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WASHINGTON, Dec. 16, 2019 -- Are bananas actually that slippery? Could spinach give you superhuman strength? And what the heck is Toon Acid? This week, watch some cartoons alongside our writer and host, Sam Jones, and learn whether their chemistry checks out: https://youtu.be/AiEgZOrRJg4.

SAN ANTONIO -- Mayo Clinic researchers will present findings at the San Antonio Breast Cancer Symposium Dec. 10-14 in San Antonio.

New Mayo Clinic studies to be presented include:

"Women at Elevated Risk of Developing Breast Cancer May Benefit From Taking Anti-inflammatory Drugs"

Embargoed until Friday, Dec. 13, at 6 p.m. EST

Research from Mayo Clinic investigators suggest that some women with an elevated risk of developing breast cancer may benefit from taking anti-inflammatory medications.

"Several studies have evaluated whether the use of anti-inflammatory medications such as aspirin, ibuprofen and naproxen affect a woman's risk of developing breast cancer," says Amy Degnim, M.D., a breast surgical oncologist at Mayo Clinic in Minnesota, "but little is known about how use of these drugs might affect their risk after a benign breast biopsy." Dr. Degnim says about one million women receive a diagnosis of benign breast disease annually in the U.S. and having this history increases their risk of developing breast cancer.

Researchers surveyed women who had undergone a benign breast biopsy at Mayo Clinic between 1992 and 2001, and asked them to report which types of these medications they had used and for how long. Researchers also obtained information on which women had developed breast cancer at any point in the years after their initial benign biopsy.

"We found that women who reported using ibuprofen or naproxen had an approximately 40% reduction in breast cancer risk, while women who reported using aspirin had no reduction in breast cancer risk," says Dr. Degnim. "Women who used the drugs more frequently on a regular basis also had greater protection from breast cancer."

Dr. Degnim says the findings suggest that women who have had a benign breast biopsy may benefit from medications that reduce inflammation, except for aspirin, in terms of reducing later breast cancer risk. She cautions that this study was not a clinical trial and she does not recommend that all women should take these medications to reduce their breast cancer risk. "Our results support the need for a clinical trial to further investigate the risks and benefits of taking these medications to lower breast cancer risk."

"Young Women With Breast Cancer May Help Preserve Fertility by Avoiding Intensive Chemotherapy"

Embargoed until Thursday, Dec. 12, at 8 a.m. EST

Young women with HER 2-positive breast cancer may help preserve their fertility by choosing one type of chemotherapy over another according to the findings of a study led by Kathryn Ruddy, M.D., an oncologist at Mayo Clinic.

"Ovarian dysfunction is an important issue after cancer treatment because it can be associated with infertility and menopausal symptoms, such as hot flashes and impaired sexual function," says Dr. Ruddy.

Dr. Ruddy and her team surveyed study participants taking part in a randomized clinical trial testing the efficacy of T-DM1 versus a combination of paclitaxel and trastuzumab. Participants were asked questions about menstrual periods. "We found that young women with HER 2-positive breast cancer may be more likely to resume menstruation after receipt of two relatively new treatments, T-DM1 or a combination of paclitaxel and trastuzumab, than we have seen previously in young women who received older, more intensive chemotherapy regimens."

Dr. Ruddy says the findings should be good news for women who want to maintain fertility after treatment for breast cancer and that menopausal symptoms such as hot flashes may be less burdensome for patients treated with the newer regimens. Dr. Ruddy and her colleagues will perform additional analyses on the effect of tamoxifen on these results before publishing a paper on this study.

"Researchers Develop Tool to Identify Patients at Higher Risk of Heart Damage From Breast Cancer Therapy"

Embargoed until Friday, Dec. 13, at 6 p.m. EST

Researchers at Mayo Clinic in Florida have developed a tool to help identify patients who may be at higher risk of developing heart damage from anti HER 2 breast cancer therapy at an early stage.

"Cardiac toxicity is a known complication of anti-HER 2 therapy," says Pooja Advani, M.B.B.S., M.D., a Mayo Clinic oncologist. Dr. Advani says clinical studies have confirmed that the use of anti-HER 2 therapy in breast cancer patients can have a profound effect on patient survival.

"The most common manifestation of cardiac toxicity in breast cancer patients receiving anti-HER 2 therapy is a reduction in the ejection fraction without any symptoms," says Dr. Advani. Ejection fraction is a measurement of the percentage of blood leaving the heart each time it contracts.

Dr. Advani says risk factors, such as older age; a lower ejection fraction prior to the start of treatment; and the use of anthracycline chemotherapy, such as doxorubin or Adriamycin, have been consistently associated with a higher risk of cardiac toxicity from anti-HER 2 therapy.

Dr. Advani and her colleagues followed 604 breast cancer patients who were treated with anti-HER 2 agents at Mayo Clinic. They collected patient data, including, age, race, gender, body mass index, smoking history, medical comorbidities, use of heart medications, baseline heart function, thickness of the heart muscle and prior use of anthracycline chemotherapy.

Researchers identified patients who developed cardiac toxicity -- asymptomatic, symptomatic, or both. They performed a statistical analysis to identify risk factors that were associated with a high risk of developing cardiac dysfunction.

"We found that patients with certain risk factors including being over the age of 55, having a lower baseline heart function (ejection fraction less than 60 percent), having received anthracycline chemotherapy or patients having enlargement and thickening of the heart walls were most significantly associated with an increased risk of developing cardiac toxicity," says Dr. Advani. "This is consistent with previously reported studies."

Dr. Advani says patients receiving radiation therapy as a part of their breast cancer treatment were not found to be at a significantly higher risk of developing cardiac toxicity from anti-HER 2 therapy based on their findings.

Dr. Advani and her colleagues created a risk prediction model by assigning a score to each factor mentioned above and found that the cumulative risk score was a highly significant predictor of cardiac toxicity in patients.

"Using a risk prediction model at therapy initiation may help us identify patients who may benefit from an early referral to a cardiologist for close cardiac monitoring and treatment with medications to protect their heart function," says Dr. Advani.

The matrix shell of the HIV-1 virus may have a different shape than previously thought, and a newly proposed model has significant implications for understanding how the virus functions, according to a new study by University of Alberta scientists.

The research suggests that the HIV-1 virus is housed within a spherical matrix shell. When it infects a healthy cell, the shell fuses to the outside of the target cell and then releases the viral capsid inside where it attacks the cell.

"Our new proposed structure for the HIV-1 virus has a very peculiar shape, almost like petals of a flower," said Sean Graves, instructor in the Department of Mathematical and Statistical Sciences and co-author on the study. "A better structural knowledge of the matrix shell may help us understand the fusing and infection process." Graves is also coordinator of the Decima Robinson Support Centre, providing support to more than 1000 undergraduate students each term.

The research shows that the previous model used to describe the structure of the HIV-1 matrix shell was mathematically impossible and provides a viable alternative. While it is too early to anticipate whether the model will translate into new treatment for HIV, the research will help scientists to better understand and make predictions about the behaviour of the HIV-1 virus. Around the world, nearly 38 million people suffer from HIV or AIDS.

"Our contribution uses mathematical principles to help guide the scientific community in the right direction," added Marcelo Marcet-Palacios, adjunct professor of medicine in the Faculty of Medicine & Dentistry and co-author. "If our model is correct, then we can begin investigating ways we could block or interrupt the mechanism of viral entry. For example, by using a medication that could cross-link the 'petals' of the structure together to prevent the opening of the particle and thus stopping entry of the viral genome into the host cell."

The model is available to anyone, anywhere in the world online.

This research is the result of the work of an interdisciplinary team from the fields of biology, mathematics and computing science. One such collaborator is Weijie Sun, Faculty of Science alumnus and a former student of Graves'.

"This collaboration made it possible to come up with a new model consistent with previously observed evidence and allowed us to develop a computer program freely accessible online that other scientists around the world can use to recreate our work and further develop this new model," said Sun. "It is incredible what can be achieved in science when experts from different disciplines get together and collaborate."

A novel technological approach developed by researchers at Baylor College of Medicine expands from two to six the number of molecular pathways that can be studied simultaneously in a cell sample with the dual luciferase assay, a type of testing method commonly used across biomedical fields.

Published in the journal Nature Communications, the report shows that multiplexed hextuple luciferase assaying, meaning a testing method that can effectively probe six different pathways. It can also be used to monitor the effects of experimental treatments on multiple molecular targets acting within these pathways. The new assay is sensitive, saves time and expense when compared to traditional approaches, reduces experimental error and can be adapted to any research field where the dual luciferase assay is already implemented, and beyond.

"One of the interests of our lab is to have a better understanding of the processes involved in cancer. Cancer usually originates through changes on many different genes and pathways, not just one, and currently most cell-based screening assays conduct single measurements," said corresponding author Dr. Koen Venken, assistant professor of biochemistry and molecular biology, and pharmacology and chemical biology at Baylor.

To get a more detailed picture of the cellular processes that differentiate normal versus cancer cells, researchers resort to conduct several independent screening assays at the expense of time and additional cost.

"Our goal in this study was to measure multiple cellular pathways at once in a single biological sample, which would also minimize experimental errors resulting from conducting multiple separate assays using different samples," said Venken, a McNair Scholar and member of the Dan L Duncan Comprehensive Cancer Center at Baylor.

Dr. Alejandro Sarrion-Perdigones, first author of the paper, focused on developing a multiplexed method - a method for simultaneously detecting many signals from complex systems, such as living cells. He developed a sensitive assay using luciferases, enzymes that produce bioluminescence. The assay includes six luciferases, each one emitting bioluminescence that can be distinguished from the others. Each luciferase was engineered to reveal the activity of a particular pathway by emitting bioluminescence.

"To engineer and deliver the luciferase system to cells, we used a 'molecular Lego' approach," said co-author Dr. Lyra Chang, post-doctoral researchers at the Center for Drug Discovery at Baylor. "This consists of connecting the DNA fragments encoding all the biological and technological information necessary to express each luciferase gene together sequentially forming a single DNA chain called vector. This single vector enters the cells where each luciferase enzyme is produced separately."

Treating the cells with a single multi-luciferase gene vector instead of using six individual vectors, decreased variability between biological replicates and provided an additional level of experimental control, Chang explained. This approach allowed for simultaneous readout of the activity of five different pathways, compared to just one using traditional approaches, providing a much deeper understanding of cellular pathways of interest.

"In addition to applications in cancer research, as we have shown in this work, our multiplex luciferase assay can be used to study other cellular pathways or complex diseases across different research fields," Venken said. "For instance, the assay can be adapted to study the effect of drugs on insulin sensitivity in different cells types, the immune response to viral infections, or any other combinations of pathways."

A new study found that people who presented to California emergency departments with deliberate self-harm had a suicide rate in the year after their visit 56.8 times higher than those of demographically similar Californians. People who presented with suicidal ideation had suicide rates 31.4 times higher than those of demographically similar Californians in the year after discharge. The findings, published in JAMA Network Open, reinforce the importance of universal screening for suicide risk in emergency departments and the need for follow-up care. The study was funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health.

More than 500,000 people present to emergency departments each year with deliberate self-harm or suicidal ideation -- both major risk factors for suicide. However, little is known about what happens to these people in the year after they leave emergency care.

"Until now, we have had very little information on suicide risk among patients after they leave the emergency department because data that link emergency records to death records are rare in the United States. Understanding the characteristics and outcomes of people with suicide risk who visit emergency departments is important for helping researchers and practitioners improve treatment and outcomes," said lead author Sidra Goldman-Mellor, Ph.D., an assistant professor of public health at the University of California, Merced.

Goldman-Mellor and colleagues sought to understand patterns of suicide and other mortality in the year after emergency department presentation -- and patient characteristics associated with suicide death -- by linking emergency department patient records from California residents who presented to a licensed emergency department between Jan. 1, 2009, to Dec. 31, 2011, with California mortality data.

The researchers divided individuals presenting to the emergency department into three groups: people with deliberate self-harm with or without co-occurring suicidal ideation (85,507 patients), people presenting with suicidal ideation but without deliberate self-harm (67,379 patients), and people without either self-harm or suicidal ideation, called "reference" patients (497,760 patients).

The researchers found that the probability of suicide in the first year after discharge from an emergency department was highest -- almost 57 times that of demographically similar Californians overall -- for people who had presented with deliberate self-harm. For those who presented with suicidal ideation, the suicide rate was approximately 31 times higher than among Californians overall. The suicide rate for the reference patients was the lowest amongst the studied groups, but still double the suicide rate among Californians overall.

The risk for death via unintentional injury (i.e., accidents) was also markedly elevated -- 16 times higher for the deliberate self-harm group and 13 times higher for the ideation group than for demographically similar Californians. Most deaths due to unintentional injury were found to be due to overdose -- 72% in the self-harm group and 61% in the ideation group -- underscoring the overlap between suicide and overdose risk.

The researchers also examined if certain clinical or demographic characteristics measured at the emergency department visit were predictive of subsequent suicide death. For all three groups, men and those over the age of 65 had higher suicide rates than women and people 10-24 years of age. In all groups, suicide rates were higher for non-Hispanic white patients than for patients of other ethnicities. In addition, for all groups, those with Medicaid insurance had lower suicide rates than those with private- or other-payer insurance.

Comorbid diagnoses were also found to be associated with suicide risk, but differently for each of the three groups studied. For patients who had presented with deliberate self-harm, those with a comorbid diagnosis of bipolar disorder, anxiety disorder, or a psychotic disorder were more likely to die by suicide than those without these co-occurring diagnoses. For patients who presented with suicidal ideation, a comorbid diagnosis of depression was found to be associated with increased suicide risk. Among reference patients, patients with bipolar disorder, depression, or alcohol use disorder had an increased risk of suicide. Of note, patients in the deliberate self-harm group who presented to the emergency department with a firearm injury had a subsequent suicide rate in the following year of 4.4%, far higher rate than any other patient group in this study.

"We think our findings will be useful for guiding intervention and healthcare quality improvement efforts," said Goldman-Mellor. "Our results also highlight the fact that patients with suicidal ideation or self-harming behaviors are at high risk not only for death by suicide, but also for death by accidents, homicide, and natural causes. We think this shows the importance of addressing the full spectrum of their health and social needs in follow-up care."

Study co-author Michael Schoenbaum, Ph.D., a senior advisor for mental health services, epidemiology, and economics at NIMH added that this type of analysis should become routine, saying, "We improve what we measure. In cancer and heart surgery, we have tracked and reported patient survival for decades -- and outcomes have steadily improved. We should do the same for people with suicide risk, to inform our prevention and treatment programs."

PROVIDENCE, R.I. [Brown University] -- A team of Brown University researchers has used a brain-computer interface to reconstruct English words from neural signals recorded in the brains of nonhuman primates. The research, published in the journal Nature Communications Biology, could be a step toward developing brain implants that may help people with hearing loss, the researchers say.

"What we've done is to record the complex patterns of neural excitation in the secondary auditory cortex associated with primates' hearing specific words," said Arto Nurmikko, a professor in Brown's School of Engineering, a research associate in Brown's Carney Institute for Brain Science and senior author of the study. "We then use that neural data to reconstruct the sound of those words with high fidelity.

"The overarching goal is to better understand how sound is processed in the primate brain," Nurmikko added, "which could ultimately lead to new types of neural prosthetics."

The brain systems involved in the initial processing of sound are similar in humans and non-human primates. The first level of processing, which happens in what's called the primary auditory cortex, sorts sounds according to attributes like pitch or tone. The signal then moves to the secondary auditory cortex, where it's processed further. When someone is listening to spoken words, for example, this is where the sounds are classified by phonemes -- the simplest features that enable us to distinguish one word from another. After that, the information is sent to other parts of the brain for the processing that enables human comprehension of speech.

But because that early-stage processing of sound is similar in humans and non-human primates, learning how primates process the words they hear is useful, even though they likely don't understand what those words mean.

For the study, two pea-sized implants with 96-channel microelectrode arrays recorded the activity of neurons while rhesus macaques listened to recordings of individual English words and macaque calls. In this case, the macaques heard fairly simple one- or two-syllable words -- "tree," "good," "north," "cricket" and "program."

The researchers processed the neural recordings using computer algorithms specifically developed to recognize neural patterns associated with particular words. From there, the neural data could be translated back into computer-generated speech. Finally, the team used several metrics to evaluate how closely the reconstructed speech matched the original spoken word that the macaque heard. The research showed the recorded neural data produced high-fidelity reconstructions that were clear to a human listener.

The use of multielectrode arrays to record such complex auditory information was a first, the researchers say.

"Previously, work had gathered data from the secondary auditory cortex with single electrodes, but as far as we know this is the first multielectrode recording from this part of the brain," Nurmikko said. "Essentially we have nearly 200 microscopic listening posts that can give us the richness and higher resolution of data which is required."

One of the goals of the study, for which doctoral student Jihun Lee led the experiments, was to test whether any particular decoding model algorithm performed better than others. The research, in collaboration with Wilson Truccolo, a computational neuroscience expert, showed that recurrent neural networks (RNNs) -- a type of machine learning algorithm often used in computerized language translation -- produced the highest-fidelity reconstructions. The RNNs substantially outperformed more traditional algorithms that have been shown to be effective in decoding neural data from other parts of the brain.

Christopher Heelan, a research associate at Brown and co-lead author of the study, thinks the success of the RNNs comes from their flexibility, which is important in decoding complex auditory information.

"More traditional algorithms used for neural decoding make strong assumptions about how the brain encodes information, and that limits the ability of those algorithms to model the neural data," said Heelan, who developed the computational toolkit for the study. "Neural networks make weaker assumptions and have more parameters allowing them to learn complicated relationships between the neural data and the experimental task."

Ultimately, the researchers hope, this kind of research could aid in developing neural implants the may aid in restoring peoples' hearing.

"The aspirational scenario is that we develop systems that bypass much of the auditory apparatus and go directly into the brain," Nurmikko said. "The same microelectrodes we used to record neural activity in this study may one day be used to deliver small amounts of electrical current in patterns that give people the perception of having heard specific sounds."

Lancaster University researchers have shed light on how the parasite which causes sleeping sickness multiples inside its host.

Human African Trypanosomiasis or sleeping sickness, only occurs in Sub-Saharan Africa where an estimated 60 million people in 36 countries are at risk.

According to the World Health Organisation (WHO), more than 95 percent of reported cases are caused by the parasite Trypanosoma brucei gambiense, which is found in western and central Africa. The other 10 percent of cases are caused by Trypanosoma brucei rhodesiense, which is found in eastern and southern Africa.

Both subspecies are harboured by both wild and domestic animals which provide a reservoir of infection for Tsetse flies which then bite humans.

The infection attacks the central nervous system, causing severe neurological disorders. Without treatment the disease is fatal.

Research led by Dr Mick Urbaniak with Dr Corinna Benz of Lancaster University reveals that the parasite's cell division differs from that of humans and animals.

The paper published in PLoS Pathogens has identified many hundreds of proteins that were not previously known to be involved in the cell division cycle.

Dr Urbaniak said: "Differences in the control in cell division may be exploited to create drugs that target the parasite but do not affect the human or animal host."

This is the first in-depth quantitative analysis of changes in the phosphoproteome that occur across the cell cycle in T. brucei. The identification of many hundred CCR phosphorylation sites confirms the importance of many known cell cycle proteins and implicates many more as having a potential role in the cell cycle.

"The data presented here will be of value to the trypanosome research community, and provides an important insight into mechanisms of post-transcriptional gene regulation that are likely to prove of relevance to the wider community as well."

WASHINGTON--While older adults with hypothyroidism face an elevated risk of death, individuals with subclinical hypothyroidism, a milder form of underactive thyroid, did not face the same risk, according to new research published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Hypothyroidism occurs when the body produces too little thyroid hormone. Thyroid hormone controls a person's metabolism and affects the way the body uses energy, consumes oxygen and regulates temperature. The condition occurs more often in women and people over the age of 60.

"Our meta-analysis is the first to evaluate and confirm the association between hypothyroidism and mortality, specifically focusing on an older population," said Carol Chiung-Hui Peng, M.D., of the University of Maryland Medical Center Midtown Campus in Baltimore, Md., and one of the study's authors.

"Our analysis found individuals with hypothyroidism aged 60 years or older were 26 percent more likely to die from all causes than individuals in the same age range who did not have the thyroid condition," said co-author, Huei-Kai Huang, M.D., of Hualien Tzu Chi Hospital and Tzu Chi University in Hualien, Taiwan.

The researchers reviewed the results of 27 published articles including over 1.1 million older individuals. Although hypothyroidism was associated with all-cause mortality risk, the studies did not find a higher incidence of cardiovascular mortality. Interestingly, studies published in Asia and North America were associated with increased all-cause mortality in the hypothyroid population, while those published in Europe and Oceania were not. Among individuals with hypothyroidism who were 80 years old or older, the researchers found no increased risk of all-cause or cardiovascular mortality.

The mortality difference was not seen in older patients with milder forms of thyroid disease. This study provides further evidence to help guide management of hypothyroidism in older adults.

"In accordance with guidelines, our findings imply that individuals with subclinical hypothyroidism--those who have milder thyroid dysfunction--may not benefit from being treated with synthetic thyroid hormone," said Kashif M. Munir, M.D., associate professor in the division of endocrinology, diabetes and nutrition at the University of Maryland School of Medicine in Baltimore, Md., and another of the study's authors. "However, treatment should be considered in individuals diagnosed with hypothyroidism, given increased all-cause mortality."

A Chinese research team has developed an advanced imaging technique to achieve super-resolution microscopy at unprecedented speeds and with many fewer images. The new method should make it possible to capture processes in living cells at speeds not previously possible.

Super-resolution techniques, often called nanoscopy, achieve nanoscale resolution by overcoming the diffraction limit of light. Although nanoscopy can capture images of individual molecules inside cells, it is difficult to use with living cells because hundreds or thousands of images are needed to reconstruct an image -- a process too slow to capture quickly changing dynamics.

In Optica, a journal for high impact research published by The Optical Society (OSA), investigators from the Chinese Academy of Sciences described how they used an unconventional imaging approach known as ghost imaging to enhance the imaging speed of nanoscopy. Their new technique produces nanometer resolution using orders of magnitude fewer images than traditional nanoscopy techniques.

"Our imaging method can potentially probe dynamics occurring on millisecond time-scales in subcellular structures with spatial resolution of tens of nanometers - the spatial and temporal resolution at which biological processes take place," said WANG Zhongyang, co-leader of the research team.

Combining techniques for faster imaging

The new approach is based on stochastic optical reconstruction microscopy (STORM), one of three researchers sharing the Nobel Prize in Chemistry in 2014. STORM, which is also sometimes called photoactivated localization microscopy (PALM), is a wide-field technique that uses fluorescent labels that switch between light-emitting (on) and dark (off) states.

Acquiring hundreds or thousands of images, each capturing the subset of fluorescent labels that are on at a given time, allows the location of each molecule to be determined and used to reconstruct a fluorescence image.

The researchers turned to ghost imaging to speed up the STORM imaging process. Ghost imaging forms a picture by correlating a light pattern that interacts with the object with a reference pattern that does not.

Individually, the light patterns don't carry any meaningful information about the object. The researchers also used compressive imaging, a computational approach that enables image reconstruction with fewer exposures because it uses an algorithm to fill in the missing information.

"While STORM requires a low density of fluorescent labels and many image frames, our approach can create a high-resolution image using very few frames and a high density of fluorophores," said one of the research team's other co-leaders, HAN Shensheng. "It also doesn't need any complex illumination, which helps reduce photobleaching and phototoxicity that could harm dynamic biological processes and living cells."

Improving imaging efficiency

To implement the new technique, the researchers used an optical component known as a random phase modulator to turn fluorescence from the sample into a random speckle pattern. Coding the fluorescence in this way allowed each pixel of a very fast CMOS camera to collect light intensity from the whole object in a single frame.

To form the image via ghost imaging and compressive imaging, the light intensity was correlated with a reference light pattern in a single step. The result was more efficient image acquisition and a reduction in the number of frames required to form a high-resolution image.

The researchers tested the technique by using it to image a 60-nanometer ring. The new nanoscopy approach resolved the ring using just 10 images while traditional STORM approaches would have needed up to 4000 frames to achieve the same result. The new approach also resolved a 40-nanometer ruler with 100 images.

"We hope this method can be applied to a variety of fluorescent samples, including those that exhibit weaker fluorescence than those used in this research," said WANG.

The researchers also want to make the technique faster to achieve video-rate imaging with a large field of view in order to acquire 3D and color images.

Glioblastoma currently has no cure. New treatments urgently needed

Powerful drug is 1,400 times more potent than current treatment against the brain tumor

Scientists applying to FDA for approval to test this novel treatment in patients with recurrent glioblastoma

CHICAGO --- One of most potent drugs for treatment of glioblastoma, the most deadly type of brain tumor, can't be used in patients because of two problems. First, it can't reach its target because it's blocked by the blood-brain barrier, a microscopic structure that protects the brain from toxins in the blood. And the conventional formulation for this drug is toxic to the brain.

But now Northwestern Medicine scientists have used a novel technology for opening the blood-brain barrier with an implantable ultrasound, and have delivered the powerful drug to the tumor in mice. In a new paper, they report on their findings of extensive preclinical research.

The scientists also discovered brain toxicity for the conventional formulation for this drug - paclitaxel -to the brain was caused by the solution required to dissolve the drug (cremophor.) Scientists tested a new formulation of the drug that uses albumin as opposed to cremophor, and it was not harmful to the brain.

Opening of the blood-brain barrier with an ultrasound increased the concentrations of this paclitaxel in the brain by five-fold. The study also showed that the brain tumor-bearing mice live much longer when treated with the powerful cancer-fighting drug paclitaxel, and survival was even further extended when treated in combination with ultrasound to open the blood-brain barrier.

The study will be published Dec. 12 in Clinical Cancer Research, a journal of the American Association for Cancer Research. 

In the laboratory, paclitaxel is much more potent than the currently used chemotherapy temozolomide. When paclitaxel was tested against the brain tumor in a dish outside an organism, a 1,400-fold lesser drug concentration was necessary to kill same number of tumor cells, compared to the conventional chemotherapy used for this cancer.

The scientists are now applying to the U.S. Food & Drug Administration to launch a clinical trial to test this concept of a new formulation of paclitaxel in combination with the novel ultrasound technology to open the blood-brain barrier in patients. The planned trial aims to determine if the treatment is safe, and if it prolongs survival of patients with brain cancer.

"Glioblastoma currently has no cure, and when the tumor recurs there are not many treatment options," said the principal investigator for this study, Dr. Adam Sonabend, an assistant professor of neurological surgery at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. "We urgently need effective new treatments."

The ultrasound technology may have broader benefits. "This ultrasound technology now will enable us to use many agents established in other cancers for patients with brain tumors," said co-investigator Roger Stupp, chief of neuro-oncology and the Paul C. Bucy Professor of Neurological Surgery at Feinberg.

Other clinical trials are testing ultrasound-based opening of the blood brain barrier with various chemotherapy agents, but none are using such a potent drug as paclitaxel.

How does it work?

The tiny ultrasound would be implanted during surgery into a window in the skull that does not contain bone. It is used in combination with microscopic gas bubbles injected into the blood at the same time the ultrasound begins. When the bubbles hit the sound waves, these vibrate and mechanically disrupt the blood-brain barrier. The opening is immediate, allowing penetration of the drug molecules. The blood-brain barrier opening is reversible and lasts for several hours after the sonication. The ultrasound emitter remains in the skull for repeated delivery of the drug.

PORTLAND, Ore. - A study of outpatient visits to health care providers in the United States during a one-year period suggests 18 percent of antibiotic prescriptions were written without a documented reason for doing so.

The findings, published today in BMJ, are important because they shed greater light on the frequency of antibiotic misuse outside of hospitals and other inpatient care facilities.

Prescribing antibiotics when not warranted needlessly exposes patients to side effects and contributes to the growing global threat of antibiotic resistance - disease-causing bacteria evolving to ward off the drugs that have been developed to kill them.

Michael J. Ray, a researcher at Oregon State University's College of Pharmacy, led the study, which builds on previous research suggesting that unnecessary prescribing in outpatient settings is a key target for improving antibiotic stewardship.

The study is one of the first to look at the proportion of prescriptions lacking a documented "indication," i.e. an accepted medical reason for giving the patient the drug.

"Antibiotic prescribing without making note of the indication in a patient's medical records might be leading to a significant underestimation of the scope of unnecessary prescribing," said Ray, who is also pursuing a Ph.D. in public health with Oregon Health & Science University and Portland State University. "When there's no indication documented, it's reasonable to think that at least some of the time, the prescription was written without an appropriate indication present."

Ray and collaborators at the College of Pharmacy, OHSU, Portland State and Pacific University used the 2015 National Ambulatory Medical Care Survey to examine visits to outpatient care providers. Nationwide there were nearly 1 billion such visits during the year, and the research sought to determine whether antibiotic prescriptions were accompanied by an appropriate documented indication, an inappropriate one, or none at all.

Roughly 13% of those ambulatory care, or outpatient, visits included an antibiotic prescription, a total of 130.5 million prescriptions. Fifty-seven percent of the prescriptions were appropriately indicated, but 25% were inappropriately indicated and 18% had no documented indication.

"What that means is an estimated 24 million antibiotic prescriptions were written without a documented indication, on top of the 32 million that came with a documented but inappropriate indication," said collaborator Jessina McGregor, a College of Pharmacy researcher who studies antibiotic stewardship.

Groups most likely to receive a prescription without a documented indication, the data showed, were adult males, patients who spent more time on average with the provider, patients with chronic conditions, and patients seeing a non-primary care specialist.

Sulfonamides and urinary anti-infectives were the classes of antibiotics most likely to be prescribed without documentation.

"Sixty percent of antibiotic expenditures originate in ambulatory care settings," Ray said. "And up to 90% of antibiotic use originates there. Clearly more focus is needed to support well-informed stewardship efforts."

For viruses to multiply, they usually need the support of the cells they infect. In many cases, only in their host's nucleus can they find the machines, enzymes and building blocks with which they can multiply their genetic material before infecting other cells. But not all viruses find their way into the cell nucleus. Some remain in the cytoplasm and thus must be able to multiply their genetic material independently. To do so, they have to bring their own "machine park". An essential role in this process plays a special enzyme composed of various subunits: the RNA polymerase. This complex reads the genetic information from the genome of the virus and transcribes it into messenger RNA (mRNA), that serves as a blueprint for the proteins encoded in the genome.

Publication in Cell

Scientists from the Biocenter of the Julius-Maximilians-Universität Würzburg (JMU) and the Max Planck Institute (MPI) for Biophysical Chemistry in Göttingen have now succeeded for the first time to solve the three-dimensional structure of a vaccinia virus RNA polymerase at atomic resolution. The vaccinia virus belongs to the poxvirus family, is harmless to humans, and forms the basis of all smallpox vaccines. Due to its benign properties it is currently tested for oncolytic virotherapy, a novel strategy in the combat against cancer.

Responsible for this work are Utz Fischer, Chair of the Department of Biochemistry I of the JMU Würzburg, and Patrick Cramer, Director and head of the Department of Molecular Biology at the MPI for Biophysical Chemistry. In two simultaneous publications in the journal Cell, they now present the results of their collaboration.

A molecular clamp that holds everything together

"The vaccinia virus RNA polymerase exists essentially in two forms: the actual core enzyme and an even larger complex, which, thanks to various additional subunits, has special functionalities," explains Fischer. The core enzyme is largely similar to another known enzyme, which has long been the focus of Cramer's department: the cellular RNA polymerase II. This is found in the cell's nucleus, where it reads the information on the genome and transcribes it into mRNA. Fischer calls the second complex of vaccinia RNA polymerase an 'all-rounder'. Composed of numerous subunits, it carries out the entire transcription process for the virus, thereby enabling an important step in the pathogen's multiplication.

The complex is held together by a molecule that the virus lends from its host cell: a so-called transfer RNA (tRNA). This type of molecule normally does not play a role in transcription, but provides the amino acid building blocks for protein production. "Without the involvement of the host tRNA, this huge machinery with all its specific subunits would fall apart," says structural biologist Clemens Grimm, who carried out the structural analysis together with Hauke Hillen of the MPI. The researchers suspect that the tRNA molecule, in addition to its connecting function, performs another important task. "This tRNA can only be loaded with glutamine, an amino acid necessary not only for the production of proteins but also an important source of energy and nitrogen for the cell," explains Aladar Szalay, co-author of the study and director of the Cancer Therapy Research Center (CTRC) at the JMU. Since the virus relies on nitrogen for its replication, the tRNA could serve as a sensor that provides the virus with information about the current nitrogen content in the host cell. If the nitrogen level falls below a certain value, this could be the signal for the virus to leave its host as soon as possible. But this is so far just a hypothesis.

To find out how the viral RNA polymerase works, the researchers also determined its three-dimensional structure during different transcription steps. With these new findings, it is now possible to understand the entire process of virus multiplication on a structural basis. Like in a film, it is possible to track how this molecular machine functions at the atomic level and how the individual processes are choreographed. "What's amazing is how the building blocks of the machine rearrange themselves after the start of transcription to drive the synthesis of the RNA product - this complex is really very dynamic," Hillen explains. To gain this insight, biochemists and structural biologists had to work closely together: The biochemists Julia Bartuli and Kristina Bedenk at the JMU have purified and biochemically characterized the polymerase complex with all its interacting components in a year-long process. The structural biologists Grimm and Hillen were then responsible for determining the three-dimensional structures.

A super microscope provides the necessary data

The researchers obtained the data from a device that has revolutionized structural analysis in recent years: the latest generation cryo-electron microscopes, which are in operation at both the JMU and the MPI. With 300,000 volts, it shoots electrons through samples cooled down to minus 180 degrees Celsius and thus delivers images with a resolution that ranges in the order of atoms. The microscope makes it possible to study biological molecules and complexes and to reconstruct their three-dimensional structure.

For about six months, Grimm and Hillen had to work with their computers until they had developed a spatial model of the polymerase complexes from several terabytes of data. "Without the new cryo-microscopes at our institutions and the excellent cooperation between the two groups, that would not have been possible so quickly and in this quality," says Grimm. With 3D glasses, everyone can now spatially visualize the complex, turn it arbitrarily and dissect it into its subunits.

Among other things, the new findings now offer the possibility to develop inhibitors and modulators to influence the viral propagation cycle. Because Vaccinia replication occurs in the cytoplasm, the scientists also expect it to have therapeutic potential. Currently, studies are underway throughout the world in which Vaccinia viruses are used in the fight against cancer. The company Genelux, which also participated in the study, has already shown in animal experiments and patients the potential of specially optimized Vaccinia viruses to shrink tumors and to detect the smallest metastases. In addition, the researchers expect new and exciting insights into the functioning of the related non-viral RNA polymerase complexes.

Using a computerised version of cognitive-behavioural therapy to treat depression in children and young adults has the potential to improve access to psychological therapies and reduce waiting lists, a new study suggests.

Cognitive behavioural therapy (CBT) - often known as talking therapy - is widely and effectively used in the mental health services to help people suffering from depression and anxiety. Reviews of CBT for adolescent depression have shown that it is effective and currently one of the main treatment options recommended for this age group

The study, led by the University of York, examined the clinical and cost effectiveness of delivering a computerised CBT programme (CCBT).

The trial which ran in community and clinical settings worked with young people aged between 12 and 18 who were suffering with low mood or depression. Most of the young people received CCBT in a private setting within their own school, and qualitative interviews showed that they reported this to be helpful and supportive.

It's estimated that between two and four per cent of adolescents suffer from depression and that early treatment can be effective but the availability of effective mental health treatments with Child and Adolescent Mental Health Services (CAMHS) is limited, with limited staff numbers and long waiting times.

Professor Barry Wright from the Child Oriented Mental Health Intervention Centre said:
"Computerised forms of CBT could offer a wider, faster delivery of CBT. Given the importance of early treatment, this study shows that CCBT can also be offered in a cost-effective manner.

"CCBT is easily accessible and addresses some young people's reluctance to access mental health services. CCBT may reduce this barrier in providing easy access in the community,
without need for regular face-to-face contact.

"The study suggests that CCBT may have a place in the care of children and young people, particularly early on if they are on waiting lists, however some young people continue to have low mood and depression and will need other forms of treatment such as face to face therapy or medication.

"Further research needs to be done to explore the place of the different treatments available for young people with low mood and depression in the care pathway. This includes preventive treatment."

A team of researchers from the University of Georgia's Regenerative Bioscience Center has found that neural exosomes--"cargo" molecules within the nervous system that carry messages to the brain--can minimize or even avert progression of traumatic brain injury when used as part of a new cell-to-cell messaging technology.

The finding could result in the first delivery platform and regenerative treatment for TBI.

The research was reported on Nov. 27 in the Journal of Neurotrauma and outlines significant steps in providing data for industry development and commercial manufacturing of a regenerative TBI-IV therapy.

The new restorative technology contains bio-manufactured exosomes that can be stored on the shelf and given as an injection into a vein. Once injected, the exosomes become message mediators to reset, regenerate and coordinate communication with both neighboring and distant cells. As a result, this novel treatment showed improved functional recovery in rats after TBI.

"The technology takes full benefit of the desirable properties of a neural stem cell therapy without introducing cells into patients," said Steven Stice, Georgia Research Alliance Eminent Scholar and D.W. Brooks Distinguished Professor in the College of Agricultural and Environmental Sciences. "We are working toward a therapeutic that has a multifunctional promise to repair brain injury and be producible in a cost-effective, off-the-shelf drug format."

Traumatic brain injuries can be difficult to detect because each TBI patient presents a unique set of circumstances determined by injury timeline and severity, as well as individual characteristics such as age, gender and occupation. With this potential new technique, RBC researchers hope to boost the brain's natural ability to recover and provide physicians with a treatment that can be administered immediately in cases of severe TBI.

"Mechanistically, TBI is a physician's nightmare," said Lohitash Karumbaiah, associate professor of regenerative medicine in UGA's College of Agricultural and Environmental Sciences and one of the publication's lead authors. "Because there are so many things going on in the brain, you can't really exactly pinpoint what is going wrong, and without therapies to immediately improve recovery, the situation becomes extremely complex."

For those affected by TBI, treatment could be administered at the time of injury with IV fluids. Using multiple low-dose, intravenous injections, the novel treatment is designed to speed up regeneration of neurons and supporting cells following injury.

"Administrating exosomes into a patient's IV drip would always be preferable to invasive brain surgery," Karumbaiah said. "What we can do is give physicians a fighting chance to regulate the inflammatory response of TBI, rather than trying to treat it after it occurs."

Another application the team has considered is the use of exosome technology as a preventive management program for all levels of TBI, including mild and moderate concussions that could minimize or prevent future damage.

Licensed to and under development by Aruna Bio, one of UGA's first Innovation Gateway startups, the exosome technology has already captured the interest and financial support of the Georgia Research Alliance's Venture Fund, one of the largest venture capital funds in the state. The GRA Venture Fund, along with other investors, contributed to the $13 million in common stock financing recently announced by Aruna Bio.

"Drug development for acute TBI has suffered so many clinical failures and will need to take an imminent paradigm shift toward a more targeted and personalized treatment," said Stice. "We still have a lot to learn, but our success could create the tipping point."

HOUSTON - (Dec. 12, 2019) - Molecular drills have gained the ability to target and destroy deadly bacteria that have evolved resistance to nearly all antibiotics. In some cases, the drills make the antibiotics effective once again.

Researchers at Rice University, Texas A&M University, Biola University and Durham (U.K.) University showed that motorized molecules developed in the Rice lab of chemist James Tour are effective at killing antibiotic-resistant microbes within minutes.

"These superbugs could kill 10 million people a year by 2050, way overtaking cancer," Tour said. "These are nightmare bacteria; they don't respond to anything."

The motors target the bacteria and, once activated with light, burrow through their exteriors.

While bacteria can evolve to resist antibiotics by locking the antibiotics out, the bacteria have no defense against molecular drills. Antibiotics able to get through openings made by the drills are once again lethal to the bacteria.

The researchers reported their results in the American Chemical Society journal ACS Nano.

Tour and Robert Pal, a Royal Society University Research Fellow at Durham and co-author of the new paper, introduced the molecular drills for boring through cells in 2017. The drills are paddlelike molecules that can be prompted to spin at 3 million rotations per second when activated with light.

Tests by the Texas A&M lab of lead scientist Jeffrey Cirillo and former Rice researcher Richard Gunasekera, now at at Biola, effectively killed Klebsiella pneumoniae within minutes. Microscopic images of targeted bacteria showed where motors had drilled through cell walls.

"Bacteria don't just have a lipid bilayer," Tour said. "They have two bilayers and proteins with sugars that interlink them, so things don't normally get through these very robust cell walls. That's why these bacteria are so hard to kill. But they have no way to defend against a machine like these molecular drills, since this is a mechanical action and not a chemical effect."

The motors also increased the susceptibility of K. pneumonia to meropenem, an antibacterial drug to which the bacteria had developed resistance. "Sometimes, when the bacteria figures out a drug, it doesn't let it in," Tour said. "Other times, bacteria defeat the drug by letting it in and deactivating it."

He said meropenem is an example of the former. "Now we can get it through the cell wall," Tour said. "This can breathe new life into ineffective antibiotics by using them in combination with the molecular drills."

Gunasekera said bacterial colonies targeted with a small concentration of nanomachines alone killed up to 17% of cells, but that increased to 65% with the addition of meropenem. After further balancing motors and the antibiotic, the researchers were able to kill 94% of the pneumonia-causing pathogen.

Tour said the nanomachines may see their most immediate impact in treating skin, wound, catheter or implant infections caused by bacteria -- like staphylococcus aureus MRSA, klebsiella or pseudomonas -- and intestinal infections. "On the skin, in the lungs or in the GI tract, wherever we can introduce a light source, we can attack these bacteria," he said. "Or one could have the blood flow through a light-containing external box and then back into the body to kill blood-borne bacteria."

"We are very much interested in treating wound and implant infections initially," Cirillo said. "But we have ways to deliver these wavelengths of light to lung infections that cause numerous mortalities from pneumonia, cystic fibrosis and tuberculosis, so we will also be developing respiratory infection treatments."

Gunasekera noted bladder-borne bacteria that cause urinary tract infections may also be targeted.

The paper is one of two published by the Tour lab this week that advance the ability of microscopic nanomachines to treat disease. In the other, which appears in ACS Applied Materials Interfaces, researchers at Rice and the University of Texas MD Anderson Cancer Center targeted and attacked lab samples of pancreatic cancer cells with machines that respond to visible rather than the previously used ultraviolet light. "This is another big advance, since visible light will not cause as much damage to the surrounding cells," Tour said.