Publisher Health

A beloved radio and television host, first in Canada and then also in the U.S., she approached the hottest topic with compassion and humor.Sue Johanson, the blunt, bawdy and beloved Canadian sex educator and host of the long-running television call-in program “Sunday Night Sex Show” and its American counterpart, “Talk Sex With Sue Johanson,” died on June 28 at a care facility in North Toronto. She was 92.Her death was confirmed by her daughter Jane Johanson.She dressed demurely, often in blazers and wire-rimmed glasses, but Ms. Johanson had a comedian’s timing and instincts, which defused the hot-button topics she addressed. (A condom evangelist, she had a way of stretching them out in demonstrations that recalled a clown making balloon animals.) And like Dr. Ruth Westheimer, the Holocaust survivor and onetime Israeli sniper turned sex therapist, Ms. Johanson, a registered nurse and mother of three who had run a birth control clinic in a public high school for nearly two decades, became a media star in midlife.“I wasn’t young,” Ms. Johanson said in “Sex With Sue,” a 2022 documentary about her directed by Lisa Rideout, with Jane as her mother’s interlocutor and the film’s creative consultant. “I wasn’t beautiful. I didn’t have bodacious tatas. I was a mother with a load of information.”Is it weird to put body glitter on your boyfriend’s testicles? Is it safe to have sex in a hot tub? Could a Ziploc baggie serve as a condom? If condoms are left in a car and they freeze, are they still good? Answers: No. No (chlorinated water is too harsh for genitals, particularly women’s). Definitely not. And yes, once they’ve been defrosted.Every Sunday night, the questions poured in about straight sex, gay sex and masturbation, along with those detailing all manner of fetishes, fantasies and fears. At the show’s peak in the early 2000s, nearly 100,000 calls were fielded and screened by operators, though only 10 or 12 made it on the air.Manufacturers of sex toys sent their wares by the boxload. Ms. Johanson would divvy them up among her young crew for road tests — “The Unofficial Sex Toy Testing Facility of Canada,” she called them — and demonstrate their features at her desk, reaching into her “hot stuff” bag, a black tote emblazoned with flames, to pull out the latest offerings. “The good, the bad and the ugly,” she liked to say. (Makers tended to gild the lily, like the company that made a vibrator with a camera at its tip. “It gives a whole new meaning to, ‘I’m ready for my close-up,’” Ms. Johanson deadpanned.)A child of the Great Depression, she was thrifty and cost-conscious, and she often presented homemade alternatives. Why not turn your cellphone ringer to vibrate, tuck it in your underpants and have your friends call nonstop?“I remember her giving a hand job to a cucumber,” Russell Peters, the Canadian comedian, said in the documentary. “I never looked at a cucumber the same.”Ms. Johanson in 1995. “I wasn’t young. I wasn’t beautiful,” she once said of her appeal. “I was a mother with a load of information.”Ron Bull/Toronto Star, via Getty ImagesMs. Johanson started her broadcasting career in radio, with a wildly popular show on a rock station that ran for more than a decade. “Sunday Night Sex Show” first aired on Canadian television in 1996. In 2002, the Oxygen network commissioned an American version, which ran right after the Canadian show, so American callers could have their shot. The U.S. audience was shyer and more naïve than her Canadian viewers, Ms. Johanson told Mireya Navarro of The New York Times in 2004; they seemed to lack basic knowledge. Many young female callers wondered if they could get pregnant from oral sex.“Ms. Johanson said she could not ride the subway or stand in a grocery line in Canada without being approached to answer the kind of question that would make even the frozen chicken blush,” Ms. Navarro wrote. “But in the United States, a much bigger market, her growing fan base seems almost bashful but mostly grateful. ‘I find that Americans are so polite and so respectful that being recognized is wonderful,’ she said. ‘People will look at me and say, ‘Hi, I love your show.’ And that’s where it ends.”She was, however, feted on the American talk-show circuit, appearing with Jay Leno, Ellen DeGeneres, David Letterman and Conan O’Brien, whom she terrified with the contents of her hot-stuff bag, which that night included a vibrating rubber duck, a dildo she strapped to her chin and a handmade, hand-operated vibrator she had fashioned from a tin can fitted with Bubble Wrap and a tube sock.“You’re like a perverted MacGyver,” Mr. O’Brien said, horrified.“I regard sex as a gift from God,” Ms. Johanson told Ms. Navarro. “We’re the only ones that really are able to enjoy sex, so we have an obligation to learn about it and enjoy it.”Susan Avis Bailey Powell was born on July 29, 1930, in Toronto. Her mother, Ethel (Bell) Powell, was a homemaker. Her father, Wilfred Bailey Powell, was in the Royal Canadian Air Force and had a number of jobs. Her mother died when she was 10, and she was raised mostly by an aunt.She met Ejnor Karl Johanson, an electrical inspector, on a blind date just before she entered nursing school at the St. Boniface Hospital in Winnipeg; they married in the early 1950s and moved to Toronto to take over her aunt’s real estate business.Ms. Johanson opened her birth control clinic in 1970, after her eldest daughter’s friend became pregnant in high school and had an abortion, which was at the time mostly illegal in Canada. “Kids get involved with sex without their parents’ consent,” she told a reporter in 1983, “and therefore they should be able to get contraceptives without their consent.”Throughout her career, high school and college students were her biggest concern. She was an indefatigable speaker, a regular at college freshman orientations each fall and at hundreds of high schools each year. Her husband, Jane Johanson said, was a reserved, private man, the opposite of his gregarious wife, but he handled her career and fame with grace, and “took it like a champ.” He died in 2014.In addition to her daughter Jane, Ms. Johanson is survived by another daughter, Carol Howard; two grandchildren; and one great-grandchild. Her son, Eric, died in 2021.Ms. Johanson also wrote a magazine column and was the author of three books: “Sex, Sex and More Sex,” “Sex Is Perfectly Natural but Not Naturally Perfect” and “Talk Sex: Answers to Questions You Can’t Ask Your Parents.”In 2000, she was awarded the Order of Canada, the country’s highest honor for pioneers in their field.Ms. Johanson’s Canadian show went off the air in 2005, and the American version in 2008. It was time: The internet had become the go-to source for sex inquiries. As Dan Savage, the sex columnist, put it in the documentary about Ms. Johanson, there was a Wikipedia page for every piece of equipment and every sex act, and Ms. Johanson felt she was unable to keep up with the times. At 77, she was ready but sad to call it quits.“There will be a great big hole in my heart,” she said as she introduced her final episode in May 2008, her voice breaking.“I love doing this show.”She added, “I’ll close with the same condom quickie that we ended the first show with 174 episodes ago: Sex will be sweeter, if you wrap your peter.”

A study led by Nagoya University in Japan has identified three previously unknown membrane proteins in ovarian cancer. Using a unique technology consisting of nanowires with a polyketone coating, the group succeeded in capturing the proteins, demonstrating a new detection method for identification of ovarian cancer.
The discovery of new biomarkers is important for detecting ovarian cancer, as the disease is difficult to detect in its early stages where it can most easily be treated. One approach to detecting cancer is to look for extracellular vesicles (EVs), especially small proteins released from the tumor called exosomes. As these proteins are found outside the cancer cell, they can be isolated from body fluids, such as blood, urine, and saliva. However, the use of these biomarkers is hindered by the lack of reliable ones for the detection of ovarian cancer.
A research group led by Akira Yokoi (he, him) of the Nagoya University Graduate School of Medicine and Mayu Ukai (she, her) at the Institute for Advanced Research extracted both small and medium/large EVs from high-grade serous carcinoma (HGSC), the most common type of ovarian cancer, and analyzed them using liquid chromatography-mass spectrometry to analyze the proteins.
Initially their research was challenging. “The validation steps for the identified proteins were tough because we had to try a lot of antibodies before we found a good target,” said Yokoi. “As a result, it became clear that the small and medium/large EVs are loaded with clearly different molecules. Further investigation revealed that small EVs are more suitable biomarkers than the medium and large type. We identified the membrane proteins FRα, Claudin-3, and TACSTD2 in the small EVs associated with HGSC.”
Now that the group had identified the proteins, they investigated whether they could capture EVs in a way that would allow for the identification of the presence of cancer. To do this, they turned to nanowire specialist Takao Yasui of the Graduate School of Engineering at Nagoya University who combined his research with that of Dr. Inokuma at the Japan Science and Technology Agency to create polyketone chain-coated nanowires (pNWs). This technology was ideal for separating exosomes from blood samples.
“pNW creation was tough,” Yokoi said. “We must have tried 3-4 different coatings on the nanowires. Although polyketones are a completely new material to use to coat this type of nanowire, in the end, they were such a good fit.”
“Our findings showed that each of the three identified proteins is useful as a biomarker for HGSCs,” said Yokoi. “The results of this research suggest that these diagnostic biomarkers can be used as predictive markers for specific therapies. Our results allow doctors to optimize their therapeutic strategy for ovarian cancer, therefore, they may be useful for realizing personalized medicine.”

Cancer cells-to-be accumulate a series of specific genetic changes in a predictable and sequential way years before they are identifiable as pre-malignancies, researchers at Stanford Medicine have found. Many of these changes affect pathways that control cell division, structure and internal messaging — leaving the cells poised to go bad long before any visible signs or symptoms occur.
The study is the first to exhaustively observe the natural evolution of the earliest stages of human cancers, starting with cells that have a single cancer-priming mutation and culminating with a panel of descendants harboring a galaxy of genetic abnormalities.
Identifying the first steps associated with future cancer development could not only facilitate earlier-than-ever diagnosis — when a deadly outcome is but a twinkle in a rogue cell’s eye — but may also highlight novel interventions that could stop the disease in its tracks, the researchers say.
“Ideally, we would find ways to intercept this progression before the cells become truly cancerous,” said Christina Curtis, PhD, professor of medicine, of genetics and of biomedical data science. “Can we identify a minimal constellation of genetic alterations that imply the cell will progress? And, if so, can we intervene? The striking reproducibility in the genetic changes we observed from multiple donors suggests it’s possible.”
Curtis is the senior author of the research, which was published on May 31 in Nature. The lead authors of the study are former postdoctoral scholar Kasper Karlsson, PhD, and visiting graduate student Moritz Przybilla.
Cells of nefarious beginnings
The research builds on previous work in Curtis’s laboratory indicating that some colon cancer cells are seemingly born to be bad — they acquire the ability to metastasize long before the disease is detectable.

“Our studies of established tumors showed us that early genomic alterations seem to dictate what happens later, and that many of these changes seem to happen before tumor formation,” Curtis said. “We wanted to know what happens at the very earliest stages. How does a cancer cell evolve, and is this evolutionary path repeatable? If we start with a given set of conditions, will we get the same result in every case?”
The researchers studied tiny, three-dimensional clumps of human stomach cells called gastric organoids. The cells were obtained from patients undergoing gastric bypass surgery to treat obesity. At the beginning of the study, the researchers nudged the cells toward cancers by disabling the production of a key cancer-associated protein called p53 that regulates when and how often a cell divides. Mutations in p53 are known to be an early event in many human cancers, and they trigger the accumulation of additional genetic changes including mutations and copy number alterations — in which repetitive regions of the genome are lost or gained during cell division.
Then they waited.
Every two weeks, for two years, Karlsson cataloged the genetic changes occurring in the dividing cells. When Karlsson and Przybilla analyzed the data they found that, although changes occurred randomly, those that conferred greater fitness gave their host cells an evolutionary advantage over other cells in the organoid. As the cells continued to divide and the cycle of mutation and competition repeated over many iterations, the researchers saw some common themes.
Predictable pathways
“There are reproducible patterns,” Curtis said. “Certain regions of the genome are consistently lost very early after the initial inactivation of p53. This was repeatedly seen in cells from independent experiments with the same donor and across donors. This indicates that these changes are cell-intrinsic, that they are hardwired into tumor evolution. At the same time, these cells and organoids appear mostly normal under the microscope. They have not yet progressed to a cancer.”

The researchers found that these early changes usually occur in biological pathways that control when and how often a cell divides, that interfere with a cell’s intricate internal signaling network coordinating the thousands of steps necessary to keep it running smoothly, or that control cell structure and polarity — its ability to know what is “up” and “down” and to situate itself with respect to neighboring cells to form a functioning tissue.
The researchers saw similar patterns occur again and again in cells from different donors. Like water flowing downhill into dry creek beds, the cells traced tried-and-true paths, gaining momentum with each new genetic change. Several of these changes mirror mutations previously observed in stomach cancer and in Barrett’s esophagus, a pre-cancerous condition arising from cells that line the colon and stomach.
“These changes occur in a stereotyped manner that suggest constraints in the system,” Curtis said. “There’s a degree of predictability at the genomic level and even more so at the transcriptomic level — in the biological pathways that are affected — that gives insights into how these cancers arise.”
Curtis and her colleagues plan to repeat the study in different cell types and initiating events other than p53 mutation.
“We’re trying to understand exactly what malignant transformation is,” Curtis said. “What does it mean to catch these cells in the act, about to topple over the edge? We’d like to repeat this study with other tissue types and initiating mutations so we can understand the early genetic events that occur in different organs. And we’d like to study the interplay between the host and the environment. Do inflammatory factors play a role in promoting progression? We know that it matters that the cells in these organoids are communicating with each other, and that is important to understanding progression and treatment response.”
Researchers from Karolinska Institutet, the University College London and the Chan Zuckerberg Biohub also contributed to the study.
The research was supported by the National Institutes of Health (grants DP1-CA238296 and U01-CA217851) and the Swedish Research Council.

Researchers have known that a lack of quality sleep can increase a person’s risk of diabetes. What has remained a mystery, however, is why.
Now, new findings from a team of sleep scientists at the University of California, Berkeley, are closer to an answer. The researchers have uncovered a potential mechanism in humans that explains how and why deep-sleep brain waves at night are able to regulate the body’s sensitivity to insulin, which in turn improves blood sugar control the next day.
“These synchronized brain waves act like a finger that flicks the first domino to start an associated chain reaction from the brain, down to the heart, and then out to alter the body’s regulation of blood sugar,” said Matthew Walker, a UC Berkeley professor of neuroscience and psychology and senior author of the new study. “In particular, the combination of two brain waves, called sleep spindles and slow waves, predict an increase in the body’s sensitivity to the hormone called insulin, which consequentially and beneficially lowers blood glucose levels.”
The researchers say this is an exciting advance because sleep is a modifiable lifestyle factor that could now be used as part of a therapeutic and painless adjunct treatment for those with high blood sugar or Type 2 diabetes.
Scientists also noted an additional benefit besides the potential new mechanistic pathway.
“Beyond revealing a new mechanism, our results also show that these deep-sleep brain waves could be used as a sensitive marker of someone’s next-day blood sugar levels, more so than traditional sleep metrics,” said Vyoma D. Shah, a researcher at Walker’s Center for Human Sleep Science and co-author of the study. “Adding to the therapeutic relevance of this new discovery, the findings also suggest a novel, non-invasive tool — deep-sleep brain waves — for mapping and predicting someone’s blood sugar control.”
The team’s findings were published today in the journal Cell Reports Medicine.

For years, researchers have studied how the coupling of non-rapid eye movement sleep spindles and deep, slow brain waves corresponded to an entirely different function — that of learning and memory. Indeed, the same team of UC Berkeley researchers previously found that deep-sleep brain waves improved the ability of the hippocampus — the part of the brain associated with learning — to retain information.
But this new research builds on a 2021 rodent study and reveals a novel and previously unrecognized role for these combined brain waves in humans when it comes to the critical bodily function of blood sugar management.
The UC Berkeley researchers first examined sleep data in a group of 600 individuals. They found that this particular coupled set of deep-sleep brain waves predicted next-day glucose control, even after controlling for other factors such as age, gender and the duration and quality of sleep.
“This particular coupling of deep-sleep brain waves was more predictive of glucose than an individual’s sleep duration or sleep efficiency,” said Raphael Vallat, a UC Berkeley postdoctoral fellow and co-author of the study. “That indicates there is something uniquely special about the electrophysiological quality and coordinated ballet of these brain oscillations during deep sleep.”
Next, the team then set out to explore the descending pathway that might explain the connection between these deep-sleep brain waves sending a signal down into the body, ultimately predicting the regulation of blood glucose.

The findings from the team reveal an unfolding set of steps that could help explain how and why these deep-sleep brain waves are related to superior blood sugar control. First, they found that stronger and more frequent coupling of the deep-sleep brain waves predicted a switch in the body’s nervous system state into the more quiescent and calming branch, called the parasympathetic nervous system. They measured that change in the body and the shift to this low-stress state using heart rate variability as a proxy.
Next, the team turned its attention to the final step of blood sugar balance.
The researchers further discovered that this deep sleep switch to the calming branch of the nervous system further predicted an increased sensitivity of the body to the glucose-regulating hormone called insulin, which instructs cells to absorb glucose from the bloodstream, preventing a deleterious blood sugar spike.
That’s particularly important for people trying to back away from hyperglycemia and Type 2 diabetes.
“In the electrical static of sleep at night, there is a series of connected associations, such that deep-sleep brain waves telegraph a recalibration and calming of your nervous system the following day,” Walker said. “This rather marvelous associated soothing effect on your nervous system is then associated with a reboot of your body’s sensitivity to insulin, resulting in a more effective control of blood sugar the next day.”
The researchers subsequently replicated the same effects by examining a separate group of 1,900 participants.
“Once we replicated the findings in a different cohort, I think we actually started to feel more confident in the results ourselves,” Walker said. “But I’ll wait for others to replicate it before I truly start believing, such is my British skepticism.”
The scientists said the research is particularly exciting given the potential clinical significance years down the line. Diabetes treatments already on the market can sometimes be difficult for patients to adhere to. The same is true of the recommended lifestyle changes, including different eating habits and regular exercise.
Sleep, however, is a largely painless experience for most people.
And while sleep is not going to be the single magic bullet, the prospect of new technologies that can safely alter brain waves during deep sleep that this new research has uncovered may help people better manage their blood sugar. That, the research team said, is reason for hope.

A novel molecular pathway to explain how a mutation in the gene ACTA2 can cause individuals in their 30s — with normal cholesterol levels and no other risk factors — to develop coronary artery disease has been identified, according to researchers with UTHealth Houston.
The study was published in the European Heart Journal.
“The gene ACTA2 codes a specific protein that has nothing to do with cholesterol,” said Dianna Milewicz, MD, PhD, senior author of the study and professor and director of the Division of Medical Genetics at McGovern Medical School at UTHealth Houston. “It was a surprise to find that people with the gene mutation had too much atherosclerosis at a young age and with no risk factors.”
A 2009 study led by Milewicz found that a number of mutations in ACTA2 predispose humans to develop early onset (30s or younger) coronary artery disease.
Atherosclerosis is a buildup of fats, cholesterol, and other substances in and on the artery walls. It can develop over time and most people don’t know they have it until they suffer a heart attack or stroke. Traditional risk factors for developing atherosclerosis include high cholesterol, high blood pressure, diabetes, smoking, obesity, lack of exercise, and consuming a high-fat diet.
ACTA2 is typically found in the smooth muscle cells, which line the arteries and allow the arteries to contract to control blood pressure and flow. Milewicz and her team found that protein coded by this gene is not folded correctly because of the mutation, and it triggers stress in the smooth muscle cell, which then forces the cell to make more cholesterol internally, regardless of the levels of cholesterol in the blood, driving atherosclerotic plaque formation.

“This finding is unique in that we found a completely new pathway to atherosclerosis. It explains why for years we have known statins protect people from heart attacks, even those people whose blood cholesterol levels are normal. In the people with ACTA2 mutations, the statins block the cholesterol made by the stressed smooth muscle cells,” said Milewicz, the President George Bush Chair in Cardiovascular Medicine with McGovern Medical School. “In our study, the mutant protein made by the ACTA2 mutation caused the cells in the artery wall to be stressed, but there are many other factors that can stress cells. We are now working on the risk factors for coronary artery disease, like hypertension, that would also stress the cells and activate this novel pathway for coronary artery disease.”
One of the results of stress in smooth muscle cells associated with atherosclerosis is the deposition of calcium in the arteries.
“Cardiac calcium imaging in individuals with ACTA2 mutations could be a useful early diagnostic tool to monitor the development of the early atherosclerosis in these people. This would allow physicians to decide at what age to start these patients on statins,” Milewicz said.
Using a genetically engineered mouse that contains a particular ACTA2 mutation and feeding the mice a diet rich in cholesterol, the researchers induced atherosclerosis and found that these mice have much more atherosclerosis than similarly treated mice normal mice. The study also found that the increased atherosclerosis could be reversed by treating the mice with pravastatin, a member of the statin group of drugs commonly prescribed to lower blood cholesterol. The researchers confirmed that same molecular pathway is activated in smooth muscles cells isolated from a human patient with an ACTA2 mutation.
Statins prevent coronary artery disease by lowering the levels of cholesterol in the blood. At the same time, more than half of heart attacks occur in apparently healthy men and women with average or low levels of plasma LDL-cholesterol. Statins also reduce heart attack events in people with normal cholesterol levels.
This work was supported by the National Heart, Lung, and Blood Institute (RO1 HL146583); an America Heart Association Merit Award, NIH T32GM120011; Marfan Foundation McKusick Fellowship Award; and American Heart Association Grant 20CDA35310689. Lipid profile analysis was performed at the Mouse Metabolism and Phenotypic Core at Baylor College of Medicine, funded by NIH RO1DK114356 and UM1HG006348. Single cell RNA sequencing was performed at the Single Cell Genomics Core at Baylor College of Medicine, funded by National Institutes of Health shared instrument grants S10OD023469, S10OD025240 and P30EY002520.
Additional UTHealth Houston authors include Kaveeta Kaw, MD, PhD; Abhijnan Chattopadhyay, PhD; Pujun Guan, MM; Jiyuan Chen, PhD; Suravi Majumder, PhD; Xue-yan Duan, PhD, and Callie S. Kwartler, PhD. Other authors include Shuangtao Ma, MD, MSc, with Michigan State University College of Human Medicine (a former postdoctoral fellow at UTHealth Houston) and Chen Zhang, MD, with Baylor College of Medicine.

The prevalence of moderate or severe joint pain due to arthritis varies strikingly across American states, ranging from 6.9% of the population in Minnesota to 23.1% in West Virginia, according to a new study led by a University at Buffalo researcher.
The paper published in the journal PAIN is providing new insights — through its novel combination of individual- and macro-level measures — into geographic differences in pain and their causes.
“The risk of joint pain is over three times higher in some states compared to others, with states in the South, especially the lower Mississippi Valley and southern Appalachia, having particularly high prevalence of joint pain,” says Rui Huang, a sociology PhD student in the UB College of Arts and Sciences, and the paper’s first author. “We also observed educational disparities in joint pain in all states that vary substantially in magnitude, even after adjusting for demographic characteristics.”
The percentage point difference in pain prevalence between people who did not complete high school versus those who obtained at least a bachelor’s degree is much larger in West Virginia (31.1), Arkansas (29.7), and Alabama (28.3) than in California (8.8), Nevada (9.8) and Utah (10.1).
“Education can function as a ‘personal firewall’ that protects more highly educated people from undesirable state-level contexts, while increasing the vulnerability of less educated individuals,” says Huang.
Nearly 59 million people in the U.S. have arthritis, and at least 15 million of them experience severe joint pain because of that condition. Severe joint pain is associated with diminished range of motion, disability and mortality.

While existing research on the social determinants of pain has relied primarily on individual-level data, individuals are embedded in social contexts, such as a specific U.S. state.
Different states can have dramatically different policies that affect many aspects of life including opportunities, resources and social relationships, which can in turn influence individuals’ pain, a potential influence that has gone largely unexplored in previous research.
“Very little research has examined the geography of chronic pain, and virtually none has examined the role of state-level policies in shaping pain prevalence,” says Hanna Grol-Prokopczyk, PhD, UB associate professor of sociology, and a co-author of the study. “We were excited to identify state characteristics that reduce residents’ risk of pain.”
The current study does so by combining data on nearly 408,000 adults (ages 25-80) from the 2017 Behavioral Risk Factor Surveillance System with state-level data about SNAP programs (formerly known as food stamps), Earned Income Tax Credits, income inequality, social cohesion (relationship strength among community members), Medicaid Generosity Scores, and tobacco taxes.
Although SNAP programs exist in all 50 states, some states offer more expansive benefits to qualifying residents than others. States with more generous SNAP benefits had a lower prevalence of pain. The same was true for states with greater social cohesion, indicating that both material resources and social functioning play critical roles in shaping pain risk.
“The increase in the generosity of SNAP benefits could potentially alleviate pain by promoting healthier eating habits and alleviating the life stress associated with food insecurity,” says Huang. “Social factors such as conflict, isolation and devaluation are also among the ‘social threats’ that can lead to physical reactions such as inflammation and immune system changes.”
In addition to providing new information on pain disparities across states, the paper might also fuel a reorientation of pain research that puts equal emphasis on macro- and individual-level factors, according to Huang.
“Chronic pain can — and should — be addressed through macro-level policies, as well as through individual-level interventions,” says Huang. “This study also implies that pain research in general should move towards a greater understanding of the macro contextual factors that shape pain and pain inequalities.”

In a world-first clinical trial published in the journal Nature Medicine, a multi-centre study from Lawson Health Research Institute, the Centre hospitalier de l’Université de Montréal (CHUM) and the Jewish General Hospital (JGH) has found fecal microbiota transplants (FMT) from healthy donors are safe and show promise in improving response to immunotherapy in patients with advanced melanoma.
Immunotherapy drugs stimulate a person’s immune system to attack and destroy cancer. While they can significantly improve survival outcomes in those with melanoma, they are only effective in 40 to 50 per cent of patients. Preliminary research has suggested that the human microbiome — the diverse collection of microbes in our body — may play a role in whether or not a patient responds.
“In this study, we aimed to improve melanoma patients’ response to immunotherapy by improving the health of their microbiome through fecal transplants,” says Dr. John Lenehan, Medical Oncologist at London Health Sciences Centre’s (LHSC) London Regional Cancer Program (LRCP), Associate Scientist at Lawson and Associate Professor in the Department of Oncology at Western University’s Schulich School of Medicine & Dentistry.
A fecal transplant involves collecting stool from a healthy donor, screening and preparing it in a lab, and transplanting it to the patient. The goal is to transplant the donor’s microbiome so that healthy bacteria will prosper in the patient’s gut.
“The connection between the microbiome, the immune system and cancer treatment is a growing field in science,” explains Dr. Saman Maleki, Scientist at Lawson and LHSC’s LRCP, Assistant Professor in Schulich Medicine’s Departments of Oncology, Pathology and Laboratory Medicine, and Medical Biophysics, and senior investigator on the study. “This study aimed to harness microbes to improve outcomes for patients with melanoma.”
The phase I trial included 20 melanoma patients recruited from LHSC, CHUM and Jewish General Hospital. Patients were administered approximately 40 fecal transplant capsules orally during a single session, one week before they started immunotherapy treatment.

The study found that combining fecal transplants with immunotherapy is safe for patients — which is the primary objective of a phase I trial (also called ‘safety trials’). The study also found 65 per cent of patients who retained the donors’ microbiome had a clinical response to the combination treatment. Five patients experienced adverse events sometimes associated with immunotherapy and had their treatment discontinued.
“We have reached a plateau in treating melanoma with immunotherapy, but the microbiome has the potential to be a paradigm shift,” says Dr. Bertrand Routy, Oncologist and Director of CHUM’s Microbiome Center. “This study puts Canada at the forefront of microbiome research by showing we can safely improve patients’ response to immunotherapy through fecal transplants.”
“These exciting results add to a rapidly growing list of publications suggesting that targeting the microbiome may provide a major advance in the use of immunotherapy for our patients with cancer,” adds Dr. Wilson H. Miller Jr. of the JGH and Professor in the Departments of Medicine and Oncology at McGill University.
The study is unique due to its administration of fecal transplants (from healthy donors) in capsule form to cancer patients — a technique pioneered in London by Dr. Michael Silverman, Lawson Scientist, Chair of Infectious Diseases at Schulich Medicine and Medical Director of the Infectious Disease Care Program at St. Joseph’s Health Care London.
“Our group has been doing fecal transplants for 20 years, initially finding success treating C. difficile infections. This has enabled us to refine our methods and provide an exceptionally high rate of the donor microbes surviving in the recipient’s gut with just a single dose,” says Dr. Silverman. “Our data suggests at least some of the success we are seeing in melanoma patients is related to the efficacy of the capsules.”
The team has already started a larger phase II trial involving centres in Ontario and Quebec. Lawson researchers are also studying the potential of fecal transplants in the treatment of other cancers, including renal cell carcinoma, pancreatic cancer and lung cancer, as well as HIV and rheumatoid arthritis.
This research is supported in part through donor funding from London Health Sciences Foundation, Western University, the Lotte and John Hecht Memorial Foundation, the JGH Foundation, Canadian Cancer Society’s Impact Grant program and The Terry Fox Foundation.

A new study shows that birth-control pills negatively impact women’s stress response.
Women have used birth-control pills since the 1960s, but researchers still do not know everything about the body’s complex reaction to the small, hormone-laden pill.
Researchers from Aarhus University and the United States have studied the stress response of 131 young women when having a blood sample taken. Some of the women were on birth-control pills, while others were not. The researchers specifically measured the levels of the stress hormone ACTH in the women’s blood.
The study showed that 15 minutes of social activity after having a blood sample taken lowers stress hormone levels in women who are not on the birth-control pill. In contrast, women who are on birth-control pills do not experience any reduction of their ACTH levels.
To avoid causing any additional stress to the test subjects, a small intravenous catheter was inserted in connection with the first blood sample. The researchers could then draw blood after the social activity without having to prick the women with a needle again.
Women played board games and sang songs together
The test subjects had an average age of 20.5 years. After having a blood sample taken, they could then participate in one of six different group activities such as playing board games, getting to know each other in a group session, singing songs together or attending a church service.

“Being with other people is one of the most effective ways of reducing stress. Our results are really important because they indicate that people who use birth-control pills do not experience the same reduced stress hormone levels in connection with social activity as people who do not use the pill,” says Michael Winterdahl. He is a visiting scholar at the Translational Neuropsychiatry Unit at the Department of Clinical Medicine and is the last author of the article.
Several competing hypotheses
The study differs from previous studies that have primarily focused on the stress hormone cortisol in extreme circumstances. In this study, the researchers measured the stress hormone ACTH, which changes significantly faster than cortisol. This makes it possible to observe and analyse rapid changes in a person’s stress response.
It has long been known that birth-control pills affect the stress response in women. However, looking at the stress hormone ACTH in connection with a social activity is a new approach.
“By studying ACTH levels, we take another step towards understanding how the brain regulates stress as ACTH acts as a neurotransmitter from the brain to the adrenal cortex, which produces cortisol. When we analyse ACTH levels, we can gain insight into the quick-response mechanism that controls the body’s reaction to stress,” says Michael Winterdahl.

Birth-control pills are known for being able to affect the hypothalamic-pituitary-adrenal (HPA) axis. As the name indicates, the stress signal travels from the hypothalamus in the brain through the pituitary gland, that releases ACTH, to the adrenal glands, that release cortisol.
The researchers still need a final explanation for why birth-control pill users do not experience the same reduction of stress hormone levels in connection with social activities as people who are not on the pill.
“There are several competing hypotheses that try to explain the lower cortisol levels in people who use birth-control pills. Our research has pushed us closer to an explanation that centres on the brain and the ACTH dynamics. The biochemistry is complex, but we are working based on the assumption that birth-control pills can suppress the body’s own production of progesterone,” says Michael Winterdahl.
Progesterone is broken down into the hormone allopregnanolone, which is involved in a wide range of calming effects and can have an influence on the stress response.
Differences between phases
The study involved women who used birth-control pills and women who didn’t. The women were at different phases of their menstrual cycle.
The study revealed that the stress response in women who do not take birth-control pills depends on where they are in their monthly cycle. The stress-reducing group activities had no effect on the ACTH levels of the women who were in the proliferative phase of their cycle — just after their period has ended and the body begins producing hormones to get ovulation started.
“Progestrone levels are very low during the proliferative phase of a natural cycle. This leads to a minimal conversion of progestrone into the hormone allopregnanolone. Since allopregnanolone is important for activating the receptors that regulate the stress response, we don’t see a reduction in ACTH levels in women with a natural cycle who have just had their period,” says Michael Winterdahl.
He points out that women are also generally more physically active during the proliferative phase, and that could be seen as an adaption in which the stress response and behaviour change in step with the cycle. In women who use birth-control pills, the stress response is ‘disconnected’, meaning it can not be adapted to a given situation.
Research still cannot explain exactly how this affects women. Additional research is therefore necessary to clarify the complex mechanisms involved in the correlation between hormone levels and the stress response.
“It’s also relevant to point out that birth-control pills aren’t just contraceptives. There are different generations of the pill, each with its own chemical structure due to the hormones used, which means the pills have different side-effect profiles. It’s therefore crucial that our experiments are reproduced with a larger and more diverse group of test subjects,” says Michael Winterdahl.

Scientists have designed an AI tool that can rapidly decode a brain tumor’s DNA to determine its molecular identity during surgery — critical information that under the current approach can take a few days and up to a few weeks.
Knowing a tumor’s molecular type enables neurosurgeons to make decisions such as how much brain tissue to remove and whether to place tumor-killing drugs directly into the brain — while the patient is still on the operating table.
A report on the work, led by Harvard Medical School researchers, is published July 7 in the journal Med.
Accurate molecular diagnosis — which details DNA alterations in a cell — during surgery can help a neurosurgeon decide how much brain tissue to remove. Removing too much when the tumor is less aggressive can affect a patient’s neurologic and cognitive function. Likewise, removing too little when the tumor is highly aggressive may leave behind malignant tissue that can grow and spread quickly.
“Right now, even state-of-the-art clinical practice cannot profile tumors molecularly during surgery. Our tool overcomes this challenge by extracting thus-far untapped biomedical signals from frozen pathology slides,” said study senior author Kun-Hsing Yu, assistant professor of biomedical informatics in the Blavatnik Institute at HMS.
Knowing a tumor’s molecular identity during surgery is also valuable because certain tumors benefit from on-the-spot treatment with drug-coated wafers placed directly into the brain at the time of the operation, Yu said.

“The ability to determine intraoperative molecular diagnosis in real time, during surgery, can propel the development of real-time precision oncology,” Yu added.
The standard intraoperative diagnostic approach used now involves taking brain tissue, freezing it, and examining it under a microscope. A major drawback is that freezing the tissue tends to alter the appearance of cells under a microscope and can interfere with the accuracy of clinical evaluation. Furthermore, the human eye, even when using potent microscopes, cannot reliably detect subtle genomic variations on a slide.
The new AI approach overcomes these challenges.
The tool, called CHARM (Cryosection Histopathology Assessment and Review Machine), is freely available to other researchers. It still has to be clinically validated through testing in real-world settings and cleared by the FDA before deployment in hospitals, the research team said.
Cracking cancer’s molecular code
Recent advances in genomics have allowed pathologists to differentiate the molecular signatures — and the behaviors that such signatures portend — across various types of brain cancer as well as within specific types of brain cancer. For example, glioma — the most aggressive brain tumor and the most common form of brain cancer — has three main subvariants that carry different molecular markers and have different propensities for growth and spread.

The new tool’s ability to expedite molecular diagnosis could be particularly valuable in areas with limited access to technology to perform rapid cancer genetic sequencing.
Beyond the decisions made during surgery, knowledge of a tumor’s molecular type provides clues about its aggressiveness, behavior, and likely response to various treatments. Such knowledge can inform post-operative decisions.
Furthermore, the new tool enables during-surgery diagnoses aligned with the World Health Organization’s recently updated classification system for diagnosing and grading the severity of gliomas, which calls for such diagnoses to be made based on a tumor’s genomic profile.
Training CHARM
CHARM was developed using 2,334 brain tumor samples from 1,524 people with glioma from three different patient populations. When tested on a never-before-seen set of brain samples, the tool distinguished tumors with specific molecular mutations at 93 percent accuracy and successfully classified three major types of gliomas with distinct molecular features that carry different prognoses and respond differently to treatments.
Going a step further, the tool successfully captured visual characteristics of the tissue surrounding the malignant cells. It was capable of spotting telltale areas with greater cellular density and more cell death within samples, both of which signal more aggressive glioma types.
The tool was also able to pinpoint clinically important molecular alterations in a subset of low-grade gliomas, a subtype of glioma that is less aggressive and therefore less likely to invade surrounding tissue. Each of these changes also signals different propensity for growth, spread, and treatment response.
The tool further connected the appearance of the cells — the shape of their nuclei, the presence of edema around the cells — with the molecular profile of the tumor. This means that the algorithm can pinpoint how a cell’s appearance relates to the molecular type of a tumor.
This ability to assess the broader context around the image renders the model more accurate and closer to how a human pathologist would visually assess a tumor sample, Yu said.
The researchers say that while the model was trained and tested on glioma samples, it could be successfully retrained to identify other brain cancer subtypes.
Scientists have already designed AI models to profile other types of cancer — colon, lung, breast — but gliomas have remained particularly challenging due to their molecular complexity and huge variation in tumor cells’ shape and appearance.
The CHARM tool would have to be retrained periodically to reflect new disease classifications as they emerge from new knowledge, Yu said.
“Just like human clinicians who must engage in ongoing education and training, AI tools must keep up with the latest knowledge to remain at peak performance.”
Authorship, funding, disclosures
Coinvestigators included MacLean P. Nasrallah, Junhan Zhao, Cheng Che Tsai, David Meredith, Eliana Marostica, Keith L. Ligon, and Jeffrey A. Golden.
This work was supported in part by the National Institute of General Medical Sciences grant R35GM142879, the Google Research Scholar Award, the Blavatnik Center for Computational Biomedicine Award, the Partners Innovation Discovery Grant, and the Schlager Family Award for Early-Stage Digital Health Innovations.

In a new study, National Institutes of Health (NIH) researchers found that altered B cell function in children with mitochondrial disorders led to a weaker and less diverse antibody response to viral infections. The study, published in Frontiers in Immunology was led by researchers at the National Human Genome Research Institute (NHGRI), who analyzed gene activity of immune cells in children with mitochondrial disorders and found that B cells, which produce antibodies to fight viral infections, are less able to survive cellular stress.
“Our work is one of the first examples to study how B cells are affected in mitochondrial disease by looking at human patients,” said Eliza Gordon-Lipkin, M.D., assistant research physician in NHGRI’s Metabolism, Infection and Immunity Section and co-first author of the paper.
Mitochondria are important components of nearly every cell in the body because they convert food and oxygen into energy. Genomic variants in more than 350 genes have been linked to mitochondrial disorders with varied symptoms depending on which cells are affected.
“For children with mitochondrial disorders, infections can be life threatening or they can worsen the progression of their disorder,” said Peter McGuire, M.B.B.Ch, NHGRI investigator, head of the Metabolism, Infection and Immunity Section and senior author of the study. “We wanted to understand how immune cells differ in these patients and how that influences their response to infections.”
Around 1 in 5,000 people worldwide have a mitochondrial disorder. Examples of mitochondrial disorders are Leigh’s syndrome, which primarily affects the nervous system, and Kearns-Sayre syndrome, which primarily affects the eyes and heart.
While mitochondrial disorders are known to affect organs such as the heart, liver, and brain, less is known how they affect the immune system.
Using a genomic technique called single-cell RNA sequencing, which analyzes gene activity in different cell types, researchers studied immune cells found in blood. These cells include different types of white blood cells that help the body fight infections. During stressful conditions, these cells produce a microRNA called mir4485. MicroRNAs are small strings of RNA that help control when and where genes are turned on and off. mir4485 controls cellular pathways that help cells survive.
“We think that B cells in these patients undergo cellular stress when they turn into plasma cells and produce antibodies, and these B cells then try to survive by producing the microRNA to cope,” said Dr. McGuire. “But the B cells are too fragile due to their limited energy, so they are unable to survive the stressful conditions.”
Researchers used a technique called VirScan to look at all past viral infections, assess how well the immune system fought those infections and see the effects of B cells and plasma cells on antibody production. With a weaker antibody response, the immune systems in children with mitochondrial disorders are less able to recognize and neutralize invading viruses and clear infections.
Researchers aim to use the results of this study to guide future treatment of patients with mitochondrial disorders, noting that more translational studies are needed in this research area.