Category: 8. Health

A new study published in the Journal of Psychopharmacology has found that MDMA’s mood-enhancing effects may be partly driven by changes in brain systems related to serotonin, oxytocin, and vasopressin—neurochemical pathways that are involved in emotional and social behavior. The results support the growing interest in MDMA as a possible treatment for mental health conditions.

MDMA, commonly known as ecstasy, is a synthetic stimulant with both energizing and hallucinogenic properties. In recent years, researchers have been exploring whether MDMA can be used in controlled therapeutic settings to help people with conditions like post-traumatic stress disorder or social anxiety. Its ability to reduce fear and increase feelings of connection makes it especially promising for patients who struggle with interpersonal difficulties. However, scientists still know relatively little about how MDMA produces these effects in the brain, or how these effects vary depending on dosage.

To explore these questions, researchers from the Medical University of Lublin and the International Institute of Molecular and Cell Biology in Poland tested the effects of MDMA on 3-week-old zebrafish. This developmental stage is roughly equivalent to adolescence in humans and represents a time when social behaviors are emerging and brain systems involved in emotion are still developing.

Zebrafish are small freshwater fish native to South Asia that have become widely used in biomedical research. They develop rapidly, are transparent in early stages, and share a high degree of genetic and physiological similarity with humans. Because their brains contain many of the same neurotransmitter systems as mammals, and their behavior can be easily observed and quantified, zebrafish are especially valuable for studying brain development, drug effects, and psychiatric disorders.

The researchers were particularly interested in how MDMA influences anxiety and sociability, and whether these effects could be linked to oxytocin—a hormone involved in social bonding and emotional regulation.

The scientists conducted several behavioral tests to assess anxiety and social behavior in the zebrafish. One test measured how closely the fish stuck to the edges of a new environment—a behavior known as thigmotaxis, which is often used as an indicator of anxiety in animals. Another test evaluated how much time the fish spent in a light versus dark area, since zebrafish tend to avoid darkness when they feel safe. Finally, a social preference test measured whether the fish were more likely to spend time near familiar conspecifics, or members of their species.

The zebrafish were divided into groups and exposed to various concentrations of MDMA. They were also treated with either an oxytocin receptor agonist, which mimics the effects of oxytocin, or an antagonist, which blocks those effects. For comparison, some fish were given diazepam, a known anti-anxiety medication. After behavioral testing, the researchers examined the expression of several genes in the fish’s brains, looking at those related to serotonin signaling, oxytocin, and vasopressin. They also analyzed how MDMA affected specific intracellular pathways involved in mood and behavior, such as AKT and ERK1/2 signaling.

The researchers found that MDMA had a dose-dependent effect on anxiety. At very low doses, it appeared to increase anxiety-like behavior. But at moderate doses, particularly 2.5 micromolar, MDMA reduced signs of anxiety. Fish at this dose spent more time in the center of a new environment and were quicker to explore dark areas—both behaviors associated with lower anxiety. However, at higher doses, MDMA began to reduce locomotion and showed signs of possible toxicity, suggesting that the therapeutic range is narrow.

In terms of social behavior, the lowest dose of MDMA (0.5 micromolar) increased the time fish spent near their peers, suggesting enhanced sociability. Interestingly, this prosocial effect was most noticeable at doses that increased anxiety, indicating a complex relationship between emotional and social responses. The oxytocin receptor agonist also promoted social interaction and showed anti-anxiety effects, but only under certain conditions.

In contrast, the antagonist had no noticeable effect on behavior, which may indicate that blocking the oxytocin system is not enough on its own to alter emotional or social responses in zebrafish.

On the molecular level, MDMA exposure led to reduced expression of genes involved in serotonin signaling, including two types of serotonin receptors and the serotonin transporter. These changes may reflect the compound’s action on serotonin release, which is known to be one of MDMA’s main effects in the brain.

At the same time, MDMA increased the expression of genes for oxytocin receptors and reduced the expression of vasopressin receptor genes. While MDMA did not appear to increase actual oxytocin levels in the brain, the changes in receptor expression suggest that it may make brain regions more sensitive to oxytocin’s effects.

The researchers also found that different doses of MDMA affected specific signaling pathways in the brain. At the lowest tested dose, MDMA reduced activation of the AKT pathway, which has been linked to social behavior in other animals. The oxytocin agonist, on the other hand, increased activity in the ERK1/2 pathway, which is known to be involved in anxiety regulation. These findings suggest that different aspects of MDMA’s effects—its influence on anxiety versus social behavior—may be driven by distinct biological mechanisms.

As with any study, there are caveats to consider. Most importantly, the study was conducted in zebrafish, whose brains are simpler than those of mammals and lack some structures found in humans. Although zebrafish share many of the same neurotransmitter systems and genetic pathways, findings in fish may not always translate directly to human biology. Additionally, the study only looked at the short-term effects of MDMA, and more work is needed to understand how repeated or long-term exposure might influence behavior or brain function.

Future research could build on these findings by examining how MDMA affects brain circuits at different developmental stages or by testing how the compound interacts with stress. The researchers also suggested that genetic tools such as CRISPR could be used to further investigate the role of specific receptors in mediating MDMA’s effects. As scientists work toward better treatments for conditions like social anxiety and post-traumatic stress, studies like this one offer a window into how compounds like MDMA could be used not just as recreational drugs, but as tools for healing.

The study, “Exploring the impact of MDMA and oxytocin ligands on anxiety and social responses: A comprehensive behavioural and molecular study in the zebrafish model,” was authored by Monika Maciag, Olga Doszyn, Artur Wnorowski, Justyna Zmorzynska, and Barbara Budzynska.

Prolonged emergency department (ED) length of stays and boarding times for older adults significantly increased between 2017 and 2024, highlighting systemic challenges for hospitals across the US, according to a research letter published in JAMA Internal Medicine.¹

The researchers noted that extended ED stays in older adults are associated with a higher risk of adverse events, such as mortality and delirium, as well as treatment delays, worse patient experiences, and loss of privacy. To improve care for this population, CMS implemented the Age-Friendly Hospital Measure in January 2025.²

This policy requires hospitals to limit total ED length of stay to under 8 hours and ensure admission to occur within 3 hours of the decision to admit. However, national data on these measures have been lacking.¹ To address this gap, the researchers conducted a cross-sectional study to establish national benchmarks.

Using the Epic Cosmos health records database, which includes data from 1633 hospitals, 295 million patients, and 78 million admissions, they analyzed ED encounters from January 2017 to December 2024.³ They focused on 2 key metrics for patients aged 65 and older, namely the proportion with an ED length of stay over 8 hours and the proportion of admitted patients waiting more than 3 hours from bed request to admission.¹

In 2017, 12% of 4,564,359 ED encounters involved a length of stay over 8 hours. By 2024, this rose to 20% of 12,392,737 encounters. The largest increase occurred in academic hospitals, where prolonged stays grew from 22% of 1,787,179 encounters in 2017 to 36% of 4,311,417 encounters in 2024.

During the same period, boarding times over 3 hours increased from 22% of 1,787,179 encounters in 2017 to 36% of 4,311,417 encounters in 2024. Again, the largest increase was seen in academic hospitals, where boarding rose from 31% in 2017 to 45% in 2024.

Trend analyses showed small annual increases in both measures from 2017 to 2020 (length of stay, 1.1% [95% CI, 0.6-1.6]; boarding, 2.8% [95% CI, 1.5-4.0]), followed by sharper rises from 2020 to 2022 during the COVID-19 pandemic (length of stay, 4.2% [95% CI, 1.7-6.7]; boarding, 6.1% [95% CI, 2.5-9.8]). In contrast, from 2022 to 2024, both trends slightly declined (length of stay, –1.7% [95% CI, –2.3 to –1.1]; boarding, –3.2% [95% CI, –4.5 to –1.9]).

Although further investigation is needed, the researchers suggested the increases may be driven by growing patient complexity, increased demand, and ongoing staffing and resource shortages.

Lastly, they acknowledged the study’s limitations, one being that Epic overrepresents larger and academic hospitals. Also, not all hospitals that use Epic contribute to Cosmos. Despite this, the researchers expressed confidence in their findings and emphasized the need to address the declining ED experience for older US adults.

“Worsening ED LOSs [lengths of stay] and boarding contribute to ED crowding, reflect systemic health care dysfunction, and, most importantly, harm individual patients,” the authors concluded. “Addressing these trends is critical to safeguarding both the health of older adults and the health systems caring for them.”

References

1. Haimovich AD, Berry SD, Landon BE. Prolonged emergency department stays for older US adults. JAMA Intern Med. doi:10.1001/jamainternmed.2025.2006
2. FY 2025 hospital inpatient prospective payment system (IPPS) and long-term care hospital prospective payment system (LTCH PPS) proposed rule—CMS-1808-P fact sheet. CMS. April 10, 2024. Accessed June 30, 2025. https://www.cms.gov/newsroom/fact-sheets/fy-2025-hospital-inpatient-prospective-payment-system-ipps-and-long-term-care-hospital-prospective
3. Fast facts on US hospitals, 2024. American Hospital Association. 2024. Accessed June 30, 2025. https://www.aha.org/system/files/media/file/2024/01/fast-facts-on-us-hospitals-2024-20240112.pdf

Inflammation, long considered a hallmark of aging, may not be a universal human experience, according to a new study from Columbia University Mailman School of Public Health. The research suggests that “inflammaging”-chronic, low-grade inflammation associated with aging-appears to be a byproduct of industrialized lifestyles and varies significantly across global populations. The findings are published in Nature Aging.

Researchers analyzed data from four populations: two industrialized groups-the Italian InCHIANTI study and the Singapore Longitudinal Aging Study (SLAS)-and two Indigenous, non-industrialized populations-the Tsimane of the Bolivian Amazon and the Orang Asli of Peninsular Malaysia. While the inflammaging signature was similar between the two industrialized populations, it did not hold in the Indigenous groups, where inflammation levels were largely driven by infection rather than age.

“In industrialized settings, we see clear links between inflammaging and diseases like chronic kidney disease,” said lead author Alan Cohen, PhD, associate professor of Environmental Health Sciences at Columbia Mailman School and faculty member of the Butler Columbia Aging Center. “But in populations with high infection rates, inflammation appears more reflective of infectious disease burden than of aging itself.”

Interestingly, while the indigenous populations, particularly the Tsimane, had high constitutive levels of inflammation, these did not increase with age and, crucially, did not lead to the chronic diseases that plague industrialized societies. In fact, most chronic diseases- diabetes, heart disease, Alzheimer’s, etc.-are rare or largely absent in the Indigenous populations, meaning that even when young Indigenous people have profiles that look similar on the surface to those of older industrialized adults, these profiles do not lead to pathological consequences.

“These findings really call into question the idea that inflammation is bad per se,” said Cohen. “Rather, it appears that inflammation-and perhaps other aging mechanisms too-may be highly context dependent. On the one hand, that’s challenging, because there won’t be universal answers to scientific questions. On the other, it’s promising, because it means we can intervene and change things.”

The study used a panel of 19 cytokines-small immune-signaling proteins-to assess inflammation patterns. While these markers aligned with aging in the Italian and Singaporean datasets, they did not replicate among the Tsimane and Orang Asli, whose immune systems were shaped by persistent infections and distinct environmental exposures.

Key findings include:

• Approximately 66 percent of Tsimane had at least one intestinal parasitic infection; over 70 percent of Orang Asli had a prevalent infection.
• Inflammaging markers were strongly linked to chronic disease in industrialized populations, but not in Indigenous groups.
• The study challenges the assumption of universal aging biomarkers, suggesting instead that immune-aging processes are population-specific and heavily influenced by the exposome-the totality of environmental, lifestyle, and infectious exposures.

“These results point to an evolutionary mismatch between our immune systems and the environments we now live in,” Cohen explained. “Inflammaging may not be a direct product of aging, but rather a response to industrialized conditions.”

The authors call for a reevaluation of how aging and inflammation are measured across populations and emphasize the need for standardized, context-aware tools. “Factors like environment, lifestyle-such as high physical activity or a very low-fat diet-and infection may all influence how the immune system ages,” said Cohen. “Understanding how these elements interact could help develop more effective global health strategies.”

Co-authors are listed in the manuscript.

The study was supported by the Impetus program, the French National Research Agency (ANR) under the Investments for the Future (Investissements d’Avenir) program, grant ANR-17-EURE-0010; the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under project ID 499552394 (SFB 1597/1) and grant HE9198/1-1, and the Intramural Research Program of the NIH, National Institute on Aging.

Although a cough medicine called Ambroxol is approved in Europe for treating respiratory conditions and has a long-standing safety record, including use at high doses and during pregnancy, it is not approved for any use in the United States or Canada.

Parkinson’s disease dementia causes memory loss, confusion, hallucinations and mood changes.

About half of those diagnosed with Parkinson’s develop dementia within 10 years, profoundly affecting patients, families and the health care system.

“Our goal was to change the course of Parkinson’s dementia,” said Dr. Stephen Pasternak, a cognitive neurologist at Parkwood Institute, St Joseph’s Health Care London and Robarts Research Institute.

“This early trial offers hope and provides a strong foundation for larger studies.”

The 12-month clinical trial involved 55 participants with Parkinson’s disease dementia.

The authors gave one group daily Ambroxol while the other group received a placebo.

They monitored memory, psychiatric symptoms and GFAP, a blood marker linked to brain damage.

According to the team, Ambroxol was safe, well-tolerated and reached therapeutic levels in the brain.

Psychiatric symptoms worsened in the placebo group but remained stable in those taking Ambroxol.

Participants with high-risk GBA1 gene variants showed improved cognitive performance on Ambroxol.

GFAP increased in the placebo group but stayed stable with Ambroxol, suggesting potential brain protection.

“Current therapies for Parkinson’s disease and dementia address symptoms but do not stop the underlying disease,” Dr. Pasternak said.

“These findings suggest Ambroxol may protect brain function, especially in those genetically at risk. It offers a promising new treatment avenue where few currently exist.”

Ambroxol supports a key enzyme called glucocerebrosidase (GCase), which is produced by the GBA1 gene.

In people with Parkinson’s disease, GCase levels are often low. When this enzyme doesn’t work properly, waste builds up in brain cells, leading to damage.

“This research is vital because Parkinson’s dementia profoundly affects patients and families,” Dr. Pasternak said.

“If a drug like Ambroxol can help, it could offer real hope and improve lives.”

The results appear in the journal JAMA Neurology.

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Carolina R. A. Silveira et al. Ambroxol as a Treatment for Parkinson Disease Dementia: A Randomized Clinical Trial. JAMA Neurol, published online June 30, 2025; doi: 10.1001/jamaneurol.2025.1687

A report comparing childhood obesity prevalence before the COVID pandemic and since the height of the pandemic shows a dramatic rise in the numbers for Black children and Black adolescents with obesity. Findings were published in the Annals of Internal Medicine.

Researchers, led by Michael Liu, MD, MPhil, with the Center for Outcomes Research at Beth Israel Deaconess Medical Center in Boston, found that overall, the prevalence of obesity didn’t change significantly. Prevalence was 20.3% from January 2011 to March 2020, when COVID shutdowns began, and rose to 22.0% from August 2021 to August 2023. But after accounting for secular trends, “no overall increase in obesity prevalence was seen during the pandemic relative to the pre-pandemic period (adjusted difference, 0.52 percentage points; 95% CI, 2.3-3.3 percentage points).

Pandemic-related increases in obesity prevalence were observed only in Black children and adolescents, the authors wrote, for whom rates were 22.4% in the decade before the pandemic and 35% in the 2 years after the height of COVID.

Racial Disparities Clear

Now, “In the US, more than in 1 in 3 Black youth, more than 1 in 4 Hispanic youth, nearly 1 in 5 White youth, and 1 in 10 Asian youth currently meet the criteria for obesity,” the authors reported.

Prevalence of severe obesity overall and across all subgroups remained stable between 2011 and August 2023.

Researchers used serial cross-sectional data from the 2011 to August 2023 survey cycles of the National Health and Nutrition Examination Survey and included 17,507 children aged 2-11 years and adolescents aged 12-19 years. Height and weight from in-person examinations were used to calculate BMI. Obesity in this study was defined as a BMI at or above the age- and sex-specific 95th percentile according to the CDC growth charts. Severe obesity was defined as a BMI of 120% or more of the 95th percentile.

Addressing Underlying Factors

The next step is to address the factors that have led to the disparities documented in this report through public health and policy interventions, Therese F. Anderson, MD, assistant professor of family medicine at Mayo College of Medicine in Jacksonville, Florida, told Medscape Medical News.

She pointed out the authors discuss multiple factors that have contributed to an increase in obesity during the COVID-19 pandemic and thereafter, including disruption in daily routines with school closures and reduced access to structured exercise and activity, leading to increased screen time and sedentary behaviors. Mealtimes were disrupted, and there was more reliance on ultraprocessed foods.

“Studies thus far have shown that Black and minority youth were disproportionately impacted due to higher rates of food insecurity, lower neighborhood resources — such as access to parks and safe spaces for exercise — as well as increased economic stress during the pandemic,” she noted.

Anderson said these new numbers add support for policies and funding in areas such as improvement of access to healthy foods, expansion of food assistance programs, incentives to build grocery stores in food deserts, and promotion of safe spaces for activity.

Medicaid Coverage for GLP-1s

“Additionally, expanding state Medicaid programs to fund weight management programs as well as medications like GLP-1s [glucagon-like peptide-1s], which are FDA approved for age 12 and up, are potential avenues for improvement. Currently, there are only 13 states with coverage for GLP-1s under Medicaid,” Anderson said.

Pediatricians have an important role in addressing childhood obesity, she said. First, she said, is promoting family-based approaches to lifestyle modifications, such as healthy meals and family exercise.

“Secondly, we need to continue to advocate for policy changes as they impact the health of Black and minority youth. For example, the American Academy of Pediatrics is urging lawmakers to reject funding cuts to Medicaid and the Children’s Health Insurance Program (CHIP),” she said. “Lastly, we need to familiarize ourselves with new interventions as they are emerging, such as telehealth and medications like GLP-1s.”

Financial disclosures for authors are available with the full article. Anderson reported having no relevant financial relationships.

Marcia Frellick is a Chicago-based, independent healthcare journalist.

Ireland has unveiled a sweeping new National Sexual Health Strategy aimed at transforming access to sexual health services over the next decade, with a strong emphasis on prevention, equity, and integration across the healthcare system.

The strategy, covering the period from 2025 to 2035, was launched by Minister for Health Jennifer Carroll MacNeill and Minister of State for Public Health, Wellbeing and the National Drugs Strategy Jennifer Murnane O’Connor. It sets out a comprehensive framework to address the evolving challenges of sexual health in Ireland, including rising rates of sexually transmitted infections (STIs), persistent stigma, and unequal access to care.

“This comprehensive Strategy reflects the evolving opportunities and challenges we face and outlines the steps we must take to ensure a healthier future for everyone, no matter their age, gender, orientation, ethnicity, or background,” said Carroll MacNeill at the launch. “Our focus now is on continuing to develop and expand services that meet the needs of our population at every stage of life.”

Access to services

The strategy builds on the foundation of the 2015-2020 plan, which was extended during the Covid-19 pandemic. It introduces four core goals: promoting sexual health education, expanding equitable access to services, supporting reproductive choice, and strengthening surveillance and research. The first of three action plans, covering 2025–2028, was published alongside the strategy and outlines immediate implementation steps.

Among the key measures are expanded access to contraception through the Free Contraception Scheme, increased availability of STI testing – including home testing kits – and enhanced support for HIV prevention and treatment, including Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP).

The strategy also commits to developing a new Model of Care for sexual health services, with a focus on geographic equity and integration into primary care.

Murnane O’Connor described the strategy as “a significant step forward in our efforts to protect and promote sexual health and wellbeing for everyone living in Ireland.”

“This Strategy reflects a modern, inclusive and evidence-based approach, one that empowers people with the information, access and support they need to make informed choices and avoid unnecessary risks, while supporting healthy relationships,” she said.

Supporting justice sector

The strategy also includes a commitment to support the Justice sector and Cuan in preventing domestic, sexual and gender-based violence (DSGBV), and to align with Ireland’s international obligations under EU, UN, and WHO frameworks.

The Irish Pharmacy Union (IPU) welcomed the strategy, highlighting the increasingly central role of community pharmacies in delivering sexual health services.

“As the most accessible healthcare providers, Irish community pharmacies play an increasingly important role in delivering sexual health services as part of community-based healthcare,” an IPU spokesperson said.

Pharmacists already provide emergency contraception without prescription, dispense free contraception to women aged 17–35 under the HSE-funded scheme, and offer confidential consultations on STI prevention and treatment. They also dispense PrEP to eligible individuals and administer HPV vaccines privately to those aged 16–44.

Empowering pharmacists

The IPU said it was particularly encouraged by proposals to empower pharmacists to initiate and extend prescriptions for contraception and to dispense PEP, especially in rural or out-of-hours settings.

“This expanded role is welcomed and promises to enhance the sexual health services provided by pharmacies,” the spokesperson said. “However, adequate resourcing is essential to ensure its success.”

Europe’s rising STI rates

The strategy’s publication comes amid growing concern across Europe about rising STI rates and uneven access to prevention and treatment services.

According to the European Centre for Disease Prevention and Control (ECDC), infections such as gonorrhoea, syphilis, and chlamydia are increasing in nearly all EU/EEA countries, with significant variation in national responses.

Northern and Western European countries – including Sweden, the Netherlands, and Germany – have led the way with comprehensive sexual education and robust public health campaigns. In contrast, several Southern and Eastern European nations continue to face cultural and financial barriers to implementing similar measures.

Access to HIV prevention tools such as PrEP also varies widely. France, Germany, and Spain have established national programmes with strong uptake, while many Central and Eastern European countries lack formal initiatives due to regulatory or funding constraints.

Surveillance systems are similarly inconsistent.

Nordic countries maintain real-time data collection, while others struggle with underreporting and limited laboratory capacity. The ECDC has warned that antimicrobial resistance in gonorrhoea is an emerging threat and has called for greater harmonisation of policies and improved access to services across the bloc.

Ireland’s new strategy aligns with these EU-wide priorities, particularly in its emphasis on integrated care, expanded access, and data-driven policy. The government has committed to cross-sectoral collaboration and public engagement in shaping the next two action plans, due in 2028 and 2031.

“The urgency of coordinated action is clear,” said Professor Mary Horgan, Ireland’s Interim Chief Medical Officer. “Sexual health is a key part of overall health and wellbeing, but also of wider public health and of infection control.”

With the publication of the National Sexual Health Strategy 2025–2035, Ireland has positioned itself at the forefront of a renewed European effort to address sexual health with clarity and inclusivity.

The last half of the 20^th century saw a sea change in our capacity to fight disease and improve health. The bedrock for this development was the consistent support for biomedical research, and the nation has benefited from scientific discoveries that have been translated into treatments for previously untreatable conditions.

For example, the discovery of how to effectively use penicillin revolutionized the treatment of infections and saved the lives of men, women, and children. Determining the structure of DNA provided the basis of modern gene therapies for disorders ranging from sickle cell disease to cancers, and the introduction of technologies that power non-invasive diagnostic scans have dramatically helped us to identify disorders early and accurately.

Academic medical centers and universities across the United States play a large role in biomedical research discovery, translation of findings, and implementation of new treatment and prevention strategies.

Since our inception in 1998, Women’s Health Research at Yale (WHRY) has initiated and supported such research on health conditions that directly affect communities all over the country. In particular, we have focused on advancing our understanding of women’s health and on sex differences in health and disease that inform our understanding and treatment of disorders in women and men.

The Practical Benefit of Research

All biomedical research begins with a fundamental question that needs to be addressed. Such questions target gaps in our knowledge about the prevalence and demographics of disorders, the factors that cause disorders, as well as how to treat or prevent disorders.

Women’s Health Research at Yale’s Pilot Project Program funds innovative and interdisciplinary studies that answer these types of questions with regard to women’s health or sex differences in health, and more than 100 Pilot Project studies have been completed on a multitude of topics critical to improving health, quality of life, and longevity. Five examples of topic areas in which studies have generated practical benefit:

Cardiovascular Disease

Recognizing that cardiovascular disease (CVD) is the leading cause of death among women and men in the U.S., CVD has been an area of investigation since the center’s inception through the current day.

For example, among our inaugural Pilot Projects, Viola Vaccarino, MD, PhD, revealed for the first time that women who had coronary bypass surgery were nearly twice as likely as men to be readmitted to the hospital, develop infections, report lower physical functioning, and experience more depressive symptoms.

This seminal work informed clinicians and researchers of the increased risk of bypass surgery for women and provided the groundwork for subsequent investigations on the biological and social factors that could be modified to change these outcomes.

Currently, one of our CVD projects, led by Samit Shah, MD, PhD, assistant professor of medicine (cardiology), centers on the important goal of understanding and detecting heart attacks due to microvascular or “small vessel” disease, which are more common in women than men.

Routine testing for someone with symptoms of heart disease focuses on the most common cause of a heart attack, which is a blockage in the major arteries that supply blood to the heart. However, heart attacks can also be caused by a lack of blood flow in the small vessels of the heart. Here, there is a great need to remedy the underdiagnosis of different types of heart attacks that are more common in women.

Shah’s two-year funding from WHRY tested the use of his novel method to detect small vessel disease and coronary vasospasm in over 175 women presenting with symptoms of heart attack at Yale New Haven Hospital.

First using routine coronary angiography and evaluating for large vessel blockages, Shah then assesses the ability of the blood vessels to open or dilate by injecting a medication called acetylcholine, which can unmask the diagnosis of coronary vasospasm. After that, a wire 14/1000^th of an inch is used to measure pressure and flow in the small vessels that infiltrate the heart to diagnose coronary microvascular disease.

Using this new technique, more than 80% of women who underwent Shah’s advanced testing protocol received an accurate diagnosis and comprehensive treatment plan, which led to symptom relief and increased quality of life. This work was published in the Journal of the American Heart Association.

Based on these findings, a Cardiovascular Diagnostics Innovation Fund named for Dr. Shah was created in early 2025 to support his efforts to develop his technique for commercialization. Shah was also awarded a 2025 Blavatnik Fund for Innovation grant to further Angiomedix, his company aimed at revolutionizing the diagnosis of heart disease.

The importance of studying sex differences in cardiovascular disease was again highlighted in a recent announcement from 58 cardiology journals including Circulation, European Heart Journal, JAMA Cardiology, and Journal of the American College of Cardiology. Moving forward, the journals recommend those submitting manuscripts for publication describe how sex was considered in their study design and analytic approach and that data are reported for both women and men. This work was begun by the White House Initiative on Women’s Health Research.

Cancer

Another early area of focus for WHRY that has grown over time is cancer research, the second most likely cause of morbidity and mortality in the U.S. for women and men. To date, 25 WHRY projects have examined cancers that are unique to women as well as cancers and their treatments that affect women and men differently.

For example, in 1998, it was known that mutations in the BRCA1 and BRCA2 genes were risk factors for occurrence of breast cancer. However, in a 15-year follow-up study of women who had been diagnosed with breast cancer, Bruce Haffty, MD, professor of diagnostic radiology, showed for the first time that these gene mutations also predicted an increased risk of recurrence compared to women without these mutations. This risk extended to both the initially affected breast and the non-affected breast.

This landmark discovery was published in The Lancet, providing women and their doctors with crucial information regarding options for follow-up and prophylactic treatment. It also paved the way for new methods that use molecular and genetic data to inform treatment that reduces radiation therapy resistance and improves outcomes.

Another discovery focusing on a type of cancer associated with BRCA 1 and 2 mutations, ovarian cancer, was found through a WHRY Pilot Project by Peter Glazer, MD, PhD, the Robert E. Hunter Professor of Therapeutic Radiology and professor of genetics. His laboratory had found that a lupus antibody (known as 3E10, which defends the body against foreign substances) can penetrate cancer cells and make them more vulnerable to radiation treatment and chemotherapy. Glazer applied for Women’s Health Research at Yale funding to begin the process of uncovering the biological basis for how this occurs – the first step necessary in using this finding to a develop a treatment intervention.

The basic work of this grant began a process that successfully led to identifying the biological underpinnings of how the antibody entered a cancer cell. With this information, Glazer now has designed a drug intervention to potentially treat ovarian cancer that develops from inherited mutations to the BRCA2 gene (which suppresses tumor development). Currently, his novel process of using this antibody as a cancer therapy is being tested in clinical trials.

In a third example of a Pilot Project focused on cancer, Pamela Kunz, MD, professor of medicine (medical oncology), determined sex differences in the adverse effects of treatment for gastrointestinal cancer known as neuroendocrine neoplasm (NEN). Though rare by incidence, these cancers are often considered chronic cancers because they grow more slowly than other cancers, requiring patients to be treated over many years.

Clinical observation has shown that women are more likely to develop adverse effects from treatments for these cancers. Kunz and her team have now examined and analyzed large national clinical trial datasets and have provided clear findings that women experience more adverse effects from chemotherapy and radiation treatment than men. This results in worse health outcomes, poorer quality of life, and increased costs of care.

Now, having shown sex differences in the effects of standard treatments, Kunz is focused on determining the gene variations associated with NEN that can predict patient response. This effort is designed to tailor therapy to specific persons and, in turn, reduce side effects and improve therapy outcomes in these patients who endure long-term cancer treatments.

Stroke

The third leading cause of death for America’s women and another area of WHRY research is stroke. Women’s Health Research at Yale investigator Lauren Sansing, MD, MS, professor of neurology, used her Pilot Project to determine whether there are differences in the way women and men respond to an intracerebral hemorrhage (ICH) – a rupture of a blood vessel in the brain – the second most common type of stroke. Previous studies indicate women experience more severe symptoms than men in response to ICH, yet limited data are available on why this occurs.

Sansing’s Pilot Project showed that women experience a greater immune response than men when a brain blood vessel ruptures, as evidenced by an increased presence of interferons (proteins produced by immune cells that combat infection). In addition, she found that sex differences in this initial inflammatory response increases with age.

In translating these findings, she is now assessing sex-specific therapies in a model system that provides immune responses to improve outcomes. This research, illustrating that sex differences occur at the molecular level, paves the way for clinical trials that are tailored to women and men.

Human Immune Response

The importance of understanding human immune response in all disorders, particularly infectious disorders, coupled with the onset of the COVID-19 pandemic, prompted funding for a first-of-its-kind study on sex differences in the immune response to COVID-19.

Early reports at the onset of the SARS-CoV-2 outbreak suggested men were dying from COVID-19 at a greater rate than women. In response to these reports, Akiko Iwasaki, PhD, Sterling Professor of Immunobiology was awarded a WHRY Pilot Project to determine whether and how sex differences in the immune response to the coronavirus accounted for this outcome in the pandemic’s earliest days.

When the body is attacked by a pathogen, such as a virus, it mounts an inflammatory response to fight the infection. This innate immune response includes the production of inflammatory proteins called cytokines. Although cytokines are key to managing infection, overproduction of these proteins can cause harm. Iwasaki’s research found that male patients often had higher plasma levels of cytokines than female patients. Additionally, female patients were more likely to have a robust activation of an adaptive immune response that produces T-cells, which are white blood cells that can recognize individual invading viruses and eliminate them.

In the August 2020 issue of Nature, Iwasaki and her team published an initial biological explanation for “… the observed sex biases in COVID-19 and an important basis for the development of a sex-based approach to the treatment and care of male and female patients with COVID-19.”

Iwasaki and her team continue to examine sex differences, now in long COVID – which is more common in women than men and in which women and men experience different sets of symptoms and distinct patterns of organ system involvement.

Alzheimer’s Disease

The prevalence and impact of Alzheimer’s disease continues to grow. Women account for two-thirds of those living with the disease in the United States, which is the fifth leading cause of death for women. Although women generally live longer than men in the U.S., this alone does not account for this difference in Alzheimer’s disease cases.

An example of WHRY studies on Alzheimer’s include a co-funded WHRY-Yale Alzheimer’s Disease Research Center Pilot Project. This study was conducted by Le Zhang, PhD, in the Department of Neuroscience and Stephen Strittmatter, MD, PhD, Vincent Coates Professor of Neurology and professor of neuroscience.

The human brain contains about 100 billion individual cells that form a variety of cellular structures in the tightly packed, interconnected landscape of the human brain. For researchers seeking precise causes of impairment from Alzheimer’s disease and other dementias, the brain’s intricacy and diversity in the molecular underpinnings of these diseases have made it difficult to devise prevention strategies and treatments.

In order to understand what is happening to people with such a complex disease, the investigators started at the cellular level and looked for sex-specific differences that exist in the brains of women and men with and without Alzheimer’s disease. Having found sex differences among cell populations in Alzheimer’s disease, they are now building upon current knowledge of abnormalities that cause cell death and how these relate to disease symptoms such as cognitive dysfunction. Such knowledge has the potential to identify hidden biological clues and produce novel therapeutic targets that will benefit women and men at risk for developing this destructive disease.

A second WHRY Pilot Project led by Carolyn Fredericks, MD, associate professor of neurology, studied the relationship of a known genetic risk factor for Alzheimer’s disease to brain circuitry in women compared with men.

Every person inherits one “APOE allele” from each parent. For women who carry one copy of the APOE-ε4 variant, the risk of developing Alzheimer’s disease can be as high as three times greater than someone without this variant. Fredericks recognized, however, that not enough is known about the impact of the genetic risk factor on brain circuitry in women compared with men. Her research evaluated a large public dataset that included brain scans and APOE test results for more than a thousand individuals who had preclinical Alzheimer’s disease – meaning, they had evidence of Alzheimer’s pathology in their brains but had yet to show cognitive symptoms of Alzheimer’s disease.

Using a technique called connectome-based predictive modeling that allows researchers to visualize communication within the brain, Fredericks and her team successfully modeled which parts of the brain had activity that was “working together” to achieve an outcome – and how that tightly correlated activity related to how much of the protein tau was in the corresponding regions. Tau is an important protein in brain health, and when it malfunctions, such as folding onto itself or becoming detached and forming tangles, it contributes to the development and progression of Alzheimer’s disease.

Over the two-year investigation, Fredericks and her team successfully developed a method for using functional connections in the brain to model and predict the location of tau in brain networks of individuals with amyloid deposits, or preclinical disease.

Opportunity Abounds

Much can be gained through biomedical research in building a base of knowledge that leads to discoveries for treatment and prevention of disorders. As women historically have been understudied and are more likely to have chronic disease and disability, investment in women’s health brings great impact.

As a recent McKinsey report indicated, if we improve women’s health over the course of working years alone, approximately 60% more healthy life years could be gained for women, thus generating more than $294 billion in the annual U.S. GDP within 15 years. Moreover, studying women’s health and sex differences in health and disease improves the lives of women, men and families, and as a consequence, the health of the nation thrives.

E-cigarettes have become increasingly popular over the last two decades, especially among young people. These sleek, deliciously flavored smoking devices are often marketed as a safer alternative to conventional cigarettes, but alarming new research challenges that assumption.

In a study published June 25 in the journal ACS Central Science, researchers tested three popular disposable vape brands for hazardous metals and metalloids such as lead, chromium, antimony, and nickel. Inhaling these toxins can increase the risk of cancer, respiratory disease, and nerve damage. The findings show that e-cigarettes emit dangerously high levels of toxic metals—orders of magnitude higher than levels emitted by traditional cigarettes and other e-cigarettes. One brand released more lead during a day’s use than nearly 20 packs of cigarettes. Given the widespread underage use of vapes, the findings underscore an urgent need for regulatory action, the researchers conclude.

“Our study highlights the hidden risk of these new and popular disposable electronic cigarettes—with hazardous levels of neurotoxic lead and carcinogenic nickel and antimony—which stresses the need for urgency in enforcement,” co-author Brett Poulin, an assistant professor of environmental toxicology at the University of California, Davis, said in a statement. “These risks are not just worse than other e-cigarettes but worse in some cases than traditional cigarettes.”

The Food and Drug Administration (FDA) has cracked down on brands selling flavored, disposable vapes in the U.S. due to concerns about youth access, health risks, and unauthorized sales. Despite issuing warning letters to popular brands, slapping retailers with civil penalties, and blocking e-cigarette imports from other countries such as China, the agency has failed to keep these devices out of the U.S. market.

In the past few years, sales of disposable vapes have overtaken sales of older, refillable vapes. According to the FDA’s Annual National Youth Tobacco Survey for 2025, disposable e-cigarettes are the most commonly used tobacco product among young people. The survey found that 5.9% of middle and high school students (1.63 million) reported current use of e-cigarettes, and of those students, 55.6% use disposable vapes.

Previous studies have investigated the elemental composition of refillable e-cigarettes, but few have looked into these newer devices. To fill that gap, Poulin and his colleagues analyzed the metals and metalloids inside seven disposable vapes made by three brands, including flavored and unflavored liquids. They selected the brands based on popularity and purchased the e-cigarettes from online vendors based in the U.S. All the devices they tested contained nicotine except one, which allowed the researchers to test if nicotine influences the metal concentrations of e-liquids (commonly known as “vape juice”).

The key components of any vape are a battery, e-liquid (commonly known as “vape juice” or “e-juice), and a heating coil. When the user presses a button on the device or—in some cases—simply inhales, the battery heats the coil and turns the e-liquid into an aerosol. These metal components can leach into the e-liquid and thus work their way into the lungs.

The researchers tested the metal concentrations of unused e-liquids and aerosols, using a special instrument to activate the e-cigarettes and generate between 500 and 1,500 puffs per device. They found that “these disposable devices have toxins already present in the e-liquid, or they’re leaching quite extensively from their components into e-liquids and ultimately transferred to the smoke,” lead author Mark Salazar, a PhD candidate in Poulin’s lab, said in the statement.

Some unused e-liquids contained high levels of antimony, a toxic metalloid. Heating coils leached nickel into the e-liquid, while leaded bronze alloy components in some devices leached nickel and lead. The vapors of some devices contained surprisingly high metal levels, including antimony and lead. Interestingly, the metal concentrations of the aerosols increased as the number of puffs increased, suggesting that exposure worsens as the device ages.

Overall, the researchers determined that disposable e-cigarette users are exposed to markedly higher levels of toxic metals and metalloids than those who use refillable vapes, which may lead to increased health risks. Three of the tested vapes produced vapors that contained nickel levels that exceeded cancer risk thresholds, and two emitted potentially cancerous amounts of antimony. Four devices had nickel and lead emissions that surpassed risk thresholds for illnesses besides cancer, such as neurological damage and respiratory disease.

Of the nearly 100 disposable e-cigarette brands available in the U.S., this study tested only three. Despite regulatory efforts, these devices remain wildly popular among adolescents. The researchers hope that their work inspires others to investigate the health risks associated with disposable e-cigarettes, as it would appear they won’t be going away anytime soon.