Category: 8. Health

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

The allure and terror of transferring your consciousness to a computer has long been fodder for cyberpunk novels and billionaire-backed immortality startups. But a substantial chunk of neuroscientists think it might be possible to extract memories from a preserved brain and store those memories inside a computer, according to a new study.

The study, published in the journal PLOS One, suggests that most neuroscientists believe that memory has a physical basis and, on average, give a 40% probability that we might one day be able to emulate a human brain. But there was little consensus as to what exactly that physical basis is, highlighting just how little we know about what memories are made of.

The authors surveyed 312 neuroscientists—both memory experts and general neuroscientists—to get their thoughts on the feasibility of preserving a human brain and later extracting its memories. It was led by Ariel Zeleznikow-Johnston, a neuroscientist at Monash University in Australia and the author of The Future Loves You: How and Why We Should Abolish Death. 

While the researchers wrote that the questions of memory extraction from preserved brains are “strange and speculative,” they provide insight into how neuroscientists think about memory formation.

Results of the survey show that neuroscientists largely agree that memories have a physical substrate rather than relying on a dynamic process that ceases at preservation; they’re likely stored in the synaptic connections between neurons, which strengthen and weaken with experience. The survey showed that 70% of neuroscientists agree that a physical, molecular record of a memory exists—stored in stable changes to neural connectivity and interactions between proteins and other cellular components—of which you could theoretically take a snapshot.

However, “there was no clear consensus on exactly which neurophysiological feature or scale is critical for memory storage,” the authors wrote in the study. The surveyed scientists didn’t agree on what resolution—from the atomic-level composition of biomolecules to nanometer-level resolution of subcellular structures—would be required to extract a memory from a preserved brain. This is largely due to the fact that, while most neuroscientists agree that memory has a physical basis, it’s still up for debate exactly what that basis is.

The survey also asked whether existing tools could theoretically preserve the structure of a brain well enough to extract memories. Preserving a brain in such a way that the proteins and cells remain intact is tricky, since freezing can damage neural tissue. But one way neuroscientists could do this is through aldehyde-stabilized cryopreservation, a technique that combines chemical fixation with vitrification—the process of turning a substance into a glass-like solid by cooling it down rapidly. The study asked neuroscientists to assign a probability that memories could be extracted from a cryopreserved brain. The participants gave a wide range of estimates, but the median answer was around a 40% probability.

The authors asked the neuroscientists how probable it might be to emulate a whole brain—like, uploading and digitizing a person’s brain onto a computer—from preserved neural tissue. That could open up the possibility of uploading your full self and consciousness into a machine. In this case, the median answer was again around 40%, though the authors note that the responses again varied widely.

“Admittedly, that’s not 100 percent,” Zeleznikow-Johnston told IFLScience. “That means that there’s not full consensus in the community that yeah, definitely this will work, but it’s not 0.1 percent, or 0.01 percent. That’s a substantial chunk of neuroscientists who think there’s a very real chance that it will work, and my guess is that actually that number will creep up over time as we get better at doing these brain implants, emulations, all these other things.”

Neuroscientists believe we’re still a long way off from being able to emulate an entire human brain, according to the study. When asked when we might be able to emulate a human brain, the respondents gave a median answer of 2125.

Still, it’s something to think about.

SIOUX FALLS, S.D. | In the time before widespread vaccination, death often came early.

Devastating infectious diseases ran rampant in America, killing millions of children and leaving others with lifelong health problems. These illnesses were the main reason why nearly one in five children in 1900 never made it to their fifth birthday.

Over the next century, vaccines virtually wiped out long-feared scourges like polio and measles and drastically reduced the toll of many others. Today, however, some preventable, contagious diseases are making a comeback as vaccine hesitancy pushes immunization rates down. And well-established vaccines are facing suspicion even from public officials, with Robert F. Kennedy Jr., a longtime anti-vaccine activist, running the federal health department.

“This concern, this hesitancy, these questions about vaccines are a consequence of the great success of the vaccines – because they eliminated the diseases,” said Dr. William Schaffner, an infectious disease expert at Vanderbilt University Medical Center. “If you’re not familiar with the disease, you don’t respect or even fear it. And therefore you don’t value the vaccine.”

Anti-vaccine activists even portray the shots as a threat, focusing on the rare risk of side effects while ignoring the far larger risks posed by the diseases themselves — and years of real-world data that experts say proves the vaccines are safe.

Some Americans know the reality of these preventable diseases all too well. For them, news of measles outbreaks and rising whooping cough cases brings back terrible memories of lives forever changed – and a longing to spare others from similar pain.

Getting rubella while pregnant shaped two lives

With a mother’s practiced, guiding hand, 80-year-old Janith Farnham helped steer her 60-year-old daughter’s walker through a Sioux Falls art center. They stopped at a painting of a cow wearing a hat.

Janith pointed to the hat, then to her daughter Jacque’s Minnesota Twins cap. Jacque did the same.

“That’s so funny!” Janith said, leaning in close to say the words in sign language too.

Jacque was born with congenital rubella syndrome, which can cause a host of issues including hearing impairment, eye problems, heart defects and intellectual disabilities. There was no vaccine against rubella back then, and Janith contracted the viral illness very early in the pregnancy, when she had up to a 90% chance of giving birth to a baby with the syndrome.

Janith recalled knowing “things weren’t right” almost immediately. The baby wouldn’t respond to sounds or look at anything but lights. She didn’t like to be held close. Her tiny heart sounded like it purred – evidence of a problem that required surgery at four months old.

Janith did all she could to help Jacque thrive, sending her to the Colorado School for the Deaf and the Blind and using skills she honed as a special education teacher. She and other parents of children with the syndrome shared insights in a support group.

Meanwhile, the condition kept taking its toll. As a young adult, Jacque developed diabetes, glaucoma and autistic behaviors. Eventually, arthritis set in.

Today, Jacque lives in an adult residential home a short drive from Janith’s place. Above her bed is a net overflowing with stuffed animals. On a headboard shelf are photo books Janith created, filled with memories like birthday parties and trips to Mount Rushmore.

Jacque’s days typically begin with an insulin shot and breakfast before she heads off to a day program. She gets together with her mom four or five days a week. They often hang out at Janith’s townhome, where Jacque has another bedroom decorated with her own artwork and quilts Janith sewed for her. Jacque loves playing with Janith’s dog, watching sports on television and looking up things on her iPad.

Janith marvels at Jacque’s sense of humor, gratefulness, curiosity and affectionate nature despite all she’s endured. Jacque is generous with kisses and often signs “double I love yous” to family, friends and new people she meets.

“When you live through so much pain and so much difficulty and so much challenge, sometimes I think: Well, she doesn’t know any different,” Janith said.

Given what her family has been through, Janith believes younger people are being selfish if they choose not to get their children the MMR shot against measles, mumps and rubella.

“It’s more than frustrating. I mean, I get angry inside,” she said. “I know what can happen, and I just don’t want anybody else to go through this.”

Delaying the measles vaccine can be deadly

More than half a century has passed, but Patricia Tobin still vividly recalls getting home from work, opening the car door and hearing her mother scream. Inside the house, her little sister Karen lay unconscious on the bathroom floor.

It was 1970, and Karen was 6. She’d contracted measles shortly after Easter. While an early vaccine was available, it wasn’t required for school in Miami where they lived. Karen’s doctor discussed immunizing the first grader, but their mother didn’t share his sense of urgency.

“It’s not that she was against it,” Tobin said. “She just thought there was time.”

Then came a measles outbreak. Karen – who Tobin described as a “very endearing, sweet child” who would walk around the house singing – quickly became very sick. The afternoon she collapsed in the bathroom, Tobin, then 19, called the ambulance. Karen never regained consciousness.

“She immediately went into a coma and she died of encephalitis,” said Tobin, who stayed at her bedside in the hospital. “We never did get to speak to her again.”

Today, all states require that children get certain vaccines to attend school. But a growing number of people are making use of exemptions allowed for medical, religious or philosophical reasons. Vanderbilt’s Schaffner said fading memories of measles outbreaks were exacerbated by a fraudulent, retracted study claiming a link between the MMR shot and autism.

The result? Most states are below the 95% vaccination threshold for kindergartners — the level needed to protect communities against measles outbreaks.

“I’m very upset by how cavalier people are being about the measles,” Tobin said. “I don’t think that they realize how destructive this is.”

Polio changed a life twice

One of Lora Duguay’s earliest memories is lying in a hospital isolation ward with her feverish, paralyzed body packed in ice. She was three years old.

“I could only see my parents through a glass window. They were crying and I was screaming my head off,” said Duguay, 68. “They told my parents I would never walk or move again.”

It was 1959 and Duguay, of Clearwater, Florida, had polio. It mostly preyed on children and was one of the most feared diseases in the U.S., experts say, causing some terrified parents to keep children inside and avoid crowds during epidemics.

Given polio’s visibility, the vaccine against it was widely and enthusiastically welcomed. But the early vaccine that Duguay got was only about 80% to 90% effective. Not enough people were vaccinated or protected yet to stop the virus from spreading.

Duguay initially defied her doctors. After intensive treatment and physical therapy, she walked and even ran – albeit with a limp. She got married, raised a son and worked as a medical transcriptionist.

But in her early 40s, she noticed she couldn’t walk as far as she used to. A doctor confirmed she was in the early stages of post-polio syndrome, a neuromuscular disorder that worsens over time.

One morning, she tried to stand up and couldn’t move her left leg.

After two weeks in a rehab facility, she started painting to stay busy. Eventually, she joined arts organizations and began showing and selling her work. Art “gives me a sense of purpose,” she said.

These days, she can’t hold up her arms long enough to create big oil paintings at an easel. So she pulls her wheelchair up to an electric desk to paint on smaller surfaces like stones and petrified wood.

The disease that changed her life twice is no longer a problem in the U.S. So many children get the vaccine — which is far more effective than earlier versions — that it doesn’t just protect individuals but it prevents occasional cases that arrive in the U.S. from spreading further. ” Herd immunity ” keeps everyone safe by preventing outbreaks that can sicken the vulnerable.

After whooping cough struck, ‘she was gone’

Every night, Katie Van Tornhout rubs a plaster cast of a tiny foot, a vestige of the daughter she lost to whooping cough at just 37 days old.

Callie Grace was born on Christmas Eve 2009 after Van Tornhout and her husband tried five years for a baby. She was six weeks early but healthy.

“She loved to have her feet rubbed,” said the 40-year-old Lakeville, Indiana mom. “She was this perfect baby.”

When Callie turned a month old, she began to cough, prompting a visit to the doctor, who didn’t suspect anything serious. By the following night, Callie was doing worse. They went back.

In the waiting room, she became blue and limp in Van Tornhout’s arms. The medical team whisked her away and beat lightly on her back. She took a deep breath and giggled.

Though the giggle was reassuring, the Van Tornhouts went to the ER, where Callie’s skin turned blue again. For a while, medical treatment helped. But at one point she started squirming, and medical staff frantically tried to save her.

“Within minutes,” Van Tornhout said, “she was gone.”

Van Tornhout recalled sitting with her husband and their lifeless baby for four hours, “just talking to her, thinking about what could have been.”

Callie’s viewing was held on her original due date – the same day the Centers for Disease Control and Prevention called to confirm she had pertussis, or whooping cough. She was too young for the Tdap vaccine against it and was exposed to someone who hadn’t gotten their booster shot.

Today, next to the cast of Callie’s foot is an urn with her ashes and a glass curio cabinet filled with mementos like baby shoes.

“My kids to this day will still look up and say, ‘Hey Callie, how are you?’” said Van Tornhout, who has four children and a stepson. “She’s part of all of us every day.”

Van Tornhout now advocates for childhood immunization through the nonprofit Vaccinate Your Family. She also shares her story with people she meets, like a pregnant customer who came into the restaurant her family ran saying she didn’t want to immunize her baby. She later returned with her vaccinated four-month-old.

“It’s up to us as adults to protect our children – like, that’s what a parent’s job is,” Van Tornhout said. “I watched my daughter die from something that was preventable … You don’t want to walk in my shoes.”

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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education and the Robert Wood Johnson Foundation. The AP is solely responsible for all content.

Related

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.

Newswise — Genome wide association studies (GWAS) have identified hundreds of genome regions containing thousands of genetic variants associated with asthma, but it’s still not clear which variants have an actual causal link to the disease. This “variant-to-function” gap is one of the biggest challenges to the usefulness of these genomic studies and has motivated researchers to develop new tools to make sense of GWAS results.

A new study by researchers from the University of Chicago combines genetic data and improved computational tools to look more closely at GWAS results for both adult-onset and childhood-onset asthma. The research identified many genetic variants with a high likelihood of having a causal effect on both types of asthma, paving the way for further studies to target the genes connected to these variants as potential treatments.

The study, published in Genome Medicine, also found significant differences in the sets of genes that could be linked to adult-onset and childhood-onset asthma, with relatively little overlap between the two.

“The real uniqueness of our study is that the differences between childhood- and adult-onset asthma were evident at every level that we looked at,” said Carole Ober, PhD, the Blum-Riese Distinguished Service Professor and Chair of Human Genetics at UChicago, and co-senior author of the paper. “You find out it’s actually different variants that are contributing to asthma. Even when the GWAS locus looks the same, the genes functionally linked to these variants are also different. So, they’re really quite different diseases.”

Fine-mapping causal variants

Researchers use GWAS to compare genome sequences from a large group of people with a disease to another set of sequences from healthy individuals. The differences identified in the disease group could point to genetic variants that increase risk for that disease and warrant further study. Most human diseases—including asthma—are not caused by a single genetic variant, however. Instead, they are the result of complex interactions among multiple genes, environmental factors, and host of other variables. As a result, GWAS often identifies too many variants across the genome to be of use without further refinement.

GWAS also identifies association only, not causality. In a typical genomic region, many variants are highly correlated with each other, due to a phenomenon called linkage disequilibrium. This is because DNA is passed from one generation to the next in entire blocks, not as individual variants. Therefore, variants nearby each other tend to be correlated. To make the problem more difficult, most of the genetic variants associated with diseases are located in non-coding regions of the genome, making their effects difficult to interpret.

In the new study, Ethan Zhong, a graduate student working with Ober and Xin He, PhD, Associate Professor of Human Genetics and another co-senior author of the paper, wanted to bridge the variant-to-function gap and find more concrete biological insights from different sets of asthma GWAS data. He worked with data from the UK Biobank, a large-scale biomedical database and research resource containing de-identified genetic data from nearly 500,000 people in the United Kingdom. Using a statistical method called “fine-mapping,” he was able to estimate the probability that a given genetic variant has a causal relationship to asthma.

The new estimates incorporated data on the accessibility of chromatin, the bundle of DNA and proteins that make up chromosomes. When a region is involved in regulating gene expression, the chromatin “opens” to become more accessible. The amount of open chromatin can be measured and used as an indicator of regulatory activity; when combined with statistical evidence, it builds an even stronger case that the variant is causally linked to asthma.

“The GWAS associations provide sets of variants associated with the disease,” Zhong said. “So, when those variants overlap with open chromatin regions in cell types that are relevant to asthma pathogenesis like lung epithelial cells, we think that they are more likely to be causal to these asthma phenotypes.”

Zhong also included data on expression quantitative trait loci (eQTLs), genetic variants associated with differences in gene expression, and chromatin interactions from blood and lung cell types, to link fine-mapped variants to their target genes. Using this information, he built a list of likely causal genes supported by genetic evidence.

Closing the gap

The fine-mapping analysis uncovered 21 independent sets of variants (called credible sets) for adult-onset asthma and 67 for childhood-onset, with only 16% shared between the two. Zhong also looked for cis-regulatory elements (CREs), short DNA sequences that control expression of nearby genes, that were linked to asthma and found 62 and 169 candidate genes for adult-onset and childhood-onset, respectively. More than 60% of these had open chromatin in different cell types, including many genes involved in immune and inflammatory responses.

The team selected six of the candidate CREs and tested them in bronchial epithelial cells to see if the variants had a regulatory effect; four of the six did, meaning their efforts are getting closer to the mark in the right kind of cells involved in asthma. The variant-to-function gap closes ever so slightly, opening the door to further studies of these candidate genes as potential targets for treatment.

The study was supported in part by a National Institutes of Health grant to discover genes in asthma and allergy, in collaboration with Marcelo Nobrega, MD, PhD, A.N. Pritzker Professor of Human Genetics at UChicago, Nathan Schoettler, MD, PhD, Assistant Professor of Medicine, and Anne Sperling, PhD, formerly of UChicago and now Professor of Medicine at the University of Virginia.

Additional authors include Robert Mitchell, Christine Billstrand, Emma Thompson, Noboru J. Sakabe, Ivy Aneas, Isabella M. Salamone, and Jing Gu.