Researchers discovered changes to 12 genetic regions in the DNA of people who have had a lacunar stroke — a type of stroke caused by weakening of the small blood vessels deep within the brain. Over time, damage to the blood vessels and subsequent interruption to blood flow can lead to long-term disability, causing difficulty with thinking, memory, walking and ultimately dementia.

There are few proven drugs to prevent or treat lacunar strokes. The blood vessels affected are less than a millimetre wide and a lacunar stroke can strike without the person knowing. It’s not usually until someone has had a number of these strokes and starts to see signs of dementia that they realise something is wrong.

To date, only one genetic fault has been associated with lacunar strokes. However, after over a decade of research, Professor Hugh Markus and his team at the University of Cambridge working with researchers from around the world now believe their genetic breakthrough holds the key to finding much-needed treatments for lacunar stroke and vascular dementia.

Researchers scanned and compared the genetic code of 7,338 patients who had a lacunar stroke with 254,798 people who had not. Participants were recruited from across Europe, United States, South America and Australia after they attended hospital and had an MRI or CT brain scan.

They discovered that many of the 12 genetic regions linked to lacunar strokes were involved in maintaining the neurovascular unit — the part of the brain that separates the blood vessels from the brain and ensures that nerves function normally. These genetic changes are thought to make the small blood vessels ‘leakier’, causing toxic substances to enter the brain, and meaning that messages travelling around the brain slow down or don’t arrive at all.

The team now plan to test whether new treatments can correct these abnormalities on brain cells in the lab. They hope to begin human clinical trials in the next ten years.

The study also highlighted that high blood pressure, type 2 diabetes and a history of smoking are causally associated with an increased risk of lacunar stroke, identifying things that we can immediately tackle.

Professor Hugh Markus, BHF-funded researcher, leader of the study and neurologist at the University of Cambridge, said:

“These small and often silent lacunar strokes have gone under the radar for a long time, and so we haven’t been able treat patients as well as we’d like to. Although small, their consequences for patients can be enormous. They cause a quarter of all strokes and they are the type of stroke which is most likely to lead to vascular dementia.

“We now plan to use this new genetic blueprint as a springboard to develop much needed treatments to prevent lacunar strokes from occurring in the first place and to help stave off dementia.”

Dr Matthew Traylor, first author of the study at Queen Mary University of London, said:

“Genetics offers one of the few ways we can discover completely new insights into what causes a disease such as lacunar stroke. It is only by better understanding of what causes the disease that we will be able to develop better treatments.”

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation and cardiologist, said:

“This is the most extensive genetic search to date which truly gets to grips with what cause lacunar strokes. These findings are a significant leap forward and we now have a much greater understanding of the genetics and biology behind what causes the small blood vessels deep in the brain to become diseased.

“Lacunar strokes affect around 35,000 people in the UK each year. This research provides real hope that we can prevent and treat this devastating type of stroke much better in the future.”

The BHF is funding £24 million of research to better understand, prevent, diagnose and treat strokes and vascular dementia.

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Materials provided by British Heart Foundation. Original written by Lisa Jones. Note: Content may be edited for style and length.

The study found the greater the activity in nerve cells in the amygdala region of the brain, the sooner the condition known as Takotsubo syndrome (TTS) can develop. The researchers suggest that interventions to lower this stress-related brain activity could help to reduce the risk of developing TTS; these could include drug treatments or techniques for lowering stress.

TTS, also known as “broken heart” syndrome, is characterised by a sudden temporary weakening of the heart muscles that causes the left ventricle of the heart to balloon out at the bottom while the neck remains narrow, creating a shape resembling a Japanese octopus trap, from which it gets its name. Since this relatively rare condition was first described in 1990, evidence has suggested that it is typically triggered by episodes of severe emotional distress, such as grief, anger or fear, or reactions to happy or joyful events. Patients develop chest pains and breathlessness, and it can lead to heart attacks and death. TTS is more common in women with only 10% of cases occurring in men.*

The amygdala is the part of the brain that controls emotions, motivation, learning and memory. It is also involved in the control of the autonomic nervous system and regulating heart function.

“The study suggests that the increased stress-associated neurobiological activity in the amygdala, which is present years before TTS occurs, may play an important role in its development and may predict the timing of the syndrome. It may prime an individual for a heightened acute stress response that culminates in TTS,” said Dr Ahmed Tawakol, co-director of the Cardiovascular Imaging Research Center at Massachusetts General Hospital and Harvard Medical School (Boston, USA), who led the study.

“We also identified a significant relationship between stress-associated brain activity and bone marrow activity in these individuals. Together, the findings provide insights into a potential mechanism that may contribute to the ‘heart-brain connection’.”

In the first study to look at brain scans using F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT) to assess brain activity before TTS develops, Dr Tawakol and colleagues analysed data on 104 people with an average age of 68 years, 72% of whom were women.

The patients had undergone scans at Massachusetts General Hospital (Boston, USA) between 2005 and 2019. Most of them had the scans to see if they had cancer and the scans also assessed the activity of blood cells in bone marrow. The researchers matched 41 people who went on to develop TTS between six months and five years after the scan with 63 who did not. The interval between the scan, the onset of TTs, last follow-up or death was an average (median) of 2.5 years for the 104 patients.

Dr Tawakol said: “Areas of the brain that have higher metabolic activity tend to be in greater use. Hence, higher activity in the stress-associated tissues of the brain suggests that the individual has a more active response to stress. Similarly, higher activity in the bone marrow reflects greater bone marrow metabolism. The PET/CT scans produce images that reflect the distribution of glucose metabolism. The brain images thereby yield a map of brain metabolic activity: the higher the values, the greater the activity in those brain regions.”

The researchers found that people who went on to develop TTS had higher stress-related amygdalar activity on initial scanning (measured as a ratio of amygdalar activity to activity of brain regions that counter stress) compared to individuals who did not subsequently develop TTS. Further, the higher the amygdalar signal, the greater the risk of developing TTS. Among the 41 patients who developed TTS, the average interval between the scan and TTS was 0.9 months, whereas among the control group of 63 patients, the average interval between the scan and last follow-up or death was 2.9 years.

“It was notable that among the 41 patients who developed TTS, the top 15% with the very highest amygdalar activity developed TTS within a year of imaging, while those with less elevated activity developed TTS several years later,” said Dr Tawakol.

He said future studies should investigate whether reducing stress-related brain activity could decrease the chances of TTS recurring among patients who have experienced TTS previously.

“These findings add to evidence of the adverse effect of stress-related biology on the cardiovascular system. Findings such as these underscore the need for more study into the impact of stress reduction or drug interventions targeting these brain regions on heart health. In the meantime, when encountering a patient with high chronic stress, clinicians could reasonably consider the possibility that alleviation of stress might result in benefits to the cardiovascular system.”

The process by which stress induces TTS is not well understood but may involve a multi-organ mechanism starting with activation of the stress-sensitive tissues of the brain. This brain activity in turn triggers several further events, including release of stress hormones, activation of the sympathetic nervous system and release of inflammatory cells, each of which can contribute to the development of TTS.

Limitations of the study include that it was a single-centre, retrospective study that consisted mainly of patients with a diagnosis of cancer, a known TTS risk factor, which may limit the generalisability of the findings. The researchers were unable to measure instantaneous changes in brain activity in response to a stressful event that led to TTS and so cannot directly show a causal relationship. Nor were they able to measure changes in activity in other regions of the brain, which could also play a role.

* TTS affects less than 3% of people who suffer a heart attack and tends to occur between the ages of 60-75.

The theory, derived from the shape of Enceladus’s ice shell, challenges the current thinking that the moon’s global ocean is homogenous, apart from some vertical mixing driven by the warmth of the moon’s core.

Enceladus, a tiny frozen ball about 500 kilometers in diameter (about 1/7th the diameter of Earth’s moon), is the sixth largest moon of Saturn. Despite its small size, Enceladus attracted the attention of scientists in 2014 when a flyby of the Cassini spacecraft discovered evidence of its large subsurface ocean and sampled water from geyser-like eruptions that occur through fissures in the ice at the south pole. It is one of the few locations in the solar system with liquid water (another is Jupiter’s moon Europa), making it a target of interest for astrobiologists searching for signs of life.

The ocean on Enceladus is almost entirely unlike Earth’s. Earth’s ocean is relatively shallow (an average of 3.6 km deep), covers three-quarters of the planet’s surface, is warmer at the top from the sun’s rays and colder in the depths near the seafloor, and has currents that are affected by wind; Enceladus, meanwhile, appears to have a globe-spanning and completely subsurface ocean that is at least 30 km deep and is cooled at the top near the ice shell and warmed at the bottom by heat from the moon’s core.

Despite their differences, Caltech graduate student Ana Lobo (MS ’17) suggests that oceans on Enceladus have currents akin to those on Earth. The work builds on measurements by Cassini as well as the research of Andrew Thompson, professor of environmental science and engineering, who has been studying the way that ice and water interact to drive ocean mixing around Antarctica.

The oceans of Enceladus and Earth share one important characteristic: they are salty. And as shown by findings published in Nature Geoscience on March 25, variations in salinity could serve as drivers of the ocean circulation on Enceladus, much as they do in Earth’s Southern Ocean, which surrounds Antarctica.

Lobo and Thompson collaborated on the work with Steven Vance and Saikiran Tharimena of JPL, which Caltech manages for NASA.

Gravitational measurements and heat calculations from Cassini had already revealed that the ice shell is thinner at the poles than at the equator. Regions of thin ice at the poles are likely associated with melting and regions of thick ice at the equator with freezing, Thompson says. This affects the ocean currents because when salty water freezes, it releases the salts and makes the surrounding water heavier, causing it to sink. The opposite happens in regions of melt.

“Knowing the distribution of ice allows us to place constraints on circulation patterns,” Lobo explains. An idealized computer model, based on Thompson’s studies of Antarctica, suggests that the regions of freezing and melting, identified by the ice structure, would be connected by the ocean currents. This would create a pole-to-equator circulation that influences the distribution of heat and nutrients.

“Understanding which regions of the subsurface ocean might be the most hospitable to life as we know it could one day inform efforts to search for signs of life,” Thompson says.

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Materials provided by California Institute of Technology. Original written by Robert Perkins. Note: Content may be edited for style and length.

MIT engineers have been investigating sapwood’s natural filtering ability, and have previously fabricated simple filters from peeled cross-sections of sapwood branches, demonstrating that the low-tech design effectively filters bacteria.

Now, the same team has advanced the technology and shown that it works in real-world situations. They have fabricated new xylem filters that can filter out pathogens such as E. coli and rotavirus in lab tests, and have shown that the filter can remove bacteria from contaminated spring, tap, and groundwater. They also developed simple techniques to extend the filters’ shelf-life, enabling the woody disks to purify water after being stored in a dry form for at least two years.

The researchers took their techniques to India, where they made xylem filters from native trees and tested the filters with local users. Based on their feedback, the team developed a prototype of a simple filtration system, fitted with replaceable xylem filters that purified water at a rate of one liter per hour.

Their results, published today in Nature Communications, show that xylem filters have potential for use in community settings to remove bacteria and viruses from contaminated drinking water.

The researchers are exploring options to make xylem filters available at large scale, particularly in areas where contaminated drinking water is a major cause of disease and death. The team has launched an open-source website, with guidelines for designing and fabricating xylem filters from various tree types. The website is intended to support entrepreneurs, organizations, and leaders to introduce the technology to broader communities, and inspire students to perform their own science experiments with xylem filters.

“Because the raw materials are widely available and the fabrication processes are simple, one could imagine involving communities in procuring, fabricating, and distributing xylem filters,” says Rohit Karnik, professor of mechanical engineering and associate department head for education at MIT. “For places where the only option has been to drink unfiltered water, we expect xylem filters would improve health, and make water drinkable.”

Karnik’s study co-authors are lead author Krithika Ramchander and Luda Wang of MIT’s Department of Mechanical Engineering, and Megha Hegde, Anish Antony, Kendra Leith, and Amy Smith of MIT D-Lab.

Clearing the way

In their prior studies of xylem, Karnik and his colleagues found that the woody material’s natural filtering ability also came with some natural limitations. As the wood dried, the branches’ sieve-like membranes began to stick to the walls, reducing the filter’s permeance, or ability to allow water to flow through. The filters also appeared to “self-block” over time, building up woody matter that clogged the conduits.

Surprisingly, two simple treatments overcame both limitations. By soaking small cross-sections of sapwood in hot water for an hour, then dipping them in ethanol and letting them dry, Ramchander found that the material retained its permeance, efficiently filtering water without clogging up. Its filtering could also be improved by tailoring a filter’s thickness according to its tree type.

The researchers sliced and treated small cross-sections of white pine from branches around the MIT campus and showed that the resulting filters maintained a permeance comparable to commercial filters, even after being stored for up to two years, significantly extending the filters’ shelf life.

The researchers also tested the filters’ ability to remove contaminants such as E. coli and rotavirus — the most common cause of diarrheal disease. The treated filters removed more than 99 percent of both contaminants, a water treatment level that meets the “two-star comprehensive protection” category set by the World Health Organization.

“We think these filters can reasonably address bacterial contaminants,” Ramchander says. “But there are chemical contaminants like arsenic and fluoride where we don’t know the effect yet,” she notes.

Groundwork

Encouraged by their results in the lab, the researchers moved to field-test their designs in India, a country that has experienced the highest mortality rate due to water-borne disease in the world, and where safe and reliable drinking water is inaccessible to more than 160 million people.

Over two years, the engineers, including researchers in the MIT D-Lab, worked in mountain and urban regions, facilitated by local NGOs Himmotthan Society, Shramyog, Peoples Science Institute, and Essmart. They fabricated filters from native pine trees and tested them, along with filters made from ginkgo trees in the U.S., with local drinking water sources. These tests confirmed that the filters effectively removed bacteria found in the local water. The researchers also held interviews, focus groups, and design workshops to understand local communities’ current water practices, and challenges and preferences for water treatment solutions. They also gathered feedback on the design.

“One of the things that scored very high with people was the fact that this filter is a natural material that everyone recognizes,” Hegde says. “We also found that people in low-income households prefer to pay a smaller amount on a daily basis, versus a larger amount less frequently. That was a barrier to using existing filters, because replacement costs were too much.”

With information from more than 1,000 potential users across India, they designed a prototype of a simple filtration system, fitted with a receptacle at the top that users can fill with water. The water flows down a 1-meter-long tube, through a xylem filter, and out through a valve-controlled spout. The xylem filter can be swapped out either daily or weekly, depending on a household’s needs.

The team is exploring ways to produce xylem filters at larger scales, with locally available resources and in a way that would encourage people to practice water purification as part of their daily lives — for instance, by providing replacement filters in affordable, pay-as-you-go packets.

“Xylem filters are made from inexpensive and abundantly available materials, which could be made available at local shops, where people can buy what they need, without requiring an upfront investment as is typical for other water filter cartridges,” Karnik says. “For now, we’ve shown that xylem filters provide performance that’s realistic.”

The report appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.

“Anabolic steroid use has been associated with a range of medical and psychological side effects,” said lead author, Astrid Bjørnebekk, PhD, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. “However, since anabolic steroids have only been in the public domain for about 35 years, we are still in the early phase of appreciating the full scope of effects after prolonged use. The least studied effects are those that relate to the brain.”

Steroid hormones readily enter the brain, and receptors for sex hormones are found throughout the brain. Because AAS are administered at much higher doses than those naturally found in the body, they could have a harmful impact on the brain, particularly over a long period of use. Previous studies have shown that AAS users performed worse on cognitive tests than non-users.

Dr. Bjørnebekk and colleagues performed magnetic resonance imaging (MRI) of the brains of 130 male weightlifters with a history of prolonged AAS use and of 99 weightlifters who had never used AAS. Using a set of data compiled from nearly 2,000 healthy males from age 18 to 92 years of age. The researchers used machine learning to determine the predicted brain age of each of their participants and then determined the brain age gap: the difference between each participant’s chronological age and their predicted brain age. Advanced brain age is associated with impaired cognitive performance and increased risk for neurodegenerative diseases.

Not surprisingly, AAS users had a bigger brain age gap compared to non-users. Those with dependence on AAS, or with a longer history of use, showed accelerated brain aging. The researchers accounted for use of other substances and for depression in the men, which did not explain the difference between the groups.

“This important study shows in a large sample that use is associated with deviant brain aging, with a potential impact on quality of life in older age. The findings could be directly useful for health care professionals, and may potentially have preventive implications, where brain effects are also included into the risk assessment for young men wondering whether to use anabolic steroids,” added Dr. Bjørnebekk.

Cameron Carter, MD, editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, said of the study: “The results of this brain imaging study should be of concern for athletes using anabolic steroids for performance enhancement and suggest that the adverse effects on behavior and cognition previously shown to be associated with long-term use are the result of effects on the brain in the form of accelerated brain aging.”

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Materials provided by Elsevier. Note: Content may be edited for style and length.