1. Ortho Molecular Products announces support for naturopathic residency consortium
BARRINGTON, IL (April 8, 2022) — Ortho Molecular Products is proud to announce a partnership with Institute for Natural Medicine (INM) and its Residency Consortium, a premier, sustainable residency model for top naturopathic doctor (ND) graduates. The goal is to create a residency cohort model that will close the gap between medical doctor (MD) and ND post-graduate training.
The need for ND residencies is significant: Five out of every six graduates are seeking a residency, yet current residency programs lag in programmatic standardization across sites and lack systems to ensure a high level of focus and participation from residents. In addition, current residency programs do not provide business training.
“To level the playing field of post-graduate residency education, INM has designed a unique three-part-funding model to help expand primary care residency access. We partner with an academic institution, select vetted multi-practitioner naturopathic primary care clinics, and stakeholder corporations in the sector to help fund two-year primary care residencies,” explained INM president and CEO Michelle Simon, PhD, ND. “Ortho Molecular Products was one of the first companies I reached out to, recognizing a natural alignment with their mission to transform the practice of medicine. Their dedication to providing efficacious products for the supplement market and tools for providers and practices make them an ideal partner for our program.”
In addition to providing nutritional solutions and clinical resources, Ortho Molecular Products is an active supporter of community clinics operated by naturopathic medical schools, such as Southwest College of Naturopathic Medicine. The opportunity to support NDs on their post-graduate journeys to clinical practice was a natural fit for the organization.
“Naturopathic doctors are some of the highest-trained practitioners in functional integrative medicine, yet they are faced with considerable headwinds post-graduation and need more support within the medical community,” said Aaron Bartz, president of Ortho Molecular Products. “Our goal as an organization is to support NDs at every stage of their careers. We look forward to partnering with INM to prepare the next generation of naturopathic doctors to be successful in clinical practice.”
About Ortho Molecular Products
For more than three decades, Ortho Molecular Products has researched and manufactured high-quality, efficacious nutraceuticals sold exclusively to thousands of health care professionals nationwide and in Canada. Ortho Molecular Products is headquartered in the Chicagoland area, with an FDA-audited, cGMP-certified manufacturing facility in Stevens Point, WI. The commitment to efficacy, uncompromising manufacturing and legendary customer service establishes Ortho Molecular Products as a leader in the nutrition industry. To learn more, visit orthomolecularproducts.com.
About Institute for Natural Medicine
The Institute for Natural Medicine is a non-profit 501(c)(3) organization, in collaboration with the American Association of Naturopathic Physicians. The mission of the organization is to transform health care in America by increasing both public awareness of naturopathic medicine and access to naturopathic doctors for patients. To learn more, visit, naturemed.org.
2. High Blood Pressure May be Related to a Bias Toward Perceiving Anger in Others
From University of Konstanz
Men with high blood pressure have a biased recognition of other people’s anger, as shown in a new study.
Hypertension is a disease. However, in the majority of cases, there is no clear medical explanation, referred to as “essential hypertension.” Could psychological factors play a role? In this context, Konstanz biological health psychologists Alisa Auer and Professor Petra Wirtz conducted a study in male participants over several years together with colleagues from Konstanz (Germany) and Switzerland. The researchers wanted to better understand the psychobiosocial mechanisms in hypertension, since previous work in this area has left many questions open.
In an article published in the Annals of Behavioral Medicine on 22nd March 2022, they show that compared to a healthy control group, men with essential hypertension more often recognized angry expressions when they looked into the faces of others. In addition, this anger recognition bias seems to contribute to blood pressure increases over time if someone tends to frequently and intensively experience anger. This tendency is called “trait anger.”
Recognition of mixed emotions
In their study in 145 hypertensive and normotensive men, researchers presented different pictures of people who were angry. However, the pictures did not just display anger alone, but combined anger with one of three other emotions: fear, happiness, and sadness. The background for this approach is that, in everyday life, people’s faces rarely show just one emotion. Mixed emotions are more prevalent. Each of the computer-morphed pictures showed two emotions with varying affect intensities. Participants were asked which emotion they saw in the pictures.
“Hypertensive men recognized anger more often than any other emotion,” Alisa Auer says. “So, they overrated anger displayed in other people’s faces as compared to our healthy control group.” Petra Wirtz adds: “Overrating anger displayed by other persons seems to affect whether high ‘trait anger’ contributes to blood pressure increases over time.” Hence, interpersonal factors seem to play a role in essential hypertension. The expectation of associations between hypertension and social aspects was one of the reasons why the study was supported by the Cluster of Excellence “Centre for the Advanced Study of Collective Behaviour.”
Improving treatment of essential hypertension
Auer and Wirtz hope that their results will be examined and confirmed by other researchers. “Then, a next step would be to offer people with essential hypertension a more targeted support,” says Alisa Auer, who is currently completing her doctorate in Psychology. Auer is thinking of “therapeutic treatments that address a person’s perception of social environments in order to protect them from other people´s anger.”
Such therapeutic interventions would be important, because blood pressure lowering medication only treats the consequences of hypertension, but does not address potential causes. In addition, hypertension is one of the major risk factors for cardiovascular disease. In 2020, as in previous years, the Federal Statistical Office (Destatis) listed cardiovascular disease as the leading cause of death in Germany. “338,001 deaths, or more than one third of all deaths (34%), can be attributed to cardiovascular disease,” Destatis reports. Cardiovascular disease is especially deadly for older people: 93% of those who died of cardiovascular disease were 65 years or older.
What about women? The researchers hope that future studies will include women. Since women may possibly differ in their emotion recognition from men and as fewer women suffer from hypertension, the study initially focused on men.
1. Alisa Auer, Roland von Känel, Ilona Lang, Livia Thomas, Claudia Zuccarella-Hackl, Cathy Degroote, Angelina Gideon, Roland Wiest, Petra H Wirtz. Do Hypertensive Men Spy With an Angry Little Eye? Anger Recognition in Men With Essential Hypertension – Cross-sectional and Prospective Findings. Annals of Behavioral Medicine, 2022; DOI: 10.1093/abm/kaab108
3. Cannabis Poses Threat to Babies Exposed During Pregnancy – Obesity and High Blood Sugar
From The Endocrine Society
Cannabis use among pregnant women is on the rise and may be associated with negative health outcomes in children, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology and Metabolism.
A 2016 study in Colorado revealed that up to 22% of pregnant women had detectable levels of cannabinoids in their body. Women who use cannabis, both tetrahydrocannabinol (THC) and cannabidiol (CBD), during pregnancy could be putting their child at risk for low birth weight and behavioral problems. Exposure to cannabinoids may also increase the child’s future risk of obesity and high blood sugar.
Part of CBD’s popularity is that it is marketing as being “nonpsychoactive,” and that consumers can reap health benefits from the plant without the high. CBD is advertised as providing relief for anxiety, depression and post-traumatic stress disorder. It is also marketed to promote sleep.
“We found that cannabis use during pregnancy was linked to increased fat mass percentage and fasting glucose levels in 5-year-old children,” said Brianna Moore, Ph.D., of the Colorado School of Public Health in Aurora, Colo. “We would encourage women to refrain from using any cannabis while pregnant or breastfeeding to minimize adverse health effects in the offspring.”
The researchers studied urine samples from 103 pregnant women, 15% of whom had detectable levels of cannabinoids (such as THC and CBD) in their urine. These mothers’ 5-year-old children had higher fat mass and fasting glucose levels compared to children who were not exposed to cannabis during pregnancy.
“More studies are needed to understand how exposure to different cannabinoids during pregnancy may impact the offspring,” Moore said.
Other authors of this study include: Katherine Sauder and Dana Dabelea of the Colorado School of Public Health and the University of Colorado School of Medicine in Aurora, Colo.; Allison Shapiro of the University of Colorado Anschutz Medical Campus in Aurora Colo.; and Tessa Crume and Gregory Kinney of the Colorado School of Public Health in Aurora Colo.
The study received funding from the National Institutes of Health.
1. Brianna F Moore, Katherine A Sauder, Allison L B Shapiro, Tessa Crume, Gregory L Kinney, Dana Dabelea. Fetal Exposure to Cannabis and Childhood Metabolic Outcomes: The Healthy Start Study. The Journal of Clinical Endocrinology & Metabolism, 2022 DOI: 10.1210/clinem/dgac101
4. “Organ Chip” Shows Effect of Breathing Motion on Immune Function
From Wyss Institute for Biologically Inspired Engineering at Harvard
The average person will take more than 600 million breaths over the course of their life. Every breath stretches the lungs’ tissues with each inhale and relaxes them with each exhale. The mere motions of breathing are known to influence vital functions of the lungs, including their development in babies, the production of air-exchange-enhancing fluid on their inner surfaces, and maintenance of healthy tissue structure. Now, new research from the Wyss Institute at Harvard University has revealed that this constant pattern of stretching and relaxing does even more — it generates immune responses against invading viruses.
Using a Human Lung Chip that replicates the structures and functions of the lung air sac, or “alveolus,” the research team discovered that applying mechanical forces that mimic breathing motions suppresses influenza virus replication by activating protective innate immune responses. They also identified several drugs that reduced the production of inflammatory cytokines in infected Alveolus Chips, which could be useful in treating excessive inflammation in the lung. Based on these studies, one of those drugs was licensed to Cantex Pharmaceuticals for the treatment of COVID-19 and other inflammatory lung diseases. Data from the research were recently included in the company’s Investigational New Drug (IND) application to the FDA to initiate a Phase 2 clinical trial for COVID-19.
“This research demonstrates the importance of breathing motions for human lung function, including immune responses to infection, and shows that our Human Alveolus Chip can be used to model these responses in the deep portions of the lung, where infections are often more severe and lead to hospitalization and death,” said co-first author Haiqing Bai, Ph.D., a Wyss Technology Development Fellow at the Institute. “This model can also be used for preclinical drug testing to ensure that candidate drugs actually reduce infection and inflammation in functional human lung tissue.” The results are published today in Nature Communications.
Creating a flu-on-a-chip
As the early phases of the COVID-19 pandemic made painfully clear, the lung is a vulnerable organ where inflammation in response to infection can generate a “cytokine storm” that can have deadly consequences. However, the lungs are also very complex, and it is difficult to replicate their unique features in the lab. This complexity has hindered science’s understanding of how the lungs function at the cell and tissue levels, in both healthy and diseased states.
The Wyss Institute’s Human Organ Chips were developed to address this problem, and have been shown to faithfully replicate the functions of many different human organs in the lab, including the lung. As part of projects funded by the NIH and DARPA since 2017, Wyss researchers have been working on replicating various diseases in Lung Airway and Alveolus Chips to study how lung tissues react to respiratory viruses that have pandemic potential and test potential treatments.
During his Ph.D. training, Bai studied diseases that affect the tiny air sacs deep inside the lungs where oxygen is rapidly exchanged for carbon dioxide. That foundation prepared him to tackle the challenge of recreating a flu infection in an Alveolus Chip so that the team could study how these deep lung spaces mount immune responses against viral invaders.
Bai and his team first lined the two parallel microfluidic channels of an Organ Chip with different types of living human cells — alveolar lung cells in the upper channel and lung blood vessel cells in the lower channel — to recreate the interface between human air sacs and their blood-transporting capillaries. To mimic the conditions that alveoli experience in the human lung, the channel lined by alveolar cells was filled with air while the blood vessel channel was perfused with a flowing culture medium containing nutrients that are normally delivered via the blood. The channels were separated by a porous membrane that allowed molecules to flow between them.
Previous studies at the Wyss Institute have established that applying cyclical stretching to Alveolus Chips to imitate breathing motions produces biological responses that mimic those observed in vivo. This is accomplished by applying suction to hollow side chambers adjacent to the cell-lined fluidic channels to rhythmically stretch and relax the lung tissues by 5%, which is what human lungs typically experience with every breath.
When the team infected these “breathing” Alveolus Chips with H3N2 influenza by introducing the virus into the air channel, they observed the development of several known hallmarks of influenza infection, including the breakdown of junctions between cells, a 25% increase in cell death, and the initiation of cellular repair programs. Infection also led to much higher levels of multiple inflammatory cytokines in the blood vessel channel including type III interferon (IFN-III), a natural defense against viral infection that is also activated in in vivo flu infection studies.
In addition, the blood vessel cells of infected chips expressed higher levels of adhesion molecules, which allowed immune cells including B cells, T cells, and monocytes in the perfusion medium to attach to the blood vessel walls to help combat the infection. These results confirmed that the Alveolus Chip was mounting an immune response against H3N2 that recapitulated what happens in the lung of human patients infected with flu virus.
Focus on your breath
The team then carried out the same experiment without mechanical breathing motions. To their surprise, chips exposed to breathing motions ??had 50% less viral mRNA in their alveolar channels and a significant reduction in inflammatory cytokine levels compared to static chips. Genetic analysis revealed that the mechanical strain had activated molecular pathways related to immune defense and multiple antiviral genes, and these activations were reversed when the cyclical stretching was stopped.
“This was our most unexpected finding — that mechanical stresses alone can generate an innate immune response in the lung,” said co-first author Longlong Si, Ph.D., a former Wyss Technology Development Fellow who is now a Professor at the Shenzhen Institute of Advanced Technology in China.
Knowing that sometimes the lungs experience greater than 5% strain, such as in chronic obstructive pulmonary disorder (COPD) or when patients are put on mechanical ventilators, the scientists increased the strain to 10% to see what would happen. The higher strain caused an increase in innate immune response genes and processes, including several inflammatory cytokines.
“Because the higher strain level resulted in greater cytokine production, it might explain why patients with lung conditions like COPD suffer from chronic inflammation, and why patients who are put on high-volume ventilators sometimes experience ventilator-induced lung injury,” Si explained.
From a chip to clinical trials
The scientists then went a step further, comparing the RNA molecules present in cells within strained vs. static Alveolus Chips to see if they could pinpoint how the breathing motions were generating an immune response. They identified a calcium-binding protein, called S100A7, that was not detected in static chips but highly expressed in strained chips, suggesting that its production was induced by mechanical stretching. They also found that increased expression of S100A7 upregulated many other genes involved in the innate immune response, including multiple inflammatory cytokines.
S100A7 is one of several related molecules known to bind to a protein on cells’ membranes called the receptor for advanced glycation end products (RAGE). RAGE is more highly expressed in the lung than in any other organ in the human body, and has been implicated as a major inflammatory mediator in several lung diseases. The drug azeliragon is a known inhibitor of RAGE, so the scientists perfused azeliragon through the blood vessel channel of strained Alveolus Chips for 48 hours, then infected the chips with H3N2 virus. This pretreatment prevented the cytokine-storm-like response that they had observed in untreated chips.
Based on this promising result, the team then infected strained Alveolus Chips with H3N2 and administered azeliragon at its therapeutic dose two hours after infection. This approach significantly blocked the production of inflammatory cytokines — an effect that was further enhanced when they added the antiviral drug molnupiravir (which was recently approved for patients with COVID-19) to the treatment regimen.
These results caught the eye of Cantex Pharmaceuticals, which owns patent rights to azeliragon and was interested in using it to treat inflammatory diseases. Based in part on the Wyss team’s work in Alveolus Chips, Cantex licensed azeliragon for the treatment of COVID-19 and other inflammatory lung diseases in early 2022. Given the drug’s excellent safety record in previous Phase 3 clinical trials, the company has applied for FDA approval to start a Phase 2 trial in patients with COVID-19 patients, and plans to follow with additional Phase 2 trials for other diseases including COPD and steroid-resistant asthma.
“Thanks to the great work of the scientists at the Wyss Institute, we now have compelling evidence that azeliragon may have the potential to prevent severe COVID-19 illness in the form of a once-a-day pill. We’re excited to have the opportunity to conduct clinical trials of azeliragon for this disease, seeking to bring this groundbreaking therapy to patients to prevent the life-threatening inflammation that is a major cause of hospitalization and death,” said Stephen Marcus, M.D., CEO of Cantex.
While azeliragon is a promising anti-inflammatory drug, the scientists warn that more studies are needed to determine a safe and effective treatment regimen in humans. RAGE is a vital player in initiating beneficial inflammation against pathogens in the early stages of an infection, and inhibiting it too soon could prevent a patient from mounting a sufficient immune response.
Given the Alveolus Chip’s many advantages over traditional preclinical models, the Wyss team is exploring the incorporation of additional cell types such as macrophages into the chips to increase their complexity and model more biological processes, such as adaptive immunity. They are also using their existing model to study the efficacy of new compounds, drugs, and biologics (such as mRNA therapeutics) against influenza, SARS-CoV-2, and other diseases.
“This important paper led to the discovery of RAGE inhibitors’ promise for treating inflammatory lung diseases, which was the basis for the recent license of azeliragon to Cantex and its movement toward human clinical trials for COVID-19. I am extremely proud of this team and how quickly this scientific finding was translated into commercialization that will hopefully lead to lifesaving treatment for patients. This is what the Wyss Institute is all about,” said senior author Donald Ingber, M.D., Ph.D., who is the Wyss Institute’s Founding Director as well as the Judah Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and Boston Children’s Hospital, and Hansjörg Wyss Professor of Bioinspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
Additional authors of the study include Amanda Jiang, Chaitra Belgur, M.S., Yunhao Zhai, Ph.D., Melissa Rodas, and Aditya Patil and Girija Goyal, Ph.D. from the Wyss Institute, and former Wyss Institute members Roberto Plebani, Ph.D., Crystal Oh, Atiq Nurani, M.S., Sarah Gilpin, Ph.D., Rani Powers, Ph.D. and Rachelle Prantil-Baun, Ph.D.
This research was supported by the Wyss Institute for Biologically Inspired Engineering at Harvard University, the US Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement HR0011-20-2-0040, and the National Institutes of Health under grants UG3-HL-141797 and UH3-HL-141797.
1. Haiqing Bai, Longlong Si, Amanda Jiang, Chaitra Belgur, Yunhao Zhai, Roberto Plebani, Crystal Yuri Oh, Melissa Rodas, Aditya Patil, Atiq Nurani, Sarah E. Gilpin, Rani K. Powers, Girija Goyal, Rachelle Prantil-Baun, Donald E. Ingber. Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-29562-4
5.Showing How Zinc Boosts Immune System
From Fred Hutchinson Cancer Research Center
Zinc’s immune-boosting properties are well-established, but scientists haven’t known exactly how it works. In a new study published online March 25 in the journal Blood, Fred Hutchinson Cancer Research Center scientists reveal two ways the mineral supports immunity and suggest how it could be used to improve health.
Using mice, the team discovered that zinc is needed for the development of disease-fighting immune cells called T cells and prompts regeneration of the thymus, the immune organ that produces T cells.
“This study adds to our knowledge of what zinc is actually doing in the immune system and suggests a new therapeutic strategy for improving recovery of the immune system,” said senior author Dr. Jarrod Dudakov, an immunologist at Fred Hutch.
The study also revealed that an experimental compound that mimics zinc’s action in this organ works even better than the natural mineral to promote immune recovery.
“We are now looking into how zinc may fit in with our other discoveries of how the immune system repairs itself and could eventually lead to therapies to improve immune function for people who receive a blood stem cell transplant for a blood cancer or people with chronic immune decline that accompanies aging,” Dudakov said.
Thymic regeneration and immune function, and zinc
Previously, Dudakov and his team have outlined the molecular pathways and cell types that govern how the immune system’s thymus repairs itself after injury. Such treatments could improve vaccine efficacy and hasten thymic regeneration after stressors like chemotherapy, blood stem cell transplant and radiation exposure.
Dudakov began studying zinc a few years ago when Dr. Lorenzo Iovino, the study’s first author and a research associate at Fred Hutch, joined Dudakov’s lab. Since the scientists knew that low levels of zinc are linked to fewer infection fighting T cells and a shrunken thymus, where T cells develop, Dudakov and Iovino explored how to supplement with zinc in mouse models where the immune system is damaged.
Iovino, who’s also a blood stem cell transplant physician, had shown in a previous study that zinc could boost immune recovery in patients undergoing stem-cell transplants for the blood cancer multiple myeloma.
But the study didn’t explain why zinc was helping.
Zinc is critical for T-cell development and thymic regeneration
As in humans, Iovino and Dudakov found that the thymuses of mice deprived of dietary zinc shrink and produce notably fewer mature T cells, even after as little as three weeks of a no-zinc diet. Iovino was able to show that without zinc, T cells cannot fully mature.
He also found that zinc deficiency slows recovery of T-cell numbers after mice receive immune-destroying treatments akin to those given to patients about to receive a blood stem cell transplant.
Conversely, extra zinc speeds this process, and T cells recover faster than normal. The team saw a similar result in a mouse model of blood stem cell transplant.
“So we had a consistent result of a better reconstitution of the thymus and also a better reconstitution of T cells in the peripheral blood after zinc supplementation,” Iovino said. “But we still didn’t know how exactly zinc was working.”
Iovino discovered that it was the change in zinc levels around cells that release a key regenerative factor that seemed to kick off the thymus’ renewal processes. T cells accumulate zinc as they develop, but release it after a damaging event — like a burst of radiation — kills them off.
Cells use a molecule called GPR39 to sense a change in external zinc, and Iovino found that an experimental compound that mimics rising external zinc levels by stimulating GPR39 could also promote renewal factor release and thymic regeneration.
“What we think is going on is, as you give zinc supplementation, that gets accumulated within the developing T cells. It gets stored and stored and stored, then the damage comes along and the zinc is released,” Dudakov said. “Now you have more zinc than you normally would, and it can instigate this regenerative pathway. With the experimental compound we can just directly target GPR39 and basically get the same effect without any of that pretreatment.”
Getting to the clinic
There’s still a lot to learn before they can turn their findings to therapeutic strategies, the scientists said.
Transplant patients already receive mineral supplements, so if extra zinc were to be incorporated into their treatment regimens, it would be important to make sure that anyone receiving it is truly zinc-deficient. Iovino thinks many patients might be, but right now there isn’t a good test to assess this. He’s currently working on developing one, which would first be used to help researchers determine whether patients’ zinc status correlates with immune recovery after blood stem cell transplant.
Dudakov will pursue GPR39-stimulating compounds as therapies to improve thymic recovery after acute injuries like pre-transplant radiation. The team is currently screening similar compounds to find any that may be more effective.
He and Iovino are also working to determine whether such compounds could help with thymic regeneration in other settings. Unfortunately, our thymuses also slowly shrink and reduce their T-cell output as we age. Dudakov and Iovino would also like to know whether this chronic degeneration could be slowed by boosting the organ’s regenerative processes.
“Our lab is continuing to piece together the molecular players that contribute to thymus regrowth,” Dudakov said. “Ultimately, we aim to develop therapies that trigger natural regeneration and restore immune health.”
The study was funded by the National Institutes of Health, the American Society of Hematology and The Rotary Foundation.
1. Lorenzo Iovino, Kirsten Cooper, Paul deRoos, Sinead Kinsella, Cindy Anggelica Evandy, Tamas Ugrai, Francesco Mazziotta, Kathleen S. Ensbey, David Granadier, Kayla Hopwo, Colton W Smith, Alex Gagnon, Sara Galimberti, Mario Petrini, Geoffrey R Hill, Jarrod A Dudakov. Activation of the Zinc-sensing receptor GPR39 promotes T cell reconstitution after hematopoietic cell transplant in mice. Blood, 2022; DOI: 10.1182/blood.2021013950
News Briefs – NaturalPath
1. Not All Dietary ‘Fiber’ Benefits Inflammation
From Columbia University’s Mailman School of Public Health
Researchers at Columbia University Mailman School of Public Health and colleagues evaluated whether dietary fiber intake was associated with a decrease in inflammation in older adults and if fiber was inversely related to cardiovascular disease. The results showed that total fiber, and more specifically cereal fiber but not fruit or vegetable fiber, was consistently associated with lower inflammation and lower CVD incidence. Until now there had been limited data on the link between fiber and inflammation among older adults, who have higher levels of inflammation compared with younger adults. The study findings are published in JAMA Network Open.
The research includes data from a large and well-characterized prospective cohort of elderly individuals, with detailed data on dietary intake, inflammation, and incidence of CVD. The research confirmed previously observed associations between dietary fiber and CVD and extended those investigations to include the source of the fiber, the relationship of fiber with multiple inflammatory markers, and to test whether inflammation mediated the relationship between dietary fiber and CVD.
Of the 4125 adults enrolled in the Cardiovascular Health Study from 1989 to 1990 participants received a food frequency questionnaire that was administered to those without prevalent CVD at enrollment and then were followed up visits for development CVD (stroke, myocardial infarction, and atherosclerotic cardiovascular death) through June 2015. Blood samples were assessed for markers of inflammation.
“Higher intakes of dietary fiber is associated with lower CVD risk. A common hypothesis has been that higher fiber intakes reduce inflammation, subsequently leading to lower CVD risk” said Rupak Shivakoti, PhD, assistant professor of epidemiology at Columbia Mailman School. ‘With findings from this study, we are now learning that one particular type of dietary fiber — cereal fiber — but not fruit or vegetable fiber was associated with lower inflammation. With findings from this study we now are learning that cereal fiber has the potential to reduce inflammation and will need to be tested in future interventional studies.”
Although there are data to suggest that fiber in general might have anti-inflammatory effects by improving gut function, modifying diet and satiety (eg, reduced fat and total energy intake), and improving lipid and glucose profile metabolism, why cereal fiber but not vegetable or fruit fiber is associated with lower inflammation is not clear and warrants further investigation, noted Shivakoti. Further, he notes that it is not clear whether cereal fiber per se or other nutrients in foods rich in cereal fiber are driving the observed relationships.
“Additionally, we learned that inflammation had only a modest role in mediating the observed inverse association between cereal fiber and CVD,” observed Shivakoti. “This suggests that factors other than inflammation may play a larger role in the cereal fiber-associated reduction in CVD and will need to be tested in future interventions of specific populations.
Co-authors are from Columbia University Mailman School of Public Health; University of Washington; Brigham and Women’s Hospital; Harvard Medical School; Boston Veterans Healthcare; Larner College of Medicine at the University of Vermont; San Francisco Veterans Affairs Health Care System; University of California-San Francisco; Kaiser Permanente Washington Health Research Institute; New York Academy of Medicine; Beth Israel Deaconess Medical Center; and Harvard Chan School of Public Health,
The research was supported by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
1. Rupak Shivakoti, Mary L. Biggs, Luc Djoussé, Peter Jon Durda, Jorge R. Kizer, Bruce Psaty, Alex P. Reiner, Russell P. Tracy, David Siscovick, Kenneth J. Mukamal. Intake and Sources of Dietary Fiber, Inflammation, and Cardiovascular Disease in Older US Adults. JAMA Network Open, 2022; 5 (3): e225012 DOI: 10.1001/jamanetworkopen.2022.5012
2. Getting Better Deep Sleep
From ETH Zurich
Researchers have developed a wearable device that plays specific sounds to enhance deep sleep. The first clinical study has now shown that the device is effective, but not at the same level of effectiveness for everyone.
Many people, especially the elderly, suffer from abnormal sleep. In particular, the deep sleep phases become shorter and shallower with age. Deep sleep is important for the regeneration of the brain and memory, and also has a positive influence on the cardiovascular system.
Researchers have shown that the brain waves characterizing deep sleep, so-called slow waves, can be improved by playing precisely timed sounds through earphones while sleeping. While this works well in the sleep laboratory under controlled conditions, there has thus far been no at home solution that can be used longer than just one night.
SleepLoop to the rescue
As part of the SleepLoop project, researchers at ETH Zurich have developed a mobile system that can be used at home and aims to promote deep sleep through auditory brain stimulation.
The SleepLoop system consists of a headband that is put on at bedtime and worn throughout the night. This headband contains electrodes and a microchip that constantly measure the brain activity of the person sleeping. Data from this is analysed autonomously in real-time on the microchip using custom software. As soon as the sleeping person shows slow waves in the brain activity characterising deep sleep, the system triggers a short auditory signal (clicking). This helps to synchronise the neuronal cells and enhance the slow waves. What makes the solution unique is that the person sleeping is not conciously aware of this sound during deep sleep.
The first clinical study
Researchers from ETH Zurich and University Hospital Zurich, led by Caroline Lustenberger, group leader at the Neural Control of Movement Lab, have conducted a clinical study with this device for the first time. The results have just been published in the journal Communications Medicine.
The study involved equipping participants, between 60 — 80 years old, with the SleepLoop system, which they were required to operate themselves in their own home. The system is designed to function independently even by users with little technical experience. “This worked very well. We had surprisingly little data loss and the participants rated the device as user-friendly,” says Lustenberger.
They wore the device every night for a total of four weeks, with the auditory stimulation given on a nightly basis for two weeks and no stimulation for the next two weeks. Neither the subjects nor the researchers knew in which two weeks the auditory signals were played and in which two they were not.
Auditory stimulation is indeed feasible
The results of 16 participants of the study show that it was indeed possible to enhance the slow waves through auditory signals during deep sleep in most participants. However, the individual differences were extensive with some of the subjects responding very well to the stimuli, while others responded minimally or not at all.
According to Lustenberger, the question of whether a person reacted to a stimulus did not depend on their well-being during the day. “Some people generally responded well to the stimuli and clearly showed enhanced slow waves, while others showed no response, regardless of their daily well-being.”
The researchers have used these individual differences to better predict how a given individual will respond to the auditory stimulus. This in turn helps them to optimise and improve the performance of SleepLoop.
On track for market launch
A spin-off company Tosoo AG, is currently working on developing the device further and preparing it for the clinical market. It is already clear that it will not be freely available, but only via a doctor’s prescription.
“This is a medical device, not just a wellness consumer product you can order online when you have trouble sleeping,” emphasises Walter Karlen, who developed the technology at ETH Zurich. 1 Karlen has been appointed Director of the Institute of Biomedical Engineering at Ulm University in May 2021. “Use of the device must be medically indicated and supervised by a doctor,” he says. Further development of the technology will now continue also in Ulm.
1. Caroline Lustenberger, M. Laura Ferster, Stephanie Huwiler, Luzius Brogli, Esther Werth, Reto Huber, Walter Karlen. Auditory deep sleep stimulation in older adults at home: a randomized crossover trial. Communications Medicine, 2022; 2 (1) DOI: 10.1038/s43856-022-00096-6
3. Post Concussion Symptoms May be From Damaged Nerve
From Lund University
Depression, dizziness, difficulty focusing the gaze and balance problems. Many professional athletes who have sustained head trauma in sports have lingering symptoms that affect everyday life. Little help has been available as the cause has been unknown. A clinical study from Lund University in Sweden can now show that the problems originate in an injury to the vestibular nerve.
Athletes in contact sports such as ice hockey, football and skiing have an increased risk of sustaining a head injury. If the impact is severe enough, the athlete can suffer a concussion. Even minor head injuries can have serious consequences. The problems have been brought to light within American football, where players who have suffered from repeated concussions have developed dementia, severe depression and cognitive impairment.
In many cases, the symptoms after a concussion are temporary, but an increasing number of athletes experience long-term problems that make it difficult to work, go to school or play sports. The symptoms are aggravated by activity or impressions and include headaches, depression, anxiety, nausea, difficulty focusing and problems with balance.
“It has been unclear what causes the symptoms, and it is difficult for healthcare professionals to help these athletes. We wanted to investigate this further to find out what really causes the symptoms,” says Niklas Marklund, professor of neurosurgery at Lund University, consultant at Skåne University Hospital with a scientific interest in sports-related head injuries and one of the researchers behind the article.
A total of 42 people were included in the study. One group included 21 healthy athletes without previous trauma to the head, and the other 21 athletes who all suffered from sports-related concussions and who had experienced persisting symptoms for more than six months. All the participants underwent various tests in which the researchers examined, among other things, their balance organs. Using a so-called 7-Tesla MRI, the athletes’ brains were studied to understand more about what caused the symptoms. The researchers found impaired function of the balance organs in the inner ear of 13 athletes in the group with long-term problems. In the group of healthy athletes 3 people had similar findings.
“The test results show that the injury is located to the vestibular nerve, which is connected to the semicircular canals in a cavity inside the skull, and which is directly adjacent to the cochlea in the ear. These injuries lead to the inward nerve impulses not working properly, and the brain therefore does not receive important information about body movements and sensory impressions required to maintain a good balance,” says Anna Gard, doctoral student at Lund University, resident in neurosurgery at Skåne University Hospital and first author of the study.
When you suffer from a concussion, it is often because the head rotates too fast, for example when tackling in ice hockey.
“We have not examined athletes with short-term problems after blows to the head, so we cannot say anything about them. This study applies to athletes with prolonged symptoms after concussion. The rotation of the head that occurs in connection with a concussion could lead to a stretch of the vestibular nerve, which then leads to impaired function. Now that we have more knowledge about where the problems are located, it is easier to find possible therapies that could help these athletes,” concludes Niklas Marklund.
1. Anna Gard, Ali Al-Husseini, Evgenios N. Kornaropoulos, Alessandro De Maio, Yelverton Tegner, Isabella Björkman-Burtscher, Karin Markenroth Bloch, Markus Nilsson, Måns Magnusson, Niklas Marklund. Post-Concussive Vestibular Dysfunction Is Related to Injury to the Inferior Vestibular Nerve. Journal of Neurotrauma, 2022; DOI: 10.1089/neu.2021.0447
4. Showing How Zinc Boosts Immune System
From Fred Hutchinson Cancer Research Center
Zinc’s immune-boosting properties are well-established, but scientists haven’t known exactly how it works. In a new study published online March 25 in the journal Blood, Fred Hutchinson Cancer Research Center scientists reveal two ways the mineral supports immunity and suggest how it could be used to improve health.
Using mice, the team discovered that zinc is needed for the development of disease-fighting immune cells called T cells and prompts regeneration of the thymus, the immune organ that produces T cells.
“This study adds to our knowledge of what zinc is actually doing in the immune system and suggests a new therapeutic strategy for improving recovery of the immune system,” said senior author Dr. Jarrod Dudakov, an immunologist at Fred Hutch.
The study also revealed that an experimental compound that mimics zinc’s action in this organ works even better than the natural mineral to promote immune recovery.
“We are now looking into how zinc may fit in with our other discoveries of how the immune system repairs itself and could eventually lead to therapies to improve immune function for people who receive a blood stem cell transplant for a blood cancer or people with chronic immune decline that accompanies aging,” Dudakov said.
Thymic regeneration and immune function, and zinc
Previously, Dudakov and his team have outlined the molecular pathways and cell types that govern how the immune system’s thymus repairs itself after injury. Such treatments could improve vaccine efficacy and hasten thymic regeneration after stressors like chemotherapy, blood stem cell transplant and radiation exposure.
Dudakov began studying zinc a few years ago when Dr. Lorenzo Iovino, the study’s first author and a research associate at Fred Hutch, joined Dudakov’s lab. Since the scientists knew that low levels of zinc are linked to fewer infection fighting T cells and a shrunken thymus, where T cells develop, Dudakov and Iovino explored how to supplement with zinc in mouse models where the immune system is damaged.
Iovino, who’s also a blood stem cell transplant physician, had shown in a previous study that zinc could boost immune recovery in patients undergoing stem-cell transplants for the blood cancer multiple myeloma.
But the study didn’t explain why zinc was helping.
Zinc is critical for T-cell development and thymic regeneration
As in humans, Iovino and Dudakov found that the thymuses of mice deprived of dietary zinc shrink and produce notably fewer mature T cells, even after as little as three weeks of a no-zinc diet. Iovino was able to show that without zinc, T cells cannot fully mature.
He also found that zinc deficiency slows recovery of T-cell numbers after mice receive immune-destroying treatments akin to those given to patients about to receive a blood stem cell transplant.
Conversely, extra zinc speeds this process, and T cells recover faster than normal. The team saw a similar result in a mouse model of blood stem cell transplant.
“So we had a consistent result of a better reconstitution of the thymus and also a better reconstitution of T cells in the peripheral blood after zinc supplementation,” Iovino said. “But we still didn’t know how exactly zinc was working.”
Iovino discovered that it was the change in zinc levels around cells that release a key regenerative factor that seemed to kick off the thymus’ renewal processes. T cells accumulate zinc as they develop, but release it after a damaging event — like a burst of radiation — kills them off.
Cells use a molecule called GPR39 to sense a change in external zinc, and Iovino found that an experimental compound that mimics rising external zinc levels by stimulating GPR39 could also promote renewal factor release and thymic regeneration.
“What we think is going on is, as you give zinc supplementation, that gets accumulated within the developing T cells. It gets stored and stored and stored, then the damage comes along and the zinc is released,” Dudakov said. “Now you have more zinc than you normally would, and it can instigate this regenerative pathway. With the experimental compound we can just directly target GPR39 and basically get the same effect without any of that pretreatment.”
Getting to the clinic
There’s still a lot to learn before they can turn their findings to therapeutic strategies, the scientists said.
Transplant patients already receive mineral supplements, so if extra zinc were to be incorporated into their treatment regimens, it would be important to make sure that anyone receiving it is truly zinc-deficient. Iovino thinks many patients might be, but right now there isn’t a good test to assess this. He’s currently working on developing one, which would first be used to help researchers determine whether patients’ zinc status correlates with immune recovery after blood stem cell transplant.
Dudakov will pursue GPR39-stimulating compounds as therapies to improve thymic recovery after acute injuries like pre-transplant radiation. The team is currently screening similar compounds to find any that may be more effective.
He and Iovino are also working to determine whether such compounds could help with thymic regeneration in other settings. Unfortunately, our thymuses also slowly shrink and reduce their T-cell output as we age. Dudakov and Iovino would also like to know whether this chronic degeneration could be slowed by boosting the organ’s regenerative processes.
“Our lab is continuing to piece together the molecular players that contribute to thymus regrowth,” Dudakov said. “Ultimately, we aim to develop therapies that trigger natural regeneration and restore immune health.”
The study was funded by the National Institutes of Health, the American Society of Hematology and The Rotary Foundation.
1. Lorenzo Iovino, Kirsten Cooper, Paul deRoos, Sinead Kinsella, Cindy Anggelica Evandy, Tamas Ugrai, Francesco Mazziotta, Kathleen S. Ensbey, David Granadier, Kayla Hopwo, Colton W Smith, Alex Gagnon, Sara Galimberti, Mario Petrini, Geoffrey R Hill, Jarrod A Dudakov. Activation of the Zinc-sensing receptor GPR39 promotes T cell reconstitution after hematopoietic cell transplant in mice. Blood, 2022; DOI: 10.1182/blood.2021013950
5. How Political Orientation Shapes How We Perceive Others
From University of Toronto
A new U of T Scarborough study finds that liberals and conservatives differ in how they perceive dominance in women, which may influence their likelihood to vote them into political office.
“We found that conservatives and liberals read dominance signals differently in the faces of men and women,” says Pankaj Aggarwal, professor of marketing in the department of management at U of T Scarborough.
“This has some practical implications for politics, gender stereotyping and how we perceive leadership roles in society.”
Aggarwal and co-author Ahreum Maeng, an associate professor at the University of Kansas, looked at the width-to-height-ratio of a face to measure perceptions of dominance. Basically, a person with a wider face is perceived as having a more dominant personality and possessing stronger leadership traits than someone with a narrower face.
In a series of experiments, the researchers found that wider faces in men are perceived as more dominant, but the same perception is less likely for women’s faces.
Political orientation plays a key role
One of the studies involved showing conservatives and liberals the faces of men and women candidates and asking them to rate their likelihood to be elected into political office. Men with wider faces were perceived as more dominant and electable, but the same wasn’t true for women with wider faces.
The researchers found conservatives showed a stronger bias against women’s faces to the point that they were less likely to elect a woman candidate due to a perceived association with lower dominance. Liberals indicated they were more likely to vote for a woman, but like conservatives, they also didn’t perceive women with a wider face as more dominant.
“While there is a gender stereotype effect that does kick in for liberals, it isn’t as strong, and on average they were more likely elect women and think of women as leaders,” says Aggarwal.
He says one reason for this difference may come down to conservatives believing in maintaining social hierarchies, while liberals actively try to override this bias and create a less hierarchical society.
As for why people perceive a wider face as more dominant and worthy of leadership, Aggarwal says the explanation is likely rooted in evolutionary psychology. In traditional societies, men held leadership roles through aggression and were perceived as more dominant.
“Humans have evolved to perceive larger faces as being more dominant, and that perception can be influenced by stereotypes.” He adds that traditionally, men have been perceived as more dominant and aggressive, while women have been stereotyped as more submissive and nurturing.
The research, which will be published in the Journal of the Association for Consumer Research, raises an interesting question about what can be done to counteract this effect. Although gender equality has improved in many societies, women leaders are still nominated less frequently than men. One of the reasons may come down to how people read the facial cues of candidates.
Aggarwal says it’s important to be aware of inherent biases and stereotypes and try to counter them. He said it’s also important not to let them cloud judgement about a candidate’s electability.
“You may be well-intentioned, but these biases can be unconscious,” says Aggarwal, whose research looks at brand anthropomorphism, the idea that human traits are often given to companies and products.
“These biases can be strong, so I think the biggest thing is to be aware and try not to be guided by them.”1. Ahreum Maeng, Pankaj Aggarwal. The Face of Political Beliefs: Why Gender Matters for Electability. Journal of the Association for Consumer Research, 2022; DOI: 10.1086/719579