Culture

Surpassing critical blood pressure threshold could signal hypertension regardless of age

Boston, MA-- Hypertension, abnormally high blood pressure, is associated with an increased risk of heart attack and stroke. Many healthcare professionals still believe that incremental changes in blood pressure are normal, and expected, with aging. A new study by investigators at Brigham and Women's Hospital, published in the journal of JAMA Cardiology, found that a systolic (top) blood pressure that regularly exceeds 120-125 mmHg could signal impending hypertension, regardless of age. These results are in line with the recently updated American College of Cardiology and American Heart Association high blood pressure guidelines, which categorize high blood pressure as greater than 130/80 mmHg.

"There used to be a widespread belief that a gradual increase in blood pressure over time is part of normal aging," says Susan Cheng, MD, a cardiologist at BWH and senior author on the paper. "But, if you look at native communities, where people live without the lifestyle exposures usually seen in industrialized societies, this trend is hard to find. And so, we wondered if blood pressure is supposed to very gradually increase over time or instead remain stable. We also wanted to find out, for people in whom blood pressure does rise, is there a tipping point at which hypertension starts to develop. In other words, if hypertension does develop, when does the change start to happen, what does it look like, and how might we prevent it?"

In the study, researchers examined data from 1,252 participants from the Framingham Heart Study, which contains one of the few existing cohorts with standardized blood pressure (BP) measurements performed at frequent intervals (every two years) over an extended period of time (1948 to 2005). The team defined hypertension onset as a blood pressure over or equal to 140/90 mmHg. Participants were categorized based on the age at which their hypertension was diagnosed (age 40-49, 50-59, 60-69, 70-79 years, or no onset).

The research team found that, among the patients who developed hypertension, blood pressure trajectories leading up to the onset of hypertension appeared similar in pattern. In fact, their blood pressure levels were generally stable until they approached the range of ~120-125 mmHg, above which their blood pressure rose rapidly and into the range of hypertension. This finding was consistent whether the hypertension developed in middle or older age, suggesting that blood pressures above this level could represent a critical threshold of vascular remodeling occurring in the body. Interestingly, this blood pressure range is in line with recently published guidelines that lowered the definition of high systolic blood pressure to 130 mmHg.

"Although our findings suggest the potential importance of working to keep your top blood pressure number below 120 mmHg, they also offer a hope for healthy aging - our results demonstrated that some individuals are able to maintain a very normal range of blood pressure throughout life," says Niiranen Teemu, MD, first author and a research associate at Brigham and Women's Hospital.

The researchers found that many people in the study were able maintain a systolic blood pressure below 120-125 mmHg and, in effect, delay the uptick of blood pressure elevation until much later in life and, in some cases, avoid it altogether. This new way of understanding life course trends in blood pressure could affect clinical practice by motivating physicians to be more vigilant when encountering blood pressure at or approaching uptick levels. Further investigations are needed to unravel the sequence of changes in the body that occur before hypertension sets in and to determine the potential benefits of interventions in preventing progressive rises in blood pressure, at any age.

Credit: 
Brigham and Women's Hospital

How often do medical problems lead to bankruptcy?

CAMBRDIGE, MASS.--A team of researchers led by an MIT economist has found that medical expenses account for roughly 4 percent of bankruptcy filings among nonelderly adults in the U.S.

The scholars combined medical records and financial data for hundreds of thousands of people to pinpoint the percentage of bankruptcies caused by medical costs, thus giving new empirical precision to a topic of considerable policy importance.

The 4 percent figure is lower than some commonly cited estimates, but the new statistic comes with a twist: It is part of a larger research project that found multiple negative economic consequences of having medical problems, including a 20 percent drop in earnings and an 11 percent drop in employment for adults between ages 50 and 59 who had been hospitalized.

This combination of effects - fewer medically rooted bankruptcies but pervasive workplace troubles for people with health issues - underscores the need to understand the full range of financial challenges people face due to their medical needs, the researchers say.

"It doesn't mean there aren't really adverse economic consequences from adverse health," says MIT economist Amy Finkelstein, co-author of a new paper outlining the findings. "It just turns out they're not [strictly] about bankruptcy. They're much more about lost employment and earnings."

The article, "Myth and Measurement - The Case of Medical Bankruptcies," appears today in the New England Journal of Medicine. The co-authors are Finkelstein, who is the John and Jennie S. MacDonald Professor of Economics at MIT; Carlos Dobkin, a professor of economics at the University of California at Santa Cruz; Raymond Kluender, a PhD student in economics at MIT; and Matthew Notowidigdo, an associate professor of economics at Northwestern University.

The study's main source of data consists of hospitalization records from the years 2003-2007 and credit reports from 2002-2011, from the state of California, for people over age 25. The study included about 780,000 people with health insurance and roughly 150,000 people without health insurance. That information was available to the research team only under particular conditions that preserved the anonymity of the people being studied.

By examining cases where previously healthy people were hospitalized, then tracking the finances of those people in subsequent years, the researchers were able to study the issue in a way that delivers a solid link between cause and effect - namely, how often medical events themselves are the principal cause of changes in financial status.

Some of the previous research on the frequency of medically caused bankruptcies used survey data to produce estimates; one commonly cited figure is that 60 percent of bankruptcies have medical causes. However, those estimates used self-reported data about health issues, among those who filed for bankruptcy, without establishing that medical costs were the principal cause of those bankruptcies.

"The approach of the prior literature was just conceptually not right," Finkelstein says.

The current study found that poor health has a larger impact on the uninsured than the insured: For instance, as a related, recently published paper by the research team shows, four years after being admitted to the hospital, people with insurance owe $300 more in unpaid medical bills, on average, while people without insurance have an average increase of $6,000 in unpaid medical bills.

The researchers also found that medically caused bankruptcies are minimal among the elderly - those over age 64 - who are likely to have Medicare and who tend to be retired, thus not suffering the earnings reductions that ill people in the workforce experience.

"We suspect what's driving the [level of] bankruptcy we find is the fact that some people lose their job because of adverse health, and in turn that causes them to go bankrupt," Finkelstein says. "That's just not going to [apply to] the elderly, because they're not working, so they don't have the labor market risk from poor health."

To be sure, Finkelstein acknowledges, the current study has some aspects that may need additional scrutiny. By focusing on examples involving hospitalization, the researchers could be missing some cases in which accumulated medical costs of other kinds drive people to bankruptcy - including medical costs incurred by children, parents, or other relatives.

"We're not going to go to the mat over the idea that [the rate of medically caused bankruptcies] is always going to be 4 percent in every context and by every measurement," Finkelstein says. Still, she notes, the accurate figure is likely to be much lower than other recent estimates imply.

To Finkelstein, the findings also have a clear upshot for policymakers and legislators. Grasping the full breadth of the economic consequences of poor health might affect the priorities of lawmakers, directing them to seek solutions for the lost income that many people endure after a serious medical event.

"Focusing on bankruptcy might lead you to think about bankruptcy protection reform," Finkelstein says, "and while that may or may not be useful in its own right, if you're interested in the economic consequences of poor health, you're missing a main issue and potential policy responses - thinking about how we might want to structure sick pay and disability insurance."

Credit: 
Massachusetts Institute of Technology

Systems approaches to optimizing deep brain stimulation therapies in Parkinson's disease

Systems biologists, physicists, and engineers have intensively worked at computational tools to analyze, predict, and optimize the effects of Deep Brain Stimulation (DBS) to treat chronic neurological diseases. These efforts often have overlapping objectives and closely-related methods, but they are rarely compared, combined, or jointly discussed, perhaps because they often target different research communities.

A new WIREs Systems Biology and Medicine review systematically brings this information together to identify the major milestones in the development of systems approaches to the modeling and study of Parkinson's disease and DBS. These approaches acknowledge the interactive nature and interdependence of various factors to optimize the therapeutic effects of DBS in individual patients.

"Although effective and generally safe, DBS remains a fascinating puzzle to scientists, physicians, and engineers. The therapeutic mechanisms of DBS, in fact, are still elusive and the current, semi-permanent stimulation protocols have often motivated the investigation of ways to make DBS less invasive and more efficient," said lead author Dr. Sabato Santaniello, of the University of Connecticut. "In this review article, we show how different strides in medical imaging, computer modeling, and control strategies have paved the way towards a truly patient-specific optimization of DBS therapy.

Credit: 
Wiley

Mat baits, hooks and destroys pollutants in water

image: Specks of titanium dioxide adhere to polyvinyl fibers in a mat developed at the Rice University-led NEWT Center to capture and destroy pollutants from wastewater or drinking water. After the mat attracts and binds pollutants, the titanium dioxide photocatalyst releases reactive oxygen species that destroy them.

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Rice University/NEWT

HOUSTON - (March 21, 2018) - A polymer mat developed at Rice University has the ability to fish biologically harmful contaminants from water through a strategy known as "bait, hook and destroy."

Tests with wastewater showed the mat can efficiently remove targeted pollutants, in this case a pair of biologically harmful endocrine disruptors, using a fraction of the energy required by other technology. The technique can also be used to treat drinking water.

The mat was developed by scientists with the Rice-led Nanotechnology-Enabled Water Treatment (NEWT) Center. The research is available online in the American Chemical Society journal Environmental Science and Technology.

The mat depends on the ability of a common material, titanium dioxide, to capture pollutants and, upon exposure to light, degrade them through oxidation into harmless byproducts.

Titanium dioxide is already used in some wastewater treatment systems. It is usually turned into a slurry, combined with wastewater and exposed to ultraviolet light to destroy contaminants. The slurry must then be filtered from the water.

The NEWT mat simplifies the process. The mat is made of spun polyvinyl fibers. The researchers made it highly porous by adding small plastic beads that were later dissolved with chemicals. The pores offer plenty of surface area for titanium oxide particles to inhabit and await their prey.

The mat's hydrophobic (water-avoiding) fibers naturally attract hydrophobic contaminants like the endocrine disruptors used in the tests. Once bound to the mat, exposure to light activates the photocatalytic titanium dioxide, which produces reactive oxygen species (ROS) that destroy the contaminants.

Established by the National Science Foundation in 2015, NEWT is a national research center that aims to develop compact, mobile, off-grid water-treatment systems that can provide clean water to millions of people who lack it and make U.S. energy production more sustainable and cost-effective.

NEWT researchers said their mat can be cleaned and reused, scaled to any size, and its chemistry can be tuned for various pollutants.

"Current photocatalytic treatment suffers from two limitations," said Rice environmental engineer and NEWT Center Director Pedro Alvarez. "One is inefficiency because the oxidants produced are scavenged by things that are much more abundant than the target pollutant, so they don't destroy the pollutant.

"Second, it costs a lot of money to retain and separate slurry photocatalysts and prevent them from leaking into the treated water," he said. "In some cases, the energy cost of filtering that slurry is more than what's needed to power the UV lights.

"We solved both limitations by immobilizing the catalyst to make it very easy to reuse and retain," Alvarez said. "We don't allow it to leach out of the mat and impact the water."

Alvarez said the porous polymer mat plays an important role because it attracts the target pollutants. "That's the bait and hook," he said. "Then the photocatalyst destroys the pollutant by producing hydroxyl radicals."

"The nanoscale pores are introduced by dissolving a sacrificial polymer on the electrospun fibers," lead author and former Rice postdoctoral researcher Chang-Gu Lee said. "The pores enhance the contaminants' access to titanium dioxide."

The experiments showed dramatic energy reduction compared to wastewater treatment using slurry.

"Not only do we destroy the pollutants faster, but we also significantly decrease our electrical energy per order of reaction," Alvarez said. "This is a measure of how much energy you need to remove one order of magnitude of the pollutant, how many kilowatt hours you need to remove 90 percent or 99 percent or 99.9 percent.

"We show that for the slurry, as you move from treating distilled water to wastewater treatment plant effluent, the amount of energy required increases 11-fold. But when you do this with our immobilized bait-and-hook photocatalyst, the comparable increase is only two-fold. It's a significant savings."

The mat also would allow treatment plants to perform pollutant removal and destruction in two discrete steps, which isn't possible with the slurry, Alvarez said. "It can be desirable to do that if the water is murky and light penetration is a challenge. You can fish out the contaminants adsorbed by the mat and transfer it to another reactor with clearer water. There, you can destroy the pollutants, clean out the mat and then return it so it can fish for more."

Tuning the mat would involve changing its hydrophobic or hydrophilic properties to match target pollutants. "That way you could treat more water with a smaller reactor that is more selective, and therefore miniaturize these reactors and reduce their carbon footprints," he said. "It's an opportunity not only to reduce energy requirements, but also space requirements for photocatalytic water treatment."

Alvarez said collaboration by NEWT's research partners helped the project come together in a matter of months. "NEWT allowed us to do something that separately would have been very difficult to accomplish in this short amount of time," he said.

"I think the mat will significantly enhance the menu from which we select solutions to our water purification challenges," Alvarez said.

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Rice University

Fixing soybean's need for nitrogen

image: A soybean root with nodules, These nodules house bacteria that "fix," or extract, nitrogen from the atmosphere for the plant's use.

Image: 
Luiz G. Moretti.

Soybean is rich in protein, which is great for the humans and animals eating it. But this high protein content comes at a cost.

To make protein, soybean plants need a lot of nitrogen. The plants get some of the nitrogen they need by working with specialized bacteria in the soil. These bacteria live in root nodules. They pull nitrogen from the atmosphere and convert it to a form the plants can use.

But this process-biological nitrogen fixation-may not provide all the nitrogen soybean crops need. Farmers may have to apply nitrogen fertilizer as well.

A new study, however, shows it's possible to increase the number of soybean root nodules--and the bacteria that live there--to increase crop yields. This could remove the need to apply additional nitrogen fertilizers.

"That opens the possibility of achieving higher yields of soybean based exclusively on biological fixation," says Mariangela Hungria, a researcher at Embrapa Soja, Brazil.

Hungria, lead author of the study, and her colleagues coated soybean seeds with the bacteria (the usual method used by growers). They supplied additional bacteria by spraying it on the plants during other stages of growth. Soybean plants that received the additional spray inoculation developed more root nodules. And more nodules led to higher yields.

In fact, adding bacteria to seeds increased yields by 27% and 28%. Spraying bacteria on the soy fields during growth pushed up yields even further.

The increase in root nodules after additional spray inoculation surprised Hungria and her colleagues. Previous research indicated that each nodule makes it more difficult for soybean plants to develop subsequent ones. But in this study, soybean plants were able to form new nodules when researchers provided more bacteria.

"To discover that nodules aren't regulated as strictly as previously thought is an important finding," says Hungria. "The limitation happens particularly at the beginning of soybean growth when the first nodules appear." After that initial stage, more nodule growth is possible.

More biological nitrogen fixation, and less nitrogen through fertilizer, can also increase sustainability. First, it reduces carbon emissions. Nitrogen fertilizers are usually produced using fossil fuels. "For every pound of nitrogen fertilizer manufactured, at least 10 pounds of carbon dioxide may be released," Hungria states.

The second improvement in sustainability is on the field. Excess nitrogen fertilizers from the field can flow into bodies of water. Too much in an aquatic ecosystem can cause algal blooms. These deplete the water of oxygen and lead to "dead zones" devoid of life. Biological fixation using bacteria, however, means more of the nitrogen is used by the crop.

Less fertilizer use also has an economic impact. Nitrogen fertilizer costs can add up quickly, both for farmers and for countries. Brazil imports about 70% of the nitrogen fertilizers used in the country.

Several farms in Brazil began using the study's strategy in October 2016 (the summer crop in Brazil). Initial results have been promising, says Hungria. The higher soybean yields seen in the study are sustained on these larger scales.

Hungria thinks these results will extend beyond Brazil as well. "But they have to be verified because the genetic background of soybean is different in each country," she says. Collaborations with Kansas State University, to verify if the results can be extended to the U.S., have just started.

Researching bacteria and nitrogen fixation may just be the beginning. "I think microorganisms can be the 'stars' of a new era of agriculture, in which we consider not only food security but also sustainability," she says.

Credit: 
American Society of Agronomy

Researchers explore enzymetic activities based on nanocomplex sensors

image: This is the Nano journal cover.

Image: 
World Scientific

A team of researchers from Ludong University compared the susceptibility of different triangle silver nanoprisms (TSNPRs) towards H2O2 and elucidated the influence of capping agents and structural size on the etching process, with the aim of optimizing TSNPRs for H2O2 etching-based biosensors, such as glucose and glucose oxidase. The result of their research was recently published in a paper in NANO.

As a characteristic two-dimensional plasmonic nanostructure, triangular silver nanoprisms (TSNPRs) possess an extreme degree of anisotropy since their lateral dimension is larger than the thickness, giving highly sensitive surface plasmon resonance (SPR) responses. Many strategies have been developed for the biosensors based on target analytes induced morphologies changes and plasmonic peak shifts. A typical approach is to etch TSNPRs by an oxidative hydrogen peroxide, also known as catalytic product of glucose oxidase (GOx). Relative TSNPRs etching-based plasmonic biosensors have been used for detecting glucose, antigen and DNA. However, synthesis of TSNPRs with well-defined tips needs the assistance of appropriate capping ligands, such as citrate, polyvinylpyrrolidone (PVP) and so on. To date, there has not been a systematic study on the influences of the capping agents on H2O2 etching of TSNPRs. Besides, the analysis of structural size could also provide valuable information since size parameter is essential for the efficacy and performance of TSNPRs for sensing and detection.

The team of researchers from the School of Life Sciences at Ludong University performed a study to compare the susceptibility of different TSNPRs towards H2O2 and elucidated the influence of capping agents and structural size on the etching process, aiming to optimize TSNPRs for glucose oxidase etching-based biosensor. Detail analysis revealed that the small sized TSNPRs capping with citrate alone have been expected to be of great interest in the trace of glucose and glucose oxidase. This research work appears in the latest issue of the journal NANO.

This work performs systematic studies on nanoprisms for glucose oxidase etching-based biosensor. Nanoprisms with a small size and citrate capping were served as a substitute for big nanoprisms to sense glucose, offering a number of advantages such as high sensitivity, improved calibration, time-saving and extend detection ranges. and These sensing assays have been expected to be of great interest in the trace of glucose, providing an ultrahigh sensitive glucose etching-based analytical platform for point-of-care diagnostics of diabetics.

Credit: 
World Scientific

In drawing tests, US children draw female scientists more today than in previous decades

The participation of women in science has risen significantly in the United States since the 1960s. A new meta-analysis reviewed five decades of "Draw a Scientist" tests to determine whether children's drawings have mirrored that change. The study found that U.S. children and adolescents today draw female scientists more often than in earlier decades, but overall, female scientists are still depicted much less frequently than males in children's and youths' drawings.

The study, conducted by researchers at Northwestern University, appears in the journal Child Development, a publication of the Society for Research in Child Development.

In the 1960s and 1970s, less than 1% of U.S. children's drawings depicted a female scientist. In the 1980s and later, that percentage had risen to 28. "These findings shed light on how children learn to associate science with men and how they respond to changes in their cultural environment such as increases in women's representation in science," says David I. Miller, Ph.D. candidate in psychology at Northwestern University, who led the study.

The researchers used literature databases such as Google Scholar to identify 78 studies of U.S. "Draw a Scientist" tests over the last 50 years. The studies included more than 20,000 children in kindergarten through 12th grade. While the first study included in the analysis collected data from 1966 to 1977, all of the other studies collected data from 1985 to 2016.

In conducting their meta-analysis of U.S. children's gender-science stereotypes linking science with men, the researchers hypothesized that these stereotypes would weaken over time as women's representation in science grew stronger and media increasingly depicted females as scientists. They found that children depicted female scientists more often in later decades.

The study also found that children did not draw significantly more male than female scientists until ages 7-8; in kindergarten, they drew approximately equal percentages of male and female scientists. During elementary and middle school, the tendency to draw male scientists increased rapidly with children's age. These developmental differences suggest a growing awareness of gender differences and greater exposure to male than female science role models in school and mass media.

"Given these results, girls today may develop interests in science more freely than before because children's stereotypes of scientists have become less masculine over time," explains Alice H. Eagly, professor of psychology at Northwestern University, who coauthored the study. "But because stereotypes remain, teachers and parents should present children with multiple examples of female as well as male scientists across many contexts such as in science courses, on television shows, and in informal conversations."

Credit: 
Society for Research in Child Development

Specific gene region in hypertension revealed

image: Renin-angiotensin.

Image: 
University of Tsukuba

Tsukuba, Japan - Genes encode proteins and proteins dictate cell function. Therefore, the thousands of genes expressed in a cell determine what that cell can do. Among the multiple elements that are involved in the precise regulation of gene expression are enhancers, which are short region of DNA that can be bound by proteins (activators) to increase the likelihood of transcription of a particular gene.

One notable regulatory cascade that involves enhancers is the renin-angiotensin system (RAS) that plays a major role in blood pressure regulation and electrolyte homeostasis. Because increased expression of the protein renin leads to a rise in blood pressure, its transcription must be finely regulated.

While upregulation of the gene renin in the promoter and enhancer elements is relatively well established, the mechanisms controlling its feedback transcriptional suppression are poorly understood. This knowledge gap prompted a team of researchers from the University of Tsukuba to delve deeper into understanding this important regulatory cascade.

"We deleted either 5? or 3? regions of the endogenous mouse renin (mRen) in mice, and placed the animals in a hypertensive environment. While the mRen gene bearing the 3? deletion was appropriately downregulated, the one bearing the 5? deletion (-5E) lost hypertension responsiveness," explains Aki Ushiki, lead author of the study, which was recently reported in Molecular and Cellular Biology. "This means the -5E region is essential for the basal expression of the mRen gene."

Based on their findings, they proposed the -5E element functions as an enhancer under normal conditions and is involved in full activation of mRen gene transcription. Conversely, in the hypertensive state, the enhancer activity somehow becomes attenuated by the hormone angiotensin signaling, which leads to suppression of mRen gene transcription.

"Understanding of this enhancer-mediated transcriptional modulatory mechanism for mRen gene has a broad impact on not only the RAS field but also enhancer biology in general," corresponding author Keiji Tanimoto says. "Also, as the mRen enhancer core sequence is fairly conserved in humans, our findings shed light on the unexplored distal regulatory region of renin genes and provide a novel mechanistic insight into renin gene regulation."

Credit: 
University of Tsukuba

US children now draw female scientists more than ever

EVANSTON, Ill. --- When drawing scientists, U.S. children now depict female scientists more often than ever, according to new Northwestern University research, which analyzed five decades of "Draw-A-Scientist" studies conducted since the 1960s.

This change suggests that children's stereotypes linking science with men have weakened over time, said the researchers, consistent with more women becoming scientists and children's media depicting more female scientists on television shows, magazines and other media.

"Given this change in stereotypes, girls in recent years might now develop interests in science more freely than before," said study lead author David Miller, a psychology Ph.D. candidate at Northwestern. "Prior studies have suggested that these gender-science stereotypes could shape girls' interests in science-related activities and careers."

The study is the first systematic, quantitative review of the "Draw-A-Scientist" literature and combined results from 78 U.S. studies, including more than 20,000 children in kindergarten through 12th grade.

In the first landmark study, conducted between 1966 and 1977, less than one percent of nearly 5,000 children drew an image resembling a woman when asked to draw a scientist. Their artwork almost exclusively depicted men working inside with laboratory equipment, often with lab coats, glasses and facial hair.

But in later studies (1985 to 2016), 28 percent of children drew a female scientist, on average. In addition, both girls and boys drew female scientists more often over time, though girls overall drew female scientists much more often than boys.

"Our results suggest that children's stereotypes change as women's and men's roles change in society," said study co-author Alice Eagly, professor of psychology in the Weinberg College of Arts and Sciences at Northwestern and a faculty fellow with the University's Institute for Policy Research. "Children still draw more male than female scientists in recent studies, but that is expected because women remain a minority in several science fields."

The researchers also studied how children form stereotypes about scientists across child development. The results suggested children did not associate science with men until grade school; around age 5, they drew roughly equal percentages of male and female scientists.

During elementary and middle school, the tendency to draw male scientists increased strongly with age. Older children were also more likely to draw scientists with lab coats and glasses, suggesting that children learn other stereotypes as they mature.

"These changes across children's age likely reflect that children's exposure to male scientists accumulates during development, even in recent years," said David Uttal, a co-author of the study and a professor of education and psychology in Northwestern's School of Education and Social Policy and Weinberg College of Arts and Sciences.

"To build on cultural changes, teachers and parents should present children with multiple examples of female and male scientists across many contexts such as science courses, television shows and informal conversations," Uttal said.

Credit: 
Northwestern University

Western diet depletes artery-protecting immune cells

image: This is a cross section of an aorta from a mouse that was fed a high-fat, high-cholesterol diet, which accelerates the build-up of plaque. The large red plaque on the inside of the aorta was labeled with oil based stain, which highlights lipids.

Image: 
Dr. Dalia Gaddis, La Jolla Institute for Allergy and Immunology

LA JOLLA, CA--New research from scientists at the La Jolla Institute For Allergy and Immunology shows how a diet high in fat and cholesterol depletes the ranks of artery-protecting immune cells, turning them into promoters of inflammation, which exacerbate atherosclerotic plaque buildup that occurs in cardiovascular disease. The team has also found that high density lipoproteins (HDL)--more commonly known as "good cholesterol"--counteract this process, helping the protective immune cells maintain their identity and keep arteries clear.

The study published March 15, 2018, in the journal Nature Communications was led by LJI scientists Dalia Gaddis, Ph.D., and Catherine Hedrick, Ph.D.

Inflammation is a key contributor to the hardening and narrowing of the arteries known as atherosclerosis--a condition that can lead to heart attack or stroke. Hedrick's lab is investigating the roles that immune cells play in this process and how the function of different immune cells can change as atherosclerosis progresses.

"People think atherosclerosis is just about cholesterol, diet, and exercise, but it's actually an immune disease," says Dalia Gaddis, Ph.D., a postdoctoral researcher in Hedrick's lab. "The blockage of arteries is very much due to the immune system reacting to excess cholesterol and lipids in the walls of blood vessels."

Different subsets of immune cells have opposing roles in atherosclerosis--some contribute to the build-up of plaques, and others protect against it, Gaddis explains. In the current study, she and her colleagues focused on protective cells called regulatory T cells, or Tregs. Tregs prevent the development of atherosclerosis. But researchers have found that when mice are fed a high-fat, high-cholesterol diet--also known as a Western diet--their numbers of protective Tregs decline.

Gaddis wanted to track regulatory T cells in the mice during this process to find out what was happening to them. Typically, scientists look for a protein called Foxp3 to identify regulatory T cells, but this marker is lost when the cells are reprogrammed into another cell type. So Gaddis used mice in which regulatory T cells would be tagged with two fluorescent markers. One, a yellow marker on the Foxp3 protein, allowed her to easily recognize all regulatory T cells. The second tag--a red one--would also be produced by regulatory T cells and then retained regardless of their fate, enabling the researcher team to track the cells in the blood vessels and atherosclerotic plaques even if they changed their identity and stopped making Foxp3.

To begin her experiments, Gaddis fed some of the mice a western diet. After 15 weeks of this regime, she examined the animals' immune cells. The differences were clear. Gaddis found regulatory T cells in the aorta--the large artery that carries blood from the heart to the rest of the body--in all of the mice. But in the animals that had consumed the Western diet, she also saw significant numbers of "ex Tregs" in the lymph nodes and aorta.

Molecular analyses revealed that some of the former regulatory T cells had become follicular helper T cells (Tfh). These are critical components of the immune system that help the body fight off viral and bacterial infections. Little was known, however, about how they impact atherosclerosis.

With further experiments, Gaddis and her colleagues established that Tfh cells promote atherosclerosis. By blocking the generation of Tfh cells, the scientists could reduce the development of plaques in the arteries of mice fed the Western diet.

The team next wanted to know whether HDL, which removes excess cholesterol from cells, might protect against atherosclerosis by preventing the loss of regulatory T cells. They tested this idea by administering the primary component of HDL, a protein called apolipoprotein AI, to their mice. With this treatment, regulatory T cells resisted the effects of the Western diet and did not change into Tfh cells.

Although it's not yet known whether regulatory T cells undergo the same conversion in humans, the finding gives a clearer picture of how diet and the immune system interact to shape cardiovascular risk.

"With a western diet, protective cells change to damaging cells, causing more inflammation," says Gaddis. "What we're finding is that HDL--the good cholesterol--actually helps shield the protective cells against the damaging changes that occur during atherosclerosis plaque development."

Credit: 
La Jolla Institute for Immunology

Marine researchers say recent sea star wasting disease epidemic defies prediction

image: White lesions on a sea star's arms are the first sign of sea star wasting syndrome.

Image: 
Melissa Miner

Beginning in 2013, a mysterious disease crippled sea star populations up and down the U.S. west coast. Over a matter of months, many sea star species died in record-breaking numbers, though Pisaster ochraceus--a keystone species known as the ochre sea star--was among the hardest hit. Now, researchers at UC Santa Cruz have analyzed just how much the populations of this species have declined, but they have not yet determined what factors might be contributing to the epidemic.

Scientists aren't sure what causes this disease, known as sea star wasting syndrome (SSWS). Some researchers think the culprit could be a viral pathogen, but evidence is inconclusive. Early signs of SSWS include lesions and tissue decay, which can spread along the sea stars' arms, leading to limb loss and eventual death, often in a matter of days.

Melissa Miner, a researcher in the Department of Ecology and Evolutionary Biology at UC Santa Cruz who is based in Bellingham, Washington, recounted that she had been observing sea stars in a local intertidal zone there during the summer of 2014. "I went back two weeks later, and it was just death," she said. "The intertidal area was littered with stars, and probably 90 percent of them were dead or dying."

While similar SSWS outbreaks were documented in southern California in the 1970s, '80s, and '90s, this most recent epidemic is unprecedented in its scale and scope. "We've been monitoring sea star populations for a long time, but this event is far broader in geographic scale than anything we've seen before," Miner said.

This latest outbreak extended from as far south as Baja California, Mexico, all the way to the southern shores of Alaska, according to Peter Raimondi, professor of ecology and evolutionary biology and director of UCSC's Institute of Marine Sciences. Raimondi is a principle investigator for the Multi-Agency Rocky Intertidal Network, or MARINe, a consortium of 18 research groups that monitor and collect data from more than 200 intertidal sites along the west coast.

In a new study published March 20 in PLOS ONE, Miner, Raimondi, and colleagues analyzed MARINe data collected between 2000 and 2016 from 90 intertidal sites on the North American Pacific coast to determine the impacts of SSWS on ochre sea star populations and try to understand what factors may have contributed to this most recent SSWS outbreak.

The data revealed that, while ochre sea star populations shrank in all coastal areas, sites in southern California and the Channel Islands experienced more severe declines than those farther north. In the south, adult sea stars declined by 99 percent or more at over half of the 39 sites surveyed, whereas only 2 sites in the north experienced similar levels of decline. Miner's group also noted that juvenile sea star mortality in the period after the initial outbreak of SSWS increased by approximately 90 percent compared to pre-outbreak levels.

Ochre sea stars are keystone predators in intertidal ecosystems--the part of the shore area submerged at high tide and uncovered at low tide--preying on organisms like the California mussel. When ochre stars are removed, mussel beds can expand, leaving less space for other organisms to flourish in those habitats. A decline in ochre sea stars could lead to a change in the make-up of intertidal communities on the west coast, although other factors are also at play, Miner said.

Unfortunately, the data didn't yield any clues about which factors might be contributing to SSWS in these different regions. A common culprit in many marine disease events is warm water. Past SSWS events were often correlated with El Niño events and their associated periods of warm water, but that was not the case with the 2013 outbreak. According to Miner, elevated sea water temperatures weren't linked to the initial emergence of the disease on a broad scale, but may have exacerbated its impact in the period that followed.

Another factor that researchers consider when trying to predict the spread of a disease is the density of the affected populations in different areas. "In areas where animals are packed closer together, it's generally more likely a disease will spread," Miner said. But her group didn't see that pattern for ochre sea stars. In fact, the outer coast of Washington--one of the regions with some of the highest densities of stars--was among the least impacted by SSWS.

Because scientists haven't found any "smoking guns" behind the disease, and factors that frequently influence the emergence and severity of marine disease events, like temperature and population density, did not correlate with this outbreak, it is difficult to address the epidemic, Miner said.

"Without information to support or discount certain environmental factors, we can't even begin to prescribe potential solutions," she said.

According to Miner, the epidemic that started in late 2013 is still ongoing, though the major population crashes noted in 2014 and 2015 have since leveled off. "I'd want to see current population levels persist for another six months or so before saying this disease event is over," she said.

Miner is now looking to the future. She thinks that prospects for ochre sea star population recovery are uncertain. If current trends hold, however, recovery will occur fastest in northern regions, where more juveniles are recruiting and appear to be surviving to adulthood following the disease outbreak. "My guess is southern California regions will take a lot longer to recover," she said.

Credit: 
University of California - Santa Cruz

Medicine that slows balding may turn stiff vessels supple, helping vital organs

WASHINGTON-(March. 20, 2018)- A medicine that slows balding and stimulates hair growth also may make stiff vessels more stretchy and improve blood flow to vital organs like the brain, according to an experimental model study published online March 2 in American Journal of Physiology--Heart and Circulatory Physiology.

Arteries in young, healthy humans and other mammals stretch easily because they contain a protein called elastin. Elastin is produced only during development, however, and is slowly lost with aging. In older people, arteries stiffen as elastin is lost. Stiff arteries contribute to development of high blood pressure and significantly increase the risk of sudden death, stroke, myocardial infarction and cognitive decline. Most treatment strategies in adults aim to reduce high blood pressure. To date, no medication has been shown to increase elastin deposition in mature human tissue.

"We know that genetic conditions, such as Williams-Beuren Syndrome (WS) and supravalvar aortic stenosis (SVAS), lead to abnormally low levels of elastin in developing arteries. As a result, children with WS or SVAS have stiff, narrow arteries and high blood pressure. Like older adults, they are also at increased risk of sudden death and stroke," says co-author Michael "Mish" Shoykhet, M.D., Ph.D.

"We theorized that in WS or SVAS, narrow arteries without enough elastin reduce blood flow to vital organs.Thus, an adult-like treatment strategy that simply reduces high blood pressure may be less desirable in children with WS or SVAS because it would further impair organ perfusion. We therefore tested whether a medicine called minoxidil would not only reduce blood pressure but also would help relax arteries and increase their diameter, thus improving organ perfusion," Dr. Shoykhet adds.

Shoykhet and a collaborator Beth A. Kozel, M.D., Ph.D., co-designed the study and co-led experiments at Washington University School of Medicine (WUSM). The research team's manuscript was finalized and published after Shoykhet joined Children's National Health System.

Minoxidil is perhaps best known for its potential to improve hair growth when applied to the skin. In a different formulation, minoxidil is sometimes prescribed orally for high blood pressure that has not responded to other medications. Earlier studies have suggested that minoxidil may increase elastin deposition even in mature tissues.

The research team conducted the work in experimental models of hypertension and chronic vascular stiffness associated with WS and SVAS. They used ultrasound imaging and magnetic resonance imaging-based arterial spin labeling to gauge minoxidil's impact on vessel mechanics, carotid and cerebral blood flow, and gene expression.

The treatment group in the study received 20 mg of minoxidil per kg daily via their drinking water, from the time they were weaned to 3 months of age. A second treatment group also received minoxidil for three months but was analyzed at 4 months of age, one month after the drug was discontinued. For the gene expression experiments, the preclinical models received minoxidil for two weeks.

"Minoxidil not only lowered blood pressure, but also increased arterial diameter and restored carotid and cerebral blood flow. Minoxidil also reduced functional arterial stiffness and increased arterial elastin content," Dr. Shoykhet says. "Equally important, these beneficial changes persisted weeks after the drug was no longer in the bloodstream. The sustained improvements and the increased elastin gene expression suggest that minoxidil treatment may help remodel stiff arteries. Such remodeling may benefit humans whose elastin insufficiency is due to either advanced age or genetic conditions."

The study team notes that additional clinical studies are needed to confirm changes in blood flow to end organs in humans and to evaluate blood-flow differences in other key vascular beds impacted by elastin insufficiency, such as in the heart, kidneys, lungs and gut.

Credit: 
Children's National Hospital

What plants can teach us about oil spill clean-up, microfluidics

image: For years, scientists have been inspired by nature to innovate solutions to tricky problems, even oil spills -- manmade disasters with devastating environmental and economic consequences. A new USC study takes a cue from leaf structure to fabricate material that can separate oil and water, which could lead to safer and more efficient oil spill clean-up methods.

Image: 
Yang Yang

For years, scientists have been inspired by nature to innovate solutions to tricky problems, even oil spills -- manmade disasters with devastating environmental and economic consequences. A new USC study takes a cue from leaf structure to fabricate material that can separate oil and water, which could lead to safer and more efficient oil spill clean-up methods.

In addition, the material is capable of "microdroplet manipulation," or the transfer of miniature volumes of liquid. Droplet-based microfluidics is a tool used in various applications like cell cultures, chemical synthesis and DNA sequencing.

Using 3-D printing, Associate Professor Yong Chen and his research team at the Daniel J. Epstein School of Industrial and Systems Engineering at the USC Viterbi School of Engineering have successfully mimicked a biological phenomenon in plant leaves called "Salvinia effect." Their study focuses on a floating fern native to South America called Salvinia molesta. The unique leaves are super-hydrophobic, meaning "water-fearing" and retain a surrounding air pocket when submerged in water due to the presence of water-resistant hairs.

"I think the reason the plant's surface is super-hydrophobic is because it lives on the water and requires air to survive," Yang Yang, a postdoctoral researcher on Chen's team, said. "If it weren't for the long-term evolution of this plant, the plant could be submerged in water and would die."

Water-repellent structure

On a microscopic level, the leaf hairs align in a structure resembling an egg-beater, or cooking whisk. Chen explains that Salvinia's leaf surface is comprised of this so-called "egg-beater" structure that is super-hydrophobic.

Using a method called immersed surface accumulation 3-D printing (ISA-3D printing), the research team successfully created the egg-beater microstructure in samples made from plastic and carbon nanotubes. Chen explains that the method allowed the team to demonstrate the fabrication of a material with both super-hydrophobic and olephilic (oil-absorbing) properties that, when combined, generate capillary forces capable of highly efficient oil and water separation.

"We tried to create one functional surface texture that would be able to separate oil from water," Chen said. "Basically, we modified the surface of the materials by using a 3-D printing approach that helped us achieve some interesting surface properties."

The team has 3-D printed a prototype, citing a growing demand for materials that can separate oil and water mixtures efficiently in vast bodies of water. Eventually, they hope the technology can be applied to manufacture materials in large scale to accommodate massive oil spills in the ocean. Current methods require tremendous energy in the form of an electric field or mechanically-applied pressure.

Microfluidics application

"Salvinia effect" also has potential for liquid-handling technology that executes "microdroplet manipulation" --a breakthrough where the adhesion of liquid to a robotic arm can be tuned accordingly and result in non-loss transfer for very tiny amounts of liquid. The technique can be applied in myriad ways, some of which include droplet-based microreactors (devices used in chemical synthesis), nanoparticle synthesis, tissue engineering, drug discovery and drug delivery monitoring.

Xiangjia Li, a PhD student on Chen's team and co-first author of the study, says one example of high-performance microdroplet manipulation could lead to more efficient blood analyses for patients. A robotic gripper could move to different stations and dispense microdroplets of blood that are then evenly mixed with different chemicals for various tests. In addition, the tests could be designed to control the ratio of chemical to droplet and result in significant conservation for source materials and chemical reagents.

"You can have a robotic arm with a gripper made to mimic 'Salvinia effect,'" Li said. "No matter which way you move the arm, the gripping force is so large that a droplet will stay attached."

Credit: 
University of Southern California

Ideal heart health less likely among lesbian, gay and bisexual adults

NEW ORLEANS, March 20, 2018 -- Lesbian, gay and bisexual (LGB) adults were less likely than heterosexuals to have ideal cardiovascular health, according to preliminary research presented at the American Heart Association's Epidemiology and Prevention | Lifestyle and Cardiometabolic Health Scientific Sessions 2018, a premier global exchange of the latest advances in population-based cardiovascular science for researchers and clinicians.

"If confirmed in other studies, our results point towards a disproportionately higher risk for cardiovascular disease among sexual-minority populations," said study lead author Anshul Saxena, M.P.H., Ph.D., a biostatistician at Baptist Health South Florida in Miami.

In the United States, heart disease is the leading cause of death, and stroke is the fifth-leading cause. Despite advances in prevention, diagnosis and treatment, heart disease alone accounts for 1 out of every 4 deaths.

Some cardiovascular risks, such as family history and age, are uncontrollable. Fortunately, many others -- including obesity, smoking, poor diet as well as high blood pressure, cholesterol and blood sugar -- are manageable through lifestyle changes. As part of a heart-healthy lifestyle, the American Heart Association recommends Life's Simple 7 lifestyle changes: 1) manage blood pressure; 2) control cholesterol; 3) reduce blood sugar; 4) get active; 5) eat better; 6) lose weight; and 7) stop smoking.

Although evidence indicates that the risk of cardiovascular disease may be greater among LGB adults than among heterosexuals, the extent of this difference was unclear. Accordingly, this study compared the seven manageable risks between the two groups. Results showed that LGB adults were 36 percent less likely than heterosexuals to have ideal cardiovascular health.

Study participants comprised 2,445 adults over 18 years old responding to the 2011-2012 National Health and Nutrition Examination Survey. This nationwide survey included interviews and physical examinations of a representative sample of the population. Five percent of participants were identified as LGB, and 95 percent as heterosexual. Transgender individuals were not included in the study.

For each participant, researchers scored each of the seven risks as ideal, intermediate or poor. From these scores, they calculated an overall risk score for cardiovascular health. Participants with ideal scores in five or more risk categories received an overall risk score of ideal.

"Two areas where fewer people among the LGB population were in the ideal health category were smoking habits and management of blood glucose," Saxena said. "Primary care physicians can address these risks and promote the healthy lifestyle changes recommended in Life's Simple 7."

Study limitations include a relatively small number of LGB participants and limited information about participants' physical activity. Still, these preliminary findings underscore the importance of reducing cardiovascular risks among LGB adults, although additional research is necessary.

Credit: 
American Heart Association

Why it doesn't pay to be just nice -- you also need to be intelligent

New research has revealed how people's intelligence, rather than their personality traits, leads to success.

Researchers at the Universities of Bristol, Minnesota and Heidelberg devised a series of games to find out which factors lead to cooperative behaviour when people interact in social and workplace situations.

Their findings, due to be published in the Journal of Political Economy, showed that people with a higher IQ displayed 'significantly higher' levels of cooperation, which in turn led to them earning more money as part of the game.

The failure of individuals with lower intelligence to appropriately follow a consistent strategy and estimate the future consequences of their actions accounted for these different outcomes.

Personality traits -- such as agreeableness, conscientiousness, trust and generosity -- also affect behaviour, but in smaller measure, and only initially.

The researchers conclude, based on their findings, that a society is cohesive if people are smart enough to be consistent in their strategies, and to foresee the social consequences of their actions, including the consequences for others.

Professor Eugenio Proto, from the Department of Economics at the University of Bristol, said: "We wanted to explore what factors make us effective social animals. In other words, what enables us to behave optimally in situations when cooperation is potentially beneficial not only to us, but to our neighbours, people in the same country or who share the same planet.

"People might naturally presume that people who are nice, conscientious and generous are automatically more cooperative. But, through our research, we find overwhelming support for the idea that intelligence is the primary condition for a socially cohesive, cooperative society. A good heart and good behaviour have an effect too but it's transitory and small.

"An additional benefit of higher intelligence in our experiment, and likely in real life, is the ability to process information faster, hence to accumulate more extensive experience, and to learn from it. This scenario can be applied to the workplace, where it's likely that intelligent people who see the bigger picture and work cooperatively, will ultimately be promoted and financially rewarded."

The findings have potentially important implications for policy, especially in the education sector, as well as international trade.

Andis Sofianos, from the Department of Economics at the University of Heidelberg, said: "The core principle of working cooperatively and seeing the bigger picture also applies to international trade, where there is overwhelming evidence that free trade is a non-zero sum game i.e. all parties could benefit.

"With education, our results suggest that focussing on intelligence in early childhood could potentially enhance not only the economic success of the individual, but the level of cooperation in society in later life."

The research involved four different games which were representative of different and very specific strategic situations. Interactions were repeated, giving time and opportunity for each participant to observe and to reflect on the past behaviour of the other.

Games used for the study included Prisoner's Dilemma, Stag Hunt and Battle of Sexes, which are often used in game theory - the science of logical decision making in humans, animals, and computers.

Where the strategy game involved a trade-off between current and future gains, those with a higher IQ won more money per round. The failure of individuals with lower intelligence to find and follow an optimal strategy and appropriately estimate the future consequences of their actions accounted for the difference in outcomes.

Perhaps surprisingly, conscientious people also tended to be more cautious, which in turn reduced their cooperative behaviour.

Credit: 
University of Bristol