MEDICAL MISOGYNY

Female patients with traumatic brain injury less likely to be admitted to trauma centres

Canadian Medical Association Journal

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Female patients with traumatic brain injury (TBI) are 26% less likely to be admitted to a specialized trauma centre than males, according to a study on data from Ontario published in CMAJ (Canadian Medical Association Journal) https://www.cmaj.ca/lookup/doi/10.1503/cmaj.251721. This difference persisted even after the researchers accounted for factors such as age, severity of injury, other health conditions, and socioeconomic circumstances.

Traumatic brain injuries, often from falls, are the leading cause of trauma-related death and disability globally.

In this study based on ICES data of 55 606 patients admitted to hospital for TBI in Ontario between April 2009 and March 2020, 39% (21 719) were female. From this total, 18 650 patients were admitted to a specialized trauma centre, with 26% (5666) of females and 38% (12 984) of males admitted. Female patients were much older (median age 78 years) than males (median age 67 years) and were more likely to have dementia and hypertension. By contrast, male patients had higher rates of severe head trauma (33%) than females (25%).

Several factors may contribute to these variations in admission rates.

“First, injuries in female patients are more often associated with lower-energy mechanisms, such as ground-level falls, that may attract less attention and may lead to lower prehospital priority,” writes Dr. Natalia Angeloni, a critical care physician at Sunnybrook Health Sciences Centre and PhD student at the University of Toronto, Toronto, Ontario, with coauthors. “Second, unconscious (implicit) sex-related bias may contribute to differential recognition of severity of injury.”

As well, smaller numbers of female patients with TBI in research studies may contribute to a narrow understanding of the way trauma presents in females.

The authors suggest more research is needed to understand sex-based discrepancies in trauma care.

“In Ontario, triage performance is suboptimal, with high rates of both overtriage and undertriage, suggesting variability in decision-making, even when standardized guidelines are in place,” say the authors. “Understanding how this variability interacts with sex and gender is critical. The role, if any, of conscious and unconscious bias in clinical decision-making in care of patients with TBI should be explored, as has been done for other clinical conditions; results should guide targeted interventions to reduce the disparities we have identified.”

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Journal

Canadian Medical Association Journal

DOI

10.1503/cmaj.251721 

Method of Research

Observational study

Subject of Research

People

Article Title

Differences in admission to trauma centres by sex among adults with traumatic brain injury: a population-based cohort study

Article Publication Date

15-Jun-2026

 

Testosterone therapy in men may be overprescribed, inconsistent with clinical guidelines

The Endocrine Society

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CHICAGO—Only a small number of men who were prescribed testosterone therapy received appropriate, guideline-concordant diagnostic testing, according to a study being presented Saturday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Ill, by Sophia Sinha, M.D., clinical assistant professor at the University of Michigan in Ann Arbor, Mich.

“Our study findings highlight opportunities to improve patient care and reduce inappropriate testosterone prescribing. Long-term, these findings can lead to quality-improvement efforts and clinical decision support tools that promote consistent, guideline-concordant testosterone prescribing,” said senior author Maria Papaleontiou, M.D., associate professor at the University of Michigan in Ann Arbor, Mich.

The retrospective chart review included a random sample of 200 males assigned at birth (mean age, 52.5 years) with at least one outpatient primary care visit at Michigan Medicine in the past year, who had a diagnosis of hypogonadism, and received an initial testosterone prescription during the study period (2020 to 2025).

The most common coexisting medical conditions in the study population included obesity (63%), hypertension (52%), depression (40%), diabetes (28%) and arthritis (28%).

That data show only 12% of men who received an initial testosterone prescription had two low morning testosterone levels (total testosterone < 300ng/dL), free testosterone < 70pg/mL, or low bioavailable testosterone, between 5 a.m. and 10 a.m.), had their LH and/or FSH measured, and had no contraindications to testosterone therapy.

More than half of the patients (62%) had a prostate-specific antigen (PSA), and 77% had a complete blood count measured in the year before the initial testosterone prescription.

Overall, 55% of the men had obstructive sleep apnea, 4% prostate cancer and 1.5% PSA >4 ng/mL before being prescribed testosterone.

Prescriptions were written by primary care physicians (45%), urologists (35.5%), endocrinologists (18%) and other specialists (1.5%). The most common testosterone prescription was a topical formulation (68.5%).

Sinha and Papaleontiou said improving guideline-concordant testosterone prescribing can help prevent avoidable risks in people who may not have a true clinical need for it.

“Future studies should evaluate whether targeted interventions are needed,” Papaleontiou said.

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Endocrinologists are at the core of solving the most pressing health problems of our time, including diabetes, obesity, infertility, bone health, and hormone-related cancers. The Endocrine Society is the largest global organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.

With more than 18,000 members in 133 countries, the Society serves as the voice of the endocrine field. Through its renowned journals and ENDO, the world's largest endocrine meeting, the Society accelerates hormone research, advances clinical excellence in endocrinology, and advocates for evidence-based policies on behalf of the global endocrine community. To learn more, visit our online newsroom.

Phthalate exposure in early life may lead to anxiety in adult male rats

Endocrine-disrupting chemical DEHP increases flexibility of plastic products

The Endocrine Society

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Chicago—Male rats that were exposed to the widely used plasticizer di-(2-ethylhexyl) phthalate (DEHP) during early development exhibited increased anxiety behavior as adults, according to a study being presented Saturday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Ill.

While the research was performed in rodents, the work suggests humans exposed to endocrine disruptors before and shortly after birth may experience behavioral changes that last a lifetime.

“This research demonstrates that one of the most widely used plasticizers worldwide is capable of causing behavioral changes when the subject is exposed during the prenatal and immediate postnatal developmental stages, with this effect lasting over time,” said Osvaldo Juan Ponzo, M.D., Ph.D., professor of physiology at University of Buenos Aires School of Medicine in Buenos Aires, Argentina.

DEHP is used in many plastic items to make them more flexible, such as medical devices, toys, shower curtains and raincoats. Numerous studies have shown that DEHP and its metabolites interfere with a number of organ systems in animals and humans, namely the reproductive and nervous systems. Scientists at the University of Buenos Aires School of Medicine wanted to examine the effects of DEHP on anxiety-like behavior in adult male rats and determine whether the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) or testosterone was involved in regulating this action.

Pregnant female rats were given DEHP orally every day, starting with the first day of gestation until they weaned their litter. After male pups reached maturity at 70 days old, the research team evaluated their anxiety-like behaviors by placing them in an elevated plus maze (EPM), a test based on the natural aversion of rodents to open spaces and heights. The EPM is shaped like a plus symbol and has two open and two closed arms. The scientists could gauge how often and how long the rats stayed in both arms, as well as how long they remained motionless, known as freezing time.

Ninety minutes before EPM testing, some of the animals were treated with GABA agonists—molecules that bind and activate GABA—while other animals received testosterone every 48 hours for 14 days prior to the test. The scientists observed that the DEHP-only group demonstrated anxiety-like behavior, spending less time exploring open arms and more time in the closed arms of the maze. They also had increased freezing time. However, the DEHP rats treated with GABA agonists and testosterone displayed the opposite characteristics.

"This work demonstrates that contact with DEHP in the early stages of life could modify behavior with regard to anxiety, even in the absence of DEHP exposure in adulthood," Ponzo said. "These neuroendocrine changes can be reversed by treating with GABA agonists or testosterone."

 

EDCs found in breast milk and infant urine up to age 6 months

Chemical exposure can interfere with hormones during baby’s development

The Endocrine Society

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Chicago—Endocrine-disrupting chemicals (EDCs) that interfere with hormones were found in breast milk and in the urine of children from birth up to 6 months, according to a study being presented Saturday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Ill.

“Breast milk is the optimal nutritional source for any child and must be protected as it is a vehicle of environmental contaminants,” said Maria Elisabeth Street, M.D., Ph.D., associate professor and Director of the Division of Pediatric Endocrinology at the University of Parma and University Hospital of Parma, Parma, Italy. “Infancy represents a critical window of exposure since effects are magnified at this age with damage becoming evident after many years.”

Street and colleagues used data from 336 mother-infant pairs enrolled in the LIFE-MILCH project. Samples were collected one month, three months, and six months after birth.

The researchers measured exposure to more than 50 different chemicals, including bisphenols (BPA), polycyclic aromatic hydrocarbons, phthalates and metabolites, parabens, polar pesticides and pyrethroids.

BPA was commonly found in breast milk one month after birth (51.2%) and at six months postpartum (49.8%). Nearly a third of the infants had BPA in their urine samples following birth. The number increased to 67.6% when the infants were 6 months old.

Bisphenol S (BPS) was found in breast milk one month after birth (10.7%), at six months after birth (18.3%), and in infant urine samples at birth (22.4%) and at six months after birth (41.2%).

Most polycyclic aromatic hydrocarbons were rarely detected in breast milk, but several were consistently found in urine (up to 27.7%).

Methylparaben (MePB) and ethylparaben (EtPB) were most commonly found one month (51.2%; 42.3%) and six months postpartum (56.2%; 52.6%) in breast milk, and increased in urine samples over time.

Glufosinate was detected in breast milk one month after birth (27.4%) and three months (31.9%) after birth, and in urine samples at birth (44.7%) and at six months of age (38.2%).

Phthalates, including dibutyl phthalate (DBP), were found in 90.2% of breast milk samples at one month postpartum and 86.5% at six months postpartum. Levels in urine samples increased from 30.3% at birth to 79.4% at 6 months of age.

Most EDCs found in breast milk and urine samples are associated with nutrition habits and products used for personal and household care, Street said.

Studies found exposure to these chemicals were linked to neurodevelopmental issues, hormonal activation at birth, and androgenization, or the development of male reproductive characteristics. EDC exposure also can alter growth, weight and obesity, Street said.

The study findings have led to a prevention campaign with results currently under evaluation, and several stakeholders have signed agreements to monitor and reduce these chemicals in their products in Italy, Street said. The researchers urge public health officials to reduce exposure to EDCs and create preventive strategies to protect breast milk in a changing world.

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Endocrinologists are at the core of solving the most pressing health problems of our time, including diabetes, obesity, infertility, bone health, and hormone-related cancers. The Endocrine Society is the largest global organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.

With more than 18,000 members in 133 countries, the Society serves as the voice of the endocrine field. Through its renowned journals and ENDO, the world's largest endocrine meeting, the Society accelerates hormone research, advances clinical excellence in endocrinology, and advocates for evidence-based policies on behalf of the global endocrine community. To learn more, visit our online newsroom.

 

Biological pacemaker dogma challenged: TBX18 fails, Hcn2 deliver

Amsterdam University Medical Center

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Researchers from Amsterdam UMC have overturned a key assumption in the biological 
pacemaker field. In a new preclinical study they show that the transcription factor TBX18 does 
not generate true biological pacemaker activity, while the ion channel Hcn2 does produce 
robust pacemaker function in the heart.

TBX18 revisited
For more than a decade, TBX18 has been reported to reprogram working ventricular cardiomyocytes 
into sinoatrial‑node–like pacemaker cells, based on widely cited high‑impact papers. Using lowimmunogenic adeno-associated virus (AAV) vectors and detailed electrophysiology, the team from 
Amsterdam UMC systematically re-examined this claim. They first showed that conventional 
high‑level TBX18 overexpression is profoundly toxic, causing severe myocardial fibrosis and scarring 
in mouse hearts, while the control did not. “We found that supraphysiological TBX18 expression is 
highly toxic for cardiomyocytes,” says senior author Gerard Boink, cardiologist and principal 
investigator at Amsterdam UMC. “That toxicity alone already questions the feasibility of TBX18 as a 
clinically relevant biological pacemaker strategy.”

Safe TBX18 levels, no pacemaker
To separate toxicity from biological functionality, the researchers engineered an optimized AAV 
cassette and reduced the TBX18 protein levels to about 1% of conventional CMV-driven expression.
This completely prevented fibrosis, yet preserved transcriptional activity of TBX18 with effective 
repression of well-known targets such as Gja1 (Connexin43). Despite this controlled, non-toxic 
expression, cardiomyocytes did not acquire a genuine pacemaker phenotype. TBX18 suppressed
multiple working-myocyte genes and lead to abnormal action potentials. However, it did not induce 
key pacemaker gene programs, nor did it induced Hcn4 protein, or the pacemaker current If. “These 
results give good reason to stop TBX18-based gene therapy efforts in the heart,” says Boink. “Our 
data show that even at realistic, non-toxic expression levels, you do not get pacemaker activity. 
Instead of providing a therapy, you risk arrhythmia by ion channel dysregulation and electrical 
instability.”

Vector artefacts exposed
In a rat model of complete atrioventricular (AV) block, both Adenoviral (AdV)-TBX18 and the AdVcontrol produced similar ectopic pacing and extensive local fibrosis, pointing to AdV vector-related
inflammation and scarring as the true driver of the earlier reported “TBX18 pacing” signals. The AAV 
system used in the present study avoided these confounders. “In some parts of the field, there has 
been a tendency to over‑value single high‑impact papers,” Boink notes. “That can unintentionally 
promote artefactual concepts, like TBX18‑mediated reprogramming, to the status of a dogma.
"Ironically, this dogma is founded on our own 20-year-old studies, which originally uncovered the 
role of TBX18 in sinus node development."

Hcn2 proves its value
In contrast to TBX18, AAV‑mediated expression of the pacemaker channel Hcn2 produced robust, 
autonomically responsive ventricular pacing in the same rat complete AV‑block model. Co‑expression 
of TBX18 did not improve Hcn2‑based pacing, underscoring that TBX18 can also not be employed to 
further promote HCN-based pacing. “With this study we also show that an efficient biological 
pacemaker can be created with Hcn2 alone,” says Boink. “That has direct implications for 
developing gene‑therapy–based pacemakers for patients with congenital complete heart block, and 
other pacemaker indications, where we are now actively moving forward.”

Valorization at Amsterdam UMC
Next to his work as cardiologist and group leader, Boink is also Chief Valorization Officer 
for Amsterdam Cardiovascular Sciences and Chief Scientific Officer at PacingCure. “I feel 
privileged to work in an environment where valorization and real‑world impact are just as 
important as publishing in high impact journals, which obviously also has our priority,” says 
Boink.

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Journal

Journal of Clinical Investigation

Article Title

AAV-mediated long-term TBX18 expression causes cardiac fibrosis and fails to induce pacemaker activity in rodents

Article Publication Date

11-Jun-2026

 

Copper drug restores memory and clears toxic Alzheimer’s proteins

Monash University

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Lead author Dr Jae Pyun (left) and senior author Professor Joseph Nicolazzo (right).

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Credit: Monash University

Monash University researchers have found in laboratory experiments that a drug which delivers copper to the brain significantly reduces toxic Alzheimer’s proteins and improves long-term spatial memory.

The study, published today in the journal ACS Chemical Neuroscience, shows the compound Cu(ATSM) repairs a vital waste-clearing pump at the blood-brain barrier – unlocking a potential new avenue of therapeutics targeting neurovascular dysfunction, caused by one of the world’s leading causes of death.

Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta. Normally, the brain flushes these out into the bloodstream through the blood-brain barrier. In Alzheimer’s, the pumps doing the heavy lifting, called P-glycoprotein (P-gp), weaken significantly, clogging the drain and trapping the toxic proteins in the brain.

Lead author Dr Jae Pyun, from the Drug Delivery, Disposition and Dynamics theme at Monash Institute of Pharmaceutical Sciences (MIPS), whose work on the study marked the final part of his PhD project, said the treatment successfully engages the brain’s blood vessels to lower toxic protein levels, which results in behavioural benefits.

“This is the first study to show that Cu(ATSM) can increase the abundance of P-gp clearance pumps in an Alzheimer’s model, by 24.1 per cent, effectively linking the repair of the blood-brain barrier to a reduction in toxic proteins and improved cognitive function,” Dr Pyun said.

“By improving the pumps, the brain can finally clear out the trapped waste. Over 56 days, the treatment reduced toxic amyloid-beta by 42 per cent and improved spatial learning by nearly 44 per cent.”

Senior author Professor Joseph Nicolazzo, the Director of the Centre for Drug Candidate Optimisation at MIPS, said the compound has strong potential to quickly transition into human clinics because it has already undergone safety evaluations for other diseases.

“Cu(ATSM) is a copper compound with anti-inflammatory and neuroprotective properties that has already progressed to clinical testing for conditions like Parkinson’s and ALS,” Professor Nicolazzo said.

“Because reducing amyloid burden is clinically proven to improve functional outcomes, these preclinical results strongly support the rationale for testing this drug in early symptomatic Alzheimer’s disease.”

While the compound reduced amyloid buildup, researchers are still mapping the exact biological routes the proteins take to leave the brain. Beyond repairing the blood-brain barrier, the researchers suspect the copper treatment may empower the brain’s own immune cells, called microglia, to consume and degrade the toxic plaques.

Future studies will focus on tracking the precise clearance mechanisms to find how the proteins exit the brain into the bloodstream. The current findings establish a strong foundation for exploring biometal therapies like Cu(ATSM) to combat blood vessel dysfunction and memory loss in Alzheimer’s disease.

Alzheimer’s and other forms of dementia are a growing global health problem that recently became Australia’s leading cause of death, overtaking coronary heart disease. As mortality rates continue to climb and the population ages, finding effective treatments to halt cognitive decline is crucial.

Read the research paper: doi.org/10.1021

RESEARCHERS

This research was led by Dr Jae Pyun with co-authors Pranav Runwal, Oliver Fuller, Casey Egan, Professor Mark Febbraio, Associate Professor Jennifer Short and Professor Joseph Nicolazzo from the Monash Institute of Pharmaceutical Sciences, along with Dr Asif Noor, Celeste Mawal, Professor Paul Donnelly, and Professor Ashley Bush from the University of Melbourne.

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Journal

ACS Chemical Neuroscience

DOI

10.1021/acschemneuro.6c00252 

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Cu(ATSM) Restores Blood−Brain Barrier Abundance of P‑Glycoprotein and Improves Cognitive Function in the APP/PS1 Mouse Model of Alzheimer’s Disease

COI Statement

The authors declare the following competing financial interest(s): Collaborative Medicinal Development LLC has licensed intellectual property related to this subject from The University of Melbourne, where Professor Paul S. Donnelly is listed as an inventor and has served as a consultant to Collaborative Medicinal Development LLC. Professor Ashley I. Bush has a profit share interest in, Collaborative Medicinal Development LLC and is a shareholder in Alterity Ltd., Cogstate Ltd. and Mesoblast Ltd.

 

Monell Center researchers find fructose sends a weaker “I’m full” signal to the brain than glucose

Findings shed light on how sugar type influences what and how much we decide to eat

Monell Chemical Senses Center

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PHILADELPHIA – JUNE 11, 2026 – Researchers at the Monell Chemical Senses Center found that common dietary sugars fructose and glucose, despite having the same amount of calories, communicate with the brain through different gut-brain pathways, a difference that may help shape our food and beverage preferences.

In mice, the team identified a dedicated gut-brain signaling pathway through which fructose communicates with the brain and found that it is much less effective than glucose in turning down the activity of hunger-related neurons.

Their findings were published June 10 in Neuron.

“This work adds to our growing understanding of how modern diets, especially those high in fructose or high-fructose corn syrup, interact with the neural systems involved in appetite,” said senior author and Monell Member Amber Alhadeff, PhD.

Recording neural activity in mice, researchers observed that fructose triggered a rise in the gut hormone PYY, which then acted through the vagus nerve to modestly inhibit agouti-related protein (AgRP) neurons, key brain cells that help drive hunger. Disrupting this pathway blocked fructose’s effect on those neurons. By contrast, glucose did not rely on this same PYY-Y2 vagus nerve route, researchers said, and caused strong suppression of AgRP neuron activity.

The team found that while both sugars had similar short-term effects on how much mice ate, the animals developed food preferences linked to the level of AgRP inhibition associated with each sugar.

The team also looked at high-fructose corn syrup (HFCS), a common food additive that contains a mixture of fructose and glucose. The mice preferred the HFCS, and HFCS more strongly inhibited AgRP neurons than fructose alone. This may help explain why some people find HFCS-containing foods and beverages especially appealing, researchers said.

The findings challenge the long-standing idea that hunger-related AgRP neurons track calorie intake regardless of nutrient source. Instead, this study suggests that these neurons distinguish between sugars and respond to them through different biological pathways. Although fructose and glucose contain the same amount of calories, the animals’ brains did not treat them equally. These new results illustrate the complexity of nutrient sensing: even simple sugars can differently influence the gut, the brain, and our behavior.

This research was supported by grants R01DK131558, DP2AT011965, R01DK116004, F31DK13558, and S10OD030354 from the National Institutes of Health; the American Heart Association; the New York Stem Cell Foundation; the Klingenstein Fund; the Simons Foundation, the Pew Charitable Trusts, the Penn Institute for Diabetes, Obesity, and Metabolism; the Hearst Fellowship, and the Monell Chemical Senses Center.

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About the Monell Chemical Senses Center

The Monell Chemical Senses Center is an independent nonprofit research institute in Philadelphia, Pennsylvania. It was founded in 1968 to advance and share discoveries in the science of the chemical senses of smell, taste, chemesthesis, and interoception to solve the world’s health, societal, and environmental challenges.
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Journal

Neuron

DOI

10.1016/j.neuron.2026.05.013 

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Attenuated hypothalamic response to fructose via a dedicated gut-brain pathway

Article Publication Date

10-Jun-2026

COI Statement

A.L.A. is a scientific advisory board member for Zealand Pharma. This work is unrelated to the work presented in this manuscript.

Type 1 diabetes diagnoses surge among Puerto Rican teens

The Endocrine Society

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Chicago—The incidence of type 1 diabetes among teens in Puerto Rico more than doubled from 2009 to 2021 and remained elevated through 2024, with an average annual increase of 4.1 percent, according to a study being presented Saturday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Ill.

The findings highlight a growing health concern. The study shows that type 1 diabetes is becoming more common among Hispanic/Latino adolescents in Puerto Rico, suggesting the need to better understand the factors driving this trend.

Because Hispanic/Latino individuals make up a large and growing share of the U.S. population, studying Puerto Rico separately provides valuable insight into health trends that may not be visible in national data, said the study’s lead author, Natalia Vázquez Colón, M.S., of the Puerto Rico Institute of Statistics in San Juan, Puerto Rico.

Researchers conducted a population-based observational study of adolescents aged 15 to 19 years in Puerto Rico from 2009 to 2024. Data included 3,156 pediatric cases aged zero to 21 years during this period. They identified 612 newly diagnosed type 1 diabetes cases among those studied. Annual incidence rates were calculated using U.S. Census population estimates and expressed per 100,000 people.

Between 2009 and 2024, annual type 1 diabetes incidence rates among adolescents aged 15 to 19 years increased from 10.1 per 100,000 in 2009 to a peak of 24.1 per 100,000 in 2021 and remained elevated through 2024 (18.3 per 100,000).

“These findings have important implications for both patient care and public health, including the need for earlier detection and increased prevention efforts, and the data may help ensure that clinical guidelines and healthcare resources better reflect the needs of Hispanic/Latino populations across the United States,” Vázquez Colón said.

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Endocrinologists are at the core of solving the most pressing health problems of our time, including diabetes, obesity, infertility, bone health, and hormone-related cancers. The Endocrine Society is the largest global organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.

With more than 18,000 members in 133 countries, the Society serves as the voice of the endocrine field. Through its renowned journals and ENDO, the world's largest endocrine meeting, the Society accelerates hormone research, advances clinical excellence in endocrinology, and advocates for evidence-based policies on behalf of the global endocrine community. To learn more, visit our online newsroom.