Past News Items - June 2023
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In the News
IFM Awards Aristo Vojdani, PhD, MSc, CLS 2023 the Linus Pauling Award in Functional Medicine
Sealing a Leaky Gut
Men’s health: Mayo Clinic Healthcare expert shares key symptoms to act on
Environmental toxicants wreaking havoc on bone development
Exercise Strengthens Immune System in Multiple Myeloma Patients
IFM Awards Aristo Vojdani, PhD, MSc, CLS 2023 the Linus Pauling Award in Functional Medicine
The Linus Pauling Award in Functional Medicine was established in 1996 at the 3rd Annual International Symposium on Functional Medicine in Vancouver, BC. Jeffrey Bland, PhD, co-founder of The Institute for Functional Medicine (IFM), worked with Dr. Pauling early in his career and admired both the man and his contributions to science and medicine. Dr. Bland felt that an award named after this visionary scientist and thinker would be the greatest way to honor his life and achievements.
Since that time, the Linus Pauling Award has been presented at IFM’s Annual International Conference. The Linus Pauling Award is given to a clinician or researcher who has made a significant contribution to the development of Functional Medicine, either through research or activities within IFM that enlarge the Functional Medicine model or extend the influence of the Functional Medicine systems approach. This award has become a recognized achievement in the field of integrative and systems medicine and is juried through a formalized process of selection.
The 2023 recipient was Aristo Vojdani, PhD, MSc, CLS. Dr Vojdani obtained his MSc and PhD in the fields of microbiology and clinical immunology from Bar-Ilan University in Israel, with postdoctoral studies in comparative immunology at UCLA and tumor immunology at Charles Drew/UCLA School of Medicine and Science. He is presently an adjunct associate professor in the Department of Preventive Medicine at Loma Linda University in California and an adjunct professor at the Lincoln College of Post professional, Graduate, and Continuing Education at the National University of Health Sciences.
Sealing a Leaky Gut
By studying the cells that line the intestines, Cedars-Sinai investigators have discovered a biological process that helps these cells repair themselves. The findings, published in the journal Cellular and Molecular Gastroenterology and Hepatology, illuminate what goes wrong in people with inflammatory bowel disease (IBD).
IBD is an autoimmune disorder primarily causing ulcerative colitis or Crohn’s disease. The immune system attacks healthy tissue in the gastrointestinal track, and can lead to severe diarrhea, malnutrition, dangerous blood clots, pancreatitis, and extensive and painful scarring.
“Almost all treatments for IBD target inflammation that occurs in this disease,” said Kathrin Michelsen, PhD, research assistant professor of Medicine and Biomedical Sciences in the F. Widjaja Foundation Inflammatory Bowel Disease Institute in the Department of Medicine at Cedars-Sinai, and senior author of the study. “We want to learn how to repair what we refer to as a ‘leaky gut,’ the damaged intestinal lining that also occurs in people with IBD.”
Scientists hypothesize that people with leaky guts are vulnerable to getting harmful substances, such as some types of bacteria, in their bloodstream.
This study by Michelsen and colleagues follows up on previous studies that investigated the function of a gene called tumor necrosis factor superfamily member 15, or TNFSF15. This is one of the first genes found to be associated with IBD.
TNFSF15 produces a protein called TL1A that is involved in intestinal inflammation. The investigators sought to know more about how the interactions between this protein and the intestinal lining might cause IBD symptoms. They focused on the TL1A receptor, a protein called death receptor 3, or DR3. Receptors are proteins that bind to molecules and aid in the communication between cells. DR3 binds to the surface of TL1A, for example.
To perform their study, the investigators observed laboratory mice carrying the TNFSF15 gene and mice not carrying it. They examined cells taken from the intestines of the mice and cultured them in a petri dish to see whether the cells expressed the gene. They also studied whether the collection of cells lining the intestines, known as the epithelial barrier, were damaged and how the cells could heal and grow again.
Epithelial barrier cells are connected by proteins that keep the lining of the intestines tight. This prevents bacteria from getting into the lamina propria, the connective tissues that also line the intestines and that form part of the immune system. People with IBD typically have inflammation in the lamina propria, which is supposed to serve as a protective physical barrier in the body.
The investigators discovered that mice that did not produce DR3 had less tightly bound epithelial cells. Their intestines were permeable enough to allow in bacteria that caused inflammation in the lamina propria.
The investigators also discovered that although laboratory mice that had inflammation in their intestines showed increased levels of TL1A, their epithelial cells did not show increased DR3 expression.
“These findings suggest that therapeutic approaches targeting TL1A rather than DR3 could reduce inflammation while preserving the repair mechanisms that DR3 is essential for in epithelial cells,” said Yosuke Shimodaira, PhD, first author of the study and a former investigator at Cedars-Sinai.
DR3, for example, contributes to the regeneration of the epithelial barrier, which is necessary for healing cell damage in the intestines caused by IBD.
“There are currently clinical trials that are studying drugs that target TL1A,” Michelsen said. “It's really important to elucidate all the potential mechanisms that could impact potential therapeutic efficiency and efficacy in those clinical trials.”
The investigators are continuing to study the effects of other genes associated with IBD.
Funding: The study was funded by the National Institutes of Health (award number DK056328) and the F. Widjaja Foundation.
Read more on the Cedars-Sinai Blog: Living a Life That Isn't Defined By IBD
Men’s health: Mayo Clinic Healthcare expert shares key symptoms to act on
As men age, even those accustomed to good health may encounter symptoms that affect their quality of life and are important to mention to their physicians. Vikas Mehta, MBCHb, a physician at Mayo Clinic Healthcare in London, describes several physical signs that are worth following up on.
"For men, very often the symptoms that affect their lives are things that they are not very comfortable talking to others about," says Dr. Mehta, a member of the Royal College of General Practitioners and of the Royal College of Obstetricians and Gynaecologists' Faculty of Sexual and Reproductive Health. "Often, these conditions are treatable."
For example:
Urological symptoms and sexual health:
The need to urinate often can signal prostate or bladder problems and/or diabetes. Painful or otherwise difficult urination should also be followed up on.
Erectile dysfunction, difficulty getting or maintaining an erection, is treatable and a good reason to have a cardiac screening, Dr. Mehta says: "If there are issues with blood vessels in one part of the body it's very likely there are issues elsewhere."
A testicular exam to look for lumps is a good idea for men who have never had one. "We find sometimes in screening tests that men have never had anyone other than their partners look at their sexual organs, and so we pick up a lot of issues or abnormalities," Dr. Mehta says.
Mental health:
"Mental health for me is a big one" for men to pay attention to, says Dr. Mehta, noting that Mayo Clinic Healthcare is located in an area known for high-stress professions such as banking and law. "Knowing when and where to get help is very important."
Musculoskeletal health:
Is it taking longer to recover from injuries? A decrease in capacity for exercise is often related to musculoskeletal issues such as muscle wasting and inflammatory issues.
Exercise can help relieve stress. For men accustomed to being active, not being able to run or engage in other exercise due to musculoskeletal conditions can affect mental health, Dr. Mehta says.
Screening for osteoarthritis and rheumatic diseases such as gout, psoriatic arthritis and rheumatoid arthritis may be called for, especially if there is a family history.
Respiratory health:
If you find yourself becoming fatigued and/or out of breath when you are exercising or just walking around or you have a chronic cough, it is time to get screened, Dr. Mehta says: "Even if it's just, `I wake up in the morning and I cough,' it shouldn't be happening every day." Respiratory conditions such as adult-onset asthma and COVID-related problems are among the possibilities.
Snoring and/or stopping breathing at times during the night can be a sign of sleep apnea and other respiratory problems. A lack of quality sleep is linked to several health problems such as higher blood pressure; increased appetite that can lead to diabetes and weight gain; anxiety; and depression.
"Snoring is a common reason for men to be kicked out of the bedroom by their partners, but the main sufferer is the person who has sleep apnea and is not getting quality sleep at night," Dr. Mehta says. "They may think, `You know, I can sleep anytime,' but they don't realize that they're not sleeping well at night and as a result can fall asleep just like that during the day."
Ear, nose and throat health:
Tinnitus—ringing and other noises in the ears—hearing better in one ear than the other, and ear pain are becoming more common as people work from home and use headphones, Dr. Mehta says.
Men with chronic sore throats, especially smokers, and/or those with white lesions in their mouths should be checked for throat cancers. "It's really important to get help in a timely manner if you have any of this," Dr. Mehta says.
Chronic congestion may mean seasonal allergies, and men with those may benefit from a seasonal shot called a hay fever injection, Dr. Mehta says.
Those with unexplained chronic congestion should be screened for nasal polyps. In some cases, a feeling that one nostril is harder to breathe out of than the other can be a symptom.
A feeling of constantly needing to clear the throat or something caught in the throat can be a sign of gastro-oesophageal reflux disease.
Diabetes:
Just as with frequent urination, often feeling thirsty means it may be time for diabetes screening.
Heavy consumers of alcohol should also be screened, Dr. Mehta says.
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About Mayo Clinic Healthcare
Mayo Clinic Healthcare, located in London, is a wholly owned subsidiary of Mayo Clinic, a not-for-profit academic medical center. Mayo Clinic is ranked the No. 1 hospital by U.S. News & World Report for a reason: quality of care. Mayo Clinic Healthcare is the U.K.’s front door to that unparalleled experience. Visit Mayo Clinic Healthcare for more information.
Environmental toxicants wreaking havoc on bone development
In a study published in the International Journal of Molecular Sciences, Nicole Sparks, PhD, corresponding author and assistant professor of environmental and occupational health at the UC Irvine Program in Public Health, highlights recent discoveries describing key hormone pathways involved in bone formation and endocrine disrupting chemicals (EDCs) that alter these pathways.
Rapid cell division and bone differentiation occur during these early developmental periods, which is also when the human body is most susceptible to environmental factors that can have an adverse influence on human bone development.
Exercise Strengthens Immune System in Multiple Myeloma Patients
Research has shown that the immune system doesn’t function properly in patients with multiple myeloma, a blood cancer that occurs when plasma cells — a type of white blood cell — multiply out of control. But a clinical trial led by Jens Hillengass, MD, PhD, Chief of Myeloma at Roswell Park Comprehensive Cancer Center, shows that exercise may have the power to strengthen the immune system in those patients, providing a nonpharmaceutical method of helping control the disease.
The results of that trial will be shared in a poster presentation, “T cell exhaustion is lower after a physical activity intervention in multiple myeloma patients,” at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. The work will be presented by first author Janine Joseph, MS, MBA, pre-doctoral trainee and Senior Research Specialist in the Department of Cancer Prevention and Control at Roswell Park, as part of a session on Hematologic Malignancies — Plasma Cell Dyscrasia.
“With these encouraging results from our pilot study, we have been able to show for the first time in myeloma patients that the immune system can be influenced by lifestyle interventions like supervised exercises,” says Dr. Hillengass, senior author on the study. “We have therefore started a larger prospective trial offering remote supervised exercise or intermittent fasting to influence parameters such as immune function, bone disease and microbiome in patients with monoclonal plasma cell disorders.”
The study focuses on CD4+ and CD8+ T cells — white blood cells that are part of the immune system and capable of fighting cancer. When those cells are exhausted, they become too weak to sustain the attack. While preclinical studies have shown that exercise can reduce immune exhaustion, few studies have examined how exercise affects biomarkers that measure immune exhaustion in cancer patients, especially those with multiple myeloma.
The research team looked at two biomarkers of T cell exhaustion: TIGIT, an immune inhibitory receptor that can reduce the effectiveness of T cells and prevent them from multiplying, and PD-1, which can exhaust T cells and suppress the immune system. The Roswell Park team measured the ratio of exhausted CD4+ and CD8+ T cells – those that expressed either marker – to non-exhausted CD4+ and CD8+ T cells, comparing this ratio before and after the exercise regimen.
The clinical trial enrolled 43 patients, who took part in a six-month program of physical activity. Approximately half the group received supervised strength training twice a week, while the other half, unsupervised, used activity trackers with remote prompts to gradually increase their walking. Participants provided blood samples before and after the exercise intervention to provide a comparison of the number of exhausted vs. non-exhausted T cells. Twenty-four participants completed the intervention and provided blood samples at two time points.
The research team used flow cytometry, a technique used to identify cell properties, to determine how many exhausted and non-exhausted T cells participants had before and after the intervention. At the end of the six-month exercise intervention, they found that the typical participant had a less-exhausted T-cell profile than at baseline. Specifically, the ratio of CD4+ TIGIT+ to non-exhausted CD4+ cells was reduced significantly, from 0.71 to 0.57. The ratio of CD8+ PD-1+ to non-exhausted CD8+ cells was somewhat reduced, from 1.81 to 1.48. These data suggest that physical activity can affect the immune systems of patients with multiple myeloma, creating an environment with fewer exhausted T cells and more robust T cells capable of fighting the cancer.
“We were excited by the outcome of this study, because it suggested that our patients might be able to achieve a less-exhausted immune system through exercise, which comes with many other health and quality-of-life benefits,” says Joseph. “There’s a lot more work to be done, but we’re hoping this study lays the groundwork for a better understanding of whether exercise should be recommended to myeloma patients to improve their immune function.”
That effort is already underway. The clinical trial, “Non-chemotherapeutic interventions for the improvement of quality of life and immune function in patients with multiple myeloma” (NCT05312255), has a targeted enrollment of 150 patients.