Type 2 diabetes accounts for 90 % of cases of diabetes around the world, afflicting 2.5 million Canadians and costing over 15 billion dollars a year in Canada. It is a severe health condition which makes body cells incapable of taking up and using sugar. Dr. Alexey Pshezhetsky of the Sainte-Justine University Hospital Research Center, affiliated with the University of Montreal, has discovered that the resistance to insulin seen in type 2 diabetics is caused partly by the lack of a protein that has not previously been associated with diabetes. This breakthrough could potentially help to prevent diabetes.
‘We discovered that Neu1, a protein nicknamed after ‘neuraminidase 1’, turns the absorption of sugar ‘on’ or ‘off’ in body cells, by regulating the amount of sialic acid on the surface of cells’, Dr. Pshezhetsky explains.
‘We are now trying to find a way to restore Neu1 levels and function in diabetes. If we can remove sialic acid residues from the cell surface, this will force the insulin receptor do its job of absorbing blood sugar properly. This could give doctors an opportunity to reduce the use of insulin therapy, and might help to reduce the diabetes epidemic, says Dr. Pshezhetsky.

Although type 2 diabetes is initially treated with diet, exercise and tobacco avoidance, doctors try to restore normal levels of insulin by prescribing it when this fails. The number of cases diagnosed around the world continues to grow incredibly quickly: according to the United States Center Disease Control, cases in that country grew on average by 82% between 1995 and 2010. In Oklahoma, the number increased by 226%. The disease accounts for 90% of diabetes cases around the world, and its prevalence has increased in parallel with the obesity epidemic. Obesity is in fact thought to cause this disease which can in turn lead to heart disease, strokes and even limb amputation due to poor circulation. University of Montreal

Life-threatening blood clots can form in anyone who sits on a plane for a long time, is confined to bed while recovering from surgery, or takes certain medications.
There is no fast and easy way to diagnose these clots, which often remain undetected until they break free and cause a stroke or heart attack. However, new technology from MIT may soon change that: A team of engineers has developed a way to detect blood clots using a simple urine test.
The noninvasive diagnostic, relies on nanoparticles that detect the presence of thrombin, a key blood-clotting factor.
Such a system could be used to monitor patients who are at high risk for blood clots, says Sangeeta Bhatia, senior author of the paper and the John and Dorothy Wilson Professor of Biochemistry.
‘Some patients are at more risk for clotting, but existing blood tests are not consistently able to detect the formation of new clots,’ says Bhatia, who is also a senior associate member of the Broad Institute and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).
Blood clotting is produced by a complex cascade of protein interactions, culminating in the formation of fibrin, a fibrous protein that seals wounds. The last step of this process — the conversion of fibrinogen to fibrin — is controlled by an enzyme called thrombin.
Current tests for blood clotting are very indirect, Bhatia says. One, known as the D-dimer test, looks for the presence of fibrin by-products, which indicates that a clot is being broken down, but will not detect its initial formation.
Bhatia and her colleagues developed their new test based on a technology they first reported last year for early detection of colorectal cancer. ‘We realised the same exact technology would work for blood clots,’ she says. ‘So we took the test we had developed before, which is an injectable nanoparticle, and made it a thrombin sensor.’
The system consists of iron oxide nanoparticles, which the Food and Drug Administration has approved for human use, coated with peptides (short proteins) that are specialized to interact with thrombin. After being injected into mice, the nanoparticles travel throughout the body. When the particles encounter thrombin, the thrombin cleaves the peptides at a specific location, releasing fragments that are then excreted in the animals’ urine.
Once the urine is collected, the protein fragments can be identified by treating the sample with antibodies specific to peptide tags included in the fragments. The researchers showed that the amount of these tags found in the urine is directly proportional to the level of blood clotting in the mice’s lungs.
In the previous version of the system, reported last December in Nature Biotechnology, the researchers used mass spectrometry to distinguish the fragments by their mass. However, testing samples with antibodies is much simpler and cheaper, the researchers say. MIT

Sensory processing disorders (SPD) are more prevalent in children than autism and as common as attention deficit hyperactivity disorder, yet it receives far less attention partly because it’s never been recognised as a distinct disease.
In a groundbreaking new study from UC San Francisco, researchers have found that children affected with SPD have quantifiable differences in brain structure, for the first time showing a biological basis for the disease that sets it apart from other neurodevelopmental disorders.
One of the reasons SPD has been overlooked until now is that it often occurs in children who also have ADHD or autism, and the disorders have not been listed in the Diagnostic and Statistical Manual used by psychiatrists and psychologists.
‘Until now, SPD hasn’t had a known biological underpinning,’ said senior author Pratik Mukherjee, MD, PhD, a professor of radiology and biomedical imaging and bioengineering at UCSF. ‘Our findings point the way to establishing a biological basis for the disease that can be easily measured and used as a diagnostic tool,’ Mukherjee said.
Children with SPD struggle with how to process stimulation, which can cause a wide range of symptoms including hypersensitivity to sound, sight and touch, poor fine motor skills and easy distractibility. Some SPD children cannot tolerate the sound of a vacuum, while others can’t hold a pencil or struggle with social interaction. Furthermore, a sound that one day is an irritant can the next day be sought out. The disease can be baffling for parents and has been a source of much controversy for clinicians, according to the researchers.
‘Most people don’t know how to support these kids because they don’t fall into a traditional clinical group,’ said Elysa Marco, MD, who led the study along with postdoctoral fellow Julia Owen, PhD. Marco is a cognitive and behavioral child neurologist at UCSF Benioff Children’s Hospital, ranked among the nation’s best and one of California’s top-ranked centers for neurology and other specialties, according to the 2013-2014 U.S. News & World Report Best Children’s Hospitals survey.
‘Sometimes they are called the ‘out of sync’ kids. Their language is good, but they seem to have trouble with just about everything else, especially emotional regulation and distraction. In the real world, they’re just less able to process information efficiently, and they get left out and bullied,’ said Marco, who treats affected children in her cognitive and behavioural neurology clinic.
‘If we can better understand these kids who are falling through the cracks, we will not only help a whole lot of families, but we will better understand sensory processing in general. This work is laying the foundation for expanding our research and clinical evaluation of children with a wide range of neurodevelopmental challenges – stretching beyond autism and ADHD,’ she said. University of California – San Francisco

What are some of the most troubling numbers in mental health? Six to 10 — the number of years it can take to properly diagnose a mental health condition. Dr. Elizabeth Osuch, a Researcher at Lawson Health Research Institute and a Psychiatrist at London Health Sciences Centre and the Department of Psychiatry at Western University, is helping to end misdiagnosis by looking for a ‘biomarker’ in the brain that will help diagnose and treat two commonly misdiagnosed disorders.
Major Depressive Disorder (MDD), otherwise known as Unipolar Disorder, and Bipolar Disorder (BD) are two common disorders. Currently, diagnosis is made by patient observation and verbal history. Mistakes are not uncommon, and patients can find themselves going from doctor to doctor receiving improper diagnoses and prescribed medications to little effect.
Dr. Osuch looked to identify a ‘biomarker’ in the brain which could help optimise the diagnostic process. She examined youth who were diagnosed with either MDD or BD (15 patients in each group) and imaged their brains with an MRI to see if there was a region of the brain which corresponded with the bipolarity index (BI). The BI is a diagnostic tool which encompasses varying degrees of bipolar disorder, identifying symptoms and behavior in order to place a patient on the spectrum.
What she found was the activation of the putamen correlated positively with BD. This is the region of the brain that controls motor skills, and has a strong link to reinforcement and reward. This speaks directly to the symptoms of bipolar disorder. ‘The identification of the putamen in our positive correlation may indicate a potential trait marker for the symptoms of mania in bipolar disorder,’ states Dr. Osuch.
In order to reach this conclusion, the study approached mental health research from a different angle. ‘The unique aspect of this research is that, instead of dividing the patients by psychiatric diagnoses of bipolar disorder and unipolar depression, we correlated their functional brain images with a measure of bipolarity which spans across a spectrum of diagnoses.’ Dr. Osuch explains, ‘This approach can help to uncover a ‘biomarker’ for bipolarity, independent of the current mood symptoms or mood state of the patient.’
Moving forward Dr. Osuch will repeat the study with more patients, seeking to prove that the activation of the putamen is the start of a trend in large numbers of patients. Lawson Health Research Institute
　

Results of EORTC trial 58951 suggest that detecting ERG gene deletion at diagnosis of childhood B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) would be useful for risk stratification. The study showed that patients with the ERG gene deletion had a very good outcome with an 8-year event-free survival of 86.4% and an overall survival of 95.6%.

ALL is the most common childhood malignancy, but it is characterised by a number of recurring genetic alterations. These alterations, each with a specific gene expression profile, can influence response to treatment. For example, high hyperdiploidy and the chromosomal translocation t(12;21)/ETV6–RUNX1 are the most prevalent alterations in young children and are associated with good treatment response and outcome. On the other hand, t(9;22)/BCR–ABL1, rearrangements of the MLL gene, low hypodiploidy, intrachromosomal amplification of chromosome 21 (iAMP21) are all associated with a high risk of relapse. In addition, IKZF1 gene deletion has been recently described as a strong marker of poor outcome.

Dr. Emmanuelle Clappier of the Hematology University Institute, St-Louis and Robert Debré Hospitals in Paris and lead author of this EORTC publication says, ‘The genetic basis of BCP-ALL is still unknown for a significant proportion of cases, and consequently outcome is unpredictable at the time of diagnosis. This is especially true for older children and adolescents, more than half of whom display no classifying genetic alteration. There is a clear need for new biological markers to assist in making treatment decisions and improve outcome for these patients.’

A genomic deletion in the ERG gene was identified by array-CGH analysis in selected patients. Then an independent non-selected cohort of 897 children aged 1-17 years and treated for BCP-ALL in the EORTC 58951 trial between December 1998 and July 2008 was screened for ERG gene deletions. ERG gene deletion was found in 3.2% of the patients (29 out of the 897 patients) and was associated with higher age (median age 7.0 years versus 4.0 years, P=0.004) and frequent IKZF1 Δ4-7 deletions (37.9% versus 5.3% in the remaining patients, P<0.001). For patients with an IKZF1 Δ4-7 deletion, those who also had ERG gene deletion had a better outcome (8-year event-free survival, 85.7% vs. 51.3%, HR: 0.16, 95% CI: 0.02-1.20, P=0.04). This work allowed the description of a new genetic marker in BCP-ALL, ERG gene deletion, and to refine the prognostic impact of IKZF1 deletions. EORTC trial 58951 was co-ordinated by the EORTC Children’s Leukemia Group and was conducted in 25 sites located in Belgium and France. It was an academic trial supported by the Laurette Fugain Foundation and the EORTC Charitable Trust. EORTC