Brain

Imaging reveals new results from landmark stem cell trial for stroke

image: Sean I. Savitz, MD from the University of Texas Health Science Center at Houston.

Image: 
UTHealth

Researchers led by Sean I. Savitz, MD, reported today in the journal Stem Cells that bone marrow cells used to treat ischemic stroke in an expanded Phase I trial were not only safe and feasible, but also resulted in enhanced recovery compared to a matched historical control group.

In addition, using serial diffusion tensor imaging, the repair of motor nerve tracts that extend from the brain through the spinal cord were captured for the first time in study participants, according to the team at The University of Texas Health Science Center at Houston (UTHealth).

"In the typical stroke injury, you can see the degeneration of the nerve tracts where it thins out," said Savitz, director of the Institute for Stroke and Cerebrovascular Disease and professor of neurology with McGovern Medical School at UTHealth. "What surprised us was that after three to six months, we could see the tracts thicken up again in some patients. We do not typically see that same level of response in patients with such severe strokes but further research will be needed to determine if the return of the nerve tracts is because of the cell treatment or part of natural recovery."

The team also reported that patients in the cell-treated group had a 1-point improvement in the Day 90 modified Rankin score, a 6-point scale considered the gold standard for rating stroke recovery and disability. The study patients were compared to a propensity score-based matched control group to estimate the improvement in effect size.

Farhaan S. Vahidy, PhD, MBBS, MPH, director of Population Health at the Institute for Stroke and Cerebrovascular Diseases and associate professor of neurology with McGovern Medical School at UTHealth, was first author of the paper and performed the analyses.

The pilot study, which began in 2009, was the first of its kind using a patient's own bone marrow cells. Results from the first 10 patients were published in 2011 in the Annals of Neurology.

The latest paper included results from 25 patients, who received an intravenous dose of their own bone marrow cells within 72 hours after first symptoms of stroke. They were followed for one year after treatment and the results compared to a control group of 185 acute ischemic stroke patients who received conventional treatment only. No definite severe adverse events related to the procedures were seen in any of the 25 patients, the research showed.

The authors wrote that the regenerative potential of bone marrow mononuclear cells is attributed to various mechanisms that impact stroke recovery and is supported by extensive preclinical studies that Vahidy analyzed in a study published in the American Heart Association journal, Stroke, in 2016. The cells migrate to the site of injury and release proteins that decrease the inflammation hindering the healing process. Bone marrow cells are also easily amenable to autologous infusion, eliminating the need for immunosuppressive drugs.

"According to our findings, it is feasible to perform a bone marrow harvest and then infuse the cells in a wide range of stroke patients," Savitz said. "Well-designed randomized clinical trials are needed to further assess safety and efficacy of this novel approach to enhance stroke recovery."

Credit: 
University of Texas Health Science Center at Houston

Study finds community-oriented policing improves attitudes toward police

New Haven, Conn. -- Brief, friendly door-to-door visits by uniformed police officers substantially improve people's attitudes toward the police and increase their trust in law enforcement, according to a new study of community-oriented policing in New Haven.

The study, published in the Proceedings of the National Academy of Sciences, is the first randomized, controlled field experiment to test the effects of community-oriented policing on people's opinions of their local police. The researchers found that a single, positive, nonenforcement-related encounter enhanced the legitimacy of police officers and increased people's willingness to cooperate with the police.

The positive effects of the unannounced door-to-door visits were durable as residents continued to report improved attitudes toward police 21 days after the initial encounters, according to the study, which was conducted in partnership with the New Haven Police Department. The researchers found that the visits were effective across racial and ethnic groups and that the long-term positive effects were strongest among non-white residents and people who held negative views of the police prior to the intervention.

"Policy makers promote community-oriented policing as a means to build trust between police officers and the communities they serve, but there has been little evidence on whether the nonenforcement interactions at the heart of community policing actually cause people to view the police differently," said Kyle Peyton, a Ph.D. candidate in political science at Yale University and lead author of the study. "We found that a single, positive nonenforcement interaction with a police officer improved residents' attitudes toward police, including perceived legitimacy and willingness to cooperate."

In response to nationwide unrest following the fatal shooting of Michael Brown by a police officer in Ferguson, Missouri, the Obama administration established the President's Task Force on 21st-Century Policing to study ways to improve police-community relations throughout the country. In its May 2015 final report, the committee emphasized the need to adopt community-oriented policing -- a law-enforcement strategy that focuses on positive, non-punitive, and nonenforcement contact with the public as a means to build trust and promote safety.

The researchers initially mailed surveys to New Haven residents containing questions about policing combined with unrelated queries concerning city government, local politics, and national politics. Of the people contacted by mail, 2013 individuals in 1,852 households completed the survey and provided contact information to participate in follow-up surveys.

The researchers assigned 926 households (1,007 individuals) to a treatment group, which received the community-policing visits, and 926 households (1,006 individuals) to a control group that was not visited. Of the treatment group, 412 people engaged with police officers during an announced visit to their homes in which the officers introduced themselves, solicited feedback, and provided personalized business cards with their work cell-phone number. Following the visits, all 2,013 people who participated in the original survey were invited via email to participate in two follow-up surveys that occurred 3 and 21 days after the visits.

Those surveys measured people's attitudes in four categories: legitimacy, perceived effectiveness, cooperation, and compliance. In both follow-up surveys, the positive effects of the door-to-door visits were evident across all four categories and the strongest effects were in legitimacy and perceptions of police effectiveness, according to the study. The researchers also found the encounters reduced negative beliefs about police (e.g. they are "cold-hearted") and increased support for a policy to hire more patrol officers through a 10% funding increase to the police department.

"We're grateful to the New Haven Police Department for partnering with us to conduct this study," said Peyton, a graduate resident in Yale's Institution for Social and Policy Studies (ISPS). "We hope these findings prove useful to police departments across the country as they consider adopting community-oriented approaches like the ones in New Haven to build trust, particularly in communities where police-community relations have been damaged by longstanding conflict and distrust."

Michael Sierra-Arévalo, assistant professor in the Rutgers School of Criminal Justice and a co-author of the study, emphasized that the study's findings should not be interpreted as a wholesale solution to persistent problems in policing.

"It would be a mistake to interpret our study as having found some magic solution to distrust in police that is often rooted in a history of mistreatment," Sierra-Arévalo said. "Positive, respectful police-community interaction should be the norm in all police departments; but community policing isn't going to solve police brutality or a lack of police accountability. Those problems demand their own attention and their own solutions."

Credit: 
Yale University

Compounds extracted from Cerrado plant combat fungus that causes candidiasis

Fungi of the genus Candida cause thrush and candidiasis, a fairly common disease in humans. It can be lethal to individuals with low immunity, especially when they are hospitalized. Although the drug most widely used to combat the disease is effective in most cases, some varieties of the fungus are drug-resistant.

Compounds that combat two species of Candida have now been isolated from a plant by researchers based in Brazil and Spain. The plant is Mimosa caesalpiniifolia, a shrub native to the Cerrado (Brazilian savanna) and called sansão-do-campo, sabiá or cerca-viva in Portuguese. The idea is to create an ointment for use as an alternative to fluconazole, long considered the best antifungal for candidiasis, which can cause itching and pain in the genitals, vaginal discharge, and sores in the mouth or elsewhere.

The results of the research, which was supported by São Paulo Research Foundation - FAPESP, are published in the Journal of Natural Products. The investigation was conducted during Marcelo José Dias Silva's postdoctoral fellowship at São Paulo State University's Bioscience Institute (IB-UNESP) in São Vicente, Brazil. Silva did part of it while he was at the University of Cádiz (UCA) in Spain, also with a scholarship from FAPESP.

The study was part of the Thematic Project "Standardized herbal medicines for the treatment of chronic diseases", for which the principal investigator was Wagner Vilegas, Full Professor at IB-UNESP. The group also received funding from the Spanish Ministry of the Economy, Industry and Competitiveness.

"This discovery and the development of novel therapeutic entities, which in the right combination could lead to a considerable reduction in the necessary concentration of drugs, can minimize the side effects and toxicity of the antimicrobial agents in conventional use," Vilegas said.

"The final cost of treatment can also be reduced, as can the resistance acquired by some microorganisms. More research is needed, including both prospection studies like this one and studies using biological models."

Ointment

A total of 23 known compounds were isolated from M. caesalpiniifolia, as well as five new flavonoids named mimocaesalpin A, B, C, D and E. Applied to samples of Candida glabrata and C. krusei, four of the 28 compounds displayed more effective antifungal activity than did fluconazole.

"We applied the different compounds to these two fungi, and most had little or no effect. However, four showed promising activity and will be tested in the form of ointments," said Silva, first author of the article.

Three formulations will be tested, using the compounds or combinations found to be most effective in inhibiting fungal growth, including a combination of a type of beta-sitosterol with ethyl gallate. These two substances are present in several plant species and are particularly abundant in M. caesalpiniifolia.

Another formulation will contain one of the new flavonoids, mimocaesalpin C. The third will combine this mimocaesalpin with beta-sitosterol.

"Beta-sitosterol on its own was not effective, but when combined with the other two compounds, it was synergistic and highly effective. Mimocaesalpin C displayed promising selective activity against C. krusei, which is resistant to fluconazole," Silva said.

Before arriving at these candidate medications, however, the researchers produced an extract from the plant and submitted it to chromatography fractionation, a laboratory technique for separating a mixture into its components.

Five fractions were produced in this manner and tested for antifungal activity. Three fractions inhibited fungal growth by 50%. These more promising fractions were then subjected to the same technique to isolate the new flavonoids and other compounds.

"M. caesalpiniifolia extract is very complex. It contains a large amount of chlorophyll and fatty acids, all of which hinder the identification of the compounds present. Thanks to our partnership with colleagues at the University of Cádiz, we were able to separate them out and focus our investigation on the most viable fractions," Silva said.

Before creating the ointments, the researchers will perform tests to determine whether the antifungal effect of the four compounds persists or even increases when they are mixed with adjuvants, substances used to enhance the efficacy or potency of a medication in the organism.

Credit: 
Fundação de Amparo à Pesquisa do Estado de São Paulo

For kids who face trauma, good neighbors or teachers can save their longterm health

image: A young child looks directly at the camera.

Image: 
BYU Photo

New research shows just how important positive childhood experiences are for our long-term health -- especially for those who experience significant adversity as a child.

Studies over the past 20 years have found a correlation between the number of adverse childhood events (such as death or divorce) and worse health outcomes later in life. A new study from professor Ali Crandall and other Brigham Young University coauthors discovered that positive childhood experiences -- like having good neighbors, regular meals or a caregiver you feel safe with -- have the potential to negate harmful health effects caused by adverse childhood experiences.

"If your child has experienced trauma and you're worried about the long-term impact it could have on them, these findings show that the positive experiences in childhood lead to better adult physical and mental health, no matter what they have faced," said Crandall, assistant professor of public health at BYU.

Specifically, the study found that even when an individual had four or more adverse childhood experiences (called ACEs), having a high number of advantageous childhood experiences (Counter-ACEs) lessened the negative effect of ACEs on adult health. This is significant because the landmark 1998 ACEs study concluded that having four or more ACEs in childhood greatly increases negative health outcomes, including higher BMI, smoking rates, depression and chronic health conditions.

BYU study participants reported the number of ACEs and Counter-ACEs they experienced in childhood. ACEs include abuse, abandonment, having a family member in jail, alcoholism, mental illness, addiction, divorce or death. The full list of Counter-ACEs includes having good friends and neighbors, beliefs that provide comfort, liking school, teachers who care, having a caregiver whom you feel safe with, opportunities to have fun, feeling comfortable with yourself and a predictable home routine like regular meals and bedtimes.

Accoring to the study findings, published recently in the journal Child Abuse & Neglect, nearly 75 percent of participants had at least one adverse childhood experience, while the average amount of ACEs was 2.67 per person. The average positive experience score was 8.15, with 39 percent of people having experienced all 10 of those Counter-ACEs.

Participants also reported their current health through a variety of physical measures -- like BMI, fruit and vegetable consumption, physical exercise, sleep difficulties and if they smoked daily -- as well as their cognitive and mental health through executive functioning abilities, perceived stress, depression, internal locus of control, gratitude, forgiveness of self and challenging situations and familial closeness. Interestingly, researchers also found that the absence of Counter-ACEs led to poor adult health regardless of the number of ACEs.

"As bad as ACEs may be, the absence of these positive childhood experiences and relationships may actually be more detrimental to lifelong health so we need more focus on increasing the positive," Crandall said.

While many of the adverse childhood experiences in this study are affected by a child's family situation, Crandall said that "other adults in a child's life that are not the parent, like extended family, teachers, neighbors, friends and youth leaders all help to increase the number of counter ACEs and boosts lifelong health."

Crandall believes that increasing counter-ACES in the home is the easiest place to start and is working to educate the community about how to do this in conjunction with United Way. BYU professors Brianna Magnusson, Len Novilla, Carl Hanson and Michael Barnes were coauthors on the study.

Credit: 
Brigham Young University

A novel tool to probe fundamental matter

Quarks, bosons, electrons ... Identifying elementary constituents of matter, and the manner by which these particles interact with each other, constitutes one of the greatest challenges in modern physical sciences. Resolving this outstanding problem will not only deepen our understanding of the early days of the Universe, but it will also shed some light on exotic states of matter such as superconductors.

Besides gases, liquids and solids, matter can exist in other forms when it is subjected to extreme conditions. Such situations were encountered in the Universe right after the Big Bang, and they can also be mimicked in the laboratory. And while a plethora of elementary particles were discovered in high-energy colliders, complex questions regarding their interactions and the existence of novel states of matter remain unanswered.

In collaboration with the experimental group of Immanuel Bloch, Monika Aidelsburger and Christian Schweizer (Munich), and theorists Eugene Demler and Fabian Grusdt (Harvard), Nathan Goldman and Luca Barbiero (Physics of Complex Systems and Statistical Mechanics, Science Faculty) propose and validate and novel experimental approach by which these rich phenomena can be finely studied. Published in Nature Physics, their work reports on the experimental realization of a "lattice gauge theory", a theoretical model initially proposed by Kenneth Wilson - Nobel Prize in Physics 1982 - to describe the interactions between elementary particles such as quarks and gluons. The authors demonstrate that their experimental setup, an ultracold gas of atoms manipulated by lasers, indeed reproduces the characteristics of such an appealing model. The challenge consisted in implementing well-defined interactions between "matter" particles and "gauge bosons", which are the mediators of fundamental forces. In the cold-atom context, these different types of particles are represented by different atomic states, which can be addressed in a very fine manner using lasers.

This novel experimental approach constitutes an important step for the quantum simulation of more sophisticated theories, which may eventually shed some light on open questions in high-energy and solid-state physics using table-top experiments.

Credit: 
Université libre de Bruxelles

Geochemists measure new composition of Earth's mantle

image: The mineral olivine contains melt inclusions (black dots), just a few micrometers in size. The geochemists isolated these inclusions and investigated the isotopic composition with mass spectrometers.

Image: 
Münster University - Felix Genske

What is the chemical composition of the Earth's interior? Because it is impossible to drill more than about ten kilometres deep into the Earth, volcanic rocks formed by melting Earth's deep interior often provide such information. Geochemists at the Universities of Münster (Germany) and Amsterdam (Netherlands) have investigated the volcanic rocks that build up the Portuguese island group of the Azores. Their goal: gather new information about the compositional evolution of the Earth's mantle, which is the layer roughly between 30 and 2,900 kilometres deep inside the Earth. Using sophisticated analytical techniques, they discovered that the composition of the mantle below the Azores is different than previously thought -suggesting that large parts of it contain surprisingly few so-called incompatible elements. These are chemical elements which, as a result of the constant melting of the Earth's mantle, accumulate in the Earth's crust, which is Earth's outermost solid layer.

The researchers conclude that, over Earth's history, a larger amount of Earth's mantle has melted - and ultimately formed the Earth's crust - than previously thought. "To sustain the material budget between Earth's mantle and crust, mass fluxes between the surface and Earth's interior must have operated at a higher rate," says Münster University's Prof. Andreas Stracke, who is heading the study.

As the material below the Azores rises from very deep within Earth's mantle - and is unexpectedly similar to most of its upper part - the composition of Earth's entire mantle may differ from current thinking. "Our results have opened up a new perspective," says Andreas Stracke, "because we will now have to reassess the composition of the largest part of the Earth - after all, Earth's mantle accounts for over 80 percent of Earth's volume." The study has been published in the journal Nature Geoscience.

Background and method:

In their study, the geochemists examined the mineral olivine and its melt inclusions, i.e. magma encapsulated during the crystallisation of olivine before the lavas erupted. The researchers isolated these melt inclusions, just a few micrometers in size, dissolved them chemically and separated certain chemical elements. These elements are altered by radioactive decay during their lifetime and ascent from Earth's interior - travelling over thousands of kilometres for hundreds or even thousands of millions of years.

The researchers analysed the isotopic composition of the melts with highly sensitive mass spectrometers. Such methods allow measurement of the relative abundance of different atoms in an element - so-called isotopes. "Owing to the high efficiency of our measurements, we were able to analyse the isotopic composition of one billionth of a gram of the element," says co-author Dr. Felix Genske from the University of Münster's Institute of Mineralogy, who carried out most of the analytical work. In this way, the researchers indirectly obtained information on the composition of the material in the Earth's mantle: the isotope analyses showed that it contains far fewer rare Earth elements such as samarium and neodymium, but also of chemically similar elements such as thorium and uranium.

"On the basis of similar geochemical data in volcanic rocks from different regions, e.g. Hawaii, other parts of the Earth's mantle may also contain a higher proportion of material that is strongly depleted in incompatible elements," says Andreas Stracke. The researchers presume that this global deficit may be compensated by a higher rate of recycling Earth's incompatible element-rich crust back into Earth's mantle. With their continuing studies the researchers want to confirm their working hypothesis by investigating samples from other volcanic islands across the globe.

Credit: 
University of Münster

New sample holder for protein crystallography

image: After their formation the tiny crystals are prepared for x-ray analysis -- without touching them. They stay onto the same sample holder.

Image: 
HZB

Proteins are huge molecules that often have complex three-dimensional structure and morphology that can include side chains, folds, and twists. This three-dimensional shape is often the determining factor of their function in organisms. It is therefore important to understand the structure of proteins both for fundamental research in biology and for the development of new drugs. To accomplish this, proteins are first precipitated from solution as tiny crystals, then analysed using facilities such as the MX beamlines at BESSY II in order to generate a computer image of the macromolecular structure from the data.

Up to now, protein crystals have first been grown and then transferred onto a sample holder for structural analysis. However, this transfer entailed a risk of destroying the often extremely fragile crystals.

This risk is no longer necessary thanks to the new sample holder developed by Dr. Manfred Weiss and Dr. Christian Feiler from the MX team together with Dr. Dirk Wallacher from the BESSY II sample environment group. Instead, the protein solution is applied directly onto the sample holder and crystallised in place, eliminating the need to transfer the delicate protein crystals to a different sample holder for analysis. "The new sample holder saves work steps and reduces the risk of damaging the sensitive protein crystals", explains Feiler. "We have a short video clip that shows step-by-step how these sample holders facilitate protein crystallography - you have to see this!" exclaims Weiss, head of the MX-Beamline.

In practice, a large number of samples are always measured at once, so 24 sample holders are grouped together onto one sample plate. The new sample holder is patented in Germany and registered for an international patent. Jena Bioscience has acquired a licence and is already marketing the new development worldwide.

Credit: 
Helmholtz-Zentrum Berlin für Materialien und Energie

In human cells and mice, a cure for the common cold, Stanford-UCSF study reports

Temporarily disabling a single protein inside our cells might be able to protect us from the common cold and other viral diseases, according to a study led by researchers at Stanford University and University of California-San Francisco.

The findings were made in human cell cultures and in mice.

"Our grandmas have always been asking us, 'If you're so smart, why haven't you come up with a cure for the common cold?'" said Jan Carette, PhD, associate professor of microbiology and immunology. "Now we have a new way to do that."

The approach of targeting proteins in our own cells also worked to stop viruses associated with asthma, encephalitis and polio.

Colds, or noninfluenza-related upper respiratory infections, are for the most part a weeklong nuisance. They're also the world's most common infectious illness, costing the United States economy an estimated $40 billion a year. At least half of all colds are the result of rhinovirus infections. There are roughly 160 known types of rhinovirus, which helps to explain why getting a cold doesn't stop you from getting another one a month later. Making matters worse, rhinoviruses are highly mutation-prone and, as a result, quick to develop drug resistance, as well as to evade the immune surveillance brought about by previous exposure or a vaccine.

In a study to be published online Sept. 16 in Nature Microbiology, Carette and his associates found a way to stop a broad range of enteroviruses, including rhinoviruses, from replicating inside human cells in culture, as well as in mice. They accomplished this feat by disabling a protein, in mammalian cells and that all enteroviruses appear to need in order to replicate.

Carette shares senior authorship with Or Gozani, MD, PhD, professor of biology at Stanford and the Dr. Morris Herzstein Professor of Biology; Raul Andino, PhD, professor of microbiology and immunology at UCSF; and Nevan Krogan, PhD, professor of cellular and molecular pharmacology at UCSF. The lead authors are former Stanford graduate student Jonathan Diep, PhD, and Stanford postdoctoral scholars Yaw Shin Ooi, PhD, and Alex Wilkinson, PhD.

Well-known and feared

One of the most well-known and feared enteroviruses is poliovirus. Until the advent of an effective vaccine in the 1950s, the virus spelled paralysis and death for many thousands of children each year in the United States alone. Since 2014, another type of enterovirus, EV-D68, has been implicated in puzzling biennial bursts of a poliolike disease, acute flaccid myelitis, in the United States and Europe. Other enteroviruses can cause encephalitis and myocarditis -- inflammation of the brain and the heart, respectively.

Like all viruses, enteroviruses travel lightly. To replicate, they take advantage of proteins in the cells they infect.

To see what proteins in human cells are crucial to enteroviral fecundity, the investigators used a genomewide screen developed in Carette's lab. They generated a cultured line of human cells that enteroviruses could infect. The researchers then used gene editing to randomly disable a single gene in each of the cells. The resulting culture contained, in the aggregate, cells lacking one or another of every gene in our genome.

The scientists infected the culture with RV-C15, a rhinovirus known to exacerbate asthma in children, and then with EV-C68, implicated in acute flaccid myelitis. In each case, some cells managed to survive infection and spawn colonies. The scientists were able to determine which gene in each surviving colony had been knocked out of commission. While both RV-C15 and EV-D68 are both enteroviruses, they're taxonomically distinct and require different host-cell proteins to execute their replication strategies. So, most of the human genes encoding the proteins each viral type needed to thrive were different, too. But there were only a handful of individual genes whose absence stifled both types' ability to get inside cells, replicate, bust out of their cellular hotel rooms and invade new cells. One of these genes in particular stood out. This gene encodes an enzyme called SETD3. "It was clearly essential to viral success, but not much was known about it," Carette said.

The scientists generated a culture of human cells lacking SETD3 and tried infecting them with several different kinds of enterovirus -- EV-D68, poliovirus, three different types of rhinovirus and two varieties of coxsackievirus, which can cause myocarditis. None of these viruses could replicate in the SETD3-deficient cells, although all proved capable of pillaging cells whose SETD3-producing capability was restored.

The researchers observed a 1,000-fold reduction in a measure of viral replication inside human cells lacking SETD3, compared with controls. Knocking out SETD3 function in human bronchial epithelial cells infected with various rhinoviruses or with EV-D68 cut replication about 100-fold.

Impervious mice

Mice bioengineered to completely lack SETD3 grew to apparently healthy adulthood and were fertile, yet they were impervious to infection by two distinct enteroviruses that can cause paralytic and fatal encephalitis, even when these viruses were injected directly into the mice's brains soon after they were newly born.

"In contrast to normal mice, the SETD3-deficient mice were completely unaffected by the virus," Carette said. "It was the virus that was dead in the water, not the mouse."

Enteroviruses, the scientists learned, have no use for the section of SETD3 that cells employ for routine enzymatic activity. Instead, enteroviruses cart around a protein whose interaction with a different part of the SETD3 molecule, in some as yet unknown way, is necessary for their replication.

"This gives us hope that we can develop a drug with broad antiviral activity against not only the common cold but maybe all enteroviruses, without even disturbing SETD3's regular function in our cells," Carette said.

Credit: 
Stanford Medicine

Radiation therapy effective against deadly heart rhythm

image: Radiation oncologist Clifford Robinson, MD, (right) and cardiologist Phillip Cuculich, MD, of Washington University School of Medicine in St. Louis, have developed a noninvasive radiation therapy approach to treating ventricular tachycardia, a deadly heart arrhythmia. Visual and electrical maps of the heart help direct a beam of radiation at the heart tissue triggering the heart to misfire, significantly reducing the arrhythmia.

Image: 
Matt Miller

A single high dose of radiation aimed at the heart significantly reduces episodes of a potentially deadly rapid heart rhythm, according to results of a phase one/two study at Washington University School of Medicine in St. Louis.

Patients in the study were severely ill and had exhausted other standard treatment options. The radiation used to treat the irregular heart rhythm -- called ventricular tachycardia -- is the same type of therapy used to treat cancer.

The research will be reported Sept. 15 at the American Society for Radiation Oncology (ASTRO) Annual Meeting in Chicago.

"Radiation therapy is a last line of defense for these patients, who are often too unwell to undergo additional traditional therapies to control heart arrhythmias," said Clifford G. Robinson, MD, an associate professor of radiation oncology and of cardiology at Washington University. "It provides hope for patients with dangerous rhythms who have run out of options."

In ventricular tachycardia (VT), the lower chambers of the heart beat exceedingly fast and fall out of sync with the upper chambers, interfering with blood flow and raising the risk of sudden cardiac death. Patients with VT typically are implanted with defibrillators that shock the heart back into a normal rhythm. In an effort to stop the episodes, patients often are treated with catheter ablation procedures, in which a catheter is inserted into the heart and used to create scars in the part of the damaged heart muscle that is causing the electrical signals to misfire. But catheter ablation is invasive, requires many hours under general anesthesia and often isn't a permanent solution. The rapid heart rhythm returns in about half of such patients.

The new method is a noninvasive outpatient procedure that involves the use of electrocardiograms and computed tomography scans of a patient's heart to locate the origin of the arrhythmia. The 3D visual and electrical maps of the heart then guide the noninvasive radiation therapy. Doctors can target the problem area of the heart with a single high-dose beam of radiation that often takes less than 10 minutes to administer and requires no anesthesia or hospitalization. The patient can go home right after treatment.

The phase one/two trial included 19 patients with ventricular tachycardia who had not responded to other therapies. In a study published in 2017 in The New England Journal of Medicine, the same research team reported a 90% reduction in episodes of tachycardia and improved survival in the six months after radiation therapy. Now, Robinson and his colleagues, including Washington University cardiologist Phillip S. Cuculich, MD, an associate professor of cardiology and of radiation oncology, report that the reduction in tachycardia episodes persists in about 80% of patients for at least two years following the single treatment. At one year after therapy, overall survival was 72%, and at two years, survival was 52%.

"These numbers are encouraging given the condition of the patients, who are too sick to undergo any more catheter ablation procedures," Robinson said. "Given the relative novelty of this treatment approach, we are continuing to follow our patients closely."

Of nine patient deaths, six were from cardiac causes, including heart failure and tachycardia recurrence, and three were from noncardiac causes, including an accident, amiodarone toxicity and pancreatic cancer. Two surviving patients experienced inflammation of the heart lining, a common side effect of this type of radiation therapy, and another developed a fistula between the stomach and the heart and needed surgery to repair it. All three of these adverse events occurred more than two years after therapy. Such side effects emphasize the importance of monitoring the patients for signs of cardiac injury, which is always a possibility following radiation therapy, according to Robinson.

Despite the severe adverse events, the researchers said they are to be expected when considering how ill these patients are. They emphasized that radiation therapy is the last option and only should be pursued when all other strategies have been exhausted. For such patients, the study suggests their tachycardia is likely to improve, leading to a reduced need for medications with adverse side effects and to an improved quality of life, at least over the first two years following treatment.

Credit: 
Washington University School of Medicine

Blink and you'll miss it

image: Polarized optical microscopy images of the molecules at 20 degrees (A) and 51 degrees Celsius (B).

Image: 
© 2019 Kato et al.

Many natural and synthetic chemical systems react and change their properties in the presence of certain kinds of light. These reactions can occur too quickly for ordinary instruments to see. For the first time, researchers adopted a novel technique to observe the high-speed reactions. A special kind of reaction observed with this method could lead to new optical nanotechnology.

In chemistry, molecules can be manipulated in different ways to produce different things. Isomerization, for example, is a process which changes the arrangement of a molecule but leaves constituent atoms as they are. The process is found in natural systems such as the retina of the eye, and artificial systems like certain kinds of chemical synthesis. In many cases isomerization essentially makes a particular region of molecules either more or less ordered.

Photoisomerization is a type of isomerization which is activated by light and it takes place quicker than the blink of an eye. Professor Takashi Kato from the Department of Chemistry and colleagues subjected liquid-crystal molecules of the chemical compound azobenzene to specific frequencies of UV light. The photoisomerization of a single azobenzene molecule typically occurs on a timescale of hundreds of femtoseconds (quadrillionths of a second). That's roughly a billionth to a trillionth the time it typically takes you to blink! The researchers found the molecule then triggers molecular interactions in liquid crystals on timescales of hundreds of picoseconds (trillionths of a second).

"We have shown how to change the shape of azobenzene molecules from a straight rod shape to a slightly bent shape in a process triggered by photo-irradiation of UV light. This bending could translate to some mechanical or electronic function," said Kato. "The reaction propagates through neighboring molecules in the sample, meaning it is an extremely efficient process."

This reaction does not take place in isolation, however; it occurs within a sample of soft matter the function of which depends on the constituent molecules and their behaviors. In this case, soft matter could mean anything from an artificial muscle to flexible photographic sensors or even things not yet imagined. The important fact is that the initial reaction which typically takes only hundreds of femtoseconds initiates a response in the surrounding soft matter in around a hundred picoseconds, and does so efficiently.

"This is the fastest intermolecular motion ever observed within soft matter. In fact what we wanted to observe was so fast we had to use some very specialized methods to acquire data and to visualize what took place during these miniscule timeframes," continued Kato. "This would not have been possible without some unique handmade spectral instruments made by my colleague Associate Professor Masaki Hada from the University of Tsukuba."

The methods are known as ultrafast transient transmission spectroscopy, which is an accurate way to record the makeup of a molecular sample, and ultrafast time-resolved electron diffraction, which is analogous to an X-ray and is how images of the reaction were observed. Note that both methods are called "ultrafast," which just goes to show other methods would have been insufficient to capture data with the time resolution the researchers desired.

"I have worked on ordered molecular assemblies such as self-assembling systems for more than 35 years as a chemist since I was a graduate student. This research advances the fundamental chemistry of photoresponsive molecules in soft matter as well as their ultrafast photomechanical applications," concluded Kato. "It is a real privilege for myself and colleagues to work on this kind of project. We hope this may contribute to the design of molecular-based materials such as soft-body mechanisms and photo-functional materials."

Credit: 
University of Tokyo

Specialized training benefits young STEM researchers

image: Students in the First-Year Research Immersion program work in a laboratory.

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Binghamton University, State University of New York

BINGHAMTON, N.Y. -- The First-year Research Immersion (FRI) program at Binghamton University, State University of New York has proven that young college students are capable of leading real research. And according to a new study, students in FRI do better when the instructors who oversee their projects are provided extra training.

FRI is a three-semester program that allows STEM (Science, Technology, Engineering, Mathematics) students at Binghamton to use their classroom knowledge in research projects. Research educators oversee the students' projects, while also teaching and coaching them.

"Given the national initiative to transform undergraduate science education, a key element of that is to provide at least some course-based research experience to every science and engineering major," said Nancy Stamp, founding director of FRI.

Stamp, along with now-current director Megan Fegley, designed a professional development training program for research educators. In new articles in the journal Microbiology Letters, they described the role of research educators and how a detailed training program guided them in their novel role. The overall goal in training research educators was to make FRI students more confident and knowledgeable in research.

"We saw that research educators needed specific help, such as with developing students' professional skills -- teamwork, collaboration, public speaking," Stamp said. "Subsequently, students reported greater learning and more benefits from the courses."

The program consisted of training 10 research educators, all of whom were recent PhD graduates in science and engineering. Though the research educators had thorough experience with research, they did not have previous experience teaching large numbers of students. 

Before the start of the semester, the research educators were brought together to learn skills in the following areas:

Research: They learned to have realistic expectations of their students' projects.

Students' Professional Development: They were trained to design assignments that allowed their students to use communication and technical skills, among others.

Pedagogy: They learned about pedagogical methods, such as teaching science writing and rubric development, among others.

Mentorship: They learned to be role models for their students.

Research educators met each week to share their challenges, as well as what was working for them. Through that process, they advised and motivated each other. 

"Our weekly team meetings helped the research educators reflect on and describe how they have grown professionally, and the role that FRI had in that," wrote the researchers. 

By the end of the FRI program, the participating students presented their research to faculty sponsors and research faculty members. In response, the faculty members were excited to see what was coming next. 

"Faculty sponsors and even other research faculty were enthusiastic about these students joining their lab groups," wrote the researchers.

"We try to be a team and help each other," said Caitlin Light, a research educator in FRI. "I think the way that research educators can come in and adapt to this unique teaching role is evidence of our training and supportive learning community."

Credit: 
Binghamton University

Gem-like nanoparticles of precious metals shine as catalysts

image: Northwestern University researchers have developed a new method for making highly desirable catalysts from metal nanoparticles that could lead to better fuel cells, among other applications. This is a false color scanning electron microscopy image of tetrahexahedral nanoparticles.

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Northwestern University

A Northwestern University research team has developed a new method for making highly desirable catalysts from metal nanoparticles that could lead to better fuel cells, among other applications. The researchers also discovered the method can take spent catalysts and recycle them into active catalysts.

Made mainly of precious metals, these coveted catalysts are shaped like gems. Each particle has 24 different faces that present atoms at the surface in ways that make them more catalytically active than those available commercially.

The methodology takes basic metal precursors, and, using heat and stabilizing trace elements, rapidly transforms their shape into structures that are highly active catalytically. Commercial products such as fuel cells -- important sources of clean energy -- rely on such catalysts.

The method is a general one; the study shows it works with five monometallic nanoparticles and a library of bimetallic nanoparticles, spanning seven different metals, including platinum, cobalt and nickel.

"Many of these precious metals are responsible for catalyzing some of the most important chemical transformations used in the chemical, oil and fuel cell industries," said Chad A. Mirkin, the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences, who led the research.

"We not only can prepare commercially desirable catalysts, but we can recycle used fuel cell catalysts into the most active forms. Catalysts slowly degrade over time and change, so the fact that we can reclaim and reactivate these catalysts made of expensive materials is extremely valuable," Mirkin said.

The study, which includes both simulations and experiments, will be published Sept. 13 in the journal Science.

The new catalysts are called high-index facet nanoparticle catalysts -- an optimal form for accelerating chemical reactions. Mirkin's team found their platinum catalysts were 20 times faster than the commercial low-index form for the formic acid electrooxidation reaction (based upon platinum content).

"Platinum in the high-index facet form is different and better than it is in other nanoparticle forms," said Chris Wolverton, a co-author of the study and the Jerome B. Cohen Professor of Materials Science and Engineering at Northwestern's McCormick School of Engineering.

"It's all about chemistry," added Mirkin, who also is director of Northwestern's International Institute for Nanotechnology.

Mirkin's multidisciplinary team also includes Vinayak Dravid, the Abraham Harris Professor of Materials Science and Engineering, at McCormick.

Catalysis contributes to more than 35% of the world's gross domestic product, according to the American Chemistry Council. The new catalysts can be made in mass and without the use of ligands, which can compromise catalytic activity. The process that can both create new catalysts and recycle spent catalysts is fast and scalable.

Mirkin said the technology may not be far away from being used commercially. "This type of technology is ready to be scaled up and utilized widely in the catalysis community," he said.

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Northwestern University

Routine sparring in boxing can affect brain performance

image: Dr Thomas Di Virgilio

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University of Stirling

Routine sparring in boxing can cause short-term impairments in brain-to-muscle communication and decreased memory performance, according to new research.

The findings emerged from a University of Stirling study that assessed boxers before and after a nine-minute sparring session - where athletes trade punches without the aim of incapacitating each other.

This study, alongside the team's 2016 research into the impact of heading footballs, is one of the first to show that routine impact in sport - thought to be innocuous - results in measurable changes in the brain. Experts believe the findings raise further questions around the safety of other sports, where similar routine impacts occur, and say further research is required.

Dr Thomas Di Virgilio, a Lecturer in Sport, led the latest study alongside colleagues in the Stirling Brains multi-disciplinary research team. He said: "There are still questions surrounding the relationship between repetitive routine head impacts - such as heading in football or sparring in boxing - and brain health. The truth is that we do not currently know how much impact is safe.

"For many years, a debate has taken place around the safety of boxing, however, these discussions often focus on heavy blows inflicted during competitive fights. In contrast, we looked at subconcussive impacts - those that are below the concussion threshold - inflicted during training sessions.

"Our findings are important because they show that routine practices may have immediate effects on the brain. Furthermore, athletes may be at greater risk of injury if the communications between the brain and muscles are impaired."

The team assessed the motor control and cognitive function of 20 boxers and Muay Thai (Thai boxing) athletes before and after a nine-minute sparring session (three rounds of three minutes). Measurements were taken immediately after the session, and then one-hour and 24 hours later.

Motor control was measured using transcranial magnetic stimulation - which uses magnetic fields to stimulate the nerve cells in the brains of participants - to understand how it communicates with the muscles. The participants also completed a series of tests (the Cambridge Neuropsychological Test Automated Battery), providing objective measures of cognitive function.

The team found that, one hour after sparring, the participants showed impaired brain-to-muscle communications and decreased memory performance, relative to controls. After 24 hours, these effects returned to baseline.

Dr Di Virgilio added: "We have previously shown that the repetitive heading of footballs results in short-term changes to brain function and this latest study sought to understand whether similar effects were observed in training practices in other sports. Although transient, we found that brain changes observed after sparring are reminiscent of effects seen following brain injury.

"As with our previous research into heading footballs, it is not possible to say whether there is a 'safe' threshold when it comes to the level of impact in sparring. Further research is required to help sportspeople - and the academic community - fully understand the dangers posed by subconcussive impacts, routine in sport, and any measures that can be taken to mitigate against these risks."

Dr Di Virgilio worked alongside Stirling colleagues Dr Angus Hunter, Dr Magdalena Ietswaart, Professor Lindsay Wilson and Professor David Donaldson.

Dr Hunter said: "Importantly, this is a breakthrough study using pioneering techniques enabling us to understand how impaired brain to muscle signalling alters electrical recruitment patterns of leg muscle. In the short-term this may negatively affect fine motor control and thus athletic performance."

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University of Stirling

Since cooling demand is primarily driven by the sun, could it also be powered by the sun?

The study is a collaborative effort of an international team of solar energy experts from Aalto University of Finland, Massachusetts Institute of Technology and SMART (Singapore-MIT Alliance for Research and Technology). It analyses the intersection of two dominant trends in the energy sector during the 21st century: the impetus to decarbonise the energy sector to mitigate dangerous anthropogenic climate change and the increased economic prosperity in tropical countries which makes for a higher demand for cooling than heating.

More specifically, the study investigates whether the several billions of air-conditioning devices expected to come online within the 21st century could be powered by clean PV electricity, avoiding the need for additional carbon-based electricity generation, and accelerating the growth of the PV industry in the process. Dr Hannu Laine, the study's lead author, says, "As we scoured through the scientific literature, we found many detailed theoretical and experimental studies demonstrating the synergy of cooling and PV on small-scale such as single buildings or communities. However, we were unable to locate a single analysis assessing the scope and degree of the synergy of cooling and PV at a global level".

Another omittance was the discussion on how the picture will change as global warming proceeds, tropical countries gain wealth and as air-conditioners grow more efficient, "This deficiency makes it impossible for policymakers, investors and researchers to estimate the global impact of the phenomenon" Dr Laine adds.

The study team set out to estimate how much PV electricity generation would be required to power the global cooling demand today and how that number would change as tropical countries gain wealth, as global warming proceeds, and as technological innovation creates more efficient air-conditioners. Using established socio-economic, climate change and energy efficiency improvement projections, they predicted that the cooling demand would increase from approximately 400 TWh/year in 2018 to nearly 14 000 TWh/year by the end of the century, a dramatic 35-fold increase, despite air-conditioners growing significantly more efficient. In monetary terms, this means that the cooling industry increases from an approximately 50 billion dollars/year industry to a 1.5 trillion dollars/year industry.

It was concluded that the potential added AC PV capacity is on par with the global PV production capacity today as a whole, or enough to power the entire country of France with PV, and by the end of the century it will grow to be enough to meet that of India. Dr Laine concludes, "We expect these results to drive significant additional policy interest as well as research and business investments into the synergy of cooling and solar photovoltaics".

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Aalto University

Study: Adults' actions, successes, failures, and words affect young children's persistence

Children's persistence in the face of challenges is key to learning and academic success. However, we know little about how parents and educators can help foster persistent behavior in children before they begin formal schooling. A new U.S. study looked at the interactions of preschool-age children with adults to determine how they affected the children's persistence. It found that the efforts adults put into their actions, successes and failures, and words affected children's persistent behavior to differing degrees.

The study was conducted by researchers at the University of Pennsylvania and the Massachusetts Institute of Technology (MIT). It appears in Child Development, a journal of the Society for Research in Child Development.

"Our work shows that young children pay attention to the successes and failures of the adults around them and, reasonably, don't persist long at tasks that adults themselves fail to achieve," notes Julia A. Leonard, MindCore postdoctoral fellow at the University of Pennsylvania, who led the study. "However, we found that when adults could complete a task successfully, speaking about the value of the effort and letting children see the hard work that went into achieving the goal, it encouraged persistence in children who were watching."

Researchers examined how the persistence of 520 children ages 4 and 5 years was affected by their observations of adults' actions (whether they put a lot of or a little effort into an action) and the outcomes of those actions (whether the adults succeeded or failed in their efforts). The children were from a range of socioeconomic and ethnic backgrounds.

The study also looked at how persistence was affected by adults' words: whether they set expectations for the children's attempts at a task that was designed to be impossible to complete. For example, adults told the children: "This will be hard," gave pep talks by saying something like "You can do this," or offered value statements by saying, for example, "Trying hard is important." There was also a condition in which adults did not say anything about children's expectations. Persistence was measured by how hard the children chose to work at the same task attempted by the adults, which was difficult and new to the children.

Children heard adults' comments without seeing an adult demonstrate the tasks or after seeing an adult demonstrate either high or low effort at the task, then succeed or fail.

The study found:

Children tried harder after they saw adults succeed than after they saw them fail at a task.

Adults' efforts affected children's persistence, but only when the adults succeeded at their task.

Children's persistence was highest when adults exerted effort at their task, succeeded, and talked about the value of making that effort.

According to the authors, these findings show that young children are attentively watching the adults around them and actively learning from their words, efforts, and outcomes how hard they themselves should try at tasks. The study suggests that to encourage children's persistence, adults should show children how hard work leads to success by demonstrating this in their own actions and by speaking about the value of effort.

"Our study suggests that children are rational learners--they pay attention first and foremost to whether adults succeed at their goals," says Laura Schulz, professor of cognitive science at MIT, who coauthored the study. "But when adults succeed, children are also watching how hard adults try and what adults say about the value of effort."

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Society for Research in Child Development