Publisher Health

Problems with the brain’s ability to ‘prune’ itself of unnecessary connections may underlie a wide range of mental health disorders that begin during adolescence, according to research published today.
The findings, from an international collaboration, led by researchers in the UK, China and Germany, may help explain why people are often affected by more than one mental health disorder, and may in future help identify those at greatest risk.
One in seven adolescents (aged 10-19 years old) worldwide experiences mental health disorders, according to the World Health Organization (WHO). Depression, anxiety and behavioural disorders, such as attention deficit hyperactivity disorder (ADHD), are among the leading causes of illness and disability among young people, and adolescents will commonly have more than one mental health disorder.
Many mental health problems emerge during adolescence. Among these are disorders such as depression and anxiety, which manifest as ‘internalising’ symptoms, including low mood and worrying. Other conditions such as attention deficit hyperactivity disorder (ADHD) manifest as ‘externalising’ symptoms, such as impulsive behaviour.
Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge said: “Young people often experience multiple mental health disorders, beginning in adolescence and continuing — and often transforming — into adult life. This suggests that there’s a common brain mechanism that could explain the onset of these mental health disorders during this critical time of brain development.”
In a study published today in Nature Medicine, the researchers say they have identified a characteristic pattern of brain activity among these adolescents, which they have termed the ‘neuropsychopathological factor’, or NP factor for short.

The team examined data from 1,750 adolescents, aged 14 years, from the IMAGEN cohort, a European research project examining how biological, psychological, and environmental factors during adolescence may influence brain development and mental health. In particular, they examined imaging data from brain scans taken while participants took part in cognitive tasks, looking for patterns of brain connectivity — in other words, how different regions of the brain communicate with each other.
Adolescents who experienced mental health problems — regardless of whether their disorder was one of internalising or externalising symptoms, or whether they experienced multiple disorders — showed similar patterns of brain activity. These patterns — the NP factor — were largely apparent in the frontal lobes, the area at the front of the brain responsible for executive function which, among other functions, controls flexible thinking, self-control and emotional behaviour.
The researchers confirmed their findings by replicating them in 1,799 participants from the ABCD Study in the USA, a long-term study of brain development and child health, and by studying patients who had received psychiatric diagnoses.
When the team looked at genetic data from the IMAGEN cohort, they found that the NP factor was strongest in individuals who carried a particular variant of the gene IGSF11 that has been previously associated with multiple mental health disorders. This gene is known to play an important role in synaptic pruning, a process whereby unnecessary brain connections — synapses — are discarded. Problems with pruning may particularly affect the frontal lobes, since these regions are the last brain areas to complete development in adolescents and young adults.
Dr Tianye Jia from the Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China and the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK said: “As we grow up, our brains make more and more connections. This is a normal part of our development. But too many connections risk making the brain inefficient. Synaptic pruning helps ensure that brain activity doesn’t get drowned out in ‘white noise’.
“Our research suggests that when this important pruning process is disrupted, it affects how brain regions talk to each other. As this impact is seen most in the frontal lobes, this then has implications for mental health.”
The researchers say that the discovery of the NP factor could help identify those young people at greatest risk of compounding mental health problems.
Professor Jianfeng Feng from Fudan University in Shanghai, China, and the University of Warwick, UK, said: “We know that many mental health disorders begin in adolescence and that individuals who develop one disorder are at increased risk of developing other disorders, too. By examining brain activity and looking for this NP factor, we might be able to detect those at greatest risk sooner, offering us more opportunity to intervene and reduce this risk.”
Funders included: the National Natural Science Foundation of China, European Union, National Institute for Health & Care Research (UK) and National Institutes of Health (NIH, USA).*

Researchers at NYU Grossman School of Medicine and Janssen Biotech, Inc. have shown in early tests that a bioengineered drug candidate can counter infection with Staphylococcus aureus — a bacterial species widely resistant to antibiotics and a major cause of death in hospitalized patients.
Experiments demonstrated that SM1B74, an antibacterial biologic agent, was superior to a standard antibiotic drug at treating mice infected with S. aureus, including its treatment-resistant form known as MRSA.
Published online April 24 in Cell Host & Microbe,the new paper describes the early testing of mAbtyrins, a combination molecule based on an engineered version of a human monoclonal antibody (mAb), a protein that clings to and marks S. aureus for uptake and destruction by immune cells. Attached to the mAb are centyrins, small proteins that prevent these bacteria from boring holes into the human immune cells in which they hide. As the invaders multiply, these cells die and burst, eliminating their threat to the bacteria.
Together, the experimental treatment targets ten disease-causing mechanisms employed by S. aureus, but without killing it, say the study authors. This approach promises to address antibiotic resistance, say the researchers, where antibiotics kill vulnerable strains first, only to make more space for others that happen to be less vulnerable until the drugs no longer work.
“To our knowledge, this is the first report showing that mAbtyrins can drastically reduce the populations of this pathogen in cell studies, and in live mice infected with drug-resistant strains so common in hospitals,” said lead study author Victor Torres, PhD, the C.V. Starr Professor of Microbiology and director of the NYU Langone Health Antimicrobial-Resistant Pathogen Program.”Our goal was to design a biologic that works against S. aureus inside and outside of cells, while also taking away the weapons it uses to evade the immune system.”
One-third of the human population are carriers of S. aureus without symptoms, but those with weakened immune systems may develop life-threatening lung, heart, bone, or bloodstream infections, especially among hospitalized patients.

Inside Out
The new study is the culmination of a five-year research partnership between scientists at NYU Grossman School of Medicine and Janssen to address the unique nature of S. aureus.
The NYU Langone team together with Janssen researchers, published in 2019 a study that found that centyrins interfere with the action of potent toxins used by S. aureus to bore into immune cells. They used a molecular biology technique to make changes in a single parental centyrin, instantly creating a trillion slightly different versions of it via automation. Out of this “library,” careful screening revealed a small set of centyrins that cling more tightly to the toxins blocking their function.
Building on this work, the team fused the centyrins to a mAb originally taken from a patient recovering from S. aureus infection. Already primed by its encounter with the bacteria, the mAb could label the bacterial cells such that they are pulled into bacteria-destroying pockets inside of roving immune cells called phagocytes. That is unless the same toxins that enable S. aureus to drill into immune cells from the outside let it drill out of the pockets to invade from the inside.
In a “marvel of bioengineering,” part of the team’s mAbtyrin serves as the passport recognized by immune cells, which then engulf the entire, attached mAbtyrin, along with its centyrins, and fold it into the pockets along with bacteria. Once inside, the centyrins block the bacterial toxins there. This, say the authors, sets their effort apart from antibody combinations that target the toxins only outside of cells.

The team made several additional changes to their mAbtyrin that defeat S. aureus by, for instance, activating chain reactions that amplify the immune response, as well by preventing certain bacterial enzymes from cutting up antibodies and others from gumming up their action.
In terms of experiments, the researchers tracked the growth of S. aureus strains commonly occurring in US communities in the presence of primary human immune cells (phagocytes). Bacterial populations grew almost normally in the presence of the parental antibody, slightly less well in the presence of the team’s engineered mAb, and half as fast when the mAbtyrin was used.
In another test, 98% of mice treated with a control mAb (no centyrins) developed bacteria-filled sores on their kidneys when infected with a deadly strain of S. aureus, while only 38% of mice did so when treated with the mAbtyrin. Further, when these tissues were removed and colonies of bacteria in them counted, the mice treated with the mAbtyrin had one hundred times (two logs) fewer bacterial cells than those treated with a control mAb.
Finally, the combination of small doses of the antibiotic vancomycin with the mAbtyrin in mice significantly improved the efficacy of the mAbtyrin, resulting in maximum reduction of bacterial loads in the kidneys and greater than 70% protection from kidney lesions.
“It is incredibly important,” said Torres, “that we find new ways to boost the action of vancomycin, a last line of defense against MRSA.”
Along with Torres, authors from the Department of Microbiology at NYU Langone were Rita Chan, Ashley DuMont, Keenan Lacey, Aidan O’Malley, and Anna O’keeffe. The study authors included 13 scientists from Janssen Research & Development (for details see the study manuscript).
This work was supported by Janssen Biotech, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, under the auspices of an exclusive license and research collaboration agreement with NYU. Torres has recently received royalties and consulting compensation from Janssen and related entities. These interests are being managed in accordance with NYU Langone policies and procedures.

CAMBRIDGE, Mass. — In the fall of 1994, the psychiatrist Dr. Judith Herman was at the height of her influence. Her book “Trauma and Recovery,” published two years earlier, had been hailed in The New York Times as “one of the most important psychiatric works to be published since Freud.”Her research on sexual abuse in the white, working class city of Somerville, Mass., laid out a thesis that was, at the time, radical: that trauma can occur not only in the blind terror of combat, but quietly, within the four walls of a house, at the hands of a trusted person.More than most areas of science, psychology has been driven by individual thinkers and communicators. So what happened to Dr. Herman — as arbitrary as it was — had consequences for the field. She was in a hotel ballroom, preparing to present her latest findings, when she tripped on the edge of a rug and smashed her kneecap.“Just, wham,” she said. “Smack.”On and off for more than two decades, Dr. Herman groped her way through a fog of chronic pain, undergoing repeated surgeries and, finally, falling back on painkillers. The trauma researchers who surrounded her in the Boston area moved on with their work, and the field of trauma studies swung toward neurobiology.“She is a brilliant woman who lost 25 years of her career,” said her friend and colleague Dr. Bessel van der Kolk, whose 2014 book, “The Body Keeps the Score,” helped propel the field toward brain science. “If you talk about tragedy, that is a tragedy.”At the age of 81, Dr. Herman has rejoined the conversation, publishing “Truth and Repair,” a follow-up to her 1992 book “Trauma and Recovery: The Aftermath of Violence — From Domestic Abuse to Political Terror.” During that period, trauma has gained broad acceptance in popular culture as a way to understand mental health.But the dominant idea now comes from Dr. van der Kolk, who argues that traumatic experiences are stored in the body and can best be addressed through the unconscious mind. “The Body Keeps the Score” has appeared on the best-seller list for an astonishing 232 weeks. TikTok bulges with testimonials from members of Gen Z, identifying all manner of habits and health conditions as trauma responses.Dr. Herman does not want to use this flush of attention to debate her old friend. But in “Truth and Repair,” she picks up where she left off in 1992, arguing that trauma is, at its heart, a social problem rather than an individual one.Drawing on interviews with survivors, she lays out a theory of justice designed to help them heal, centering on collective acknowledgment of what they have suffered. Her approach is frankly political, rooted in the feminist movement and unlikely to go viral on TikTok.This does not seem to trouble her at all. “In my own life, I feel like I’m in a good place,” she said. “On the other hand, I think psychiatry will have to be dragged, kicking and screaming, into any kind of progressive future.”A pledgeDr. Bessel van der Kolk, Dr. Herman’s friend and colleague. “We noted that people in academia were often very cruel to each other,” he said, “and we made a pledge to have each other’s back.” Kayana Szymczak for The New York TimesWhen Dr. Herman and Dr. van der Kolk met in the 1980s, she was treating the daughters of working-class Irish and Italian families, who were coming forward with stories of sexual abuse. He had been treating veterans who seemed trapped in the past, exploding with extreme rage at minor frustrations.She was reserved; he was expansive. Dr. Herman likes to call herself “plain vanilla,” doggedly faithful to psychodynamic psychotherapy; Dr. van der Kolk is “flavor of the month,” always exploring new treatments, first Prozac, then body work and eye movement desensitization and reprocessing.They had this in common: The patients they treated had been routinely dismissed by the psychiatric establishment as malingerers or hysterics. “We were in explicit agreement,” Dr. van der Kolk said. “We noted that people in academia were often very cruel to each other, and we made a pledge to have each other’s back.”The diagnosis of PTSD was brand-new, having first appeared in the Diagnostic and Statistical Manual of Mental Disorders, or DSM, in 1980, and the Boston area, Dr. van der Kolk said, “was to trauma what Vienna was to music.” A trauma study group convened monthly in the elegant stretch of Cambridge mansions known as Professors’ Row.Passing around glasses of sherry and cups of coffee, they argued, Dr. Herman said, about “what counted” as trauma. “The guys who worked with the vets, we had some back and forth, shall we say,” she said. “We had some knockdown drag-outs, calling out the sexism of the men who thought combat trauma was trauma and everything else was just whining.”Dr. Herman is widely credited with putting this question to rest. “Trauma and Recovery” addressed a general audience in “measured, gripping, almost surgically precise” language, as the Times review put it, and with the authority of a Harvard psychiatrist.Her ideas also radiated into the communities where she practiced, said Rosie McMahan, whose family worked with Dr. Herman and her colleague Emily Schatzow to confront sexual abuse by her father.“She did this remarkable thing — ‘Wait a minute, the same things that were happening to those soldiers, in a sense, happened in families,’” said Ms. McMahan, whose book, “Fortunate Daughter,” describes her family’s reconciliation. “They recognized that it was trauma and called it such. They behaved as if it was.”Their ideas were gaining ground. In 1994, the editors of the DSM expanded the definition of PTSD, dropping the requirement that the traumatic event be “outside the range of usual human experience.” Dr. Herman and Dr. van der Kolk began lobbying for the inclusion of complex PTSD, the result of recurring or long-term traumatic events.Dr. Herman at the 130th meeting of the American Psychiatric Association in Toronto in 1977.via Judith HerhamThen came what’s known as the “memory wars” — a pushback from leading psychiatrists against therapy that encouraged patients to unearth memories of sexual abuse. The criticism often zeroed in on Dr. van der Kolk, who served as an expert witness in high-profile cases, and Dr. Herman, whose work on dissociation was regularly cited by defenders of repressed-memory therapy.Dr. Herman shrugged off this critique as “predictable,” the same resistance that Vietnam War veterans and rape victims had encountered when they came forward. “You know, history is a dialectical process,” she said. “When you have a movement that challenges the power structure, you’re going to have a backlash.”Some clinicians did go overboard, Dr. van der Kolk said. They “started talking about satanic ritual abuse, kids being sacrificed in altars,” he said. “It got a little bit weird. Judy and I never went with that crowd. But they were part of our crowd.”By the time the debate faded, his laboratory at Massachusetts General Hospital had been shut down, and he lost his affiliation with Harvard Medical School. “Almost all of us bit the dust in the memory wars,” he added.Since the mid-1990s, the editors of the DSM have consistently opposed further expanding the definition of PTSD. The original definition was “intentionally strict, meant to avoid the possibility that all mental disorders are simply caused by trauma,” said Dr. Allen Frances, who chaired the task force for the DSM’s fourth edition.While stress contributes to most psychiatric problems, he said, PTSD diagnoses can be made quickly and carelessly, without pursuing underlying mental disorders, such as anxiety and depression. Taking that leap, he added, means “all the rest of the knowledge ever accumulated about mental disorders goes out the window.”Dr. Frances was similarly skeptical of “trauma-informed therapy,” which he said provided “a misleadingly reassuring explanation” to complicated psychiatric problems. He added that proponents of the idea, like Dr. Herman and Dr. van der Kolk, had succeeded in winning over a large part of the general public.“You can write best-sellers on this because it’s an appealing model for people searching for an explanation for the distress in life,” Dr. Frances said. That avenue was closing. But that wasn’t the only thing that happened.Pain of unexplained originA page from Dr. Herman’s personal journal from 1976, around the time she started writing her first book.Kayana Szymczak for The New York TimesOn the day she broke her kneecap, Dr. Herman was preparing to deliver a workshop on her latest findings, and was carrying a carousel of slides to a projector. She was distracted and did not see that a binding had come loose from the rug.Dr. Herman has offered vague explanations for the 30-year gap between her books. “Life intervened, in the form of illnesses and a move to an assisted-living community,” she writes in a forward to “Truth and Repair.” In an interview, she flicked away the question, calling it “a very long, sad tale which I won’t bore you with.”But there is a story. Her kneecap healed, but nerve tumors had formed in her leg, and the pain grew steadily worse. For long stretches, daily life became a challenge. There were remissions, but there were also times she could not get out of bed, where even changing positions was “extremely, extremely painful.” At one point, she was so desperate that she asked a doctor if he could amputate her leg.“All you could think about was pain,” she said. “It wasn’t even thinking about pain. It was being pain. One’s existence was just pain. It’s like being in a tunnel.” Like “your whole existence is pain, and nothing exists outside of it,” she added.There was a subtext in her doctors’ response, early on, which she, as a fellow physician, was uniquely qualified to identify: They did not quite believe her. “I was a middle-aged woman with pain of unexplained origin,” she said. In the jargon of medical residents, she said, she was a “crock,” or a female hypochondriac.Eleven years and three surgeries later, her doctors said there was nothing more they could do. This was the worst of it, when there was no hope of reprieve. “It made me not want to live,” she said. “That is literally what happened.”“Judy’s fall had a gigantic impact,” Dr. van der Kolk said. “When you talk about suffering, that was suffering. She was really suffering physically. A large part of the joy and triumph of publishing a great book she did not get to enjoy.”He also said the injury had created a distance in their relationship. He was on fire with the ideas that would later become “The Body Keeps the Score,” among them a view that chronic pain may be an expression of suppressed trauma. He thought he could help. But she was, he said, “too injured to be all that curious.” After that, he said, “Judy and I started to go in different directions.”“It really was the source of sadness on my part, as I was entering this body world, that Judy did not go in the same direction,” he said.Dr. Herman had little recollection of this exchange. But she did not see any larger meaning to her pain; it was just pain, a bunch of malfunctioning neurons, and it preoccupied her entirely. She was fitted with a brace and crutches, and managed to continue teaching and supervising trainees by taking a large doses of fentanyl, applied through a transdermal patch.Asked what the experience taught her, she paused and said, “I guess I just had more empathy for people who go through various forms of torture.”A remedy appeared in 2019, almost by chance. She had gone to see a surgeon about arthritis in her hand, and instead, he peered at her knee. After she left, he emailed her an article about a surgery that had been developed at Walter Reed National Military Medical Center to treat amputees, war veterans from Iraq and Afghanistan.Later that year, surgeons removed the damaged nerves, sutured them to a motor nerve harvested from her quadriceps and then implanted them into her muscle. She weaned herself off fentanyl, set aside the brace and the crutches. She compared the relief she felt to the sensation women have when childbirth ends.“I mean, it’s really heavenly,” she said. “I’m in a permanent state of gratitude.”And that, she said, was why she had the energy to finish another book.“It’s a totally crazy story,” she said. “I owe it all to the forever wars.”The queen of traumaDr. Herman’s new book, her first in 30 years.Kayana Szymczak for The New York TimesWhen Dr. Herman walked into a launch event at the Harvard Book Store last month, wearing orthopedic shoes and multiple shades of purple, there was an intake of breath from the audience, largely made up of older women in mental health professions.The store offered books on healing trauma through weight lifting, quitting one’s job or blocking the nerves known as the stellate ganglion; books on trauma in the music of Dolly Parton, polyamorous families and the Indian caste system; and, of course, “The Body Keeps the Score,” one of those books that, the store’s buying manager said, “even people who aren’t necessarily readers have heard about.”This did not escape Dr. Herman’s admirers, who waited in folding chairs, grumbling discreetly about the authors who rode on her coattails. “All the noise around trauma is all about white men,” remarked Mary Gorman, a psychiatric nurse specialist. “It’s like she’s the forgotten stepchild.”Dr. van der Kolk, who has been helping Dr. Herman to publicize her book, was acutely aware of this dynamic. “The Body Keeps the Score,” he said, benefited enormously from its focus on neurobiology. “In the culture right now, if it’s based on the brain, it’s real,” he added. “Everything else is woozy stuff.”As his book neared publication, he said, he worried that it would supplant Dr. Herman’s as the best-known title on trauma. “She must have known that, to some degree, I would bump her to second position,” he said. “I wondered how she would deal with it.”Considering the whole story, he sounded stricken. Were it not for her injury, he said, “Judy really would have been the queen of trauma.”Dr. Herman, in contrast, sounded cheerful as she looked back on it all. For a woman of her generation to become a full professor at Harvard was a big deal, she said. As for the years lost to pain, she said that the work she had done in her 40s and 50s had already helped to launch a generation of younger scholars.“It wasn’t so much of a cult of personality,” she said. “The field is haunted by all that. But in my case, once ‘Trauma and Recovery’ came out, I wasn’t the only messenger.”At 81, she has the aches and pains of old age, but cannot shake the feeling of having been reborn. In the Black Lives Matter and the #MeToo movements, and in the psychiatric residents she supervises, she sees a return to the politics that shaped her as a young doctor. “I’m back in that exploring kind of moment,” she said. “It’s quite exciting. I just wish I had a 40-year-old body instead of an 80-year-old body to be able to keep up with it.”

Despite the promise of new medications that promote cancer cell death in people with acute myeloid leukemia, leukemic cells often adopt features that let them evade the drugs’ effects within a year.
Now, new research using human tissue samples and mouse models has found that resistance of leukemia cells to a widely prescribed drug called venetoclax occurs because of a rapid increase in the breakdown and turnover of mitochondria, structures inside the cell that help power its functions. In addition to their role in producing energy, mitochondria also tell cells to die under certain adverse conditions.
This process of “programmed cell death” often goes wrong in cancer. Damaged mitochondria can also undergo a form of “self-eating” termed mitophagy that prevents them from sending “death signals.”
Led by scientists at NYU Langone Health and its Perlmutter Cancer Center, the study showed that mitophagy helps leukemia cells to evade the killing effects of venetoclax, a drug in a class of medications known as BH3 mimetics.
Publishing in the journal Cancer Discovery online April 24, researchers found that the levels of several genes associated with mitophagy were increased in 20 leukemia patient samples compared with normal controls. The level of these genes was even higher in samples from leukemia patients with drug resistance than in those leukemic patients who were not. Particularly notable was the increased expression of the gene for Mitofusin-2 (MFN2), which codes for a key protein in the outer mitochondrial membrane.
Further experiments using mice into which bone marrow from acute myeloid leukemia patients was transplanted showed that the drug chloroquine, a known mitophagy inhibitor, restored the ability of venetoclax to kill the cancer cells.

“Overcoming resistance to BH3 mimetic drugs like venetoclax is of unique clinical significance because these medications are often used for treating people with acute myeloid leukemia,” said study co-lead investigator Christina Glytsou, PhD, a former postdoctoral researcher at NYU Grossman School of Medicine and now an assistant professor at Rutgers University.
“Acute myeloid leukemia is notoriously difficult to treat, with fewer than a third of those affected living longer than five years after their diagnosis, so it is important to maximize the impact of existing therapies,” said study co-lead investigator Xufeng Chen, PhD, an instructor in the Department of Pathology at NYU Grossman.
“Our preclinical findings suggest that combining BH3 mimetics like venetoclax with either MFN2 or general mitophagy inhibitors could possibly serve as a future therapy for acute myeloid leukemia, as current drug treatments are stalled due to drug resistance,” said study senior investigator Iannis Aifantis, PhD.
Aifantis, the Hermann M. Biggs Professor and chair of the Department of Pathology at NYU Grossman and Perlmutter, says the research team plans to design a clinical trial to test whether chloroquine, when used in combination with venetoclax, prevents drug resistance in people with acute myeloid leukemia.
Speaking about other study results, the researchers say they not only found that MFN2 was overly active in people with drug-resistant disease, but also that cancer cells exposed to similar cell-death-inducing compounds demonstrated a doubling in mitophagy rates.

Additional testing in cancer cells engineered to lack MFN2 showed increased sensitivity to drugs similar to venetoclax compared with cells that had functional MFN2. The new study and previous research by the team showing misshapen mitochondria in drug-resistant leukemic cells confirmed that increased mitophagy was the source of the problem.
Acute myeloid leukemia, the most common form of adult leukemia, originates in the bone marrow cells and involves the rapid buildup of abnormal blood cells. The blood cancer results in the deaths of more than 11,500 Americans annually. Current treatments include chemotherapy and a limited number of targeted drug therapies. Bone marrow transplantation has also been used when other options fail.
Funding support for the study was provided by National Institutes of Health grants P30CA016087, P30CA013330, R01CA178394, R01CA173636, R01CA228135, R01CA229086, R01CA242020, and K99CA252602. Additional funding support was provided by the Leukemia & Lymphoma Society and by AstraZeneca, which provided several of the BH3 mimetic drugs used in these experiments.
Aifantis has received additional research funding from AstraZeneca. This arrangement is being managed in accordance with the policies and practices of NYU Langone Health.
Besides Glytsou, Chen, and Aifantis, other NYU Langone study investigators are Wafa Al-Santli, Hua Zhou, Bettina Nadorp, Soobeom Lee, Audrey Lasry, Zhengxi Sun, Dimitrios Papaioannou, Michael Cammer, Kun Wang, and Aristotelis Tsirigos. Other study co-investigators are Emmanouil Zacharioudakis and Evripidis Gavathiotis, at Albert Einstein College of Medicine in New York, who have filed a patent on mitofusin inhibition based on this research; Tomasz Zal, Malgorzata Anna Zal, Bing Carter, Jo Ishizawa, and Michael Andreeff, at the University of Texas MD Anderson Cancer Center in Houston; and Raoul Tibes, at AstraZeneca in Cambridge, the United Kingdom.

Researchers at Ruhr University Bochum, Germany, have successfully implemented a special form of classical conditioning. They showed on a group of 75 people that effects of transcranial magnetic stimulation (TMS) can be triggered solely by listening to a tone. Professor Burkhard Pleger from the Neurology Department at Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil describes the results together with the medical doctoral students Stefan Ewers and Timo Dreier and other colleagues in the journal Scientific Reports, published online on 16 April 2023.
Magnetic stimulation triggers contraction of the thumb muscle
To perform TMS, a magnetic coil is placed externally over a specific part of the brain. The strong magnetic field stimulates the underlying nerve cells to become active. If a certain area of the motor cortex is stimulated in this way, the index finger or thumb, for example, will move. For their research, the Bochum-based team used the so-called paired-pulse transcranial magnetic stimulation (TMS). This involved two TMS stimuli spaced twelve milliseconds apart, which leads to a stronger contraction of a muscle than a single TMS. In the conditioning phase, the researchers always combined this paired-pulse TMS with a tone that the participants heard via headphones while the TMS was applied.
Conditioned tone intensifies muscle contraction
In the test phase, the participants were no longer exposed to double TMS, but only to a single TMS pulse — paired either with the conditioned tone or with a tone that the participants hadn’t heard before. At the same time, the researchers once again measured the intensity of the muscle contraction on the thumb: it was significantly stronger when the participants listened to the conditioned tone, as opposed to the tone that they hadn’t heard during conditioning.
Conditioning could be useful for therapeutic applications
“Our basic research proves that traditional conditioning works not only with conscious behaviour patterns,” concludes Burkhard Pleger. “Brain activity can also be conditioned when manipulated through external brain stimulation.” This is interesting, because TMS can also be used as a therapeutic approach, for example to improve the mobility of people with Parkinson’s disease or to treat depression. “Generally, the effects of TMS are only temporary. They disappear if the stimulation is not continued. If these effects could be maintained by conditioned tones, therapy could become much more straightforward,” as Pleger describes one possible benefit of the research.

The notion that in a group of cyclists, the person in front of the group is always the most exposed to harmful vehicle pollutants has been debunked by the University of Surrey.
A series of unique experiments were carried out in Surrey’s Environmental Flow (EnFlo) wind tunnel, capturing results from a vehicle driving in front and adjacent to the riders.
With a vehicle in front of a cycling group and little wind movement, the findings confirm that pollutant exposure decreases the further the cyclist is from the vehicle. However, with more wind, riding towards the back of the group can be a good strategy to minimise exposure.
When the vehicle is adjacent to the cycling group, results show how exhaust fumes can be trapped by a complex aerodynamic field, making the front riding position the place with the least exposure despite its proximity with the vehicle.
Joy Schmeer, Postgraduate Researcher at the University of Surrey and lead author said:
“Cycling is encouraged to reduce congestion on the roads, as well as traffic emissions, yet despite many encouraging health aspects of cycling, the exposure to and inhalation of vehicle pollutants is something not to be forgotten, especially when used as a regular alternative transport method.
“The findings of these experiments highlight group cyclists needs to consider their routes and position within a group, especially when roads become busier and narrower.”
Dr Marco Placidi, Senior Lecturer in Experimental Fluid Mechanics at the University of Surrey commented:
“The results of these experiments reveal important recommendations that cyclists and drivers should know to increase health and safety while cycling in groups.
“While drivers need to maximise their distance away from riders before overtaking them, cyclists should aim to distance themselves from the vehicle’s exhaust, but also potentially from other riders if a vehicle is driving adjacent to them. As for further recommendations, experiments like these show the need to consider repercussion of peak utilisation of urban cycle lanes during their design stages.”

New research finds there is significant variation in the anatomy of the human digestive system, with pronounced differences possible between healthy individuals. The finding has implications for understanding the role that the digestive tract’s anatomy can play in affecting human health, as well as providing potential insights into medical diagnoses and the microbial ecosystem of the gut.
“There was research more than a century ago that found variability in the relative lengths of human intestines, but this area has largely been ignored since then,” says Amanda Hale, co-first author of the study and a Ph.D. candidate at North Carolina State University. “When we began exploring this issue, we were astonished at the extent of the variability we found.”
“If you’re talking to four different people, odds are good that all of them have different guts, in terms of the relative sizes of the organs that make up that system,” says Erin McKenney, corresponding author of the study and an assistant professor of applied ecology at NC State. “For example, the cecum is an organ that’s found at the nexus of the large and small intestine. One person may have a cecum that is only a few centimeters long, while another may have a cecum the size of a coin purse. And we found similar variability for many digestive organs.”
In another striking example, the researchers found that women tend to have longer small intestines than men.
“Because having a longer small intestine helps you extract nutrients from your diet, this finding supports the canalization hypothesis, which posits that women are better able to survive during periods of stress,” says Hale.
“Given that there is more variation in human gut anatomy than we thought, this could inform our understanding of what is driving a range of health-related issues and how we treat them,” says McKenney. “Basically, now that we know this variability exists, it raises a number of research questions that need to be explored.”
For this study, the researchers measured the digestive organs of 45 people who donated their remains to the Anatomical Gifts Program at the Duke University School of Medicine.
In addition to shedding light on the unexpected variability in human anatomy, this project also led to rediscovering the importance of teaching anatomical variation to medical students.
“It’s particularly important in medical training, because if students are only learning about a ‘normal’ or ‘average’ anatomy, that means they are not going to be familiar with the scope of human variation,” says Roxanne Larsen, co-author of the paper and an associate professor of veterinary and biomedical sciences at the University of Minnesota. “It’s increasingly clear that the medical field is moving toward individualized medicine to improve patient outcomes and overall health and well-being. Garnering experience in understanding anatomical variation can play a critical role in helping future doctors understand the importance of individualized medicine.”
“We’re excited about this discovery and future directions for the work,” McKenney says. “It underscores just how little we know about our own bodies.”

Arterial stiffness may be a novel risk factor for metabolic syndrome in teens, a paper published in the American Journal of Physiology-Heart and Circulatory Physiology concludes. The study was conducted in collaboration between the University of Bristol in the UK, the University of Exeter in the UK, and the University of Eastern Finland.
The World Health Organization describes metabolic syndrome as the constellation of three or more of the following: abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. The prevalence of metabolic syndrome in US middle-aged adults is 30%, increasing to 50% in adults older than 60 years. In Finland, the prevalence of metabolic syndrome is 30% in men and 25% in women. Metabolic syndrome increases the risk of worsening obesity, type 2 diabetes, cardiovascular disease, and premature death.
Already among children aged 6 — 12 years, the prevalence of metabolic syndrome is approximately 3% while among adolescents aged 13 — 18 years, the prevalence is approximately 5% globally. Among children who are overweight, the prevalence of metabolic syndrome is 12% but 29% among children who are obese. This trend in the prevalence of metabolic syndrome is consistent across the globe; hence the need to identify novel causes and prevent or reverse the disease.
A new risk factor for childhood and adolescent metabolic disease such as obesity and insulin resistance is arterial stiffness. This risk factor is being established as a potential cause of type 2 diabetes among adults globally. However, it is not clear whether arterial stiffness causes metabolic syndrome.
The current study included 3,862 adolescents (1,719 males and 2,413 females) aged 17 years who were followed up until age 24 years. These adolescents had dual-energy Xray absorptiometry measurement for trunk fat mass and skeletal muscle mass, as well as fasting blood samples such as glucose, insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and high sensitivity C-reactive protein, in addition to smoking status, socio-economic status, family history of cardiovascular disease, and moderate-to-vigorous physical activity. Arterial stiffness was measured with carotid-femoral pulse wave velocity and the presence of any three of high blood pressure, high trunk fat mass, high fasting glucose, high fasting triglyceride, or low fasting high-density lipoprotein cholesterol was considered to describe metabolic syndrome.
The prevalence of metabolic syndrome in the study was 5% in males and 1.1% in females at age 17 years but 8.8% in males and 2.4% in females at age 24 years. This significant sex-difference in the prevalence of metabolic syndrome is due to a higher proportion of males having elevated systolic blood pressure, hyperglycemia, elevated triglyceride, and reduced high-density lipoprotein cholesterol compared to females. However, females had significantly higher trunk fat mass than males.
During the 7-year follow-up, worsening arterial stiffness was associated with a 9% risk of metabolic syndrome in males but there was no statistically significant risk among females. It was also observed that arterial stiffness potentially caused metabolic syndrome; however, metabolic syndrome did not cause arterial stiffness. The pathway through which arterial stiffness caused metabolism syndrome could be partly explained by an increase in fasting insulin (12% contribution) and low-density lipoprotein cholesterol (9% contribution).
“We are seeing for the first time that arterial stiffness in adolescents is an unknown risk factor for metabolic syndrome which may initiate a cascade of disease processes that might lead to type 2 diabetes, cardiovascular disease, and premature death. Early intervention might likely reduce high fasting insulin and low-density lipoprotein cholesterol thereby cutting off 20% of the potential causal effect of arterial stiffness on metabolic syndrome,” says Andrew Agbaje, a physician and clinical epidemiologist at the University of Eastern Finland.
“Pending when randomized clinical trials will be successful in reversing and treating arterial stiffness, it is expedient for caregivers, pediatricians, public health experts, and policymakers to focus on ways to reduce high fasting insulin or insulin resistance and low-density lipoprotein cholesterol, particularly from adolescence through improvement in diet and physical activity,” Agbaje continues.
Dr Agbaje’s research group (urFIT-child) is supported by research grants from Jenny and Antti Wihuri Foundation, the Finnish Cultural Foundation Central Fund, the Finnish Cultural Foundation North Savo Regional Fund, the Orion Research Foundation sr, the Aarne Koskelo Foundation, the Antti and Tyyne Soininen Foundation, the Paulo Foundation, the Yrjö Jahnsson Foundation, the Paavo Nurmi Foundation, the Finnish Foundation for Cardiovascular Research and the Foundation for Pediatric Research.

A woman who met her kidney donor by chance on a day out at the seaside is urging others to consider donating their organs.Lucy Humphrey, 44, from Caerphilly, was told in 2019 that without a kidney transplant, she would only have five years to live.She was diagnosed with lupus – a condition which causes inflammation to the organs – in 2001.After a chance conversation at Cold Knap beach in Barry, with 40-year-old Katie James – who was then a stranger, – they were found to be a perfect match.The transplant took place in October last year, and both women are doing well.

Published7 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesWalking for three minutes every half an hour could help improve blood sugar levels, a small trial presented at a UK diabetes charity’s conference suggests.The study of 32 people with type 1 diabetes showed blood sugar levels lowered when they took regular walking breaks over a seven-hour period.Diabetes UK said these “activity snacks” could offer practical, cost-free changes.Type 1 diabetes affects about 400,000 people in the UK.Type 1 diabetes: ‘People don’t know how hard it is’Game-changing type 1 diabetes drug approved in USThe condition happens when the body’s immune system attacks insulin-producing cells in the pancreas. This means the pancreas can no longer produce insulin – leading to high blood sugar levels. People need to take regular insulin medication. ‘Walking phone calls’Over long periods of time high blood sugar can result in complications like kidney failure, eye problems and heart attacks. Dr Elizabeth Robertson, director of research at Diabetes UK, which funded the study, said for people with type 1 diabetes, managing blood sugar levels day in, day out, can be “relentless”. She added: “It is incredibly encouraging that these findings suggest that making a simple, practical change – such as taking phone calls while walking, or setting a timer to remind you to take breaks – to avoid sitting for long periods – could have such a profound effect on blood sugar levels.Image source, Getty Images”We look forward to further research to understand the long-term benefits of this approach.”Lead researcher Dr Matthew Campbell, from the University of Sunderland, said he was surprised by the magnitude of the results with low level activity. He said for some people with type 1 diabetes “activity snacking” could be an important stepping stone towards more regular physical activity and for others it could be a simple intervention to help manage blood glucose levels.He added: “Importantly, this strategy does not seem to increase the risk of potentially dangerous blood glucose lows which are a common occurrence with more traditional types of physical activity and exercise.”In the early-stage trial, which has not yet been published, 32 adults with type 1 diabetes completed two seven-hour sessions of sitting down. In one session they remained seated. In the other they broke up the seven hours with three-minute bouts of light intensity walking (at their own pace) every 30 minutes.Their blood sugars were monitored continuously for 48 hours from the start of each session and they all had similar food during the seven hours and did not change their insulin treatment.Taking regular walking breaks resulted in lower average blood sugar levels (6.9 mmol/L) over the 48-hour study period compared to uninterrupted sitting (8.2 mmol/L). Walking breaks also increased the time people spent with their sugar levels within a desirable range. Dr Campbell said he hoped to complete larger studies over a longer period to better understand the benefits of this approach. He added: “The reality is simple ways of encouraging moving more through the day should benefit the vast majority of people.”What is diabetes?Diabetes is a lifelong condition that causes a person’s blood sugar level to become too high.There are two main types:type 1 – where the body’s immune system attacks and destroys the cells that produce insulintype 2 – where the body does not produce enough insulin, or the body’s cells do not react to insulinType 2 diabetes is far more common than type 1.Source: NHS & Diabetes UKMore on this storyGame-changing type 1 diabetes drug approved in US18 November 2022Type 1 diabetes: ‘People don’t know how hard it is’9 May 2022Related Internet LinksDiabetes UKThe BBC is not responsible for the content of external sites.