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Environmental Factor – June 2021: In conversation with Elizabeth Martin, Independent Research Scholar

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The strength of the NIEHS research company is, in my opinion, reflected in the roughly 200 postdoctoral, PhD, and postdoctoral researchers who advance the institute’s important mission to promote healthier lives by discovering the impact of the environment on people. I take pride in our trainees receiving support, mentoring and professional development that pave the way for their professional success, be it at NIEHS or beyond.

I recently interviewed such a success story. Elizabeth Martin, Ph.D., is a postdoctoral fellow in the Institute’s Epigenetics and Stem Cell Biology Laboratory, led by Paul Wade, Ph.D. Martin has just received a National Institutes of Health Prize for independent research fellow, which is awarded to outstanding young scientists who are committed to promoting diversity in the workforce.

“I was fortunate to work at NIEHS, which has a wealth of resources for trainees, including world-renowned environmental health professionals willing to share their expertise,” said Martin. (Courtesy photo by Steve McCaw / NIEHS)

I was delighted to speak to her about the award, her research interests, and her future goals. I am happy to report that with people like Martin on the rise, the future of environmental research is indeed in good hands.

Pregnancy as a window of susceptibility

Rick Woychik: Can you say something about your Independent Research Scholar Award?

Elizabeth Martin: I was fortunate enough to win this award as it gives me a three-year, non-temporary position as a Principal Investigator at NIEHS and is geared towards enhancing diversity in research science. I will continue to work with my mentor Dr. Wade will work together, but I will also research independently from his work how eukaryotic cells regulate gene expression.

I plan to view pregnancy as a mother’s window of exposure to environmental toxins. We often think that the baby is the more vulnerable during pregnancy. However, I am genuinely interested in whether there is an epigenetic reprogramming event in the mother and whether this increases her vulnerability to environmental influences, which may lead to negative health consequences later in life.

Understand individual risk

RW: Epigenetics refers to chemical modifications of DNA or the proteins associated with DNA that affect how genes are turned on and off. Understanding how environmental exposures affect such epigenetic changes is one of the key goals of the NIEHS Strategic Plan 2018-2023. So I think it’s great that you are pursuing this line of research.

Prior to joining the institute, you earned your PhD from the University of North Carolina at Chapel Hill under the direction of NIEHS Superfund Research Program Fellow Rebecca Fry, Ph.D. They investigated how prenatal exposure to arsenic and other metals can affect people differently, based on, for example, how they metabolize these substances.

This work is closely related to the concept of precise environmental health that I recently discussed in the Director’s Corner. treated Cheryl Walker, Ph.D., from Baylor College of Medicine. Can you talk about this research that was the basis of your dissertation project?

Rick Woychik, Ph.D., NIEHS Director's Corner While working in Wade’s laboratory, Martin began thinking about science at both the population and molecular levels, a skill that is critical to precise environmental health research. (Image courtesy of NIEHS)

IN THE: Absolutely. The motivation for my previous and current research comes from the idea of ​​precise environmental health, which is about expanding knowledge about individual risks and working on disease prevention. I was heavily influenced by a Comment from 2014 by [former NIEHS and National Toxicology Program Director] Dr. Ken Olden. He discussed how scientists could incorporate epigenetic data into risk assessment and what such data could tell us about how chemical and non-chemical stressors can exacerbate health inequalities.

Take complexity into account

One challenge is to take into account the complexity and diversity of these stressors. Take arsenic as an example. If we look at different parts of the world, we see that there is no uniform exposure because we are dealing with mixtures that contain not only arsenic but also diet, different types of pollution, psychosocial stress, etc. Then there is the question of timing – whether exposure occurred prenatally, during puberty, or in adulthood.

Dr. Fry and I found inconsistent epigenetic changes in all populations, making it difficult to determine which changes are true indicators of individual vulnerability. We hypothesized that exposures to so-called Transcription factors – Proteins that switch genes on or off by binding to DNA – and not directly on the DNA. This research was one of the reasons I turned to Dr. Wade wanted to work on a lab that looks at how transcription factors affect the epigenetic landscape.

View of the belly of a pregnant woman during a doctor's visit I look forward to following Martin’s research into how certain environmental factors during pregnancy can affect the mother later in life. (Courtesy Photo of Blue Planet Studio / Shutterstock.com)

Going forward, I hope to build on my work at Chapel Hill and NIEHS related to pregnancy. I want to identify consistent biological changes that may result from a given exposure to improve understanding of maternal disease risk later in life.

Maternal Health and Phthalates

RW: You and 14 other NIEHS scientists are working on one Special edition of the Journal of Women’s Health with a focus on maternal health, released in February. Can you talk about your involvement in this project?

IN THE: Together with Dr. Sue Fenton of the NIEHS division of the National Toxicology Program worked on the breast cancer section of this publication. Through this project I realized that there is too little research into pregnancy on the maternal side, especially with regard to how certain environmental pressures can lead to complications that lead to problems in later life such as diabetes or cardiovascular disease.

When I was thinking about what chemicals could affect pregnancy, I landed on DEHP [Di(2-ethylhexyl) phthalate], which is one of the most common – and most toxic – phthalates. These are man-made chemicals that are used to make a wide variety of plastics, solvents, and personal care products. Almost all women are exposed to DEHP. In addition, DEHP is believed to interfere with progesterone signaling, which is critical in pregnancy. Imbalances in this signaling can lead to preterm and prolonged labor.

Quotes:
Olden K, Lin YS, Gruber D, Sonawane B. 2014. Epigenome: Biosensor of cumulative exposure to chemical and non-chemical stressors related to environmental justice. Am J Public Health 104 (10): 1816-21.

Martin EM, Fry RC. 2016. A cross-study analysis of prenatal exposure to environmental pollutants and the epigenome: Supporting stress-responsive transcription factor occupation as a mediator of gene-specific CpG methylation patterns. Environment Epigenet 2 (1): dvv011.

Boyles AL, Beverly BE, Fenton SE, Jackson CL, Jukic AMZ, Sutherland VL, Baird DD, Collman GW, Dixon D, Ferguson KK, Hall JE, Martin EM, Schug TT, White AJ, Chandler KJ. 2021. Environmental factors involved in maternal morbidity and mortality. J Women’s Health (Larchmt) 30 (2): 245-252.

(Rick Woychik, Ph.D., directs NIEHS and the National Toxicology Program.)


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Women’s Health

Putting artificial intelligence at the heart of health care — with help from MIT | MIT News

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Artificial intelligence is transforming industries around the world – and healthcare is no exception. A recent Mayo Clinic study found that AI-assisted electrocardiograms (EKGs) have the potential to save lives by speeding up the diagnosis and treatment of heart failure patients treated in the emergency room.

The study’s lead author is Demilade “Demi” Adedinsewo, a non-invasive cardiologist at Mayo Clinic who actively integrates the latest AI advances into cardiac care and draws heavily on her learning experience with MIT Professional Education.

Identifying AI opportunities in healthcare

Adedinsewo is a dedicated practitioner and a Mayo Clinic Florida Fellow for Women’s Health and Director of Research for the Cardiovascular Disease Fellowship program. Her clinical research interests include cardiovascular disease prevention, women’s heart health, cardiovascular health disparities, and the use of digital tools in the treatment of cardiovascular disease.

Adedinsewo’s interest in AI became apparent towards the end of her cardiology fellowship when she began researching its potential to transform the healthcare industry. “I started to wonder how we could use AI tools in my field to improve health equity and reduce inequalities in cardiovascular care,” she says.

During her fellowship at Mayo Clinic, Adedinsewo began studying how AI with EKGs could be used to improve clinical care. To determine the effectiveness of the approach, the team used deep learning retrospectively to analyze EKG results from patients with shortness of breath. They then compared the results to the current standard of care – a blood test analysis – to see if the AI ​​improvement improved the diagnosis of cardiomyopathy, a condition in which the heart is unable to pump blood adequately to the rest of the body . While understanding the clinical implications of the research, she found the AI ​​components challenging.

“Although I have a degree in medicine and a master’s in public health, these qualifications are not really enough to work in this field,” says Adedinsewo. “I was looking for a way to learn more about AI so that I could speak the language, bridge the gap and bring these groundbreaking tools to my field.”

Building a bridge at MIT

Adedinsewo’s desire to bring together advanced data science and clinical care led her to MIT Professional Education, where she recently completed the Professional Certificate Program in Machine Learning & AI. To date, she has completed nine courses, including AI strategies and roadmap.

“All of the courses were great,” says Adedinsewo. “I particularly appreciate how the faculty, like Professors Regina Barzilay, Tommi Jaakkola and Stefanie Jegelka, have provided practical examples from healthcare and other areas to illustrate what they have learned.”

Adedinsewo’s goals are closely aligned with those of Barzilay, the AI ​​director at the MIT Jameel Clinic for Machine Learning in Health. “There are so many areas of healthcare that can benefit from AI,” says Barzilay. “It is exciting to see how practitioners like Demi participate in the discussion and help to find new ideas for effective AI solutions.”

Adedinsewo also valued the opportunity to work and learn in the larger MIT community with experienced colleagues from around the world, and stated that she learned different things from each person. “It was great to get different perspectives from students using AI in other industries,” she says.

Putting knowledge into practice

Equipped with their updated AI toolkit, Adedinsewo was able to make significant contributions to the research of the Mayo Clinic. The team successfully completed and published their EKG project in August 2020, with promising results. When analyzing the EKGs of around 1,600 patients, the AI-assisted method was both faster and more effective – it outperformed standard blood tests with a measure of performance (AUC) of 0.89 versus 0.80. This improvement could improve health outcomes by improving diagnostic accuracy and increasing the speed at which patients receive adequate care.

But the benefits of Adedinsewo’s MIT experience extend beyond a single project. Adedinsewo says the tools and strategies she acquired have helped her communicate the complexities of her work more effectively and expand its reach and impact. “I feel better able to explain research – and AI strategies in general – to my clinical colleagues. Now people turn to me and ask, ‘I want to work on this project. Can I use AI to answer that question? ” She said.

Look into the AI-supported future

What’s next with Adedinsewo’s research? Mainstream AI in cardiology. Although AI tools are not currently widely used in evaluating patients at the Mayo Clinic, she believes they have the potential to have a significant positive impact on clinical care.

“These tools are still in the research phase,” says Adedinsewo. “But I hope that within the next few months or years we can do more implementation research to see how well they improve care and outcomes for heart patients over time.”

Bhaskar Pant, Executive Director of MIT Professional Education, said, “At MIT Professional Education, we’re particularly excited to be able to bring real-world insights and tools into machine learning and AI from MIT experts to health researchers like Dr. Demi. Adedinsewo working on ways to significantly improve clinical care and health outcomes in cardiac and other patient populations. This is also in line with MIT’s mission to ‘work with others for the good of humanity!’ “

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Women’s Health

Health: Perimenopause: Symptoms can begin long before your periods stop – and it’s impacting women’s mental health

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A senior gynecologist explains the importance of empowering women with perimenopausal symptoms to Abi Jackson.

We’re finally talking more about menopause, but what about perimenopause?

Just like menopause, it can have a significant impact – especially emotionally and mentally. 86% of women said they had mental health problems as a result, according to a new survey from Healthandher.com.

For 58%, low energy and motivation were the main problems, while 53% said they were low mood and depression, along with anxiety (50%), anger, and mood swings (42%). One in ten women even said they had thoughts of suicide, according to a survey of 2,000 British women.

View this post on InstagramA post posted by Dr. Nitu Bajekal MD FRCOG IBLM (@drnitubajekal)

So what do women need to know? We worked with leading gynecologist Dr. Nitu Bajekal (nitubajekal.com) spoken to learn more …

What is perimenopause?

Menopause, in general, is when your periods stop and you haven’t had a period for 12 consecutive months. It’s a natural part of aging that occurs when estrogen levels drop, but it can cause a variety of physical and mental symptoms that can range from mild to debilitating. “The median age for menopause is between 45 and 55 years old, with most going through menopause around 51,” says Dr. Bajekal (although some may experience it even earlier).

“Perimenopause means ‘menopause in transition’. It is the time that leads to a complete missed period. This usually takes about four years but can take anywhere from two to eight years 45, some women with perimenopause can have symptoms by their late 30s, and many people don’t know it. ”

What are the signs of perimenopause?

The symptoms are basically the same as during menopause – such as hot flashes, difficulty sleeping, decreased sex drive, depression, anxiety, and just not feeling like yourself. Some people experience things like brain fog and difficulty concentrating. With perimenopause, Dr. However, Bajekal states that the symptoms can “increase and decrease” and your periods become irregular for a few months and then return to normal for a while.

This up and down pattern can amplify the mental health effects: “Sometimes you may think you’re going crazy for having symptoms for two or three months, but then you don’t, your hormone levels are fluctuating. ‘Did I imagine that? Is that really happening? ‘”

Why is perimenopause awareness important?

Dr. Bajekal agrees that there is “a lack of awareness” among women themselves and sometimes health professionals. This means that women may not just miss out on treatments and advice that might help them. Not knowing exactly what is going on can make the problems worse. “Empowering women with knowledge is the key, because once you know something, you are not afraid of it,” says Bajekal. “You don’t think too much, your brain doesn’t go into overdrive and think, ‘Oh God, what’s wrong with me? Do I need antidepressants, why sometimes don’t I feel like doing something, why do I feel a little bit? removed from my relationship? ‘”

Dr. Bajekal says it is important that women do not feel “fobbed off” by their general practitioners. But it’s also important that doctors investigate other possible causes if necessary: ​​”Because people can be depressed, for example. But the point is to be open to the idea that perimenopause also needs the attention it doesn’t. ” [been getting]. ”

How Can Your Doctor Help With Perimenopause?

Tests don’t diagnose perimenopause, Bajekal explains (although some people get tests done to look for other possible causes). However, if you have symptoms that suggest perimenopause and it is adversely affecting you, you can try hormone replacement therapy. Your GP may schedule a try to see if it helps.

What if your doctor just refuses or tells you to come back at 50? Dr. Bajekal recommends asking about someone who has a particular interest in the subject. “In the family doctor group there will be people who have a special interest in things like cholesterol, high blood pressure, diabetes, women’s health and menopause,” she says.

Knowledge is power

As mentioned earlier, Dr. Bajekal that it can be very helpful to have these conversations and have your concerns explained and confirmed. “It’s about becoming more aware of the symptoms and the condition, and then women can decide what they need,” she says. “Do I just need to know more about it so that I feel empowered? Do I need a hormone replacement?

View this post on InstagramA post posted by Dr. Nitu Bajekal MD FRCOG IBLM (@drnitubajekal)

She is also a big advocate of the role of lifestyle, citing diet, sleep, and regular exercise as key. Bajekal says a diet full of plants and whole foods – high in legumes, beans, whole grains, soy, green leafy vegetables, and fruits – is high in fiber, nutrients, and plant-based estrogens. This is great news for health in general and for perimenopausal support to help balance hormones and inflammation.

“And stress,” says Bajekal. “Identify your sources of stress and find ways to deal with it, whether it be through breathing exercises, yoga, meditation, walking with a friend. Avoid alcohol, excessive caffeine, and smoking; all of these can make menopause and perimenopause worse. Whether you use medication ingestion or not, “she adds,” the lifestyle should always be there – the diet, exercise, laughing with friends, and taking care of your sanity. ”

Never ignore red flags

Dr. Bajekal’s last advice? Even if you are pretty sure that you are in perimenopause, never ignore any gynecological changes that may need more thorough investigation and stay up to date with swab tests. “I see it every day, patients who have been told, ‘Don’t worry, you have heavy periods because you are going through menopause.’ No – it’s not normal. If you have heavy periods, very irregular periods, new pain in your period, you shouldn’t ignore it. And if you have pain or bleeding after sex, make sure this is investigated. ” It could be nothing, or something else – possibly serious – could happen. The review of things will either put you at ease or make sure you are dealt with quickly.

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Women’s Health

Menopause: Answering your queries

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Menopause can often be easily dismissed as a hot flash or two. It is so much more, but a serious lack of understanding and awareness can diminish any person’s experience of menopause. This can result in no questions being asked, which limits the ability to make informed decisions. When it comes to menopause, there are no awkward or ridiculous questions. Learning about menopause is crucial. Always ask.

Dr. Caoimhe Hartley founded Menopausal Health in 2021 to make menopausal women easier to access to the best advice and care. Dr. Hartley is committed to women’s health and is aware of the difficulties women face in understanding and navigating their menopause. Dr. Deirdre Lundy, of the Bray Women’s Health Center, is a women’s health specialist and leads menopausal training for Irish GPs at the Irish College of General Practitioners.

You are responding to some of our menopause concerns here.

I’m 49, but I’m not going through menopause. Does every woman have menopausal symptoms?

“Most women experience perimenopausal or menopausal symptoms,” says Dr. Hartley. “It can affect their mood, sleep, or physical symptoms such as hot flashes or night sweats. Some women may experience vaginal dryness or bladder symptoms. The loss of bone density that occurs when our estrogen production drops during menopause is largely silent.

“Fortunately, however, there is a percentage of women who have no symptoms at all. Likewise, not all postmenopausal women experience significant loss in bone density. Why some women have symptoms and others don’t may depend on genetic factors. If you have missed your period for more than a year [and you are over the age of 50], you can be sure that you are going through menopause. “

My body aches. Is that a sign of menopause?

“Generalized pain is common during menopause,” advises Dr. Hartley. “This may be due to the loss of estrogen, which has some weak anti-inflammatory properties. Similar symptoms have been seen with aromatase inhibitors, which are anti-estrogen drugs that are sometimes used in patients with breast cancer.

“This pain can have secondary effects, including lack of sleep and decreased ability to exercise or be active. Living with pain can also negatively affect our mood. You may find that an old injury is flaring up again or it is a completely new symptom. Know that you are not alone and that there are ways you can help. Joint pain can also be due to other causes such as osteoarthritis, inflammatory arthritis, and other conditions. It is always a good idea to discuss this with your GP as you may need further tests. “

My symptoms are relentless. What can I do?

“A lot,” says Dr. Hartley. “The first step is to get advice and help. Do not suffer in silence! The route of treatment will depend on what symptoms you are experiencing, what background health risks and levels you may have. I usually start by talking to patients about lifestyle interventions, exercise, CBT. to entertain [cognitive behavioural therapy], Reducing caffeine and alcohol, and a discussion of sleep hygiene, etc.

“There are also non-hormonal and hormonal options for treating menopausal symptoms. estrogen [as part of hormone replacement therapy] is most effective for treating symptoms such as hot flashes and night sweats, as well as vaginal symptoms, and also protects against the development of bone loss and osteoporosis.

“If lifestyle changes do not relieve menopausal symptoms, and this is often the case, we recommend speaking to a doctor who has been trained in menopause,” says Dr. Lundy.

I’m going through menopause and so anxious. Is that normal?

“It is very common for mood swings and anxiety to change during menopause,” says Dr. Hartley. “Many women report a loss of self-confidence, low self-esteem, irritability or loss of motivation. Sometimes these symptoms come and go and can be mild. For others, they can be debilitating.

“Women who have had a history of depression, anxiety, significant premenstrual symptoms, or postnatal depression / anxiety may be at greater risk of developing mood or anxiety disorders at the time of menopause. It is important to speak to your GP about the many options for treating all of these symptoms. “

Menopause ruins my sex life. What can I do?

“It depends on so many factors,” says Dr. Hartley. “What are the underlying problems affecting your sex life? Do you have vaginal dryness that makes sex uncomfortable or painful? Are you suffering from poor sleep or a bad mood? There are many things that can affect sexual desire and function. I would advise you to speak to your family doctor. “

I am full of anger! Why is this happening to me?

“There can be many reasons for this,” says Dr. Hartley. “The fluctuating levels of estrogen that occur during perimenopause [the years of hormonal changes that lead up to menopause, the final period] can have a huge impact on mood, irritability, anxiety, and self-confidence. Estrogen plays an important role in our nervous system and affects the production of neurotransmitters, the expression of hormone receptors in our brain and the protection of our nerve cells from damage.

“Anger is not uncommon during menopause. It has to be tackled with healthcare, ”says Dr. Lundy. “HRT can help, but sometimes hormonal changes during menopause only trigger the onset of underlying mental disorders such as bipolar disorder, severe anxiety, and depression.

“The susceptibility to mood swings or irritability is compounded by poor sleep, fatigue, and other possible symptoms,” advises Dr. Hartley. “Know that you are not alone and that there are many options to help you cope.”

Is Hormone Replacement Therapy Right For Me?

“This question is very difficult to answer because it depends on so many different factors,” says Dr. Hartley. “Hormone Therapy in Menopause” [HRT] is one of several different treatment options that we have to help women relieve symptoms of menopause. HRT also protects against bone density loss and can reduce the risk of cardiovascular disease in some women. It depends on your own background risk and the symptoms you are trying to treat. It depends on your own health values ​​and goals.

“For the majority of women, the benefits of hormone therapy for both symptom relief and health improvement outweigh the potential marginally increased risks. The type of HRT, what hormones are prescribed, and how long you take them are also important when considering the risk. Again, for most women, the benefits outweigh the risks. How long you take HRT is also very individual and there is no arbitrary age or how long you need to stop taking your medication.

“It is important to consider lifestyle factors such as smoking, physical activity, alcohol consumption and diet that can affect the long-term risk of developing osteoporosis or bone density loss and cardiovascular disease.

“It’s also important to have your blood pressure and cholesterol checked annually, and to keep up to date with breast and cervical checkups. There are many alternatives to HRT, but these depend on the symptoms affecting your quality of life and thus the goal of treatment. Whichever treatment path you choose, you should be well informed and discuss in detail with your doctor what is the best option for you. “

How long until I feel like myself again?

“This question is difficult to answer,” replies Dr. Hartley. “The duration and severity of the symptoms depend on many factors and are very individual. The average duration of hot flashes and night sweats is five to seven years. Most symptoms will improve over time, but some problems, such as vaginal dryness and discomfort, may get worse over time. “

Dr. Lunday says, “Most women between the ages of 55 and 60 feel a lift. Others can be stressed for much longer and remember that some women have no symptoms at all. “

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