Posts tagged with "National Institutes of Health"

Dentistry illustration by Kaelen Felix for 360 Magazine

Cold Sore Flareup Triggers

Virus Highjacks Important Immune Response, UVA Discovery Reveals

Researchers at the University of Virginia School of Medicine have shed light on what causes herpes simplex virus to flare up, explaining how stress, illness and even sunburn can trigger unwanted outbreaks.

The discovery could lead to new ways to prevent cold sores and recurrent herpes-related eye disease from reoccurring, the researchers report.

“Herpes simplex recurrence has long been associated with stress, fever and sunburn,” said researcher Anna R. Cliffe, PhD, of UVA’s Department of Microbiology, Immunology and Cancer Biology. “This study sheds light on how all these triggers can lead to herpes simplex-associated disease.”

About Herpes Simplex Recurrence

Once you’re infected with herpes simplex virus (HSV) – and more half of Americans are – the virus never really goes away. Instead, it lurks inside neurons, waiting for the right moment to strike again, a process known as reactivation.

Cold sores, also known as fever blisters, are one of the most common symptoms of HSV reactivation. Recurrent reactivation in the eye leads to herpes keratitis, which, if left untreated, can result in blindness. HSV infection has also been linked to the progression of Alzheimer’s disease.

Recurrences of HSV are typically associated with stress, illness or sunburn, but doctors have been uncertain exactly what causes the virus to reactivate. Cliffe and her collaborators found that when neurons harboring the virus were exposed to stimuli that induce “neuronal hyperexcitation,” the virus senses this particular change and seizes its opportunity to reactivate.

Working in a model developed by the Cliffe lab using mouse neurons infected with HSV, the researchers determined that the virus highjacks an important immune response within the body. In response to prolonged periods of inflammation or stress, the immune system releases a particular cytokine, Interleukin 1 beta. This cytokine is also present in epithelial cells in the skin and eye and is released when these cells are damaged by ultraviolet light.

Interleukin 1 beta then increases the excitability in the affected neurons, setting the stage for HSV to flare up, the UVA researchers discovered.

“It is really remarkable that the virus has hijacked this pathway that is part of our body’s immune response,” Cliffe said. “it highlights how some viruses have evolved to take advantage of what should be part of our infection-fighting machinery.”

The scientists say that more research will need to be done to fully understand the potential factors which play into herpes simplex disease. It may vary depending on the virus strain or the type of neuron infected, even. And it is still unknown if the virus alters how neurons respond to cytokines such as Interleukin 1 beta. But the new insights help doctors better understand what is happening in neurons and the immune system, and that could lead to ways to prevent unwanted outbreaks, the researchers hope.

“A better understanding of what causes HSV to reactivate in response to a stimulus is needed to develop novel therapeutics,” Cliffe said. “Ultimately, what we hope to do is target the latent virus itself and make it unresponsive to stimuli such as Interleukin 1 beta.”

Findings Published

The researchers have published their findings in the scientific journal eLife. The research team consisted of Sean R. Cuddy, Austin R. Schinlever, Sara Dochnal, Philip V. Seegren, Jon Suzich, Parijat Kundu, Taylor K. Downs, Mina Farah, Bimal N. Desai, Chris Boutell and Cliffe.

The work was supported by the National Institutes of Health’s National Institute of Neurological Disorder and Stroke, grant R01NS105630; the National Institute of Allergy and Infectious Diseases, grant T32AI007046; the National Eye Institute, grant F30EY030397; the National Institute of General Medical Sciences, grants T32GM008136, T32GM007267, GM108989 and GM007055and Medical Research Council grant MC_UU_12014/5.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog.

Nanodroplets & Ultrasound ‘Drills’ Prove Effective at Tackling Blood Clots

Engineering researchers have developed a new technique for eliminating particularly tough blood clots, using engineered nanodroplets and an ultrasound “drill” to break up the clots from the inside out. The technique has not yet gone through clinical testing. In vitro testing has shown promising results.

Specifically, the new approach is designed to treat retracted blood clots, which form over extended periods of time and are especially dense. These clots are particularly difficult to treat because they are less porous than other clots, making it hard for drugs that dissolve blood clots to penetrate into the clot.

The new technique has two key components: the nanodroplets and the ultrasound drill.

The nanodroplets consist of tiny lipid spheres that are filled with liquid perfluorocarbons (PFCs). Specifically, the nanodroplets are filled with low-boiling-point PFCs, which means that a small amount of ultrasound energy will cause the liquid to convert into gas. As they convert into a gas, the PFCs expand rapidly, vaporizing the nanodroplets and forming microscopic bubbles.

“We introduce nanodroplets to the site of the clot, and because the nanodroplets are so small, they are able to penetrate and convert to microbubbles within the clots when they are exposed to ultrasound,” says Leela Goel, first author of a paper on the work. Goel is a Ph.D. student in the joint biomedical engineering department at North Carolina State University and the University of North Carolina at Chapel Hill.

After the microbubbles form within the clots, the continued exposure of the clots to ultrasound oscillates the microbubbles. The rapid vibration of the microbubbles causes them to behave like tiny jackhammers, disrupting the clot’s physical structure, and helping to dissolve the clots. This vibration also creates larger holes in the clot mass that allow blood borne anti-clotting drugs to penetrate deep into the clot and further break it down.

The technique is made possible by the ultrasound drill – which is an ultrasound transducer that is small enough to be introduced to the blood vessel via a catheter. The drill can aim ultrasound directly ahead, which makes it extremely precise. It is also able to direct enough ultrasound energy to the targeted location to activate the nanodroplets, without causing damage to surrounding healthy tissue. The drill incorporates a tube that allows users to inject nanodroplets at the site of the clot.

In in vitro testing, the researchers compared various combinations of drug treatment, the use of microbubbles and ultrasound to eliminate clots, and the new technique, using nanodroplets and ultrasound.

“We found that the use of nanodroplets, ultrasound and drug treatment was the most effective, decreasing the size of the clot by 40%, plus or minus 9%,” says Xiaoning Jiang, Dean F. Duncan Distinguished Professor of Mechanical and Aerospace Engineering at NC State and corresponding author of the paper. “Using the nanodroplets and ultrasound alone reduced the mass by 30%, plus or minus 8%. The next best treatment involved drug treatment, microbubbles, and ultrasound – and that reduced clot mass by only 17%, plus or minus 9%.  All these tests were conducted with the same 30-minute treatment period.

“These early test results are very promising.”

“The use of ultrasound to disrupt blood clots has been studied for years, including several substantial studies in patients in Europe, with limited success,” says co-author Paul Dayton, William R. Kenan Jr. Distinguished Professor of Biomedical Engineering at UNC and NC State.  “However, the addition of the low-boiling point nanodroplets, combined with the ultrasound drill has demonstrated a substantial advance in this technology.”

“Next steps will involve pre-clinical testing in animal models that will help us assess how safe and effective this technique may be for treating deep vein thrombosis,” says Zhen Xu, a professor of biomedical engineering at the University of Michigan and co-author of the paper.

SonoVascular, Inc.

A startup called SonoVascular, Inc., which was co-founded by Jiang, has licensed the ultrasound “drill” technology from NC State. SonoVascular and NC State are hoping to work with industry partners to advance the technology. The low-boiling point nanodroplets, co-invented by Dayton, have also been issued a U.S. patent. That technology has been licensed by spinout company Triangle Biotechnology, Inc., which was co-founded by Dayton. Study co-authors Dayton, Kim, Xu and Jiang have also filed a patent application related to nanodroplet-mediated sonothrombolysis.

For More Information

The paper, “Nanodroplet-Mediated Catheter-Directed Sonothrombolysis of Retracted Blood Clots,” is published open access in the journal Microsystems & Nanoengineering. The paper was co-authored by Huaiyu Wu and Bohua Zhang, who are Ph.D. students at NC State; and Jinwook Kim, a postdoctoral researcher in the Joint Department of Biomedical Engineering at UNC and NC State.

The work was done with support from the National Institutes of Health, under grant R01HL141967.

Andrew Exner, a graduate research assistant in Purdue’s Motor Speech Lab, is working to help Parkinson’s patients during the COVID-19 pandemic as announced by 360 MAGAZINE.

AI Technology Helps Parkinson’s Patients During COVID-19

The COVID-19 pandemic is leading a Purdue University innovator to make changes as she works to provide new options for people with Parkinson’s disease.

Jessica Huber, a professor of Speech, Language, and Hearing Sciences and associate dean for research in Purdue’s College of Health and Human Sciences, leads Purdue’s Motor Speech Lab. Huber and her team are now doing virtual studies to evaluate speech disorders related to Parkinson’s using artificial intelligence technology platforms.

Huber and her team have been working to develop telepractice tools for the assessment and treatment of speech impairments like Parkinson’s disease. They received a National Institutes of Health small business innovation and research grant to develop a telehealth platform to facilitate the provision of speech treatment with the SpeechVive device, which has received attention at the Annual Convention of the American Speech-Language-Hearing Association.

In the current study, Huber and her team are collaborating with a startup company, Modality AI, which developed the AI platform that will be used in the study.

“The application of the technology we are evaluating may lead to far-reaching insights into more standardization in assessments, earlier diagnoses and possibly an easier way to track discrete changes over time to guide interventions,” said Andrew Exner, a graduate research assistant in the Motor Speech Lab. “My personal research passion, and the mission of our lab, is to find ways to improve the quality of life for people with Parkinson’s and other related diseases.”

Exner is leading the virtual study for participants across the country to evaluate an AI platform that can collect and automatically measure the speech skills of people with Parkinson’s disease. The need for AI platforms is increasing as the use of telepractice explodes as a result of the COVID-19 pandemic.

“My interest in speech-language pathology actually started during my training as an actor and opera singer,” Exner said. “I saw the effects of pathology on the voice and wanted to extend that interest into speech disorders.”

SpeechVive Inc. is an Indiana startup company based on Huber’s research. The company has developed a wearable medical device to improve the speech clarity of people with Parkinson’s.

Anyone interested in learning more about the virtual studies or taking part, can email Exner at exner@purdue.edu.

Image courtesy of Purdue University.

Cash and wallet illustration for 360 Magazine

Women Surgeons Earn NIH Funding

Women are underrepresented in the field of academic surgery, but women surgeons are earning a disproportionate share of research grants from the National Institutes of Health, a new study has found.

Women make up 19% of surgery faculty at academic health systems but held 26.4% of prestigious “R01” grants in place at surgery departments as of October 2018, the researchers found.

“Female surgeon-scientists are underrepresented within academic surgery, but hold a greater than anticipated proportion of NIH funding,” said researcher Shayna L. Showalter, MD, a breast surgical oncologist at UVA Health and the UVA Cancer Center. “This means that female surgeon-scientists are a crucial component of future surgical research.”

Women in Surgery

Showalter and colleagues queried the number of grants from surgery departments throughout the country to determine the percentage of R01 grants held by women. They identified 212 grants held by 159 principal investigators. Of those 159 investigators, 42 were women, holding a total of 49 R01 grants. “Female surgeon scientists are doing impressive work and have been able to succeed in a very competitive research environment,” Showalter said.

Diving deeper, the researchers determined that women were more likely than men to be first-time grant recipients. More than 73% of women were first-time recipients, compared with 54.8% of men. “Within the research community, we are potentially moving away from the tradition of awarding funding to longstanding, proven researchers,” Showalter said. “Females in this study were twice as likely to be first-time grant recipients. I hope that the focus continues to be on awarding funding to a diverse group of surgeon-scientists.”

Women who held R01 grants were more likely to be part of a department with a female chair or that is more than 30 percent female, the researchers determined. They also found that women had fewer research articles published in scientific journals than did their male colleagues. “This finding may be related to the number of first-time grants and is consistent with previous studies that have demonstrated that women in academic surgery have fewer publication in general than men,” Showalter said.

The researchers encouraged surgery departments to nurture and promote female faculty, and to advocate for women in leadership positions. Strong mentorship programs are important, Showalter said.

“Currently, there are a number of accomplished female surgeon-scientists, and I am confident that many more will play crucial roles in the future of surgical research,” she said. “As a community within academia, we need to support and promote a diverse faculty.”

Findings Published

The researchers have published their findings online in the Journal of the American College of Surgeons. The research team consisted of Elizabeth D. Krebs, Adishesh K. Narahari, Ian O. Cook-Armstrong, Anirudha S. Chandrabhatla, J. Hunter Mehaffey, Gilbert R. Upchurch Jr. and Showalter.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog here.

Brain Cancer illustrated by Mina Tocalini for 360 MAGAZINE.

Brain Cancer Gene Identified

Scientists have identified an oncogene (a cancer-causing gene) responsible for glioblastoma, the deadliest brain tumor. The discovery offers a promising new treatment target for a cancer that is always fatal.

The researchers say the oncogene is essential to the survival of the cancer cells. Without it, the cancer cells die. Scientists have already developed many targeted therapies for other cancers with a similar “oncogene addiction.”

“Glioblastoma is one of the most deadly cancers. Unfortunately, there is no effective treatment option for the disease. The current standard option, radiation plus temozolomide, which displayed a 2.5-month better survival rate, was hailed as a great success. Clearly, better understanding and new therapeutic targets are urgently needed,” said researcher Hui Li, PhD, of the University of Virginia School of Medicine. “The novel oncogene we discovered promises to be an Achilles’ heel of glioblastoma, with its specific targeting potentially an effective approach for the treatment of the disease.”

Targeting Glioblastoma

Oncogenes are naturally occurring genes that spiral out of control and cause cancer. The oncogene Li and his colleagues identified, AVIL, normally helps cells maintain their size and shape. But the gene can be shifted into overdrive by a variety of factors, the researchers found. This causes cancer cells to form and spread.

Blocking the gene’s activity completely destroyed glioblastoma cells in lab mice but had no effect on healthy cells. This suggests targeting the gene could be an effective treatment option.

“AVIL is overexpressed in 100% of glioblastoma cells and clinical samples, and is expressed at even higher level in so-called glioblastoma stem cells, but hardly expressed in normal cells and tissues,” said Li, of UVA’s Department of Pathology. “Silencing the gene wiped out glioblastoma cells in culture and prevented animal xenografts, while having no effect on normal control cells. Clinically, high AVIL expression correlates with worse patient outcome. These findings and classic transformation assays proved AVIL being a bona fide oncogene.”

Identifying Oncogenes

Identifying an oncogene, as Li and his colleagues have done, is an important step toward developing a treatment. But identifying oncogenes is very difficult. The environment inside cells is so complex that it’s hard to determine cause-and-effect.

Li and his team weren’t even working on glioblastoma when they first caught the scent that led to the discovery. Instead, they were studying a rare childhood cancer called rhabdomyosarcoma. (Childhood cancers typically are easier to understand and involve fewer mutations than adult cancers.)

During their research, the scientists discovered an abnormality in the AVIL gene. That prompted them to examine adult cancers to see if the gene could be contributing there. And it was. The researchers concluded the gene plays a “critical role” in glioblastoma, they report in a new scientific paper outlining their findings.

Li and his team believe their approach can be used to discover other oncogenes – hopefully leading to new treatments for a variety of cancers.

“In this day and age, many people thought that all the significant oncogenes have been discovered, Here we uncovered a novel, powerful oncogene and elucidated its signaling pathways, all starting from studying a structure variant in pediatric cancer. In the past, numerous significant discoveries in cancer also stemmed from studying pediatric tumors,” Li said. “We believe this is a strategy that can be applied to find novel players in other adult cancers.”

Glioblastoma Findings Published

The researchers have published their findings in the scientific journal Nature Communications. The research team consisted of Zhongqiu Xie, Pawel Ł. Janczyk, Ying Zhang, Aiqun Liu, Xinrui Shi, Sandeep Singh, Loryn Facemire, Kristopher Kubow, Zi Li, Yuemeng Jia, Dorothy Schafer, James W. Mandell, Roger Abounader and Li.

The research was supported by the National Institutes of Health’s National Cancer Institute, grant CA240601, and Stand Up To Cancer, grant SU2C-AACR-IRG0409.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog.

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Mina Tocalini, 360 Magazine, COVID-19

Rice University’s Charcoal Research

Researchers at Rice University find that charcoal, and other materials described in the American Chemical Society journal ACS Applied Nano Materials, could aid treatment COVID-19 patients.

In the project co-led by Rice chemist James Tour, researchers found oxidized charcoal nanoparticles are not only effective antioxidants, but can also be made from an activated carbon source that is inexpensive, good manufacturing practice (GMP) certified, and already being used in humans to treat acute poisoning.

“That these nanozymes are made from a GMP source opens the door for drug manufacturers,” said Tour, who led the project with A&M neurologist Thomas Kent and UTHealth biochemist Ah-Lim Tsai. “While coal was effective, an issue is that it can have a variety of toxic metallic elements and impurities that are not consistent across samples. And the clusters made from carbon nanotubes are very expensive.”

The researchers noted it may be worthwhile to study the application of their nanozymes to treat the cytokine storms – an excessive immune system response to infection – suspected of contributing to tissue and organ damage in COVID-19 patients.

“While speculative that these particles will be helpful in COVID-19, if administration is timed correctly, they could reduce the damaging radicals that accompany the cytokine storm and could be further chemically modified to reduce other injury-causing features of this disease,” Kent said.

Gang Wu, an assistant professor of hematology at McGovern, and Rice graduate student Emily McHugh are co-lead authors of the study. Co-authors are Vladimir Berka, a senior research scientist at McGovern; Rice graduate students Weiyin Chen, Zhe Wang and Jacob Beckham; Rice undergraduate Trenton Roy; and Paul Derry, an assistant professor at Texas A&M’s Institute of Biosciences and Technology.

Tour is the T.T. and W.F. Chao Chair in Chemistry as well as a professor of computer science and of materials science and nanoengineering at Rice. Kent is the Robert A. Welch Chair Professor in the Institute of Biosciences and Technology at Texas A&M-Houston Campus and an adjunct chemistry professor at Rice and at Houston Methodist Hospital. Tsai is a professor of hematology at UTHealth. Click here to read all of the findings of the Rice University researchers’ work.