a big sigh of relief when a stress test comes back negative for blockages in their blood vessels. But a new study by cardiac researchers at the Intermountain Medical Center Heart Institute in Salt Lake City found they may not be off the hook after all.

Researchers studied 658 men and women between the ages of 57 and 77 who passed a stress test for blocked arteries and who were later found to have calcium in their arteries after being screened by imaging technology that measured their total coronary artery calcification.

They found that five percent of patients who passed their stress test and later tested high for calcium in their arteries – 31 of 658 patients – went on to have an adverse cardiac event within one year. Such events included death, heart attack and stroke.

Researchers say there is something more doctors can do to assess a patient’s risk of future heart attack: check the calcium – a sign of plaque build-up – in a patient’s arteries.

‘We now have the ability to better measure coronary artery calcification,’ says Viet Le, MPAS, PA-C, lead author of the Intermountain Medical Center Heart Institute study.

‘People say, I’m good. They gave me a stress test,” said Le. ‘But it doesn’t tell the whole story. The story it tells is that on that day your engine – your heart – passed the test. Some of these people die within a year from a heart attack.’

Cardiac experts have known for years that calcium left by plaque is a good marker of heart disease, but there was not good imaging technology to measure it without exposing the patient to too much radiation, Le said. That changed about five years ago.

PET/CT, an advanced nuclear imaging technology that combines positron emission tomography (PET) and computed tomography (CT) in one machine, allows physicians doing a chemical stress test to also measure coronary artery calcification.

Calcification cannot be reversed, but the plaque that causes it can be reduced or stabilized with proper medication, diet and exercise.

Researchers found that 33 patients in the study, or five percent, had no or mild calcification, and they had no cardiac events. But there was a significant correlation between the amount of calcium and the occurrence of cardiac events in the remainder of the patients.

Twelve of 309 (3.88 percent) patients with moderate calcification had a cardiac event within a year, 10 of 190 (5.26 percent) with severe calcification had a cardiac event within a year, and nine of 126 (7.14 percent) with very severe calcification had a cardiac event within a year. In total, 16.28 percent of calcified patients in the study had a heart event.

The results confirmed for Le the value of assessing calcification in patients suspected of having clogged arteries.

‘Right now, it’s a neglected tool that should better be utilized,’ he said.

Intermountain Healthcare intermountainhealthcare.org/news/2016/11/cardiac-pet-ct-imaging-effective-calcium-blockage-assessing-heart-attack-risk/

Scientists at EPFL and ETHZ have developed a new method for building microrobots that could be used in the body to deliver drugs and perform other medical operations.
For the past few years, scientists around the world have been studying ways to use miniature robots to better treat a variety of diseases. The robots are designed to enter the human body, where they can deliver drugs at specific locations or perform precise operations like clearing clogged-up arteries. By replacing invasive, often complicated surgery, they could optimize medicine.
EPFL scientist Selman Sakar teamed up with Hen-Wei Huang and Bradley Nelson at ETHZ to develop a simple and versatile method for building such bio-inspired robots and equipping them with advanced features. They also created a platform for testing several robot designs and studying different modes of locomotion. Their work produced complex reconfigurable microrobots that can be manufactured with high throughput. They built an integrated manipulation platform that can remotely control the robots’ mobility with electromagnetic fields, and cause them to shape-shift using heat.
Unlike conventional robots, these microrobots are soft, flexible, and motor-less. They are made of a biocompatible hydrogel and magnetic nanoparticles. These nanoparticles have two functions. They give the microrobots their shape during the manufacturing process, and make them move and swim when an electromagnetic field is applied.
Building one of these microrobots involves several steps. First, the nanoparticles are placed inside layers of a biocompatible hydrogel. Then an electromagnetic field is applied to orientate the nanoparticles at different parts of the robot, followed by a polymerization step to ‘solidify’ the hydrogel. After this, the robot is placed in water where it folds in specific ways depending on the orientation of the nanoparticles inside the gel, to form the final overall 3D architecture of the microrobot.
Once the final shape is achieved, an electromagnetic field is used to make the robot swim. Then, when heated, the robot changes shape and ‘unfolds’. This fabrication approach allowed the researchers to build microrobots that mimic the bacterium that causes African trypanosomiasis, otherwise known as sleeping sickness. This particular bacterium uses a flagellum for propulsion, but hides it away once inside a person’s bloodstream as a survival mechanism.
The researchers tested different microrobot designs to come up with one that imitates this behaviour. The prototype robot presented in this work has a bacterium-like flagellum that enables it to swim. When heated with a laser, the flagellum wraps around the robot’s body and is ‘hidden’.
‘We show that both a bacterium’s body and its flagellum play an important role in its movement,’ said Sakar. ‘Our new production method lets us test an array of shapes and combinations to obtain the best motion capability for a given task. Our research also provides valuable insight into how bacteria move inside the human body and adapt to changes in their microenvironment.’
For now, the microrobots are still in development. ‘There are many factors we have to take into account,’ says Sakar. ‘For instance, we have to make sure that the microrobots won’t cause any side-effects in patients.’

EPFL http://tinyurl.com/zg3rssf

Researchers working in four labs at UT Southwestern Medical Center have found a chink in a so-called ‘un-druggable’ lung cancer’s armour – and located an existing drug that might provide a treatment.

The study describes how the drug Selinexor (KPT-330) killed lung cancer cells and shrank tumours in mice when used against cancers driven by the aggressive and difficult-to-treat KRAS cancer gene. Selinexor is already in clinical trials for treatment of other types of cancer, primarily leukaemia and lymphoma but also gynaecological, brain, prostate, and head and neck cancers.

Lung cancer is the No. 1 cancer killer in the U.S., responsible for more than 158,000 deaths a year, according to the National Cancer Institute (NCI), and the KRAS oncogene is believed to be responsible for about 25 percent of all lung cancer cases. The 5-year survival rate for lung cancer is below 18 percent.

Cancers caused by the KRAS mutation have been a target for researchers since the mutation was discovered in humans in 1982. But, due in part to this oncogene’s almost impervious spherical shape, no one was able to find an opening for attack, said Dr. Pier Scaglioni, Associate Professor of Internal Medicine at UT Southwestern and a contributing author to the study.

Dr. Michael A. White, Adjunct Professor of Cell Biology and senior author of the study, assembled multiple research teams and used robotic machines to create and sift through trays with thousands of cancer cell/potential drug combinations to uncover the KRAS mutation’s weakness.

The scientists found that targeting and inactivating the protein XPO1, found in the cell nucleus and used to transport gene products from the nucleus to the cytoplasm, killed most of the KRAS mutant cancer cells.

‘We found that inhibiting the XPO1 gene kills lung cancer cells that are dependent on KRAS,’ Dr. Scaglioni said. ‘The unexpected coincidence here is that there is an existing drug that will inhibit XPO1.’

‘We know that this drug hits the XPO1 target in people,’ added Dr. White, also a research executive at Pfizer Inc. ‘But we will not know whether the drug will be effective until clinical trials are done, which should be completed in about two years.’

Based on the results of this study, Selinexor, developed by Karyopharm Therapeutics, will be the focus of a multi-centre lung cancer clinical trial led by UT Southwestern’s Dr. David Gerber, Associate Professor of Internal Medicine. That trial is expected to open for enrolment next year.

UT Southwestern Medical Center www.utsouthwestern.edu/newsroom/news-releases/year-2016/september/kras-cancer-white.html