A study led by investigators from the Ragon Institute of MGH, MIT and Harvard finds evidence that antibody protection may help control infection with the bacteria that causes tuberculosis (TB). In their study the research team describes finding consistent differences in both the structure and function of antibodies targeting the TB bacteria between individuals with active TB disease and those with latent TB, which neither produces symptoms nor can be transmitted. The findings may lead to better ways of distinguishing between active and latent disease and to a more effective vaccine against a disease that kills more than 1.5 million people each year.

‘Ending tuberculosis by 2030 is one of the targets of the World Health Organization’s newly adopted Sustainable Developmental Goals,’ says Lenette Lu, MD, PhD, of the Ragon Institute and the Massachusetts General Hospital (MGH) Department of Medicine. ‘A more effective vaccine against TB could substantially contribute towards that goal, impacting the nearly one in three people worldwide who are infected and addressing the leading killer of individuals infected with HIV.’

The only currently available preventive against infection with the TB bacteria – the BCG vaccine – has been available since the 1920s; but its effectiveness against pulmonary TB, the most common form of the disease, has always been uncertain. BCG is believed to work by stimulating cellular immunity, which is carried out by specialized immune cells including T cells and the macrophages that are directly infected by TB bacteria. Previous investigations into a possible role for antibodies in the immune response to TB have had conflicting results, but the Ragon team – led by Galit Alter, PhD, of MGH Department of Medicine and Sarah Fortune, MD, of the Harvard T.H. Chan School of Public Health – used a novel approach.

In addition to binding to their target pathogens and marking them for destruction by the immune system, antibodies also directly stimulate pathogen-killing cells of the innate immune system by binding to a cell-surface protein called the Fc receptor. The Ragon team profiled TB-specific antibodies from 22 individuals with latent TB and 20 with active TB for 70 different features associated with Fc-mediated antibody function. They first identified nine characteristics that differentiated between antibodies of the two groups of participants, and further investigation identified the biomarker that best distinguished between them.

A key regulator of Fc-mediated immune function is the addition to antibodies of compounds called glycans, made up of sugar molecules; and distinct differences in glycosylation patterns were found to clearly distinguish latent TB antibodies from active TB antibodies. To confirm these results in the initial group of participants, who were from South Africa, the team conducted a similar analysis of antibodies from 20 individuals from Texas and Mexico – half with latent and half with active TB – and had the same results. Further experiments revealed that application of latent TB antibodies to TB-infected human macrophages not only increased the activation of several antimicrobial processes but also reduced the survival of the TB bacteria.

Co-lead author Amy Chung, PhD, now at the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia – a joint venture between The University of Melbourne and The Royal Melbourne Hospital – explains, ‘This is a completely new area of immune research in tuberculosis, since these antibodies don’t just recognize the infection, they also recruit immune cells to target it. People with latent infection have inactive disease for a reason, and if antibodies are playing a role in controlling the infection, the mechanism they use could be harnessed for future vaccine development.’

Alter, an associate professor of Medicine at Harvard Medical School, adds, ‘The diagnostic potential of these findings should not be overlooked. The detection of Fc-related modifications of TB-specific antibodies could be easily translated into a rapid, inexpensive point-of-care diagnostic that could have enormous public health impact, particularly in those parts of the globe where TB is endemic.’

Massachusetts General Hospitalwww.massgeneral.org/about/pressrelease.aspx?id=1992

It’s a Catch-22 with potentially deadly consequences: People trying to overcome addiction can’t get treatment for their pain, because the most powerful pain medicines also carry an addiction risk.
And so their pain continues to get in the way of their addiction recovery – or they seek pain relief in the same addictive substances they’re trying to avoid.

But a new study shows the potential for patients to break out of that cycle through a non-drug approach that combines behavioural therapy and social support to help them manage their pain. The low-cost approach, grounded in psychological theories of pain, could help address the nation’s epidemic of addictions to opioid painkillers and illicit drugs.

Veterans who received this pain-focused care while also being treated for addiction found that the intensity of their pain decreased, their ability to function increased, and their alcohol use went down, compared to veterans who received a less-focused approach. However, the two groups had similar rates of drug use.

Just 10 weekly sessions of the approach, called ImPAT for Improving Pain during Addiction Treatment, had an effect that lasted up to a year in 55 veterans who took part, according to the new results published by a team from the VA Ann Arbor Healthcare System’s Center for Clinical Management Research and University of Michigan Medical School’s Addiction Center.

The researchers have already launched a follow-up study in a larger group of 480 non-veterans in a residential addiction treatment program. And the study’s authors note that the ImPAT approach has the potential to be easily and inexpensively adopted by addiction treatment centers and groups worldwide, through team members trained in standard psychological techniques.

Addiction treatment programs often have patients who suffer from chronic pain, but offer few options to treat them, Ilgen says.’These results highlight the need for addiction treatment programs to offer a multifaceted approach that doesn’t only address substance use but also the other factors that might be driving substance use, including pain,’ says Mark Ilgen, Ph.D., the study’s lead author and a VA and U-M psychologist specializing in addiction research. ‘We’ve shown that it’s possible to improve pain outcomes in people with addiction, and even have some spillover effects on their substance use.’

To make matters worse, ‘Past studies of psychosocial approaches for pain have often excluded people with drug or alcohol problems, addiction treatment programs do not usually have providers trained in pain care, and many pain specialists will not treat people who also have addiction. So patients are caught in the middle.’

All 129 patients in the study, most of them men in their 40s and 50s, were receiving outpatient addiction treatment in a CBT-based, non-abstinence setting at the Ann Arbor VA. Half were randomly assigned to ImPAT sessions, the other half to support groups of peers, led by a therapist, where pain and addiction could be discussed.

ImPAT combines elements of cognitive behavioural therapy with another psychosocial approach called acceptance and commitment therapy.

While the two approaches aren’t usually used together, they are often used in pain treatment settings – but those clinics and programs don’t often accept people who also acknowledge they have addiction issues. Ilgen and his colleagues hope their results will help bring the techniques into addiction treatment settings, where the cognitive behavioural therapy approach is often used.

The ImPAT technique seeks to use integrated approaches both to help patients focus less on their pain and more on other aspects of life. This includes techniques to help people adapt to their pain, find ways to distract themselves from their pain, and think of ways to function in the face of pain.

‘We want to take the focus off pain and put it onto functioning, and finding pleasurable ways to spend time,’ Ilgen says. ‘There’s also a strong link between depression and pain. Pain is responsive to mood, and mood is responsive to social support.’

University of Michigan www.uofmhealth.org/news/archive/201607/treating-pain-without-feeding-addiction-study-shows-promise

Researchers at the University of Arizona are developing a non-invasive brain-scanning technology that could produce images far superior to those obtained with the most commonly used systems – electroencephalography and functional magnetic resonance imaging.
The technique, which incorporates sound waves to measure electrical activity in neural tissue, could improve diagnosis and treatment of many disorders, including epilepsy, Parkinson’s disease and traumatic brain injury.
Russell Witte, a UA associate professor of medical imaging, biomedical engineering and optical sciences, is principal investigator of the research project.
‘We know very little about how neurons act collectively to guide our thoughts, emotions and behaviours – or cause seizures or mood swings,’ Witte said.
‘Functional magnetic resonance imaging and electroencephalography have provided some clues. But both fMRI and EEG share a major limitation: They produce images with poor resolution,’ he said. ‘We think our new technology could overcome that limitation.’
Researchers have long known of the acoustoelectric effect, in which ultrasound energy alters a material’s physical properties like electrical conductivity.
Witte is one of the first researchers to apply the phenomenon to biomedical imaging.
He has developed a non-invasive imaging technique for detecting irregular heartbeats and is working with Tech Launch Arizona, the UA office that commercializes inventions stemming from University research, to create a startup for acoustoelectric cardiac imaging.
With the new study, Witte takes his research into new terrain: the brain.
The research team will develop and test the non-invasive technology, called acoustoelectric brain imaging, or ABI, on mammalian brains for the first time.
ABI involves applying ultrasound waves externally to the brain, where they interact with electrical currents to produce a ‘signature’ wave that is picked up by an electrode attached outside the head. ABI can better localize the source of electrical activity than EEG, because it overcomes the problem of interference from the skull, and it works much faster than fMRI, which measures metabolic activity.
‘Sensory input, thoughts and behaviours are happening so fast,’ said Cowen, a neuroscientist.
‘With speech or motor activity, many actions require split-second decisions – actually, on the scale of tens of milliseconds,’ Cowen said. ‘If a brain-imaging technology is working only in seconds – fMRI, for example, can measure brain activity once every two seconds – it may be missing some of the most important details.’
Cowen added: ‘This is a very interesting adventure we’re undertaking, because nobody knows what ABI will actually measure. Will it measure the activity of tens of thousands, or hundreds of thousands, of neurons? Will it detect the activity at a specific frequency, or at a range of frequencies?’
ABI also could provide a clearer picture of activity in structures deep in the brain, such as the amygdala and hippocampus.

University of Arizona http://tinyurl.com/zw5f6he

The human body is controlled by electrical impulses in, for example, the brain, the heart and nervous system. These electrical signals create tiny magnetic fields, which doctors could use to diagnose various diseases, for example diseases of the brain or heart problems in young foetuses. Researchers from the Niels Bohr Institute have now succeeded in developing a method for extremely precise measurements of such ultra-small magnetic fields with an optical magnetic field sensor.

Small magnetic fields from the human body can usually only be picked up by very sensitive superconducting magnetic field sensors that have to be cooled by liquid helium to near absolute zero (which is minus 273 degrees Celsius). But now researchers from the Niels Bohr Institute at the University of Copenhagen have developed a much cheaper and more practical optical magnetic field sensor that even works at room temperature or at body temperature.

‘The optical magnetic field sensor is based on a gas of caesium atoms in a small glass container. Each caesium atom is equivalent to a small bar magnet, which is affected by external magnetic fields. The atoms and thus the magnetic field are picked up using laser light. The method is based on quantum optics and atomic physics and can be used to measure extremely small magnetic fields,’ explains Kasper Jensen, assistant professor in the Center for Quantum Optics, Quantop at the Niels Bohr Institute at the University of Copenhagen.

The researchers at the Niels Bohr Institute have been developing the sensitive magnetic field sensor for several years in the Quantum research group laboratories.

The magnetic field sensor itself consists of a glass container, which has a channel that is approximately 1cm long and 1 mm wide. At the bottom of the glass container is caesium metal. Caesium evaporates into gas at room temperature and the gas atoms rise up into the small channel in the sensor head. Each caesium atom rotates around itself and the axis is like a tiny bar magnet. Now the sensor is held close to a nerve, which emits an electrical nerve pulse. The electrical pulse has a magnetic field that causes a change in the tilt of the axes of the caesium atoms and by sending a laser beam through the gas, you can read the ultra-small magnetic fields of the nerve signals.

The laboratory tests, which were carried out in collaboration with researchers from the Faculty of Health and Medical Sciences, have shown that you can use the magnetic field sensor to detect the magnetic fields from the electrical impulses from the nervous system. The tests were done on the sciatic nerve from a frog, which in many ways resemble the nerves in the human body. For practical reasons, the nerve was removed from the frog before the tests, but it is also possible to pick up electrical impulses from live frogs or from humans.

The advantage of the optical sensor is precisely that the magnetic fields and electrical impulses can be safely and easily picked up at a distance of a few millimetres or centimetres – without the sensor actually coming into contact with the body.

‘We expect that the sensor will be used for special medical examinations, where it is important for the sensor not to be directly in contact with the body, for example, for diagnosing heart problems in tiny foetuses. Here the magnetic field sensor is placed on the mother’s abdomen and you can easily and safely detect the heartbeat of the foetus and you will be able to diagnose any heart problems at an early stage so that the foetus can get the right treatment quickly,’ explains Eugene Polzik, professor and head of Quantop at the Niels Bohr Institute.

University of Copenhagen Niels Bohr Institute news.ku.dk/all_news/2016/07/optical-magnetic-field-sensor-can-detect-signals-from-the-nervous-system/