Publisher Health

Although there are some cultural exceptions to the rule, medicines for children are often given in liquid form that is sweetened to make it taste good. But not every child experiences the same medicine in the same way.
A multidisciplinary research group specializing in pediatrics, genetics, and psychophysics, co-led by Julie A. Mennella, PhD, Principal Investigator at the Monell Chemical Senses Center, has identified wide variation in the sensory perception of a pediatric formulation of ibuprofen — some that were tied to genetic ancestry, and some that were not. These findings indicate that a range of factors come into play in determining how a medicine tastes to an individual. Their work, recently published in the International Journal of Molecular Sciences, is the first in a series of studies funded by the National Institutes of Health to look at variation in the taste of medicines.
“Taste is personal and determining how individuals differ and why is critical to understanding medication adherence and personal risks,” said Mennella. Bitter taste and irritating sensations in the throat are the top reasons for non-compliance, as a child (or adult) is less likely to ingest a medicine that is unpleasant (or tastes bad). However, if a child finds the medicine bottle uncapped and finds it tastes sweet like candy, they may ingest too much. Discovering how individuals differ in sensory perception is especially key when it comes to liquid ibuprofen, which accounts for many unintentional poison exposures among children under the age of six years in the US, according to the U.S. Poison Centers.
“Sweetening medicines like ibuprofen is a delicate balance between having it taste good enough that kids take it, but bitter enough that, should they get unguarded access to it, it’s irritating enough that they stop drinking it and don’t poison themselves” said Mennella. “We found genetic markers, both ancestry-related and independent of it, that could predict if someone would find a medication irritating or pleasantly sweet. If we get to the point of tailor-making medications in the future, knowing these associations could help us design taste specifically for each child in the not-so-distant future.”
The study included 154 adult panelists from Philadelphia, who represented the diversity of their city. According to a genome-wide association study, 63 had African ancestry, 51 European, 13 South Asian, seven East Asian, and seven American. They underwent training in sensory methods and then rated the sweetness, irritation, bitterness, and palatability of a pediatric formulation of a berry-flavored ibuprofen after swallowing, and also after just tasting it without swallowing.
Researchers found that panelists of African genetic ancestry had fewer chemesthetic sensations such as tingling or an urge to cough, rated the medicine as tasting sweeter and more palatable than those of European genetic ancestry. Researchers also found a novel association between the TRPA1rs1198875 genetic variation and tingling sensations, independent of ancestry. This is significant as TRPA1 is a family of neuron receptors that are involved in sensory neural response to a variety of chemical irritants found in foodstuff and other medicines.
Discovering both an ancestry-related link and non-ancestry-related genetic variation to taste and irritation perception shows that who perceives a medicine as palatable or not is a complicated picture and must consider a variety of factors.

As the days get shorter and chillier in the northern hemisphere, those who choose to work out in the mornings might find it harder to get up and running. A new study in PNAS identifies a protein that, when missing, makes exercising in the cold that much harder — that is, at least in fruit flies.
A team from University of Michigan Medical School and Wayne State University School of Medicine discovered the protein in flies, which they named Iditarod after the famous long distance dog sled across Alaska, while studying metabolism and the effect of stress on the body.
They were particularly interested in a physiological process called autophagy wherein damaged parts of cells are removed from the body. In screening the fly genome, they found a candidate for regulating the critical housekeeping procedure.
They demonstrated the link between autophagy and Iditarod, or Idit, by tweaking the genetic makeup of some flies to overactivate autophagy in their eyes. Flies with too much autophagy had massive cell death leading to visible degeneration of the eye. Inactivating Idit gene restored the normal eye structure, indicating that Idit gene is involved in the autophagy process.
The team’s next step was to look for a similar gene, or homolog, in humans.
“When we queried this gene in the human genome, a gene called FNDC5, which is a precursor to the protein irisin, was the top hit,” said Jun Hee Lee, Ph.D, of the U-M Department of Molecular and Integrative Physiology.
Previous research has shown irisin to be an important hormone involved in producing musculoskeletal and other benefits of exercise in mammals, as well as playing a role in adaptation to cold temperatures.

One promising approach to treating Type 1 diabetes is implanting pancreatic islet cells that can produce insulin when needed, which can free patients from giving themselves frequent insulin injections. However, one major obstacle to this approach is that once the cells are implanted, they eventually run out of oxygen and stop producing insulin.
To overcome that hurdle, MIT engineers have designed a new implantable device that not only carries hundreds of thousands of insulin-producing islet cells, but also has its own on-board oxygen factory, which generates oxygen by splitting water vapor found in the body.
The researchers showed that when implanted into diabetic mice, this device could keep the mice’s blood glucose levels stable for at least a month. The researchers now hope to create a larger version of the device, about the size of a stick of chewing gum, that could eventually be tested in people with Type 1 diabetes.
“You can think of this as a living medical device that is made from human cells that secrete insulin, along with an electronic life support-system. We’re excited by the progress so far, and we really are optimistic that this technology could end up helping patients,” says Daniel Anderson, a professor in MIT’s Department of Chemical Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES), and the senior author of the study.
While the researchers’ main focus is on diabetes treatment, they say that this kind of device could also be adapted to treat other diseases that require repeated delivery of therapeutic proteins.
MIT Research Scientist Siddharth Krishnan is the lead author of the paper, which appears today in the Proceedings of the National Academy of Sciences. The research team also includes several other researchers from MIT, including Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, as well as researchers from Boston Children’s Hospital.
Replacing injections
Most patients with Type 1 diabetes have to monitor their blood glucose levels carefully and inject themselves with insulin at least once a day. However, this process doesn’t replicate the body’s natural ability to control blood glucose levels.

Adding more natural areas across our towns and cities could cool them by up to 6°C during heatwaves, according to new research from the University of Surrey’s Global Centre for Clean Air Research (GCARE).
After a year of monitoring temperatures in four distinct areas of Guildford, England, researchers found that nature-based locations — woodlands, grasslands, and lakes — were up to 3°C cooler on average than built-up areas.
Researchers from the GCARE are now urging town and city planners to focus on adding ‘green’ and ‘blue’ areas to help combat increasingly frequent annual heatwaves.
Professor Prashant Kumar, co-author of the study and Founding Director of GCARE, is endorsing a national tree-planting and nature-based solutions initiative:
“With global temperatures soaring and the UK recording its hottest-ever temperature in July 2022, our research adds to the growing body of evidence that confirms that nature is the key to keeping our urban areas cool.
“We recommend planting trees in as many public spaces as possible, especially around our schools, as a great starting point to help communities tackle the urban heat island effect. Water bodies, such as lakes and ponds, can also help cool areas, and could be useful for managing excess stormwater.”
Researchers monitored temperatures continuously from June 2021 until the end of August 2022, with temperature sensors placed two to three metres above ground level. The sensors captured data every minute, taking 633,780 readings in total.
Researchers found that during the summer of 2022, there was an increased likelihood of more intense and longer-lasting heatwaves compared to 2021. The built-up area frequently exceeded the heatwave threshold of 28°C. On 19 July 2022, which was the most extreme day of the year and the hottest day ever recorded in the UK, the temperature soared to 40.7°C.
Professor Kumar added:
“We want our data to help build city-scale environmental models and assist planners and ordinary citizens in incorporating natural elements into built-up areas. This work aligns with Sustainable Development Goals 11 (sustainable cities and communities) and 13 (climate action).”

A UCSF telecare program that improves outcomes for patients with dementia and lightens the load for unpaid caregivers also has the surprising bonus of cutting Medicare costs, according to UC San Francisco research.
In the study, publishing in JAMA Internal Medicine on Sept. 18, 2023, researchers, led by UCSF, compared the Medicare costs of 780 patients with dementia. The patients were randomized 2:1 to receive Care Ecosystem support — which included medical and practical assistance — or their usual care for a 12-month period. Both groups were similar in age, severity of dementia and other illnesses, as well as age of the caregiver, who was typically a spouse or adult child.
The researchers found that the average monthly Medicare cost, per patient, for those in the Care Ecosystem was $526 lower than for those receiving usual care.
Starting July 2024, the UCSF telecare program, together with similar initiatives, will be available to patients with dementia living at home or in an assisted living facility, who are covered by Medicare fee-for-service or have dual Medicare and Medicaid eligibility.
Navigators help with meds, transportation, daycare, respite care
The Care Ecosystem was implemented by UCSF in 2014 and has since been replicated by more than 25 organizations, including health systems, specialty practices and community-based groups. The program connects patients and caregivers with a navigator, who serves as the central hub, and helps to troubleshoot issues as they arise by conveying instructions from clinicians and other experts.
Navigators deal with issues as diverse as medication and symptom management, daycare placement, respite care, transportation and home safety hacks.

Scientists at the Max Planck Institute for Chemical Ecology in Jena are investigating the previously largely unknown biosynthetic pathway that leads to the formation of cardenolides in plants. In a study published in the journal Nature Plants, they present two enzymes from the CYP87A family as key enzymes that catalyze the formation of pregnenolone, the precursor for the biosynthesis of plant steroids, in two different plant families. The discovery of such enzymes should help to develop platforms for the cheap and sustainable production of high quality steroid compounds for medical use.
Plants produce an impressive array of metabolites, including many medically valuable steroids. Well-known examples of this class of substances obtained from plants are cardenolides. As early as 1785, the British physician William Withering (1741-1799) published a book on the red foxglove and its use in medicine (An account of the foxglove, and some of its medical uses: with practical remarks on dropsy, and other diseases. Birmingham 1785). He had found out in experiments that taking extracts of the plant increased the flow of urine in sick people, thus treating water retention in the body. However, he did not know that the active ingredients in foxglove leaves had a direct effect on the heart. Since the second half of the 19th century, cardenolides, cardiac glycosides from plants, have been used to treat of heart failure or arrhythmia because of their effect on the heart muscle.
“In addition to their effect on the contractility of the heart, cardenolides have been used with great success in recent years for the treatment of various cancers. However, the corresponding plant biosynthetic pathways have remained largely unknown despite the success of these steroid molecules in human medicine. Our goal was therefore to understand how plants synthesize these highly complex molecules from predicted but simple precursors,” explains first author Maritta Kunert.
In addition to foxglove Digitalis purpurea, the research team also studied another plant species, the rubber tree Calotropis procera. Although these two plants belong to different plant families, they both produce large amounts of cardenolides. Since the species studied are not model plants whose genomes have been sequenced and for which many gene functions are known, the project was initially something of a “black box” for the researchers, as they had no existing data sets or standard methods to fall back on. The starting point for the study was earlier work in a related species of foxglove, which suggested that the biosynthesis occurred via the molecule pregnenolone, sometimes referred to as the “mother of all steroid hormones” because all major steroid hormones such as testosterone, progesterone and estrogen in humans can be traced back to the precursor pregnenolone.
“We identified the candidate genes involved in cardenolide biosynthesis by comparative analysis of the two plant species. The structures of the cardenolides in these plants have both overlapping and divergent profiles. Therefore, comparing information about the plants’ genomes, in particular which genes are expressed in these two plants in relation to the formation of metabolites, was very helpful in identifying the enzymes involved in the formation of pregnenolone,” says study leader Prashant Sonawane, who heads the project group “Steroidal Specialised Metabolism in Plants” in the Department of Natural Product Biosynthesis.
In addition, the scientists did not even know where the metabolites of interest were accumulated in the different parts of plants. “The tissue-specific localization of the cardenolides was crucial for using the genetic data sets in a way that allowed the selection of 13 candidate genes. Comparing these datasets across different plants helped us to reduce the number of candidate genes for further characterization,” explains Prashant Sonawane.
Finally, two enzymes of the cytochrome P450 family 87A were identified that catalyze the conversion of both cholesterol and phytosterols into pregnenolone in foxglove and Calotropis procera. This was the first step in the cardenolide biosynthetic pathway in these two only distantly related plants. Importantly, this is the first enzymatic function reported for this subfamily of cytochrome P450.
The scientists tested their findings by modifying plants of the model system Arabidopsis thaliana to produce more CYP87A enzymes. The genetically modified Arabidopsis plants accumulated unusually high levels of pregnenolone. Further evidence for the involvement of CYP87A enzymes in the formation of pregnenolone came from genetically modified foxglove plants that lacked CYP87A enzymes in their leaves. In these plants, the formation of pregnenolone and cardenolides was greatly reduced. The authors established the first stable transformation system to modify foxglove plants for the study of specialised metabolites.
The research team is far from satisfied with deciphering the first enzymatic step of cardenolide biosynthesis. “We are already working on the downstream steps for the formation of cardenolides in different plant species. This biosynthetic pathway is long and highly complex. With the ability to apply the latest sequencing, bioinformatics and metabolomics methods across multiple plant species, we hope to solve this puzzle soon,” says Prashant Sonawane.
Plants produce many pharmaceutical compounds. The extraction of these natural products is still very complex and often not very sustainable. The Department of Natural Product Biosynthesis at the Max Planck Institute for Chemical Ecology, led by Sarah O’Connor, aims to elucidate the biosynthetic pathways of important phytochemicals with medical relevance. “The discovery of enzymes such as CYP87A can help develop biological platforms for the sustainable production of high-value plant compounds by using other plants for their biosynthesis,” says Sarah O’Connor.

New research provides insight about the bedrock scientific principle that mitochondrial DNA — the distinct genetic code embedded in the organelle that serves as the powerplant of every cell in the body — is exclusively passed down by the mother.
The study, a collaboration among Oregon Health & Science University and other institutions, published today in the journal Nature Genetics.
Scientists have long recognized the fact that mitochondrial DNA, or mtDNA, comes exclusively from egg cells in humans, meaning only the mother contributes the genetic code carried by thousands of mitochondria necessary for energy production in every cell in the body.
Previously, it was believed that paternal mtDNA was eliminated soon after a sperm fuses with an oocyte, or developing egg, during fertilization, possibly through an immune-like search-and-destroy response.
However, the study found that while mature sperm do carry a small number of mitochondria, they lack intact mtDNA.
“We found that each sperm cell does bring 100 or so mitochondria as organelles when it fertilizes an egg, but there is no mtDNA in them,” said co-author Shoukhrat Mitalipov, Ph.D., director of the Center for Embryonic Cell and Gene Therapy at OHSU.
Researchers found that sperm cells are not only devoid of intact mtDNA, but they also lacked a protein essential for mtDNA maintenance, known as mitochondrial transcription factor A, or TFAM.

Researchers at The University of Texas MD Anderson Cancer Center have discovered that certain nano-based cancer therapies may be less effective in younger patients, highlighting the need for further investigation into the impact of aging on the body’s ability to respond to treatment.
The researchers found age-related differences are due to how effectively the liver filters the bloodstream. Younger livers are more efficient at this process, which helps limit toxins in the blood but also filters out beneficial treatments, potentially rendering them ineffective.
The study, published today in Nature Nanotechnology, was led by Wen Jiang, M.D., Ph.D., associate professor of Radiation Oncology, and Betty Kim, M.D., Ph.D., professor of Neurosurgery.
“Put simply, our liver is designed to protect us, but for young people it might also be protecting them in a way that limits the effectiveness of nanotherapies,” Jiang said. “There’s so much interest right now in nano-scale delivery systems and designs, but nobody has really considered how age plays a role in the effectiveness of these systems. In preclinical models, younger livers actually work so well that they filter out a significant amount of the nanomedicine. That means, in some cases, these drugs may be less effective in younger patients than in older ones.”
Unlike traditional cancer therapies, in which medicine is directly introduced to the body, nanomedicines use nano-scale carriers to deliver treatments. Some of the advantages of nanomedicine formulations can include reduced toxicity, increased target specificity and increased dosage, depending on the goal of the treatment.
To date, more than 50 nano-based therapies have been approved by the Food and Drug Administration, including 19 currently listed by the National Cancer Institute for use in cancer. The study treatment was nanoparticle-albumin-bound paclitaxel, which has been used since 2005 for certain refractory or relapsed cancers.
Scientists do not fully understand all the mechanisms for how, exactly, the liver filters the bloodstream, but previous studies have indicated a correlation between the rate of clearance and the expression of the scavenger receptor MARCO. This protein is expressed more in younger Kupfer cells, the immune cells that reside in the liver.

Artificial intelligence (AI) and machine learning (ML) can effectively detect and diagnose Polycystic Ovary Syndrome (PCOS), which is the most common hormone disorder among women, typically between ages 15 and 45, according to a new study by the National Institutes of Health. Researchers systematically reviewed published scientific studies that used AI/ML to analyze data to diagnose and classify PCOS and found that AI/ML based programs were able to successfully detect PCOS.
“Given the large burden of under- and mis-diagnosed PCOS in the community and its potentially serious outcomes, we wanted to identify the utility of AI/ML in the identification of patients that may be at risk for PCOS,” said Janet Hall, M.D., senior investigator and endocrinologist at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, and a study co-author. “The effectiveness of AI and machine learning in detecting PCOS was even more impressive than we had thought.”
PCOS occurs when the ovaries do not work properly, and in many cases, is accompanied by elevated levels of testosterone. The disorder can cause irregular periods, acne, extra facial hair, or hair loss from the head. Women with PCOS are often at an increased risk for developing type 2 diabetes, as well as sleep, psychological, cardiovascular, and other reproductive disorders such as uterine cancer and infertility.
“PCOS can be challenging to diagnose given its overlap with other conditions,” said Skand Shekhar, M.D., senior author of the study and assistant research physician and endocrinologist at the NIEHS. “These data reflect the untapped potential of incorporating AI/ML in electronic health records and other clinical settings to improve the diagnosis and care of women with PCOS.”
Study authors suggested integrating large population-based studies with electronic health datasets and analyzing common laboratory tests to identify sensitive diagnostic biomarkers that can facilitate the diagnosis of PCOS.
Diagnosis is based on widely accepted standardized criteria that have evolved over the years, but typically includes clinical features (e.g., acne, excess hair growth, and irregular periods) accompanied by laboratory (e.g., high blood testosterone) and radiological findings (e.g., multiple small cysts and increased ovarian volume on ovarian ultrasound). However, because some of the features of PCOS can co-occur with other disorders such as obesity, diabetes, and cardiometabolic disorders, it frequently goes unrecognized.
AI refers to the use of computer-based systems or tools to mimic human intelligence and to help make decisions or predictions. ML is a subdivision of AI focused on learning from previous events and applying this knowledge to future decision-making. AI can process massive amounts of distinct data, such as that derived from electronic health records, making it an ideal aid in the diagnosis of difficult to diagnose disorders like PCOS.

Hospital staff spend a significant amount of time working to protect patients from acquiring infections while they are being cared for in the hospital. They employ various methods from hand hygiene to isolation rooms to rigorous environmental sanitation. Despite these efforts, hospital-onset infections still occur — the most common of which is caused by the bacterium Clostridioides difficile, or C. diff, the culprit of almost half a million infections in the U.S. each year.
Surprising findings from a new study in Nature Medicine suggest that the burden of C. diff infection may be less a matter of hospital transmission and more a result of characteristics associated with the patients themselves.
The study team, led by Evan Snitkin, Ph.D. and Vincent Young, M.D., Ph.D., both members of the Departments of Microbiology & Immunology and Internal Medicine/Infectious Diseases at University of Michigan Medical School and Mary Hayden, M.D. of Rush University Medical Center, leveraged ongoing epidemiological studies focused on hospital-acquired infections that enabled them to analyze daily fecal samples from every patient within the intensive care unit at Rush University Medical Center over a nine-month period.
Arianna Miles-Jay, a postdoctoral fellow in Dr. Snitkin’s lab, analyzed the over 1,100 patients in the study, and found that a little over 9% were colonized with C. diff. Using whole genome sequencing at U-M of 425 C. difficile strains isolated from nearly 4000 fecal specimens, she compared the strains to each other to analyze spread.
“By systematically culturing every patient, we thought we could understand how transmission was happening. The surprise was that, based on the genomics, there was very little transmission.”
Essentially, there was very little evidence that the strains of C. diff from one patient to the next were the same, which would imply in-hospital acquisition. In fact, there were only six genomically supported transmissions over the study period. Instead, people who were already colonized were at greater risk of transitioning to infection.
“Something happened to these patients that we still don’t understand to trigger the transition from C. diff hanging out in the gut to the organism causing diarrhea and the other complications resulting from infection,” said Snitkin.