Publisher Health

Exposure to a large-scale disaster, such as a tsunami, impacts population health over a decade later. A new study by an inter-disciplinary team of researchers in the United States and Indonesia has found that women who lived along the coast of Aceh, Indonesia when it was hit by waves from the 2004 tsunami have lower cortisol levels 14 years later than women who lived in other, nearby coastal communities that were not directly affected.
Cortisol is a stress hormone produced by the adrenal glands. Cortisol levels rise in response to stress as part of the fight or flight response, but consistently elevated stress can result in dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. The study links the stresses from exposure to the tsunami to “burnout” of the HPA-axis manifest in low cortisol levels over the long-term.
“These effects are greatest for women who reported elevated levels of post-traumatic stress symptoms for two years after the tsunami,” said Elizabeth Frankenberg who, with Duncan Thomas and Cecep Sumantri, leads a long-term survey project, the Study of the Tsunami Aftermath and Recovery (STAR).
They and their colleagues have been studying survivors of the Indonesian tsunami who were first interviewed before the tsunami. For this research, they collected hair samples from adults 14 years after the tsunami. “Ralph Lawton was a Duke undergraduate and Robertson Scholar when he went to Indonesia to collect the hair and establish the assay in our lab in Yogyakarta: he is incredibly impressive and the first author of the manuscript,” said Duncan Thomas.
He continued that “An important finding is that people with low levels of cortisol are in worse physical and psycho-social health 14 years after the tsunami, evidence of the long reach of the stresses of the tsunami and its aftermath.”
Elizabeth Frankenberg pointed out that visually, the damage wrought by the Indian Ocean tsunami on the built and natural landscape along the coast of Aceh, Indonesia, looks remarkably similar to the damage from hurricanes and intense storms along the coast of North Carolina and other parts of the U.S. “Lessons learned from following people in Aceh over 20 years provides important insights into the likely longer-term impacts of climate change on populations in the U.S. and across the globe,” said Frankenberg.
STAR is a collaborative project involving investigators at the University of North Carolina at Chapel Hill, Duke University, SurveyMETER (Indonesia), Harvard University, the University of California, Los Angeles (UCLA) and the University of Southern California. This research received financial support from the National Institutes on Aging (R01AG031266, R01 AG065395, R24AG054365 and T32AG51108), the Eunice Kennedy Shriver National Institute for Child Health and Human Development (R01HD052762, P2C HD050924), National Institute of General Medical Sciences (T32GM144273) and the Wellcome Trust (OPOH 106853/A/15/Z).

People overeat and become overweight for a variety of reasons. The fact that flavorful high-calorie food is often available nearly everywhere at any time doesn’t help. Buck researchers have determined for the first time why certain chemicals in cooked or processed foods, called advanced glycation end products, or AGEs, increase hunger and test our willpower or ability to make healthy choices when it comes to food.
“This research, done in tiny nematode worms, has immense implications for human dietary choices and the propensity to overeat certain foods,” said Buck professor Pankaj Kapahi, PhD, the senior author of the study. “Processed modern diets enriched with AGEs are tempting to eat but we know very little about their long-term consequences on our health.” The work is currently published in eLife.
“Humans evolved certain mechanisms that encourage us to eat as much food as possible during times of plenty. We store the excess calories as fat that we use to survive times of fasting,” explained Muniesh Muthaiyan Shanmugam, PhD, a postdoctoral research fellow in the Kapahi laboratory, and the lead author of the study. “Natural selection favored genes that makes us preferentially consume flavorful food, especially those with higher sugar content. But what is the mechanism that makes it so hard to say ‘no’ to them?”
AGEs are metabolic by-products that occur when a sugar combines with part of a protein, lipid or nucleic acid. They occur naturally when we metabolize sugars in a cell, but AGEs are also created during baking, frying and grilling, and are in many processed foods. “The brown color that occurs during cooking, which makes food look and smell delicious is a result of AGEs,” said Shanmugam. “Basically, we are finding that AGEs make food more appetizing and harder to resist.”
The “browning” reaction that occurs when sugar and protein interact with heat, beloved among chefs, is called the Maillard reaction. It results in the formation of hundreds to thousands of enticing AGEs.
But while the Maillard reaction’s claim to fame is its ability to make foods taste delicious, the resulting chemicals wreak all kinds of havoc in the body. They cause inflammation and oxidative damage, contributing to the development of blood vessel stiffening, hypertension, kidney disease, cancer, and neurological problems. The accumulation of these metabolic by-products in several organs is probably one of the major drivers of aging of various organs and the organism as a whole, said Kapahi, whose lab focuses on how nutrients influence health and disease.
“Once advanced glycation products are formed, they cannot be detoxified,” Shanmugam said. Just as toasted white bread becomes brown, the process can’t be reversed to make the bread white again. “Similarly, there is no way to reverse the AGEs,” adding that the body’s ability to clear AGEs declines with age, providing another link to age-related disease.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide, with a 5-year survival rate of less than 10%. Many PDAC tumors in early stage go undetected because they are not found using conventional imaging methods, including fluorodeoxyglucose positron emission tomography (PET) scans. To more efficiently combat this pancreatic cancer, a team led by researchers at Osaka University is combining diagnostic and therapeutic procedures into a single integrated process: ‘theranostics’.
In an article recently published in Journal of Nuclear Medicine, the team has developed a ‘radio-theranostics’ strategy that uses a new radioactive antibody to target glypican-1 (GPC1), a protein highly expressed in PDAC tumors. Theranostics, particularly radio-theranostics, has been receiving increasing attention because, by radio-labeling the compounds used to target certain molecules in cancer cells, diagnosis and treatment can be carried out sequentially.
“We decided to target GPC1 because it is overexpressed in PDAC but is only present in low levels in normal tissues,” explains Tadashi Watabe, lead author of the study.
The team used a monoclonal antibody (mAb), an antibody designed to target a certain molecule, to target GPC1. The mAb could be labeled with radioactive zirconium (89Zr) or radioactive astatine (211At). They worked with a xenograft mouse model, which involved human pancreatic cancer cells being injected into a mouse that developed into a full tumor that could be experimentally treated and monitored. These mice were intravenously administered 89Zr-labeled GPC1 mAb. They were also given 211At-labeled GPC1 mAb to examine the antitumor effects.
“We monitored 89Zr-GPC1 mAb internalization over seven days with PET scanning,” explains Kazuya Kabayama, the second author of the article. “There was strong uptake of the mAb into the tumors, suggesting that this method could support tumor visualization. We confirmed that this was mediated by its binding to GPC1, as the xenograft model that had GPC1 expression knocked out showed significantly less uptake.”
The researchers next tested this model with alpha therapy using 211At-GPC1 mAb, a method that could support radioactive label-based delivery of a therapeutic molecule to its target. Administration of 211At-GPC1 mAb resulted in DNA double-strand break induction in the cancer cells, as well as significantly reduced tumor growth. Control experiments showed that these antitumor effects did not occur when mAb internalization was blocked. Additionally, non-radiolabeled GPC1 mAb did not induce these effects.
“Both radiolabeled versions of the GPC1 mAb we examined showed promising results in PDAC,” says Watabe. “89Zr-GPC1 mAb showed high tumoral uptake, while 211At-GPC1 mAb could be used for targeted alpha therapy to support suppression of PDAC tumor growth.”
These highly impactful data demonstrate the potential for using a theranostics approach in PDAC, a disease in dire need of new diagnostic and therapeutic options. In the future, this could lead to early detection of PDAC with PET imaging and systemic treatment with alpha therapy.

What if organ damage could be repaired by simply growing a new organ in the lab? Improving researchers’ ability to print live cells on demand into geometrically well-defined, soft complex 3D architectures is essential to such work, as well as for animal-free toxicological testing.
In a study recently published in ACS Biomaterials Science and Engineering, researchers from Osaka University have overcome prior limitations that have hindered cell growth and the geometrical fidelity of bioprinted architectures. This work might help bring 3D-printed cell constructs closer to mimicking biological tissue and organs.
Ever since bioprinting was first reported in 1988 by using a standard inkjet printer, researchers have explored the potential of this layer-by-layer tissue assembly procedure to regrow damaged body parts and test medical hypotheses. Bioprinting is to eject a cell-containing “ink” from a printing nozzle to form 3D structures. It is usually easier to print hard rather than soft structures. However, soft structures are preferable in terms of cell growth in the printed structures. When printing soft structures, doing so in a printing support is effective; however, solidification of ink in the support filled in a vessel can result in its contamination with unwanted substances from the support. Ink solidification into a soft matrix using a printing support without contamination, while retaining cell viability, was the goal of this work.
“In our approach, a 3D printer alternately dispenses the cell-containing ink and a printing support,” explains Takashi Kotani, lead author of the study. “The interesting point is that the support also plays a role in facilitating the solidification of the ink. All that’s necessary for ink solidification is in the support, and after removing the support, the geometry of the soft printed cell structures remains intact.”
Hydrogen peroxide from the support enabled an enzyme in the ink to initiate gelation of the ink, resulting in a gel-enclosed cell assembly within a few seconds. This rapid gelation prevented contamination of the assembly during formation. After removing the support, straightforward 3D constructs such as inverted trapezium geometries as well as human nose shapes — including bridges, holes, and overhangs — were readily obtained.
“We largely retain mouse fibroblast cell geometry and growth, and the cells remain viable for at least two weeks,” says Shinji Sakai, senior author. “These cells also adhere to and proliferate on our constructs, which highlights our work’s potential in tissue engineering.”
This new technique is an important step forward to engineering human cell assemblies and tissues. Further work might involve further optimizing the ink and support, as well as incorporating blood vessels into the artificial tissue to improve its resemblance to physiological architectures. Regenerative medicine, pharmaceutical toxicology, and other fields will all benefit from this work and further improvements in the precise fidelity of bioprinting.

An international team of interdisciplinary researchers has successfully created a method for better 3D modelling of complex cancers.
The University of Waterloo-based team combined cutting-edge bioprinting techniques with synthetic structures or microfluidic chips. The method will help lab researchers more accurately understand heterogeneous tumours: tumours with more than one kind of cancer cell, often dispersed in unpredictable patterns.
Traditionally, medical practitioners would biopsy a patient’s tumour, extract cells, and then grow them in flat petri dishes in a lab. “For fifty years, this was how biologists understood tumours,” said Nafiseh Moghimi, an applied mathematics post-doctoral researcher and the lead author of the study. “But a decade ago, repeated treatment failures in human trials made scientists realize that a 2D model does not capture the real tumour structure inside the body.”
The team’s research addresses this problem by creating a 3D model that not only reflects the complexity of a tumour but also simulates its surrounding environment.
The research, which took place in the Mathematical Medicine Lab under the supervision of applied mathematics professor Mohammad Kohandel, united advancements from several disciplines. “We are creating something that is very, very new in Canada. Maybe just a couple of labs are doing something even close to this research,” Moghimi said.
First, the team created polymer “microfluidic chips”: tiny structures etched with channels that mimic blood flow and other fluids surrounding a patient’s tumour.
Next, the team grew multiple types of cancer cells and suspended these cell cultures in their own customized bioink: a cocktail of gelatine, alginate, and other nutrients designed to keep the cells cultures alive.

You might imagine that you’re healthier in the summer. The sun is shining, we get plenty of vitamin D, and the days are long.
However, recent research from the University of Copenhagen suggests that eating habits in winter may be better for our metabolic health than eating habits in summer, at least if you’re a mouse. Researchers have examined the metabolism and weight of mice exposed to both ‘winter light’ and ‘summer light’.
“We found that even in non-seasonal animals, differences in light hours between summer and winter do cause differences in energy metabolism. In this case, body weight, fat mass and liver fat content,” says Lewin Small, who carried out the research while a postdoc at Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen. He adds:
“We found this mostly in mice exposed to winter light hours. These mice had less body weight gain and adiposity. They have more rhythmicity in the way they eat over a 24-hour period. And this then led to benefits in metabolic health.”
The study is the first of its kind to examine light hour’s influence on metabolism in mice, that are not considered seasonal animals as like humans they do not only breed in specific seasons. Animals breeding in specific seasons gain weight before the breeding season to save energy supplies.
Light hours affect the metabolism
The researcher’s inspiration for initiating the study stemmed from the significant variation in daylight hours across various regions of the world.

Playing a single 18-hole round of golf or completing 6 km of either Nordic walking or regular walking may significantly improve immediate cognitive function in older individuals, according to a recent study published in BMJ Open Sport & Exercise Medicine.
An international team of researchers from the University of Eastern Finland, the University of Edinburgh and ETH Zürich aimed to explore the immediate effects of three distinct cognitively demanding aerobic exercises on cognition and related biological responses in older, healthy adults.
The study involved 25 healthy older golfers, aged 65 and above, who participated in three different acute bouts of aerobic exercise: an 18-hole golf round, a 6 km Nordic walking session, and a 6 km regular walking session. Each exercise was conducted in a real-life environment, with participants maintaining their typical pace, corresponding to brisk walking.
Cognitive function was assessed using the Trail-Making Test (TMT) A and B, a widely used tool for evaluating cognitive function in older adults. The TMT-A test measures lower cognitive functions, such as attention and processing speed, while the TMT-B test measures more demanding executive functions such as task-switching ability. Additionally, blood samples were collected to measure brain-derived neurotrophic factor (BDNF) and cathepsin B (CTSB) levels. Both have been suggested to reflect the benefits of exercise in the brain. Participants also wore fitness monitoring devices to record exercise-specific data like distance, duration, pace, energy expenditure and steps. An ECG sensor with a chest strap was used to monitor heart rate.
The study showed that a single session of any of the three exercises — 18 holes of golf, 6 km of Nordic walking or 6 km of regular walking — improved lower cognitive functions measured with the TMT-A test in older adults, although no significant effects were seen on the levels of BDNF and CTSB. Furthermore, Nordic walking and regular walking were associated with enhanced executive functions measured with the TMT-B test.
Previous research has indicated the potential cognitive benefits of acute bouts of aerobic exercise, with factors like exercise intensity, duration and type influencing the extent of improvement.
“These findings underscore the value of age-appropriate aerobic exercise, such as golf, Nordic walking and regular walking, in maintaining and enhancing cognitive function among older adults. Previous research has shown that exercise also holds promise as a potential strategy for those experiencing cognitive decline,” says Julia Kettinen, the first author of the article and a Doctoral Researcher in Sports and Exercise Medicine at the Institute of Biomedicine, University of Eastern Finland.

A research team led by Beate Averhoff and Volker Müller of Goethe University Frankfurt has discovered a fundamental mechanism that helps the dreaded hospital pathogen Acinetobacter baumannii to survive. This mechanism explains why the pathogen is difficult to eradicate in hospitals and why infections flare up again and again in patients: When living conditions become too unfavorable for the bacteria, they fall into a kind of slumber. In this state, conventional diagnostic methods can no longer detect them nor is it possible to kill them off. When living conditions improve again, they awaken from this “deep sleep.”
The bacterium Acinetobacter baumannii is an extremely dangerous pathogen that is found, among other places, in hospitals: Many of the bacterial strains are resistant to different classes of antibiotics. Infections with Acinetobacter baumannii were first observed on a greater scale during the Iraq War and have increased worldwide at a rapid pace ever since. This is the reason why the World Health Organization (WHO) has ranked Acinetobacter baumannii top of the list of bacteria for which new drugs are urgently needed. However, the dangerous spread of Acinetobacter baumannii is not only due to antibiotic resistance but also to its enormous adaptability: It flourishes even under harsh conditions, such as desiccation and high salinity, and is therefore able to colonize different ecosystems in the human body such as the bladder, the surface of the skin and the lungs. Research Unit (FOR) 2251 of the German Research Foundation, of which Professor Volker Müller of Goethe University Frankfurt is the spokesperson, has been studying the molecular basis of these adaptation strategies since 2017.
The research team led by Professor Beate Averhoff and Professor Volker Müller, the two FOR 2251 subproject leaders, has now discovered an adaptation mechanism previously unknown in Acinetobacter. When living conditions become inhospitable, many bacteria enter a dormant state that is almost death-like: They develop permanent forms with no metabolic activity. These are known as spores.
However, and as the research team discovered, Acinetobacter baumannii can form special cells as an alternative, which are in a kind of deep sleep. Although these cells still show signs of life and breathe, it is no longer possible to cultivate them on culture media in Petri dishes. “We know this state from cholera bacteria, for example; it is referred to as the viable but non-culturable (VBNC) state,” explains Müller. Patricia König, the first author of the study, which was published recently in the journal mBio, reports that the bacteria can survive for a long time in this state: “We have kept the bacteria in VBNC deep sleep for eleven months now and check regularly whether we can still wake them up. The study is still ongoing and there is no end in sight.”
The researchers were able to trigger the VBNC state in the Acinetobacter bacteria by raising the salt content of the culture medium, but also — with a time delay — through refrigerator (4 °C) and fever temperatures (42 °C), desiccation and by removing oxygen. In all cases, it was possible to “wake the bacteria up again” after two days of “rehab” in the shaker with an optimum supply of nutrients and oxygen.
The problem is that detecting bacteria by cultivating them on culture media is still the gold standard both in medicine as well as food control. Beate Averhoff explains: “Imagine the following: A patient with an Acinetobacter baumannii infection is treated with antibiotics, and after seven days no more Acinetobacter bacteria grow on the Petri dishes. Doctor and patient assume that the bacterium has disappeared, but it is in fact just asleep in the nooks and crannies of the body, waiting to wake up again at the next, better opportunity, multiply and trigger symptoms in the patient again. This is extremely dangerous, particularly in the case of multidrug-resistant bacteria.”
Patricia König says: “We hope that this will help us to contribute to developing more effective treatment concepts against Acinetobacter baumannii. Above all, we need to use more sensitive methods — in addition to Petri dishes — to detect it, such as PCR, which can also be used to spot VBNC cells.”
In terms of therapy, the proteins that appear to play an important role in the transition to the slumber state might constitute new entry points. The research team has already identified several such proteins. König says: “We must learn to understand the role of these proteins. This will form the basis for developing inhibitors against them, which can be administered together with antibiotics to prevent the bacteria falling into a dangerous slumber.”

When Hurricane Ian struck southwest Florida in September 2022, it unleashed a variety of Vibrio bacteria that can cause illness and death in humans, according to a new study published in the journal mBio.
Using a combination of genome sequencing and satellite and environmental data, a team of researchers from the University of Maryland, the University of Florida and microbiome company EzBiome detected several pathogenic Vibrio species in water and oyster samples from Florida’s Lee County, a coastal region that was devastated by Hurricane Ian. The samples, which were collected in October 2022, revealed the presence of two particularly concerning species: Vibrio parahaemolyticus and Vibrio vulnificus.
“We were very surprised to be able to detect — without any difficulty — the presence of these pathogens,” said the study’s senior author Rita Colwell, a Distinguished University Professor in the University of Maryland Institute for Advanced Computer Studies (UMIACS) who has studied Vibrio for the last 50 years.
The study’s findings correspond with a reported increase in V. vulnificus cases in the state of Florida in October 2022. According to the Florida Department of Health, Lee County, which had the highest caseload in the state, reported 38 infections and 11 deaths linked to vibriosis.
Vibrio bacteria naturally occur in the ocean, where they live symbiotically with crustaceans, zooplankton and bivalves. When the bacteria come in contact with humans, some species can cause an infection known as vibriosis, but the side effects depend on the type of Vibrio and severity of the infection. V. parahaemolyticus can cause gastroenteritis and wound infections, while the V. vulnificus species can cause necrotizing fasciitis — a flesh-eating infection — and kills 1 in 5 infected people.
People can contract vibriosis by eating raw or undercooked seafood or by getting seawater in an open wound. Because Vibrio thrive in warm saltwater, hurricanes and floods can increase the chances of a person becoming exposed.
Several conditions during and after Hurricane Ian favored the growth of Vibrio bacteria, including the amount of rainfall, changes in sea surface temperature and concentrations of chlorophyll in the ocean, which can indicate densities of phytoplankton — and subsequently zooplankton — in an area. In places with plankton blooms, the researchers found an abundance of Vibrio bacteria.

Neurons, the main cells that make up our brain and spinal cord, are among the slowest cells to regenerate after an injury, and many neurons fail to regenerate entirely. While scientists have made progress in understanding neuronal regeneration, it remains unknown why some neurons regenerate and others do not.
Using single-cell RNA sequencing, a method that determines which genes are activated in individual cells, researchers from University of California San Diego School of Medicine have identified a new biomarker that can be used to predict whether or not neurons will regenerate after an injury. Testing their discovery in mice, they found that the biomarker was consistently reliable in neurons across the nervous system and at different developmental stages. The study was published October 16, 2023 in the journal Neuron.
“Single-cell sequencing technology is helping us look at the biology of neurons in much more detail than has ever been possible, and this study really demonstrates that capability,” said senior author Binhai Zheng, PhD, professor in the Department of Neurosciences at UC San Diego School of Medicine. “What we’ve discovered here could be just the beginning of a new generation of sophisticated biomarkers based on single-cell data.”
The researchers focused on neurons of the corticospinal tract, a critical part of the central nervous system that helps control movement. After injury, these neurons are among the least likely to regenerate axons — the long, thin structures that neurons use to communicate with one another. This is why injuries to the brain and spinal cord are so devastating.
“If you get an injury in your arm or your leg, those nerves can regenerate and it’s often possible to make a full functional recovery, but this isn’t the case for the central nervous system,” said first author Hugo Kim, PhD, a postdoctoral fellow in the Zheng lab. “It’s extremely difficult to recover from most brain and spinal cord injuries because those cells have very limited regenerative capacity. Once they’re gone, they’re gone.”
The researchers used single-cell RNA sequencing to analyze gene expression in neurons from mice with spinal cord injuries. They encouraged these neurons to regenerate using established molecular techniques, but ultimately, this only worked for a portion of the cells. This experimental setup allowed the researchers to compare sequencing data from regenerating and non-regenerating neurons.
Further, by focusing on a relatively small number of cells — just over 300 — the researchers were able to look extremely closely at each individual cell.