Publisher Health

A monoclonal antibody used to treat asthma and eczema can improve survival for patients with moderate to severe COVID-19, a clinical trial conducted at UVA Health suggests.
The small trial, designed and led by Jennifer Sasson, MD, found that dupilumab improved patient survival at 60 days and reduced the number of patients who needed intensive care. Almost 90% of patients who received dupilumab in the randomized trial were alive at 60 days, compared with 76.2% of patients who received a placebo (a harmless sham treatment).
“Our clinical trial suggests that treatment with the anti-allergy medicine dupilumab may decrease deaths due to COVID-19. UVA is the first to test this novel and promising approach to COVID-19 treatment, which also proved safe in this small study — as we had expected, as dupilumab has proven safe and effective as an allergy medicine,” said Sasson, of the University of Virginia School of Medicine’s Division of Infectious Diseases and International Health. “A large multi-institution study to validate these preliminary results is being designed. If successful, this multi-site trial will open a new window to treatment of COVID-19 and potentially other viral pneumonias.”
Treating COVID-19
Sasson and her collaborators were inspired to launch the trial after discovering that patients with COVID-19 were at significantly greater risk of needing a ventilator if their blood contained high levels of interleukin-13, a driver of inflammation in the body. Dupilumab, sold under the brand name Dupixent, works by blocking the effects of IL-13. The federal Food and Drug Administration approved dupilumab in 2017 for the treatment of moderate to severe eczema (an itchy skin condition also known as atopic dermatitis). Dupilumab is now also used to treat patients with asthma and chronic sinus inflammation.
To see if dupilumab could improve the body’s immune response to COVID-19, Sasson and her collaborators enrolled 40 patients with moderate to severe cases in a clinical trial. The trial was double-blinded, meaning neither the patients nor the doctors knew whether the patient was receiving the antibody or a placebo. Both groups of trial participants otherwise received standard care.

A new study from researchers at the Johns Hopkins Bloomberg School of Public Health estimates that the overall number of undiagnosed diabetes cases in the U.S. is significantly lower than current government estimates suggest.
The findings, published online July 11 in Diabetes Care, suggest that public health efforts to improve diabetes awareness and screening over the past three decades have translated into better detection of type 2 diabetes in the U.S. At the same time, the study showed major disparities in the burden of undiagnosed diabetes in certain population subgroups.
For their analysis, the researchers used government health survey data covering thousands of people over more than 30 years, 1988 to 2020. Instead of estimating undiagnosed diabetes from single blood test results, as the Centers for Disease Control and Prevention does, the researchers used the two-test criterion that doctors use when screening for diabetes. The researchers found that about 9.5 percent of the total diabetes burden in the U.S. is undiagnosed, versus estimates in the 20-to-30 percent range.
“Our findings suggest that the true figure is much lower and that providers in the U.S. are doing a good job overall with diabetes screening and diagnosis,” says study senior author Elizabeth Selvin, PhD, professor in the Bloomberg School’s Department of Epidemiology. “Nonetheless, undiagnosed diabetes remains high in some subgroups, indicating that there’s still a long way to go.”
The analysis found that undiagnosed diabetes is more prevalent in older and obese adults, racial/ethnic minorities, notably Mexican Americans and Asian Americans, and those without health care access. Individuals who reported an interval of more than one year since their last health care visit also had a high estimated prevalence of confirmed undiagnosed diabetes.
“It’s a real concern that certain populations are being missed by the health care system. This is likely a major reason why undiagnosed diabetes remains high in these groups,” says Michael Fang, PhD, assistant professor in the Department of Epidemiology at the Bloomberg School and the paper’s first author.

New research led by scientists at Mass Eye and Ear and Brigham and Women’s Hospital, member hospitals of Mass General Brigham, reveals the role that a genetic variant associated with Alzheimer’s disease, APOE4, plays in protecting against glaucoma. In the new study, published August 16 in Immunity, the researchers also used a pharmacologic treatment to successfully prevent the destruction of neurons in the eyes of mice with glaucoma by targeting the APOE signaling pathway.
Specifically, the scientists demonstrated that the APOE4 gene variant, which increases risk for Alzheimer’s but decreases risk of glaucoma in humans, blocks a disease cascade that leads to the destruction of retinal ganglion cells in glaucoma. Additionally, they showed in separate mouse models that the death of retinal ganglion cells — the cause of vision loss in glaucoma — can be prevented by using medications to inhibit a molecule called Galectin-3, which is regulated by the APOE gene. These findings taken together emphasize the critical role of APOE in glaucoma and suggest that Galectin-3 inhibitors hold promise as a glaucoma treatment, according to the authors.
“Our research provides greater understanding of the genetic pathway that leads to irreversible blindness in glaucoma, and importantly, points to a possible treatment to address the root cause of the vision loss,” said lead study author Milica Margeta, MD, PhD, a glaucoma specialist and scientist at Mass Eye and Ear, and assistant professor of ophthalmology at Harvard Medical School. “This study shows that the APOE-mediated disease cascade is clearly harmful in glaucoma, and that when you interfere with it genetically or pharmacologically, you can actually stop the disease.”
Understanding and halting the cause of vision loss in glaucoma
Glaucoma is a leading cause of blindness, affecting an estimated 80 million people worldwide. Despite how common the disease is, little is known about the underlying mechanisms that lead to the loss of retinal ganglion cells, which ultimately results in vision loss. Accordingly, there is no treatment to directly promote survival of these cells; current treatments, including medications, laser therapies and surgeries are aimed at lowering eye pressure, the only modifiable risk factor for glaucoma. However, the disease often progresses despite these interventions and can result in complete blindness.
Scientists have suspected that glaucoma may be the result of a microscopic inflammatory process in the eyes. Previous studies by this research team and others, showed that this inflammatory process occurs in the optic nerve of glaucoma patients, as indicated by the presence of activated microglia, which are cells that act as first-line immune responders in the eye and brain. Microglia can be beneficial in healthy tissue; however, in eye diseases and neurodegenerative conditions like Alzheimer’s and Parkinson’s disease, microglia can produce toxic molecules, destroy living neurons, and make neighboring cells become inflammatory.

During the COVID-19 pandemic, many live musical events and festivals were postponed and even canceled to protect musicians and audience members. When they started performing again, many groups resorted to performing with remote or limited crowds. They also adapted their repertoire to promote pieces featuring strings and made significant changes in the number of musicians and their positions in the auditorium.
Orchestral ensembles have faced a particular challenge. Contamination is a chief concern: specifically, whether wind instruments are vectors of contamination through aerosol dispersion.
In Physics of Fluids, by AIP Publishing, researchers from the University of Pennsylvania worked with musicians from the Philadelphia Orchestra to deepen our understanding of how much aerosol is produced and dispersed by wind instruments.
“Ideally, musicians would sit near one another to compose the best sound, but such an arrangement became an issue during the COVID pandemic,” said author Paulo Arratia, of the University of Pennsylvania.
The researchers used visualization to characterize the flow and then tracked fog particles in the air with a laser. They also measured aerosol concentration from wind instruments with a particle counter.
Then they combined these two measurements to develop a simple equation to describe aerosol dispersion, in which the aerosol speeddecays with distance from the instrument. The idea is to help other researchers determine how far aerosols will travel by measuring the exit flow speed. This informs how fast the flow will decay.
Aerosols emitted by wind instruments shared a similar concentration and size distribution compared to normal speech and respiration events.
“We were surprised that the amount of aerosol produced is of the same range as normal speech,” said Arratia. “I was expecting much higher flow speeds and aerosol concentrations.”
Flow measurements (using particle image velocimetry) showed that exit jet speeds are much lower than coughing and sneezing events. For most instruments, the maximum decay length is less than 2 meters from the instrument’s opening. Consequently, wind musicians should stay 6 feet apart, similar to the recommendation for individuals.
The researchers will next look at contamination through aerosol dispersion from a group standpoint to understand how much aerosol and flow is produced by the whole orchestra playing together.
“Hopefully, this manuscript will guide health officials to develop protocols for safe, live musical events,” said Arratia.
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

Salk scientists have uncovered a molecular pathway that distills threatening sights, sounds and smells into a single message: Be afraid. A molecule called CGRP enables neurons in two separate areas of the brain to bundle threatening sensory cues into a unified signal, tag it as negative and convey it to the amygdala, which translates the signal into fear.
The research, published in Cell Reports on August 16, 2022, may lead to new therapies for fear-related disorders such as post-traumatic stress disorder (PTSD) or hypersensitivity disorders such as autism, migraines and fibromyalgia.
“The brain pathway we discovered works like a central alarm system,” says senior author Sung Han, assistant professor in Salk’s Clayton Foundation Laboratories for Peptide Biology. “We were excited to find that the CGRP neurons are activated by negative sensory cues from all five senses — sight, sound, taste, smell and touch. Identifying new threat pathways provides insights into treating fear-related disorders.”
Most external threats involve multisensory cues, such as the heat, smoke and smell of a wildfire. Previous research showed that different pathways independently relay sound, sight, and touch threat cues to multiple brain areas. A single pathway that integrates all these cues would be beneficial to survival, but no one had ever found such a pathway.
Previous research also showed that the amygdala, which initiates behavioral responses and forms fear memories to environmental and emotional stimuli, receives heavy input from brain regions that are laden with a chemical associated with aversion, the neuropeptide CGRP (calcitonin gene-related peptide).
“Based on these two pools of research, we proposed that CGRP neurons, found especially in subregions of the thalamus and the brainstem, relay multisensory threat information to the amygdala,” says co-first author Shijia Liu, a graduate student in the Han lab. “These circuits may both generate appropriate behavioral responses and help form aversive memories of threat cues.”
The team conducted several experiments to test their hypotheses. They recorded CGRP neuron activity using single-cell calcium imaging while presenting mice with multisensory threat cues, enabling the researchers to pinpoint which sensory modality involved which sets of neurons. They determined the path the signals took after leaving the thalamus and brainstem using different colored fluorescent proteins. And they conducted behavioral tests to gauge memory and fear.

Researchers at McMaster University have found a class of well-known antiviral drugs could be part of a one-two punch to treat seasonal influenza and prevent a flu pandemic when used in combination with antibody therapies.
Antiviral drugs such as Tamiflu have been prescribed for decades to treat flu symptoms in people at risk for serious complications.
Researchers found when these medications were used with antibody therapy, the combination was more effective than either approach alone: the antibodies were significantly more efficient at killing infected cells and the drugs were more potent.
The findings, published today in the journal Cell Reports Medicine, could inform new approaches to protecting high-risk groups, including the elderly and children during an emerging influenza pandemic, the researchers say.
“Antibody therapies were used to treat COVID-19, and in theory they could be used to treat flu as a new therapeutic approach,” says Matthew Miller, a lead author of the study and director of McMaster’s Michael G. DeGroote Institute for Infectious Disease Research.
“We really need to have better strategies to protect people from flu pandemics because right now we don’t have anything,” he says. “Our seasonal vaccines don’t protect us. And we’ve learned that we can’t make them quickly enough to vaccinate everybody if a new pandemic were to emerge.”
Miller and his team have studied broadly neutralizing antibodies — which fend off a wide range of respiratory viruses — for over 10 years. They are examining how these antibodies could be tapped to protect against all strains of flu, in their urgent pursuit of a universal flu vaccine.

One thing you might want even less than a ‘kiss’ from a kissing bug is its feces. Scientifically referred to as triatomine bugs, these blood-sucking insects can carry in their feces and pass on to humans the parasite Trypanosoma cruzi that causes Chagas disease, a lifelong infection that takes a heavy toll on community health in poor populations, particularly in El Salvador.
Efforts to eliminate Chagas disease require active and effective vector control measures in response to a change of the principal triatomine vector species. Osaka Metropolitan University scientists and their Salvadoran colleagues addressed this need with their two-year nationwide survey on vector infestation, results of which signaled potential active transmission of Chagas disease and identified areas where vectors have high parasite infection rates, thereby strengthening vector control capabilities in the country. Their findings were published in Infectious Diseases of Poverty.
One of 20 WHO-designated neglected tropical diseases, which are prevalent among the world’s impoverished communities but often draw limited attention, Chagas afflicts more than 7 million people living in Lantin America. Though not usually resulting in death, this disease has lasting adverse impacts, underlining the need for regular attention to control measures for current and emerging vector insects (i.e., triatomine bugs). However, previous vector surveillance and control programs, including routine spraying, were conducted indiscriminately without an objective risk evaluation of vector infestation and parasite prevalence, raising questions about their efficacy.
The research team led by Professor Yasutoshi Kido, in cooperation with the El Salvador Ministry of Health and local governments, addressed this shortcoming by conducting a targeted house-to-house survey of vector species throughout El Salvador. With this purposeful sampling method, the team selected surveyed houses based on their materials and triatomine infestation history before searching for triatomine bugs there. Morphological examination was conducted to identify the insects’ species. Feces from the collected insects were examined by microscope to detect parasite infection. PCR was performed to confirm the presence of Trypanosoma cruzi.
The survey showed that the infestation rate of the principal vector species was as high as 34% (107 out of 311 surveyed houses) and the prevalence of the parasite Trypanosoma cruzi infection in these insects was roughly 10%. Whilst these particular triatomine bugs were ubiquitous across the country, the Trypanosoma cruzi infection was unevenly distributed among the 14 Salvadoran departments (administrative divisions). The findings signal potential active transmission of Chagas disease, suggesting the need for continued and more selective vector control efforts, with particular attention and resources allocated to areas with high infection rates.
This research signifies an intensive collaboration between the OMU scientists and the local and national governments of El Salvador. “This research would not have been possible without the support we received from the Ministry of Health and local governments of El Salvador,” expressed Professor Kido.
Co-first author Yuko Nitahara, M.D., concluded, “Our findings are expected to contribute to cost-effective methods of Chagas vector control, making an advance in our ongoing battle against this real-world neglected tropical disease.”
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Materials provided by Osaka Metropolitan University. Note: Content may be edited for style and length.

Using UT Southwestern’s Cryo-Electron Microscopy Facility, researchers have captured images of an enzyme for Wnt lipidation, which is pivotal to human development and cancer and crucial for Wnt signaling activation. The findings, reported in Nature, shed light on the mechanisms behind this activity and could eventually lead to new drugs to treat various malignancies.
“We are able to push the research envelope further into the key area of cancer-related signaling pathways thanks to UT Southwestern’s state-of-the-art cryo-electron microscopy (cryo-EM) facility,” said Xiaochun Li, Ph.D., Associate Professor of Molecular Genetics and Biophysics, who co-led the study with Yang Liu, a fourth-year graduate student, and Xiaofeng Qi, Ph.D., a postdoctoral researcher. Both Mr. Liu and Dr. Qi work in the Li lab. “The revealed scientific mechanism could accelerate the development of novel cancer-fighting drugs toward advanced solid tumors.”
Scientists have long known that members of the Wnt family of proteins are pivotal for embryonic development, kicking off signaling pathways necessary for functions such as axis formation, cell fate specification, and cell proliferation and migration. When Wnt proteins were first discovered in the early 1980s, they were immediately associated with cancer; aberrant Wnt signaling is known to contribute to pancreatic cancer, melanoma, triple-negative breast cancer, and other types of malignancies.
To perform their signaling functions, Dr. Li explained, Wnt proteins must first be activated by the addition of a lipid molecule, a job performed by an enzyme called Porcupine (PORCN). How this occurs structurally and the mechanism by which investigational drugs inhibit this activity have been unknown.
To investigate, Dr. Li and his colleagues gathered cryo-EM images of four structures: PORCN bound to a co-enzyme called palmitoleoyl-CoA, which contributes the lipid molecule to activate Wnt; PORCN bound to LGK974, an investigational drug known to inhibit Wnt signaling; PORCN bound to LGK974 and WNT3A, a Wnt family member; and PORCN bound to an activated, lipid-modified WNT3A protein. Cryo-EM, a technique recognized by a 2017 Nobel Prize, freezes proteins in place to get atomic-resolution microscopic images.
These images showed that WNT3A, PORCN, and palmitoleoyl-CoA come together in a sandwich-type configuration, with PORCN in the middle flanked by the two other precursors. When WNT3A and PORCN were incubated with LGK974 instead of palmitoleoyl-CoA, the investigational drug took the place of the palmitoleoyl-CoA, blocking its ability to bind and contribute the lipid molecule; without this lipid modification, Dr. Li said, WNT3A can’t set off a signaling cascade.
Additionally, the images solved a decades-old mystery as to why the lipid chain that modifies Wnt proteins differs structurally from that on a related protein called Hedgehog, which is also involved in human development and cancer and activated by lipid modification. While the lipid chain on Hedgehog is made of a saturated fatty acid, causing it to extend into a straight line, the one on PORCN is unsaturated, causing it to kink into a C-shape. The researchers found that this kink is necessary for the lipid chain to fit into a cavity on PORCN, a critical step before transferring it onto Wnt.
Dr. Li noted that LGK974 is one of several drugs that affect Wnt signaling that is currently in clinical trials against various cancers. Knowing the atomic structures of Wnt, PORCN, palmitoleoyl-CoA, and their complexes could lead to drugs better designed to block these interactions.
Dr. Li is a Rita C. and William P. Clements, Jr. Scholar in Biomedical Research.
Other researchers who contributed to this study include Linda Donnelly, Tao Long, Rich W. Zhou, Yingyuan Sun, and Boyuan Wang of UTSW; and Nadia Elghobashi-Meinhardt of Technical University Berlin in Germany.
This work was supported by grants from the Damon Runyon Cancer Foundation (DRR-53S-19), the National Institutes of Health (P01 HL020948, P01 HL160487, R01 GM135343), The Welch Foundation (I-1957), and the Life Sciences Research Foundation. Cryo-EM data were collected at the UT Southwestern Medical Center Cryo-EM Facility, funded in part by an award from the Cancer Prevention and Research Institute of Texas (RP170644).