Patients with spinal cord injuries might one day regain use of paralyzed arms and legs thanks to research that demonstrates how limbs can be controlled via a tiny array of implanted electrodes.

The work focused on controlling electrical stimulation pulses delivered to peripheral nerve fibres. When a patient is paralyzed, one of the possible causes is damage to the spinal cord, which along with the brain makes up the central nervous system. The brain is working, and so are motor and sensory nerves in the peripheral nervous system, but electrical signals can’t flow between those nerves and the brain because of the spinal cord injury.

That communication problem is what researchers sought to address, through experiments that involved transmitting precisely controlled electrical pulses into nerves activating plantar-flexor muscles in an ankle of an anesthetized cat.

V John Mathews, professor of electrical engineering and computer science in the Oregon State University College of Engineering, lead researcher Mitch Frankel, then a Ph.D. student at the University of Utah, and three other researchers, all faculty members at Utah, conducted the study.

Researchers sent the pulses using an optimized PIV controller – proportional-integral-velocity – and the cat’s nerves received them via a 100-electrode array whose base measured just 16 square millimeters; it’s known as the Utah Slanted Electrode Array, named for where it was developed and the angled look produced by the electrode rows’ differing heights.

Thanks to specific electrodes being able to activate the right nerve fibres at the right times, the controller made the cat’s ankle muscles work in a smooth, fatigue-resistant way.

The results suggest that someday a paralyzed person might be equipped with a wearable, smartphone-sized control box that would deliver impulses to implanted electrodes in his or her peripheral nervous system, thus enabling at least some level of movement.

‘Say someone is paralyzed and lies in bed all day and gets bed sores,’ Mathews said. ‘Early versions of this technology could be used to help the person get up, use a walker and make a few steps. Even those kinds of things would have an enormous impact on someone’s life, and of course we’d like people to do more. My hope is in five or 10 years there will be at least elemental versions of this for paralyzed persons.’

While this particular study focused on helping the paralyzed, a related research area involves amputees: neuroprostheses that can be controlled by thought based on decoding what goes on electrically inside a person’s brain when he or she wants to, for example, move his or her arm or leg.

‘We can learn from the brain what the intent is and then produce the signals to make the movement happen,’ Mathews said. ‘Another way to get the control information is from the peripheral nerves,’ via electromyography, a diagnostic procedure for evaluating muscle and nerve health.

Generally, Mathews said, an electromyogram can produce the necessary control information.

Putting sensors in a person’s brain, either by deep brain implant or just inside the cranium, is another way to crack the intent code. Electroencephalography – electrode plates attached to the scalp that upload the brain’s electrical activity to a computer – can be used as well.

‘There are a lot of things going on right now in the prosthetic arena,’ Mathews said.

OSU College of Engineering oregonstate.edu/ua/ncs/archives/2016/nov/precise-nerve-stimulation-electrode-implants-offers-new-hope-paralysis-patients

Overweight and obesity in adolescents have increased substantially in recent decades, and currently affect a third of the adolescent population in some developed countries. This is an important public health concern because obesity early in life is considered to be a risk factor for death from cardiovascular disease and from all causes in adulthood.
Some studies suggest that an elevated body-mass index is associated with an increased risk of death from cardiovascular causes. However, a determination of the BMI threshold that is associated with increased risk of fatality remains uncertain. (BMI is a calculation of a person’s weight in kilograms divided by the square of their height in meters, to quantify body mass and enable categorization as underweight, normal weight, overweight, or obese.)
In light of the worldwide increase in childhood obesity, Prof. Jeremy Kark from the Hebrew University-Hadassah Braun School of Public Health and Community Medicine, in the Hebrew University of Jerusalem’s Faculty of Medicine, together with Dr. Gilad Twig of Sheba Medical Center, and Dr. Hagai Levine also of the Braun School of Public Health and other colleagues in Israel, set out to determine the association between body-mass index (BMI) in late adolescence and death from cardiovascular causes in adulthood.
Their study was based on a national database of 2.3 million Israeli 17-year olds in whom height and weight were measured between 1967 and 2010. The researchers assessed the association between BMI in late adolescence and death from coronary heart disease, stroke, and sudden death in adulthood by mid-2011.
During 42,297,007 person-years of follow- up, 2918 of 32,127 deaths (9.1percent) were from cardiovascular causes, including 1497 from coronary heart disease, 528 from stroke, and 893 from sudden death. The results showed an increase in the risk of cardiovascular death in the group that was considered within the ‘accepted normal’ range of BMI, in the 50th to 74th percentiles, and of death from coronary heart disease at BMI values above 20. The researchers concluded that even BMI considered ‘normal’ during adolescence was associated with a graded increase in cardiovascular and all-cause mortality during the 40 years of follow-up. This included increased rates of death from coronary heart disease, stroke, and total cardiovascular causes among participants.
As BMI scores increased into the 75th to 84th percentiles, adolescent obesity was associated with elevated risk of death from coronary heart disease, stroke, sudden death from unknown causes, and death from total cardiovascular causes, as well as death from non-cardiovascular causes and death from all causes. Participants also had an increased risk of sudden death.
The rates of death per person-year were generally lowest in the group that had BMI values during adolescence in the 25th to 49th percentiles, although higher rates were observed among those below the 5th percentile.
How might adolescent BMI influence cardiovascular outcomes in adulthood? The researchers considered two possible pathways. First, obesity may be harmful during adolescence, since it has been associated with unfavourable metabolic abnormalities through risk factors such as unfavourable plasma lipid or lipoprotein levels, increased blood pressure, impaired glucose metabolism, insulin resistance, and formation of coronary and aortic atherosclerotic plaques. Furthermore, the timing of exposure to obesity during a person’s lifetime may play an important role. Second, BMI tends to ‘track’ along the life course so that overweight adolescents tend to become overweight or obese adults, and overweight or obesity in adulthood affects the risk of cardiovascular disease.
‘Our findings appear to provide a link between the trends in adolescent overweight during the past decades and coronary mortality in midlife,’ said the paper’s senior author, Prof. Jeremy Kark. ‘The continuing increase in adolescent BMI, and the rising prevalence of overweight and obesity among adolescents, may account for a substantial and growing future burden of cardiovascular disease, particularly coronary heart disease.’

The Hebrew University of Jerusalem http://tinyurl.com/zwt4n4d

A small device implanted under the skin can improve breast cancer survival by catching cancer cells, slowing the development of metastatic tumours in other organs and allowing time to intervene with surgery or other therapies. These findings, reported in Cancer Research, suggest a path for identifying metastatic cancer early and intervening to improve outcomes.

‘This study shows that in the metastatic setting, early detection combined with a therapeutic intervention can improve outcomes. Early detection of a primary tumour is generally associated with improved outcomes. But that’s not necessarily been tested in metastatic cancer,’ says study author Lonnie D. Shea, Ph.D., William and Valerie Hall Department Chair of Biomedical Engineering at the University of Michigan.

The study, done in mice, expands on earlier research from this team showing that the implantable scaffold device effectively captures metastatic cancer cells. Here, the researchers improve upon their device and show that surgery prior to the first signs of metastatic cancer improved survival.

‘Currently, early signs of metastasis can be difficult to detect. Imaging may be done once a patient experiences symptoms, but that implies the burden of disease may already be substantial. Improved detection methods are needed to identify metastasis at a point when targeted treatments can have a significant beneficial impact on slowing disease progression,’ says study author Jacqueline S. Jeruss, M.D., Ph.D., associate professor of surgery and biomedical engineering and director of the Breast Care Center at the University of Michigan Comprehensive Cancer Center.

Jacqueline Jeruss and Lonnie SheaThe scaffold is made of FDA-approved material commonly used in sutures and wound dressings. It’s biodegradable and can last up to two years within a patient. The researchers envision it would be implanted under the skin, monitored with non-invasive imaging and removed upon signs of cancer cell colonization, at which point treatment could be administered.

The scaffold is designed to mimic the environment in other organs before cancer cells migrate there. The scaffold attracts the body’s immune cells, and the immune cells draw in the cancer cells. This then limits the immune cells from heading to the lung, liver or brain, where breast cancer commonly spreads.

‘Typically, immune cells initially colonize a metastatic site and then pave the way for cancer cells to spread to that organ. Our results suggest that bringing immune cells into the scaffold limits the ability of those immune cells to prepare the metastatic sites for the cancer cells. Having more immune cells in the scaffold, attracts more cancer cells to this engineered environment,’ Shea says.

In the mouse study at day 5 after tumor initiation, the researchers found a detectable percentage of tumor cells within the scaffold but none in the lung, liver or brain, suggesting that the cancer cells hit the scaffold first.

At 15 days after tumour initiation, they found 64 percent fewer cancer cells in the liver and 75 percent fewer cancer cells in the brains of mice with scaffolds compared to mice without scaffolds. This suggests that the presence of the scaffold slows the progress of metastatic disease.

The researchers removed the tumours at day 10, which is after detection but before substantial spreading, and found the mice that had the scaffold in place survived longer than mice that did not have a scaffold. While surgery was the primary intervention in this study, the researchers suggest that additional medical treatments might also be tested as early interventions.

In addition, researchers hope that by removing the scaffold and examining the cancer cells within it, they can use precision medicine techniques to target the treatment most likely to have an impact.

This system is early detection and treatment, not a cure, the researchers emphasize. The scaffold won’t prevent metastatic disease or reverse disease progression for patients with established metastatic cancer.

The team will develop a clinical trial protocol using the scaffold to monitor for metastasis in patients treated for early stage breast cancer. In time, the researchers hope it could also be used to monitor for breast cancer in people who are at high risk due to genetic susceptibility. They are also testing the device in other types of cancer.

University of Michigan Comprehensive Cancer Center. www.mcancer.org/news/archive/how-small-implanted-device-could-help-limit-metastatic-breast-cancer

A centuries-old herbal medicine, discovered by Chinese scientists and used to effectively treat malaria, has been found to potentially aid in the treatment of tuberculosis and may slow the evolution of drug resistance.

In a promising study led by Robert Abramovitch, a Michigan State University microbiologist and TB expert, the ancient remedy artemisinin stopped the ability of TB-causing bacteria, known as Mycobacterium tuberculosis, to become dormant. This stage of the disease often makes the use of antibiotics ineffective.

‘When TB bacteria are dormant, they become highly tolerant to antibiotics,’ Abramovitch said, an assistant professor in the College of Veterinary Medicine. ‘Blocking dormancy makes the TB bacteria more sensitive to these drugs and could shorten treatment times.’

One-third of the world’s population is infected with TB and the disease killed 1.8 million people in 2015, according to the Centers for Disease Control and Prevention.

Mycobacterium tuberculosis, or Mtb, needs oxygen to thrive in the body. The immune system starves this bacterium of oxygen to control the infection. Abramovitch and his team found that artemisinin attacks a molecule called heme, which is found in the Mtb oxygen sensor. By disrupting this sensor and essentially turning it off, the artemisinin stopped the disease’s ability to sense how much oxygen it was getting.

‘When the Mtb is starved of oxygen, it goes into a dormant state, which protects it from the stress of low-oxygen environments,’ Abramovitch said. ‘If Mtb can’t sense low oxygen, then it can’t become dormant and will die.’

Abramovitch indicated that dormant TB can remain inactive for decades in the body. But if the immune system weakens at some point, it can wake back up and spread. Whether it wakes up or stays asleep’ though, he said TB can take up to six months to treat and is one of the main reasons the disease is so difficult to control.

‘Patients often don’t stick to the treatment regimen because of the length of time it takes to cure the disease,’ he said. ‘Incomplete therapy plays an important role in the evolution and spread of multi-drug resistant TB strains.’

He said the research could be key to shortening the course of therapy because it can clear out the dormant, hard-to-kill bacteria. This could lead to improving patient outcomes and slowing the evolution of drug-resistant TB.

After screening 540,000 different compounds, Abramovitch also found five other possible chemical inhibitors that target the Mtb oxygen sensor in various ways and could be effective in treatment as well.

‘Two billion people worldwide are infected with Mtb,’ Abramovitch said. ‘TB is a global problem that requires new tools to slow its spread and overcome drug resistance. This new method of targeting dormant bacteria is exciting because it shows us a new way to kill it. ‘

Michigan State University msutoday.msu.edu/news/2016/ancient-chinese-malaria-remedy-fights-tb/

Neurosurgeons want the quickest, most accurate information to help them make decisions during brain tumour surgery. A new method could accelerate that process.

Neurosurgeons and pathologists at Michigan Medicine are the first to execute stimulated Raman histology (SRH), a method that improves speed and diagnostic efficiency, in an operating room.

The researchers imaged tissue from 101 neurosurgical patients using conventional methods and the new method. Both techniques produced accurate results, they found, but the new method was much faster.

SRH, if applied widely, could change the pace and structure of an operation.

‘By achieving excellent image quality in fresh tissues, we’re able to make a diagnosis during surgery,’ says first author Daniel A. Orringer, M.D., assistant professor of neurosurgery at the University of Michigan Medical School. ‘This eliminates the lengthy process of sending tissues out of the OR for processing and interpretation.’

Today’s workflow for determining a diagnosis during an operation requires the surgeon wait 30 to 40 minutes while tissue is sent to a pathology lab for processing, sectioning, staining, mounting and interpretation. The entire team in the operating room may be idle while waiting for pathology results, Orringer says.

‘Our technique may disrupt the intraoperative diagnosis process in a great way, reducing it from a 30-minute process to about three minutes,’ Orringer says. ‘Initially, we developed this technology as a means of helping surgeons detect microscopic tumour, but we found the technology was capable of much more than guiding surgery.’

Stimulated Raman scattering microscopy, the technology behind SRH, was developed in 2008, but the hazardous lasers involved made it unsuitable for use in an operating room. A clinical version has now been developed and tested in the operating room for more than a year at U-M, with the fibre-laser-based microscope mounted onto a clinical cart that plugs into the wall.

To interpret the samples, researchers developed SRH, which creates images similar to those currently in use.

SRH uses virtual colouring to highlight the cellular and architectural features of brain tumours, with a result resembling traditional staining. The pathologist is then able to differentiate the tumour tissue from normal brain as usual.

‘It’s very similar to what we currently do in our intraoperative diagnosis, with the exception that the tissue is fresh, has not been processed or stained,’ says senior author Sandra Camelo-Piragua, M.D., assistant professor of pathology at U-M.

In the Nature Biomedical Engineering study, neuropathologists were given 30 specimen samples processed by SRH or traditional methods. They were told the same information about each patient’s medical history and the location of the tumour and asked to make a diagnosis.

Those pathologists, the U-M researchers found, were equally likely to make a correct diagnosis, whether they used SRH or conventional slides.

‘SRH imaging will ensure that appropriate and good-quality tissue is collected to reach our ultimate goal: accurate diagnosis,’ Camelo-Piragua says.

University of Michigan labblog.uofmhealth.org/health-tech/new-technique-slashes-diagnosis-time-during-brain-surgery