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A recent study led by researchers at the Virginia Commonwealth University (VCU) Massey Cancer Center found strong evidence that prolactin, a hormone responsible for breast growth and production of milk during pregnancy acts as a major contributor to breast cancer development and that the hormone could inform the creation of targeted drugs to treat multiple forms of the disease.

Hormones have proteins on their cell surface called receptors that receive and send biological messages and regulate cell function. Through research published in the journal npj (Nature Partner Journals) Breast Cancer, VCU Massey Cancer Center researcher Charles Clevenger, M.D., PhD, and his lab discovered a new, altered form of the prolactin receptor called the human prolactin receptor intermediate isoform (hPRLrI) that directly drives breast cancer. The researchers observed that this modified version of the prolactin receptor interacted with other forms of the receptor to turn benign breast cells into malignant ones, and the presence of hPRLrI in breast cancer cells was associated with triple-negative breast cancer, a rapid rate of cell reproduction and poor outcomes.

“This research challenges the dogma that prolactin only functions in milk production and highlights the unique discovery that the hormone can contribute to breast cancer,” said Clevenger, who is the associate director for precision oncology, Carolyn Wingate Hyde Endowed Chair in Cancer Research and member of the Cancer Biology research program at Massey as well as chair of the Department of Pathology at the VCU School of Medicine.

“By understanding how the prolactin receptor correlates to breast cancer, novel therapeutic and prognostic agents can be developed to effectively treat the disease,” he added.

Clevenger said these findings support the argument that future approaches in drug design may need to specifically target hPRLrI, and could ultimately inform advanced diagnostic applications for breast cancer as well.

Through a separate study published in Endocrinology and prominently showcased on the journal’s website as the Featured Article for a week, Clevenger’s lab substantially prevented tumour growth in preclinical models of ER-positive breast cancer using an HDAC6 inhibitor, a drug that blocks a protein associated with prolactin.

Clevenger has previously found success in the lab stunting breast cancer growth by deactivating Stat5, the genetic pathway responsible for the production of prolactin.

In this new research, the scientists found that the prolactin-regulating function of Stat5 is dually dependent on the enzyme histone deacetylase-6 (HDAC6) and the gene HMGN2.

They also discovered that the estrogen receptor (ER), a hormone widely believed to influence breast cancer development, was high and almost exclusively interactive with Stat5 at sites where HDAC6 and HMGN2 were also present. This suggests that both the estrogen receptor and prolactin receptor can cooperate through the activation of Stat5 to initiate the development of breast cancer. Treating ER-positive breast cancer cells with an HDAC6 inhibitor drastically hindered tumour progression.

“Global analysis of gene expression again revealed that prolactin is closely associated with breast cancer growth and could be subdued by treatment with an HDAC6 inhibitor,” Clevenger said.

Clevenger has dedicated a significant amount of his scientific career to understanding how prolactin might have implications in the growth and progression of breast tumours. In future studies, he plans to further test and develops breast cancer drugs using prolactin as a primary target. WITH ANI INPUTS

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Medically Speaking

Illness related messages significant motivators for exercise



Fitness apps that emphasize illness- or death-related messaging are more likely to be effective in motivating participation than are social stigma, obesity, or financial cost messaging, according to a recent study led by researchers at the University of Waterloo.

The study, ‘The Relationship between Perceived Health Message Motivation and Social Cognitive Beliefs in Persuasive Health Communication’, was published in the journal MDPI (Multidisciplinary Digital Publishing Institute) and was authored by Oyibo, with Julita Vassileva, a Persuasive System Design professor at the University of Saskatchewan, assisting with the data collection.

Previous studies, especially on smoking cessation and risky sexual behaviour, found that messages related to mortality could be a barrier to acknowledging health risks, but the study found this is the opposite for fitness apps.

The study asked 669 research participants to indicate how persuasive these five types of messages were in terms of motivating them to work out at home with a fitness app, to uncover their effectiveness, connection with social-cognitive beliefs such as self-regulation (goal setting), self-efficacy, and outcome expectation, and seeing what role male/female gender played.

“I did not expect only illness- and death-related messages to be significant and motivational,” said Kiemute Oyibo, a postdoctoral fellow at the University of Waterloo’s School of Public Health Sciences.

Oyibo added, “Not only were illness- and death-related messages motivational, they had a significant relationship with self-regulatory belief and outcome expectation, and there was no significant difference between males and females.”

Oyibo said he had expected obesity-related messages (such as “one in four Canadians has clinical obesity”) to be motivational and have a significant relationship with self-regulatory belief, given that obesity is associated with the leading causes of global mortality.

“This study is important because it helps us – especially designers of health apps – understand the types of messages that individuals, regardless of gender, are likely to be motivated by in persuasive health communication, and that are likely to influence individuals’ social-cognitive beliefs about exercise,” Oyibo said.

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Researchers find why people remember stressful experiences better



Researchers have analysed the reasons why stressful experiences are usually remembered more easily than neutral experiences.

When the brain stores memories of objects, it creates a characteristic pattern of activity for each of them. Stress changes such memory traces. The findings of the study were published in the journal ‘Current Biology’.

The research team, headed by Anne Bierbrauer, Professor Oliver Wolf and Professor Nikolai Axmacher from the RUB Institute of Cognitive Neuroscience, put people in stressful situations during simulated job interviews and then recorded their memory of objects from these interviews.Using functional magnetic resonance imaging, they analysed brain activity while the participants saw the objects again. Memories of objects from stressful situations seem to rely on similar brain activity as memories of the stress trigger itself.

The neuroscientists at RUB would like to understand the reasons for this phenomenon. Earlier studies and theoretical considerations had led to different predictions about how memories of stressful experiences differ from neutral ones: “One idea was that very different memory representation might have been the key to more powerful memories; on the other hand, there were indications that stress memories have resembled each other more closely,” explained Anne Bierbrauer.

The current study provides evidence for the second theory. Unlike in many laboratory studies, the researchers set out to record the memory trace of a real event in their experiments, using the so-called Trier Social Stress Test for this purpose.

During the job interview simulation, the committee used a number of everyday objects; for example, one of the committee members took a sip from a coffee cup. The control group was confronted with the same objects, but the participants were not subjected to any stress.

One day later, the researchers showed the objects to participants in both groups while recording brain activity in a magnetic resonance imaging scanner. The stressed participants remembered the objects better than members of the control group.

The researchers analysed primarily the brain activity in the amygdala, a region whose main functions include emotional learning. They compared the neuronal traces of objects that had been used by the committee members in the stress situation with those of objects that hadn’t been used.

The result was: the memory traces of objects that had been used resembled each other more closely than those of objects that hadn’t been used. This was not the case in the control group. In other words, the brain representations of the objects from stressful situations were very closely linked, and they were thus clearly set apart from other experiences.

“The committee members triggered the stress in the interview situation. Accordingly, it seems that the link between the objects and the stress triggers was crucial for the enhanced memory,” concluded Nikolai Axmacher.

The findings obtained argue against the theory that stronger memories are triggered by memory representations that differ from each other as much as possible — at least when it comes to emotional or stressful memories.Rather, the mechanism that reinforces emotional memories appears to be rooted in the fact that the important aspects of the episode are linked at the neural level and become more closely related to the stress trigger.

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According to the findings of new research, practice makes one perfect, but sleep helps, too. Learning and executing a new motor skill can be enhanced if a person can get additional memory processing during sleep.

The findings of the study were published in the journal JNeurosci. Researchers at Northwestern University compared how well participants performed a challenging motor task with and without the extra processing during sleep. The participants played a computer game using a myoelectric computer interface, which enabled them to move a cursor by activating specific arm muscles.

Each command to move the cursor in a particular direction was paired with a unique sound; after practising, the participants played the game blindfolded and moved the cursor based on the sound cue alone.

After completing a test round, the participants took a 90-minute nap. The researchers played half of the sound cues during the nap, reactivating the motor memories associated with each cue. After the nap, the participants performed the motions cued during sleep better than the uncued ones.

It took less time to move the cursor, the cursor travelled a more direct route, and fewer superfluous muscles were activated.

These results show people can improve the performance of new motor skills by reactivating memories during sleep. This approach could be a way to enhance rehabilitation for stroke or other neurological disorders.

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Telehealth evaluation could help improve access to care for infants with an elevated likelihood of autism, suggests a new UC Davis MIND Institute research.

The study, published recently in Autism, found that telehealth approaches in the first year of life could help families facing barriers to care such as geographic distance and long waitlists and aid in early diagnosis and intervention. “The goal is not to diagnose infants with autism,” said Meagan Talbott, an assistant professional researcher in the Department of Psychiatry and Behavioral Sciences and a MIND Institute faculty member. “It is to provide a developmental evaluation to help bridge the gap that we know parents face when they first notice symptoms until their children ultimately receive an autism diagnosis.”

Talbott notes that many families seeking early evaluations for autism face long provider waitlists, must often travel to centres with appropriate expertise and are frequently told by providers to “wait and see.”

Since specialized services for autism are generally tied to having a formal diagnosis, there are usually years between when parents first have questions and when they can access services.

“This results in significant stress for families and delayed support to infants and their caregivers. We hope this study shows one way that we can help improve families’ access to early evaluations and early services and support them,” said Talbott.

Developmental evaluations via telehealth

The study involved 41 infants, ages 6-12 months, whose parents had concerns about social communication or autism. They were recruited nationally in three cohorts. One-quarter of the infants had siblings with autism.

Talbott’s team used the TEDI (Telehealth Evaluation of Development for Infants), a protocol for conducting behavioural assessments that they previously developed. It uses a parent-coaching model to engage parents and infants in a specific set of interactions such as peek-a-boo, playing with toys and reading a book over 45-90 minutes. The examiner scored social communication, play, imitation and other developmental domains. Parents also filled out a series of questionnaires. All families were also sent a small kit of toys needed for the assessment, including blocks, a soft book, rattles, a small blanket and bubbles.

The majority of infants demonstrated an elevated likelihood of autism on both the parent-reported questionnaires and examiner-rated behaviour. This included decreased communication skills and delayed achievement of developmental milestones. Caregivers’ ratings of the usefulness of the TEDI evaluation were very positive.

The findings may also help to expand infant autism research beyond sibling studies, which have dominated the field. “We hope developing these tools for telehealth will help us to expand infant research beyond the sibling context and help us to understand early development in other groups,” explained Talbott.

What’s next for telehealth evaluation?

“My vision is that in the future if a family has a concern about their infant’s development, we could incorporate a telehealth evaluation like this as a second-level screener to help families figure out whether pursuing a full autism diagnostic assessment makes sense for their infant,” Talbott explained. “We’re very lucky in Sacramento that we have the MIND Institute, but there are many places where families are pretty far from somebody who has our level of expertise.”

The research team will soon start working with community members, families, paediatricians and other providers involved in early autism intervention to find out how developmental evaluation and monitoring via telehealth may fit into the existing care system. In the future, they hope to develop additional online programs to pair with these evaluations to further support families during this early period.

Talbott’s work started before the COVID-19 pandemic, but she noted it was nice to have already done the telehealth legwork.

“The pandemic illustrated how critically important telehealth can be,” Talbott said.

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A study has suggested that high maternal cholesterol in pregnancy is associated with more serious heart attacks in young adult offspring.

The research was published in the European Journal of Preventive Cardiology, a journal of the European Society of Cardiology (ESC).

“Cholesterol is not routinely measured during pregnancy in most countries so there are few studies on its association with the health of offspring,” said study author Dr. Francesco Cacciatore of the University of Naples Federico II, Italy.

“More research is needed to verify our findings. If confirmed, this association would indicate that high cholesterol in pregnancy should be considered a warning sign and women should be encouraged to exercise and reduce their cholesterol intake. In addition, affected children could be provided dietary and lifestyle guidance aimed at preventing heart disease later in life,” he continued.

The retrospective study included 310 patients who were admitted to the hospital between 1991 and 2019. Of those, 89 patients were admitted with a heart attack, and 221 controls were hospitalised for other reasons. For all 310 participants, data were obtained on the mother’s cholesterol during the first and second trimester of pregnancy with that individual.

The average age of the 89 heart attack patients was 47 years and 84 per cent were men. Patients were classified as having a severe or non-severe heart attack according to: 1) the number of coronary arteries involved (severe attack = involving three arteries); 2) pump function of the heart (severe attack = left ventricular ejection fraction 35 per cent or less); 3) peak levels of creatinine kinase (CK) and CK-MB enzymes, with higher levels indicating more extensive heart damage (severe attack = CK-peak above 1200 mg/dL or CK-MB peak above 200 mg/dL).

The heart attack was considered severe when at least one of the criteria were met.

Maternal cholesterol during pregnancy was significantly correlated with each measure of heart attack severity (number of vessels, ejection fraction, CK and CK-MB).

The researchers analysed the association between maternal cholesterol during pregnancy and heart attack severity after adjusting for age, sex, body mass index (BMI), number of cardiovascular risk factors (obesity, smoking, high blood pressure, family history of heart disease, or high cholesterol, diabetes, prior angina), and serum cholesterol measured after hospitalisation for the heart attack.

Maternal cholesterol during pregnancy predicted heart attack severity independently of age, sex, BMI, number of risk factors, and serum cholesterol after hospitalisation, with an odds ratio of 1.382 (95 per cent confidence interval 1.046-1.825; p=0.023).

In a second analysis including all 310 patients, the researchers examined the association between maternal cholesterol during pregnancy and atherosclerosis in adult offspring. Because no measurements of atherosclerosis were available for most controls, two surrogate measures were used. These were: 1) a number of cardiovascular risk factors; and 2) a number of cardiovascular risk factors plus clinical manifestations such as heart attack or stroke.

Pregnant mothers’ cholesterol level was significantly correlated with both measures of atherosclerosis risk, even after adjusting for age, sex, and cardiovascular risk factors.

Dr. Cacciatore said, “Our observations suggest that a mother’s cholesterol level during pregnancy impacts the developmental programming of offspring and heart attack severity in adulthood. However, the study does not establish causality, nor does it allow us to estimate how much maternal cholesterol may contribute to heart attack severity.”

He concluded, “Prospective studies are needed to better evaluate the magnitude by which maternal cholesterol may influence the development of atherosclerosis in offspring and the combined effect of risk factors throughout the life.”

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Stanford researchers have observed higher levels of air pollutants within 2.5 miles of oil and gas wells, likely worsening negative health outcomes for residents.

The findings of the study were published in the journal ‘Science of The Total Environment’.

The scientists analysed local air quality measurements in combination with atmospheric data and found that oil and gas wells are emitting toxic particulate matter (PM2.5), carbon monoxide, nitrous oxide, ozone and volatile organic compounds (VOCs). The findings will help researchers determine how proximity to oil and gas wells may increase the risk of adverse health outcomes, including preterm birth, asthma and heart disease.

“In California, Black and Latino communities face some of the highest pollutions from oil and gas wells. If we care about environmental justice and making sure every kid has a chance to be healthy, we should care about this. What’s novel about our study is that we’ve done this at a population, state-wide scale using the same methods as public health studies,” said lead author David Gonzalez, who conducted research for the study in Stanford’s Emmett Interdisciplinary Program in Environment and Resources (E-IPER).

The findings align with other smaller-scale studies that have measured emissions from a handful of wells. At least two million Californians live within one mile of an active oil or gas well.

“It’s really hard to show air quality impacts of an activity like oil and gas production at a population scale, but that’s the scale we need to be able to infer health impacts,” said senior study author Marshall Burke, an associate professor of Earth system science at Stanford’s School of Earth, Energy and Environmental Sciences (Stanford Earth).

The research has revealed that when a new well is being drilled or reaches 100 barrels of production per day, the deadly particle pollution known as PM2.5 increases by two micrograms per cubic meter about a mile away from the site.

A recent study published in ‘Science Advances’ found that long-term exposure to one additional microgram per meter cubed of PM2.5 increases the risk of death from COVID-19 by 11 per cent.

“We started in 2006 because that’s when local agencies started reporting PM2.5 concentrations. We’re very concerned about the particulate matter because it’s a leading global killer,” said Gonzalez.

The team evaluated about 38,000 wells that were being drilled and 90,000 wells in production between 2006 and 2019. They developed an econometric model incorporating over a million daily observations from 314 air monitors in combination with global wind direction information from the National Oceanic and Atmospheric Administration (NOAA) to determine if the pollutants were coming from the wells. They analysed locations with air quality data of before and after a well was drilled.

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