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Scientists Develop ‘Contact Lens’ Patch To Treat Eye Diseases

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Nanyang Technological University, Singapore (NTU Singapore) scientists have developed a ‘contact lens’ patch with microneedles that could provide a painless and efficient alternative to current methods of treating eye diseases such as glaucoma and macular degeneration.

Current localised treatment methods such as eye drops and ointments are hindered by the eye’s natural defences, blinking and tears. Eye injections can be painful and carry a risk of infection and eye damage. As a result, some patients are unable to keep up with the prescribed regime for their eye ailments, many of which require long-term management.
The proof-of-concept patch, successfully tested in mice, is covered with biodegradable microneedles that deliver drugs into the eye in a controlled release. After pressing it onto the eye surface briefly and gently – much like putting on contact lenses – the drug-containing microneedles detach by themselves and stay in the cornea, releasing the drug over time as they dissolve.
When tested on mice with corneal vascularisation, a single application of the patch was 90 per cent more effective in alleviating the condition than applying a single eye drop with 10 times more drug content.
This novel approach, developed by a team led by NTU Singapore Professor Chen Peng from the School of Chemical and Biomedical Engineering (SCBE), with clinical insights from Singapore National Eye Centre’s Associate Professor Gemmy Cheung, was published in Nature Communications earlier this month.
The team includes Assistant Professor Wang Xiaomeng from NTU’s Lee Kong Chian School of Medicine, and Assistant Professor Xu Chenjie and research fellow Dr Aung Than from SCBE.
Professor Chen, the biotechnology expert who also developed the fat-burning microneedle patch, said this approach could realise the unmet medical need for a localised, long-lasting and efficient eye drug delivery with good patient compliance.
He said, “The microneedles are made of a substance found naturally in the body, and we have shown in lab tests on mice that they are painless and minimally invasive. If we successfully replicate the same results in human trials, the patch could become a good option for eye diseases that require long-term management at home, such as glaucoma and diabetic retinopathy.
“Patients who find it hard to keep up with the regime of repeatedly applying eye drops and ointments would also find the patch useful as well, as it has the potential to achieve the same therapeutic effect with a smaller and less frequent dosage.”
Prof Chen added that the patch could also help to tackle the rising disease burden of eye conditions. A local 2018 study projected that patients with eye diseases in Singapore will rise significantly by 2040, with glaucoma, diabetic retinopathy and age-related macular degeneration cases set to double.

Novel approach in treating eye diseases

Currently, localised treatment options are hampered by the eye’s physiological and structural barriers, including blinking and tears that wash out any drugs applied directly to the eye’s surface.
Topical drugs such as eye drops and ointments require repetitive applications with high dosage as less than 5 per cent of the drug is absorbed by the eye each time, and the drug is quickly cleared out by the eye.
Conventional eye injections can penetrate the surface barriers, but face the same problem or poor drug retention due to the backflow of injected solution and subsequent tear wash-out. Aside from carrying a risk of infection or permanent eye damage, patient compliance is poor due to pain and the need for frequent clinic visits.
Prof Chen added, “These two current methods only produce a burst release of drug with a short effective duration. This is not ideal, especially when treating chronic progressive eye diseases that require slow and sustained treatment, such as glaucoma.”
To tackle these problems, the team developed a 2mm by 2mm patch with nine microneedles that can be loaded with drugs for lab tests.
Each needle, thinner than a strand of hair, is shaped like a pyramid for optimal tissue penetration. The needle is made of hyaluronic acid, a substance found in the eye and is used often in eye drops. A modified version of the hyaluronic acid is added to form a second layer of the needle to slow down the rate at which the needle degrades, ensuring a slower release of the drug.
Dr Aung Than, NTU research fellow at SCBE, then planned and conducted experiments over a week on mice with corneal vascularisation, a sight-threatening condition where new blood vessels grow into the corneal tissue due to oxygen deprivation. In this study, the researchers loaded the microneedles with DC101, an antibody that targets the growth factor that promotes blood vessel formation.
In mice with the patches applied, there was a 90 per cent reduction in the area of blood vessels with a single treatment dose of 1 microgram. In contrast, when a single drop of the same drug with a much higher dose of 10 micrograms was applied, there was no significant reduction.
There was also no puncture found on the cornea after a week, suggesting that the microneedles are strong enough to penetrate the cornea, but not too stiff to spear through the whole cornea.
Prof Chen said the team has filed a patent, and is currently working on further improving the eye patch technology. They are also looking to partner clinician scientists to study the feasibility of conducting medical trials.

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Children Carry Evidence Of Toxins From Home Flooring And Furniture

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Children living in homes with all vinyl flooring or flame-retardant chemicals in the sofa have significantly higher concentrations of potentially harmful semi-volatile organic compounds (SVOCs) in their blood or urine than children from homes where these materials are not present, according to a new Duke University-led study.

The researchers presented their findings Sunday, Feb. 17 at the annual meeting of the American Association for the Advancement of Science in Washington, D.C.

They found that children living in homes where the sofa in the main living area contained flame-retardant polybrominated diphenyl ethers (PBDEs) in its foam had a six-fold higher concentration of PBDEs in their blood serum.

Exposure to PBDEs has been linked in laboratory tests to neurodevelopmental delays, obesity, endocrine and thyroid disruption, cancer and other diseases.

Children from homes that had vinyl flooring in all areas were found to have concentrations of benzyl butyl phthalate metabolite in their urine that were 15 times higher than those in children living with no vinyl flooring.

Benzyl butyl phthalate has been linked to respiratory disorders, skin irritations, multiple myeolma and reproductive disorders.

“SVOCs are widely used in electronics, furniture and building materials and can be detected in nearly all indoor environments,” said Heather Stapleton, an environmental chemist at Duke’s Nicholas School of the Environment, who led the research.

“Human exposure to them is widespread, particularly for young children who spend most of their time indoors and have greater exposure to chemicals found in household dust.”

“Nonetheless, there has been little research on the relative contribution of specific products and materials to children’s overall exposure to SVOCs,” she noted.

To address that gap, in 2014 Stapleton and colleagues from Duke, the Centers for Disease Control & Prevention, and Boston University began a three-year study of in-home exposures to SVOCs among 203 children from 190 families.

“Our primary goal was to investigate links between specific products and children’s exposures, and to determine how the exposure happened — was it through breathing, skin contact or inadvertent dust inhalation,” Stapleton said.

To that end, the team analyzed samples of indoor air, indoor dust and foam collected from furniture in each of the children’s homes, along with a handwipe sample, urine and blood from each child.

“We quantified 44 biomarkers of exposure to phthalates, organophosphate esters, brominated flame retardants, parabens, phenols, antibacterial agents and perfluoroalkyl and polyfluoroalkyl substances (PFAS),” Stapleton said.

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Your Home Is A Hidden Source Of Air Pollution

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Cooking, cleaning and other routine household activities generate significant levels of volatile and particulate chemicals inside the average home, leading to indoor air quality levels on par with a polluted major city, University of Colorado Boulder researchers have found.

What’s more, airborne chemicals that originate inside a house don’t stay there: Volatile organic compounds (VOCs) from products such as shampoo, perfume and cleaning solutions eventually escape outside and contribute to ozone and fine particle formation, making up an even greater source of global atmospheric air pollution than cars and trucks do.

The previously underexplored relationship between households and air quality drew focus today at the 2019 AAAS Annual Meeting in Washington, D.C., where researchers from CU Boulder’s Cooperative Institute for Research in Environmental Sciences (CIRES) and the university’s Department of Mechanical Engineering presented their recent findings during a panel discussion.

“Homes have never been considered an important source of outdoor air pollution and the moment is right to start exploring that,” said Marina Vance, an assistant professor of mechanical engineering at CU Boulder.

“We wanted to know: How do basic activities like cooking and cleaning change the chemistry of a house?”

In 2018, Vance co-led the collaborative HOMEChem field campaign, which used advanced sensors and cameras to monitor the indoor air quality of a 1,200-square-foot manufactured home on the University of Texas Austin campus. Over the course of a month, Vance and her colleagues conducted a variety of daily household activities, including cooking a full Thanksgiving dinner in the middle of the Texas summer.

While the HOMEChem experiment’s results are still pending, Vance said that it’s apparent that homes need to be well ventilated while cooking and cleaning, because even basic tasks like boiling water over a stovetop flame can contribute to high levels of gaseous air pollutants and suspended particulates, with negative health impacts.

To her team’s surprise, the measured indoor concentrations were high enough that that their sensitive instruments needed to be recalibrated almost immediately.

“Even the simple act of making toast raised particle levels far higher than expected,” Vance said.

“We had to go adjust many of the instruments.”

Indoor and outdoor experts are collaborating to paint a more complete picture of air quality, said Joost de Gouw, a CIRES Visiting Professor. Last year, de Gouw and his colleagues published results in the journal Science showing that regulations on automobiles had pushed transportation-derived emissions down in recent decades while the relative importance of household chemical pollutants had only gone up.

“Many traditional sources like fossil fuel-burning vehicles have become much cleaner than they used to be,” said de Gouw.

“Ozone and fine particulates are monitored by the EPA, but data for airborne toxins like formaldehyde and benzene and compounds like alcohols and ketones that originate from the home are very sparse.”

While de Gouw says that it is too early on in the research to make recommendations on policy or consumer behavior, he said that it’s encouraging that the scientific community is now thinking about the “esosphere,” derived from the Greek word ‘eso,’ which translates to ‘inner.’

“There was originally skepticism about whether or not these products actually contributed to air pollution in a meaningful way, but no longer,” de Gouw said.

“Moving forward, we need to re-focus research efforts on these sources and give them the same attention we have given to fossil fuels. The picture that we have in our heads about the atmosphere should now include a house.”

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Diet Drinks May Be Associated With Strokes Among Post-Menopausal Women

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Among post-menopausal women, drinking multiple diet drinks daily was associated with an increase in the risk of having a stroke caused by a blocked artery, especially small arteries, according to research published in Stroke, a journal of the American Heart Association.

This is one of the first studies to look at the association between drinking artificially sweetened beverages and the risk of specific types of stroke in a large, racially diverse group of post-menopausal women. While this study identifies an association between diet drinks and stroke, it does not prove cause and effect because it was an observational study based on self-reported information about diet drink consumption.

Compared with women who consumed diet drinks less than once a week or not at all, women who consumed two or more artificially sweetened beverages per day were:

  • 23 percent more likely to have a stroke;
  • 31 percent more likely to have a clot-caused (ischemic) stroke;
  • 29 percent more likely to develop heart disease (fatal or non-fatal heart attack); and
  • 16 percent more likely to die from any cause.

Researchers found risks were higher for certain women. Heavy intake of diet drinks, defined as two or more times daily, more than doubled stroke risk in:

  • women without previous heart disease or diabetes, who were 2.44 times as likely to have a common type of stroke caused by blockage of one of the very small arteries within the brain;
  • obese women without previous heart disease or diabetes, who were 2.03 times as likely to have a clot-caused stroke; and
  • African-American women without previous heart disease or diabetes, who were 3.93 times as likely to have a clot-caused stroke.

“Many well-meaning people, especially those who are overweight or obese, drink low-calorie sweetened drinks to cut calories in their diet. Our research and other observational studies have shown that artificially sweetened beverages may not be harmless and high consumption is associated with a higher risk of stroke and heart disease,” said Yasmin Mossavar-Rahmani, Ph.D., lead author of the study and associate professor of clinical epidemiology and population health at the Albert Einstein College of Medicine in the Bronx, New York.

Researchers analyzed data on 81,714 postmenopausal women (age 50-79 years at the start) participating in the Women’s Health Initiative study that tracked health outcomes for an average of 11.9 years after they enrolled between 1993 and 1998. At their three-year evaluation, the women reported how often in the previous three months they had consumed diet drinks such as low calorie, artificially sweetened colas, sodas and fruit drinks. The data collected did not include information about the specific artificial sweetener the drinks contained.

The results were obtained after adjusting for various stroke risk factors such as age, high blood pressure, and smoking. These results in postmenopausal women may not be generalizable to men or younger women. The study is also limited by having only the women’s self-report of diet drink intake.

“We don’t know specifically what types of artificially sweetened beverages they were consuming, so we don’t know which artificial sweeteners may be harmful and which may be harmless,” Mossavar-Rahmani said.

The American Heart Association recently published a science advisory that found there was inadequate scientific research to conclude that low-calorie sweetened beverages do – or do not – alter risk factors for heart disease and stroke in young children, teens or adults. The Association recognizes diet drinks may help replace high calorie, sugary beverages, but recommends water (plain, carbonated and unsweetened flavored) as the best choice for a no calorie drink.

“Unfortunately, current research simply does not provide enough evidence to distinguish between the effects of different low-calorie sweeteners on heart and brain health. This study adds to the evidence that limiting use of diet beverages is the most prudent thing to do for your health,” said Rachel K. Johnson, Ph.D., R.D., professor of nutrition emeritus, University of Vermont and the chair of the writing group for the American Heart Association’s science advisory, Low-Calorie Sweetened Beverages and Cardiometabolic Health.

“The American Heart Association suggests water as the best choice for a no-calorie beverage. However, for some adults, diet drinks with low calorie sweeteners may be helpful as they transition to adopting water as their primary drink. Since long-term clinical trial data are not available on the effects of low-calorie sweetened drinks and cardiovascular health, given their lack of nutritional value, it may be prudent to limit their prolonged use” said Johnson.

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