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  • High maternal cortisol levels linked to unexpected birth problems

    High maternal cortisol levels linked to unexpected birth problems

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    A snippet of hair can reveal a pregnant person’s stress level and may one day help warn of unexpected birth problems, a study indicates.

    Washington State University researchers measured the stress hormone cortisol in hair samples of 53 women in their third trimester. Of that group, 13 women who had elevated cortisol levels later experienced unpredicted birth complications, such as an early birth or hemorrhaging.

    While more research is needed with larger groups, this preliminary finding could eventually lead to a non-invasive way to identify those at risk for such complications. The researchers reported their findings in the journal Psychoneuroendocrinology.

    There was otherwise nothing about these women that would suggest a disease or anything else complicating the pregnancy. This confirmed some hypotheses that levels of stress, related specifically to cortisol levels, might be associated with adverse birth outcomes.”


    Erica Crespi, a WSU developmental biologist and study’s corresponding author

    As part of the study, the participants all answered survey questions about their levels of psychological distress in addition to having cortisol measurements taken in the third trimester of pregnancy and after they gave birth. The women who experienced unexpected birth complications had elevated cortisol concentrations in their hair, a measure that indicates the stress hormone’s circulating levels in the body during the three months prior to collection. These women also reported feelings of stress, anxiety and depression, but on average, only high cortisol levels during pregnancy showed a strong link to adverse birth outcomes.

    Cortisol, a steroid hormone, rises in humans and many animals to help regulate the body’s response to stress, but prolonged high cortisol is associated with major health problems including high blood pressure and diabetes. Throughout pregnancy, cortisol levels naturally rise two to four times and peak during the third trimester, but the measurements in this study showed even more pronounced elevated cortisol levels among the women who had unexpected birth complications.

    “If this finding holds up, it could be a non-invasive way to get greater insight into who might be at risk because it is information we didn’t get from the survey,” said co-author Sara Waters, a WSU human development researcher. “This was not something we could find out just from asking people about their stress.”

    Two months after giving birth, the group that experienced birth complications continued to show elevated cortisol and gave survey answers indicating continued stress, anxiety and depression. At six months, their cortisol remained elevated, but they started to report lower psychological distress on the survey, which the authors noted might be a sign of recovery.

    Finding ways to reduce stress around birth could help improve outcomes for both infants and mothers, the researchers said. They point out that adverse birth outcomes are rising in the country. The U.S. also notoriously has one of the highest maternal mortality rates among developed countries, with deaths disproportionately impacting Black women and other people of color.

    More needs to be done to improve healthcare and support systems for pregnant people and new parents, Waters said. This study is also a reminder to expectant and new mothers to prioritize their health.

    “It’s very easy to sacrifice our own health and well-being to prioritize our children’s, especially when it feels like resources are scarce,” said Waters. “But our ability to show up as parents comes from a foundation of getting our needs met too – like the saying, ‘you can’t pour from an empty cup.’”

    This study involved an interdisciplinary research team at WSU. In addition to Crespi and Waters, co-authors include first author Jennifer Madigan, a Ph.D. candidate in stress physiology research; Maria Gartstein, a psychology professor; Jennifer Mattera, a psychology Ph.D. student; and Chris Connelly, an associate professor of kinesiology. This research received support from a WSU Grand Challenges Grant as well as interdisciplinary grants from the WSU College of Arts and Sciences, and the WSU Office of Research.

    Source:

    Washington State University

    Journal reference:

    Madigan, J. A., et al. (2023). Perinatal hair cortisol concentrations linked to psychological distress and unpredicted birth complications. Psychoneuroendocrinology. doi.org/10.1016/j.psyneuen.2023.106921.

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  • Stroke survivors exposed to sexual assault face greater recovery challenges

    Stroke survivors exposed to sexual assault face greater recovery challenges

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    Stressors and traumatic events experienced over the course of a lifetime may negatively impact subsequent stroke recovery; specifically, stroke survivors exposed to sexual assault at any point in their life had poorer physical functioning and cognitive outcomes one year after a stroke, according to a preliminary study to be presented at the American Stroke Association’s International Stroke Conference 2024. The meeting will be held in Phoenix, Feb. 7-9, and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

    It is important to know what has happened to a patient in their life when taking care of them post-stroke. Screening for lifetime stress and trauma is important when caring for a patient who has had a stroke because those experiences often have far-reaching impact and may predict how well a person does over time.”


    E. Alison Holman, Ph.D., lead study author, professor of nursing and psychological science at the University of California, Irvine

    Researchers examined data from the STRONG (Stroke, sTress, RehabilitatiON, and Genetics) study to investigate specific types of stressors that may contribute to adverse physical function and cognitive outcomes one year after stroke. In the STRONG study, stroke survivors were assessed four times during the year. Assessments included the Lifetime Stress and Trauma Exposure survey, completed approximately 90 days after the stroke. Participants reported their lifetime exposure to 31 different types of stressful and/or traumatic events, including witnessing a loved one being injured or killed; sexual assault; divorce; emotional and physical abuse in childhood; and poverty. Additionally, one year after the stroke, participants were assessed for physical function and cognitive abilities. The researchers evaluated the relationships among lifetime stress and trauma exposure and functional and cognitive outcomes among 763 stroke survivors, average age of 63 years.

    The analysis found:

    • Sexual assault was the traumatic event most strongly associated with a moderate decrease in the ability to perform activities of daily living and lower scores on the modified Rankin Scale (describes a person’s ability to function) and Telephone Montreal Cognitive Assessment scores one year after stroke, after controlling for age, gender, race and National Institutes of Health stroke scale score (a measure of stroke severity) three months after a stroke.

    • Other adverse experiences – witnessing a family member be injured or killed; going through a divorce; and/or suffering childhood physical abuse – were also independently associated with a moderate decrease in ability to perform daily living activities one year after stroke.

    • These associations remained even when early post-stroke acute stress levels were accounted for in the analysis.

    • In contrast, taking care of a seriously ill loved one was associated with better scores on the Telephone Montreal Cognitive Assessment. Holman noted that people taking care of others are more actively engaged in everyday life, which may keep the mind sharper. 

    • Women were significantly more likely to report being sexually assaulted and having a seriously ill loved one.

    Holman emphasized that health care professionals should be aware of the potentially lasting physical health impact of sexual assault and other traumatic events that occur over the course of a person’s life. Understanding that these prior life experiences can shape how patients respond to a subsequent stroke may encourage more compassionate communication.

    “Bad things happen to people, so the goal is to intervene in the immediate aftermath of the stroke to prevent its worst effects. We should be able to use this information to allocate resources in a targeted way to provide better support for people during post-stroke recovery,” she said. “Health care professionals can use psychological first aid strategies to support the patients’ basic needs, help them cope and refer them to resources such as a support group or community agency. Sometimes just acknowledging the experience is itself freeing.”

    “This study raises our awareness of how important it is to manage stressors and to increase our physical and mental resilience,” said Randi Foraker, Ph.D., M.A., FAHA, vice chair of the American Heart Association’s Epidemiology & Cardiovascular Stroke Nursing Prevention Science Committee, and professor of medicine, Institute for Informatics, Data Science and Biostatistics and director, Center for Population Health Informatics at Washington University in St. Louis, School of Medicine, Missouri. “Some of the ways we can bolster our resilience and our wellness is to engage in mindful meditation, social engagement and physical activity. As clinicians, researchers and caregivers, we need to make sure we are giving stroke survivors their best chance at living longer, healthier lives.” Dr. Foraker was not involved in the study.

    Study details and background:

    • The study included 763 stroke survivors (average age of 63; 41.3% female; 60.9% white adults).

    • The STRONG study was conducted at 28 stroke centers across the U.S. from 2016-2021.

    • The current study findings build on the STRONG study, led by Holman and her colleague Steven Cramer, M.D., that was previously published in the American Heart Association’s Stroke journal (Sept. 2023), which also suggested that cumulative traumatic stress exposure impairs recovery from stroke.

    The main study limitations were that patients with a severe stroke and those who did not speak English were excluded, so we do not know whether the findings would apply to those patients. Additional research is needed to investigate the potential mechanisms that link these traumatic events to worse outcomes after stroke. Holman suggests it is important to examine both psychological and physiologic processes that may explain the findings.

    Source:

    American Heart Association

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  • Nerve stimulation plus physical rehabilitation may boost recovery of arm and hand function

    Nerve stimulation plus physical rehabilitation may boost recovery of arm and hand function

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    Combining brain stimulation with intense physical rehabilitation helped stroke survivors recover movement in their arms and hands and maintain these improvements for one year, according to a study to be presented at the American Stroke Association’s International Stroke Conference 2024. The meeting will be held in Phoenix, Feb. 7-9, and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

    The recovery of arm and hand function after a stroke often stalls or even declines, leaving many patients with chronic motor deficits that limit their independence and quality of life. New treatments that can boost the benefits of physical rehabilitation are desperately needed.”


    Teresa J. Kimberley, Ph.D., study’s lead author, professor of rehabilitation science and physical therapy at MGH Institute of Health Professions in Boston

    Vagus nerve stimulation is the first approved neuromodulation device to aid in chronic stroke recovery. It was approved by the U.S. Food and Drug Administration in 2021 to treat moderate to severe upper extremity motor function deficits (physical movement and coordination of arms and hands) associated with chronic stroke.

    “This is the first time that brain stimulation combined with rehabilitation therapy for stroke is available outside of a clinical trial. It could set the stage for even more advancements in recovery from other impairments beyond the arm,” Kimberley said. “This is a watershed moment for rehabilitation science.”

    This study represents one-year outcomes in the VNS-REHAB pivotal trial, which studied people who had a stroke resulting in moderate to severe upper extremity impairment.

    Two groups of participants (108 total people) -; a control group and an experimental group -; completed six weeks of in-clinic, intense rehabilitation paired with active or sham vagus nerve stimulation. All participants were implanted with the nerve stimulation device and then randomized to receive either real nerve stimulation or a sham stimulation that only turned on for a few pulses. The in-clinic therapy was followed by a three-month home exercise program for both groups. The active vagus nerve stimulation group continued the home exercise program for a year. After the six-week period of sham stimulation, the control group crossed over and received six weeks of active vagus nerve stimulation followed by a year of the home exercise program.

    Before and after the stimulation and rehabilitation therapies, motor function was assessed with the Fugl-Meyer Assessment-Upper Extremity, which assesses motor impairment, and the Wolf Motor Function Test, which is a time-based method to evaluate upper extremity motor ability while providing a better understanding of joint-specific and total limb movements.

    The final study results represent outcomes for arm and hand function in 74 stroke survivors after one year of physical rehabilitation treatment. Data was unavailable for the remaining 34 participants mainly due to the COVID-19 pandemic.

    This analysis found:

    • At one-year, upper limb function improved by 5.3 points in the Fugl-Meyer Assessment-Upper Extremity and by 0.51 points in the Wolf Motor Function Test when compared to baseline.

    • Vagus nerve stimulation therapy improved hand and arm function by 2-3 times more than intense rehabilitation alone.

    “The pairing of rehabilitation therapy with vagus nerve stimulation likely helps the brain strengthen new neural pathways – like building a bridge to bypass a damaged area,” Kimberley said.

    “These long-term, pivotal results mirror our long-term results from an earlier pilot study where we found that patients continue to improve or maintain their gains up to three years after starting vagus nerve stimulation therapy paired with rehabilitation,” she said. “As a clinician, it is surprising to see someone with chronic stroke – stroke that in many ways is a progressive disease – continue to improve and not show a decline.”

    Study details and background:

    • The vagus nerve stimulation device in this study included a pacemaker connected to a lead that wraps around the vagus nerve in the neck region. There’s one vagus nerve on each side of the body; each one runs from the lower part of the brain through the neck to the chest and stomach.

    • VNS-REHAB trial participants were between the ages of 22-80 and had a stroke nine months to 10 years prior to study enrollment.

    • Study participants in the experimental group were 64% male and 36% female; 79% white, 17% African American adults, 2% Asian, Indian or other adults, and 1% did not have any race reported. The control group was 65% male and 35% female; 78% white, 16% African American adults, 7% Asian, Indian or other adults, and 1% did not have any race reported.

    • The study took five years to complete: 2017-2019 for enrollment, and the study ended in 2021.

    • The study was triple-blinded, meaning neither the participants, the researchers testing participants nor the health care professionals treating participants knew which intervention group participants were in.

    Study limitations included the small sample size and lack of details about the rehabilitation therapy regimens followed by each participant over the one-year period, which were variable.

    Future studies and an ongoing clinical registry will explore the long-term impact of active vagus nerve stimulation in real-world settings.

    “Often after a stroke, people don’t seek additional treatment, thinking that their current impairments are permanent. This is not true! Paired vagus nerve stimulation opens a new avenue and new hope for these patients. I’m also excited about future research that will investigate vagus nerve stimulation paired with rehabilitation for other conditions, such as gait and speech impairments after stroke,” Kimberley said.

    “These are encouraging findings,” said Joel Stein, M.D., FAHA, chair of the writing group for the American Heart Association’s/American Stroke Association’s 2021 Clinical Performance Measures for Stroke Rehabilitation and the Simon Baruch Professor and chair of the department of rehabilitation and regenerative medicine at Columbia University’s Vagelos College of Physicians and Surgeons; professor and chair of the department of rehabilitation medicine at Weill Cornell Medicine; and physiatrist-in-chief at NewYork-Presbyterian Hospital. “These results demonstrate the durability of the effects of vagus nerve stimulation, an important finding that supports the use of this modality to enhance recovery post-stroke. There is some evidence for lasting improvement with continued use outside of a formal exercise program, which is intriguing, although further research is needed to confirm this finding and clarify who is likely to experience ongoing improvements.” Dr. Stein was not involved in this study.

    Source:

    American Heart Association

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  • Stroke survivors in gym-rich neighborhoods more likely to stay physically active

    Stroke survivors in gym-rich neighborhoods more likely to stay physically active

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    Stroke survivors were more likely to remain physically active or even exercise more after their stroke if they lived in neighborhoods with easy access to recreational centers and gyms, according to a preliminary study to be presented at the American Stroke Association’s International Stroke Conference 2024. The meeting will be held in Phoenix, Feb. 7-9, and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

    We know that stroke survivors need to be physically active as part of their recovery. Our findings suggest that it’s important to have a conversation with stroke patients about physical activity resources available in their area so they are able to continue their recovery after hospital discharge. If their neighborhood does not offer fitness resources, neurologists should consider discharging the patient to a rehabilitation facility where they can participate in physical activities.”


    Jeffrey Wing, Ph.D., M.P.H., lead study author, assistant professor of epidemiology at The Ohio State University in Columbus, Ohio

    In this study, researchers examined the potential link between available fitness/exercise centers, pools and gyms and physical activity among 333 people living in New York City who had a mild stroke.The data was geocoded, assigned to the U.S. census tracts, and merged with data from the National Neighborhood Data Archive (collects information about the number of physical activity resources at the census tract level). Geocoding is the process of transforming a description of a location -; such as an address or a name of a place -; to a location on the earth’s surface. Researchers then examined the association between the number of fitness and recreational centers, such as pools, gyms and skating rinks per square mile, and the self-reported change in physical activity levels -; more active, about the same or less active -; one year after stroke.

    The analysis found:

    • About 17% of participants reported being more physically active one year after stroke, and 48% reported having about the same level of physical activity as before the stroke.

    • The odds of being more active were 57% higher among participants who lived in areas with more recreational and fitness resources (about 58 fitness resources) compared to people living in neighborhoods with fewer or no fitness resources, after controlling for age, gender, race, ethnicity, education, health insurance and body mass index.

    • Similarly, the odds of reporting the same level of physical activity one year after stroke were 47% higher in participants who lived in areas with more recreational centers and fitness resources compared to those who lived in areas with fewer or no resources available.

    Previous research has shown that even moderate physical activity is beneficial for stroke recovery and can include walking, Wing said. “However, it’s important to recognize the availability or limited availability of exercise resources in a person’s immediate neighborhood and to be able to feel safe while participating in exercise activities.”

    Previous research has found that the characteristics of the built environment of a neighborhood, such as access to healthy food or recreational spaces promoting physical activity, were also linked to lower incidence of stroke, Wing noted.

    “The takeaway from this analysis is that it’s not that people should move to a location where there are more resources to engage in physical activity, but to urge people to find ways to be active in their own neighborhood,” said study co-author Julie Strominger, a Ph.D. student of epidemiology at The Ohio State University. “It’s the action that will lead to better outcomes, so just the action of being physically active is what really matters.”

    “This study is consistent with prior research on the importance of physical activity for optimal health. The new aspect is the focus on stroke survivors,” said American Stroke Association volunteer expert and EPI and Stroke Council member Daniel T. Lackland, Dr.P.H., FAHA, professor of epidemiology and director of the Division of Translational Neurosciences and Population Studies in the department of neurology at the Medical University of South Carolina in Charleston. “It’s important for health care professionals to discuss maintaining physical activity with stroke survivors: find out if they know of a safe place to exercise, and if they do not, have that information readily available.” Lackland was not involved in the study.

    Study details and background:

    • The analysis included 333 adults hospitalized for mild stroke and enrolled in the Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) study.

    • The DESERVE study was a randomized clinical trial of 546 stroke survivors and conducted in New York City from 2012-2016.

    • Participants were 52% women, with an average age of 65 years; they self-identified as 35% Hispanic adults, 31% Black adults, 28% white adults and 6% as “other” race.

    The main limitations of the study, according to the authors, are that the findings may not be generalizable to non-urban neighborhoods in the U.S. In addition, the data was extracted from a clinical trial that included only stroke survivors who had a mild stroke, therefore, this association may not hold true for survivors of severe stroke. Also, while people in certain neighborhoods reported more physical activity, that does not necessarily mean that they used the fitness and recreational resources in their neighborhood.

    Source:

    American Heart Association

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  • Unveiling the mystery behind rapid memory loss in cancer patients

    Unveiling the mystery behind rapid memory loss in cancer patients

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    In a rare but serious complication of cancer, the body’s own immune system can start attacking the brain, causing rapid-onset memory loss and cognitive deficits. What triggers this sudden biological civil war was largely unknown.

    Now, researchers at University of Utah Health have found that some tumors can release a protein that looks like a virus, kickstarting an out-of-control immune reaction that may damage brain cells.

    Their findings published in Cell on Jan. 31, 2024.

    A rapid immune attack

    Jason Shepherd, Ph.D., associate professor of neurobiology at University of Utah Health and last author on the study, explains that the swift escalation of symptoms-;which can include memory and behavioral changes, loss of coordination, and even seizures-;is a hallmark of the disease, called anti-Ma2 paraneoplastic neurological syndrome. The disease is one of a group of cancer-related neurological syndromes that occur in less than one in 10,000 people with cancer. The precise symptoms of these diseases vary, but all involve rapid immune reactions against the nervous system. “The symptoms come in quickly and can be quite debilitating,” Shepherd says.

    This fascinating research illustrates how tumor cells can manipulate their environment. We hope that this innovative transdisciplinary research will positively impact both the lives of cancer patients and of those who experience neurological symptoms.”


    Neli Ulrich, Ph.D., executive director of the Comprehensive Cancer Center at Huntsman Cancer Institute at the University of Utah and a Jon M. and Karen Huntsman Presidential Professor in Cancer Research at the U

    Stacey L. Clardy, M.D., Ph.D., a neurologist at U of U Health and a coauthor on the study, adds, “Most patients begin to experience these unusual neurologic symptoms before they even know they have a cancer.”

    These rapid-onset symptoms are the result of the immune system suddenly starting to target specific proteins that are found in the brain. Scientists knew that this flare of immunity often targets a protein called PNMA2. But nobody knew why PNMA2 provokes such a strong immune response, which left researchers at a loss for ways to prevent it. “We do not understand what is happening at the cellular or molecular level to actually cause the syndrome,” Clardy says, “and understanding the mechanism of disease is crucial to developing better treatments.”

    A virus lookalike

    To figure out how PNMA2 kickstarts an immune reaction, Junjie Xu, a graduate researcher in neurobiology at U of U Health and the lead author on the study, examined the protein’s structure using advanced microscopy. When he saw the first clear image of the protein, he was “so, so excited,” Xu says. Multiple PNMA2 proteins had spontaneously self-organized into 12-sided complexes that bore a striking resemblance to the geometric protein shells of some viruses.

    One of the immune system’s healthy functions is to attack viruses, and PNMA2’s virus-like structure makes it particularly prone to being targeted as well, the researchers found. In fact, in experiments in mice, the immune system only attacked PNMA2 protein when it was assembled into virus-like complexes.

    Wrong place, wrong time

    The location of PNMA2 in the body is also a crucial piece of the puzzle, the scientists found. “This protein normally is only expressed in the brain, in neurons,” Xu says, “but some cancer cells can express it, which can trigger an immune response.”

    As long as PNMA2 stays in the brain, the immune system won’t react to it. But rarely, a tumor elsewhere in the body will start producing PNMA2 protein. And when the immune system detects PNMA2 protein outside the brain, it reacts like it would to any foreign invader. The immune system makes antibodies that bind to the unfamiliar substance, and those antibodies direct immune cells to attack.

    But, once activated, the immune system doesn’t just attack the PNMA2 produced by the cancer. It also targets the parts of the brain that produce PNMA2 normally, including regions involved in memory, learning, and movement. The brain normally has a degree of protection from the immune system, but cancer weakens that barrier, leaving the brain especially vulnerable to this immune onslaught.

    In future work, the researchers aim to figure out which aspect of the immune response leads to patients’ rapid cognitive decline-;the antibodies themselves, immune cells making their way into the brain, or some combination of the two.

    Understanding how the immune system causes neurological symptoms may help scientists design targeted treatments, Shepherd says. “If we show that PNMA2 antibodies are the culprit that really drives the neurological symptoms, you could devise a way to block those antibodies from getting into the brain or mop them up with something as a treatment… If you can alleviate some of those neurological symptoms, it really would be huge.”

    Source:

    University of Utah Health

    Journal reference:

    Xu, J., et al. (2024) PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome. Cell. doi.org/10.1016/j.cell.2024.01.009.

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