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Study unveils many ways carcinogens trigger development of breast cancer

Because only 5 to 10 percent of breast cancers are due to high risk inherited mutations, such as BRCA1 and BRCA2, scientists say a better understanding of how environmental factors contribute to the disease is needed to prevent future breast cancers and lower incidence rates.

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In the most comprehensive review to date of how breast cancer develops, scientists have created a detailed map that describes the many ways in which environmental chemicals can trigger the disease. Using ionizing radiation as a model, the researchers identified key mechanisms within cells that when disrupted cause breast cancer. Because the findings can be generalized to other environmental carcinogens, they could help regulators identify chemicals that increase breast cancer risk.

“We know exposure to toxic chemicals can play an important role in the development of breast cancer,” says Ruthann Rudel, an environmental toxicologist at Silent Spring Institute and one of the study’s co-authors. “Yet, when regulators try to evaluate whether a chemical is harmful or not, the tests they use do not capture the effects on the breast. This gap in testing means potential breast carcinogens are being given the green light for use in our consumer products.”

Breast cancer is the most common invasive cancer in women, with incidence rates highest in North America and Europe, and rates increasing globally. Because only 5 to 10 percent of breast cancers are due to high risk inherited mutations, such as BRCA1 and BRCA2, scientists say a better understanding of how environmental factors contribute to the disease is needed to prevent future breast cancers and lower incidence rates.

Toward that end, researchers at Silent Spring looked at ionizing radiation–an established risk factor for breast cancer. People can be exposed to ionizing radiation from many sources, including X-rays, CT scans and radiation treatment. The effects of radiation on breast cancer have been extensively studied, based in large part on studies of survivors of the atomic bombings in Hiroshima and Nagasaki and women who were exposed to medical radiation as adolescents.

Reporting in the journal Archives of Toxicology, Rudel and co-author Jessica Helm reviewed 467 studies to identify the sequence of biological changes that occur in breast cells and tissue from the time of radiation exposure to the formation of a tumor. They then created a map of these sequential changes, revealing multiple interconnected pathways by which ionizing radiation leads to breast cancer.

The researchers created the map using a framework called an Adverse Outcome Pathway (AOP). AOPs were designed by the Organisation for Economic Co-operation and Development (OECD) as a way to represent how complex diseases develop, and to help regulators, chemical manufacturers, and drug companies predict how chemicals might affect diseases early in the research process.

“It turns out, not surprising, breast cancer is a lot more complex than how it’s conveyed in traditional cancer models,” says Rudel. In traditional models, ionizing radiation triggers breast cancer solely through DNA damage. The new model by Silent Spring integrates recent findings in cancer biology that show radiation, in addition to DNA damage, also increases the production of molecules called reactive oxygen and nitrogen species. These molecules wreak havoc inside cells, causing inflammation, altering DNA, and disrupting other important biological activities.

“This study is important and highlights the need for a holistic consideration of mechanistic evidence when identifying potential carcinogens,” says Kathryn Guyton, a senior toxicologist at the International Agency for Research on Cancer. “In reality there are multiple key characteristics of carcinogens. Increasingly, we are appreciating that human carcinogens may exhibit different combinations of these key characteristics.”

The Silent Spring team also found that the biological changes that lead to breast cancer are highly influenced by reproductive hormones, such as estrogen and progesterone. Reproductive hormones stimulate the proliferation of cells within the breast, so chemicals that similarly encourage cell proliferation could make the breast more susceptible to tumors. “Critical periods of development, such as during puberty or pregnancy when the breast undergoes important changes, are times when the breast is especially vulnerable,” says Rudel.

To address gaps in chemical safety testing, the Silent Spring researchers identified a series of tests regulators could use to find chemicals that disrupt the pathways outlined in their new model. Chemicals that disrupt these pathways would be considered potential breast carcinogens, thereby discouraging their use in products.

“This study is an invaluable contribution to the field and a real wake-up call for regulators,” says Linda Birnbaum, former director of the National Institute for Environmental Health Sciences. “By holding on to an oversimplified model of how chemicals cause cancer, regulators have been missing critical information, potentially allowing toxic chemicals to enter our products, our air, and our water.”

The AOP project is part of Silent Spring Institute’s Safer Chemicals Program which is developing new cost-effective ways of screening chemicals for their effects on the breast. Knowledge generated by this effort will help government agencies regulate chemicals more effectively and assist companies in developing safer products.

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Study finds low-dose eye drops successful in managing adult myopia for 24 hours

A single low-dose atropine eye drop can produce daylong effects in managing myopia, or nearsightedness.

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Groundbreaking research from the University of Houston shows that a single low-dose atropine eye drop can produce daylong effects in managing myopia, or nearsightedness, which affects roughly one-third of U.S. adults.   

Professor of Optometry Lisa Ostrin and postdoctoral researcher Barsha Lal are reporting that even one drop in the eye of low-dose atropine (0.01%–0.1%) produces clear changes in pupil size and focusing ability that persist for at least 24 hours. Importantly, they also found that the drop shows no short-term structural effects on the eye, with only temporary changes in blood flow inside the retina. 

Ostrin’s latest research is published in the journal Eye and Vision. It adds to a growing body of vision research from David Berntsen, Golden-Golden Professor of Optometry at the University of Houston, who is co-leading a national $25 million NIH-funded clinical trial to delay the development of myopia in children by using the atropine drops. 

Low concentration atropine is widely prescribed to slow myopia progression in children, yet its short-term retinal and choroidal effects remain incompletely understood. Ostrin’s new study evaluated short-term effects of a range of low atropine concentrations on the length of the eye, the blood vessels in the retina and the thickness of the retina and choroid, which sits just behind the retina. These are important measurements because longer eye length is associated with myopia and as it gets longer, the retina and choroid are stretched.  

“These findings indicate that a single instillation of atropine does not alter axial length or retinal or choroidal thickness over 24 hours but may transiently affect superficial retinal perfusion in a time-dependent manner,” said Ostrin.  

In the double-masked, randomized study, twenty healthy adults received a single instillation of either a placebo or atropine in the right eye during five separate sessions. Researchers then checked the eye structure, thickness, and length in the central retina both one-hour and 24-hours later.  

“Characterizing these short-term effects is important for a better understanding of the physiological responses to atropine in clinical and research settings,” said Ostrin who previously published research results of a study investigating the short-term effects of a range of low-dose atropine concentrations on the pupils of young adults. In that study, she found similar results with a single drop of atropine inducing significant changes in the pupils. 

Together, the studies indicate that atropine induces early functional and vascular effects in the eye, in the absence of structural change.  

“By linking objective ocular responses with subjective visual experience, this work advances our understanding of how atropine works and supports more precise, evidence-based, and individualized approaches to myopia management,” said Ostrin. 

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Study: Egg consumption is associated with a lower risk of Alzheimer’s Disease

Compared to never eating eggs, eating at least five eggs per week can decrease risk of Alzheimer’s.

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Consumption of eggs is associated with a lower risk of being diagnosed with Alzheimer’s Disease for those 65 years and older, according to researchers at Loma Linda University Health

Eating one egg per day for at least five days a week reduces risk of Alzheimer’s by up to 27%, researchers found.

“Compared to never eating eggs, eating at least five eggs per week can decrease risk of Alzheimer’s,” said Joan Sabaté, MD, DrPH, a professor at Loma Linda University School of Public Health and the study’s principal investigator.

Even less frequent consumption of eggs significantly reduced the risk of Alzheimer’s. Researchers found that eating eggs 1 to 3 times per month had a 17% decrease in risk, while eating eggs 2 to 4 times per week had a 20% decrease in risk, Sabaté said.

The study, Egg intake and the incidence of Alzheimer’s disease in the Adventist Health Study-2 cohort linked with Medicare datawas published last week in the Journal of Nutrition.

Researchers said they embarked on the study because of a substantial knowledge gap in the relationship between modifiable dietary factors and risk of Alzheimer’s disease risk.

Eggs are known to be a source of key nutrients that support brain health. Sabaté said. Eggs provide choline, a precursor to acetylcholine and phosphatidylcholine, both of which are critical for memory and synaptic function, the study stated. Eggs also contain lutein and zeaxanthin—carotenoids that accumulate in brain tissue and are associated with improved cognitive performance and reduced oxidative stress. Eggs also contain key omega-3 fatty acids, and yolks are particularly rich in phospholipids, which constitute nearly 30% of total egg lipids and are essential for neurotransmitter receptor function.

Researchers said they studied the consumption of eggs in visible ways — such as eating eggs in various forms, like scrambled, fried, boiled, etc. — and hidden ways, such as eggs included in baked goods and packaged foods.

The cases of Alzheimer’s Disease in the Adventist Health Study 2 cohort were diagnosed by physicians, according to Medicare records, among the study population of 40,000 subjects. Eligibility was determined using the Medicare Master Beneficiary Summary Files. The average follow-up period was 15.3 years.

The team emphasized that moderate egg consumption should be  part of a balanced diet.

“Research supports eggs as part of a healthy diet,” said Jisoo Oh, DrPH, MPH, an associate professor of epidemiology at Loma Linda University School of Public Health and the study’s lead author. “Seventh-day Adventists do eat a healthier diet than the general public, and we want people to focus on overall health along with this knowledge about the benefit of eggs.”

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Telling people they might lose motivates more than telling them they might win, research shows

How managers choose to frame problems directly influences employees’ motivation to speak up at work. For managers, this is an insightful approach for building more open and collaborative teams.

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Athletes say they hate to lose more than they love to win. New research finds the same sentiment is shared in organizations.

A Virginia Tech researcher and his colleagues discovered that when managers frame work problems as a potential loss, employees are more likely to take action than when those problems are framed as potential gains. The research also revealed that when the potential loss impacts a larger group, employees are more likely to take action in the form of speaking up to a supervisor in hopes of finding a solution. The findings were recently published in the Journal of Applied Psychology.

For managers, this research suggests that framing work problems as potential losses can influence employees to speak up more.

“Employee voice occurs when suggestions are made to improve organizational functioning,” said Phil Thompson, associate professor in the Pamplin College of Business Department of Management. “From an organizational perspective, the positive outcomes of employee voice include improved performance, effectiveness, and workplace safety. From an employee level, speaking up is positively related to creativity, innovation, engagement, and ethical behavior.”

At its core, this research shows that how managers choose to frame problems directly influences employees’ motivation to speak up at work. For managers, this is an insightful approach for building more open and collaborative teams.

“When managers say, ‘If we don’t get this done, not only will you lose the $5,000 bonus, but everybody in this work group is going to lose a $5,000 bonus,’ it magnifies an employee’s motivation to act in a proactive way,” said Thompson. “This suggests that framing work problems as what will be collectively lost – compared to what can be individually lost – makes employees want to speak up more.”

Thompson was part of a research team led by Jeffery Thomas and Jonathan Booth from The London School of Economics and Mark Bolino from Oklahoma University. Together they analyzed responses from nearly 2,000 full-time employees, MBA students, and employee-supervisor pairs for their experience in situations where work problems were framed as either a gain or a loss. Across three different studies, framing something as a loss yielded employees to voice a work suggestion more.

For example, a manager dealing with a reputational crisis of their team, such as a product quality issue, can frame the problem in a way to spark helpful employee suggestions on how to resolve the issue. For example, instead of saying “if this product has great quality, our company will look really good” a manager saying “if this product is not up to quality standards, our reputation will be damaged” carries more weight for the team. When this reputational risk is shared by everyone, employees are more willing to step forward to help the problem.

In the first study, participants were asked to think about a problem at work that was significant for them. From there, they were randomly assigned to write about the potential losses or gains from that problem. They were also asked to indicate how likely they were to talk about these problems to their supervisor. Participants who reflected on their potential losses showed a 16 percent higher willingness to speak up compared to those who focused on the potential gains.

When it came to the MBA students, they read a fictional performance review scenario where a workplace problem was described. They then rated how willing they would be to speak up about that scenario if they were in the situation. One example suggested that the entire team might fall short of its goals if an issue was not addressed. This specific scenario yielded the most likelihood of speaking up 35 percent more than the scenario’s suggesting that only they would miss their goal, supporting the research’s findings that an employee is more likely to speak up when the loss impacts more people.

The third study looked at employee-supervisor pairings to understand how these relationships play out in the real world. Using pairings from across three industries, employees reported a workplace problem they encountered and their supervisor rated how often that employee spoke up on the job. While the first two studies involved hypothetical scenarios, this real-world evidence showed that employees were 8-10 times more likely to speak up when issues were framed as a potential collective loss compared with a potential collective gain. 

“This research is really geared toward managers so they can facilitate and understand how and why their employees will speak up,” said Thompson. “You can talk about the issue, but it always ends in terms of how we frame things.” 

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