Publisher Health

New research published in JAMA recommends daily steroid doses for children with Duchenne muscular dystrophy (DMD), marking a significant change in how the disease is treated. University of Rochester Medical Center (URMC) neurologist Robert Griggs, M.D., and Michela Guglieri, M.D., with Newcastle University in the U.K., led the study, which was conducted by a global team of researchers dedicated to improving care for this fatal disease.
“Corticosteroids are likely to remain the main treatment for DMD for the foreseeable future and worldwide so it is critical that we establish a standard of care that is backed by scientific evidence,” said Griggs. “This study shows that health concerns over the daily use of corticosteroids are overstated and that there is a clear benefit in terms of improved motor and pulmonary functions. These findings clearly support the daily regimen over an intermittent one as an initial treatment for boys with DMD.”
DMD is a condition found almost exclusively in boys and characterized by muscle weakness, which appear at age 3-4 and progresses rapidly leading to significant disability. The symptoms eventually spread to the heart and muscles responsible for breathing, and the disease is often fatal by the time the boy reaches his late teens. An estimated 28,000 people in the U.S. suffer from the disease.
While corticosteroids prednisone and deflazacort are known to improve muscle strength and function in patients with DMD and have been a frontline treatment for years, there is currently no universally accepted standard for steroid use in DMD. A global survey of physicians who treat DMD found 29 different regimens, with the most common being ten days on and ten days off. This intermittent dosing regimen was put in place in an effort to limit the potential side effects associated with prolonged steroid use in children, such as weight gain, stunted growth, and loss of bone density.
The Finding the Optimum Regimen of Corticosteroids for DMD (FOR-DMD) study was launched in 2013 to compare daily and intermittent steroid use and establish, from clinical benefit and safety perspective, the most beneficial regimen for DMD patients. Griggs and Kate Bushby, M.D., with Newcastle University initiated the phase 3 clinical trial conducted through the Muscle Study Group, an international network of muscular dystrophy researchers that Griggs helped create in 1997 to advance clinical research in neuromuscular disorders, including DMD.
The new study recruited 196 boys with DMD at 32 research sites across North American and Europe and followed them for three years. Participants were assigned to three groups consisting of daily regimens of prednisone or deflazacort, or intermittent prednisone, and followed for three years. The researchers found that the daily regimens of both drugs significantly slowed disease progression as measured by strength testing and muscle function, as compared to the intermittent group. While the daily regimen increased side effects overall, there were minimal serious side effects.
The lead biostatistician for this study was Michael McDermott, Ph.D., and other URMC investigators include Kimberly Hart, Rabi Tawil, William B. Martens, Barbara E. Herr, and Mary Brown. Other investigators involved in study include Elaine McColl, Chris Speed, Jennifer Wilkinson and Michelle Eagle with Newcastle University, Janbernd Kirschner with University Hospital Frieburg, Germany, Wendy King with Ohio State University, Tracey Willis with the Robert Jones and Agnes Hunt Orthopaedic Hospital in the U.K. The FOR-DMD study was supported with funding from National Institute of Neurological Diseases and Stroke, the Muscular Dystrophy Association, the Parent Project for Muscular Dystrophy, PTC Therapeutics, Sarepta Therapeutics, and Santhera Pharmaceuticals.
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Materials provided by University of Rochester Medical Center. Original written by Mark Michaud. Note: Content may be edited for style and length.

A study by a team of researchers at the Marshall University Joan C. Edwards School of Medicine provides the first published in-depth description of the anti-cancer activity of capsaicin sustained release formulations. Capsaicin is naturally found in chili peppers and is the agent that provides the hot and spicy taste when eating chili peppers. Sustained release formulation of capsaicin are being explored for extended anti-cancer activity.
Recently published in Pharmacology & Therapeutics, a leading medical review journal in the field of pharmacology, the article chronicles the growth-suppressive activity of sustained release capsaicin drugs, including solid dispersion systems, liposomes, phospholipid complexes and nanoparticles. This is the first publication to provide an in-depth description of the anti-cancer activity of capsaicin sustained release formulations. The research team was led by Associate Professor of Biomedical Sciences Piyali Dasgupta, Ph.D., and Professor of Biomedical Sciences Monica Valentovic, Ph.D.
“This review article is the first to provide a comprehensive overview of capsaicin formulations in human cancer,” said Dasgupta, corresponding author on the publication. “Previous publications in the literature only briefly address sustained release formulations of capsaicin.”
The nutritional agent capsaicin displayed robust growth-inhibitory activity in a diverse array of human cancers. However, the clinical applications of capsaicin as a viable anti-cancer agent were hindered by three factors — poor solubility, low bioavailability and spicy flavor.
“Oral use of capsaicin is associated with unfavorable side effects such as stomach cramps, nausea, a burning sensation in the gut and gastrointestinal irritation,” said Valentovic, a senior author on the publication. “A strategy to overcome these drawbacks is the development of different delivery systems, such as encapsulating capsaicin in long-acting sustained release drug delivery systems could allow for more consistent capsaicin levels that could be more efficient as anti-cancer agents.”
In addition to Dasgupta and Valentovic, clinical faculty Maria T. Tirona, M.D., Joshua Hess, M.D., and Paul Finch, M.D., contributed to the publication as well as co-authors Stephen Richbart, Justin Merritt, Ashley Cox, Emily Moles and Katie Brown.
This research was supported by the R15 Academic Research Enhancement Award Grants from the National Institutes of Health (1R15CA161491-01A1, 2R15CA161491-02, 2R15CA161491-03, R15AI151970-01 and1R15HL145573-01), the West Virginia IDeA Network of Biomedical Research Excellence (WV-INBRE) grant (P20GM103434) as well as the National Science Foundation (SURE) and West Virginia NASA State Grant Consortium.
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Skin biopsies are no fun: doctors carve away small lumps of tissue for laboratory testing, leaving patients with painful wounds that can take weeks to heal. That’s a price worth paying if it enables early cancer treatment. However, in recent years, aggressive diagnostic efforts have seen the number of biopsies grow around four times faster than the number of cancers detected, with about 30 benign lesions now biopsied for every case of skin cancer that’s found.
Researchers at Stevens Institute of Technology are now developing a low-cost handheld device that could cut the rate of unnecessary biopsies in half and give dermatologists and other frontline physicians easy access to laboratory-grade cancer diagnostics. “We aren’t trying to get rid of biopsies,” said Negar Tavassolian, director of the Bio-Electromagnetics Laboratory at Stevens. “But we do want to give doctors additional tools and help them to make better decisions.”
The team’s device uses millimeter-wave imaging — the same technology used in airport security scanners — to scan a patient’s skin. (In earlier work, Tavassolian and her team had to work with already biopsied skin for the device to detect if it was cancerous.)
Healthy tissue reflects millimeter-wave rays differently than cancerous tissue, so it’s theoretically possible to spot cancers by monitoring contrasts in the rays reflected back from the skin. To bring that approach into clinical practice, the researchers used algorithms to fuse signals captured by multiple different antennas into a single ultrahigh-bandwidth image, reducing noise and quickly capturing high-resolution images of even the tiniest mole or blemish.
Spearheaded by Amir Mirbeik Ph.D. ’18, the team used a tabletop version of their technology to examine 71 patients during real-world clinical visits, and found their methods could accurately distinguish benign and malignant lesions in just a few seconds. Using their device, Tavassolian and Mirbeik could identify cancerous tissue with 97% sensitivity and 98% specificity — a rate competitive with even the best hospital-grade diagnostic tools.
“There are other advanced imaging technologies that can detect skin cancers, but they’re big, expensive machines that aren’t available in the clinic,” said Tavassolian, whose work appears in the March 23 issue of Scientific Reports. “We’re creating a low-cost device that’s as small and as easy to use as a cellphone, so we can bring advanced diagnostics within reach for everyone.”
Because the team’s technology delivers results in seconds, it could one day be used instead of a magnifying dermatoscope in routine checkups, giving extremely accurate results almost instantly. “That means doctors can integrate accurate diagnostics into routine checkups, and ultimately treat more patients,” said Tavassolian.
Unlike many other imaging methods, millimeter-wave rays harmlessly penetrate about 2mm into human skin, so the team’s imaging technology provides a clear 3D map of scanned lesions. Future improvements to the algorithm powering the device could significantly improve mapping of lesion margins, enabling more precise and less invasive biopsying for malignant lesions.
The next step is to pack the team’s diagnostic kit onto an integrated circuit, a step that could soon allow functional handheld millimeter-wave diagnostic devices to be produced for as little as $100 a piece — a fraction of the cost of existing hospital-grade diagnostic equipment. The team is already working to commercialize their technology and hopes to start putting their devices in clinicians’ hands within the next two years.
“The path forward is clear, and we know what we need to do,” said Tavassolian. “After this proof of concept, we need to miniaturize our technology, bring the price down, and bring it to the market.”
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Materials provided by Stevens Institute of Technology. Note: Content may be edited for style and length.

Mosquitoes. Bane of backyard picnics — and deadly in Zika- and dengue-prone regions.
Most of the world’s mosquitos are opportunistic, willing to drink blood from any nearby source. But in some regions, the mosquitoes that carry Zika, dengue and yellow fever — Aedes aegypti — have evolved to bite humans almost exclusively. But to succeed as a specialized feeder, depending on just one species — ours — to survive, they must have evolved incredibly precise targeting strategies. How do they do it?
“We set out to try to understand how these mosquitoes distinguish human and animal odor,” said Carolyn “Lindy” McBride, an assistant professor of ecology and evolutionary biology and neuroscience, “both in terms of what it is about human odor that they cue in on and what part of their brain allows them to cue in on those signals.”
After years of dedicated work, including countless scientific and technological challenges, her team has discovered answers to both parts of this equation. What is it that the mosquitos are detecting, and how do they detect it? Their results appear in the current issue of Nature.
McBride described their mosquito-centric approach: “We sort of dove into the brain of the mosquito and asked, ‘What can you smell? What lights up your brain? What’s activating your neurons? And how is your brain activated differently when you smell human odor versus animal odor?'”
Then-graduate student Zhilei Zhao, a 2021 Ph.D. alumnus who is now at Cornell, pioneered their novel approach: imaging mosquito brains at very high resolution to watch how the mosquito identifies its next victim. To do that, he had to first genetically engineer mosquitos whose brains lit up when active, and then the team had to deliver human- and animal-flavored air in ways that the mosquitos could detect while inside the team’s custom-built imaging equipment.

A new Yale-led study has for the first time identified which risk factors are more likely to trigger a heart attack or acute myocardial infarction (AMI) for men and women 55 years and younger.
Researchers discovered significant sex differences in risk factors associated with AMI and in the strength of associations among young adults, suggesting the need for a sex-specific preventive strategy. For example, hypertension, diabetes, depression, and poverty had stronger associations with AMI in women compared with men, they found.
The study was published May 3 in JAMA Network Open.
While heart attacks are often associated with older adults, this population-based case-control study examined the relationship between a wide range of AMI-related risk factors among younger adults. The researchers used data from 2,264 AMI patients from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients) study and 2,264 population-based controls matched for age, sex, and race from the National Health and Nutrition Examination Survey (NHANES).
The key finding is that young men and women often have different risk factors. Seven risk factors — including diabetes, depression, hypertension or high blood pressure, current smoking, family history of AMI, low household income, and high cholesterol — were associated with a greater risk of AMI in women. The highest association was diabetes, followed by current smoking, depression, hypertension, low household income, and family history of AMI. Among men, current smoking and family history of AMI were the leading risk factors.
Rates of AMI in younger women have increased in recent years said Yuan Lu, an assistant professor at Yale School of Medicine and the study’s lead author.

Researchers have developed a genetic-risk score for identifying individuals who would benefit the most from lifestyle counselling to prevent gestational and postpartum diabetes.
Gestational diabetes is the most common health-related challenge during pregnancy. Today, it is diagnosed in every fifth expectant mother in Finland. Gestational diabetes has a significant impact on the health of both the mother and the child, both during pregnancy and after delivery.
A study conducted at the University of Helsinki investigated the effects of lifestyle intervention on the prevention of gestational diabetes in women at high risk of developing gestational diabetes. In the Finnish Gestational Diabetes Prevention Study (RADIEL), the study subjects received intensified physical exercise and dietary counselling during pregnancy and for the first year following delivery.
In this study, a polygenic risk score (PRS) describing the genetic risk of diabetes was calculated using gene variants known to increase the risk of type 2 diabetes. The risk score for type 2 diabetes was associated with elevated glucose levels in mid- and late pregnancy as well as one year after delivery.
“Gestational diabetes as well as prediabetes and diabetes one year after delivery were also more common among those with higher scores,” says Emilia Huvinen, specialist in obstetrics and gynaecology.
Targeted measures produce better results
The study discovered that genetic risk also affected the link between lifestyle counselling and gestational diabetes as well as diabetes.
“Based on our research, intensified lifestyle interventions benefitted only women at highest genetic risk of developing type 2 diabetes,” Huvinen confirms.
According to her, the results are significant and even globally unique.
“Our study offers one possible explanation for the contradictory results of previous studies investigating the prevention of gestational diabetes till now ,” Huvinen explains.
According to the researchers, genetic-risk scoring would make it possible to identify the expectant mothers most at risk as well as to direct resources and the most effective preventive measures specifically at them. This would be of great importance in terms of both limited societal resources and the health of these mothers and their children.
“At the same time, it’s important to realise that, in the case of diabetes, our genetic background does not determine our future. With the help of a healthy lifestyle, you can reverse the effect of a high genetic diabetes risk,” Huvinen says, offering encouragement.
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Materials provided by University of Helsinki. Note: Content may be edited for style and length.

Stimulation of certain cerebellar areas could help combat absence seizures. However, what happens at the cellular and molecular level in the brain in this form of epilepsy and how exactly stimulation has an effect is not yet understood in detail. Researchers at Ruhr-Universität Bochum (RUB) have gained new insights by conducting experiments with mice. The team led by Dr. Jan Claudius Schwitalla and Professor Melanie Mark from the RUB Behavioral Neuroscience research group describes the results in the journal “Cellular and Molecular Life Sciences” from 19 March 2022. They cooperated with the Erasmus Medical Center in Rotterdam and Utrecht as well as with colleagues from Bonn, Münster and München.
Abrupt loss of consciousness
More than 1.5 million people worldwide suffer from absence seizures, also known as petit mal seizures. Patients experience an abrupt loss of consciousness and lapse into a paralysis of behaviour that lasts for a few seconds. Absence seizures often occur in children between the ages of four and twelve and are often mistaken for daydreaming. They are linked to altered brain activity, which is visible in brain activity recordings as so-called spike-and-wave discharges (SWDs). The characteristic activity pattern originates from the rhythmic and synchronized activity of nerve cells in the cerebral cortex and thalamus.
Since the nuclei located deep in the cerebellum have a widespread connectivity to various regions of the brain, researchers proposed that it might be possible to treat seizures by stimulating the cerebellar nuclei. Experiments with rodents by other research groups showed that such stimulation can indeed stop absence seizures. However, it is unclear what underlies this effect at the cellular and molecular level.
Cerebellar stimulation against abnormal brain activity
The Bochum-based researchers worked with mice that develop absence seizures due to a lack of the P/Q-type calcium channel in nerve cells of the cerebellum. They found that cells of the cerebellar nuclei were firing abnormally, and that stimulation of these cells could prevent further SWDs. Therefore, they stimulated the cerebellar nuclei by administering a pharmacological substance or via chemogenetic stimulation. For chemogenetic stimulation, a genetically modified receptor is introduced into cells so that they can be activated by a specifically designed molecule normally not present in the brain. This allowed the researchers to slowly increase the activity of the cerebellar nuclei cells and thus prevent the occurrence of further SWDs in mice.
Furthermore, the team used optogenetic stimulation to briefly increase the activity of cells in the cerebellar nuclei and to stop on-going SWDs after they have started. This technique uses proteins from algae that can be turned on by light to increase the activity of nerve cells. Overall, the study confirmed that targeted stimulation of the cerebellar nuclei could become a therapeutic approach for people suffering from absence seizures.
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Materials provided by Ruhr-University Bochum. Original written by Julia Weiler. Note: Content may be edited for style and length.

When the COVID-19 pandemic emerged in early 2020, ultraviolet radiation became one of the go-to methods for preventing the spread of the SARS-CoV-2 virus, along with facemasks, hand sanitizer and social distancing.
The problem: There was little research showing what UV dosage kills the virus. What wavelength? How long? And could UV systems be installed in public places such as airports, bus stations and stores without causing long-term damage to people?
In a newly published study, researchers from Binghamton University’s Thomas J. Watson College of Engineering and Applied Science answer many of those questions and lay the foundation for health standards about what offers true disinfection.
The paper, titled “Systematic evaluating and modeling of SARS-CoV-2 UVC disinfection” and published in Scientific Reports, is written by Distinguished Professor Kaiming Ye, chair of the Department of Biomedical Engineering; BME Associate Professor Guy German and BME Professor Sha Jin, along with PhD student Sebastian Freeman; Zachary Lipsky, PhD ’21; and Karen Kibler from the Biodesign Institute at Arizona State University.
The idea for the research came when shortages of personal protective equipment (PPE) early in the pandemic inspired Ye, German and Binghamton University staff members to quickly build UV disinfection stations for hospitals in the region, so that N-95 masks and other items could be reused.
“There is a lot of research on UV dosages in the scientific literature, but not in a systematic way,” Ye said. “When we started this project, there were really no data or experiments that had been done because the pandemic happened very quickl
Ye and German received funding to pursue their questions through a mid-2020 grant for $182,728 from the National Science Foundation. The Binghamton team added a retrovirus similar to SARS-CoV-2 to three different media (a cell-culture medium, water and an artificial re-creation of human saliva) and exposed them to three different wavelengths in the UVC range. UVC kills viruses and other microorganisms by damaging their DNA and RNA, which are the bioorganic building blocks for life.

Mitochondria serve as the main source of energy production in our cells, and endurance exercise is generally known to improve the function of mitochondria. However, the benefits of exercise in patients with primary mitochondrial diseases, which are heterogeneous and caused by a variety of genetic mutations, were largely unknown.
In a new study, researchers at Children’s Hospital of Philadelphia (CHOP) demonstrated that the benefits of endurance exercise can vary based on the type of mutation involved in mitochondrial disease, and while the benefits of exercise outweigh the risks, the mitochondrial genetic status of patients should be taken into consideration when recommending exercise as therapy. The findings were published online today by the Proceedings of the National Academy of Sciences.
Primary mitochondrial diseases represent the most prevalent inherited metabolic disorders, affecting approximately 1 in every 4,200 people. These disorders can be caused by hundreds of different mutations in the nuclear DNA (DNA within our cells) or mitochondrial DNA (mtDNA, or the DNA within the mitochondria within our cells). Universal treatments for these patients are limited. However, endurance exercise has been shown to improve mitochondrial function in healthy people and reduce the risk of developing secondary metabolic disorders like diabetes or neurodegenerative diorders.
However, these recommendations were based on healthy people without primary mitochondrial disease. Therefore, researchers wanted to determine effectiveness for these patients and whether they are actually benefitting from endurance exercise.
“There was not a concensus among clinicians who see patients with mitochondrial disease whether endurance exercise truly offers benefits,” said Patrick Schaefer, PhD, a postdoctoral fellow at the Center for Mitochondrial and Epigenomic Medicine at CHOP and first author of the study. “Exercise helps create more mitochondria, but if those mitochondria still have the mutations associated with primary mitochondrial disease, there is a chance that exercise may put some patients at risk.”
Because of the heterogeneity of primary mitochondrial disease among patients, the researchers used animal models to study five mutations responsible for the disease. The goal of the study was to determine the relationship between mitochondrial mutations, endurance exercise response, and the underlying molecular pathways in these models with distinct mitochondrial mutations.
The study found that endurance exercise had different impacts on the models depending on the mutation involved. Exercise improved response in the model with the mtDNA ND6 mutation in complex I. The model with a CO1 mutation affecting complex IV showed significantly fewer positive effects related to exercise, and the model with a ND5 complex 1 mutation did not respond to exercise at all. In the model that was deficient in nuclear DNA Ant1, endurance exercise actually worsened cardiomyopathy.
Additionally, the researchers were able to correlate the gene expression profile of skeletal muscle and heart in the model with exercise response and identified oxidative phosphorylation, amino acid metabolism, and cell cycle regulation as key pathways in exercise response, suggesting how the model might be adapted to study exercise responses in humans with primary mitochondrial disease.
Despite mixed responses of the models used in this study, the authors note that the benefits of exercise outweigh the risks in most cases. However, the physical and mitochondrial status of the patient should be taken into account when recommending therapeutic exercises. Additionally, the study could help researchers identify biomarkers and pathways to help predict the mitochondrial response to exercise both in mitochondrial patients and the healthy population harboring different mitochondrial haplogroups.
“This work is of fundamental importance in demonstrating that individuals with different mitochondrial bioenergetics will respond differently to endurance exercise,” said senior study author Douglas C. Wallace, PhD, director of the Center for Mitochondrial and Epigenomic Medicine at CHOP and the Michael and Charles Barnett Endowed Chair in Pediatric Mitochondrial Medicine and Metabolic Diseases. “This is of broad relevance to individuals ranging from athletes to patients with mitochondrial disease, and everyone in between.”
This study was supported by the German Research Foundation through grant SCHA 2182/1-1, the National Institutes of Health grants NS021328, MH108592, and OD010944, and U.S. Department of Defense grants W81XWH16-1-0401 and W81XWH-21-1-0128. Schematics were created with BioRender.com.

Genes are the carriers of our genetic information. They are read in our cells and used to produce ribonucleic acids (RNAs). During this process, termed transcription, the enzyme RNA polymerase II has a decisive influence on the exact time at which genes are read and on the intensity with which this happens. In their recent Nature Communications article, researchers from the University of Bayreuth have shown exactly how RNA polymerase II is activated in nerve cells, and how this stimulates gene expression, the targeted use of genetic information. Their discoveries contain valuable starting points for further biomedical research.
The new research results were obtained in close cooperation between the Bayreuth research team led by Dr. Claus-D. Kuhn and partner universities in South Korea and Switzerland. In the jointly discovered mechanism the team found enhancer RNAs (eRNAs) to play a key role in activating RNA polymerase II — Pol II for short. Enhancer RNAs are non-coding, i.e. they are RNA molecules that are not used as blueprints for protein production. As the researchers were able to decipher, enhancer RNAs switch on the activity of Pol II. They do so by detaching NELF (Negative Elongation Factor), a large molecular complex bound to Pol II, from Pol II. NELF normally blocks Pol II activity by binding to it.
However, enhancer RNAs can only act as “liberators” of Pol II under two conditions: They need to have a minimum length and they need to be of a characteristic molecular composition. If both these conditions are met, multivalent interactions occur between the long enhancer RNAs and the NELF complex, as the Bayreuth researchers discovered. This means that enhancer RNAs simultaneously dock to a number of different binding sites that are distributed over several subunits of NELF. Only by means of these interactions are they able to detach NELF from Pol II. Enhancer RNAs thereby ensure that Pol II is reactivated and resumes the process of transcription following the NELF-induced paused state. “For the first time, we have succeeded in demonstrating a direct mechanistic connection between enhancer RNAs and the transcription process controlled by Pol II, which is a key component of gene expression,” says Dr. Claus-D. Kuhn, Heisenberg Professor for RNA Biochemistry at the University of Bayreuth.
The Bayreuth researchers and their cooperation partners gained their new insights by studying cortical neurons in mice. As soon as these neurons are stimulated by electrical stimuli, they produce large amounts of enhancer RNAs for a short period of time. These non-coding RNAs then activate genes that are important for nerve growth and their improved interconnectivity. They achieve this by detaching the NELF complex from Pol II. “To the best of our knowledge, this is the first time that a direct, mechanistic link between neuronal activity, enhancer transcription, and gene activation has been shown,” says Bayreuth biochemist Dr. Vladyslava Gorbovytska, first author of the study. “In the future, the knowledge we have gained could make it possible to specifically modulate brain activity. This would be a significant asset for the treatment of many neurodegenerative diseases.”
The study, published in Nature Communications, also expands previous knowledge regarding the role of enhancers, which are regulatory areas in DNA. Enhancers are known to be indispensable for initiating transcription in higher organisms, such as humans. This is the case as they serve as binding platforms for so-called transcription factors. The research conducted at the University of Bayreuth now shows that they influence gene expression in yet another, universally applicable way: Enhancers are read by Pol II, resulting in large amounts of enhancer RNAs. In this respect, these non-coding RNAs owe their existence precisely to the enzyme that they later release from a paused state and activate.
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