A fundamental goal of physics is to explain the broadest range of phenomena with the fewest underlying principles. Remarkably, seemingly disparate problems often exhibit identical mathematical descriptions. For instance, the rate of heat flow can be modeled using an equation very similar to that governing the speed of particle diffusion. Another example involves wave equations, which apply to the behavior of both water and sound. Scientists continuously seek such connections, which are rooted in the principle of the “universality” of underlying physical mechanisms.

In a study published in the journal Royal Society Open Science, researchers from Osaka University uncovered an unexpected connection between the equations for defects in a crystalline lattice and a well-known formula from electromagnetism. They demonstrated that the fields representing the strain generated around lattice dislocations in crystalline materials, modeled by Cartan’s First Structure Equation, obey the same equations as the more familiar Biot-Savart law. The former can be quite complex and challenging to visualize, while the latter describes how electric currents generate magnetic fields, and is essential for understanding numerous modern devices, including electric motors.

“Searching for Universality relationships can be valuable in emerging scientific fields, especially when the governing equations are newly established, and the nature of their solutions remains elusive,” explains lead author of the study Shunsuke Kobayashi. The Biot-Savart law states that an electrical current flowing through a wire will generate a magnetic field around itself represented by vectors that twist around like a vortex. Similarly, the effect of certain types of atomic dislocation in a crystalline lattice will induce a strain vector field on the surrounding atoms.

Using the analogous Biot-Savart law from electromagnetism, it will be possible to analytically determine the effect of dislocations, instead of the more arcane Cartan Structure Equations. “This discovery is expected to serve as a fundamental theory for describing the plastic deformation of crystalline materials, opening the way for a wide range of applications in material science,” senior author Ryuichi Tarumi says. The researchers also believe that finding these kinds of connections across areas of study can spur new discoveries.

Dr. Bruce Montgomery, a UW Medicine oncologist, hopes that patients won’t see these numbers and just throw up their hands in fear or resignation.

“Being diagnosed with prostate cancer is not a death knell,” said Montgomery, senior author of a literature and trial review that appeared in JAMA today. Montgomery is the clinical director of Genitourinary Oncology at Fred Hutch Cancer Center and University of Washington Medical Center, and a professor of medicine and urology at the UW School of Medicine.

He encourages patients to ask their primary-care doctor specific questions about this cancer too. Montgomery also encourages his fellow doctors to bring up the question of prostate cancer screening with their patients.

“Knowing whether there is prostate cancer and how risky it is can be the first step. Not every cancer needs to be treated,” he said. “Sometimes it’s safe to just watch and use active surveillance.”

A 2024 study coauthored by UW Medicine urologist Dr. Daniel Lin showed that active surveillance can be extremely safe: 0.1% of men who opted for surveillance died of prostate cancer after 10 years.

“We need to realize that prostate cancer is not one disease,” Montgomery said. “As a provider, you need to personalize your approach to the patient you’re seeing and to the disease that they personally are dealing with.”

For example, if a 50-year-old man develops prostate cancer that is only in the prostate, then more aggressive measures may need to be considered. However, if the disease, which can be slow-moving, develops in an 80-year-old patient, the discussion may be quite different.

“I’ve seen men that age (80s) develop prostate cancer and they’ve opted for no therapy,” he said. “They know that treatment, such as radiation, might make them feel terrible … so they just say ‘no.’

You, as their physician, he noted, must respect that.

“But if you’re 50 and have 25 to 30 years in which prostate cancer can become a bigger issue, even with the downsides, most patients should get therapy,” he said.

For more advanced prostate cancer, the number of effective treatments developed has markedly increased, as has the survival rate of men with whose prostate cancer has spread to other parts of their bodies.

“Metastatic prostate cancer needs therapy and research over the past 10 to 20 years has improved and continues to improve survival substantially,” he said. “Knowing who needs treatment, which treatment to use and when is both an art and a science.”

The article covered facts that men and their doctors should know, including:

• Approximately 1.5 million new cases of prostate cancer are diagnosed annually worldwide. Approximately 75% of cases are first detected when the cancer is still localized to the prostate. This early detection was associated with a five-year survival rate of nearly 100%.
• Management includes active surveillance, prostatectomy surgical removal of the prostate, or radiation therapy, depending on risk of progression.
• Approximately 10% of cases are diagnosed after the cancer has spread. This stage of prostate cancer has a five-year survival rate of 37%.
• The most common prostate cancer is adenocarcinoma, a type that starts in gland cells, and the median age at diagnosis is 67 years.
• More than 50% of prostate cancer risk is attributable to genetic factors and older age.

Prostate cancer came to public attention, both nationally and internationally last year, when famed local travel writer, Rick Steves, announced he had developed prostate cancer. He proclaimed last month via his X account, formerly Twitter, that after radiation and surgery at UW Medicine and Fred Hutch, he was cancer free.

The study, published in Psychoneuroendocrinology, is the first to examine weekly stress across 27 weeks of pregnancy to pinpoint when it most affects a newborn’s stress response and temperament — two measures that indicate infant biobehavioral reactivity.

“Prenatal stress has a well-established link to negative health, including mental health, outcomes in children and adults, but most studies conclude that the biggest effects are on girls. Our study found that not to be the case. It’s in fact, just different timing,” said Alytia Levendosky, lead investigator of the study and professor in MSU’s Department of Psychology.

The researchers recruited 396 pregnant women, specifically from a high stress-risk population due to low income and/or exposure to intimate partner violence. Weekly stress assessments were conducted via email or text from week 15 through week 41 of pregnancy. At six months postpartum, infant cortisol levels were collected before and after a mildly stressful laboratory task to see how their hypothalamic-pituitary-adrenal system, or HPA axis, responded to stress. Mothers also reported on infant temperament.

The study found periods of higher sensitivity to stress in both mid and late gestation but found that girls and boys had differing patterns of sensitivity. The data showed that experiencing stress in mid-gestation affected girls’ HPA axis and temperament, while late gestation stress impacted boys. Previous studies in this field stopped their last stress assessment between 32-34 weeks. Because this study ran through week 41, Levendosky and her team were able to locate the time that was most sensitive for boys.

“This study is an essential step in correcting our understanding around prenatal stress effects for boys and girls,” said Joseph Lonstein, investigator on the study and professor in MSU’s Department of Psychology. “We hope that our findings inspire additional research so we can better understand what is happening in fetal brain development across pregnancy and how it is affected by stress.”

Current funding allows the team of researchers to continue following these participants until the age of four — with assessments at 2.5 years old and again at 4 years old. Amy Nuttall, co-author of this study and associate professor in the Department of Human Development and Family Studies at MSU, hopes to continue the study through even later childhood.

A total of six participants will be included in the Phase 1 trial that will track the patients for 12 months and beyond to determine the safety of the procedure and monitor for any improvements in Parkinson’s disease. Following the first 6 patients transplanted in the Phase 1 study, the researchers hope to expand and recruit more patients as part of Phase 2A study.

This novel therapeutic approach for treating Parkinson’s disease incorporates the use of stem cells derived from a patient’s own blood that had been converted into induced pluripotent stem cells (iPSCs). These cells are then reprogrammed to turn into specific midbrain dopaminergic neurons ready for transplantation. The autologous transplantation approach of using a person’s own cells circumvents the requirement for immunosuppressive treatments, which are necessary when cells from other donors are used.

Cell replacement for Parkinson’s disease replaces the dopamine neurons lost to degeneration and can restore dopaminergic function in the brain, providing a completely new treatment modality compared to the currently available treatments. The NRI’s founding director, Ole Isacson, Dr Med Sci, who is also a professor of neurology (neuroscience) at Harvard Medical School and Mass General Brigham, has pioneered work in cell therapy for Parkinson’s disease over the past 30 years and laid the foundation for this clinical trial.

“Seeing this transformational new patient cell-based replacement of their own dopamine neurons come to fruition — from the very basic science breakthroughs in our lab to be completely translated into a clinical application for patient’s suffering from Parkinson’s disease — is very gratifying,” said Isacson. “We believe this approach may open up a new treatment paradigm and lead to the development of many additional cell therapies to restore damaged brain systems and replace degenerated brain cells in other diseases.”

Under Isacson’s leadership, the NRI at McLean has developed and patented autologous cell-based restoration in Parkinson’s disease with a pioneering preclinical publication in 2002 using stem cells and the first preclinical demonstration of effective human iPS cell-derived dopamine neuron use in 2010. In 2015, the NRI team, led by Isacson and Penny Hallett, PhD, co-director of the NRI at McLean and associate professor of psychiatry at Harvard Medical School, provided the first evidence of long-term safety and benefits of autologous stem cell therapy in a highly relevant Parkinson’s disease non-human primate animal model.

The NRI received official authorization from the U.S. Food and Drug Administration (FDA) on August 23, 2023, approving its Investigational New Drug (IND) application for a phase 1 clinical trial to test this unique, autologous dopamine neuron cell therapy.

Following this FDA approval for the phase 1 clinical trial, the NRI’s innovative preclinical work was translated into the clinic with the first patient treated on September 9, 2024. This collaboration includes NRI investigators James Schumacher, MD, and Oliver Cooper, PhD, and colleagues in the Neurology (Michael Hayes, MD) and Neurosurgery (John Rolston, MD, PhD, principal investigator of the Phase 1 trial) Departments at Brigham and Women’s Hospital. Isacson is not directly involved in the clinical trial because he is the innovator patent holder of the technology and also a co-founder of Oryon Cell Therapies, which has the license to this technology. The trial is directed by Hallett and colleagues within the Mass General Brigham healthcare system and its Harvard Medical School-affiliated institutions.

“It is extraordinary to witness that investigators at our institution can bring new treatments to patients through the entire process of laboratory “bench to bedside,” and it inspires many investigators to similarly pursue their scientific and medical insights to reach patients in need,” said Kerry Ressler MD, PhD, chief scientific officer at McLean Hospital.

The Phase 1 open-label clinical trial will be the first such trial to test blood-derived autologous iPSC-derived dopamine neurons in patients with Parkinson’s disease and is funded by the National Institute of Health’s National Institute of Neurological Disorders and Stroke (NINDS). The NINDS awarded the highly competitive Cooperative Research to Enable and Advance Translational Enterprises for Biologics (CREATE Bio) grant for this work in 2020.

People seeking more information in the trial can email: @bwh.harvard.edu” title=”mailto:neurosurgerycrc@bwh.harvard.edu”>neurosurgerycrc@bwh.harvard.edu

For More Information:

• McLean Hospital Receives Coveted NIH Grant to Clinically Study Autologous Stem Cell Therapy for Parkinson’s Disease
• Patient-derived stem cells could improve drug research for Parkinson’s

Funding: The study was supported by a NINDS CREATE Bio grant (U01NS109463).

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Disclosure:Isacson has co-founded a company (Oryon Cell Therapies) which has licensed the patents and know-how for developing autologous cell therapies for Parkinson’s disease. Isacson’s interests were reviewed and are managed by McLean Hospital and Mass General Brigham in accordance with their conflict of interest polices.

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About Mass General Brigham

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