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Newswise — ST. LOUIS — Saint Louis University researchers report in Molecular Metabolism new findings that the nuclear receptor REV-ERB appears to play a key role in muscle regeneration, suggesting the receptor may be a good target for new drugs to treat a variety of muscle disorders and injuries. Colin Flaveny, Ph.D. assistant professor of pharmacology and physiology and Thomas Burris, Ph.D., chair of pharmacology and physiology at Saint Louis University, focus their work on identifying natural hormones that regulate nuclear receptors and then developing synthetic compounds to target these receptors in order to develop drugs to treat diseases. Earlier this year, Burris published findings showing that a nuclear receptor called REV-ERB is involved in lowering LDL cholesterol. He previously studied REV-ERB’s role in regulating mammals’ internal clocks. Now teaming up, Flaveny and Burris are uncovering REV-ERB’s role in muscle regeneration. “REV-ERB is an interesting nuclear receptor that helps coordinate our metabolism with our daily routine,” Flaveny said. “We’re studying the protein to see if turning its activity up or down can influence the way muscle regenerates after injury or illness.” Skeletal muscle comprises 40 to 50 percent of our total body mass and is essential for postural support, locomotion and breathing. With a high capacity for regeneration, skeletal muscle normally maintains muscle mass and function in response to minor injuries and normal wear and tear without much trouble. However, in cases of traumatic injury or illnesses like congestive heart failure, chronic obstructive pulmonary disease, severe burns, cancer and HIV infection, the body’s natural muscle regeneration may not be able to keep up and the loss of skeletal muscle mass and strength is common. When injuries are severe – with more than 20 percent loss of muscle mass – normal muscle regeneration often cannot keep pace with the regenerative demands. In this scenario, the loss of skeletal muscle mass can trigger widespread fibrosis and loss of muscle function. Eventually, muscle regeneration may become unable to keep up, even with assistance through dietary interventions, anabolic steroids or non-steroidal anti-inflammatories (NSAIDs). The use of anabolic steroids and NSAIDs are accompanied by severe side effects that may further reduce quality of life. Often, pharmacological interventions fail to stem long-term decline in quality of life or enhance survival for those with degenerative muscle tissue diseases. “Identifying new means of accelerating muscle regeneration has proved a daunting challenge,” Burris said. “Therefore understanding the underlying mechanisms that regulate muscle cell regeneration and coordinate regenerative repair could provide future therapeutic options for stymieing the loss of muscle function in the traumatically injured.” A simplified version of muscle cells’ life-cycle looks like this: muscle stem cells produce myoblasts that will either reproduce (proliferate) or form muscle tissue (differentiate). Successful regeneration of skeletal muscle after traumatic injury depends on the replenishment of muscle fibers through elevated myoblast proliferation and differentiation. Scientists were fascinated to see that REV-ERB appears to play different roles for different stages of muscle tissue development. A decline in expression of REV-ERB precedes myoblast differentiation. Conversely, an increase in REV-ERB expression is involved in the regulation of mitochondrial and metabolic function in fully differentiated skeletal muscle. The research team identified a mechanism through which REV-ERB may regulate gene expression pre and post muscle differentiation. They show that REV-ERB is a regulator of muscle differentiation that can be targeted to stimulate muscle regeneration and may be useful in treating numerous muscle diseases, including muscular dystrophy, sarcopenia and cachexia, in addition to acute injury. “We demonstrate that REV-ERB can stimulate muscle regeneration upon acute muscle injury in an animal model,” Burris said. “Our findings reveal that REV-ERB may be a potent therapeutic target for the treatment of a myriad of muscular disorders.” Other researchers on the study include Ryan D. Welch, Chun Guo, Monideepa Sengupta, Katherine J. Carpenter, Natalie A. Stephens, Stacy A. Arnett, Marvin J. Meyers, Lauren M. Sparks, Steven R. Smith and Jinsong Zhang. This work was supported by grants from the National Institutes of Health (MH093429 and R01HL093195). Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious diseases.   SEE ORIGINAL STUDY

Newswise — Most people are aware of post-traumatic stress disorder, an anxiety disorder that can develop after a shocking, scary or dangerous event. It can cause irritability, emotional numbing, sleeplessness and other problems. What’s less well-known is how a parent’s PTSD can affect their children. That’s an area that Tom Babayan, a licensed marriage and family therapist at UCLA, wants to draw attention to during PTSD Awareness Month in June. Based at the Nathanson Family Resilience Center at UCLA’s Semel Institute, Babayan helps people with PTSD learn to communicate about their symptoms to their children. Parents don’t need to talk about their trauma to share their struggles, Babayan says. Instead, they should explain the PTSD-related behavior their children might be witnessing. For example: “Mom is having some bad memories once in a while; that’s why she seems irritated. It’s something we’re working on.” “Keep in mind the age, and perspective, of your child,” Babayan says. “A lot of times kids are asking less about what actually happened, and more about the present moment; they’re concerned about who’s going to take them to baseball practice. Parents can imagine what’s important to child – and if they aren’t sure, explore it.”

Newswise — MINNEAPOLIS – For people with headache, seeing the neurologist by video for treatment may be as effective as an in-person visit, according to a study published in the June 14, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology. “Headache is the most common neurologic disorder, yet is often not diagnosed or people don’t receive adequate treatment,” said study author Kai I. Müller, MD, of the Arctic University of Norway in Tromsø. “New technology is available to diagnose and treat people through telemedicine, but few studies have looked at whether it is effective for people with headache.” The study involved 402 people with non-acute headaches, or headaches that came on gradually, who had been referred from a primary care doctor to a neurologist. Half of the participants then had a traditional office visit with a neurologist at a hospital in northern Norway. The other half came to the hospital but saw the neurologist through video conference. Participants completed questionnaires about the impact their headaches had on their daily life and about the level of pain at the beginning of the study and again after three months and one year.  The researchers found no differences between the people treated using telemedicine and those who had traditional office visits. The study was what is called a non-inferiority study, which is designed to show that the new type of treatment is not clinically worse than the current type of treatment. To assess the safety of using telemedicine, the researchers looked to see whether participants had secondary headache a year after the visit. Secondary headache is a headache that is a symptom of a disease or another underlying condition. “We wanted to make sure that the neurologists were not missing any underlying diseases that were causing the headaches when they were treating people via telemedicine, but there was only one person in each group who had a secondary headache, so there was no difference in the diagnosis and treatment,” Müller said. The researchers estimated that in every 20,200 consultations by telemedicine, one diagnosis of secondary headache would be missed. “Northern Norway covers a huge area and it is broken up by mountains, valleys and fjords into many sparsely populated places, so traveling to see a doctor can be cumbersome and expensive for many people,” Müller said. “But telemedicine may be valuable for people all over the world who are suffering with headaches and want to see a specialist without any extra hassle or inconvenience.” Müller noted that having all of the participants come to the hospital made the study conditions less realistic. He said that other weaknesses of the study were the lack of a placebo group and blinding, but that those would be difficult to implement. The study was supported by the Northern Norway Regional Health Authority. To learn more about headache, visit www.aan.com/patients. The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with 32,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy. For more information about the American Academy of Neurology, visit http://www.aan.com or find us on Facebook, Twitter, Google+, LinkedIn and YouTube.

Newswise — The developmental period from adolescence to adulthood is accompanied by a greater vulnerability to addictions – including alcohol use disorders – than is seen in other periods of life. This increased risk may be due to genetic predisposition, poor impulse control, or heightened sensitivity of the still-developing brain to drug-related toxicity. This report describes a study in mice of the neurobehavioral impact of chronic, intermittent alcohol-vapor exposure during adolescence, in an effort to model periodic heavy drinking and compare it with similar drinking behavior during adulthood. Researchers conducted two parallel tests in adult male mice following their exposure to alcohol vapors during adolescence (4-6 weeks old) or adulthood (8-10 weeks old).  First, they tested the adult mice for changes in the density and structure of dendritic spines (nerve endings) in the infralimbic cortex (IL), prelimbic cortex (PL) and basolateral amygdala (BLA) regions of the brain. Second, they tested the adult mice for alcohol drinking, sensitivity to alcohol intoxication, blood-alcohol clearance, and measures of response to food reward. Chronic exposure to alcohol vapors during adolescence produced significant, persistent, and strong regional-specific alterations in neuronal dendritic spine density in IL and BLA neurons, accompanied by a limited set of behavioral alterations. Comparable effects were not seen in the mice exposed to alcohol only during adulthood.  Together, these data demonstrate that specific key brain circuits are vulnerable to alcohol’s effects during adolescence, with lasting and potentially detrimental consequences for behavior.   SEE ORIGINAL STUDY

Newswise — A plant found throughout Southeast Asia traditionally used to treat arthritis and rheumatism contains a potent anti-HIV compound more powerful than the drug AZT, according to a new paper published in the Journal of Natural Compounds. The chemical, patentiflorin A, is derived from the willow-leaved Justicia, and was identified in a screening of more than 4,500 plant extracts for their effect against the HIV virus. The discovery is one of the results of a multi-year research partnership made up of scientists from the University of Illinois at Chicago, Hong Kong Baptist University, and the Vietnam Academy of Science and Technology working together as an International Cooperative Biodiversity Group. These groups, funded by the National Institutes of Health, National Science Foundation and the U.S. Department of Agriculture, look for natural products that may have applications in health and medicine, and also work to support sustainable use of these resources in low-income countries. Lijun Rong, professor of microbiology and immunology in the UIC College of Medicine; Harry Fong, associate director of the World Health Organization Program for Traditional Medicine; and Doel Soejarto, professor emeritus of medicinal chemistry and pharmacognosy in the UIC College of Pharmacy, led the UIC team. Rong is an expert at identifying antiviral agents, Soejarto is a renowned plant scientist, and Fong is a well-known pharmacologist. The willow-leaved Justicia extract had been taken from the leaves, stems and roots of plants that had been collected in Cuc Phuong National Park in Hanoi, Vietnam more than 10 years ago by Soejarto. The UIC/Hong Kong/Vietnam ICBG analyzed the extract along with thousands of others as part of their efforts to identify new drugs against HIV, tuberculosis, malaria and cancer. Rong and his colleagues zeroed in on patentiflorin A because of its ability to inhibit an enzyme needed for HIV to incorporate its genetic code into a cell’s DNA. AZT, the first anti-HIV drug developed and marketed in 1987, and which remains the cornerstone of HIV drug cocktails today, inhibits this enzyme, called reverse transcriptase. In studies of human cells infected with the HIV virus, patentiflorin A had a much more significant inhibition effect on the enzyme. “Patentiflorin A was able to inhibit the action of reverse transcriptase much more effectively than AZT, and was able to do this both in the earliest stages of HIV infection when the virus enters macrophage cells, and alter infection when it is present in T cells of the immune system,” said Rong. It also was effective against known drug-resistant strains of the HIV virus, making it a very promising candidate for further development into a new HIV drug. “Patentiflorin A represents a novel anti-HIV agent that can be added to the current anti-HIV drug cocktail regimens to increase suppression of the virus and prevention of AIDS,” Rong said. The researchers were also able to synthesize patentiflorin A. “If we can make the drug in the lab, we don’t need to establish farms to grow and harvest the plant, which requires significant financial investment, not to mention it has an environmental impact,” Rong said. Along with Soejarto and Fong, additional co-authors on the paper include Emily Rumschlag-Booms, UIC College of Medicine; Hong-Jie Zhang, Yi-Fu Guan, Dong-Ying Wang, Kang-Lun Liu, and Wan-Fei Li, Hong Kong Baptist University; and Van Nguyen and Nguyen Cuong, Vietnam Academy of Science and Technology. This project was supported by the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKBU 262912); the Health and Medical Research Fund (12132161) of the Food and Health Bureau, Hong Kong SAR; the Hong Kong Baptist University Interdisciplinary Research Matching Scheme (RC-IRMS/15-16/02), Hong Kong Baptist University (FRG2/11-12/134 and FRG2/14-15/047); NIH Grants 3U01TW001015-10S1 and 2U01TW001015-11A1, administered by the Fogarty International Center, as part of an International Cooperative Biodiversity Groups program; and a grant from the Mr. Kwok Yat Wai and Madam Kwok Chung Bo Fun Graduate School Development Fund.   SEE ORIGINAL STUDY    

Newswise — The world may be closer to knowing why Ebola spreads so easily thanks to a team of researchers from Tulane University and other leading institutions who discovered a new biological activity in a small protein from the deadly virus. The team’s findings were recently published in the Journal of Virology. The discovery comes as health workers try to contain another Ebola outbreak in a remote area of the Democratic Republic of the Congo. Ebola, which is highly fatal, causes severe vomiting, internal bleeding and extreme gastrointestinal distress. A compound known as the “delta peptide” is produced in large amounts in Ebola virus-infected patients, but its function isn’t yet known. The investigators tested the effects of purified delta peptide on cells from humans and other mammals and found that it could be a viroporin, a type of viral protein that damages host cells by making the membranes become permeable. “Our leading hypothesis is that the delta peptide affects the gastrointestinal tract by damaging cells after its release from infected cells,” says William Wimley, George A. Adrouny Professor of Biochemistry and Molecular Biology at Tulane University School of Medicine. “This effect may be a major contributor to the severe GI illness of patients with the Ebola virus.” During the West African Ebola that began in late 2013, the virus spread rapidly principally because of the presence of the virus in GI fluids.  The lack of effective countermeasures led to the death of more than 11,000 people. Tulane researchers say the immediate next step is to begin developing therapies that target the delta peptide. The research involved laboratories from Tulane University School of Medicine, which participated in the fight against Ebola virus on the front lines in Sierra Leone during the outbreak, as well as researchers from Johns Hopkins University and the Louisiana State University Health Sciences Center.   SEE ORIGINAL STUDY

Newswise — Despina Stavrinos, Ph.D., is a distracted driving researcher at the University of Alabama at Birmingham who is available to speak about Apple's announcement today of the new "Do Not Disturb While Driving" mode to be released in the upcoming iOS update. UAB has the capability to accomodate live or taped interviews via Skype or our fully functioning news studio (see more details below). Broll from the Stavrinos driving simulator is also available.  Stavrinos, an assistant professor in the Department of Psychology in the University of Alabama at Birmingham's College of Arts and Sciences and director of the UAB Translational Research for Injury Prevention Laboratory, has published several recent studies on distracted driving: Youth's use of technology drives home need for evolution in distracted walking, bicycling and driving policies Personality may dictate how distracted you are while driving The core of Stavrinos’ work is the prevention of injury, particularly unintentional injuries like those that result from distracted driving behaviors. She conducts the studies in a first-of-its kind driving simulator lab on campus. Link to Stavrinos bio. To secure an interview with Stavrinos, contact Katherine Shonesy, public relations specialist, at (205) 975-3997 or kshonesy@uab.edu.  UAB News Studio is available for live or taped interviews with UAB experts: IFB: 205-975-3190

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Newswise — BOSTON – People who suffer from insomnia are three times more likely to report thoughts of suicide and death during the past 30 days than those without the condition, reports a new meta-analysis from researchers at the Perelman School of Medicine at the University of Pennsylvania. The study is the first to control for depression and anxiety and evaluate in-depth the relationship between the broadly defined terms of insomnia and suicidality to reveal trends that may inform future targeted treatment for 32 million individuals struggling with insomnia in the United States each year. The findings (abstracts #0409 and #422) will be presented at SLEEP 2017, the 31st Annual Meeting of the Associated Professional Sleep Societies LLC (APSS). The researchers evaluated self-report survey data assessing insomnia, depression, and anxiety symptoms among 1,160 U.S. Army servicemembers (84 percent male and average age of 31). Controlling for anxiety and depression, the researchers mapped suicidality into multiple dimensions: thoughts of killing oneself, having a plan to commit suicide, intention to kill oneself, thoughts of death (wishing you were dead), and telling people you want to commit suicide. They separated insomnia sufferers into sub-groups – those who have so-called global insomnia (insomnia as a general term), initial (trouble falling asleep at the beginning of the night), middle (trouble maintaining sleep), and terminal insomnia (waking too early from sleep), and nocturnal awakenings (frequently waking up at night) – and studied the association between each of those subgroups and dimensions of suicidality. The team found that 2.3 percent of those in the population without insomnia reported any indices of suicidality, while 13.1 percent of those experiencing insomnia reported at least one type of suicidality. The group also found a significant association between insomnia and suicide (which echoes earlier studies), but the new research parsed out the broad concepts of insomnia and suicide to explain what aspects of these two are related in a population of military personnel. Even after eliminating the established role of depression and anxiety in suicide, people who suffer from insomnia are three times more likely to report thoughts of suicide and death during the past 30 days. Insomnia was also found to be a significant predictor for suicidality. Although waking up multiple times throughout the night was significantly associated with greater suicidal ideation, the team was surprised that having difficulty maintaining sleep in the middle of the night was actually associated with a lower likelihood of having thoughts of suicide or having a suicidal plan. This does not mean that those at risk for suicide should try keeping themselves up during the middle of the night, however. The association between awakenings and suicidality follows senior author Michael Perlis’ “sleep of reason” hypothesis, such that, risk for suicidality is highest as someone is awake with insomnia at night when their ability to reason, think rationally, and engage in impulse control are lowest. The team’s findings suggest that the increased awakenings at night and the decreased executive function associated with it foster dimensions of suicidality in those who are pre-disposed to thinking about committing suicide. “It’s a bad thing to be awake when reason sleeps,” said Michael Perlis, PhD, an associate professor of Psychiatry and director of the Behavioral Sleep Medicine program, and senior author on the research. “Being awake at night, coupled with the decreased frontal lobe function that happens with sleep loss may explain the mechanism for how insomnia relates with suicide risk.” Frequently waking up throughout the night was the only type of insomnia associated with four of the five dimensions of suicidality. One possible explanation for this finding may be that it is related to other comorbid conditions, such as obstructive sleep apnea and chronic pain. “Middle insomnia might give them an external factor to attribute to their distress,” said Ivan Vargas, PhD, a postdoctoral fellow and first author of abstract (#0409). “Most of the participants in this study were not presently depressed - so they’re less likely to internalize stress and subsequently experience suicidal ideation. Following a night of insomnia, they may be more likely to attribute any daytime impairment to their poor sleep and not to themselves. In this case, insomnia would buffer their negative attributions about themselves and lower their risk for suicidality. This really speaks to the dynamic relationship between insomnia and depression in predicting suicidality. ” The authors note that further research may benefit from studying this in additional populations, or in a majority female population. Previous research from the Perlis team has shown that suicides are more likely to occur after midnight than during the daytime or evening and another study showing that more sleep reduces suicide risk in those with insomnia.     In addition to Vargas and Perlis, additional authors on (#0409) include Amy Gencarelli, from Penn, Alexandria Muench from the Philadelphia College of Osteopathic Medicine, Elaine Boland from the Cpl. Michael J. Crescenz VA Medical Center, Jennifer R. Goldschmied from Penn, and Philip Gehrman, from Penn and the Cpl. Michael J. Crescenz VA Medical Center, and additional authors on (#0422) include Amy Gencarelli, from Penn, Waliuddin Khader, from Penn, Alexandria DiGuiseppe from the Philadelphia College of Osteopathic Medicine, Jennifer Goldschmied from Penn, Elaine Boland from the Cpl. Michael J. Crescenz VA Medical Center, and Philip Gehrman from Penn and the Cpl. Michael J. Crescenz VA Medical Center. ###

Newswise — Guidelines by the National Comprehensive Cancer Network (NCCN) recommend testing for seven known genetic changes in patients with Acute Myeloid Leukemia (AML). A study presented today at the American Society for Clinical Oncology (ASCO) Annual Meeting 2017 shows that only 67 percent of 259 evaluated patients received any genetic testing. Of the 173 patients that received any genetic testing, only 9 percent received all seven of the NCCN-recommended genetic tests. “We now know a tremendous amount about the genetic underpinnings of the disease. We can test for these genetic changes in the clinic to see what’s making a patient’s disease tick. And often there are targeted therapies that can be matched with these genetic changes. But there’s a disconnect between what can be done, what should be done, and what is being done,” says Daniel A. Pollyea, MD, MS, investigator at the University of Colorado Cancer Center, clinical director of Leukemia Services at the CU School of Medicine, and the study’s lead author. For example, FLT3 is a commonly mutated gene with several drugs in clinical development to specifically target this mutation. But this drug can only be used once genetic testing pinpoints the patients likely to benefit, namely those with FLT3 activation. Additional targeted treatments for AML are in development, such as Pollyea’s own work with the drugs AG-120 and AG-221, which target the 15-20 percent of AML harboring mutations in the genes IDH1 and IDH2. Previously, the majority of data describing rates of genetic testing in AML patients have come from clinical trials, where adherence to guidelines is, as expected, very high. The current study hoped to evaluate adherence to genetic testing guidelines in AML treated outside clinical trials, in academic medical centers and in community settings. The data comes from the new, unique resource of the CONNECT MDS/AML Disease Registry, which collects treatment and outcome statistics from 86 sites distributed across the United States. Current results reflect data gathered from 2013 to 2016. Overall, rates of patients receiving any genetic testing were higher in patients treated at academic medical centers than those treated at community clinics (76 percent versus 62 percent); higher in patients younger than 65 years old than in older patients (83 percent versus 60 percent); and higher in patients with non-Medicare insurance than in patients with Medicare (74 percent versus 61 percent). “Basically, we’re not seeing adherence to these guidelines. It’s still a big challenge for a lot of institutions,” Pollyea says. He points out that often a major barrier to genetic testing in AML (and many other cancers) is the willingness of insurance companies to pay for testing. He also suggests that with adherence to these guidelines so low, perhaps the guidelines themselves need adjustment, though, “I think the guidelines are pretty solid and, in my opinion, I would say they don’t go far enough in recommending genetic testing,” he says. The major accomplishment of the current study may be setting a baseline against which future data can be measured. “We’re in our infancy with this testing, and even earlier than infancy in seeing how we’re doing on testing. But now with this registry we at least have the infrastructure available to ask these kinds of questions,” Pollyea says. As known genetic drivers of AML are successfully paired with targeted treatments and more of both are discovered, genetic testing is likely to become an even more essential component of clinical care. Now with an understanding of the current state of genetic testing in AML, Pollyea and colleagues will be able to evaluate changes in these data as diagnostic, prognostic and treatment options evolve.

Newswise — When teens have troubling thoughts or are prompted by a peer’s concerning behavior or news story to educate themselves on mental health, they often turn to internet search engine links – many hosted by unreliable sources. To help combat misinformation, the Traumatic Loss Coalitions for Youth (TLC), New Jersey’s primary youth suicide prevention program at Rutgers’ University Behavioral Health Care, has launched TLC4Teens (tlc4teens.org), a resource website for children, which includes organizations, hotlines and relevant articles that have been vetted by TLC. Many also are listed on the Substance Abuse and Mental Health Services Administration’s National Registry of Evidence-based Programs and Practices. Funded by the New Jersey Department of Children and Families, TLC4Teens links to state and national resources for issues such as grief, suicide prevention, mental health, depression, substance abuse, dating, bullying, anxiety, self-care, underage drinking, sexuality and gender identity. A parent section includes resources on how to understand and handle a child’s grief or emotional or behavioral crises. “The site was designed to give children easy access to the information they seek online with minimal clicks,” says Maureen Brogan, TLC statewide coordinator. “It also features a video by Olympic Gold medalist Laurie Hernandez, who reminds her fellow teens that seeking help is not a weakness and that they should use the site as a ‘resource to connect to in difficult times.’” Brogan encourages children as young as elementary school who are using mobile devices to bookmark the site. “Children are being exposed to vicarious traumas on the internet through their smartphones or iPads. They can’t escape this and it shatters their assumptions that the world is a safe place to be – which causes stress,” she explains. In her outreach with TLC, Brogan is seeing stressors, such as concerns over grades, that usually don’t manifest until high school occur at younger ages. While these children might not have anxiety and depression at a clinical level, the stress can become disruptive to their everyday lives, she says. “Through education, we can empower students to watch for concerning signs among their peers or siblings and know what to do if a situation arises,” Brogan says. “We want to encourage resiliency so they can get the help they need and say ‘OK, I’ve got this.’”