Microplastic waste becomes 'hubs' for pathogens, antibiotic-resistant bacteria

 It's estimated that an average-sized wastewater treatment plant serving roughly 400,000 residents will discharge up to 2,000,000 microplastic particles into the environment each day. Yet, researchers are still learning the environmental and human health impact of these ultra-fine plastic particles, less than 5 millimeters in length, found in everything from cosmetics, toothpaste and clothing microfibers, to our food, air and drinking water.

Now, researchers at New Jersey Institute of Technology have shown that ubiquitous microplastics can become 'hubs' for antibiotic-resistant bacteria and pathogens to grow once they wash down household drains and enter wastewater treatment plants -- forming a slimy layer of buildup, or biofilm, on their surface that allows pathogenic microorganisms and antibiotic waste to attach and comingle.

In findings published in Elsevier's Journal of Hazardous Materials Letters, researchers found certain strains of bacteria elevated antibiotic resistance by up to 30 times while living on microplastic biofilms that can form inside activated sludge units at municipal wastewater treatment plants.

"A number of recent studies have focused on the negative impacts that millions of tons of microplastic waste a year is having on our freshwater and ocean environments, but until now the role of microplastics in our towns' and cities' wastewater treatment processes has largely been unknown," said Mengyan Li, associate professor of chemistry and environmental science at NJIT and the study's corresponding author. "These wastewater treatment plants can be hotspots where various chemicals, antibiotic-resistant bacteria and pathogens converge and what our study shows is that microplastics can serve as their carriers, posing imminent risks to aquatic biota and human health if they bypass the water treatment process."

"Most wastewater treatment plants are not designed for the removal of microplastics, so they are constantly being released into the receiving environment," added Dung Ngoc Pham, NJIT Ph.D. candidate and first author of the study. "Our goal was to investigate whether or not microplastics are enriching antibiotic-resistant bacteria from activated sludge at municipal wastewater treatment plants, and if so, learn more about the microbial communities involved."

In their study, the team collected batches of sludge samples from three domestic wastewater treatment plants in northern New Jersey, inoculating the samples in the lab with two widespread commercial microplastics -- polyethylene (PE) and polystyrene (PS). The team used a combination of quantitative PCR and next-generation sequencing techniques to identify the species of bacteria that tend to grow on the microplastics, tracking genetic changes of the bacteria along the way.

The analysis revealed that three genes in particular -- sul1, sul2 and intI1-- known to aid resistance to common antibiotics, sulfonamides, were found to be up to 30 times greater on the microplastic biofilms than in the lab's control tests using sand biofilms after just three days.

When the team spiked the samples with the antibiotic, sulfamethoxazole (SMX), they found it further amplified the antibiotic resistance genes by up to 4.5-fold.

"Previously, we thought the presence of antibiotics would be necessary to enhance antibiotic-resistance genes in these microplastic-associated bacteria, but it seems microplastics can naturally allow for uptake of these resistance genes on their own." said Pham. "The presence of antibiotics does have a significant multiplier effect however."

Eight different species of bacteria were found highly enriched on the microplastics. Among these species, the team observed two emerging human pathogens typically linked with respiratory infection, Raoultella ornithinolytica and Stenotrophomonas maltophilia, frequently hitchhiking on the microplastic biofilms.

The team say the most common strain found on the microplastics by far, Novosphingobium pokkalii, is likely a key initiator in forming the sticky biofilm that attracts such pathogens -- as it proliferates it may contribute to the deterioration of the plastic and expand the biofilm. At the same time, the team's study highlighted the role of the gene, intI1, a mobile genetic element chiefly responsible for enabling the exchange of antibiotic resistance genes among the microplastic-bound microbes.

"We might think of microplastics as tiny beads, but they provide an enormous surface area for microbes to reside," explained Li. "When these microplastics enter the wastewater treatment plant and mix in with sludge, bacteria like Novosphingobium can accidentally attach to the surface and secrete glue-like extracellular substances. As other bacteria attach to the surface and grow, they can even swap DNA with each other. This is how the antibiotic resistance genes are being spread among the community."

"We have evidence that the bacteria developed resistance to other antibiotics this way as well, such as aminoglycoside, beta-lactam and trimethoprim," added Pham.

Now, Li says the lab is further studying the role of Novosphingobium in biofilm formation on microplastics. The team is also seeking to better understand the extent to which such pathogen-carrying microplastics may be bypassing water treatment processes, by studying resistance of microplastic biofilms during wastewater treatment with disinfectants such as UV light and chlorine.

"Some states are already considering new regulations on the use of microplastics in consumer products. This study raises calls for further investigation on microplastic biofilms in our wastewater systems and development of effective means for removing microplastics in aquatic environments," said Li.

https://www.eurekalert.org/pub_releases/2021-03/njio-hom031921.php

New treatment shows promise in preventing heart failure after heart attack

 A study in mice finds treatment with a molecule called MCB-613 repairs heart tissue after a severe heart attack, preventing damage that can lead to heart failure. The findings are being presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

"This is a remarkable discovery that may lead to effective and safe treatments to prevent the progression to heart failure after a heart attack," said lead researcher Lisa K. Mullany, Ph.D., of Baylor College of Medicine in Houston.

Heart failure after a heart attack is the leading cause of death in humans, and currently there are no definitive therapies other than heart transplantation.

Researchers had previously found that MCB-613 stimulates proteins called steroid receptor coactivators (SRCs). These proteins are responsible for cellular changes and growth during both normal and abnormal tissue growth. After a heart attack, the damaged tissue scars. This results in tissue loss, as well as increased inflammation, scarring and decrease in heart function--all hallmarks of heart failure caused by a heart attack.

In the new study, the researchers were able to show that when mice were given MCB-613 within hours after a heart attack, the molecule decreased inflammation and scarring, and prevented the progressive decrease in heart function.

"Our findings show us that we can directly modulate heart tissue repair to prevent heart failure," Mullany said.

https://www.eurekalert.org/pub_releases/2021-03/tes-nts031621.php

Few at risk for common high blood pressure disorder are screened

 Only 3% of patients at high risk for primary aldosteronism (PA), a common disorder that causes high blood pressure and can lead to heart and kidney complications, are screened for the condition, according to a study that will be presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

"The results of our study indicate that initiatives to encourage PA screening are crucial for preventing cardiovascular and kidney disease in many patients with hypertension," said lead researcher Seda Grigoryan, M.D., of Michigan State University in Lansing, Mich.

PA is the most common form of secondary hypertension--high blood pressure caused by another disease. Nearly half of adults in the United States have high blood pressure. PA occurs when the adrenal glands produce too much aldosterone, the hormone responsible for balancing potassium and sodium in the body. Overproduction of aldosterone causes the body to retain more sodium and lose potassium. This leads to elevated blood pressure, increasing the risk of heart and kidney disease.

Patients with PA have a higher risk of developing cardiovascular and kidney complications compared with patients with primary hypertension (high blood pressure without an apparent cause) with similar blood pressure.

The researchers reviewed data for adult patients with hypertension seen in outpatient clinics between 2010 and 2019 who were known to be at risk for PA. Of 11,627 patients, only 3% were ever screened for PA. Risk factors included hypertension resistant to treatment, hypertension below age 40, hypertension and obstructive sleep apnea, hypertension and potassium deficiency, and hypertension and a mass in the adrenal gland.

Patients who were screened generally were younger, and Black patients were more likely to be screened than those of other races. Grigoryan found the diagnosis of PA was suspected more often after complications--such as strokes and kidney disease--had already developed. Of the patients at risk for PA, screening was done most often in those with adrenal nodules (35%) and least often in those with sleep apnea (2%).

https://www.eurekalert.org/pub_releases/2021-03/tes-fpa031621.php

Supplements may protect those with low vitamin D levels from severe COVID-19

 Patients with low vitamin D levels who are hospitalized for COVID-19 may have a lower risk of dying or requiring mechanical ventilation if they receive vitamin D supplementation of at least 1,000 units weekly, according to a study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

"Given how common vitamin D deficiency is in the world and the United States, we believe that this research is highly relevant right now," said co-author Sweta Chekuri, M.D., of Montefiore Health System and Albert Einstein College of Medicine in the Bronx, New York.

Research has shown that vitamin D supplementation can prevent inflammation in other respiratory diseases, but there have been limited studies examining the role of vitamin D supplementation in COVID-19. The purpose of the study was to determine whether being supplemented with vitamin D before being admitted to the hospital with COVID-19 resulted in less severe COVID-19 disease in patients with a low vitamin D level.

The researchers studied 124 adult patients with low vitamin D that was measured up to 90 days before their admission for COVID-19. They compared the patients who were supplemented with at least 1,000 units of vitamin D weekly to those who had not received vitamin D supplements in terms of whether they were mechanically ventilated or died during admission.

They found that patients who were supplemented were less likely to be mechanically ventilated or to die following admission, though the finding wasn't statistically significant (37.5 percent of patients who were not supplemented vs. 33.3 percent of those who were) They also found that more than half of those who should have been supplemented were not.

"Though we weren't able to show a definitive link to severe COVID-19, it is clear that patients with low vitamin D should receive supplementation not only for bone health, but also for stronger protection against severe COVID-19," said co-author Corinne Levitus, D.O., of Montefiore Health System and Albert Einstein College of Medicine. "We hope this research will encourage clinicians to discuss adding this supplement with their patients who have low vitamin D, as this may reduce the odds of people developing severe COVID-19."

A study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism last fall found over 80 percent of 200 COVID-19 patients in a hospital in Spain had vitamin D deficiency.

https://www.eurekalert.org/pub_releases/2021-03/tes-smp031621.php

Common drugs for type 2 diabetes and obesity do not raise breast cancer risk

 Commonly used medications for type 2 diabetes and obesity called glucagon like peptide-1 receptor agonists (GLP-1 RAs), are not associated with an increased risk of breast cancer, despite previous studies that suggested a possible link, according to a study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

"GLP-1RAs can be used as adjunct to diet and exercise in subjects with type 2 diabetes and those without type 2 diabetes and excess weight, without an increased risk of breast cancer or noncancerous masses in the breast," said lead researcher Giovana Fagundes Piccoli, M.D., of the Universidade Federal do Rio Grande do Sul in Brazil.

GLP-1 RAs have been shown to be effective in treating obesity and type 2 diabetes and in reducing heart disease. These drugs include albiglutide (Tanzeum); dulaglutide (Trulicity); exenatide (Byetta); extended-release exenatide (Bydureon); liraglutide (Victoza, Saxenda); lixisenatide (Adlyxin); and semaglutide (Ozempic, Rybelsus). In clinical trials of liraglutide, subjects treated with the active drug instead of a placebo had a higher number of breast cancers. The new study was designed to assess whether patients treated with GLP-1 RAs had a higher risk of breast cancer or benign growths in the breasts called neoplasms.

Piccoli reviewed 52 randomized controlled trials that compared GLP-1 RAs with non-GLP-1 RAs (either other diabetes or weight-loss drugs or placebos) in adults with overweight, obesity, prediabetes or diabetes. The studies had a minimum follow-up period of 24 weeks and reported at least one event of breast cancer or benign breast neoplasm. They included a total of 90,360 participants.

The analysis found treatment with GLP-1 RAs was not associated with increased rates of breast cancer or benign or premalignant breast neoplasms, compared to placebo or other diabetes or weight-loss drugs. Among 48,267 subjects treated with GLP-1 RAs, 130 developed breast cancer, compared to 107 of 40,755 controls.

https://www.eurekalert.org/pub_releases/2021-03/tes-cdf031621.php

Increased risk of hearing impairment with new thyroid eye disease treatment

 More patients than previously reported may experience hearing symptoms such as hearing loss or muffled hearing from a new treatment for thyroid eye disease, teprotumumab (Tepezza), according to a small study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

Teprotumumab, approved by the U.S. Food and Drug Administration in January 2020, is the first and only drug to be approved for thyroid eye disease. In two clinical trials conducted prior to FDA approval of the drug, otologic symptoms were reported in 10 percent of patients. The new study found the rate could be as high as 65 percent.

The treatment is administered to patients once every three weeks for a total of eight infusions. It has shown significant improvement in abnormal protrusion of the eyes (proptosis), double vision, soft tissue inflammation and quality of life.

Andrea Lora Kossler, M.D., assistant professor of ophthalmology at the Stanford University School of Medicine, is the senior author on the research. She and fellow researchers state that teprotumumab is an effective therapy for thyroid eye disease, but as with all therapeutics, there are known risks, including hearing impairment. The authors aim to better understand the risk of hearing loss and recommend tests to reduce this risk.

Thyroid eye disease is an autoimmune disease in which the eye muscles and fatty tissue behind the eye become inflamed. Symptoms can include dry, watery, red or bulging eyes, a "stare," double vision, difficulty closing the eyes, and problems with vision. It is primarily associated with an overactive thyroid gland due to Graves' disease.

To explore the incidence of hearing symptoms in patients treated with teprotumumab, the researchers evaluated 26 patients treated with at least four infusions of the drug. Seventeen patients (65 percent) complained of otologic symptoms when questioned. The most common symptoms were subjective hearing loss (n=6, 23 percent), tinnitus, or ringing in the ears (n=7, 27 percent), ear plugging sensation (n=3, 12 percent), and autophony, an unusually loud hearing of a person's own voice (29 percent). Otologic symptoms developed after an average of 3.6 infusions.

Of the 17 patients with new hearing symptoms, four had new or worsening sensorineural hearing loss, a type of hearing loss resulting from damaged hair cells in the inner ear. Three patients had patulous eustachian tube, a disorder in which the channel that runs between the middle ear and back of the nose and throat stays open. Normally, these eustachian tubes remain closed and open only occasionally to regulate air pressure around the ear drum. After three months, symptoms of patulous eustachian tube improved, but did not completely disappear. Two patients with sensorineural hearing loss had improvement in symptoms at one and six months.

The authors aim to raise awareness on the incidence of otologic symptoms & recommend screening precautions, such as baseline audiogram testing to better understand this potential side effect. The follow up period of 3 months after stopping the drug is too short to assess the reported reversibility of otologic symptoms. Future studies will evaluate risk factors for hearing loss and the reversibility of symptoms.

https://www.eurekalert.org/pub_releases/2021-03/tes-iro031621.php

Tubeless automated insulin delivery improves blood glucose outcomes

 People with type 1 diabetes can improve their blood sugar control while reducing time with low blood sugar, or hypoglycemia, using Insulet Corporation's Omnipod 5 Automated Insulin Delivery System compared to their standard insulin therapy. Results from an industry-sponsored study of the latest Omnipod, the first tubeless, wearable insulin pump, will be presented at ENDO 2021, the Endocrine Society's annual meeting.

The Omnipod 5 System underwent three months of at-home testing in 128 adults and adolescents ages 14 to 70 years and 112 children ages 6 to less than 14 years. All study participants have type 1 diabetes and were first followed for two weeks using their standard therapy, either multiple daily insulin injections or an insulin pump. Using Omnipod 5, participants experienced significant average improvements in both hemoglobin A1c, a measure of blood glucose (sugar) control over the past several months, and the percentage of time the participants stayed within the recommended target glucose range (70 to 180 milligrams per deciliter), the researchers reported.

"These study results represent an advancement in diabetes therapies with a fully wearable device that enables continuous automated insulin modulation. This will expand the available treatment options for people with type 1 diabetes," said the study's senior investigator, Trang Ly, MBBS, FRACP, PhD, Senior Vice President and Medical Director of Insulet Corporation.

Insulet funded this study and manufactures Omnipod 5, which is under review by the U.S. Food and Drug Administration. It is an update to the Omnipod DASH and the original Omnipod System, which are sold in the U.S., Canada, Europe and the Middle East.

The Omnipod 5 System, according to Ly, is the first tubeless automated insulin delivery system integrated with the Dexcom G6 continuous glucose monitoring (CGM) system. She said this commonly used glucose monitor automatically measures glucose levels every five minutes and communicates directly with Omnipod 5. The Pod is now designed with an embedded algorithm that adjusts the pump's insulin delivery automatically to a customizable glucose target, based on the CGM value and trend.

Users of Omnipod 5 inject insulin into a single-use Pod, which adheres to their skin for 72 hours of continuous infusion of insulin. At mealtimes, the user administers a bolus dose of insulin which is controlled by the Omnipod 5 app on the user's personal smartphone or a separate wireless controller. Ly said the new system will have the ability to control the Pod from a compatible smartphone, making the wireless controller optional.

Ly reported that the adult/adolescent group's A1c averaged 0.4 percent lower with Omnipod 5 than when they used their standard insulin therapy, an improvement from 7.2 percent to 6.8 percent.

With Omnipod 5, their average time in the glucose range recommended by the American Diabetes Association (70 to 180 milligrams per deciliter) was 2.2 hours a day longer, or 9.3 percent better, Ly stated. Overall, this group was in target range nearly 74 percent of the time when they used Omnipod 5, while the general population with type 1 diabetes is often in target glucose range 60 percent or less of the time.

"Even though many of the study participants had their diabetes well controlled before the study, they still experienced improved time in the target glucose range, regardless of their baseline control. This shows the potential of the technology in the broader population with diabetes," Ly said.

One of their most important findings in the adult/adolescent group, according to Ly, was a reduction of time in hypoglycemia, measured on the sensor as glucose levels below 70 milligrams per deciliter, down to a median of 1.1 percent. Hypoglycemia is a dangerous drop in blood glucose levels. Only two episodes of severe hypoglycemia occurred, reportedly after user-initiated bolus doses.

Most study participants chose to continue using the Omnipod 5 during an extension of the original three-month study, which Ly said suggests a preference over their previous therapy.

Children participating in the study also had improved blood sugar control after using Omnipod 5. The average A1c dropped by 0.7 percent, to 7 percent, and the time in range improved by nearly four hours per day. One event of diabetic ketoacidosis (excessive ketones in the blood due to insufficient insulin) occurred, which Ly attributed to infusion site failure. She said one severe hypoglycemia event occurred that was not attributable to device malfunction.

"Omnipod 5 protects you from both high and low glucose values," Ly said. "It also is simple, intuitive, and easy to use."

Sue Brown, M.D., of the University of Virginia in Charlottesville, Va., will present the data for adults and adolescents during an oral presentation at the meeting. Bruce Buckingham, M.D., of Stanford University, will present the pediatric data in a poster presentation.

https://www.eurekalert.org/pub_releases/2021-03/tes-tai031721.php