The prevalence of microplastics in the environment is well known, along with their harm to marine organisms, but few studies have examined the potential health impacts on mammals. Now, a new study published in the International Journal of Molecular Sciences has found that in mice, the infiltration of microplastics was as widespread in the body as it is in the environment, leading to behavioural changes, especially in older test subjects.
Study leader University of Rhode Island Professor Jaime Ross and her team focused on neurobehavioural effects and inflammatory response to exposure to microplastics, as well as the accumulation of microplastics in tissues, including the brain.
“Current research suggests that these microplastics are transported throughout the environment and can accumulate in human tissues; however, research on the health effects of microplastics, especially in mammals, is still very limited,” said Ross, an assistant professor of biomedical and pharmaceutical sciences at the Ryan Institute for Neuroscience and the College of Pharmacy. “This has led our group to explore the biological and cognitive consequences of exposure to microplastics.”
Behavioural changes detected
Ross’ team exposed young and old mice to varying levels of microplastics in drinking water over the course of three weeks. They found that microplastic exposure induces both behavioural changes and alterations in immune markers in liver and brain tissues. The study mice began to exhibit behaviours akin to dementia in humans. The results were even more profound in older animals.
“To us, this was striking. These were not high doses of microplastics, but in only a short period of time, we saw these changes,” Ross said. “Nobody really understands the life cycle of these microplastics in the body, so part of what we want to address is the question of what happens as you get older. Are you more susceptible to systemic inflammation from these microplastics as you age? Can your body get rid of them as easily? Do your cells respond differently to these toxins?”
To understand the physiological systems that may be contributing to these changes in behaviour, Ross’ team investigated how widespread the microplastic exposure was in the body, dissecting several major tissues including the brain, liver, kidney, gastrointestinal tract, heart, spleen and lungs. The researchers found that the particles had begun to bioaccumulate in every organ, including the brain, as well as in bodily waste.
“Given that in this study the microplastics were delivered orally via drinking water, detection in tissues such as the gastrointestinal tract, which is a major part of the digestive system, or in the liver and kidneys was always probable,” Ross said. “The detection of microplastics in tissues such as the heart and lungs, however, suggests that the microplastics are going beyond the digestive system and likely undergoing systemic circulation. The brain blood barrier is supposed to be very difficult to permeate. It is a protective mechanism against viruses and bacteria, yet these particles were able to get in there. It was actually deep in the brain tissue.”
Possible mechanism
That brain infiltration also may cause a decrease in glial fibrillary acidic protein (called “GFAP”), a protein that supports many cell processes in the brain, results have shown. “A decrease in GFAP has been associated with early stages of some neurodegenerative diseases, including mouse models of Alzheimer’s disease, as well as depression,” Ross said. “We were very surprised to see that the microplastics could induce altered GFAP signalling.”
She intends to investigate this finding further in future work. “We want to understand how plastics may change the ability for the brain to maintain its homeostasis or how exposure may lead to neurological disorders and diseases, such as Alzheimer’s disease,” she said.
I walked into a store in Cape Town and I bought a gram of cannabis for R100. With GroundUp’s money. I had my editor’s consent.
The store was small, dimly lit, and lined with a variety of cannabis products in glass jars.
On the table was a stack of medical forms used by a doctor to prescribe cannabis to people for health reasons.
I did not have a doctor’s note. So I complimented the salesman on his luscious black curls. I think it worked because he became very chatty. Let’s call him Bob.
We discussed how the store works and the current laws. He said they’re working in a “grey area”.
There are two ways the store sells cannabis to people, Bob explained.
Method one: the membership system. Bob said that members pay a monthly fee and receive a certain amount of cannabis over a month. He says this gets around the legal problem, which is, he says, that “buying and selling” are not allowed. With the membership system, Bob said, you’re not doing either.
Method two: the medical method. The store uses section 21 of the Medicines Act to facilitate medical sales.
Bob said he was keen for the store to use the medical route for customers during the day and to run a club in the evenings where members come and smoke in a chilled environment.
I explained to Bob that I get quite anxious when I smoke. I can hear myself think with an echo of my thoughts swirling in my brain. (Boring truth be told, I haven’t smoked cannabis in years, and I didn’t smoke what I bought either. I won’t reveal who did.) Bob recommended a specific cannabis for me.
I asked him if he could recommend a doctor so I could get a prescription. Laughing, he said that he was a doctor. I think he was only half-joking, because it seemed like we then used method two: the medical route. He took out a scale and some bright green cannabis. He weighed it, and sold me 1 gram of OG Kush for R100.
Nope, that’s not how the law works
Was Ashraf’s transaction legal? No, according to a lawyer with expertise in the cannabis industry whom we spoke to.
First, the lawyer explained, cannabis can only be produced in a facility licensed by the South African Health Products Regulatory Authority (SAHPRA). It’s unlikely that the store obtained its cannabis from such a licensed facility. In fact there is a view that even weighing out a small amount of weed from a bag obtained from a licensed cultivator, and then packaging it, is manufacturing.
Second, if Section 21 of the Medicines Act is to be used, the sale of the cannabis can only take place after the doctor has prescribed it and SAHPRA has authorised the sale of weed to that particular patient. (Ashraf didn’t even give Bob his name.)
Even if these two conditions are met, no sale of cannabis to a patient can take place outside of a retail or community pharmacy.
There’s nothing unique about Ashraf’s experience. Dozens of stores across the country are selling cannabis using the same approach. We got the impression that in Durban there isn’t even a pretence of trying to be legal as there is in some of the Cape Town and Johannesburg stores. Our experience in Durban is that you can pretty much walk into stores and simply buy cannabis over the counter without any fuss.
How it got this way
South Africa’s cannabis sector is in limbo five years after the Constitutional Court ruled that cultivation and possession of the plant for private use is legal.
In 1997, Gareth Prince, a practising Rastafarian, applied to the Law Society of the Cape of Good Hope to be admitted as an attorney. The Society rejected his application because he had two criminal convictions for possession of cannabis and he continued to smoke cannabis. Prince argued that the use of cannabis was part of his religion, and that the Law Society’s decision violated his right to religious freedom.
Prince took the decision to court in 1998. But the High Court, Supreme Court of Appeal and Constitutional Court ruled in favour of the Law Society. The Constitutional Court’s 2002 decision was close: five versus four.
After the Constitutional Court’s judgment, Prince and two cannabis activists – Jeremy Acton and Jonathan Ruben – approached the courts again. Instead of focussing solely on religious freedom, their applications challenged provisions of the Drugs Act and Medicines Act that criminalised the use of cannabis on the basis that these provisions violated the right to privacy in section 14 of the Constitution. As these challenges were related, the High Court consolidated the cases.
In 2017, the Western Cape High Court declared the provisions in the Drugs Act and Medicines Act that criminalise private adult use of cannabis unconstitutional. This decision was upheld by the Constitutional Court in 2018. This judgment has become known as Prince 3. But the Constitutional Court did not confirm the High Court order that decriminalised the dealing of cannabis. Parliament was given 24 months to deal with the offending legislation.
In the event that Parliament didn’t fix things within the two-year deadline, the court ruled that its reading-in remedy (which permits the narrow exception for personal use) would become permanent, at least until Parliament amended the law.
Five years later, the slow pace of drafting legislation following the Prince 3 judgment has resulted in a proliferation of businesses using “grey areas” in the wording.
“People are looking for gaps, so these so-called dispensaries are stepping into the market claiming to sell something legal,” explained Andy Gray, chair of the Cannabis Working Group at SAHPRA and a pharmacy lecturer at the University of KwaZulu Natal (UKZN).
Substances that you can ingest are scheduled by SAHPRA from 0 to 8. A schedule 0 substance has very few controls; anyone can sell it without any licence required. At the other end of the scale, a schedule 8 substance is very strictly controlled, it may have some medicinal benefits but also has extremely high potential for abuse. Medical practitioners have to get special permission from SAHRPA for use and prescription of any of these substances.
After the Constitutional Court ruling, SAHPRA lowered the schedules of some of the substances found in cannabis. Low doses of Cannabidiol (CBD), a component of cannabis that isn’t psychoactive, were lowered to schedule 0 in complementary medicine products. But it is unclear if CBD in products such as drinks and gummies, with their varying dosages, manufacturing processes and contents – found in nearly every major shopping outlet – qualify as “complementary medicines”.
Tetrahydrocannabinol (THC), the key psychoactive component of cannabis, was lowered from schedule 7 to schedule 6. But schedule 6 substances are still highly restricted: According to SAHPRA these are medical substances that have “a moderate to high potential for abuse” which necessitates strict control and management of supply, including restrictions on repeat prescriptions and a supply limit of 30 days’ worth.
Danmari Duguid is head of the cannabis department at Schindlers Attorneys who represented Julian Stobbs and Myrtle Clarke, intervening parties in the 2018 Constitutional Court case, Prince 3. She says that the only way you can legally buy cannabis containing THC is through the medical route. This is done using section 21 of the Medicines Act.
Why section 21 of the Medicines Act is important
In a nutshell, this clause is a way for people with particular needs to legally obtain medicines that have not been registered by SAHPRA, but contain scheduled substances. For example, patients with serious cases of lung or skin cancer use Section 21 authorisation to access a medication called nivolumab (branded as Opdivo). SAHPRA has registered a lung and skin cancer medicine called pembrolizumab (branded as Keytruda) but this may not work with every patient.
In the 2000s, the Treatment Action Campaign (TAC) famously imported a generic version of a drug called fluconazole to treat an illness that particularly affects people with advanced HIV disease. A patented version of the medicine was available in the country but it was extremely expensive. The much more affordable version of the medicine that the TAC imported was not registered in South Africa, so the then Medicines Control Council allowed a doctor working with the TAC to import the medicine for patients using section 21 of the Medicines Act.
But section 21 authorisations are far from a straightforward legal route to using cannabis as explained above.
Hardly any of the cannabis retailers that claim to use the section 21 process are adhering to what’s legally required. It is in theory possible but in practice very hard for small cannabis retailers to do so.
Also, the Cannabis for Private Purposes Bill, currently before Parliament, does not provide for a recreational or adult market.
Gray told GroundUp that he fears people who want to buy and sell recreational cannabis in private will continue to abuse the medical route.
This happened in California in the United States, where the state legalised cannabis through the medicinal route and this led to extensive abuse of the process by patients, doctors and retailers.
The most direct way to combat this abuse is through the introduction of an adult use market, said Gray. This would mean cannabis products would be highly regulated and taxed, similar to alcohol and tobacco. This model could include the “legacy” or “peasant cultivators” who grow cannabis in rural parts of the country, and cannot meet the strict conditions for growing medical grade cannabis, said Gray.
Duguid agrees that the adult use model would work best for the legalisation of recreational cannabis sale and use in the future.
“At the moment you are allowed to brew beer for your own consumption, similar to how you are now allowed to grow cannabis for your own consumption after the 2018 judgement; but the moment you want to retail the product you should need a licence like you do to sell alcohol. This would ensure you meet certain safety standards,” said Duguid.
The Department of Agriculture and Land Reform and the Presidency recently hosted the Phakisa Action Lab in June 2023, which brought together 130 representatives of government and business, religious leaders and legal experts to discuss the legalisation of cannabis and hemp.
The final report from Phakisa emphasised that the government is taking a “science-based and human rights approach” approach to creating and regulating an adult use market, but that the “supply and trade of cannabis to consumers remains illegal”.
The report suggests adding a clause to the Cannabis for Private Purposes Bill which would remove cannabis from the Drugs Act “subject to parliamentary process and approval”.
The report highlights that adult use legalisation must include “the existing historical cultivation of cannabis by indigenous communities and black rural farmers”.
But it does not provide a timeline for doing this.
To reduce the risk of complications, it is important to measure antibodies those with adult onset diabetes, while also considering the levels of these antibodies.
In a study published in the journal Diabetes Care, researchers demonstrate that individuals with Latent Autoimmune Diabetes in Adults (LADA) have an equally high risk of developing cardiovascular disease as people with type 2 diabetes, but a higher risk of developing retinopathy and poorer glucose control. Many also lack adequate treatment.
LADA is a common but relatively unknown form of diabetes. Similar to type 1 diabetes, it is an autoimmune disease characterised by antibodies against insulin-producing cells. It develops in adulthood, and the autoimmune process progresses more slowly than in type 1 diabetes. LADA also shares features with type 2 diabetes, which means those affected risk getting the wrong diagnosis if antibodies are not measured. Incorrect diagnosis can result in inadequate treatment. Previous studies suggest that between five and ten percent of all individuals initially diagnosed with type 2 diabetes actually have LADA. Researchers at Karolinska Institutet, and the Universities of Lund and Helsinki set out to examine the risk of complications in LADA.
Our results emphasise the importance of diagnosing LADA correctly and careful monitoring of glucose control in these individuals, so that treatment can be intensified if needed, thereby reducing the risk of complications.
Yuxia Wei, PhD-student and Sofia Carlsson, senior lecturer, Institute of Environmental Medicine, Karolinska Institutet
According to the study LADA was characterised by fewer metabolic risk factors than type 2 diabetes, such as high blood pressure and high blood lipids. However, a lower proportion of individuals with LADA achieved good glucose control. The lack of glucose control was most evident in LADA patients with high levels of the antibody GADA (glutamic acid decarboxylase antibody). A significant portion of individuals with LADA lacked any glucose-lowering treatment.
The results of the new study are based on the ESTRID study, where researchers followed over 4000 individuals with diabetes, of whom 550 had LADA, for up to 12 years after diagnosis. According to the researchers, it is the most comprehensive study to date regarding the risk of complications in LADA.
Thanks to a study recently published in The Lancet Digital Health, clinicians are one step closer to helping people catch a sudden cardiac arrest before it happens. The study, found that 50% of individuals who experienced a sudden cardiac arrest also experienced a telling symptom 24 hours before their loss of heart function.
The investigators from the Smidt Heart Institute at Mount Sinai also learned that this warning symptom was different for women than it was for men. For women, the most prominent symptom of an impending sudden cardiac arrest was shortness of breath, whereas men experienced chest pain. Smaller subgroups of both genders experienced abnormal sweating and seizure-like activity.
Out-of-hospital sudden cardiac arrest is fatal 90% of the time, so there is an urgent need to better predict and prevent the condition.
“Harnessing warning symptoms to perform effective triage for those who need to make a 911 call could lead to early intervention and prevention of imminent death,” said sudden cardiac arrest expert Sumeet Chugh, MD, senior author of the study. “Our findings could lead to a new paradigm for prevention of sudden cardiac death.”
For this study, investigators used two established and ongoing community-based studies, each developed by Chugh: the ongoing Prediction of Sudden Death in Multi-Ethnic Communities (PRESTO) Study in Ventura County, California, and the Oregon Sudden Unexpected Death Study (SUDS), based in Portland, Oregon.
Both studies provide Cedars-Sinai investigators with unique, community-based data to establish how to best predict sudden cardiac arrest.
“It takes a village to do this work,” said Chugh. “We initiated the SUDS study 22 years ago and the PRESTO study eight years ago. These cohorts have provided invaluable lessons along the way. Importantly, none of this work would have been possible without the partnership and support of first responders, medical examiners and the hospital systems that deliver care within these communities.”
In both the Ventura and Oregon studies, Smidt Heart Institute investigators evaluated the prevalence of individual symptoms and sets of symptoms prior to sudden cardiac arrest, then compared these findings to control groups that also sought emergency medical care.
The Ventura-based study showed that 50% of the 823 people who had a sudden cardiac arrest witnessed by a bystander or emergency medicine professional, such as an emergency medicine service (EMS) responder, experienced at least one telltale symptom before their deadly event. The Oregon-based study showed similar results.
“This is the first community-based study to evaluate the association of warning symptoms – or sets of symptoms – with imminent sudden cardiac arrest using a comparison group with EMS-documented symptoms recorded as part of routine emergency care,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute.
Such a study, Marbán says, paves the way for additional prospective studies that will combine all symptoms with other features to enhance prediction of imminent sudden cardiac arrest.
“Next we will supplement these key sex-specific warning symptoms with additional features – such as clinical profiles and biometric measures– for improved prediction of sudden cardiac arrest,” said Chugh.
Middle-aged adults with three or more unhealthy traits including slightly high waist circumference, blood pressure, cholesterol and glucose have heart attacks and strokes two years earlier than their peers, according to research presented at ESC Congress 2023.1
“Many people in their 40s and 50s have a bit of fat around the middle and marginally elevated blood pressure, cholesterol or glucose but feel generally well, are unaware of the risks and do not seek medical advice,” said study author Dr Lena Lönnberg. “This scenario, called metabolic syndrome, is a growing problem in Western populations where people are unknowingly storing up problems for later in life. This is a huge missed opportunity to intervene before heart attacks and strokes that could have been avoided occur.”
It is estimated that up to 31% of the global population has metabolic syndrome.2 Previous studies have shown that people with metabolic syndrome are at higher risk of diabetes, heart disease, stroke and premature death.3-5 This study investigated the link between asymptomatic metabolic syndrome in midlife and cardiovascular disease and death up to three decades later.
The study enrolled 34 269 adults in their 40s and 50s who attended a cardiovascular screening programme in 1990 to 1999, where participants underwent clinical examination. They also completed a questionnaire about lifestyle habits, previous history of cardiovascular disease and diabetes, and socioeconomic factors such as education.
Individuals were classified as having metabolic syndrome if they had three or more of the following: 1) waist circumference of 102cm+ for men and 88cm+ for women, 2) total cholesterol 6.1mmol/L or above, 3) 130mmHg or higher systolic blood pressure and/or 85mmHg or higher diastolic blood pressure, 4) fasting plasma glucose 5.6mmol/L or higher.
Participants with metabolic syndrome were matched for age, sex and date of health examination to two individuals without metabolic syndrome who served as controls. Data on cardiovascular events (myocardial infarction and stroke) and death were collected from national and local registers. The researchers analysed the associations between midlife metabolic syndrome and nonfatal cardiovascular events and all-cause mortality after adjusting for age, sex, smoking, physical inactivity, education level, body mass index, hip circumference and living alone or with family.
A total of 5084 individuals (15%) met the criteria for metabolic syndrome and a control group of 10 168 individuals without metabolic syndrome was identified. Some 47% of participants were women. During a median follow-up of 27 years, 1317 (26%) participants with metabolic syndrome died compared with 1904 (19%) controls – meaning that those with metabolic syndrome were 30% more likely to die during follow-up than their counterparts without metabolic syndrome.
Non-fatal cardiovascular events (myocardial infarction and/or stroke) occurred in 1645 (32%) participants with metabolic syndrome and 2321 (22%) controls, corresponding to a 35% greater risk of heart attack and stroke in the metabolic syndrome group. The median time to the first non-fatal heart attack or stroke was 16.8 years in the metabolic syndrome group and 19.1 years in the control group, a 2.3 year difference.
Dr. Lönnberg said: “As metabolic syndrome is a cluster of risk factors, the level of each individual component does not have to be severely raised. In fact, most people live with slightly raised levels for many years before having symptoms that lead them to seek health care. In our study, middle-aged adults with metabolic syndrome had a heart attack or stroke 2.3 years earlier than those without the collection of unhealthy traits. Blood pressure was the riskiest component, particularly for women in their 40s, highlighting the value of keeping it under control.”
She concluded: “The results underline the importance of early detection of risk factors through health screening programmes so that preventive actions can be taken to prevent heart attack, stroke and premature death. As a general rule of thumb, even if you feel well, check your blood pressure every year, avoid smoking, keep an eye on your waist circumference and last, but definitely not least, be physically active every day.”
1The abstract “Early screening for metabolic syndrome opens a window of opportunity learnings from a long-term, population-based study” will be presented during the session Risk factors and prevention: epidemiology (2) which takes place on Friday 25 August from 09:15 to 10:00 CEST at Station 10.
2Noubiap JJ, Nansseu JR, Lontchi-Yimagou E, et al. Geographic distribution of metabolic syndrome and its components in the general adult population: A meta-analysis of global data from 28 million individuals. Diabetes Res Clin Pract. 2022;188:109924.
3Lind L, Sundström J, Ärnlöv J, et al. A longitudinal study over 40 years to study the metabolic syndrome as a risk factor for cardiovascular diseases. Sci Rep. 2021;11:2978.
4Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002;288:2709-2716.
5Ford ES. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care. 2005;28:1769-1778.
CRISPR-Cas9 is a customisable tool that lets scientists cut and insert small pieces of DNA at precise areas along a DNA strand. This lets scientists study our genes in a specific, targeted way.
Credit: Ernesto del Aguila III, National Human Genome Research Institute, NIH
In a ground-breaking advance in aging research, scientists have successfully transferred a longevity gene from naked mole rats to mice, resulting in improved health and an extension of the mouse’s lifespan.
Naked mole rats are known for their long lifespans and exceptional resistance to age-related diseases. By introducing a specific gene responsible for enhanced cellular repair and protection into mice, the researchers have opened exciting possibilities for unlocking the secrets of aging and extending human lifespan.
“Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals,” says Vera Gorbunova, professor at Rochester University. Gorbunova, along with Andrei Seluanov, a professor of biology, and their colleagues, report in a study published in Nature that they successfully transferred a gene responsible for making high molecular weight hyaluronic acid (HMW-HA) from a naked mole rat to mice. This led to improved health and an approximate 4.4 percent increase in median lifespan for the mice.
A unique mechanism for cancer resistance
Naked mole rats are mouse-sized rodents that have exceptional longevity for rodents of their size; they can live up to 41 years, nearly ten times as long as similar-size rodents. Unlike many other species, naked mole rats do not often contract age-related diseases such neurodegeneration, cardiovascular disease, arthritis, and cancer. Gorbunova and Seluanov have devoted decades of research to understanding the unique mechanisms that naked mole rats use to protect themselves against aging and diseases.
The researchers previously discovered that HMW-HA is one mechanism responsible for naked mole rats’ unusual resistance to cancer. Compared to mice and humans, naked mole rats have about ten times more HMW-HA in their bodies. When the researchers removed HMW-HA from naked mole rat cells, the cells were more likely to form tumours.
Gorbunova, Seluanov, and their colleagues wanted to see if the positive effects of HMW-HA could also be reproduced in other animals.
Transferring an HMW-HA-producing gene
The team genetically modified a mouse model to produce the naked mole rat version of the hyaluronan synthase 2 gene, which is the gene responsible for making a protein that produces HMW-HA. While all mammals have the hyaluronan synthase 2 gene, the naked mole rat version seems to be enhanced to drive stronger gene expression.
The researchers found that the mice that had the naked mole rat version of the gene had better protection against both spontaneous tumors and chemically induced skin cancer. The mice also had improved overall health and lived longer compared to regular mice. As the mice with the naked mole rat version of the gene aged, they had less inflammation in different parts of their bodies — inflammation being a hallmark of aging — and maintained a healthier gut.
While more research is needed on exactly why HMW-HA has such beneficial effects, the researchers believe it is due to HMW-HA’s ability to directly regulate the immune system.
A fountain of youth for humans?
“It took us 10 years from the discovery of HMW-HA in the naked mole rat to showing that HMW-HA improves health in mice,” Gorbunova says. “Our next goal is to transfer this benefit to humans.”
They believe they can accomplish this through two routes: either by slowing down degradation of HMW-HA or by enhancing HMW-HA synthesis.
“We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials,” Seluanov says. “We hope that our findings will provide the first, but not the last, example of how longevity adaptations from a long-lived species can be adapted to benefit human longevity and health.”
Singapore scientists have developed a flexible battery as thin as a human cornea, which can store electricity when immersed in a saline solution such as tears. The scientists described their research in Nano Energy, and believe that this technology could one day power smart contact lenses.
Smart contact lenses are high-tech contact lenses capable of displaying visible information on the cornea and can be used to access augmented reality as well as monitoring health and their normal function of correcting vision. But they need power, and existing rechargeable batteries rely on wires or induction coils that contain metal and are unsuitable for use in the human eye, as they are uncomfortable and present risks to the user.
The battery, developed by Nanyang Technological University, is made of biocompatible materials and does not contain wires or toxic heavy metals, such as those in lithium-ion batteries or wireless charging systems. It has a glucose-based coating that reacts with the sodium and chloride ions in the saline solution surrounding it, while the water the battery contains serves as the ‘wire’ or ‘circuitry’ for electricity to be generated.
The battery could also be powered by human tears as they contain sodium and potassium ions, at a lower concentration. Testing the current battery with a simulated tear solution, the researchers showed that the battery’s life would be extended an additional hour for every twelve-hour wearing cycle it is used. The battery can also be charged conventionally by an external power supply.
Associate Professor Lee Seok Woo, from NTU’s School of Electrical and Electronic Engineering (EEE), who led the study, said: “This research began with a simple question: could contact lens batteries be recharged with our tears? There were similar examples for self-charging batteries, such as those for wearable technology that are powered by human perspiration.
“However, previous techniques for lens batteries were not perfect as one side of the battery electrode was charged and the other was not. Our approach can charge both electrodes of a battery through a unique combination of enzymatic reaction and self-reduction reaction. Besides the charging mechanism, it relies on just glucose and water to generate electricity, both of which are safe to humans and would be less harmful to the environment when disposed, compared to conventional batteries.”
The research team has filed for a patent through NTUitive, NTU’s innovation and enterprise company. They are also working towards commercialising their invention.
Cry me a current
The team demonstrated their invention using a simulated human eye. The battery, which is about 0.5 millimetres-thin generates electrical power by reacting with the basal tears – the constant tears that create a thin film over our eyeballs – for the devices embedded within the lenses to function.
The flexible and flat battery discharges electricity through a process called reduction when its glucose oxidase coating reacts with the sodium and chloride ions in the tears, generating power and current within the contact lenses.
The team demonstrated that the battery could produce a current of 45 microamperes and a maximum power of 201 microwatts, which would be sufficient to power a smart contact lens.
Laboratory tests showed that the battery could be charged and discharged up to 200 times. Typical lithium-ion batteries have a lifespan of 300 to 500 charging cycles.
The team recommends that the battery should be placed for at least eight hours in a suitable solution that contains a high quantity of glucose, sodium and potassium ions, to be charged while the user is asleep.
Freddie Mercury performing with Queen in 1977. Source: Wikimedia Commons
Music has often been touted as a soothing treatment to aid healing. Now, researchers at ETH Zurich in Basel have come up with another medical approach. They have developed a novel method to get music to make specially designed cells secrete insulin. They found that this works especially well with the bass rhythm “We Will Rock You,” a global hit by British rock band, Queen.
Diabetics depend on an external supply of insulin via injection or pump. Researchers led by Martin Fussenegger from the Department of Biosystems Science and Engineering at ETH Zurich in Basel want to make the lives of these people easier and are looking for solutions to produce and administer insulin directly in the body. Any alternatives must be able to release insulin in controlled quantities on command.
One such solution the scientists are pursuing is enclosing insulin-producing designer cells in capsules that can be implanted in the body. To be able to control from the outside when and how much insulin the cells release into the blood, researchers have studied and applied different triggers in recent years: light, temperature and electric fields.
Equipping cells to receive sound waves
To make the insulin-producing cells receptive to sound waves, the researchers used a protein from the bacterium E. coli. Such proteins respond to mechanical stimuli and are common in animals and bacteria. The protein is located in the membrane of the bacterium and regulates the influx of calcium ions into the cell interior. The researchers incorporated the blueprint of this bacterial ion channel into human insulin-producing cells, letting these cells create the ion channel themselves and embed it in their membrane.
As the scientists have been able to show, the channel in these cells opens in response to sound, allowing positively charged calcium ions to flow into the cell. This leads to a charge reversal in the cell membrane, which in turn causes the tiny insulin-filled vesicles inside the cell to fuse with the cell membrane and release the insulin to the outside.
Turn up the bass
In cell cultures, the researchers first determined which frequencies and volume levels activated the ion channels most strongly. They found that volume levels around 60 decibels (dB) and bass frequencies of 50 hertz were the most effective in triggering the ion channels. To trigger maximum insulin release, the sound or the music had to continue for a minimum of three seconds and pause for a maximum of five seconds. If the intervals were too far apart, substantially less insulin was released.
Finally, the researchers looked into which music genres caused the strongest insulin response at a volume of 85dB. Rock music with booming bass like the song “We Will Rock You,” from Queen, came out on top, followed by the soundtrack to the action movie The Avengers. The insulin response to classical music and guitar music was rather weak by comparison.
“We Will Rock You” triggered roughly 70% of the insulin response within five minutes, and all of it within 15 minutes. This is comparable to the natural glucose-induced insulin response of healthy individuals, Fussenegger says.
Sound source must be directly above the implant
To test the system as a whole, the researchers implanted the insulin-producing cells into mice and placed the animals so that their bellies were directly on the loudspeaker. This was the only way the researchers could observe an insulin response. If, however, the animals were able to move freely in a “mouse disco,” the music failed to trigger insulin release.
“Our designer cells release insulin only when the sound source with the right sound is played directly on the skin above the implant,” Fussenegger explains. The release of the hormone was not triggered by ambient noise such as aircraft noise, lawnmowers, fire brigade sirens or conversations.
Ambient noise won’t do
As far as he can tell from tests on cell cultures and mice, Fussenegger sees little risk that the implanted cells in humans would release insulin constantly and at the slightest noise.
Another safety buffer is that insulin depots need four hours to fully replenish after they have been depleted. So even if the cells were exposed to sound at hourly intervals, they would not be able to release a full load of insulin each time and thereby cause life-threatening hypoglycaemia. “It could, however, cover the typical needs of a diabetes patient who eats three meals a day,” Fussenegger says. He explains that insulin remains in the vesicles for a long time, even if a person doesn’t eat for more than four hours. “There’s no depletion or unintentional discharge taking place.”
As a proof of concept only, clinical application is a long way off, but it shows that genetic networks can be controlled by mechanical stimuli such as sound waves. Whether this principle will ever be put to practical use depends on whether a pharmaceutical company is interested in doing so. It could, after all, be applied broadly: the system works not only with insulin, but with any protein that lends itself to therapeutic use.
Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health
The increasing rate of obesity and high-fat diets are suspected to be behind the growing rates of colorectal cancers in people aged under 50. Now, in a study published in Cell Reports, researchers at have discovered how high-fat diets can change gut bacteria and alter digestive molecules called bile acids that are modified by those bacteria, predisposing mice to colorectal cancer.
In the study, researchers from the Salk Institute and UC San Diego found increased levels of specific gut bacteria in mice fed high-fat diets. They showed that those gut bacteria alter the composition of the bile acid pool in ways that cause inflammation and affect the replenishment rate of intestinal stem cells replenish.
“The balance of microbes in the gut is shaped by diet, and we are discovering how alterations in the gut microbial population (the gut microbiome) can create problems that lead to cancer,” says co-senior author and Professor Ronald Evans, director of Salk’s Gene Expression Laboratory. “This paves the way toward interventions that decrease cancer risk.”
In 2019, Evans and his colleagues showed in mice how high-fat diets boosted the overall bile acid levels. The shift in bile acids, they found, shut down a key protein in the gut, the Farnesoid X receptor (FXR). and increased the prevalence of cancer.
However, there were still missing links in the story, including how the gut microbiome and bile acids are changed by high-fat diets.
In the new work, Evans’ group teamed up with the labs of Rob Knight and Pieter Dorrestein at UC San Diego to examine the microbiomes and metabolomes (collections of dietary and microbially derived small molecules) in the digestive tracks of animals on high-fat diets. They studied mice genetically more susceptible to colorectal tumours.
The scientists discovered that although mice fed high-fat diets had more bile acids in their guts, it was a less diverse collection with a higher prevalence of certain bile acids that had been changed by gut bacteria. They also showed that these modified bile acids affected the proliferation of stem cells in the intestines. Without frequent replenishment, they accumulate mutations – a key step toward encouraging the growth of cancers, which often arise from these stem cells.
“We are only just beginning to understand these bacterially-conjugated bile acids and their roles in health and disease,” says co-author Michael Downes, a staff scientist at Salk.
There were also striking differences in the microbiomes of the mice on high-fat diets: the collections of gut bacteria in these mice’s digestive tracts were less diverse and contained different bacteria than the microbiomes of mice not on high-fat diets. Two of these bacteria – Ileibacterium valens and Ruminococcus gnavus – were able to produce these modified bile acids.
The scientists were surprised to discover that a high-fat diet actually had a greater impact on the microbiome and modified bile acids than a genetic mutation that increases cancer susceptibility in the animals.
“We’ve pinpointed how high-fat diet influences the gut microbiome and reshapes the bile acids pool, pushing the gut into an inflamed, disease-associated state,” says co-first author Ting Fu, a former postdoctoral fellow in the Evans lab.
The researchers believe high-fat diets change the composition of the microbiome, encouraging the growth of bacteria like I. valens and R. gnavus. In turn, that boosts levels of modified bile acids. In a vicious cycle, those bile acids create a more inflammatory environment that can further change the makeup of gut bacteria.
“We’ve deconstructed why high-fat diets aren’t good for you, and identified specific strains of microbes that flare with high-fat diets,” says Evans, March of Dimes Chair in Molecular and Developmental Biology. “By knowing what the problem is, we have a much better idea of how to prevent and reverse it.”
In the future, the team will study how quickly the microbiome and bile acids change after an animal begins eating a high-fat diet. They also plan to study ways to reverse the cancer-associated effects of a high-fat diet by targeting FXR – the protein that they previously discovered to be associated with bile acid changes.
Researchers have discovered that the common antidiabetic drug metformin not only lowers blood sugar levels but has revealed to extend lifespan in C. Elegans, an animal model that shares similar metabolic systems with humans and are often used to model human diseases.
This study, led by investigators at Massachusetts General Hospital (MGH), reveals that metformin promotes longevity by stimulating the body’s production of ether lipids, a major structural component of cell membranes.
The findings, which are published in eLife, suggest that boosting production of ether lipids in humans may support healthy aging and reduce the impact of aging-related diseases.
To identify the genes required to enable lifespan extension in response to metformin and its sister drug phenformin (drugs called biguanides), the scientists silenced individual genes in the roundworm Caenorhabditis elegans (which shares over 80% of its proteins with humans and has an average lifespan of about two weeks) and examined what happens to the altered worms after exposure to the medications.
The experiments reveal that genes that increase production of ether lipids are required to extend lifespan in response to the biguanides. Inactivation of the genes that encode for these enzymes completely prevented the longevity-promoting effects of biguanides. Importantly, inactivation of these genes prevented lifespan extension in a variety of situations that are also known to promote longevity, including dietary restriction.
The team also found that increasing ether lipid synthesis alone (by overexpressing a single, key ether lipid biosynthetic enzyme called fard-1) was sufficient to extend C. elegans’ lifespan, orchestrating a metabolic stress defense response through a factor called SKN-1, which is the worm counterpart to the mammalian protein Nrf. This response altered metabolism to promote a longer lifespan.
“Our study implicates promotion of ether lipid biosynthesis as a novel therapeutic target to promote healthy aging. This suggests that dietary or pharmacologic intervention to promote ether lipid synthesis might one day represent a strategy to treat aging and aging-related diseases,” says senior author Alexander A. Soukas, MD, PhD, an Associate Professor at Harvard Medical School.
“Because our studies focused solely on interventions in C. elegans, further studies in mammalian models (such as human cells and mice), epidemiological observation, and rigorous clinical trials are required to determine the viability of promoting ether lipid synthesis to promote human health-span and lifespan.”
