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brain optics graphicIn 2015, the National Science Foundation's (NSF) Experimental Program to Stimulate Competitive Research (EPSCoR) focused on three priority areas: the complexity of the brain, clean energy, and food security. After reviewing nearly sixty applications, the NSF awarded eight awards to the tune of $42 million in early August. Only three of these awards were for brain research, and MUSC was a recipient. A $4 million grant to MUSC will be used to develop and implement new optical technologies to image brain function at a very high resolution. The Principal Investigators of the grant (Peter W. Kalivas, Ph.D., and Prakash Kara, Ph.D., both from the Department of Neurosciences at MUSC) felt that partnering with the University of Alabama at Birmingham (UAB) played an important role in securing this grant. UAB and MUSC will bring complementary technologies to develop a parallel pipeline of state-of-the-art brain scanners in both states. Optical technologies previously used to look at the stars in the sky will now be miniaturized to look inside the brain. Additional partners in this grant include Furman University, the University of South Carolina Beaufort, and Clemson University.

The NSF recognizes the importance of funding new research projects that merge science, technology, engineering, and mathematics (STEM). Grant recipients must also develop a STEM workforce in order to grow their research programs. While the NSF funds basic science research, this infrastructure often leads to new discoveries that improve health care. For example, this grant thematically focuses on developing tools to determine the precise mechanisms (on the microcircuit scale) by which neurons normally communicate with blood vessels in the brain. However, this “neurovascular” communication breaks down in many neurological diseases. Thus, this grant will have far-reaching impacts in the fields of neuroimaging, neurology, and neuroscience education.

fingertips touchingSending imperceptible white-noise vibrations through the wrist could increase the dexterity of those recovering from stroke, according to an article published in Physiological Results July 14.

Patients who have experienced a stroke can have lasting side effects, such as a diminished tactile response in their fingers and hands. A decrease in sensory feedback from the fingers can cause insufficient grip force control, decreased dexterity, decreased fine object manipulation, and an unstable grip, often causing patients to drop objects.

Na Jin Seo, Ph.D., Assistant Professor in the Division of Occupational Therapy at MUSC Health, was the senior investigator for this study, which applied perceptible and imperceptible white-noise vibrations at various intensities and in separate locations on patients’ extremities to determine the optimal level of white-noise vibration needed to improve signal detection. V. Ramesh Ramakrishnan, Ph.D., and Abigail W. Lauer, M.S., in the Department of Public Health Sciences at MUSC Health performed the statistical analyses for the study. The patients’ non-dominant hands were used for the test because it was postulated to be more sensitive to somatosensory feedback. The vibration was then applied to areas of the palm, back of the hand, and inner wrists an attempt to increase sensitivity in the finger pads. The intensities of the vibration varied from 0% to 120% of the threshold.

At 60% of the threshold, the imperceptible white-noise vibrations significantly improved finger tactile sensation in the thumb and index finger when compared to 0%. At 80% of the threshold, no significant changes were seen, and at 120% of the threshold degraded sensory feedback was observed in the fingers, conforming to stochastic resonance behavior.

While the vibration stimuli would quickly decrease as it moved away from the application site, not reaching the fingertips, each site reacted similarly to the same intensities. According to the study, these results indicate that neuronal activity in the fingers is influenced by the vibration.

“This finding suggests a potential for a sensory orthotic that can be worn at the wrist,” says Seo. “It would provide minute vibration and enhance patients’ touch sensation and dexterity, improving their ability for activities of daily living.” 

This study suggests that patients who have experienced an injury or a stroke could gain access to the neuronal network in their hands through imperceptible white-noise vibrations. Wearing a vibrating device on their wrists could help these patients gain back some of the control they may have lost.

photo fo pill bottle and paperworkThe FDA approved alirocumab (Praluent; Sanofi and Regeneron Pharmaceuticals) for patients with heterozygous familial hypercholesterolemia (HeFH) and for patients with clinical atherosclerotic cardiovascular disease, according to a press release from the FDA July 24.

HeFH is an inherited disease that causes high levels of low-density lipoprotein (LDL) cholesterol in patients. Alirocumab is designed to lower this “bad” cholesterol and is an injectable monoclonal antibody and is the first in its class of PCSK9 inhibitors.

"This new class of medications can significantly and effectively lower LDL cholesterol in very high-risk patients who could not otherwise achieve acceptable LDL cholesterol levels,” said MUSC Health cardiologist Pamela B. Morris, M.D., who is the principal investigator for multiple trials of PCSK9 inhibitors at MUSC. “Long-term outcomes trials in progress will determine if this dramatic reduction in LDL-C results in a reduction in cardiovascular events," says Morris. (To learn more about PCSK9 inhibitors, their mechanism of action, and clinical trials with these inhibitors at MUSC, click here.)

This new drug is most successful when combined with a healthy diet and maximum-tolerated statin therapy. It is not indicated, however, for statin-intolerant patients without established clinical atherosclerotic cardiovascular disease.

Clinical trials for this drug in children have not yet been performed, so it is only prescribed to patients 12 years of age and older.

The side effects of this drug include itching, swelling, pain, or bruising at the injection site, nasopharyngitis, and the flu. There have also been reported cases of allergic reactions to this drug, causing hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization.

It is expected the FDA will approve a second PCSK9 inhibitor called evolocumab (Repatha; Amgen) by August 27.

MUSC Awarded Four Million Dollar Grant to Study Health Disparities in Stroke Recovery

Stroke disparities blog post imageAfrican Americans are more likely to both experience a stroke and be more adversely affected by it than their white counterparts. In South Carolina, the buckle of the stroke belt, African Americans are twice as likely to die from stroke when compared to whites. Less well known is that recovery after stroke is poorer for African Americans than whites, and that access to rehabilitation (or lack thereof) does not completely account for this discrepancy.

With the support of a four million dollar grant from the American Heart Association (AHA), the largest AHA grant ever given to an institution in South Carolina, MUSC is endeavoring to improve stroke recovery in African Americans through a multidisciplinary project that brings together basic and translational researchers in regenerative medicine, neuroscience, and nursing. The four-year project, entitled Wide spectrum Investigation of Stroke Outcome Disparities on Multiple Levels (WISSDOM), includes research projects with the potential to not only improve our understanding of why African Americans don’t fare well in recovery but to use those insights to make a difference in the lives of stroke patients through community interventions.

Leonardo Bonilha, M.D., Ph.D. (photo, left), and Mark Kindy, Ph.D. (photo, center) of the College of Medicine and Gayenelle Magwood, Ph.D., R.N. (photo, right) of the  College of Nursing are all principal investigators of the subprojects being conducted through WISSDOM. Kindy is exploring whether known stroke risk factors such as hypertension and diabetes that disproportionately affect African Americans also play a role in their recovery from stroke. To do this, he will study the effect of such metabolic factors on vascular stiffness in animal models. Bonilha is using innovative neuroimaging techniques to assess the integrity of brain tissue and neuroplasticity (i.e., the ability of the brain to repair itself) in black and white patients so that questions about why African Americans have poorer stroke recovery than whites can be answered. Magwood is exploring whether a community-based intervention—a 12-week home-based intervention coordinated by a nurse and delivered by a community health worker— can improve stroke recovery after patients finish with rehabilitation.

As Director of WISSDOM, Robert Adams, M.D. will oversee the four-year project in its entirety and serve as its key contact. Daniel T. Lackland, Ph.D., a long-time collaborator of Adams who has devoted his 30-year career to addressing disparities in South Carolina and beyond, will serve as WISSDOM’s Training Director, and Bruce Ovbiagele, M.D., Chair of Neurology, as the head of its advisory committee.

This grant builds upon the 10.8 million dollar COBRE (Center Of Biomedical Research Excellence) grant awarded last year to MUSC to found the South Carolina Stroke Recovery Research Center. The COBRE grant is led by Steve Kautz, Ph.D., Chair of the Department of Health Sciences Research and Co-Director of the Center for Rehabilitation Research. (Read more about the COBRE grant here).

Photograph courtesy of Sarah Pack. 

photo of a box of fruits and vegetablesA recent study led by MUSC professor David P. Turner, Ph.D. finds that lifestyle habits such as diet and exercise could affect the progression of cancer and the rate of survival, but so could race. According to the study published in Cancer Research in May, our bodies have to metabolize food to obtain the sugars we need, thus leaving behind a reactive-metabolite waste product. These leftovers are referred to as advanced glycation end-products (AGE), and this study addresses the apparent correlation between AGE levels and the prevalence of age-related diseases among non-Hispanic whites and African Americans. 

High levels of AGE are associated with diabetes, cardiovascular disease, Alzheimer’s, and cancer. These levels are highest in African American men with prostate cancer—they are 1.5 times more likely to be diagnosed with this cancer and twice as likely to die from it than non-Hispanic whites. Consumption of sugar and processed food can contribute to AGE levels. Food preparation (i.e., browning) also plays a large role in these levels. They are higher in the West, where the diet commonly consists of red meat, refined grains, and high sugar and fatty foods.

 When analyzing serum from cancer patients, Turner found that AGE levels were significantly higher in patients with cancer than those without. Breast and prostate immortalized cancer cell lines grew more, migrated farther, and invaded more when treated with AGE. In conjunction with higher AGE levels, African Americans have more C-reactive protein (CRP), making them more susceptible to chronic inflammation. Chronic inflammation is one of the key factors implicated in the development of cancer, along with oxidative stress, an increased immune response, and the presence of AGE.

AGE cannot be completely eliminated, but levels of circulating AGE can be lowered. Simply changing lifestyle habits can slow down the accumulation of AGE in the body. Avoid food with high protein, sugar, and fat, as well as processed foods. Then increase your intake of natural grains, fruits, and vegetables. Change the way you prepare your food by cooking meats at a lower temperature for a longer period of time, skipping the browning step of a dish. You can also replace high-sugar, oil-based marinades with lemon juice, vinegar, and tomato juice. The last big step of lowering your AGE levels is exercise. A sedentary lifestyle only allows for more AGE to accumulate.

image of patient getting mriImplantable cardioverter-defibrillators (ICDs) and magnetic resonance imaging (MRI) were previously contraindicated, but that is no longer the case thanks to a study (NCT02117414) led by Michael Gold, M.D., Ph.D., Director of the Division of Adult Cardiology at MUSC, the results of which were published in the June 23, 2015 issue of the Journal of the American College of Cardiology. Gold is one of the worldwide principal investigators for the study.

ICDs are used in patients at risk of cardiac arrest (sudden cardiac death); the device is placed underneath the patient’s skin in the upper chest to monitor and stabilize their heartbeat. If the heart beats uncontrollably quickly or abnormally slowly, the device will send a small electrical signal to pace or a larger electrical shock to the heart to normalize the beat.

In the past, physicians were unable to use the most popular method of imaging on patients with ICDs. The magnetic field caused by the MRI could either decrease the overall efficacy of the heart-pacing device, or it could overheat the wires, causing the heart to enter tachyarrhythmia — meaning it was beating too quickly.

The study led by Gold tested the efficacy and safety of an ICD that has a “sleep mode” and that has been modified to protect its internal circuits. This sleep mode is referred to as SureScan (Medtronic; Minneapolis, MN) and disables tachyarrhythmia sensing and defibrillation therapies within the device. It can still monitor the patient’s heartbeat, but the device is temporarily incapable of sending an electric shock to the heart. After placing these novel ICDs under the skin of 275 study participants, researchers conducted either a full-body MRI scan with 1.5T of the chest, cervical, and head regions to ensure maximum radiofrequency exposure up to 2W/kg specific absorption rate (SAR) and gradient field exposure to 200 T/m/s per axis or kept the patient waiting for an hour with no MRI. Researchers then monitored the study participants for adverse changes in their ICD over the next 30 days. The device showed no change in its ability to pace or accurately sense ventricular fibrillation following the scan. The novel ICD was thus deemed to be compatible with MRI. 

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