A study from the University of Bonn, claimed to be groundbreaking, has identified a powerful new compound that may offer relief for patients suffering from hard-to-treat allergic and inflammatory conditions, including irritable bowel syndrome (IBS), asthma, chronic pruritus, and potentially microscopic colitis (MC) and other IBDs. The compound, named PSB-172656, works by blocking a little-known immune receptor called MRGPRX2, which is found on mast cells. Mast cells are heavily involved in inflammatory reactions, especially those that occur without IgE antibodies,such as drug-induced allergies, neuroinflammation, or non-IgE mediated hypersensitivity. The research was published in Signal Transduction and Targeted Therapy and widely reported by Medical Xpress on April 24, 2025 (Al Hamwi, et al., 2025; Seiler, 2025, April 24).1, 2 Note that the receptor MRGPRX2 is primarily involved in non-IgE mediated mast cell activation. It does not directly bind IgA, and IgA immune complexes are not known to activate mast cells through MRGPRX2. Instead, MRGPRX2 is activated by other signals such as:
In other words, MRGPRX2 is part of a non-antibody, direct activation system, distinct from classic antibody-driven responses. How does this compare with normal IgE and IgA reaction pathways? IgE Pathway: IgE antibodies bind to FcεRI receptors on mast cells. When allergens cross-link these IgE molecules, mast cells rapidly release histamine and other inflammatory mediators, causing classic allergic reactions like hives or anaphylaxis. MRGPRX2 Pathway: Certain peptides, medications, and irritants directly activate MRGPRX2 receptors on mast cells without needing antibodies. This causes rapid mast cell degranulation and inflammation, often seen in drug reactions and chronic inflammation. IgA Pathway: IgA antibodies mainly interact with FcαRI (CD89) receptors on immune cells (such as macrophages and neutrophils, rarely mast cells directly). In special cases, IgA immune complexes can trigger inflammation indirectly, but mast cell activation through IgA is much less common and not through MRGPRX2. Therefore, mast cells can be activated through IgE for classic allergies, through MRGPRX2 for direct non-antibody triggers, and only rarely and indirectly through IgA immune complexes—each pathway driving inflammation in different ways. Here's why MRGPRX2 matters. MRGPRX2 is a mast cell receptor involved in non-traditional allergic responses and chronic inflammatory signaling. Unlike classic IgE-mediated allergic reactions (like hay fever or food allergies), MRGPRX2 triggers localized or systemic inflammation in response to certain medications, neuropeptides, and environmental stimuli. This receptor is implicated in a variety of painful and difficult-to-treat conditions, including:
The University of Bonn researchers found that PSB-172656 is capable of binding to and inhibiting MRGPRX2 with extremely small (subnanomolar) potency, preventing mast cell degranulation and the release of inflammatory mediators. The compound stopped anaphylactic reactions in mice and reduced local inflammation in tracheal and skin models. It was shown to be highly selective for MRGPRX2 and its mouse counterpart MRGPRB2. The effect was replicated in human skin mast cells and mast cell lines, confirming its potential relevance in human disease. The molecule was engineered for metabolic stability, low toxicity, and prolonged action, making it a strong candidate for drug development. Why might this matter for MC patients? Although the study did not specifically test PSB-172656 regarding MC, the mechanism of action and targeted pathway suggest strong potential relevance:
Will this discovery resolve MC cases that are refractive to treatment? For MC patients, many of whom struggle with ongoing symptoms despite dietary changes and medical treatments using corticosteroids, this novel MRGPRX2 blocker might one day offer a targeted, non-steroidal alternative. As understanding of mast cell-related gut inflammation grows, therapies like PSB-172656 may finally bring relief to those whose condition defies conventional treatment. References 1. Al Hamwi, G., Alnouri, M.W., Verdonck, S., Leonczak, P., Chaki, S., Frischbutter, S., . . . Müller, C. E. (2025). Subnanomolar MAS-related G protein-coupled receptor-X2/B2 antagonists with efficacy in human mast cells and disease models. Signal Transduction Targeted Therapy, (10)128. Retrieved from https://www.nature.com/articles/s41392-025-02209-8 2. Seiler, J. (2025, April 24), Bioactive compound blocks key immune receptor to ease hard-to-treat allergic reactions. Medical Xpress, Retrieved from https://medicalxpress.com/news/2025-04-bioactive-compound-blocks-key-immune.html
0 Comments
In recent years, there has been an explosive growth of DO (Doctor of Osteopathic Medicine) graduates from medical schools. From 1980 to 2005, annual DO graduates jumped over 150%, from about 1000 to 2800 yearly. By 2015, there were 5000 annual DO graduates, according to Wikipedia. In the spring of 2024, over 8200 new DO's graduated, and nearly 10,000 students were enrolled in osteopathic programs. Although there are almost four times as many MD schools as DO schools (155 versus 40), DO school enrollment has surged 77% in a decade compared with an 18% growth in MD program enrollments. As a result, approximately one in four current U.S. medical students is a DO. If you can't beat 'em, join 'em. Prior to 2020, DO residencies were often siloed under American Osteopathic Association (AOA), while MDs used the Accreditation Council for Graduate Medical Education (ACGME) pathways. In August of 2020, a merger created single accreditation under ACGME, enabling DOs access to all U.S. residencies. DO graduates now achieve record match rates, nearly matching MD grads. These changes ensure DO and MD doctors receive equivalent residency training, leveling the playing field. Note, however, that this did not apply to med school graduates prior to August 2020. Comparing MD versus DO training and practice:
DO training distinctions:
But daily clinical practices between MDs and DOs have converged significantly. Why this shift matters for patients:
The bottom line suggests that whether MD or DO, your doctor delivers competent, comprehensive medical care. The takeaway: DO graduates are rapidly increasing, and MD numbers are diminishing, especially in primary care. This underscores a broader acceptance and integration of osteopathic practices within mainstream medicine. For the average patient (hopefully, at least), this means more choice, a more holistic perspective, and consistently high-quality medical care, regardless of our doctor’s degree initials. But what about us? For patients with microscopic colitis (MC) or other inflammatory autoimmune diseases, the growing number of DO physicians, alongside MDs, offers several meaningful differences that may impact diagnosis, treatment style, and patient experience. While both MDs and DOs are fully licensed physicians with equivalent prescribing and procedural rights, their training philosophy and clinical emphasis can influence how they approach complex, chronic illnesses like autoimmune conditions. Will DO's holistic approach help? DOs are trained to view the body as an interconnected system, emphasizing the relationship between structure and function. For MC and IBD patients, this might mean:
DO training emphasizes prevention and chronic care. DO training traditionally includes more primary care orientation, and focuses on preventing disease recurrence, not just managing flare-ups. In conditions like MC, this could mean:
The many hours of musculoskeletal training that DOs eceive should help with:
Though not all DOs use osteopathic manipulative treatment (OMT) practice, those who do might offer gentle manual therapy as a complementary treatment — particularly helpful for patients with functional abdominal pain, stress-related GI symptoms, or pelvic floor dysfunction. Of course OMT does not "cure" autoimmune disease, but cit an offer non-pharmacological symptom relief, especially for associated conditions like IBS, fibromyalgia, or joint pain. And DOs may be more familiar (or open) to patients whose symptoms cross conventional diagnostic boundaries:
At least in theory, this all appears promising. I suppose we'll see how it works out in the real world. But whether our doctor is an MD or DO, we need to look for a provider who understands the complexity and individuality of autoimmune conditions, values shared decision-making, and doesn't rush to dismiss unexplained symptoms, because despite having many of the same symptoms, we're all different, in many respects.
A recent study published in the European Heart Journal, reveals that receiving a shingles (herpes zoster) vaccine may significantly reduce the risk of major cardiovascular events, including stroke, heart failure, and coronary heart disease, by as much as 23% (Lee, et al., 2025).1 The protective effect of the vaccine was found to last up to eight years, making it a potential game-changer, not just for preventing shingles, but also for reducing heart-related illness and death. The research was conducted by Professor Dong Keon Yon and colleagues at Kyung Hee University in South Korea. The massive population-based study followed more than 1.2 million people over a median of six years. Using national insurance and health records, the researchers tracked vaccine status and health outcomes. They found that individuals who received the live zoster vaccine experienced a:
The study is the first of its kind to evaluate 18 different types of cardiovascular disease outcomes following shingles vaccination. The benefit was strongest during the first 2–3 years following vaccination, although the protective effect lasted for up to eight years. The vaccine’s cardiovascular protective effects were even more pronounced in younger individuals (under 60), men, and those with unhealthy lifestyles (such as smokers, drinkers, and physically inactive individuals). The findings were also significant among rural and low-income populations, suggesting the vaccine could help reduce health disparities. Although this study doesn't establish a direct causal link, the researchers propose that preventing shingles — an infection known to trigger inflammation, blood vessel damage, and clot formation, may help reduce downstream cardiovascular risk. Vaccination likely prevents these inflammatory episodes, helping to maintain vascular health over time. These findings suggest the shingles vaccine could become a dual-purpose public health tool, especially for populations at risk for both shingles and cardiovascular disease. However, the study focused on the live zoster vaccine, which is gradually being replaced in many countries by the non-live recombinant shingles vaccine. Future research will be needed to assess whether similar cardiovascular benefits extend to the recombinant version. The take away: Shingles vaccination may protect more than just your skin. It may help protect your heart. As countries consider expanding vaccine recommendations, this study provides strong evidence that shingles vaccines could play a broader role in chronic disease prevention, particularly for vulnerable or high-risk populations. Reference 1. Lee, S., Lee, K., Oh, J., Kim, H. J., Son, Y., Kim, S., . . . Yon, D. K. (2025). Live zoster vaccination and cardiovascular outcomes: a nationwide, South Korean study, European Heart Journal, ehaf230, Retrieved from https://academic.oup.com/eurheartj/advance-article-abstract/doi/10.1093/eurheartj/ehaf230/8124786
Whether we realize it or not, many of us are perfectionists. I certainly am. In fact, published research shows that perfectionism is often associated with microscopic colitis (MC). Perfectionism arises from a blend of genetic factors and environmental influences, including childhood experiences and inherent personality traits. This trait is often esteemed due to its association with high achievement and success, and many MC patients tend to be overachievers. Although perfectionism itself is not classified as a psychological disorder, it's closely linked to anxiety and other mental health conditions, such as obsessive-compulsive disorder (OCD). For example, approximately 12.5% of microscopic colitis patients have obsessive-compulsive disorder (OCD), compared to about 1.2% in the general population. This somewhat common characteristic of MC patients is not well explored. The exact percentage of microscopic colitis patients who are perfectionists is not well-documented in scientific literature. However, anecdotal evidence and clinical observations suggest that a significant number of patients with microscopic colitis exhibit perfectionist traits, potentially due to the stress and anxiety associated with managing a chronic condition. Of course, this is a two-way street, and the trait of perfectionism may be associated with MC as an initial trigger for the disease, rather than as a result of the disease. Perfectionists tend to overthink most issues. Overthinking is characterized by excessive rumination and analysis, and it's closely associated with perfectionism. Perfectionists tend to set unattainably high standards for themselves and are often overly critical of their own performance. This constant self-scrutiny can lead to overthinking as they replay scenarios and outcomes in their minds, striving to find flaws and areas for improvement. Many of us try to overthink every detail of our recovery journey. As we attempt to understand MC, and develop our own personal recovery plan, many of us tend to overthink every little detail. The chronic nature of this disease, coupled with the need for constant vigilance, can encourage tendencies towards overthinking and perfectionism due to the following issues:
Perfectionism and overthinking can make MC symptoms worse by:
The medical community acknowledges this problem. A recent Medical Xpress article titled How can I stop overthinking everything?, addresses a common problem for chronic disease patients, including microscopic colitis (MC) patients (Ross, 2024, March 5).1 Recognizing and addressing emotions such as worry, anger, or sadness can help manage stress levels. MC patients can benefit from discussing their feelings with a therapist or support group. Developing plans for dealing with potential issues can reduce anxiety. For MC patients, this might involve preparing for flare-ups by having medication and dietary plans in place. Accepting that not all outcomes can be controlled and focusing on managing reactions can reduce stress. MC patients should focus on what they can control, such as diet, medication adherence, and stress management techniques. Reference: 1. Ross, K. (2024, March 5). "How can I stop overthinking everything?" A clinical psychologist offers solutions. Medical Xpress, Retrieved from https://medicalxpress.com/news/2024-03-overthinking-clinical-psychologist-solutions.html
A huge study published in JAMA Network Open, has uncovered significant differences in life expectancy across the United States, exposing how deeply geography, public health policy, and socioeconomic conditions shape the lives, and lifespans of Americans (Holford, McKay, Tam, Jeon, and Meza, 2025).1 Led by researchers from Yale University, the University of Michigan, and the University of British Columbia, the study offers an interesting view of mortality trends by birth, by analyzing over 179 million deaths across all 50 states and the District of Columbia (D. C.), based on people born from 1900 to 2000. The study showed that while many states in the Northeast, West, and D.C. experienced dramatic gains in life expectancy between 1900 and 2000, Southern states such as Mississippi, Alabama, and Kentucky saw stagnating progress, particularly among wome In New York and California, life expectancy increased by over 20 years. In some Southern states, women saw gains of less than 3 years over the entire century. After 1950, men in many Southern states saw life expectancy increases stall at less than two years, highlighting a widening gap that persists today. The study examined how quickly death rates increased after age 35, a measure of aging health. States with slower increases in death risk, like New York and Florida, had longer "doubling times" (over 9 years for females and over 11 for males). States like Oklahoma and Iowa had faster increases, indicating less healthy aging patterns. The researchers applied an age-period-cohort model using detailed mortality data from national databases. By tracking individuals by “birth cohort”,rather than simply summing and comparing annual death rates, they revealed how the historical, social, and environmental conditions people are born into can shape their health outcomes over a lifetime. This approach allowed the team to identify long-term effects of:
According to Dr. Theodore Holford of Yale, “These disparities are not historical accidents. They reflect decades of differences in policy, healthcare access, smoking prevalence, environmental exposure, and economic inequality.” Dr. Jamie Tam, a co-author and assistant professor of health policy, emphasized that poverty and weak public health systems remain key barriers to progress in states with poor outcomes. Washington D.C. showed the biggest gains in life expectancy. Once at the bottom of life expectancy rankings in 1900, D.C. posted the largest improvements, with gains of 30 years for females and 38 years for males by 2000. Researchers credit progressive urban policies, improved healthcare access, and changing demographics. Does that sound similar to political doublespeak? The researcher's observations are undoubtedly true, of course, but why did these changes and the health trends that they generated, occur in the first place? The study didn't investigate this, but everything occurs for a reason. There's a very good chance that these changes occurred mostly because the federal government headquarters are located in Washington D.C. As of July 2022, for example, approximately 25% of the workforce in Washington, D.C. were employed directly by the federal government. In addition to direct federal employment, a substantial portion of D.C.'s economy is tied to politics-related sectors, including:
While precise figures are not available, estimates suggest that up to 50% or more of D.C.'s workforce is employed in roles directly or indirectly connected to politics and government. This suggests that a high percentage of residents are well-educated and have relatively high-paying jobs, which translates to better access to health care, and and other benefits not shared by many locations. And why did the other longevity trends occur? Life expectancy trends of this sort aren't very surprising when we consider that this study covered the 20th century, which included the dustbowl years, the Great Depression, massive population shifts from rural lifestyles to urban and industrialized lifestyles, and immense civil rights changes. In 1900, about 41% of the workforce was employed in agriculture. This reflects the rural, agrarian nature of American society at the time, with the majority of people living in rural areas and depending on farming for their livelihood. By 2000, that number had dropped to about 1.9% of the workforce. This dramatic decline reflects over a century of industrialization, urbanization, and technological advancement in farming, which allowed fewer people to produce more food. This shift represents one of the most profound transformations in American economic and social life over the 20th century. And last, but certainly not least: Disparities in infrastructure funding by the federal government date back to at least the Civil War. When the Civil War ended, it left behind an atmosphere of persistent government bias against the South that lingered well into the 20th century. While this lingering bias didn't have any effect on the findings of the longevity study mentioned in this article, it certainly explains some of the reasons why these health problems in the South persisted throughout the 20th century. And it's important to remember that this too was primarily the result of political effects. The Compromise of 1877: After the Civil War, the South faced widespread destruction, economic collapse, and institutional chaos. During reconstruction, federal investment in rebuilding was significant, but ended abruptly in 1877, largely due to Northern political fatigue and racial backlash, leading to a withdrawal of federal oversight and funding. The “Compromise of 1877” allowed Southern states to reinstate white-dominated governments, which reversed many of the gains made by Black citizens and slowed regional development. Institutional underdevelopment and racial segregation (Jim Crow laws) entrenched poverty, and limited educational and health infrastructure. New Deal programs of the 1930s didn't resolve uneven distribution problems. From the 1900s through the 1950s, federal investments in infrastructure, public health, and education were unevenly distributed, with Northern and Western states often receiving more funding per capita in key areas. Southern states often had weaker political representation in federal decision-making bodies, particularly for the poorest communities. New Deal programs in the 1930s technically applied nationwide, but in practice:
The long-term effect of the New Deal programs reinforced economic underdevelopment (especially in the South) and contributed to public health disparities, which are reflected in the longevity statistics. The post-World War II era saw more federal investment in Southern infrastructure (for example, interstate highways, and defense contracts), which helped drive economic growth in states like Texas and North Carolina. However, health and education funding often still lagged behind, particularly in rural and poor Southern areas. Southern states often maintained lower tax bases, which, of course, limited their ability to match or supplement federal funds. Many historians and policy scholars agree that historical regional funding disparities were not solely caused by post-Civil War bias, but it clearly had a persistent long-term effect, especially in some southern states. But the study's most important finding was: Life expectancy is not just about individual choices — it's profoundly shaped by where we live and the policies that govern our environment. States that adopted progressive public health strategies, like anti-smoking laws or Medicaid expansion, reaped the benefits in population longevity. Summarizing: This century long analysis offers a sobering view of how structural inequality has shaped, and continues to shape, health outcomes across the U.S. It also provides a compelling argument for the power of early investment in public health. For policymakers, the message is clear: where we’re born still largely determines how long we live, and that could surely be changed by the proper legislation. Reference: 1. Holford, T.R., McKay, L., Tam, J., Jeon, J., and Meza, R. (2025). All-Cause Mortality and Life Expectancy by Birth Cohort Across US States. JAMA Network Open, 8(4), e257695. Retrieved from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2833159
|
AuthorWayne Persky Archives
February 2026
Categories |
Offices: 19242 Darrs Creek Rd, Bartlett, Texas 76511-4460
RSS Feed 
