Planned early birth for pregnant women with high blood pressure cuts maternal complications by nearly half and reduces the risk of stillbirth, without increasing the likelihood of cesarean section, according to data published in the Cochrane Database of Systematic Reviews.

Hypertensive disorders of pregnancy, which include pre-eclampsia, gestational hypertension, and chronic hypertension, are the second leading cause of maternal death globally. For women with pre-eclampsia, early birth remains the only definitive treatment, as the condition is driven by the placenta and will only resolve once it is delivered.

This review, led by King’s College London, pooled data from six randomized controlled trials involving 3,491 women, comparing planned early birth after 34 weeks to watchful waiting. The trials included women with one or more types of hypertensive disorder and took place across a range of settings, including the Netherlands, UK, US, India, and Zambia.

Benefits for mother and baby

The findings show high-certainty evidence that serious maternal complications were nearly halved in women who had a planned early birth compared to those managed with watchful waiting.

Planned early birth also likely reduces the risk of stillbirth by approximately 75%, though this should be interpreted with caution. The finding is based on moderate-certainty evidence, and the reduction was driven by a single trial conducted in India and Zambia, where stillbirth rates are higher.

There were no stillbirths recorded in the high-income country trials. Reassuringly, planned early birth also likely results in no increase in neonatal unit admission, though this finding is also based on moderate-certainty evidence.

Importantly, the maternal benefit held across both high- and low-income settings, suggesting that early birth reduces complications even when women are already receiving appropriate monitoring and care.

“These findings give clinicians and women clearer guidance about the timing of birth when high blood pressure develops in pregnancy,” said Prof Catherine Cluver, senior author of the review and researcher at Stellenbosch University and Tygerberg Hospital.

“For women with pre-eclampsia in particular, the evidence supports offering planned early birth from 34 weeks, and no later than 37 weeks.”

“Judging when to offer birth is the question that we battle with clinically every day,” said Dr. Alice Beardmore-Gray, lead author of the review, and obstetrician at King’s College London.

The authors added that in two of the trials included, over half the women allocated to watchful waiting ended up needing emergency birth before 37 weeks, typically just three to five days later than women allocated to planned early birth, and often experiencing more complications.

“A common misconception is that by waiting longer, mum and baby are gaining more time, but often what you are doing is just delaying an inevitable emergency birth, when both may be in a worse condition,” explained Dr. Beardmore-Gray.

No increased risk of C-section

The review found high-certainty evidence of no increased risk of cesarean section associated with planned early birth. This is a finding the authors consider particularly important for clinical counseling and women’s decision-making.

“That is the first question anyone asks when you offer them an early induction: won’t it increase my risk of a C-section?” said Dr. Beardmore-Gray. “Being able to clearly answer no is a really important piece of information to give women when counseling them about the timing of their birth.”

The authors advise that the timing of birth should take into account the woman’s preferences and the severity of her condition. These findings are consistent with and reinforce current international guidelines, which recommend that all women with pre-eclampsia should be offered planned early birth no later than 37 weeks.

Women with gestational hypertension or chronic hypertension without severe features may choose to continue with careful monitoring, with planned early birth considered from 39 weeks onward.

Further research is needed on longer-term outcomes for infants born late preterm and on the long-term cardiovascular health of mothers affected by hypertensive disorders of pregnancy.

Obesity affects far more than metabolism and fat storage. It alters immune activity, nerve structure, and tissue organization across multiple organ systems, increasing the risk of diseases including type 2 diabetes, cardiovascular disease, stroke, neuropathy and cancer. Yet despite these systemic effects, researchers have lacked tools capable of studying disease-associated changes across the entire body in intact organisms and at high resolution.

A team led by Prof. Ali Ertürk, Director of the Institute for Biological Intelligence (iBIO) at Helmholtz Munich and Professor at the LMU, has now developed MouseMapper, a suite of foundation-model-based deep-learning algorithms designed to analyze whole-body biological imaging data. The framework automatically segments 31 organs and tissue types while quantitatively mapping nerves and immune cells throughout the body, enabling comprehensive multi-system analysis in intact mice.

“MouseMapper is built on a foundation model, which means it generalizes far beyond the data it was originally trained on,” says Ying Chen, co-first author of the study published in Nature.

Looking inside an entire transparent mouse

To create whole-body maps, the researchers labeled nerves and immune cells in mice with fluorescent markers visible under the microscope. They then used tissue-clearing techniques to render the animals transparent while preserving the fluorescent signals, allowing imaging deep inside intact bodies.

Using specialized light-sheet microscopy, the team captured detailed three-dimensional images of entire mice, producing datasets containing tens of millions of cellular structures across organs and tissues. MouseMapper then analyzed these data automatically, identifying nerves, immune-cell clusters, and anatomical regions throughout the body.

This allowed the researchers to determine precisely where inflammation and structural damage occur across different tissues—including fat, muscle, liver, and peripheral nerves—without requiring researchers to preselect specific regions of interest.

New insights into obesity, from mouse to human

To investigate how obesity reshapes the body, the researchers fed mice a high-fat diet that induced obesity and metabolic dysfunction similar to that observed in humans. Applying MouseMapper revealed widespread changes in both immune-cell organization and nerve architecture across the body.

One of the most striking findings was a structural change to part of the trigeminal nerve, a major facial nerve that is responsible for facial sensation and motor functions. In obese mice, these sensory nerves had far fewer endings and branches, suggesting a loss of normal nerve function. Behavioral experiments further showed that the animals responded less to sensory stimulation than lean mice, linking the structural damage to impaired sensory function.

The researchers next examined the trigeminal ganglion, the structure containing the cell bodies of facial sensory neurons. Using spatial proteomics, they identified molecular alterations associated with nerve remodeling and inflammation. Remarkably, many of the same molecular signatures were also detected in trigeminal tissue from people with obesity, suggesting that the obesity-associated nerve alterations observed in mice also occur in humans.

“We revealed previously unknown structural and molecular changes in the trigeminal ganglion and its facial branches, and the same molecular signature was conserved in human tissue. This kind of finding simply cannot emerge from studying one organ at a time,” says Dr. Doris Kaltenecker, senior scientist at the Institute for Diabetes and Cancer (IDC) at Helmholtz Munich and first author of the study.

A platform for studying systemic disease

Beyond obesity, the researchers believe MouseMapper could transform the study of complex diseases that affect multiple organ systems simultaneously, including diabetes, cancer, neurodegeneration and autoimmune disorders. Unlike earlier methods focused on selected organs or tissues, MouseMapper provides an integrated whole-body analysis platform capable of identifying disease “hotspots” throughout the organism.

The team has made whole-body datasets publicly available online, allowing scientists worldwide to explore obesity-associated changes across tissues and organ systems.

“Our goal is to create a comprehensive framework for understanding how diseases affect the body as an interconnected system,” says Ertürk. “Our long-term vision is to build truly realistic digital twins of mice in health and disease: cell-level atlases that we can query, perturb and screen in silico computationally. That would let us pinpoint the earliest changes a disease causes, design interventions to prevent them, and accelerate the discovery of new treatments while reducing the number of physical experiments we need to run.”

Researchers from the University of California San Diego School of Medicine have found that women not only experience a higher burden of certain modifiable dementia risk factors, but also appear more vulnerable to their effects on cognitive function. The study, which analyzed data from more than 17,000 middle-aged and older adults, is published in Biology of Sex Differences.

“Looking beyond which risk factors are most common, we found that some have a disproportionately larger impact on women’s cognition,” said Megan Fitzhugh, Ph.D., assistant professor of neurosciences at UC San Diego School of Medicine and first author of the study. “This suggests that prevention efforts may be more effective if they are tailored not just to risk factor prevalence, but to how strongly each factor affects cognition in women versus men.”

Dementia, including Alzheimer’s disease, affects women at higher rates than men, a disparity that has drawn increasing scientific attention. In fact, of the seven million adults living with Alzheimer’s disease, nearly two-thirds are women. While women tend to live longer, longevity alone does not fully explain the difference in Alzheimer’s outcomes. Researchers are now examining how combinations of biological, social, and lifestyle factors contribute to this imbalance—particularly those that can be modified over time.

Study design and risk factors examined

In the new study, Fitzhugh and Judy Pa, Ph.D., professor of neurosciences at UC San Diego School of Medicine and corresponding author of the study, evaluated 13 established, modifiable dementia risk factors using data from the Health and Retirement Study, a nationally representative cohort of U.S. mid- to late-life adults. These factors included education level, hearing loss, smoking, alcohol use, obesity, depression, physical inactivity, and cardiometabolic conditions such as hypertension and diabetes.

The analysis revealed clear sex-based differences in the prevalence of these risk factors. Women were more likely than men to report:

• Depression (nearly twice as common in women as men—17% vs. 9%)
• Physical inactivity (48% vs. 42%)
• Sleep problems (45% vs. 40%)

Women also had slightly lower average educational attainment—a known risk factor for later-life cognitive decline.

How risk profiles differ by sex

Men, on the other hand, had:

• Higher rates of hearing loss (64% vs. 50%)
• Diabetes (24% vs. 21%)
• Heavy alcohol use (22% vs. 12%)

Hypertension was common in both groups, affecting about six in 10 participants, while average body mass index in both sexes fell in the overweight-to-obese range.

Beyond prevalence, the study found that several risk factors were more strongly associated with poorer cognitive performance in women. For example, cardiovascular and metabolic conditions such as hypertension and increased BMI showed steeper negative associations with cognition in women compared to men. However, hearing loss and diabetes—both more common among men—were linked to poorer cognitive scores in women.

These findings suggest that the same risk factor may not carry equal meaning across sexes. A condition that is moderately associated with cognitive decline in men may have a substantially stronger effect in women, amplifying its overall contribution to dementia risk.

Implications for research and prevention

“These differences highlight the importance of considering sex as a key variable in dementia research,” said Pa. “Sex differences are profoundly overlooked among many leading causes of death like Alzheimer’s, heart disease, and cancer.”

The study’s results align with a broader push toward precision medicine—developing prevention and treatment strategies tailored to individual characteristics, including sex. Rather than focusing solely on the most common risk factors in the population, the findings suggest it may be more effective to prioritize those with the strongest cognitive impact within each group.

The researchers emphasize that these risk factors are modifiable, offering actionable opportunities for intervention. For example, this could mean placing greater emphasis on managing depression, increasing physical activity, and improving cardiovascular health—such as untreated hypertension—among women, as these factors are strongly associated with cognitive health.

Next steps in understanding sex differences

Looking ahead, Fitzhugh and Pa call for further research to better understand the biological and social mechanisms driving sex-based differences in Alzheimer’s risk factors. Hormonal influences, genetic susceptibility, and disparities in health care access may all play a role, but more work is needed to clarify how they interact over time.

“Ultimately, a more nuanced understanding of these differences could help us design smarter, more targeted interventions,” Fitzhugh said. “That’s an essential step toward reducing the burden of dementia for everyone, but especially for women, who are disproportionately affected.”

A new Penn Nursing study suggests that the specific sedatives used during critical illness in early childhood may have long-term implications for a child’s neurocognitive development. Martha A.Q. Curley, Ph.D., RN, FAAN, Professor in the Department of Family and Community Health, and the Ruth M. Colket Endowed Chair in Pediatric Nursing at Children’s Hospital of Philadelphia, co-led the study with R. Scott Watson, MD, from Seattle Children’s Hospital.

The research, published in JAMA Network Open, found that while most children who survived a critical illness requiring sedation had IQ scores within the normal range, those treated with a combination of only opioids and benzodiazepines scored lower on later neurocognitive tests than those whose treatment included the sedative dexmedetomidine.

Assessing long-term impact

Critically ill young children often require days or even weeks of sedation to tolerate life-saving treatments like mechanical ventilation. While these medications are necessary, concerns have persisted about their potential toxicity to the developing brain.

The RESTORE-Cognition Study followed 256 children who were age eight or younger when they were hospitalized for acute respiratory failure. Researchers conducted comprehensive neurocognitive testing—including assessments of IQ, memory, and attention—three to eight years after the children were discharged from the pediatric intensive care unit (PICU).

Key findings

• General Cognitive Function: The average estimated IQ of the study participants was 100.3, which is consistent with the general population mean.
• Sedative Strategy Matters: When adjusting for factors like socioeconomic status and the severity of the original illness, children who received only opioids and benzodiazepines had an adjusted mean IQ approximately four points lower than those who received dexmedetomidine as part of their care.
• Vulnerability in High Doses: The difference was even more pronounced in children who required the highest doses of benzodiazepines; in this group, those treated with only opioids and benzodiazepines had an IQ score nearly eight points lower than those who also received dexmedetomidine.
• Specific Deficits: Beyond global IQ, researchers observed lower-than-average scores in areas such as nonverbal memory, visuospatial skills, and fine motor control across the entire group of survivors.

Clinical implications

“For a long time, we haven’t had clear evidence on which sedatives are best for critically ill children on ventilators,” said Curley. “Our study shows that the choice we make in the pediatric ICU can affect a child’s brain development years later. Specifically, adding dexmedetomidine to our treatment plan may help protect a child’s long-term thinking and learning skills better than using opioids and benzodiazepines alone.”

The study highlights the importance of long-term follow-up for PICU survivors to identify and support children who may experience subtle but impactful neurocognitive challenges.

A once-nightly oral pill helped control obstructive sleep apnea in a large, Phase III clinical trial presented at the 2026 ATS International Conference. The drug, called AD109, is the first therapy to treat OSA by addressing its underlying mechanisms and targeting the neuromuscular causes of airway collapse.

The study, “Aroxybutynin and Atomoxetine (AD109) for Obstructive Sleep Apnea: A Randomized Phase 3 Trial,” is published in the American Journal of Respiratory and Critical Care Medicine.

How the new pill performed

The trial, called SynAIRgy, showed that patients who took AD109 had fewer breathing interruptions during sleep, less oxygen deprivation, and improved blood oxygen levels overall. More than 40% of patients saw their OSA disease severity category improve, and 18% achieved complete disease control.

“These results provide encouraging evidence that targeting neuromuscular dysfunction can translate into meaningful clinical outcomes, aligning with our evolving understanding of the disease biology,” said first author Patrick John Strollo, MD, a sleep medicine physician at the University of Pittsburgh Medical Center.

Why patients need more options

Continuous Positive Airway Pressure (CPAP) is the gold standard treatment for OSA, but many patients are unable to tolerate treatment. AD109 could help fill that gap with an easier treatment option, Dr. Strollo said.

“In many other chronic diseases, such as cardiovascular disease, asthma, or type 2 diabetes, it would be unthinkable for the majority of diagnosed patients to remain untreated or undertreated. Yet that remains the reality in OSA,” he said.

“An oral pill that targets the underlying neuromuscular drivers of airway collapse during sleep could help address this gap and broaden the range of effective options for patients who remain untreated today.”

What AD109 is made of

AD109 combines two medications, aroxybutynin and atomoxetine, which work together to support muscles in the throat and prevent the airway from sagging or collapsing during sleep.

For the trial, which ran for six months at 69 sites across the U.S. and Canada, researchers enrolled 646 adults with mild to severe OSA who couldn’t tolerate or refused CPAP.

Patients taking AD109 saw their apnea-hypoxia index, which measures the number of breathing interruptions per hour, decrease by about 44%, compared with 18% in the placebo group. Oxygen desaturation index (the number of times during the night that blood oxygen drops) and hypoxic burden (oxygen deficiency) also improved in the AD109 group.

Importantly, improvements were observed consistently across a broad range of patients, including those with varying severity levels and body types.

Safety profile and side effects

Along with improved outcomes, the drug showed an acceptable safety profile with mild, expected side effects. The most common side effects were dry mouth, nausea, insomnia, and difficulty urinating. Around 21% of patients discontinued therapy due to side effects.

Dr. Strollo noted that the results will be published alongside a companion mechanistic review by ATS in the American Journal of Respiratory Cell and Molecular Biology.

“Together, these peer-reviewed articles connect late-stage clinical outcomes with the biological mechanisms that drive the disease, targeted by the mechanism of action of AD109, providing a more complete and integrated view of OSA and strengthening confidence in the approach,” he said.

Regulatory status and next steps

AD109 has received Fast Track designation from the FDA for the treatment of OSA, recognizing the significant unmet need for effective, well-tolerated pharmacologic therapies for OSA.

Apnimed has submitted its New Drug Application (NDA) for AD109 to the FDA. Based on FDA feedback, Apnimed expects a potential PDUFA target action date in 1Q 2027, subject to FDA acceptance of the NDA for review.

Obesity has long been the invisible health crisis looming over humanity, with rates climbing globally. There is some positive news now emerging from a multi-decade study spanning several nations. A recent study published in Nature by the Non-Communicable Disease Risk Factor Collaboration (NCD-RisC), a global network of health scientists, analyzed obesity-related data from 232 million people aged 5 years or older, spanning 45 years.

The data revealed that obesity trends may finally be slowing in many high-income Western countries, including Western Europe, North America, and Australasia, as well as in some high-income Asian countries, with several showing signs of plateauing and even slight declines, particularly among children and adolescents.

The picture across low and middle-income countries tells a far more alarming story. Childhood and adolescent obesity is not only rising, but accelerating rapidly in parts of Asia, Africa, Latin America, the Caribbean, and the Pacific Islands.

Obesity beyond weight
Nearly 1 in 8 people is living with obesity, which equates to more than 1 billion people, making this non-communicable disease nothing short of an epidemic.

Several long and short-term studies conducted across the world have found that obesity is far more than a weight issue. It can quietly make the way for a wide range of serious health conditions, increasing the risk of heart, kidney, liver, and respiratory diseases. It is also linked to musculoskeletal disorders affecting the muscles, bones, and joints, which in turn can affect quality of life. The dangers of obesity became even more evident during the COVID-19 pandemic, where individuals with obesity faced a significantly higher risk of severe infection, leading to greater rates of hospitalization and even death.

Even though it sounds counterintuitive, obesity is considered malnutrition, which by definition refers to deficiencies, excesses, or imbalances in a person’s intake of nutrients. However, nutrition and how much one exercises aren’t the only factors driving obesity.

The factors differ from country to country and continue to change over time due to shifts in food production, processing, and other influences on food prices and availability. It is also influenced by economic factors, such as living conditions, social habits, and the kind of food policies created by the government.

Global or local?
Most global obesity reports focus on long-term trends and overlook the smaller year-by-year shifts that reveal how the crisis is evolving. They also failed to closely track how obesity patterns differ across countries, age groups, and shorter time periods.

In this study, researchers analyzed data from 4,050 population-based studies conducted between 1980 and 2024 across 200 countries and territories. They aimed to build a detailed year-by-year picture of global obesity trends, so instead of simply measuring how many people were obese at a given point in time, they tracked the annual pace at which obesity rates were rising or falling.

Using a computer-based pattern-recognition technique called clustering, the researchers also identified distinct phenotypes, or groups of countries that shared similar obesity patterns across children, adolescents, and adults.

The results exposed an emerging global divide in the obesity crisis. In many of the world’s richest countries, obesity rates are beginning to stabilize, but across several developing nations, the crisis is accelerating at an alarming pace. In high-income countries, obesity rates in children and teenagers began to slow as early as the 1990s; in adults, a similar trend began around 2000.

Access to healthy food and health information may have helped slow rates in wealthier countries. In developing nations, urbanization, transition from physically demanding to sedentary work, and dependence on imported processed foods might have quietly changed how people live, and unfortunately, public health systems failed to keep up.

These findings show that the global obesity crisis is far from uniform. So, the researchers argued that obesity cannot be considered a single global epidemic, as trends vary widely across the world. Some countries are stabilizing, others are still seeing rapid rises. This makes it quite evident that the obesity crisis can no longer be addressed with a one-size-fits-all approach. To combat this, we need more tailored policies and public health education programs.

People who carry the APOE2 version of the apolipoprotein E gene are more likely to live to advanced age and are partly protected against Alzheimer’s disease, but scientists have struggled to explain why. A new study from the Buck Institute for Research on Aging, now published in Aging Cell, offers a mechanistic answer: APOE2 helps human neurons keep their DNA intact and resist becoming senescent, a damaged, dysfunctional state that accumulates with age and contributes to neurodegeneration.

The findings shift attention away from APOE’s well-known role in cholesterol transport and toward a previously underappreciated function of the gene: shaping how brain cells maintain the integrity of their genome as they age.

“We’ve known for years that APOE2 carriers tend to live longer and have a lower risk of Alzheimer’s, but the protective mechanism has been a black box,” says senior author Lisa M. Ellerby, Ph.D., professor at the Buck Institute. “Our work shows that APOE2 neurons are better at preventing and repairing DNA damage, and they resist the cellular aging program that drives so much of late-life decline. Our findings point to entirely new therapeutic directions.”

What the researchers did

APOE comes in three common forms, APOE2, APOE3, and APOE4, that differ by just two amino acids. APOE4 is the strongest known genetic risk factor for late-onset Alzheimer’s disease (typically after age 65), while APOE2 is consistently linked in population studies to exceptional longevity and reduced dementia risk.

To isolate what APOE itself contributes to neuronal aging, the Buck team used human induced pluripotent stem cells (iPSCs) genetically engineered to differ only at the APOE locus. They generated two types of brain neurons from these cells, inhibitory GABAergic neurons and excitatory glutamatergic neurons, and compared how the different APOE versions affected each cell type. They also examined hippocampal tissue from aged mice carrying the human APOE2, APOE3, or APOE4 gene.

Key findings include:

• APOE2 neurons accumulate less DNA damage. Bulk and single-cell RNA sequencing showed that APOE2 GABAergic neurons strongly upregulate DNA repair and damage-response pathways, while APOE4 neurons show transcriptional signatures associated with Alzheimer’s disease. Direct measurements of DNA strand breaks confirmed that APOE2 neurons carried significantly less damage.
• APOE2 neurons resist becoming senescent. When the team stressed excitatory neurons with radiation or the chemotherapy drug doxorubicin, APOE2 neurons showed lower levels of senescence markers (including p16 and CRYAB), smaller nucleoli, and better-preserved nuclear architecture compared with APOE3 and APOE4 neurons.
• APOE2 protein can protect APOE4 neurons. Adding recombinant APOE2 protein to APOE4 neurons reduced DNA damage signaling after radiation, an early hint that the protective effect might be transferable, not just genetic.
• The mouse brain agrees. Aged APOE2 knock-in mice showed smaller nucleoli, higher levels of the nuclear scaffolding protein Lamin A/C, and better-preserved heterochromatin in the hippocampus than APOE3 or APOE4 mice, features associated with healthier brain aging.

Why it matters

Cellular senescence and accumulated DNA damage are now recognized as central drivers of aging and age-related disease, including Alzheimer’s. “Until now, the APOE field has focused largely on lipid handling and amyloid-beta biology,” says Ellerby. “By showing that APOE alleles also tune how neurons defend their genome, this study connects a major longevity gene to two of the most actively studied hallmarks of aging.”

Ellerby says the work suggests that strategies aimed at boosting DNA repair or clearing senescent cells in the brain could mimic some of the natural protection conferred by APOE2, potentially benefiting people who carry the higher-risk APOE4 variant.

“What surprised us was how consistent the picture was across two very different neuron types and across human cells and mouse brain tissue,” said co-first author Cristian Gerónimo-Olvera, Ph.D., a postdoctoral fellow at the Buck Institute. “APOE2 neurons aren’t just less damaged at baseline, they recover faster when stressed.”

Next steps

The authors note that the precise molecular mechanism by which APOE2 stabilizes the nuclear envelope and supports DNA repair remains to be defined. Future studies will explore whether APOE2-mimetic compounds or targeted DNA repair therapies can confer similar protection in APOE4 carriers, the population at highest genetic risk for Alzheimer’s disease.

Obesity has long been the invisible health crisis looming over humanity, with rates climbing globally. There is some positive news now emerging from a multi-decade study spanning several nations. A recent study published in Nature by the Non-Communicable Disease Risk Factor Collaboration (NCD-RisC), a global network of health scientists, analyzed obesity-related data from 232 million people aged 5 years or older, spanning 45 years.

The data revealed that obesity trends may finally be slowing in many high-income Western countries, including Western Europe, North America, and Australasia, as well as in some high-income Asian countries, with several showing signs of plateauing and even slight declines, particularly among children and adolescents.

The picture across low and middle-income countries tells a far more alarming story. Childhood and adolescent obesity is not only rising, but accelerating rapidly in parts of Asia, Africa, Latin America, the Caribbean, and the Pacific Islands.

Obesity beyond weight

Nearly 1 in 8 people is living with obesity, which equates to more than 1 billion people, making this non-communicable disease nothing short of an epidemic.

Several long and short-term studies conducted across the world have found that obesity is far more than a weight issue. It can quietly make the way for a wide range of serious health conditions, increasing the risk of heart, kidney, liver, and respiratory diseases. It is also linked to musculoskeletal disorders affecting the muscles, bones, and joints, which in turn can affect quality of life. The dangers of obesity became even more evident during the COVID-19 pandemic, where individuals with obesity faced a significantly higher risk of severe infection, leading to greater rates of hospitalization and even death.

Even though it sounds counterintuitive, obesity is considered malnutrition, which by definition refers to deficiencies, excesses, or imbalances in a person’s intake of nutrients. However, nutrition and how much one exercises aren’t the only factors driving obesity.

The factors differ from country to country and continue to change over time due to shifts in food production, processing, and other influences on food prices and availability. It is also influenced by economic factors, such as living conditions, social habits, and the kind of food policies created by the government.

Global or local?

Most global obesity reports focus on long-term trends and overlook the smaller year-by-year shifts that reveal how the crisis is evolving. They also failed to closely track how obesity patterns differ across countries, age groups, and shorter time periods.

In this study, researchers analyzed data from 4,050 population-based studies conducted between 1980 and 2024 across 200 countries and territories. They aimed to build a detailed year-by-year picture of global obesity trends, so instead of simply measuring how many people were obese at a given point in time, they tracked the annual pace at which obesity rates were rising or falling.

Using a computer-based pattern-recognition technique called clustering, the researchers also identified distinct phenotypes, or groups of countries that shared similar obesity patterns across children, adolescents, and adults.

The results exposed an emerging global divide in the obesity crisis. In many of the world’s richest countries, obesity rates are beginning to stabilize, but across several developing nations, the crisis is accelerating at an alarming pace. In high-income countries, obesity rates in children and teenagers began to slow as early as the 1990s; in adults, a similar trend began around 2000.

Access to healthy food and health information may have helped slow rates in wealthier countries. In developing nations, urbanization, transition from physically demanding to sedentary work, and dependence on imported processed foods might have quietly changed how people live, and unfortunately, public health systems failed to keep up.

These findings show that the global obesity crisis is far from uniform. So, the researchers argued that obesity cannot be considered a single global epidemic, as trends vary widely across the world. Some countries are stabilizing, others are still seeing rapid rises. This makes it quite evident that the obesity crisis can no longer be addressed with a one-size-fits-all approach. To combat this, we need more tailored policies and public health education programs.

The antiviral drug ensitrelvir prevents infection in household contacts of COVID-19 patients when given within 72 hours after symptom onset in the index patient, according to a Phase III randomized controlled trial published in the New England Journal of Medicine.

A team led by researchers from the University of Virginia and ensitrelvir maker Shionogi randomly assigned participants aged 12 years and older who tested negative for COVID-19 but lived with an infected patient to receive either oral ensitrelvir (375 milligrams [mg] on day 1 and 125 mg on days 2 through 5) or a placebo within 72 hours after the index patient developed symptoms.

Nasopharyngeal swabs were collected from participants for testing on days 1, 3, 6, 10, 15, 21, and 28. The trial was conducted in the United States, Japan, Argentina, South Africa, and Vietnam from June 2023 to September 2024.

Households ‘key sites for transmission’

The primary study end point was confirmed symptomatic COVID-19 infection by day 10 in a household member in the modified intention-to-treat population, which included all participants who received at least one dose of ensitrelvir (1,030 participants) or placebo (1,011).

The average participant age was 42.4 years, 71.1% underwent randomization within 48 hours after symptom onset in the index patient, and 37.0% had at least one risk factor for severe COVID-19.

Ensitrelvir is approved in Japan for the treatment of mild-to-moderate COVID-19 in people aged 12 years and older, and, based on the findings of this trial, it is also approved in that country for postexposure prevention in contacts.

“Households are key sites for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with secondary attack rates of up to 32 to 48% among household contacts during the omicron era,” the authors wrote.

“Nonpharmaceutical interventions (e.g., masking, isolation, and ventilation) may lower the risk of household transmission, but such interventions are not fully protective and their use in households varies widely.”

Similar adverse-event rates in two groups

Over 98% of household contacts were positive for SARS-CoV-2 antibodies, indicating previous exposure to the virus. Antiviral therapy—most often with ensitrelvir (13.6%)—was started in 18.7% of the 1,319 index patients. About 83% of index patients had multiple household contacts.

The COVID-19 infection rate was 67% lower in the ensitrelvir group than in placebo recipients (2.9% vs. 9.0%; risk ratio, 0.33). The incidence of adverse events was similar in the two groups (15.1% in ensitrelvir recipients and 15.5% in the placebo group), as was the rate of serious adverse events (0.2% in each group). No COVID-related hospitalizations or deaths occurred.

In the intention-to-treat population, the COVID-19 infection rate was significantly lower in ensitrelvir recipients than in the placebo group (4.4% vs. 10.2%; risk ratio, 0.43) through day 10.

In contrast to a rapid increase in illnesses by day 2 in placebo recipients, fewer events occurred in the ensitrelvir group by days 10 to 12; subsequently, new events occurred in a similar proportion of participants in the two groups, showing that the lower incidence of COVID-19 in the ensitrelvir group was maintained.

Ensitrelvir showed significant reductions in the relative risk of COVID-19 infection through day 10 of 67% in the modified intention-to-treat population and of 57% in the intention-to-treat population.

“In addition, in the subgroup analysis involving the household contacts with risk factors, the percentage of those in whom COVID-19 developed was 2.4% in the ensitrelvir group and 9.9% in the placebo group,” the authors wrote. “Ensitrelvir postexposure prophylaxis was also associated with a 34% relative risk reduction in SARS-CoV-2 transmission within households.”

Possible tool for congregate living

The benefits of ensitrelvir generally appeared consistent across most subgroups, including older adults and participants at risk for severe disease.

Post hoc analyses suggested that SARS-CoV-2 viral loads were lower in the ensitrelvir group than in placebo recipients in those infected at baseline or infected while they were receiving postexposure prevention. In both of these subgroups, ensitrelvir recipients appeared to have lower symptom scores early in their illness than the placebo group.

Among household contacts given ensitrelvir, genome sequencing identified viral variants with amino acid substitutions incurred during therapy in 1.9% of the modified intention-to-treat population and 14.9% of the intention-to-treat baseline COVID-positive population.

Of the associated index patients, 20 received no antiviral treatment, while 10 were given ensitrelvir, two received molnupiravir, and three received nirmatrelvir–ritonavir (Paxlovid).

“These findings suggest the potential effectiveness of ensitrelvir in reducing the risk of illness in other unprotected contexts, such as during outbreaks in acute and long-term care facilities,” the researchers conclude.

In a Shionogi news release, Aeron Hurt, Ph.D., the company’s vice president of global medical science, said, “By preventing COVID-19, people can avoid not only potentially serious consequences of acute disease, but also the risk of exacerbating pre-existing conditions or acquiring new conditions, such as long COVID.

“Ensitrelvir cuts the chances of developing COVID-19 by two-thirds, which is substantial, particularly in households where the risk of spread is high.”

Barrier organs that form boundaries between the body and the outside environment, such as the lungs, skin, and intestines, face a difficult balancing act. They must respond quickly to threats such as infection, but they also need to avoid triggering unnecessary inflammation that can damage the tissue. A new study led by Whitehead Institute member Pulin Li and graduate student in her lab Diep Nguyen reveals one way the lung manages that tradeoff.

Published in Cell Systems, the research found that immune sensitivity is not evenly distributed across the lung. Instead, it arranges in tiers: cells at the outer surface respond cautiously, while cells deeper in the tissue are more likely to sound the alarm when a threat breaks through.

“The central question was how tissues balance the benefits and harmful effects of immune activation when they face different degrees of danger or stress,” says Li, who is also a professor of biology at MIT. “Too little immune activation leaves the tissue unprotected, but too much can create inflammation and damage.”

The team focused on the lung, where epithelial cells line the airways and air sacs and form a physical barrier between the body and the outside world. These cells sit at the point of first contact with inhaled viruses, microbes, allergens, and other particles. For that reason, they are often thought of as front-line defenders.

But the new study suggests that the lung’s outermost defenders are deliberately cautious.

Using mouse models of influenza infection and imaging methods that allowed them to measure infection and immune responses in individual cells, the researchers found that epithelial cells were the least likely to respond to infection by producing interferons, signaling proteins that help alert the immune system. Cells deeper in the tissue, especially endothelial cells that line blood vessels, were much more likely to respond.

This arrangement suggests that the lung uses location as a clue to the seriousness of a threat. A stimulus that remains at the surface may not require a large immune response. But when infection breaches the epithelial barrier and reaches deeper tissue, the lung treats that as a more dangerous threat and activates a stronger defense.

“A less severe threat only requires a lower level of immune response,” says Nguyen. “As a threat goes deeper into the tissue, the inner cell types can encode that information and indicate that the threat has invaded further.”

The researchers traced these differences in sensitivity, in part, to immune-sensing proteins called pattern recognition receptors. These receptors detect molecular signs of infection or damage. One receptor, RIG-I, helps cells recognize viral RNA. Epithelial cells had relatively low levels of RIG-I and related sensors, while deeper stromal cells had higher levels.

That lower sensitivity appears to protect the lung from unnecessary damage. When the researchers increased RIG-I levels in lung epithelial cells in mice, the animals mounted a stronger immune response to a non-infectious inflammatory trigger. But the heightened response caused more tissue damage and interfered with repair.

The finding helps explain why the lung’s surface cells may be tuned not to overreact. The lung constantly encounters harmless or low-level irritants. If epithelial cells respond too readily, they could turn minor disturbances into damaging false alarms.

The researchers also found evidence that similar patterns may exist in other barrier organs, including the intestine and trachea. That raises the possibility that spatially tiered immune sensing is a broader strategy for protecting organs that face the outside world.

“One impact of this work is that it helps us look at an old question in a new way: how do tissues balance protection with tissue damage?” says Nguyen. “We can start to understand that when we look at the building blocks of the tissue and how they work together.”

Li says the work also reflects the value of studying tissues as communities of cells rather than collections of identical responders.

“To understand physiology, you have to take a multicellular approach,” she says. “Thinking about tissues as communities of cells can reveal new insights into how they function.”