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Tiny electric generators could accelerate wound healing

The natural wound healing process involves complex interactions between ions, cells, blood vessels, genes and the immune system; with every player triggered by a sequence of molecular events.

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Tiny dressings that generate electricity in response to movement could accelerate wound healing and tissue regeneration. Scientists in Taiwan reviewed the latest advances and potential applications of wound healing technology in the journal Science and Technology of Advanced Materials

The natural wound healing process involves complex interactions between ions, cells, blood vessels, genes and the immune system; with every player triggered by a sequence of molecular events. An integral part of this process involves the generation of a weak electric field by the damaged epithelium – the layer of cells covering tissue. The electric field forms as a result of an ion gradient in the wound bed, which plays an important role in directing cell migration and promoting blood vessel formation in the area.

Scientists discovered in the mid- to late-1900s that stimulating tissue with an electric field could improve wound healing. Current research in this field is now focused on developing small, wearable, and inexpensive patches that aren’t encumbered by external electrical equipment. 

This has led to research on piezoelectric materials, including natural materials like crystals, silk, wood, bone, hair and rubber, and synthetic materials such as quartz analogs, ceramics and polymers. These materials generate an electric current when exposed to mechanical stress. Nanogenerators developed using the synthetic materials are especially promising.

For example, some research teams are exploring the use of self-powered piezoelectric nanogenerators made with zinc oxide nanorods on a polydimethylsiloxane matrix for accelerating wound healing. Zinc oxide has the advantage of being piezoelectric and biocompatible. Other scientists are using scaffolds made from polyurethane and polyvinylidene fluoride (PVDF) due to their high piezoelectricity, chemical stability, ease of manufacturing and biocompatibility. These and other piezoelectric nanogenerators have shown promising results in laboratory and animal studies.

Another type of device, called a triboelectric nanogenerator (TENG), produces an electric current when two interfacing materials come into and out of contact with each other. Scientists have experimented with TENGs that generate electricity from breathing movements, for example, to accelerate wound healing in rats. They have also loaded TENG patches with antibiotics to facilitate wound healing by also treating localized infection.

“Piezoelectric and triboelectric nanogenerators are excellent candidates for self-assisted wound healing due to their light weight, flexibility, elasticity and biocompatibility,” says bioengineer Zong-Hong Lin of the National Tsing Hua University in Taiwan. “But there are still several bottlenecks to their clinical application.” 

For example, they still need to be customized so they are fit-for-size, as wound dimensions vary widely. They also need to be firmly attached without being negatively affected or corroded by the fluids that naturally exude from wounds.

“Our future aim is to develop cost-effective and highly efficient wound dressing systems for practical clinical applications,” says Lin.

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Popular prescription weight loss drugs linked to uncommon blinding condition

Patients prescribed semaglutide (as Ozempic or Wegovy) for diabetes or weight loss had a higher risk of having a potentially blinding eye condition called NAION than similar patients who had not been prescribed these drugs.

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A new study led by investigators from Mass Eye and Ear found that patients prescribed semaglutide (as Ozempic or Wegovy) for diabetes or weight loss had a higher risk of having a potentially blinding eye condition called NAION than similar patients who had not been prescribed these drugs.

Notably, the study found people with diabetes who had been prescribed semaglutide by their physician and then filled the prescription were more than four times more likely to be diagnosed with NAION. Those who were overweight or had obesity and prescribed this drug were more than seventimes more likely to get the diagnosis.

The study, which was led by Joseph Rizzo, MD, director of the Neuro-Ophthalmology Service at Mass Eye and Ear and the Simmons Lessell Professor of Ophthalmology at Harvard Medical School,  published July 3rd in JAMA Ophthalmology.

“The use of these drugs has exploded throughout industrialized countries and they have provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” said Rizzo, the study’s corresponding author. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.” 

NAION is relatively rare, occurring up to 10 out of 100,000 people in the general population. NAION is the second-leading cause of optic nerve blindness (second only to glaucoma) and it is the most common cause of sudden optic nerve blindness. NAION is thought to be caused by reduced blood flow to the optic nerve head, with the consequence of permanent visual loss in one eye. According to Rizzo, the visual loss caused by NAION is painless and may progresses over many days before stabilizing, and there is relatively little potential for improvement. There are currently no effective treatments for NAION. 

The impetus for the study occurred in the late summer of 2023 when Rizzo, a resident (study co-author Seyedeh Maryam Zekavat, MD, PhD) and other Mass Eye and Ear neuro-ophthalmologists noticed a disturbing trend — three patients in their practice had been diagnosed with vision loss from this relatively uncommon optic nerve disease in just one week. The physicians observed all three were taking semaglutide.

This anecdotal recognition led the Mass Eye and Ear research team to run a backward-looking analysis of their patient population to see if they could identify a link between this disease and these drugs, which had been surging in popularity.

Semaglutide was developed to treat type 2 diabetes. The drug encourages weight loss, and its use has snowballed since its launch as Ozempic for diabetes in 2017. The drug was also approved for weight management, branded as Wegovy, and released in 2021.

The researchers analyzed the records of more than 17,000 Mass Eye and Ear patients treated over the six years since Ozempic was released and divided the patients in those who were diagnosed with either diabetes or overweight/ obesity. The researchers compared patients who had received prescriptions for semaglutide compared to those taking other diabetes or weight loss drugs. Then, they analyzed the rate of NAION diagnoses in the groups, which revealed the significant risk increases.

There are several limitations to the study. Mass Eye and Ear sees an unusually high number of people with rare eye diseases, the study population is majority white, and the number of NAION cases seen over the six-year study period is relatively small. With small case numbers, statistics can change quickly, Rizzo noted. The researchers also couldn’t determine if the patients actually took their medication or if they started and then stopped taking semaglutide at some point and how this might have impacted their risk.  

Importantly, the study does not prove causality, and the researchers don’t know why or how this association exists, and why there was a difference reported in diabetic and overweight groups.

“Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population,” Rizzo said. “This is information we did not have before and it should be included in discussions between patients and their doctors, especially if patients have other known optic nerve problems like glaucoma or if there is preexisting significant visual loss from other causes.”

Authorship: In addition to Rizzo and Zekavat, other Mass General Brigham co-authors include Jimena Tatiana Hathaway, MD, MPH (MEE); Madhura P. Shah, BS (MEE); David B. Hathaway, MD (BWH); Drenushe Krasniqi, BA (MEE); John W. Gittinger Jr, MD (MEE); Dean Cestari, MD (MEE); Robert Mallery, MD (MEE); Bardia Abbasi, MD (MEE); Marc Bouffard, MD (MEE); Bart K. Chwalisz, MD (MEE) and Tais Estrela, MD (MEE).

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New study confirms forever chemicals are absorbed through human skin

New research, published in Environment International proves for the first time that a wide range of PFAS (perfluoroalkyl substances) – chemicals which do not break down in nature – can permeate the skin barrier and reach the body’s bloodstream.

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A study of 17 commonly used synthetic ‘forever chemicals’ has shown that these toxic substances can readily be absorbed through human skin. 

New research, published in Environment International proves for the first time that a wide range of PFAS (perfluoroalkyl substances) – chemicals which do not break down in nature – can permeate the skin barrier and reach the body’s bloodstream.  

PFAS are used widely in industries and consumer products from school uniforms to personal care products because of their water and stain repellent properties. While some substances have been banned by government regulation, others are still widely used and their toxic effects have not yet been fully investigated. 

PFAS are already known to enter the body through other routes, for example being breathed in or ingested via food or drinking water, and they are known to cause adverse health effects such as a lowered immune response to vaccination, impaired liver function and decreased birth weight.  

It has commonly been thought that PFAS are unable to breach the skin barrier, although recent studies have shown links between the use of personal care products and PFAS concentrations in human blood and breast milk.  The new study is the most comprehensive assessment yet undertaken of the absorption of PFAS into human skin and confirms that most of them can enter the body via this route. 

Lead author of the study, Dr Oddný Ragnarsdóttir carried out the research while studying for her PhD at the University of Birmingham. She explained: “The ability of these chemicals to be absorbed through skin has previously been dismissed because the molecules are ionised. The electrical charge that gives them the ability to repel water and stains was thought to also make them incapable of crossing the skin membrane. 

“Our research shows that this theory does not always hold true and that, in fact, uptake through the skin could be a significant source of exposure to these harmful chemicals.” 

The researchers investigated 17 different PFAS. The compounds selected were among those most widely used, and most widely studied for their toxic effects and other ways through which humans might be exposed to them. Most significantly, they correspond to chemicals regulated by the EU’s Drinking Water Directive.   

In their experiments the team used 3D human skin equivalent models – multilayered laboratory grown tissues that mimic the properties of normal human skin, meaning the study could be carried out without using any animals. They applied samples of each chemical to measure what proportions were absorbed, unabsorbed, or retained within the models. 

Of the 17 PFAS tested, the team found 15 substances showed substantial dermal absorption – at least 5% of the exposure dose. At the exposure doses examined, absorption into the bloodstream of the most regulated PFAS (perfluoro octanoic acid (PFOA)) was 13.5% with a further 38% of the applied dose retained within the skin for potential longer-term uptake into the circulation.  

The amount absorbed seemed to correlate with the length of the carbon chain within the molecule. Substances with longer carbon chains showed lower levels of absorption, while compounds with shorter chains that were introduced to replace longer carbon chain PFAS like PFOA, were more easily absorbed. Absorption of perfluoro pentanoic acid for example was four times that of PFOA at 59%. 

Study co-author, Dr Mohamed Abdallah, said “our study provides first insight into significance of the dermal route as pathway of exposure to a wide range of forever chemicals.  Given the large number of existing PFAS, it is important that future studies aim to assess the risk of broad ranges of these toxic chemicals, rather than focusing on one chemical at a time.”  

Study co-author, Professor Stuart Harrad, of the University of Birmingham’s School of Geography, Earth and Environmental Sciences, added: “This study helps us to understand how important exposure to these chemicals via the skin might be and also which chemical structures might be most easily absorbed. This is important because we see a shift in industry towards chemicals with shorter chain lengths because these are believed to be less toxic – however the trade-off might be that we absorb more of them, so we need to know more about the risks involved.” 

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Chronic loneliness may increase stroke risk among older adults

When loneliness was assessed at baseline only, the participants considered lonely had a 25% higher risk of stroke than those not considered lonely. Among the participants who reported loneliness at two time points, those in the “consistently high” group had a 56% higher risk of stroke than those in the “consistently low” group, even after accounting for a broad range of other known risk factors.

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Chronic loneliness may significantly raise older adults’ risk of stroke, according to a new study led by Harvard T.H. Chan School of Public Health. 

“Loneliness is increasingly considered a major public health issue. Our findings further highlight why that is,” said lead author Yenee Soh, research associate in the Department of Social and Behavioral Sciences. “Especially when experienced chronically, our study suggests loneliness may play an important role in stroke incidence, which is already one of the leading causes of long-term disability and mortality worldwide.”

While previous research has linked loneliness to higher risk of developing cardiovascular diseases, few have examined the impact on stroke risk specifically. This study is one of the first to examine the association between loneliness changes and stroke risk over time.

Using 2006-2018 data from the Health and Retirement Study (HRS), the researchers assessed the association between changes in loneliness and stroke incidence over time. During 2006-2008, 12,161 participants—all adults ages 50 and above who never had a stroke—responded to questions on the Revised UCLA Loneliness Scale, from which the researchers created summary loneliness scores. Four years later (2010-2012), 8,936 participants who remained in the study responded to the same questions again. The researchers then placed the participants into one of four groups according to their loneliness scores across the two time points: “consistently low” (those who scored low on the loneliness scale at both baseline and follow-up); “remitting” (those who scored high at baseline and low at follow-up); “recent onset” (those who scored low at baseline and high at follow-up); and “consistently high” (those who scored high at both baseline and follow-up).

Among the participants whose loneliness was measured at baseline only, 1,237 strokes occurred during the follow-up period (2006-2018). Among the participants who provided two assessments of loneliness over time, 601 strokes occurred during the follow-up period (2010-2018). The researchers analyzed each group’s risk of stroke over the follow-up period in the context of their experiences with loneliness, controlling for other health and behavioral risk factors. These included social isolation and depressive symptoms, which are closely related but distinct from loneliness.

The findings showed a link between loneliness and higher risk of stroke and found that chronic loneliness heightened risk the most. When loneliness was assessed at baseline only, the participants considered lonely had a 25% higher risk of stroke than those not considered lonely. Among the participants who reported loneliness at two time points, those in the “consistently high” group had a 56% higher risk of stroke than those in the “consistently low” group, even after accounting for a broad range of other known risk factors. While the baseline analyses suggest loneliness at one time point was associated with higher risk, those who experienced remitting or recent onset loneliness did not show a clear pattern of increased risk of stroke—suggesting that loneliness’ impact on stroke risk occurs over the longer term.

“Repeat assessments of loneliness may help identify those who are chronically lonely and are therefore at a higher risk for stroke. If we fail to address their feelings of loneliness, on a micro and macro scale, there could be profound health consequences,” said Soh. “Importantly, these interventions must specifically target loneliness, which is a subjective perception and should not be conflated with social isolation.”

The authors noted that further research examining both nuanced changes in loneliness over the short-term, as well as loneliness patterns over a longer period of time, may help shed additional light on the loneliness-stroke association. They also noted that more research is needed to understand the potential underlying mechanisms, and that the study findings were limited to middle-aged and older adults and may not be generalizable to younger individuals.

Other Harvard Chan authors included Ichiro Kawachi, Laura Kubzansky, Lisa Berkman, and Henning Tiemeier.

Chronic Loneliness and the Risk of Incident Stroke in Middle and Late Adulthood: A Longitudinal Cohort Study of U.S. Older Adults” was written by Yenee Soh, Ichiro Kawachi, Laura D. Kubzansky, Lisa F. Berkman, Henning Tiemeier, and appeared in eClinicalMedicine.

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