Publisher Health

New research from the Healthy Nevada Project® found associations between genetics, obesity, and childhood trauma, linking social health determinants, genetics, and disease. The study, which was published this week in Frontiers in Genetics, found that participants with specific genetic traits and who experience childhood traumas are more likely to suffer from adult obesity.
In 2016, DRI and Renown Health launched the Healthy Nevada Project®, the nation’s first community-based, population health study, which now has more than 60,000 participants. The project is a collaboration with personal genomics company, Helix, and combines genetic, environmental, social, and clinical data to address individual and community health needs with the goal of improving health across the state and the nation.
The new study focuses on Adverse Childhood Experiences (ACEs), which are traumatic and unsafe events that children endure by the age of 18. Over 16,000 participants in the Healthy Nevada Project® answered a mental health survey, and more than 65 percent of these individuals self-reported at least one ACE occurrence. These 16,000 participants were cross-referenced with their genetic makeup, and clinical Body Mass Index (BMI) measures.
According to the research team’s findings, study participants who had experienced one or more types of ACE were 1.5 times more likely to become obese adults. Participants who experienced four or more ACEs were more than twice as likely to become severely obese.
“Understanding that Adverse Childhood Experiences, like abuse, poverty, food insecurity, and poor relationships with primary caregivers increase a person’s risk for obesity but also interact with your genetics — are key to understanding how we might provide earlier interventions, help reduce health disparities, and create a Healthier Nevada for all,” said Tony Slonim, MD, DrPH, President & CEO of Renown Health. Slonim, CEO of Reno, NV-based Renown Health, is the first quadruple-board-certified doctor in the United States with certifications in adult critical care, internal medicine, pediatric critical care, and pediatrics and holds a Doctorate in Public Health.
“Our analysis showed a steady increase in BMI for each ACE a person experienced, which indicates a very strong and significant association between the number of adverse childhood experiences and adult obesity,” said lead author Karen Schlauch, Ph.D., of DRI. “More importantly, participants’ BMI reacted even more strongly to the occurrence of ACEs when paired with certain mutations in several genes, one of which is strongly associated with schizophrenia.”
“We know that genetics affect disease in the Healthy Nevada Project® [https://pubmed.ncbi.nlm.nih.gov/31888951/], and now we are recognizing that ACEs also affect disease,” said Healthy Nevada Project® Principal Investigator Joseph Grzymski, Ph.D., of DRI and Renown Health. “Our new study shows that the combination of genes and environmental factors like ACEs, as well as many social determinants of health, can lead to more serious health outcomes than either variable alone. More broadly, this new work emphasizes how important it is for population genetic studies to consider the impact of social determinants on health outcomes.”

Researchers have developed a huggable, cushion-like device that mechanically simulates breathing, and preliminary evidence suggests it could help reduce students’ pre-test anxiety. Alice Haynes of the University of Bristol, U.K., and colleagues present the device and findings in the open-access journal PLOS ONE on March 9, 2022.
Treatments for anxiety disorders primarily include therapy and medications. However, these can be costly, and medications may have unwanted side effects. At-home anxiety aids could complement treatments for anxiety disorders and also benefit people experiencing temporary anxiety. Within this category, a small but growing body of research highlights the anxiety-reducing potential of touch-based devices, such as TouchPoints wearables and Paro the seal, an interactive therapeutic robot.
Now, Haynes and colleagues have developed a new, touch-based device that could ease anxiety. They initially built several prototype devices that simulated different sensations, such as breathing, purring, and a heartbeat. Each prototype took the form of a soft, huggable cushion that was meant to be intuitive and inviting. Focus group testing identified the “breathing” cushion as being the most pleasant and calming, so the researchers further developed it into a larger, mechanical cushion.
To test the new device, the research team recruited 129 volunteers for an experiment involving a group mathematics test. Using pre- and post-test questionnaires, the researchers found that students who used the device were less anxious pre-test than those who did not. The experiment also compared the breathing cushion to a guided meditation, and found that both were equally effective at easing anxiety.
These findings suggest that the breathing cushion could be used to reduce anxiety, for example for students who are anticipating exams. The researchers now hope to further refine the cushion for testing in people’s homes. They also plan to investigate people’s physiological response to the device — for instance, changes in heart rate or breathing patterns — in order to elucidate the particular mechanisms by which the device might ease anxiety.
The authors add: “We were excited to find that holding the breathing cushion, without any guidance, produced a similar effect on anxiety in students as a meditation practice. This ability of the device to be used intuitively opens it up to providing wider audiences with accessible anxiety relief.”
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Treatments integrating music and auditory beat stimulation are effective in reducing state anxiety in some patients, according to a new study published this week in the open-access journal PLOS ONE by Adiel Mallik and Frank Russo of the Ryerson University, Canada.
Anxiety has been steadily increasing, particularly in the adolescent and young adult populations, over recent decades. Studies have previously shown that listening to music can reduce anxiety, perhaps even more effectively than some anti-anxiety medications. However, quantitative data on the effects of personalized music on anxiety has been lacking.
In the new study, the researchers randomized 163 patients taking anti-anxiety medications to participate in an at-home treatment session involving music, auditory beat stimulation, both, or pink noise — background sounds similar to white noise. The music was selected for each patient using LUCID’s artificial intelligence which curates music based on the patient’s emotional state and music preferences. Auditory beat stimulation involves combinations of tones, played in one or both ears, designed to trigger changes to brain activity. In all groups, patients were asked to download a customized application on their smart phone for the treatment, close their eyes, and listen to a 24-minute session.
Among people with moderate anxiety before the treatment session, greater reductions in somatic anxiety — the physical symptoms of anxiety — were seen in people who listened to both music and ABS (p=0.04, effect size=0.83), or those who listened to music alone (p=0.05, effect size=0.52), compared to those who listened to pink noise. The greatest reductions in cognitive state anxiety — the aspect of anxiety related to thoughts and feelings — were also seen in moderate trait anxiety participants who listened to both music and ABS. Among people with high trait anxiety before the session, the music-alone group had significantly higher reductions in anxiety compared to the ABS-alone group (p=0.04, effect size=0.72).
The authors conclude that sound-based treatments can be effective in reducing state anxiety and potentially offer a simple and easily distributable method of treating anxiety in a segment of the population.
Drs. Russo and Malik add: “With the pandemic and remote work, there has been a remarkable uptick in the use of digital health tools to support mental health. The results of this clinical trial indicate great promise for the use of digital health tools, such as LUCID’s digital music therapy, in the management of anxiety and other mental health conditions.”
“The findings from this research are exciting as they indicate that personalized music shows great promise in effectively reducing anxiety in specific segments of the population that suffer from anxiety. Hopefully, with additional research, we can help build a solid evidence base which further supports the use of personalized music as an additional tool in the clinician’s toolbox that can be used to help reduce anxiety in the patient population.”
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Low-consumption office buildings with infrequent water use could have chemical and microbiological safety issues, according to a study published in PLOS Water by Andrew Whelton at Purdue University, Indiana, United States, and colleagues. The research could have implications for office buildings used less frequently during pandemic lockdowns, and suggests that regular water testing in commercial buildings may be needed.
Many office buildings have decreased occupancy during weekends and holidays — and recently, during pandemic lockdowns — increasing water stagnation in plumbing. Green buildings are designed to reduce water consumption using efficient fixtures and alternative water supplies. However, due to the combination of lower building water use and low occupancy periods, the safety of water from green buildings is unknown. To better understand chemical and microbiological quality in a green commercial office building plumbing after weekend stagnation, researchers sampled water from a ten-year-old, three story, LEED-certified office building in Indiana between January and February 2020. Samples from all water sources in the building were tested for pH, metals, ions, as well as bacterial strains of Legionella.
Researchers found that copper and lead levels increased over the weekend, and that Legionella counts were highest at a fixture which had no use recorded during sampling. Additionally, the concentration of the disinfectant chlorine decreased over the weekend. The study had several limitations as it relied on self-reported data for measurements of fixture use and may have misreported usage frequency at some locations. Future studies are needed to further analyze how water-saving appliances may impact water quality.
According to the authors, “To prepare plumbing to code, water chemical and microbiological testing is not required or recommended. The green office building studied had many features that are increasingly common in new buildings, including low-flow faucets, automatic faucets, and alternative piping systems for major water uses like toilet flushing and irrigation. These design elements can change water temperature profiles and significantly reduce the amount of water used compared to traditional office buildings, raising concerns for water quality degradation.”
The authors add: “The first people in the office on a Monday morning may, in fact, be using contaminated drinking water. To better understand if the water we are using is safe, much more water testing at the faucet must be conducted. Plumbing design standards and codes must also be revised.”
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A new study of brain development in mice shortly after birth may provide insights into how early life events can affect wiring patterns in the brain that manifest as disease later in life — specifically such disorders as schizophrenia, epilepsy and autism.
Researchers focused on two types of brain cells that have been linked to adult neurological disorders: neurons in a modulating system nestled deep in the brain and other neurons in the cortex, the brain’s outermost layer, that counteract excitation in other cells using inhibitory effects. The modulating cells send long-range cables to the cortex to remotely influence cortical cell activity.
The study is the first to show that these two types of cells communicate very early in brain development. A chemical released from the modulating cells initiates the branching, or arborization, of axons, the long, slender extensions of nerve cell bodies that transmit messages, on the cortical cells — and that arborization dictates how effective the cells in the cortex are at doing their job.
Though there is still a lot to learn about the impact of this cellular interaction in the postnatal brain, the researchers said the study opens the door to a better understanding of how neurological diseases in adults may relate to early-life events.
“It’s known that abnormal early-life experiences can impact kids’ future sensation and behavior. This finding may help explain that kind of mechanism,” said Hiroki Taniguchi, associate professor of pathology in The Ohio State University College of Medicine and senior author of the study.
“This study provides new insight into brain development and brain pathology. It’s possible that during development, depending on animals’ experiences, this modulating system activity can be changed and, accordingly, the cortical circuit wiring can be changed.”
Taniguchi completed the work with co-authors André Steinecke and McLean Bolton while he was an investigator at the Max Planck Florida Institute for Neuroscience.

Irish and German scientists have just identified how specific immune cells can work together in fat to cause inflammation that leads to weight gain and obesity. Their work pinpoints new avenues to exploit the regulation of that inflammation in fat tissue, thereby suggesting new ways to manage obesity [Wednesday 9th March 2022].
There is a global epidemic in obesity in adults and children, with obese people predisposed to develop diabetes, cardiovascular disease, and cancer. New therapies are needed to help tackle this issue.
In their research, the scientists identified how “checkpoint proteins” and immune cells alter inflammatory cells within the fat tissue to cause obesity. In people with obesity (Body Mass Index BMI > 30 kg/m²) these changes in checkpoint expression in the visceral fat was predictive of the person’s weight.
The scientists then showed that modifications in the so-called immune checkpoint proteins of mice on a Western “high fat” diet were linked to dramatic reductions in the development of obesity and diabetes.
The study, just published in the leading international biomedical journal Science Translational Medicine, was led by Professor Padraic Fallon from Trinity College Dublin’s School of Medicine, and Dr Christian Schwartz, a former EMBO Fellow in Trinity and now a Principal Investigator at the University Hospital Erlangen.
Prof. Fallon commented: “This new process of checkpoint regulation of cells in visceral fat of obese individuals advances our understanding of how the immune system controls diet-induced weight gain that can lead to conditions such as obesity and type 2 diabetes.
“Our discovery has broader impacts on addressing how obesity influences co-morbidity with other diseases, as shown in the COVID-19 pandemic, where obese individuals that are infected with SARS-CoV-2 are more likely to develop severe disease that requires intensive care and also have an increased risk of mortality.”
Dr Schwartz commented: “In our study, we analysed the function of immune checkpoints on specific cells and it is fascinating to see that a small change on one of many cell populations in the fat has such an impact on the outcome of the disease. Only through our basic research efforts using pre-clinical models, were we able to gain access to patients’ samples and link our findings to human disease. It will be interesting to investigate now how we can manipulate this checkpoint on specific cell populations of interest to help people with obesity.”
The study investigated inflammatory changes in patients with obesity, with or without type 2 diabetes, in collaboration with Dr Andy Hogan (Maynooth University), Profs. Donal O’Shea and Helen Heneghan (St Vincent’s Hospital and University College Dublin) and Dr Christian Krautz (University Hospital Erlangen).
The work was funded by Science Foundation Ireland, the National Children’s Research Centre, Interdisciplinary Center for Clinical Research, University Hospital of the University of Erlangen?Nuremberg and the Else Kröner?Fresenius?Stiftung. Dr Schwartz was an EMBO Long-Term visiting Fellow. Dr Heike Hawerkamp is an Irish Research Council Fellow.
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High levels of anti-Mullerian hormone (AMH) have traditionally been thought of as merely a passive byproduct of polycystic ovary syndrome (PCOS), but a new preclinical study by Weill Cornell Medicine researchers suggests that the hormone plays an active role in the disorder and may contribute to problems with ovulation and fertility.
In the study, published March 9 in Science Advances, the investigators discovered that AMH may cause follicles, the multicellular, fluid-filled sacs that contain developing eggs in the ovary, to mature too quickly.
“AMH is routinely measured in the clinic to give an indication of how many follicles a woman has growing in her ovaries, and this value is often high in women with PCOS. But no one has ever determined whether a high level of AMH, by itself, can have a negative influence,” said senior author Dr. Daylon James, assistant professor of stem cell biology in obstetrics and gynecology and in reproductive medicine at Weill Cornell Medicine. “A better understanding of the root causes of PCOS is critical to mitigating the condition’s many health consequences.”
Developing eggs, called oocytes, are produced in the ovaries within follicles, which support their growth. As the follicle grows, the egg that resides within it gradually matures, and in a normal reproductive cycle, that follicle ultimately undergoes ovulation to release an egg capable of being fertilized. However, in patients with PCOS, a hormonal disorder that impacts up to 10 percent of women, the ovaries contain numerous smaller follicles that produce AMH, but fail to progress to later stages and ovulate.
While fertility treatments can help with conception, women with PCOS contend with a variety of other symptoms, said Dr. James. For example, PCOS is often accompanied by hyperandrogenism, or high levels of hormones such as testosterone that are collectively called androgens. An overabundance of these hormones can cause an array of secondary complications, including unwanted growth of body and facial hair. Women with PCOS can also be prone to diabetes and metabolic disease and are more susceptible to endometrial cancer.
Dr. James and his research team hypothesized that AMH is directly contributing to at least some of the constellation of symptoms associated with the disorder. To isolate the effects of AMH, the researchers utilized a xenograft system in which ovarian tissue from human organ donors is engrafted onto the flank of immunocompromised mice. One group of mice was transplanted along with cells that continuously supplied AMH directly to the grafted tissue, and the other group of mice was transplanted with control cells without AMH.

Scientists may better understand and test for the genetic variations that cause cancer and other heritable diseases through the application of a novel strategy for securely sharing and analyzing genomic data developed at the UC Santa Cruz Genomics Institute.
Understanding the clinical significance of rare genetic variants requires analyzing large amounts of genomic and clinical data. Privacy policies, however, restrict the sharing of this information between institutions, and no single institution is likely to have all the resources needed for a robust analysis.
In a paper published March 9 in the journal Cell Genomics, UCSC researchers showed that an approach called federated analysis can overcome this problem by “bringing the code to the data.” This is the first application of federated analysis to enable classification of previously unclassified genetic variants.
“We have to find ways to get to the data that respect privacy, but still let researchers do their research, so the federated model is definitely the way of the future,” said James Casaletto, a PhD candidate at UCSC’s Baskin School of Engineering and the paper’s lead author.
The study focused on genetic variants of the breast cancer genes BRCA1 and BRCA2. People who inherit harmful variants of one of these genes have increased risks of breast, ovarian and other cancers. Many people, however, have variants of unknown significance (VUS) in these genes, meaning scientists don’t know if these variants are harmful or not.
The new study provides a more nuanced understanding of BRCA1 and BRCA2 variants. It also serves as a “proof of concept” of a novel data sharing and analysis technique for assessing the clinical implications of genetic variants.

Every year, thousands of biochemistry majors and medical students around the world learn to memorize the major biochemical pathways that allow cells to function. How these 10 or so pathways are described in textbooks hasn’t changed much since the early 20th century, when they were first discovered.
But with the resurgence of interest in cancer metabolism in the past decade, researchers are coming to realize that there is more to a cell’s biochemistry than once thought.
The latest plot twist comes from a team of scientists at the Sloan Kettering Institute who report that they have discovered a previously unappreciated metabolic pathway — an alternate version of the famous Krebs cycle, also known as the tricarboxylic acid (TCA) cycle.
The TCA or Krebs cycle — named after Hans Krebs, the German-born biochemist who discovered it in 1937 — is a central hub of cellular metabolism. It is a core part of the process by which cells “burn” sugars to make ATP, the cell’s energy-carrying molecule. In its standard form, the cycle occurs entirely in a cell’s mitochondria.
“We and other scientists have recognized for a while that there is variation in the degree to which cells use parts of the TCA cycle, suggesting that cells may have multiple ways to meet their fundamental metabolic needs,” says Lydia Finley, a cell biologist in SKI who led the team. “Now, with this latest research, we can say there is a complete alternative to the canonical TCA cycle, and we explain how it works.”
Implications for Understanding Cancer Cell Metabolism
Through several converging lines of evidence, Dr. Finley’s team showed that an alternate version of the TCA cycle takes place partly in the mitochondria and partly in the cytosol. Rather than burning sugar for energy, this alternate version of the TCA cycle allows cells to use the carbons in sugar to build important molecules such as lipids for cell membranes.

As assistant professor of orthopedics at the University of Colorado School of Medicine, David Howell, PhD, understands the relationship between concussions and subsequent injury in athletes — namely, that after suffering a concussion, athletes at all levels are more likely to sustain another injury within the next year.
“Any athlete may experience an injury such as an ankle sprain or an ACL rupture — that’s just a part of sports,” says Howell, lead researcher for sports medicine at Children’s Hospital Colorado. “However, people with recent concussions tend to be particularly vulnerable to these. Even after symptoms have subsided and an athlete is cleared to go back to sports, we still see neuromuscular motor control deficits, particularly when they are paired with a cognitive task. Those lingering deficits might predispose them to further injury.”
Enter the intervention
Looking for techniques to keep young athletes safer post-concussion, Howell and the investigative team devised a study in which teenage athletes who suffered concussions were randomized either to standard of care — typically returning to play after clearing a set of standardized protocols that assess symptoms, cognition, and balance — or completing the same protocol and then working with an athletic trainer on a specific neuromuscular training intervention that includes guided strength exercises and a focus on posture and landing stability.
“It’s similar to injury risk reduction programs that are used more in population-level studies,” Howell says. “You take an entire high school soccer team and run them through these neuromuscular training programs over a season, then compare them to a team that didn’t do the program. Those studies showed that if you have a team go through this, it can reduce the risk of ACL tears, for example, pretty significantly.”
Howell enrolled 27 post-concussion youth athletes in the study, most of whom were patients in the Sports Medicine Center at Children’s Hospital Colorado. The athletes who were randomized to the intervention worked with an athletic trainer two times a week for eight weeks; researchers followed them for a full year following their concussion.
“We asked them every month over the following year, ‘Did you play sports? How many games did you have? How many practices do you have? How many hours did you participate’ — plus, ‘Did you get injured or not?'” Howell says. “What we found is that the people who went through the intervention had about a three-and-a-half times reduced injury risk compared to the ones that did not go through the intervention over that next year.”
Changing the rules on return-to-play
Howell hopes the results from his study will eventually change the way athletes are returned to play, shifting focus from computerized tests and self-reported symptoms to a standardized intervention that can help stave off additional injuries.
He and his research team are even working on an app that will support athletes through a self-guided training program in situations where they don’t have access to a trained clinician, such as an athletic trainer or physical therapist.
“When you think about sports, it’s not just looking at a computer screen, doing a reaction time test or a single balance test,” he says. “It’s an integration of many different systems. You think about a soccer pass, for example — you’re standing here, there’s a teammate across the way to try to pass it to. But what’s your angle of your foot doing? Where are the opponents? All those things require a lot of cognitive and fine motor skills that happened in rapid succession.
“If this can help with at least some of those elements that can contribute to safety, we think that can have an effect,” he says. “The results of this preliminary study were really encouraging, and I’m excited about where we’re going from here.”
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Materials provided by University of Colorado Anschutz Medical Campus. Original written by Greg Glasgow. Note: Content may be edited for style and length.