The Krembil Research Institute has partnered with The Globe and Mail to release a magazine series highlighting Krembil research advancements.
The third magazine in the series was distributed to Globe and Mail subscribers across Canada on September 7, 2017 and focuses on success stories in arthritis research. Read the full issue online here.
“At Krembil, we’ve diligently built one of the top research programs in the world dedicated to finding [the cure for arthritis],” says Dr. Nizar Mahomed, Medical Director of the Arthritis Program at UHN. “We employ a collaborative, innovative team-first approach that’s committed to stopping this disease in its tracks.”
The current issue features the following Krembil researchers and arthritis research projects:
Also featured are philanthropists Tony Fell and Bryce Douglas, who are the founding co-chairs of the Campaign to Cure Arthritis. As longtime supporters of the Arthritis Program at Toronto Western Hospital, they understand the devastating impact that arthritis can have on people’s lives and the economy, and why private sector donations are critical to finding cures.
“There are many exciting stories of progress and success emerging from our laboratories,” explains Dr. Donald Weaver. “Some of these stories are told in this magazine. This is only a sampling of what we do and what we are capable of.”
Links to all three Globe and Mail magazines are available here.
Dr. Gelareh Zadeh has been appointed as the Program Medical Director for the Krembil Neuroscience Centre at Toronto Western Hospital. She is an award-winning teacher, a highly published scientist and neurosurgeon with specialization and academic focus in neuro-oncology and skull base surgery.
Dr. Zadeh completed her neurosurgery training, and a PhD in brain tumor research at University of Toronto. She joined the neurosurgery division in 2008 as a surgeon-scientist. She is presently a Scientist at the PM Cancer Centre and Head of the Division of Surgical Oncology at UHN and Mount Sinai. She holds the Wilkins Family Chair in Brain Tumor Research, which aims to promote surgical clinical trials and translation of neuro-oncologic discoveries to clinical practice. She is also a scientist in the Macfeeters-Hamilton Neuro-oncology Program, a recognized program with strong peer review funding from national and international granting agencies.
Gelareh is internationally recognized in the field of neurosurgery and neuro-oncology and holds active roles in various societies as the Secretary/Treasurer of The Society of Neuro-Oncology (SNO) and North American Skull Base Society. Her research has been recognized through numerous awards: the America Brain Tumour Association Young Investigator Award, Society of Neuro-oncology Translational Award and the PAIRO Resident Advocate Award – given by the Residents and Interns Association of Ontario.
“The Krembil Neuroscience Centre is a program that serves many people throughout the Province of Ontario. Dr. Zadeh is a leader who is completely familiar with the program and its people and will work with everyone to ensure that Krembil continues to lead in all areas,” said Brian Porter, Chair of UHN’s Board of Trustees.
Please join us in congratulating Gelareh on her appointment. She is committed to promoting the Krembil Neuroscience Centre to advance clinical, academic and educational missions; working closely in partnership with the wide range of expertise and talent both within and outside of UHN.
Your genetic makeup is more than 99 percent similar to that of every other person. So, if we share so much similarity in our genes, what makes us different?
Part of the reason for our differences is that we inherit gene variants—called alleles—from our parents. While many alleles can exist for any given gene, each of us only has two per gene: one allele comes from our father and the other allele comes from our mother.
The different allele combinations for each of our tens of thousands of genes result in different observable traits, such as height or eye colour.
A new study by Krembil Senior Scientist Dr. Dafna Gladman shows that allele variation may also explain why some people are more susceptible to psoriasis, a common immune-mediated skin disease, and its related arthritis, psoriatic arthritis.
To demonstrate this, Dr. Gladman and her research team focused on the KIR3DL1 gene, which encodes a protein that is known to play a key role in activating the immune system. The team developed a genetic method to identify different KIR3DL1 alleles and classify them into four categories based on the corresponding state of the protein: high levels of protein, low levels of protein, null (undetectable) protein, and a shortened form of the protein.
Using this novel approach, the team identified and categorized KIR3DL1 alleles from 652 people with psoriatic disease (including 260 patients with psoriasis only and 392 patients with psoriatic arthritis) and 371 people without the disease. They found that the null protein category was more frequent in those without psoriatic disease. There was no difference between those with psoriasis alone and those with psoriatic arthritis.
"Our results suggest that when alleles fall within the ‘null’ category, they may confer some type of protection against psoriasis," explains Dr. Gladman. "Our work lays the foundation for the development of clinical tools that may help clinicians better predict who is at risk for developing the disease, enabling earlier treatments and preventing long-term consequences."
This work was supported by the Krembil Foundation, the Canadian Institutes of Health Research and the Toronto General & Western Hospital Foundation.
Berinstein J, Pollock R, Pellett F, Thavaneswaran A, Chandran V, Gladman DD. Association of variably expressed KIR3dl1 alleles with psoriatic disease. Clin Rheumatol. 2017 Aug 11. doi: 10.1007/s10067-017-3784-5.
Our bodies depend on electricity. Electrical signals are crucial for your heart to beat, and the electrical activity in your brain enables you to read and understand this sentence. When the electrical signaling goes awry, major health issues can arise.
Epilepsy is a neurological disorder characterized by recurrent surges of abnormal electrical activity in the brain that produce seizures. The cause of the surges is not well understood; however, researchers have shown that it can involve genetics, head trauma, developmental disorders, prenatal brain damage and infections.
Accurately diagnosing the cause of seizures is necessary for prescribing the best treatments. Despite this, in almost half of those affected by epilepsy, the cause of seizures is unknown.
Krembil Clinician Investigator Dr. Danielle Andrade recently examined the utility of a genetic test to help determine the cause of unexplained epilepsy in adults with intellectual disability (ID). The test detects a type of genetic alteration known as copy number variation (CNV), which has been linked to other diseases.
Dr. Andrade and her colleagues performed the genetic test on 143 adults and interpreted the results in the context of each patient’s clinical features. They found that a high proportion (16%) of these patients carried rare CNVs that contributed to their epilepsy. Of the CNVs identified, eight were found to affect genes previously implicated in ID, autism and/or epilepsy. Moreover, the researchers pinpointed five altered genes that most likely contributed to patients’ clinical features.
"This study shows that genetic testing could provide clinicians with important information that may improve the diagnosis and treatment of epilepsy. Adults with epilepsy of unknown cause should be re-investigated with the modern DNA technologies available today”, says Dr. Andrade.
This work was supported by the Ontario Brain Institute, the Government of Ontario and the Toronto General & Western Hospital Foundation. A Bassett holds a Tier 1 Canada Research Chair in Schizophrenia Genetics and Genomic Disorders.
Borlot F, Regan BM, Bassett AS, Stavropoulos DJ, Andrade DM. Prevalence of Pathogenic Copy Number Variation in Adults With Pediatric-Onset Epilepsy and Intellectual Disability. JAMA Neurol. 2017 August 28. doi:10.1001/jamaneurol.2017.1775
(TORONTO, Canada – Sept. 8, 2017) – A task force consisting of researchers from around the world and led by a scientist at the Krembil Research Institute in Toronto has released a set of recommendations that advise against the use of brain imaging as a test for chronic pain.
“It’s not possible at this point in time to say with any degree of certainty that a person does or does not have chronic pain based on brain imaging,” said Dr. Karen Davis, Head, Division of Brain, Imaging and Behaviour-Systems Neuroscience at UHN’s Krembil Research Institute and a Professor in the Department of Surgery and Institute of Medical Science at the University of Toronto. “The only way to truly know if someone is in pain is if they tell you because pain is subjective and it is a complex experience. No brain scan can do that.”
The recommendations of the task force—which consisted of clinicians, brain imaging researchers as well as experts in functional magnetic resonance imaging (fMRI), neuroethics and law—were published today in the journal Nature Review: Neurology in a paper titled “Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations”.
In recent years, advances in brain imaging have led to a shift in understanding of acute and chronic pain and prompted the search for brain-based biomarkers for key characteristics of pain. However, as brain imaging measures become more acceptable for directing personalized pain management, the demand is also growing for this data to be used for legal purposes, including the development of a potential ‘lie detector’ test for chronic pain.
“Use of such tools would be inappropriate and unethical,” said Dr. Davis. “This technology is not foolproof. There are vast issues of variability between people and even within a person at different times. As a result, brain imaging must not be used as a lie detector for chronic pain.”
The task force’s recommendations include the suggestion that any brain-based biomarkers should be used only as an adjunct to rather than a replacement for subjective reports of pain, even if testing is improved and valid protocols developed. Dr. Davis noted that the task force hopes the recommendation will be used as a blueprint by health care systems, governments and legal policy makers.
“We are working towards biomarkers for chronic pain, but the goal is not as a lie detector test but rather to help provide personalized pain treatment options for patients,” said Dr. Davis. “We expect many people will be relieved that there is now a blueprint in place for moving forward with this research. People outside of the field of imaging might be disappointed, but the fact of the matter is the technology cannot be used to support or dispute a claim of chronic pain.”
Story adapted from UHN.ca.
Have you ever heard of a disorder known as train brain? How about bicycle face?
Both are bygone conditions that were, at one time, considered to be serious health problems. They also gained popularity when disruptive technologies (ie, train and bicycle travel, respectively) were first introduced on a grand scale.
The word ‘disruptive’ is used to describe technologies that reshape the world in which we live by creating new markets, changing how we do things or by impacting our core our values.
The connections between disruptive technologies and the rise of associated health concerns are discussed in a recent article by Krembil Director and Senior Scientist Dr. Donald Weaver. In the article, which was published in the journal Neurology, Dr. Weaver creates a new term to describe these disorders, known as disruptive technology disorders (DTDs).
Dr. Weaver also defines four predictable and step-wise stages through which the popularity of DTDs rise and fall. These include the introduction of the new technology in the ‘preliminary phase’; the first description of the DTD, known as the ‘initial moderate phase’; to an ‘extreme phase’ during which the number of purported sufferers quickly increases; and, finally, a ‘second moderate phase’ in which the pandemonium of the ‘extreme phase’ subsides.
One example of this, already alluded to above, is train brain (or railway spine). The term was first used in 1866 by British surgeon John Erichsen, during a time when commercial rail travel was gaining popularity, to describe posttraumatic back pain and headaches that were believed to be caused by the frequent accidents of early rail travel. Despite improvements that made rail travel safer, train brain continued to be diagnosed, such that even minor accidents were implicated. By the early 1900s, close to the peak of rail use, and after various studies failed to identify physical injury associated with the condition, diagnosis of train brain subsided.
Other DTDs include elevator sickness, automobile-induced neurasthenia and phonograph-induced musicophobia. One commonality between these disorders is that they often involve neurologic symptoms, such as headaches, dizziness and feelings of weakness.
The most recent DTD included in the article is cell phone sickness. In 1998, at the peak of cell phone-related health concerns, a Royal Society of Canada panel investigated the condition, which was characterized by headaches, dizziness and the fear of brain cancer. Since then, as cell phone use has increased immensely, the number people suffering from the disorder has sharply declined, suggesting that this DTD has progressed beyond the ‘extreme phase’ and has entered the final, and more moderate phase of the DTD lifecycle.
With the advent of smart phones and social media, a new condition is emerging known as net-brain (also iDisorder) which is characterized by ‘narcissism, poor attention span and fear of missing out.’ While you may think that you know someone with this disorder, only time will tell whether net-brain is the next DTD.
To learn more about the interplay between disruptive technology and health, read more at UHN.ca.
Supported by the Toronto General & Western Hospital Foundation. DF Weaver holds a Tier 1 Canada Research Chair in Clinical Neuroscience. Disruptive technology disorder: A past, present, and future neurologic syndrome. Weaver DF. Neurology. 2017 Jul 25;89(4):395-398. doi: 10.1212/WNL.0000000000004095.
It happens during a long day of sitting in the office, while cramped into your seat on long-haul flights, and it can harm your health.
During periods of inactivity, fluids pool in your lower legs. This can lead to serious health issues, including the formation of blood clots in the leg, which if left untreated can cause a life-threatening condition known as a pulmonary embolism.
As well as being harmful during the day, the pooled fluids can cause havoc when you lie down at night. The fluids shift from the lower extremities towards the head, where they can obstruct breathing and worsen conditions such as sleep apnea, a disorder in which breathing slows or stops for minutes at a time during sleep.
Wearing compression stockings can help prevent pooling of blood in the legs. However, for those with spinal cord injuries and the elderly, compression stockings can be difficult to put on and remove and many people report discomfort while wearing them. Thus, most of the people who may benefit from compression stockings don’t use them.
To address this problem, TRI Scientist Dr. Azadeh Yadollahi explored a new therapy to prevent fluid buildup that uses electrical stimulation to make the calf muscles in the leg contract.
Dr. Yadollahi’s team was particularly interested in whether the new therapy could help those with sleep apnea. With this in mind, her team enrolled 13 men with sleep apnea. The chosen study participants were free from other chronic or debilitating illnesses, had normal blood pressure and were not obese.
In order to test whether the new therapy was effective, fluid buildup in the legs of participants was measured as they sat stationary for 150 minutes during two separate sessions. In one session, the electrical therapy was applied; while in the other session, participants received a mock therapy.
The results revealed that after 150 minutes of electrical stimulation, fluid buildup was reduced by 43%. Furthermore, swelling of the legs (measured as a change in calf circumference) was reduced by almost 90%.
“Our findings show that electrical stimulation of the calf is a promising strategy to prevent leg fluid accumulation. The improvements that we observed, when compared to previous studies, suggest that our approach has the potential to reduce the severity of sleep apnea by around a third,” said Dr. Yadollahi.
Future work will focus on developing the approach into a compact and easy to use therapeutic device—one that could help a wide range of individuals affected by leg fluid buildup, including office workers, cashiers, flight attendants, frequent flyers, and those suffering from sleep apnea and spinal cord injuries.
This work was supported by the Toronto Rehab Foundation.
The Effect of Electrical Stimulation of the Calf Muscle on Leg Fluid Accumulation over a Long Period of Sitting. Vena D, Rubianto J, Popovic MR, Fernie GR, Yadollahi A. Sci Rep. 2017 Jul 20;7(1):6055. doi: 10.1038/s41598-017-06349-y.
