Using data generated from patients and mice with genetic mutation for the disorder Usher syndrome, researchers from the University of Maryland School of Medicine (UMSOM), the National Institutes of Health’s National Eye Institute (NEI), and National Institute on Deafness and Other Communication Disorders (NIDCD), documented the natural history of vision impairment in patients and identified the cell mechanism behind progressive vision loss.
Based on these findings, published on November 9, 2021, in the journal eLife, the team was able to test a retinoid therapy that improved vision in mice with Usher syndrome. The researchers said assessing a similar therapy should now be considered in people with Usher syndrome to see if this therapy might slow vision loss.
Usher syndrome type 1F (USH1F) causes deafness, progressive vision loss, and balance issues. Among Ashkenazi Jews, there is a 2% chance each person is a carrier of the Usher syndrome type 1F mutation, accounting for approximately 60% of their Usher syndrome type 1 cases. There are no approved therapies to prevent vision loss or restore vision in people with Usher syndrome.
“The drug we used in mice may provide a first step to improve eye health in people with Usher syndrome type 1F,” said Zubair M. Ahmed, PhD, Professor of Otorhinolaryngology — Head & Neck Surgery and Ophthalmology at UMSOM. “Unfortunately, these drugs will not permanently cure loss of vision, as the drug does not repair damage or prevent degeneration of the eyes. However, it should improve the function of the tissue that these patients still have.”
First author of the study Saumil Sethna, PhD, Instructor in Otorhinolaryngology — Head & Neck Surgery, said, “There are currently FDA-approved relatives of these retinoid drugs that are available and have passed clinical trials for safety, along with others that are in phase II clinical trials to treat other types of vision loss disorders.”
The team hopes to partner with one of the companies testing these drugs to launch a clinical trial in patients with Usher syndrome type 1F to see if it can help by preventing continuing vision loss.

New research suggests there may someday be a role for ibuprofen in providing older adults with lasting immunity against RSV, a virus commonly associated with infants and young kids that also rivals the flu as a dangerous wintertime infection for the elderly.
RSV, or respiratory syncytial virus, accounts for an estimated 14,000 deaths and 177,000 hospitalizations annually among U.S. adults over 65. RSV is problematic for older people in part because an initial infection isn’t effective at inducing a long-term immune response to the virus.
The study showed that geriatric cotton rats given ibuprofen for a week before initial infection with RSV cleared the virus more quickly than those that didn’t receive ibuprofen. When researchers re-infected those ibuprofen-treated rats a month later, the elderly animals were completely protected from the virus.
In contrast, young adult cotton rats were able to clear the virus fairly effectively and mount a suitable immune response to re-infection a month later — but got no benefit from the ibuprofen.
With ibuprofen showing effectiveness only in geriatric animals, the findings suggest that the drug improves the immune response by lowering aging-related inflammation. Though there is still a lot to learn, the Ohio State University researchers speculate that the reduced inflammation restored the function of specific immune cells needed to clear the virus.
“For a long time, people have thought that certain immune cells get burned out and can’t function properly any longer. And then we started treating against inflammation, and suddenly the old cells can do their job like young cells,” said senior study author Stefan Niewiesk, professor of veterinary biosciences at Ohio State.

Exposure in utero to a drug used to prevent miscarriage can lead to an increased risk of developing cancer, according to researchers at The University of Texas Health Science Center at Houston (UTHealth Houston).
The study was published today in the American Journal of Obstetrics and Gynecology.
The drug, 17α-hydroxyprogesterone caproate (17-OHPC), is a synthetic progestogen that was frequently used by women in the 1950s and 1960s, and is still prescribed to women today to help prevent preterm birth. Progesterone helps the womb grow during pregnancy and prevents a woman from having early contractions that may lead to miscarriage.
“Children who were born to women who received the drug during pregnancy have double the rate of cancer across their lifetime compared to children born to women who did not take this drug,” said Caitlin C. Murphy, PhD, MPH, lead author on the study and associate professor in the Department of Health Promotion and Behavioral Sciences at UTHealth School of Public Health in Houston. “We have seen cancers like colorectal cancer, pancreatic cancer, thyroid cancer, and many others increasing in people born in and after the 1960s, and no one really knows why.”
Researchers reviewed data from the Kaiser Foundation Health Plan on women who received prenatal care between June 1959 and June 1967, and the California Cancer Registry, which traced cancer in offspring through 2019.
Out of more than 18,751 live births, researchers discovered 1,008 cancer diagnoses were made in offspring ages 0 to 58 years. Additionally, a total of 234 offspring were exposed to 17-OHPC during pregnancy. Offspring exposed in the womb had cancer detected in adulthood more than twice as often as offspring not exposed to the drug — 65% of cancers occurred in adults younger than 50.
“Our findings suggest taking this drug during pregnancy can disrupt early development, which may increase risk of cancer decades later,” Murphy said “With this drug, we are seeing the effects of a synthetic hormone. Things that happened to us in the womb, or exposures in utero, are important risk factors for developing cancer many decades after we’re born.”
A new randomized trial shows there is no benefit of taking 17-OHPC, and that it does not reduce the risk of preterm birth, according to Murphy.
The U.S. Food and Drug Administration proposed in October 2020 that this particular drug be withdrawn from the market.
This work was supported by two National Institutes of Health: The National Cancer Institute (R01CA242558) and the National Institute of Child Health and Development (HHSN275201100020C).
Additional authors include Piera M. Cirillo, MPH; Nickilou Y. Krigbaum, MPH; and Barbara A. Cohn, PhD, all with Child Health and Development Studies at the Public Health Institute.
 
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Materials provided by University of Texas Health Science Center at Houston. Original written by Jeannette Sanchez. Note: Content may be edited for style and length.

Type 1 diabetes, rheumatoid arthritis, and cancer are just some of the disorders associated with specific genes not “turning on” and “turning off” as they should. By using new CRISPR/Cas9 genome editing technology, in a recent paper in Nature Communications, McGill University researchers have described a new technique that scientists across the world can potentially use to explore novel ways of treating diseases associated with dysregulation in DNA methylation.
All the cells in an individual’s body bear the same genetic code. It is the reading and writing of this code — the “turning on” and “turning off” of specific genes in specific cells — that gives the cells their identities. Imagine, for example, the disastrous situation wherein the genes that encode the digestive enzymes of the stomach would be turned on in the retinal cells of the eye and begin to devour the surrounding tissue. One of the ways by which a cell turns off specific genes is by the reversible addition to the DNA of a minuscule chemical called a methyl group at the precise location of that specific gene.
Scientists know that genes with more of this “DNA methylation” tend to be “turned off” and that genes with less of this methylation tend to be “turned on.” But because until now it hasn’t been possible to manipulate the levels of DNA methylation at specific genes, there remain many questions about what specific instances of DNA methylation do, how they contribute to normal cellular function, and how their dysregulation contributes to disease.
In a recent study, published in Nature Communications, McGill University researchers demonstrate how they have managed to remove specific instances of DNA methylation at specific genes in mouse and human cells grown in culture by using CRISPR/Cas9 genome editing technology. They show that this DNA “de-methylation” activity can be targeted to anywhere in the DNA — any gene of interest — without editing the genetic code, and with no off-target activity at undesired locations in the DNA. The researchers also describe the approaches needed to produce complete removal of DNA methyl marks in the hopes that scientists around the world can use this new technique to start to discover actionable instances where genes that should be on have been turned off by DNA methylation — such as, for example, the insulin gene in diabetes — and use this technique to establish new paradigms for disease treatment.
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Researchers at the University of Toronto (U of T) and Unity Health Toronto have demonstrated that repeated listening to personally meaningful music induces beneficial brain plasticity in patients with mild cognitive impairment or early Alzheimer’s disease.
Changes in the brain’s neural pathways correlated with increased memory performance on neuropsychological tests, supporting the clinical potential of personalized, music-based interventions for people with dementia.
The landmark multi-modal study was published today in the Journal of Alzheimer’s Disease.
“We have new brain-based evidence that autobiographically salient music — that is, music that holds special meaning for a person, like the song they danced to at their wedding — stimulates neural connectivity in ways that help maintain higher levels of functioning,” says Dr. Michael Thaut, senior author of the study, director of the Music and Health Science Research Collaboratory, Tier One Canada Research Chair in Music, Neuroscience and Health, and professor at U of T’s Faculty of Music and Temerty Faculty of Medicine.
“Typically, it’s very difficult to show positive brain changes in Alzheimer’s patients. These preliminary yet encouraging results show improvement in the integrity of the brain, opening the door to further research on therapeutic applications of music for people with dementia — musicians and non-musicians alike.”
The research team reported structural and functional changes in neural pathways of study participants, notably in the prefrontal cortex, the brain’s control centre where deep cognitive processes occur. Researchers showed that exposing the brains of patients with early-stage cognitive decline to autobiographically salient music activated a distinct neural network — a musical network — comprised of diverse brain regions that showed differences in activation after a period of daily music listening. Differences were also observed in the brain’s connections and white matter, providing further evidence of neuroplasticity.

St. Jude Children’s Research Hospital scientists looking for drugs to improve survival of children with high-risk neuroblastoma found a promising candidate in CX-5461. Then researchers identified safety concerns with the experimental drug that have implications for current clinical trials in adults. The study appears today in Nature Communications.
CX-5461 is a small molecule that has been studied for more than a decade. It has been widely described as a first-in-human inhibitor of the enzyme RNA polymerase 1. Phase II clinical trials of CX-5461 are underway in adults with leukemia, lymphoma and breast cancer.
St. Jude researchers demonstrated in this study that CX-5461 killed neuroblastoma tumor cells primarily by targeting and disrupting the activity of the enzyme topoisomerase II beta (TOP2β) and not by inhibiting RNA polymerase 1.
“These new details of CX-5461’s mechanism of action in cancer treatment have potentially important safety implications for patients,” said Paul Geeleher, Ph.D., St. Jude Department of Computational Biology. He and John Easton, Ph.D., St. Jude Computational Biology, are the study’s corresponding authors. The first author is Min Pan, Ph.D., a scientist in the Geeleher lab.
“Decades of study of an existing class of chemotherapy agents have shown that off-target drug interactions with TOP2βleave patients at risk for serious and life-threatening side effects such as acute myeloid leukemia or cardiotoxicity that emerge years later,” Geeleher said. “The findings highlight a previously unappreciated safety concern with CX-5461.”
Search for new high-risk neuroblastoma drugs took unexpected turn
The study began as a quest to find new treatments for children with high-risk neuroblastoma, whose survival rates have remained about 50% for the last 20 years. Neuroblastoma arises from cells of the developing peripheral nervous system and is diagnosed in about 800 children annually in the U.S.
CX-5461 showed significant anti-tumor activity in combination therapy in preclinical studies of pediatric neuroblastoma, but safety concerns must be addressed before planning clinical trials in children, Geeleher said. “Patients enrolled in ongoing CX-5461 phase II trials should be closely monitored for these late-emerging TOP2β-related adverse events,” the researchers noted.
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On the Scene: Vaccine Clinics at SchoolsAshley Wong and Sharon Otterman📍Reporting from New York CityParents leaving P.S. 21 Monday afternoon in Bedford-Stuyvesant, Brooklyn, said only about eight students were waiting inside. The scene was similarly peaceful at P.S. 5, also in Bedford-Stuyvesant. Candace Floyd, 36, said it was a relief to get her 10-year-old son, Jeremiah Augustine, vaccinated. He and his classmates have already had to quarantine twice after potential exposure.“You’re in and out,” Floyd told me as she left the clinic.

Leptin, a molecule produced by fat cells, appears to cancel out the effects of the estrogen-blocking therapy tamoxifen, a drug commonly used to treat and prevent breast cancers, suggests a new study led by researchers from the Johns Hopkins Kimmel Cancer Center. The findings, published online Aug. 13 in npj Breast Cancer, could help explain why obese patients with breast cancer often experience worse outcomes, and may eventually lead to more effective treatments for this group.
“Obese women may not get the full benefit of tamoxifen, one of the most widely prescribed medications for estrogen receptor-positive breast cancer treatment and prevention,” says study leader Dipali Sharma, Ph.D., professor of oncology at the Johns Hopkins University School of Medicine. “With obesity increasing worldwide and 40% of the U.S. population already obese, there are a lot of breast cancer patients at risk for poor outcomes.” Estrogen receptor-positive breast cancer is the most common type of breast cancer, and relies on the hormone estrogen to grow and spread. As a result, it usually responds well to hormone therapies that interfere with the body’s production of estrogen.
Researchers have long known that obesity is associated with an increased risk of breast cancer, as well as larger tumors, more metastatic progression, a higher risk of recurrence and worse overall survival. However, Sharma says, the reasons for these connections have been unclear.
She and her colleagues suspected that some of these poor outcomes may be due to a worse response to cancer therapies, an effect influenced by endocrine molecules — cytokines — produced by fat cells. They focused on leptin in particular, a fat-secreted hormone that plays a role in producing feelings of satiety and has been linked to cancer growth and progression.
To see whether leptin might affect therapeutic response, the researchers fed mice a high-fat diet for eight weeks, causing these animals to become obese — which increased the animals’ circulating leptin levels. They then implanted human estrogen receptor-positive breast cancer cells, a type responsible for nearly 70% of breast cancer cases, in the mammary pads of the obese mice and in lean animals.
When Sharma and her team gave these mice tamoxifen, the lean animals’ tumors responded well, regressing quickly. But the obese animals’ tumors didn’t shrink; rather, they responded as if they hadn’t been treated at all. Administering leptin along with tamoxifen caused the same poor response in lean animals, suggesting that leptin was somehow negating tamoxifen’s cancer-fighting effects.
Searching for a mechanism for this phenomenon, Sharma and her colleagues found that leptin appears to activate the estrogen receptors on breast cancer cells, even when estrogen isn’t present, in turn setting off a cascade of cancer-promoting genes. One key gene in this cascade is Med1, which associates with dozens of obesity-related genes. When the researchers silenced this gene, rendering it nonfunctioning, implanted tumors responded to tamoxifen even in the presence of leptin. The researchers were able to achieve this same effect by giving mice another fat-secreted molecule called adiponectin or a compound called honokiol that’s derived from magnolia trees. Both agents target Med1 and were previously known to have a protective effect on cancers.
Sharma says interventions that can lower leptin, such as losing weight, or target Med1, such as adiponectin or honokiol, could eventually be used to improve tamoxifen’s success in obese patients with breast cancer. She and her team are studying some of these potential treatments in mice, a step toward testing them in human clinical trials.
This work was supported by grants from the National Cancer Institute of the National Institutes of Health (RO1CA204555), the Avon Foundation and the Breast Cancer Research Foundation (90047965).
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Both moderate and strenuous exercise alleviate symptoms of anxiety, even when the disorder is chronic, a study led by researchers at the University of Gothenburg shows.
The study, now published in the Journal of Affective Disorders, is based on 286 patients with anxiety syndrome, recruited from primary care services in Gothenburg and the northern part of Halland County. Half of the patients had lived with anxiety for at least ten years. Their average age was 39 years, and 70 percent were women.
Through drawing of lots, participants were assigned to group exercise sessions, either moderate or strenuous, for 12 weeks. The results show that their anxiety symptoms were significantly alleviated even when the anxiety was a chronic condition, compared with a control group who received advice on physical activity according to public health recommendations.
Most individuals in the treatment groups went from a baseline level of moderate to high anxiety to a low anxiety level after the 12-week program. For those who exercised at relatively low intensity, the chance of improvement in terms of anxiety symptoms rose by a factor of 3.62. The corresponding factor for those who exercised at higher intensity was 4.88. Participants had no knowledge of the physical training or counseling people outside their own group were receiving.
“There was a significant intensity trend for improvement — that is, the more intensely they exercised, the more their anxiety symptoms improved,” states Malin Henriksson, doctoral student at Sahlgrenska Academy at the University of Gothenburg, specialist in general medicine in the Halland Region, and the study’s first author.
Importance of strenuous exercise
Previous studies of physical exercise in depression have shown clear symptom improvements. However, a clear picture of how people with anxiety are affected by exercise has been lacking up to now. The present study is described as one of the largest to date.

Bacteria found in children’s upper respiratory systems could help fight chronic middle ear infections, the leading cause of preventable hearing loss and deafness in Indigenous communities.
The University of Queensland’s Dr Seweryn Bialasiewicz said this discovery helped explain a long-held mystery, while providing hope for potential treatments.
“We’ve been puzzled for years now, trying to work out why some children never develop chronic ear disease, despite being in a high-risk category for contracting it,” Dr Bialasiewicz said.
“By focusing on the microbiomes in the upper respiratory tracts of disease-resistant kids, we could investigate the ecological networks of bacterial interactions that seemed to be working together to protect against the condition.
“It was clear that these two groups of bacteria needed to not only be present, but to be interacting with each other, to provide protection from middle ear infections.”
Dr Bialasiewicz said they were hoping to use this information to figure out what the exact mechanism of protection is, and then mimic it in the very young children, as a therapy or a preventative measure.