Wednesday, January 18, 2023

New research shows pandemic's toll on frontline healthcare workers

Much of the attention on the mental toll suffered by frontline workers has focused on post-traumatic stress disorder (PTSD). New research from a collaboration between Syracuse University and the University of Pittsburgh reveals that even those who are not

Peer-Reviewed Publication

SYRACUSE UNIVERSITY

For frontline healthcare workers, the mental health impact from the pandemic is extending beyond career burnout.  Much of the attention on the mental toll suffered by frontline workers has focused on post-traumatic stress disorder (PTSD). New research from a collaboration between Syracuse University and the University of Pittsburgh reveals that even those who are not formally diagnosed as suffering from PTSD still experience critical health symptoms that could lead to other overall health problems.

“While there has been a lot of attention paid to elevated symptom levels indicative of a clinical diagnosis, little attention has been paid to subclinical symptom levels,” said Bryce Hruska, assistant professor of public health at Syracuse University’s Falk College and lead author of the publication reporting this research.

Subclinical (or subthreshold) symptoms refer to psychiatric symptoms – PTSD symptoms in the case of this study – that are not severe enough to be considered indicative of a clinical diagnosis. Hruska and his collaborator Dr. Maria Pacella-LaBarbara at the University of Pittsburgh examined the prevalence and significance of subthreshold PTSD symptom levels (known as PTSS) in frontline healthcare workers responding to the pandemic nearly one year after it started, from December 2020 through February 2021. Data from this study were collected from emergency healthcare workers located primarily in Western Pennsylvania and surrounding areas.

“This is an important study that captures what frontline healthcare workers were experiencing during the pandemic’s second wave and continue to experience as COVID approaches the start of its fourth year in the U.S . It could not have been possible without the work of many people including other researchers and medical personnel who assisted with ensuring that these workers’ experiences were represented,” said Hruska.

“In fact, we found that while 5.5% of the healthcare workers in our sample met criteria for probable PTSD, over half (55.3%) experienced subthreshold symptoms,” said Hruska.  So, even though they weren’t reporting symptoms indicative of a clinical diagnosis of PTSD, these workers were still feeling its effects.

Researchers found that workers experiencing these symptoms levels reported:

  • 88% more physical health symptoms (e.g., constant fatigue, weight change, low energy, headache).
  • 36% more sleep problems (e.g., daytime sleepiness, difficulty getting things done) than healthcare workers not experiencing any PTSD symptoms.

“This is a big oversight because these subthreshold symptom levels are common and often confer risk for other health problems,” according to Hruska, who explains that these subthreshold symptoms are often overlooked. That in turn leads to an increase in the risk for subsequently experiencing clinical symptom levels when another significant trauma, such as the current rise in COVID cases, is experienced.

“Thus, while the world tries to move on from the pandemic, our healthcare workers continue to face a significant mental health risk with every surge in cases as is happening now,” said Hruska.

The research was published in January’s edition of the Journal of Psychiatric Research.

Family dynamics and doctors' emotions drive useless end-of-life care

Peer-Reviewed Publication

RUTGERS UNIVERSITY

Researchers from Rutgers and other universities have developed a behavioral model that explains a long-standing healthcare mystery: Why do so many terminally ill patients undergo intense last-ditch treatments with little chance of meaningful life extension?

Surveys repeatedly indicate that nearly all people would rather die peacefully at home, yet painful, long-shot treatments remain common, and efforts to reduce usage have failed.

Previous analyses have mostly emphasized patients’ treatment preferences at the end of life. The new model, which its creators named the Transtheoretical Model of Irrational Biomedical Exuberance (TRIBE), focuses squarely on clinician psychology and family dynamics.

“Old models tended to assume that clinicians were purely rational agents, leading patients toward logical choices,” said Paul R. Duberstein, lead author of the study and chair of the Department of Health Behavior, Society and Policy at the Rutgers School of Public Health. “Once doctors have recommended a treatment or procedure, there’s enormous pressure on patients to undergo it.”

The TRIBE model combines two older theories – Socioemotional Selectivity Theory and Terror Management Theory – to explain why this happens. The model shows how emotional pressures on doctors and complex family dynamics provoke excessive efforts to cure incurable conditions.

“This model incorporates research showing that clinicians are emotional beings, like all people, and these emotions strongly impact their patients’ choices,” Duberstein said. “Doctors hate to ‘give up’ on patients, so they often recommend treatments with very little chance of success. That won’t change until we improve medical education and the culture of irrational biomedical exuberance.”

“Irrational exuberance” is a term that economist Alan Greenspan famously used to describe investor sentiment in the lead-up to the dot-com crash, but Duberstein and his colleagues said it has long affected doctors and patients as much as it has affected Wall Street. They read of one-in-a-million cures and irrationally believe that they or their patients will be that one in a million – just as people who purchase lottery tickets think they’ll be the lucky winners.

Pointing out the irrationality of the choice doesn’t affect doctors any more than it affects lottery players. Indeed, the researchers believe, it affects doctors less because, unlike gambling, which is often portrayed as a vice, the struggle to preserve life is typically portrayed as a virtue.  Motives to prescribe long-shot treatments are noble – to avoid death, save a life, “do all we can,” “fight a battle” and “never give up.” In this view, failing to prescribe long-shot treatments is tantamount to abandoning patients and, for patients, failing to try these treatments is tantamount to abandoning loved ones.

The authors, who also hail from Tulane, Rochester and Rowan, call for new approaches to clinical care and public education that will address the emotions that fuel useless treatments at the end of life. “At some level, every patient death is a potential source of shame for doctors and a source of guilt for surviving family members,” Duberstein said. “By changing the culture of medical education and broader cultural attitudes toward death, we can address the emotions and family dynamics that have prevented too many patients from receiving quality care in their final days and weeks of life.”

New roundtable on health equity in communities of color

Peer-Reviewed Publication

MARY ANN LIEBERT, INC./GENETIC ENGINEERING NEWS

Health Equity 

IMAGE: JOURNAL MEETS THE URGENT NEED FOR AUTHORITATIVE INFORMATION ABOUT HEALTH DISPARITIES AND HEALTH EQUITY AMONG VULNERABLE POPULATIONS. WITH COVERAGE RANGING FROM TRANSLATIONAL RESEARCH TO PREVENTION, DIAGNOSIS, TREATMENT, AND MANAGEMENT OF DISEASE AND ILLNESS, THE JOURNAL SERVES AS A PRIMARY RESOURCE FOR ORGANIZATIONS AND INDIVIDUALS WHO SERVE THESE POPULATIONS AT THE COMMUNITY, STATE, REGIONAL, TRIBAL, AND NATIONAL LEVELS. view more 

CREDIT: MARY ANN LIEBERT INC., PUBLISHING

A new Roundtable focusing on health equity in communities of color features the expertise and insights of five distinguished academic and social justice leaders. Moderated by Gail Christopher, DN, Executive Director of the National Collaborative for Health Equity (NCHE), the Roundtable was published today on the National Day of Racial Healing in the peer-reviewed journal Health EquityClick here to read the roundtable now.

"At this unique moment in our nation's history, we have collectively endured the most devastating health crisis in our history, the COVID-19 pandemic," says Christopher.  "Its harmful effects have been disproportionately experienced by communities of color. Within every crisis, there is an opportunity for healing and growth. The National Collaborative for Health Equity is pleased to offer this roundtable and the accompanying articles as a contribution to our healing journey." 

Participants in the Roundtable represent the inaugural group of NCHE Senior Scholars. They include Charmaine Royal, PhD, MS, Robert O. Keohane Professor of African & African American Studies, Biology, Global Health, and Family Medicine & Community Health at Duke University; Lisa Sockabasin, MS, a Citizen of the Passamaquoddy Tribe at Motahkomikum and co-CEO of Wabanaki Public Health and Wellness; Mindy Thompson Fullilove, MD, LFAPA, a Social Psychiatrist and Professor of Urban Policy and Health at The New School; Alan Jenkins, JD, MA, Professor of Practice at Harvard Law School; and Algernon Austin, PhD, Director for Race and Economic Justice at the Center for Economic and Policy Research

Also included in the issue of Health Equity to be published on January 20, 2023, are comprehensive articles by each of the Roundtable participants that align with the pillars of the Truth, Racial Healing & Transformation™ (TRHT™) Framework, a national and community-based effort established by the W.K. Kellogg Foundation to engage communities, organizations, and individuals from multiple sectors across the United States in racial healing and addressing present-day inequities linked to historic and contemporary beliefs in a hierarchy of human value. 

About the Journal
Health Equity is the Official Journal of the National Collaborative for Health Equity. The peer-reviewed open-access journal meets the urgent need for authoritative information about health disparities and health equity among vulnerable populations. With coverage ranging from translational research to prevention, diagnosis, treatment, and management of disease and illness, the Journal serves as a primary resource for organizations and individuals who serve these populations at the community, state, regional, tribal, and national levels. 

About the National Collaborative
Officially launched in 2014, National Collaborative for Health Equity builds on 18-years of comprehensive efforts to advance health equity.  The National Collaborative was established to promote health and racial equity through action, leadership, and collaboration. Health equity, in our view, requires creating the conditions that foster the best possible health for all populations, regardless of race, ethnicity, socioeconomic status, or nativity. 

About the Publisher
Mary Ann Liebert, Inc., publishers is known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research. A complete list of the firm's 90 journals, books, and newsmagazines is available on the  Mary Ann Liebert, Inc., publishers website.

New research furthers case for exercise promoting youthfulness

Evidence shows that exercise promotes a molecular profile in muscle that is consistent with expression of youthfulness-promoting Yamanaka factors

Peer-Reviewed Publication

UNIVERSITY OF ARKANSAS

Kevin Murach 

IMAGE: KEVIN MURACH view more 

CREDIT: UNIVERSITY RELATIONS

A recent paper published in the Journal of Physiology deepened the case for the youthfulness-promoting effects of exercise on aging organisms, building on previous work done with lab mice nearing the end of their natural lifespan that had access to a weighted exercise wheel. 

The densely detailed paper, “A molecular signature defining exercise adaptation with ageing and in vivo partial reprogramming in skeletal muscle,” lists a whopping 16 co-authors, six of whom are affiliated with the U of A. The corresponding author is Kevin Murach, an assistant professor in the U of A’s Department of Health, Human Performance and Recreation, and the first author is Ronald G. Jones III, a Ph.D. student in Murach’s Molecular Muscle Mass Regulation Laboratory.

For this paper, the researchers compared aging mice that had access to a weighted exercise wheel with mice that had undergone epigenetic reprogramming via the expression of Yamanaka factors.

The Yamanaka factors are four protein transcription factors (identified as Oct3/4, Sox2, Klf4 and c-Myc, often abbreviated to OKSM) that can revert highly specified cells (such as a skin cell) back to a stem cell, which is a younger and more adaptable state. The Nobel Prize in Physiology or Medicine was awarded to Dr. Shinya Yamanaka for this discovery in 2012. In the correct dosages, inducing the Yamanaka factors throughout the body in rodents can ameliorate the hallmarks of aging by mimicking the adaptability that is common to more youthful cells.

Of the four factors, Myc is induced by exercising skeletal muscle. Myc may serve as a naturally induced reprogramming stimulus in muscle, making it a useful point of comparison between cells that have been reprogrammed via over expression of the Yamanaka factors and cells that have been reprogrammed through exercise — “reprogramming” in the latter case reflecting how an environmental stimulus can alter the accessibility and expression of genes. 

The researchers compared the skeletal muscle of mice who had been allowed to exercise late in life to the skeletal muscle of mice that overexpressed OKSM in their muscles, as well as to genetically modified mice limited to the overexpression of just Myc in their muscles.

Ultimately, the team determined that exercise promotes a molecular profile consistent with epigenetic partial programming. That is to say: exercise can mimic aspects of the molecular profile of muscles that have been exposed to Yamanaka factors (thus displaying molecular characteristics of more youthful cells). This beneficial effect of exercise may in part be attributed to the specific actions of Myc in muscle.

While it would be easy to hypothesize that someday we might be able to manipulate Myc in muscle to achieve the effects of exercise, thus sparing us the actual hard work, Murach cautions that would be the wrong conclusion to draw. 

First, Myc would never be able to replicate all the downstream effects exercise has throughout the body. It is also the cause of tumors and cancers, so there are inherent dangers to manipulating its expression. Instead, Murach thinks manipulating Myc might best be employed as an experimental strategy to understand how to restore exercise adaptation to old muscles showing declining responsiveness. Possibly it could also be a means of supercharging the exercise response of astronauts in zero gravity or people confined to bed rest who only have a limited capacity for exercise. Myc has many effects, both good and bad, so defining the beneficial ones could lead to a safe therapeutic that could be effective for humans down the road.

Murach sees their research as further validation of exercise as a polypill. “Exercise is the most powerful drug we have,” he says, and should be considered a health-enhancing — and potentially life-extending — treatment along with medications and a healthy diet.

Murach and Jones’ co-authors at the U of A included exercise science professor Nicholas Greene, as well as contributing researchers Francielly Morena Da Silva, Seongkyun Lim and Sabin Khadgi.

Body Dissatisfaction Can Lead to Eating Disorders at Any Age

New study suggests that perimenopause may be an especially risky time for women who are trying to overcome a poor body image

Peer-Reviewed Publication

THE NORTH AMERICAN MENOPAUSE SOCIETY (NAMS)

CLEVELAND, Ohio (Jan 18, 2023)—Eating disorders are stereotypically associated with adolescents and young adults. Growing evidence, however, suggests that these conditions can occur at any time during a woman’s lifespan, including at midlife. A new study finds that body dissatisfaction is a primary cause of eating disorders, especially during perimenopause. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Eating disorders are serious mental health conditions characterized by disturbances in eating behavior and body image that occur in approximately 13.1% of women across the lifespan. The prevalence of any eating disorder specifically for women aged older than 40 years is roughly 3.5%, with specific symptoms such as dissatisfaction with eating patterns being documented as high as 29.3%.

Serious complications such as high mortality and morbidity are associated with eating disorders. These adverse health events are likely to be magnified when present at older ages. However, few studies on eating disorders have included participants at midlife, including premenopause, perimenopause, and postmenopause.

There is some evidence that supports the idea that perimenopausal women have the highest rates of dysregulated eating behaviors (eg, weight-control behaviors such as regular counting of calories or consumption of diet foods) of any reproductive stage at midlife and are significantly different from premenopausal women with regard to body dissatisfaction and feelings of fatness. Although findings such as these remain scant; the association between eating disorders and symptoms of perimenopause (eg, negative mood, depression, and fatigue) confirm that perimenopause may be a particularly risky time for eating pathology.

In this new small study, which sought to investigate the structure of eating disorder symptoms specifically during perimenopause and early postmenopause, the researchers used network analysis statistical models to compare the structure and importance of specific eating disorder symptoms across reproductive stages. Although they admit that larger studies are necessary with this underrepresented female population, the researchers believe that the study confirms that dissatisfaction with body image is a key risk factor for eating disorders across the lifespan, especially at midlife.

Study results are published in the article “Network analysis of eating disorder symptoms in women in perimenopause and early postmenopause.”

“This study shows that, similar to studies in young adults, dissatisfaction with body image remains a core feature of eating disorder pathology in midlife women. Specifically, fear of gaining weight and fear of losing control over eating habits are central symptoms of eating disorders in perimenopause and early postmenopause. These findings may help direct more targeted treatment strategies in women during midlife,” says Dr. Stephanie Faubion, NAMS medical director.

For more information about menopause and healthy aging, visit www.menopause.org. Founded in 1989, The North American Menopause Society (NAMS) is North America’s leading nonprofit organization dedicated to promoting the health and quality of life of all women during midlife and beyond through an understanding of menopause and healthy aging. Its multidisciplinary membership of 2,000 leaders in the field—including clinical and basic science experts from medicine, nursing, sociology, psychology, nutrition, anthropology, epidemiology, pharmacy, and education—makes NAMS uniquely qualified to serve as the definitive resource for health professionals and the public for accurate, unbiased information about menopause and healthy aging. To learn more about NAMS, visit www.menopause.org. 

New study showed how people interacted with chatbots during COVID-19 pandemic

Conversation with AI chatbot was found to reduce negative moods during COVID-19 lockdowns

Peer-Reviewed Publication

INSTITUTE FOR BASIC SCIENCE

Figure 1 

IMAGE: TOPICS DISCUSSED BY USERS WITH THE CHATBOT IDENTIFIED BY THE LATENT DIRICHLET ALLOCATION TOPIC MODEL AND THEIR PREVALENCE. view more 

CREDIT: INSTITUTE FOR BASIC SCIENCE

The COVID-19 pandemic has increased people's reliance on digital platforms, such as social media, to obtain information and communicate their thoughts and emotions with their peers. The sudden shift from offline to online interactions due to the COVID-19 pandemic has fueled the popularity of chatbots in many fields, including the medical domain. The World Health Organization (WHO) has even used a chatbot to fight against false information, and they are still looking into how this new technology can help them prepare for future pandemics.

A new study has shown the potential of AI chatbots to relieve users' anxiety and quickly deliver information during major social upheavals. Led by Chief Investigator CHA Meeyoung of the Data Science Group within the Institute for Basic Science (IBS) and Dr. CHA Chiyoung from Ewha Woman's University's College of Nursing, the researchers analyzed nearly 20,000 conversations between online users and a chatbot called SimSimi. This commercial chatbot has served over 400 million users worldwide in 81 languages. The joint research team investigated how users from the United States, United Kingdom, Canada, Malaysia, and the Philippines used the chatbot during the COVID-19 pandemic.

This study is one of the first to analyze large-scale data on conversations related to COVID-19 between chatbots and humans.

Dr. CHIN Hyojin, the lead author of the study said, “Chatbots are a promising tool to fulfill people's informational needs in challenging times. While health institutions such as the Korea Center for Disease Control and Prevention and the World Health Organization (WHO) have used chatbots to provide the most up-to-date information on the spread and symptoms of COVID-19 to billions of people, it was unclear how users interacted with such systems in times of crisis.”

The researchers employed natural language processing (NLP) techniques to identify a series of topics discussed by online users when talking to the chatbot. The results show that users use the chatbot to ask questions about the disease and have a small talk during periods of social isolation due to the pandemic.

During the pandemic's lockdowns, the chatbot frequently served as a conversation companion for obtaining information and expressing emotions. The researchers found 18 COVID-19-related topics that people conversed with the chatbot using topic modeling, a machine learning technique that discovers conversation topics from large-scale text data, and classified them into overarching themes.

Some of these themes included the outbreak of COVID-19, preventative behaviors, the physical and psychological impact of COVID-19, people and life in the pandemic, and questions about COVID-19. This showed that many users sought information and queried the chatbot about the pandemic, even though the particular chatbot under study was not designed to deliver specific information on COVID-19.

In terms of how people felt, the team employed computational tools to compare how each of these themes made them feel. Although some topics, such as masks, lockdowns, and disease dread elicited negative emotions, it was discovered that daily chatter with the chatbot mostly led to positive emotions. There were also regional differences based on geographics. For example, U.S.-based users were found to more frequently use negative keywords in comparison to users from Asia.

Chief Investigator Cha said, “This study is unique because it is the first to use commercial chatbot conversations that are not dedicated to mental support during the pandemic. Because individuals are sharing their concerns and seeking assistance from social chatbots, they can be an essential tool for healthcare during crises like the COVID-19 pandemic. The next stage is understanding individuals' intentions and utilizing the knowledge to create systems that better respond to user demands during difficult times.”

The study was published in the Journal of Medical Internet Research (JMIR) as part of a series called "Chatbots and COVID-19," which was organized by the WHO.

The average percentage of positive and negative-related words in COVID-19–related conversations by country according to the Linguistic Inquiry and Word Count dictionary.

During the Covid-19 pandemic, users sought health-related information and shared emotional messages with the chatbot, indicating the potential use of chatbots to provide accurate health information and emotional support.

CREDIT

Institute for Basic Science

EMOTIONAL PLAGUE

Negative marital communications leave literal, figurative wounds

Study links destructive interaction patterns to lower immune function

Peer-Reviewed Publication

OHIO STATE UNIVERSITY

COLUMBUS, Ohio – A tendency for one or both spouses to avoid or withdraw from tough conversations could set up married couples for emotional distress, bad feelings about their relationship, chronic inflammation and lowered immune function, new research suggests.

The analysis revisits data from a 2005 Ohio State University study that showed the stress couples feel during a brief argument could slow their bodies’ ability to heal from wounds by at least a day – a landmark finding at the time showing how psychological stress affects immunity.

A fresh look at the data shows that when married couples typically communicate with each other in negative ways, both spouses – and women in particular – suffer emotionally and their immune function wanes, in the form of having wounds that take longer to heal. The analysis revealed that the health consequences of negative communication patterns were evident even before the 2005 study began: These couples arrived at the lab with higher blood markers for inflammation.

The initial trial showed that one stressful argument – in a lab, recorded and analyzed by researchers – could harm immune function. This new study suggests that the more combative arguments in the lab were linked to more negative typical marital communication for these couples – and those daily patterns are a likely culprit behind persistent negative emotions and biological markers that can lead to poorer health outcomes.

“Marriage is associated with better health, but chronically distressed marriages can worsen health,” said first author Rosie Shrout, who completed this work as a postdoctoral researcher in Ohio State’s Institute for Behavioral Medicine Research (IBMR). “It’s important to understand what is going on behind the scenes that contributes to these effects.

“What we’re seeing is that both chronic daily negativity and acute negativity, and their combination – experiencing both of those – is particularly bad for couples’ emotions, relationships and immune functioning,” said Shrout, now an assistant professor of human development and family science at Purdue University.

The new study was published recently in the journal Psychoneuroendocrinology.

The 2005 research was co-led by Jan Kiecolt-Glaser, senior author of the new study and professor emerita of psychiatry and psychology at Ohio State, whose decades of discoveries as a leader of the IBMR have shown the many ways in which stressful life events are detrimental to health.

The 2005 work involved 42 married heterosexual couples who had been together for an average of 12 years. Researchers tested the baseline level of a proinflammatory protein in their blood and used a device to raise small blisters on each partner’s forearm – the wounds’ healing progress was monitored as an indicator of how well each participant’s immune system was functioning.

Participants completed questionnaires assessing their typical communication patterns when problems arise – mutual constructive or symmetrical positive communication, or variations of negative communication patterns that involved either mutual avoidance or instances where one partner made demands and the other withdrew from the discussion in response.

Couples were recorded having discussions in two separate lab visits: The first focused on social support and the second was an attempt to resolve a known source of tension in the marriage, such as finances or in-laws. Researchers coded negative and positive behaviors during these talks.

In follow-ups, couples evaluated the discussions – whether they were satisfied with the conversation, and the degree to which they felt supported and understood by their partner, and in control and working productively while sorting out a problem. Their blister wound healing was assessed daily for eight days and then again on day 12.

In the new study, statistical modeling of the qualitative and biological data showed that couples’ negative communication patterns – specifically mutual avoidance or demand/withdrawal – had cascading effects on how they felt after the lab conversations, and on their inflammation and immune function measures.

“If they were more negative typically on a day-to-day basis, and were negative in those specific interactions, they rated the discussion more negatively and less positively, they felt fewer positive emotions, and their wounds healed more slowly,” Shrout said. “That chronic negativity and acute negativity had emotional, relational and immune effects – most notably for women.”

In contrast, couples who reported more mutual constructive communication patterns rated the lab conversations more favorably.

A few specific findings suggested how insidious the effects of poor communication patterns could be: Wounds healed more slowly in couples who mutually avoided talking about tough topics and also showed fewer positive behaviors during lab discussions. Even when mutual avoiders were more positive while trying to resolve conflict, that positivity didn’t help their wounds heal more quickly.

Kiecolt-Glaser, who has led a number of marriage and health studies, said it doesn’t take long for married couples to have expectations of what the marriage is like that can override any evidence to the contrary. In a bad marriage, a negative behavior is perceived as reinforcement of this expectation, while in a good marriage, a negative behavior is taken as a sign one’s partner is in distress.

“This study provides a window into relationships: What couples say about their relationship really did translate not only into how they behaved, but also what they said about the behavior, and their biology,” she said. “They walked into this study situation, and the way they’re responding may in part be because that’s what they’re expecting. They have such well-worn tracks in terms of interactions that it’s hard to derail the train.”

That doesn’t mean all is lost, Shrout noted – couples have lots of options to pursue education or therapy to help them learn better communication skills.

This work was supported by an Ohio State Presidential Postdoctoral Scholars Fellowship and the National Institutes of Health.

Additional co-authors include Megan Renna of the University of Southern Mississippi, and Annelise Madison and William Malarkey of Ohio State.

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Contacts:

Rosie Shrout, Shrout@purdue.edu
Jan Kiecolt-Glaser, Kiecolt-Glaser.1@osu.edu

Written by Emily Caldwell, Caldwell.151@osu.edu; 614-292-8152

 

Study indicates likely cause of common penis birth-defect

Peer-Reviewed Publication

WASHINGTON STATE UNIVERSITY

PULLMAN, Wash. –An alarming increase in the occurrence of the most common genital malformation in male babies, hypospadias, is likely due to environmental factors, such as toxicant exposure, which alter epigenetic programming in a forming penis. 

That’s according to a new study in Science Reports that identified a direct link between hypospadia tissue samples and the presence of epigenetic alterations, or changes to the molecular factors and processes around DNA that determine how genes behave. Conversely, epigenetic alternations were not found in penile tissue samples taken from the foreskin of healthy babies without hypospadias, according to the Washington State University-led analysis. 

The research helps answer long-standing questions surrounding the increased frequency and potential root cause of hypospadias, a birth defect in which the opening of the urethra is located on the underside of the penis instead of the tip. 

“Previous researchers have done extensive analyses and not found any kind of genetic DNA sequence mutations that correlate with the presence of the disease, so there has always been a big question mark regarding where it comes from,” said Michael Skinner, corresponding senior author of the study and a WSU professor of biology. “Our study shows the etiology of the disease is environmentally driven through epigenetics rather than a result of changes to the DNA sequence. It gives us a clearer picture of what is going on.” 

While the research is still in an early stage of development, it could ultimately lead to earlier detection and better clinical management of hypospadias, the prevalence of which has increased by 11.5% in recent decades, making it the most common genital malformation in newborn males. 

One potential path forward would be to identify a specific epigenetic biomarker that could be collected with a simple cheek swab from the parents of a baby to determine the likelihood of the newborn developing a hypospadia. 

“This is not so far-fetched,” Skinner said. “We have identified these types of biomarkers for other diseases. Early detection means they could do clinical management sooner which could result in fewer complications for the baby and more peace of mind for the parents.” 

A major question that remains to be answered is specifically what environmental factors (i.e. toxicants) are promoting the epigenetic alterations that are causing hypospadias. 

One potential culprit the researchers mentioned in the study is a pharmaceutical drug called diethylstilbestrol (DES) that was used in the late 50s and early 60s to ease the later stages of pregnancy for women. 

“There was never really evidence that it helped with pregnancy, but after the fact, doctors started to find severe developmental effects from the drug on babies. Hypospadias were one of the issues,” Skinner said. “Unfortunately, because epigenetic changes caused by drugs like this and other environmental toxicants are epigenetically heritable, they are often passed down from one generation to the next after they are contracted. Over time, the detrimental effects can persist and spread.” 

Another interesting finding from the study was that tissues samples with mild cases of hypospadias had a greater degree of epigenetic alterations than tissue samples with more severe versions of the disease. 

“What this suggests is that cells with really severe epigenetic alterations are probably dying and not surviving whereas a mild case of hypospadia will have lots of these diseased cells still alive,” Skinner said. “This gives us new insights into how epigenetic control is affecting tissue development.” 

This study was conducted in collaboration with researchers from the Departments of Pediatrics and Pediatric Urology at the Indiana University School of Medicine. Funding for the research was provided by the John Templeton Foundation. 

New initiative provides biomedical research experience to West Virginia high school students

Business Announcement

MARSHALL UNIVERSITY JOAN C. EDWARDS SCHOOL OF MEDICINE

HUNTINGTON, W.Va. – A new initiative at the Marshall University Joan C. Edwards School of Medicine offers West Virginia high school students an opportunity to explore the field of biomedical research while working to facilitate a more diverse research workforce across Appalachia. As part of the Health Care Pathways Initiative (HCPI), a four-week summer residential experience at Marshall University for minorities underrepresented in STEM careers, three local high school students will be selected for the new program that combines hands-on research experience with mentoring.   

Students will participate in three eight-week rotations throughout the school year, working in the laboratories of scientists at the Joan C Edwards School of Medicine. After completion of their research rotations, students will select a "permanent" mentor to work alongside for the rest of the program. Student participants will receive additional mentorship from teachers at their home high schools as well as junior graduate students or undergraduate mentors at Marshall.

Participating faculty members, undergraduate and graduate student trainees in their labs, and the high school trainees will meet for a bi-weekly lab and mentoring meeting that will include professional development training in topics such as time management, reading scientific literature, and careers in biomedical research. During the summer of 2023, students will perform full time research and have the opportunity to present their research findings at the WV-INBRE annual summer research symposium.  

“At Marshall, we are passionate about cultivating a passion for science and discovery that can impact the field of medicine and our communities for decades to come,” said Shelvy L. Campbell-Monroe, Ph.D., associate dean of diversity and inclusion for the Marshall University schools of medicine and pharmacy.

“This initiative is the first step in developing a comprehensive biomedical research pathway spanning high school students to postdoctoral trainees.” said Daniel Morgan, Ph.D., associate professor and vice chair of biomedical sciences at the Joan C. Edwards School of Medicine and principal investigator on the grant. “Our focus on high school students stems from a commitment to encourage scientific engagement and curiosity at a younger age.”

This project is funded by a one-year supplemental award from the National Institutes of Health (DA044999). The grant covers the cost of a paid research experience for the students, travel to the Annual Biomedical Research Conference for Minoritized Scientists (ABRCMS), as well as college entrance exams for student participants. Dr. Morgan and Dr. Brandon Henderson, Ph.D., associate professor and co-investigator on the grant, hope to seek additional funding to sustain and expand the program to include research training for minority undergraduate and graduate students as well as postdoctoral fellows.

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