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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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Report Reveals Link Between Air Pollution And Increased Risk For Miscarriage

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Air quality has been associated with numerous adverse health outcomes from asthma to pre-term birth. Researchers at University of Utah Health found women living along the Wasatch Front — the most populous region in the state of Utah — had a higher risk (16 percent) of miscarriage following short-term exposure to elevated air pollution. The results are available online on December 5 in the journal Fertility and Sterility.

“Not being from Salt Lake originally, I noticed a pattern in the relation to air quality and pregnancy loss,” said Matthew Fuller, M.D., assistant professor of Surgery at U of U Health and senior author on the paper.

“I knew this was an understudied question so we decided to dig deeper.”

Fuller joined University of Utah research analyst Claire Leiser on a retrospective study consisting of more than 1,300 women (54 percent Caucasian, 38 percent Hispanic, and other/missing 8 percent; average age 28 years). The women in the study sought help at the U of U emergency department following a miscarriage (up to 20-weeks gestation) between 2007 to 2015.

The team examined the risk of miscarriage during a three- or seven-day window following a spike in the concentration of three common air pollutants: small particulate matter (PM 2.5), nitrogen dioxide and ozone. The study excluded women who lived outside Utah.

“We are really only seeing the most severe cases during a small window of time,” said Leiser, first author on the paper.

“These results are not the whole picture.”

Leiser notes the results suggest there could be an increased risk for an individual. Their research only captured women who sought help at an emergency department at one hospital in the region. It does not account for women who may have sought outpatient care through their obstetric or primary care providers.

The team found a slight increased risk in miscarriage for women exposed to elevated levels of nitrogen dioxide (16 percent for 10 ppb increase during the seven-day window). Although small particulate matter does track with nitrogen dioxide, these results did not significantly associate with an increased risk of miscarriage.

“While we live in a pretty unique geographic area, the problems we face when it comes to air pollution are not unique,” said Fuller.

“As the planet warms and population booms, air pollution is going to become a bigger problem not only in the developing world but across the United States.”

The Wasatch Front experiences short-periods of poor air quality, primarily during the winter months, when inversions trap pollutants close to the ground (for the 7-day window: PM2.5 min = 0.3 μg/m3; PM2.5 max = 73.0 μg/m3; O3 min = 4 ppb; O3 max= 80 ppb; NO2min = 0.5 ppb; NO2 max = 65 ppb). The researchers tracked air quality by zip code, establishing six designated air basins within the Wasatch Front. They compared air quality in each basin to their patients’ outcomes.

The team conducted a case cross-over study that estimated a woman’s risk of miscarriage multiple times in a month where air pollution exposure varied. This approach removed other risk factors, like maternal age, from the study. The scientists were unable to ascertain the age of the fetus at the time of the miscarriage and were unable pinpoint a critical period when the fetus may be most vulnerable to pollutants.

“The results of this study are upsetting, and we need to work together as a society to find constructive solutions,” Fuller said.

Fuller recommends women speak with their doctor about any health concerns. Women can manage the risk by using a N95 particulate respirator face mask to filter out pollutants or avoid outdoor physical activity on poor air quality days. Women can also use filters to lower indoor pollution and, if possible, time conception to avoid seasonal episodes of poor air quality.

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Alcohol Intake May Be Key to Long-term Weight Loss for People with Diabetes

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Research shows that losing weight can help prevent or delay the onset of diabetes. While best practice for weight loss often includes decreasing or eliminating calories from alcohol, few studies examine whether people who undergo weight loss treatment report changes in alcohol intake and whether alcohol influences their weight loss.

A new study from the University of Pennsylvania School of Nursing (Penn Nursing) suggests that alcohol consumption may attenuate long-term weight loss in adults with Type 2 diabetes.

In the study, close to 5,000 people who were overweight and had diabetes were followed for four years. One group participated in Intensive Lifestyle Intervention (ILI) and the other in a control group consisting of diabetes support and education. Data showed that participants in the ILI group who abstained from alcohol consumption over the four-year period lost more weight than those who drank any amount during the intervention. Results from the study also showed that heavy drinkers in the ILI group were less likely to have clinically significant weight loss over the four years.

“This study indicates that while alcohol consumption is not associated with short‐term weight loss during a lifestyle intervention, it is associated with worse long‐term weight loss in participants with overweight or obesity and Type 2 diabetes,” says lead investigator Ariana M. Chao, PhD, CRNP, Assistant Professor of Nursing in the Department of Biobehavioral Health Sciences.

“Patients with Type 2 diabetes who are trying to lose weight should be encouraged to limit alcohol consumption.”

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Hang In There. As Couples Age, Humor Replaces Bickering

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Honeymoon long over? Hang in there. A new UC Berkeley study shows those prickly disagreements that can mark the early and middle years of marriage mellow with age as conflicts give way to humor and acceptance.

Researchers analyzed videotaped conversations between 87 middle-aged and older husbands and wives who had been married for 15 to 35 years, and tracked their emotional interactions over the course of 13 years. They found that as couples aged, they showed more humor and tenderness towards one another.

Overall, the findings, just published in the journal Emotion, showed an increase in such positive behaviors as humor and affection and a decrease in negative behaviors such as defensiveness and criticism. The results challenge long-held theories that emotions flatten or deteriorate in old age and point instead to an emotionally positive trajectory for long-term married couples.

“Our findings shed light on one of the great paradoxes of late life,” said study senior author Robert Levenson, a UC Berkeley psychology professor.

“Despite experiencing the loss of friends and family, older people in stable marriages are relatively happy and experience low rates of depression and anxiety. Marriage has been good for their mental health.”

Consistent with previous findings from Levenson’s Berkeley Psychophysiology Laboratory, the longitudinal study found that wives were more emotionally expressive than their husbands, and as they grew older they tended toward more domineering behavior and less affection. But generally, across all the study’s age and gender cohorts, negative behaviors decreased with age.

“Given the links between positive emotion and health, these findings underscore the importance of intimate relationships as people age, and the potential health benefits associated with marriage,” said co-lead author Alice Verstaen, who conducted the study as a Ph.D. student at UC Berkeley and is currently a postdoctoral fellow at the VA Puget Sound Health Care System.

The results are the latest to emerge from a 25-year UC Berkeley study headed by Levenson of more than 150 long-term marriages. The participants, now mostly in their 70s, 80s and 90s, are heterosexual couples from the San Francisco Bay Area whose relationships Levenson and fellow researchers began tracking in 1989.

In their investigation of marital relationships, researchers viewed 15-minute interactions between spouses in a laboratory setting as they discussed shared experiences and areas of conflict. They tracked the emotional changes every few years.

The spouses’ listening and speaking behaviors were coded and rated according to their facial expressions, body language, verbal content and tone of voice. Emotions were coded into the categories of anger, contempt, disgust, domineering behavior, defensiveness, fear, tension, sadness, whining, interest, affection, humor, enthusiasm and validation.

Researchers found that both middle-aged and older couples, regardless of their satisfaction with their relationship, experienced increases in overall positive emotional behaviors with age, while experiencing a decrease in overall negative emotional behaviors.

“These results provide behavioral evidence that is consistent with research suggesting that, as we age, we become more focused on the positives in our lives,” Verstaen said.

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