Going through surgery can take a significant toll on a patient’s physical health and capabilities, especially if they are elderly. A recent study found that the effects extend far beyond mobility and pain management, as the operation may also lead to a significant loss of overall cognitive sharpness.

Researchers tracked 560 adults over 70 with no signs of dementia for six years after major surgeries such as hip replacements and abdominal procedures, watching how their memory and thinking skills changed over time. They found that nearly 15% of participants experienced a sharp decline in memory and thinking abilities shortly after surgery, with their condition continuing to deteriorate over time.

The three biggest warning signs that made a person more likely to fall into a severe decline were: being older, having lower mental test scores before the surgery, and developing postoperative delirium, which is a mental state where a person has episodes of confusion and disordered thinking that can develop over hours or days after the surgery.

The findings are published in the Journal of the American Geriatrics Society.

Brain after surgery

How going under for a surgery affects the brain has tickled the gray cells of anesthesia researchers for decades. During this exploration, they uncovered a cluster of conditions called postoperative neurocognitive disorders (PND), and the findings were concerning.

PND has been linked to higher mortality rates and lasting cognitive decline that can persist for years after surgery. For older adults in particular, these effects following surgery are well-established risks.

With more than 20% of the US population turning 65 by 2030, looking into post-surgery brain health matters more than ever. Many older adults are often faced with the difficult decision of whether to undergo major surgery, weighing the hope of improved mobility or a better quality of life against the possibility of long-term cognitive and functional decline.

To help doctors, patients and families make more informed decisions, it is crucial to understand which individuals are most at risk of experiencing severe cognitive decline after surgery.

The researchers behind the study set out to understand how major surgery impacts the aging brain over time and which groups are most vulnerable to serious cognitive decline. They collected their data from the Successful Aging after Elective Surgery (SAGES) study, a large multi-center research project.

For this analysis, they focused on 560 adults aged 70 and older who were undergoing major elective non-cardiac surgeries, such as hip replacements and abdominal procedures, all of which required a hospital stay of at least three days.

The participants were followed for up to six years, during which researchers gathered three main types of information to get a complete picture of their brain health.

First, they measured Brain Performance Scores by having them complete neuropsychological tests and brain games before surgery. Second, they monitored for delirium during hospitalization post-surgery using a standardized tool called the Confusion Assessment Method. To ensure the results were accurate, the researchers also tracked 119 seniors who did not undergo surgery as the comparison group.

When they analyzed the data, three distinct patterns of cognitive change emerged. Around one in four patients remained mentally sharp with no noticeable decline. More than half of the patients (59%) experienced a minor drop in mental ability, consistent with normal effects of aging.

A smaller group, however, showed a significant and progressive decline in mental performance that continued to worsen over the years. Among all the risks examined, delirium stood out as the strongest predictor of long-term cognitive decline; those experiencing it were twice as likely to suffer from severe deterioration compared to those who did not.

The researchers highlighted that the findings provide valuable information about how major surgery can shape long-term brain health in older adults. Further studies with a much larger and more diverse population are required to integrate it into clinical practice.

Once established, it can be a game-changer, offering doctors a better chance to identify high-risk patients early and take steps to prevent complications such as delirium.

Mental health disorders are now the leading cause of disability worldwide, according to a major new study.

Researchers found nearly 1.2 billion people were living with a mental health disorder in 2023—almost twice as many as in 1990.

“These rising trends may reflect both the lingering effects of pandemic-related stress and longer-term structural drivers such as poverty, insecurity, abuse, violence and declining social connectedness,” said first author Damian Santomauro, an associate professor at the Queensland Center for Mental Health Research in Australia.

The global analysis looked at data from 204 countries and found anxiety and depression have surged since the COVID-19 pandemic.

Rates of major depressive disorder have risen about 24% since 2019, while anxiety disorders skyrocketed more than 47%.

“Our findings show that mental disorder burden peaks among 15-to-19-year-olds, which is a critical developmental period that can shape trajectories for education, employment and relationships,” said co-author Alize Ferrari, who is also from the Queensland Center for Mental Health Research.

The study also found that women are disproportionately affected, possibly due to caregiving pressures, gender inequality and higher rates of abuse.

Addressing the growing crisis will require more investment in mental health care, expanded access to treatment and better support for at-risk populations, the authors said.

The findings were recently published in The Lancet.

When most humans reach late adulthood, their ability to coordinate movements and maintain balance, broadly referred to as motor control, tends to gradually decline. While these changes in motor control are widely documented, the extent to which they also affect sensorimotor learning (i.e., the adaptation of movements based on information from the environment) remains unclear.

Researchers at University of California-Berkeley (UC Berkeley) and Carnegie Mellon University recently set out to better understand two distinct types of sensorimotor learning, referred to as explicit and implicit learning. Their paper, published in Nature Human Behavior, summarizes earlier findings in the field, while also presenting the results of new experiments.

“This project emerged from a longstanding puzzle in the motor learning literature,” Jonathan S. Tsay, senior author of the paper, told Medical Xpress. “Some studies suggested that aging impairs motor learning, others reported little change, and a few even found improvements in older adults. As researchers interested in how humans learn and adapt movement, we found these inconsistencies both fascinating and concerning.”

Combining a meta-analysis with new experiments

When they were reviewing earlier studies focusing on sensorimotor learning in late adulthood, Tsay and his colleagues realized that they often only involved small numbers of participants. In addition, many earlier works treated motor adaptation as a single process, rather than considering its implicit and explicit dimensions.

“Over the past decade, however, the field has increasingly recognized that sensorimotor learning reflects multiple interacting systems,” said Tsay. “In particular, there is an important distinction between implicit learning—the automatic, unconscious recalibration of movement—and explicit learning, which involves deliberate strategies and conscious problem solving.”

The researchers hypothesized that aging affects explicit and implicit learning systems differently. These differences could potentially explain why earlier studies gathered contradictory findings.

“To test this hypothesis, we took a two-pronged approach,” said Tsay. “First, we conducted a large systematic review and meta-analysis spanning several decades of research and more than 2,300 participants. Second, we carried out a series of new, well-powered experiments specifically designed to isolate implicit and explicit forms of learning. Ultimately, our goal was not simply to ask whether aging impairs motor learning, but rather to understand which mechanisms change with age and why.”

To assess people’s sensorimotor learning skills, researchers typically ask participants to complete simple tasks that entail moving toward a target while what they are seeing is subtly distorted. For example, while participants are moving the mouse to click on a specific object on the screen, the cursor might be subtly rotated, so that it no longer closely reflects the true position of their hand.

“Over time, people learn to compensate for this mismatch,” explained Tsay. “The challenge is that successful adaptation can arise from at least two very different processes. One is implicit recalibration: the nervous system automatically and unconsciously adjusts movements. The other is explicit strategy use: participants consciously discover ways to counteract the perturbation, such as deliberately aiming away from the target.”

Tsay and his colleagues found that most previous studies only assessed people’s overall performance on sensorimotor learning tasks. This made it difficult to determine whether they were relying on explicit or implicit learning strategies.

“To disentangle these systems, we first performed a systematic review and meta-analysis of prior studies,” said Tsay. “We specifically examined measures that could separately estimate overall adaptation versus implicit recalibration. Interestingly, this revealed a striking pattern: older adults tended to perform worse overall, but they showed stronger implicit recalibration.”

Isolating explicit and implicit motor learning

To further explore how explicit and implicit sensorimotor learning change as people age, the researchers designed a new behavioral experiment. Their experiment was specifically designed to isolate the adaptation of skills via explicit strategies from implicit sensorimotor learning.

“For explicit learning, we used tasks that largely suppress implicit recalibration by delaying visual feedback,” explained Tsay. “Under these conditions, participants must rely on deliberate strategies to solve the task.”

The researchers observed that most of the older adults who took part in their experiments struggled to uncover effective strategies to adapt their movements based on visual changes. This effect was particularly evident when the task they were completing required participants to remember specific associations between a stimulus and correct responses.

“For implicit learning, we instead used experimental designs that minimize strategic contributions and instead isolate automatic recalibration processes,” said Tsay. “Surprisingly, older adults consistently showed enhanced implicit adaptation. Together, these experiments revealed that aging does not uniformly impair sensorimotor learning. Instead, aging appears to weaken explicit strategic processes while simultaneously enhancing implicit recalibration.”

A new perspective on motor learning in older age

The results of this recent study challenge existing assumptions and views about how motor learning changes in older age. Instead, it suggests that explicit and implicit movement adaptation processes are affected differently in older adults.

“For many years, the prevailing assumption was that aging broadly impairs adaptation. Our findings show that the story is much more nuanced,” said Tsay. “Older adults are not simply ‘worse learners.’ Rather, different learning systems are affected in different ways.”

Tsay and his colleagues were also surprised to discover that while explicit sensorimotor learning declined, implicit recalibration (i.e., the automatic component of motor learning) tends to improve with age. This finding was confirmed both by their meta-analysis and their new behavioral experiments.

“Importantly, the observed deficits in explicit strategy discovery did not reflect a generalized inability to learn or reason cognitively,” explained Tsay. “Rather, the impairment appeared most pronounced in situations with limited environmental support—contexts in which individuals had to independently discover, maintain, and retrieve effective stimulus–response mappings without rich external cues to guide behavior. In contrast, when the task environment provided stronger structural support for problem solving, older adults often performed comparably to younger adults.”

Notably, the team’s observations appear to support emerging psychological theories of sensorimotor learning. These theories suggest that implicit adaptation is not solely driven by visual error signals, but that it also reflects the integration of numerous sensory stimuli and proprioceptive processes (i.e., people’s sense of their own body’s position in space).

“Because proprioceptive function changes with age, this may alter the way the nervous system computes movement error signals,” said Tsay. “More broadly, these findings may have important implications for rehabilitation and healthy aging. Understanding which learning systems remain preserved—or are even enhanced—could help us design more effective interventions for older adults and patients with neurological disorders.”

Tsay and his colleagues are now planning further studies aimed at further testing their hypothesis and validating their observations. For instance, they would like to determine whether the patterns they reported also emerge in real-world learning environments, outside of laboratory settings.

“Another important direction for future research will involve studying pathological aging and neurological disease,” added Tsay. “For example, we are beginning to investigate how disorders such as Parkinson’s disease and cerebellar degeneration differentially impact implicit and explicit learning systems. We hope this work will ultimately help bridge basic neuroscience with clinical rehabilitation.”

Alzheimer’s disease is a neurodegenerative disease characterized by a progressive decline in mental functions and memory loss. Along with frontotemporal dementia and some other neurodegenerative disorders, Alzheimer’s disease has been associated with an accumulation inside neurons of abnormal clumps of a protein called “tau.”

The tau protein is important for brain health, stabilizing structures called microtubules inside neurons. In Alzheimer’s disease and other tauopathies (i.e., diseases linked with the abnormal accumulation of tau), tau proteins aggregate into toxic and insoluble clumps that are harmful to brain cells, gradually leading to their death.

Researchers at Zhejiang University, Xiamen University and other institutes in China recently carried out a study aimed at better understanding the processes via which tau aggregation contributes to the death of neurons in patients with Alzheimer’s disease. Their findings, published in Nature Neuroscience, suggest that these tau clumps prompt the reactivation of transposable DNA elements in neurons, which can in turn lead to their death.

“Once tau aggregates are formed, their neurotoxicity significantly contributes to neuronal death and cognitive decline in tauopathies, with Alzheimer’s disease being the most well-known example,” wrote Wei Liu, Song-Ang Wu and their colleagues in their paper. “Despite its central pathogenic role, however, effective therapeutic strategies targeting the neurotoxicity of tau remain poor. We demonstrate the pathogenic role of neuronal cell death in tau-related neurodegeneration (PS19 mouse model).”

How tau aggregates affect transposable DNA elements

The researchers carried out experiments involving mice that are genetically engineered to also exhibit abnormal tau aggregation in neurons, resembling the one associated with Alzheimer’s disease and other tauopathies. These mice, called PS19 mice, also typically behave in ways that indicate their memory and brain functions are progressively declining.

Liu, Wu and their colleagues tried to better understand how tau aggregates influence the organization of DNA inside their neurons. They specifically looked at whether the tau clumps disrupted heterochromatin, a tightly packed form of DNA that typically prevents harmful genetic code from being activated.

The team found that tau aggregates did in fact influence heterochromatin, leading to the activation of genes that are typically silent. These genes prompted the production of RNA molecules called Z-RNAs, which in turn activated a molecule that plays a role in inflammation and cell death, called Z-DNA-binding protein 1 (ZBP1).

“Tau-expressing neurons undergo cell death through Z-DNA-binding protein 1 (ZBP1) activation triggered by endogenous Z-RNAs,” wrote the authors. “These Z-RNAs are derived from reactivated transposable elements that are typically silenced within heterochromatin. Tau aggregates show a strong affinity for H3K9me3-modified chromatin, effectively sequestering these epigenetic marks from heterochromatin protein 1 (HP1), thereby disrupting the condensation of constitutive heterochromatin.”

A new possible route for preventing neuronal death

The recent paper by Liu, Wu and their collaborators pin-points a process via which the aggregation of tau could lead to neuronal death in tauopathies. In addition, it shows that blocking ZBP1 activity could be a possible therapeutic target for preventing or limiting tau aggregation-related cell death.

“Clinically, an inverse correlation between ZBP1 expression levels in excitatory neurons and cognitive performance in individuals with Alzheimer’s disease was observed,” wrote Liu, Wu and their colleagues. “Importantly, Zbp1 haploinsufficiency significantly ameliorated cognitive deficits in aged (24-month-old) tau-transgenic mice, highlighting the therapeutic potential of ZBP1 inhibition to combat neurodegeneration in tauopathies.”

Other researchers could soon set out to investigate the new mechanisms uncovered by the authors further. If they are validated in humans, the team’s findings could eventually guide the development of new treatments designed to limit cell death and the associated decline in mental functions in patients with Alzheimer’s disease or other tauopathies.

Chikungunya virus, which is transmitted to people by infected Aedes mosquitoes and characterized by high fever and intense joint swelling and pain, has made a resurgence in many countries around the world in recent years.

In the first nine months of 2025, the World Health Organization reported more than 445,000 cases and 155 deaths from 40 countries.

Researchers estimate that about half of people infected with chikungunya virus will progress to a chronic form of the disease and experience relapsing arthralgia and arthritis that can span years and currently has no treatment.

Scientists haven’t known why some patients develop chronic joint pain and swelling. However, University of Colorado Anschutz immunologist Thomas “Tem” Morrison, Ph.D., professor of Immunology and Microbiology, and his lab at the CU Anschutz School of Medicine are beginning to understand more about the progression of the infection. This work could help lead to treatments that would be significant for public health in regions of the world hit hardest by the virus.

In a new paper published in Nature Microbiology, Morrison and his colleagues, including Kristen Zarrella, Ph.D.; Ryan Sheridan, Ph.D.; and Brian Ware, say they’ve discovered that chikungunya virus, an arthritogenic alphavirus, persists in joint-associated macrophages, a specialized type of white blood cell that helps the body defend against pathogens.

“We’ve been interested in trying to better understand how this infection leads to chronic symptoms. Mosquito-transmitted viruses are significant problems in resource-limited regions of the world where many people rely on physical work for their financial well-being. Having chronic musculoskeletal pain is a big problem for people who contract the virus,” Morrison says.

Macrophages act as a ‘sanctuary’

Chikungunya virus symptoms typically occur four to eight days after exposure and include headache, nausea, fatigue, rash, high fever, and joint pain and swelling. For some, those symptoms subside within a few weeks, and they return to normal life. For others, intense joint pain ensues for years.

Morrison’s research, which found macrophages in joints harbor the virus, utilized single-cell RNA sequencing, spatial transcriptomics, and flow cytometry to investigate tissues in alphavirus-infected animal models.

Previously, researchers were unsure what caused the chronic pain. Some hypothesized that the virus triggered an autoimmune response, causing symptoms similar to rheumatoid arthritis. Supporting research for this theory has so far been inconclusive.

Another hypothesis, which is what Morrison and his lab have been exploring, is that there is long-term persistent infection, and when a person acquires the virus and experiences the acute infection there is an immune response to control that infection. However, that immune response fails to eliminate the virus from some tissues.

“This is known to occur in virus infections where the immune response can clear the infection from some parts of the body but struggles or fails to clear the infection from other parts of the body,” Morrison explains.

“So, this is a virus that gets into people, and it spreads systemically. It gets into a lot of tissues. The idea here is that the immune response is unable to clear it from certain tissues, and in this case, those are the joint-associated tissues.”

For years, the Morrison Lab has been able to detect long-term infection in joint-associated tissues. In their latest study, they dived deeper. The team used advanced techniques including single-cell RNA sequencing and spatial transcriptomics—together, these methods allowed the researchers to map gene activity in tissue sections and profile individual cells—to better understand precisely where in the tissue which cell types are harboring the virus.

The lab also asked whether the detection of persistent infection was actually contributing to the disease and chronic symptoms or if it was some other mechanism.

“We hadn’t had a way to really answer that question for a while, until this study, which was supported by the development of small molecule antivirals that can inhibit viral replication,” Morrison says.

“Using those sequencing techniques, we found the virus in specific cell populations—which include macrophages—present in the joint-associated tissue. This means that macrophages seem to act like a sanctuary.”

Moving toward treatment

In the study, the small molecule inhibitor—which can stop the virus’s ability to replicate—reduced chronic viral RNA and joint inflammation. This signaled to Morrison and the research team that the macrophage sanctuary contributed to sustained inflammation.

Researchers were able to take joint tissue, digest it into single cells, and study it. Analyzing each cell with single cell RNA sequencing, researchers could distinguish cell types and then determine if the cell had the viral RNA causing chronic disease.

“This allowed us to, for the first time, identify the precise cells in this tissue that are harboring the viral RNA,” Morrison says.

Answering the question of what is driving chronic symptoms has opened new doors for additional research. Morrison says his team are now interested in how the virus is able to persist in macrophages and why these cells become a “safe reservoir” for the virus.

Most important, the findings highlight a path toward treating people with chronic pain from the virus.

“People have been trying to understand what the best way would be to prevent the progression to this chronic state. Our data signal that antiviral therapy may be useful to prevent the development of or to resolve chronic disease,” Morrison says. “This research suggests that persistent virus infection may be at the root of the chronic disease symptoms.”

Dental implants have given tens of millions of people something dentures never could: a full set of fixed and fully functioning teeth. Unfortunately, 10% to 20% of implant patients eventually experience an aggressive jawbone infection called peri-implantitis. Antibiotics usually fail to stop the infection for reasons that researchers have not understood until now.

Study uncovers a surprising culprit

A recent study in PNAS Nexus by researchers with the Rutgers School of Dental Medicine has found that bacteria corrode implants, causing them to shed microscopic titanium particles into the surrounding tissue. Those particles hijack the immune cells sent to clear the infection and lock them into a state of inflammation that destroys the jawbone they are supposed to protect.

Working with human tissue samples, cultured human immune cells and a genetically engineered mouse model, the team pinpointed a specific calcium channel in the body’s bacteria-eating macrophages that the titanium particles activate. Switching that channel off in mice prevented the disease. The result is the first credible drug target for a condition that affects up to one in five implant recipients and costs the global health system more than a billion dollars a year.

“For the first time, we show why all the antibiotic treatments that work around teeth do not work around implants,” said Georgios Kotsakis, the study’s senior author and the assistant dean for clinical research at the dental school. “Now that we know the cause, we can start developing therapeutics.”

Why implants behave differently than teeth

Peri-implantitis has long been a puzzle because it initially looks like its counterpart in natural teeth, which is called periodontitis and begins with the same oral bacteria. In patients with natural teeth, antibiotics and routine cleaning resolve the infection. In patients with implants, the same drugs against the same bacteria succeed less than half the time, while the bone underneath continues to disappear.

Most research over the past 20 years has focused on the bacteria. Members of Kotsakis’s lab took a different approach and began looking at the implants. Bacteria living on the implant surface produce acidic biofilms that slowly corrode the titanium, releasing billions of particles smaller than a red blood cell. The same shedding can occur during routine cleaning, especially with instruments that dentists typically use on natural teeth.

Inside the gum, those particles get coated with a bacterial toxin called lipopolysaccharide. To the immune system, they suddenly look like enormous, indigestible bacteria. Macrophages, a type of white blood cell that surrounds and kills microorganisms, engulf them but cannot digest metal. The cells become trapped in a hyperinflammatory state, pumping out signaling molecules including interleukin-1 beta, an inflammatory protein also implicated in rheumatoid arthritis and Alzheimer’s disease.

How titanium particles hijack immunity

That inflammation eats away at bone. Worse, the immune cells lose their ability to deal with the original infection. In the lab, macrophages exposed to titanium particles took up less than half as many bacteria as unexposed cells.

“These particles are little magnets that attract the bacterial toxin, and they hijack the immune system, preventing it from clearing bacteria,” said Kotsakis. “You have a perfect storm that defies antibiotics.”

Team members traced the cascade to a calcium channel (a specialized, pore-forming protein structure within cell membranes) called TRPC1. In mice engineered without it, the immune cells handled the same titanium-plus-bacteria challenge normally: Abscesses were dramatically smaller, inflammatory cytokines dropped, and bacterial clearance was restored.

New treatment avenues and safer cleanings

Members of Kotsakis’s group are now testing drug candidates that target the same pathway in human cells.

For people who already have implants, the most useful finding may be a quieter one. The strongest known protective factor is regular professional cleaning, but the kind of cleaning matters. Until roughly a decade ago, many dentists scraped implants with the metal scalers used on teeth, a method the Rutgers lab and others have shown can itself corrode the implant and accelerate the disease. Nonabrasive techniques are now standard.

Scientists have developed a powerful new technique that allows them to observe how individual cells manufacture proteins during aging, offering an unprecedented glimpse into the hidden molecular activity of stem cells in living tissue. As a result of the research, conducted at the Institute for Regenerative Medicine in Switzerland, scientists were able to observe aging unfold inside individual epidermal stem cells.

What scientists saw was the intricate choreography within stem cells and how those molecular dance steps slow and change with age. The team of Swiss scientists has concluded that the process of aging reshapes how skin stem cells manufacture proteins. The findings are published in the journal Molecular Cell.

Protein production impacted

The study revealed that aging epidermal stem cells undergo distinct shifts in their protein-production capabilities, changes that could help explain declining regenerative capacity of these cells in older tissue.

Using an advanced form of single-cell ribosome profiling in an animal model, investigators were able to map the “translational landscapes” of aging skin—essentially tracking how stem cells control protein production over time. Translational landscapes refer to the overall pattern of protein production.

Mechanistically, ribosome profiling allows scientists to determine which messenger RNAs are actively being translated into proteins inside cells at a given moment. The profiling technique not only allowed researchers to eavesdrop on living cells but led to the discovery that aging stem cells in the skin become reprogrammed.

“Stem cells are characterized by two features: their ability to self-renew throughout life and to differentiate into other cell types,” wrote Dr. Clara Duré, lead author of the new research, who—along with a team of investigators—has opened a new window of understanding into stem cells throughout various stages of life.

Stem cells are blank slates

Because stem cells are essentially blank slates capable of morphing into any cell type, their biological role and fate differ significantly from other cell types. By tracking them through stages of life, it’s possible to see how they impact processes such as inflammation and immunity, the team found.

Paradoxically, even during youth, stem cells are not high-energy cells that keep their ribosomes busy with the production of proteins. Instead, these workbenches in stem cells where proteins are constructed exist as relatively quiescent structures.

“Somatic stem cells are characterized by their low overall protein-synthesis rates, a feature implicated in driving their stemness,” Duré continued, noting that the term “stemness,” refers to the cells’ capacities for self-renewal and remaining unspecialized until needed.

Both of these functions are closely linked to their precise regulation of gene expression. Somatic stem cells exhibit a unique signature marked by high ribosome biogenesis and a low protein synthesis rate.

Aging reshapes translational capacity

Yet, exactly how aging reshapes the translational landscape of stem cells had remained poorly understood until the new research helped illuminate what was occurring within stem cells themselves.

The ribosome profiling technique allowed the Zurich-based team to determine which messenger RNAs were being actively translated into proteins inside cells at any given moment, and across different stages of aging in the mouse model, which was used in the study.

“Somatic stem cells exhibit a unique signature marked by high ribosome biogenesis and low protein synthesis rates, a feature that is implicated in independently driving their stemness, regardless of cellular proliferation, cell cycle, or total mRNA content,” Duré and colleagues noted in the study.

Several takeaways from the research suggest that the potent new technique for studying stem cells in living tissue could eventually permit research on aging tissue in unprecedented detail, illuminating why these cells lose regenerative power over time.

“Our study focuses on the epidermis. This tissue is highly heterogeneous, including epidermal stem cells, differentiated keratinocytes, hair follicle cells, and resident immune cells such as macrophages, dendritic cells, and T cells,” Duré concluded. “We note, however, that extending the single-cell ribosome profiling protocol to additional tissues may require further optimization.”

Immunotherapies such as so-called checkpoint inhibitors activate the body’s own immune system to fight cancer cells and have revolutionized the treatment of many types of tumor. In breast cancer, however, these therapies are often only of limited effectiveness. An international research team led by the Medical University of Vienna has now identified a previously underestimated mechanism by which breast tumors evade the immune system.

The findings, published in the journal Nature Communications, also provide a new starting point for improving the effectiveness of immunotherapies in breast cancer.

Sialylation is the name given to the biochemical process that the research team led by Stefan Mereiter (Department of Obstetrics and Gynecology, MedUni Vienna) and Josef Penninger (Clinical Institute of Laboratory Medicine, MedUni Vienna) has identified as a central mechanism of immune suppression in breast cancer.

This involves a specific sugar modification on the surface of tumor cells that impairs communication between cells and the immune system.

“We were able to show that around two-thirds of all breast tumors exhibit increased sialylation. In these cases, significantly fewer T-cells—i.e., immune cells that fight cancer cells—were detectable in the tumor tissue,” reports lead author Mereiter. Analyses of patient cohorts comprising a total of 136 breast cancer cases confirmed this link.

Targeted inhibition of the mechanism

In detail, the researchers discovered that sialylation, among other things, enhances the effect in the blood of the immunomodulatory growth factor G-CSF produced by cancer cells. This leads to an increased recruitment of immunosuppressive cells into the tumor, which in turn prevents cytotoxic, i.e. cell-killing, T-cells from efficiently penetrating the tumor tissue.

At the same time, sialylation makes tumor cells less recognizable to existing T cells, thereby allowing them to evade the immune system. In preclinical research models, however, the targeted pharmacological inhibition of sialylation led to T cells spreading throughout the tumor again and being able to combat it more effectively.

“More activated cytotoxic T cells reach the tumor, while at the same time, immunosuppressive neutrophil cells decrease,” explains study leader Josef Penninger.

Breast cancer is the most common cancer in women. Immunotherapies, such as so-called checkpoint inhibitors, which are designed to activate the body’s own immune system to defend against cancer cells, are only of limited effectiveness against this type of tumor.

The current study results provide both a possible explanation and a solution for this.

“Our study shows that therapeutically blocking sialylation causes even tumor models that were previously resistant to treatment to respond to immunotherapies. Our findings therefore suggest that the targeted modulation of tumor sialylation could be a promising new approach to overcoming immune-suppressive mechanisms within the tumor and thus significantly improving the efficacy of immunotherapies in breast cancer,” said Mereiter and Penninger.

The findings are now to be further investigated in additional studies within the newly established research group led by Mereiter at the Department of Obstetrics and Gynecology at MedUni Vienna, with the aim of developing future therapies.

Evening coffee has sparked controversy for years. Some people fall asleep without difficulty, while others toss and turn for half the night. However, a growing body of research suggests the question of whether coffee makes it harder to fall asleep may be too simplistic. What appears to matter far more is what happens in the brain during sleep.

Scientists studying the effects of caffeine on sleep are increasingly turning to EEG, or electroencephalography, a method used to record the brain’s electrical activity. Thanks to EEG, it is possible to observe not only sleep duration or moments of awakening, but also the biological quality of sleep itself.

“EEG allows scientists to see not only whether a person is sleeping, but also how the brain is sleeping. Classical sleep assessment measures sleep duration and its stages, whereas quantitative EEG analysis reveals more subtle changes, such as reduced slow-wave activity, which is an important marker of sleep depth and its restorative character,” said Prof. Donata Kurpas of the Department of Nursing at Wroclaw Medical University.

Slow waves are one of the key components of deep sleep, the phase responsible for bodily regeneration, restoration of energy resources, and proper brain function.

Caffeine may cause ‘shallow’ sleep

The research published in Nutrients shows the effects of caffeine do not always manifest as shorter sleep or difficulty falling asleep. Much more often, the changes concern the quality of nighttime rest.

“Caffeine may shorten sleep or make it more difficult to fall asleep. However, even when sleep duration appears normal, it may reduce slow-wave activity and shift the EEG pattern toward a more wakeful brain,” Kurpas said.

This means the body may spend eight hours in bed, but the brain may fail to fully regenerate. People are often unaware of this.

“The subjective feeling of having slept well does not always correspond to what researchers observe in neurophysiological recordings. A person may fall asleep without major difficulty and not remember awakenings, while the brain may display fewer features of deep sleep,” she added.

Why does coffee affect everyone differently?

One of the most interesting conclusions emerging from research is the enormous individual variability in response to caffeine. Genetics, metabolic rate, age, stress levels and chronic fatigue all play a role.

For some individuals, even coffee consumed in the morning may be problematic. “It is not only about coffee consumed just before bedtime. For some people, the total amount of caffeine consumed during the day and whether the body has enough time to metabolize it before nightfall may also be important,” Kurpas said.

This is particularly important information for people engaged in intellectual work, athletes and anyone who regularly uses caffeine to improve performance and concentration.

Energy is borrowed from the body

Caffeine improves alertness and reduces the sensation of fatigue, but experts point out its effects may sometimes resemble borrowing energy at the expense of nighttime regeneration.

“If caffeine helps a person function during the day while simultaneously worsening the quality of nighttime recovery, a vicious circle may develop: greater fatigue, greater need for stimulation and poorer sleep,” Kurpas said.

For this reason, modern sleep research is increasingly moving away from simple questions about sleep duration and focusing instead on how the brain functions during nighttime rest.

“Caffeine is neither good nor bad. It is a biologically active substance whose effects depend on dose, time of day, age, lifestyle, sleep quality, stress burden and individual sensitivity,” she said.