James' World 2

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Amy Bies was recovering in the hospital from injuries inflicted during a car accident in May 2007 when routine laboratory tests showed that her blood glucose and cholesterol were both dangerously high. Doctors ultimately sent her home with prescriptions for two standard drugs, metformin for what turned out to be type 2 diabetes and a statin to control her cholesterol levels and the heart disease risk they posed.

The combo, however, didn’t prevent a heart attack in 2013. And by 2019, she was on 12 different prescriptions to manage her continued high cholesterol and her diabetes and to reduce her heart risk. The resulting cocktail left her feeling so terrible that she considered going on medical leave from work. “I couldn’t even get through my day. I was so nauseated,” she said. “I would come out to my car in my lunch hour and pray that I could just not do this anymore.”

Medical researchers now think Bies’s conditions were not unfortunate co-occurrences. Rather, they stem from the same biological mechanisms. The medical problem frequently begins in fat cells and ends in a dangerous cycle that damages seemingly unrelated organs and body systems: the heart and blood vessels, the kidneys, and insulin regulation, and the pancreas. Harm to one organ creates ailments that assault the other two, prompting further illnesses that circle back to damage the original body part.

Diseases of these three organs and systems are “tremendously interrelated,” says Chiadi Ndumele, a preventive cardiologist at Johns Hopkins University. The ties are so strong that in 2023 the American Heart Association grouped the conditions under one name: cardio-kidney-metabolic syndrome (CKM), with “metabolic syndrome” referring to diabetes and obesity.

The good news, says Ndumele, who led the heart association group that developed the CKM framework, is that CKM can be treated with new drugs. The wildly popular GLP-1 receptor agonists, such as Wegovy, Ozempic, and Mounjaro, target common pathology underlying CKM. “The thing that has really moved the needle the most has been the advances in treatment,” says Sadiya Khan, a preventive cardiologist at Northwestern University. Although most of these drugs come only in injectable forms that can cost several hundred dollars a week, pill versions of some medications are up for approval, and people on Medicare could pay just $50 a month for them under a new White House pricing proposal. The appearance of these drugs on the scene is fortunate because researchers estimate that 90 percent of Americans have at least one risk factor for the syndrome.

More than a century before Bies entered the hospital, doctors had noticed that many of the conditions CKM syndrome comprises often occur together. They referred to the ensemble by terms such as “syndrome X.” People with diabetes, for instance, are two to four times more likely to develop heart disease than those without diabetes. Heart disease causes 40 to 50 percent of all deaths in people with advanced chronic kidney disease. And diabetes is one of the strongest risk factors for developing kidney conditions.At present, around 59 million adults worldwide have diabetes, about 64 million are diagnosed with heart failure, and approximately 700 million live with chronic kidney disease.

The first inkling of a connection among these disparate conditions came as far back as 1923, when several lines of research started to spot links among high blood sugar, high blood pressure, and high levels of uric acid—a sign of kidney disease and gout.

Then, several decades ago, researchers identified the first step in these tangled disease pathways: dysfunction in fat cells. Until the 1940s, scientists thought fat cells were simply a stash for excess energy. The 1994 discovery of leptin, a hormone secreted by fat cells, showed researchers a profound way that fat could communicate with and affect different body parts.

Since then, researchers have learned that certain kinds of fat cells release a medley of inflammatory and oxidative compounds that can damage the heart, kidneys, muscles, and other organs. The inflammation they cause impairs cells’ ability to respond to the pancreatic hormone insulin, which helps cells absorb sugars to fuel their activities. In addition to depriving cells of their primary energy source, insulin resistance causes glucose to build up in the blood—the telltale symptom of diabetes—further harming blood vessels and the organs they support. The compounds also reduce the ability of kidneys to filter toxins from the blood.

Insulin resistance and persistently high levels of glucose trigger a further cascade of events. Too much glucose harms mitochondria—tiny energy producers within cells—and nudges them to make unstable molecules known as reactive oxygen species that disrupt the functions of different enzymes and proteins. This process wrecks kidney and heart tissue, causing the heart to enlarge and blood vessels to become stiffer, impeding circulation and setting the stage for clots. Diabetes reduces levels of stem cells that help to fix this damage. High glucose levels also prod the kidneys to release more of the hormone renin, which sets off a hormonal cascade critical to controlling blood pressure and maintaining healthy electrolyte levels.

At the same time, cells that are resistant to insulin shift to digesting stored fats. This metabolic move releases other chemicals that cause lipid molecules such as cholesterol to clog blood vessels. The constriction leads to spikes in blood pressure and heightens a diabetic person’s risk of heart disease.

The circular connections wind even tighter. Just as diabetes can lead to heart and kidney conditions, illnesses of those organs can increase a person’s risk of developing diabetes. Disruption of the kidneys’ renin-angiotensin system—named for the hormones involved, which regulate blood pressure—also interferes with insulin signaling. Adrenomedullin, a hormone that increases during obesity, can also block insulin signaling in the cells that line blood vessels and the heart in humans and mice. Early signs of heart disease, such as constricted blood vessel,s can exhaust kidney cells, which rely on a strong circulatory system to filter waste effectively.

The year before Bies’s car accident, when she was in her early 30s, her primary care doctor diagnosed her with prediabetes—part of metabolic syndrome—and recommended changes such as a healthier diet and more exercise. But at the time, the physician didn’t mention that this illness also increased her risk of heart disease.

Not seeing these connections creates dangers for patients like Bies. “What we’ve done to date is really look individually across one or two organs to see abnormalities,” says nephrologist Nisha Bansal of the University of Washington. And those narrow views have led doctors to treat the different elements of CKM as separate, isolated problems.

For instance, doctors have often used clinical algorithms to figure out a patient’s risk of heart failure. But in a 2022 study, Bansal and her colleagues found that one common version of this tool does not work as well in people with kidney disease. As a result, those who had kidney disease—who are twice as likely to develop heart disease as are people with healthy kidneys—were less likely to be diagnosed and treated in a timely manner than those without kidney ailments.

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Jennifer N. R. Smith

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Key Points

• Today’s teens are drinking and smoking less, but many are spending more time online, where risky behaviors can be harder for parents to spot.
• Experts say this shift from in-person rebellion to digital risk-taking may leave kids more isolated and struggling with anxiety and loneliness.
• Parents can help by staying connected to their child’s online world, setting clear screen limits, and encouraging face-to-face friendships and activities.

If you ever snuck home smelling like cheap wine and cigarettes in an act of teenage rebellion, well, you might be showing your age. Research suggests substance abuse isn’t the vice it once was for teenagers.

According to new data from consumer research platform Attest, 20% of 15- to 16-year-olds have tried alcohol, down from 71% of 10th graders in 2000. The same survey, based on results from 1,000 U.S. parents, revealed that cigarette and drug use is also lower, with 14% and 6% of teens trying them, respectively. Meanwhile, 44% of 10th graders in 2000 had tried marijuana, according to the report.1

While these figures are parent-led (and therefore potentially conservative), it’s reflective of an overall decrease in trends of substance use, says Joel Stoddard, MD, child and adolescent psychiatrist at Children’s Hospital Colorado. Previous research confirms substance use among adolescents is on the decline.2

But experts warn this doesn’t necessarily mean teenagers are making healthier choices. In fact, our youngest teens, Generation Alpha—those born between 2010 and 2024—as well as older ones, could be at risk of something else insidious.

“The rebellion has moved online, and it’s much harder for adults to see,” explains Saba Harouni Lurie, LMFT, ATR-BC, family therapist and owner and founder of Take Root Therapy. “When I was younger, rebellion was visible. Now, a teen can sit in their room looking perfectly compliant while they’re engaging in all kinds of boundary-pushing behavior on their phone.”

So, what does this mean for parents? Experts say there are a few things they need to be aware of.

A Generational Change

The new study is part of a bigger, generational picture. And it’s global.

For example, a recent study into more than 23,000 Australians by Flinders University found Gen Z (born between 1997 and 2012) are almost 20 times more likely to say “no” to alcohol compared to Baby Boomers (born between 1946 and 1964).3 

While fewer teens engaging in substance use sounds like great news, Lurie says Gen Alpha may be avoiding one set of risks, while becoming vulnerable to another. 

“What concerns me as both a clinician and a parent is that while substance use has declined, so has in-person socialization,” she says. 

Teens are going out less, spending far less time with friends in person, and engaging in fewer unstructured social activities. 

“So while the reduction in risky behavior is positive, I’m not sure we can conclude that Gen Alpha is simply choosing healthier lifestyles,” says Lurie.

Mackenzie Sommerhalder, PhD, assistant professor in child and adolescent psychiatry at Johns Hopkins School of Medicine, agrees, saying, “One might conceptualize increased use of social media and artificial intelligence (AI) as risk-taking behavior. The negative side-effects of these tools on adolescent development are well known, and yet adolescents continue to engage with the tools.”

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Photo: Parents/GettyImages/martin-dm

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“What else is being covered up?” the post said. “We need transparency for the American public.”

Twelve of the other missing photos pictured the infamous massage room on the third floor of Mr. Epstein’s mansion in New York. The room, which sat down the hall from Mr. Epstein’s bedroom, was where investigators say that many of his sexual assaults occurred — some of them against teenage victims. The shelves in the room were stocked with lubricants and a silver ball and chain, among other things.

The massage room images that were removed depicted paintings and photographs of nude women, some with their faces redacted. But other images and artwork featuring nude women remained on the site. And some photos of the massage room — including the nude imagery — also remained.

The missing photos were part of a vast collection of materials that the Trump administration was compelled to release after the passage last month of a law mandating that the Justice Department disclose all files in its possession related to Mr. Epstein, a convicted sex offender who died in jail in 2019 while awaiting trial on charges of trafficking minors.

Despite mounting expectations, the released files, which included thousands of photographs and investigative documents, were something of an anticlimax. They added little to the public’s understanding of Mr. Epstein’s conduct, and also did not provide much additional insight into his connections to wealthy and powerful businessmen and politicians who associated with him.

Mr. Trump has, uncharacteristically, said nothing about the files, which contained far more material about one of his political adversaries, former President Bill Clinton, than about him. Still, the Justice Department has said that more disclosures from its files about Mr. Epstein would be coming in the next few weeks.

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A photo taken of a credenza in Jeffrey Epstein’s home — which contained at least one image of President Trump — was among the material removed from the site. Credit…Department of Justice

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By the time Maggie May, an Arkansas resident in her 30s, was admitted to a psychiatric clinic in 2024, she had been struggling for years with atypical anorexia nervosa, an eating disorder that leads to severe food restriction and profound disturbances in body image. (Her name has been changed for privacy.) She had already tried traditional interventions with a psychotherapist and a dietitian, but they had failed to improve her condition. So when May heard about a trial of a new and unconventional therapy, she jumped at the opportunity.

The treatment was unusual in that, alongside talk therapy, May underwent several sessions in a sensory-deprivation chamber: a dark, soundproof room where she floated in a shallow pool of water heated to match the temperature of her skin and saturated with Epsom salts to make her more buoyant. The goal was to blunt May’s external senses, enabling her to feel from within—focusing on the steady thudding of her heart, the gentle flow of air in and out of her lungs, and other internal bodily signals.

The ability to connect with the body’s inner signals is called interoception. Some people are better at it than others, and one’s aptitude for it may change. Life events can also bolster or damage a person’s interoceptive skills. Sahib Khalsa, a psychiatrist and neuroscientist at the University of California, Los Angeles, and his colleagues think a disrupted interoception system might be one of the driving forces behind anorexia nervosa. So they decided to repurpose a decades-old therapy called flotation-REST (for “reduced environmental stimulation therapy”) and launched a trial with it in 2018. They hypothesized that in people with anorexia and some other disorders, an underreliance on internal signals may lead to an overreliance on external ones, such as how one looks in the mirror, that ultimately causes distorted body image, one of the key factors underlying these conditions. “When they’re in the float environment, they experience internal signals more strongly,” Khalsa says. “And having that experience may then confer a different understanding of the brain-body relationship that they have.”

Studies have implicated problems with this inner sense in a wide variety of conditions, including anxiety disorders, post-traumatic stress disorder, and borderline personality disorder. Some researchers and clinicians now think that problems in interoception might contribute to many mental illnesses. Alongside this research, which itself is complicated by challenges in testing design and by a less than clear understanding of interoception, other groups are also developing therapies that aim to target this inner sense and boost psychological well-being.

This work is circling in on a central message: the body and mind are inextricably intertwined. “We have always thought about [mental health conditions] as being in the brain or the mind,” says Camilla Nord, a professor of cognitive neuroscience at the University of Cambridge. But clinicians have long noted that people with mental illness frequently report physical symptoms such as abnormalities in heartbeats, breathing, and appetite, she adds.

The idea that the body can influence the mind dates back centuries. In the 1800s, two psychologists on opposite ends of the globe independently proposed a then novel idea: emotions are the result of bodily reactions to a specific event. Called the James-Lange theory after its founders, American psychologist William James and Danish doctor Carl Lange, this view ran counter to the long-dominant belief that emotions were the cause, not a consequence, of corresponding physiological changes.

Although this notion has garnered critics, it inspired a slew of studies. The 1980s saw a surge of interest in the role of physiological signals in panic disorders. Researchers discovered that they could bring on panic attacks by asking people to inhale carbon dioxide–enriched air, which can increase breathing rates, or by injecting them with isoproterenol, a drug that increases heart rate.

Breathing rate can affect how someone perceives the intensity and unpleasantness of pain.

 

These findings led some psychologists to suggest that physical sensations were the primary trigger of panic attacks. In the early 1990s, Anke Ehlers, a psychologist then at the University of Göttingen in Germany, and her team examined dozens of people with panic disorders and reported that these patients were better able to perceive their heartbeats than healthy individuals—and that this greater awareness was linked to more severe symptoms. On top of that, a small, preliminary study by Ehlers of 17 patients revealed that those who were more skilled at this task were more likely to relapse and start having panic attacks again. These observations hinted at a two-way dynamic: not only could physical sensations within the body cause psychological effects, but the ability to perceive and interpret those signals—in other words, one’s interoceptive ability—could have a profound influence on mental health.

Over the years, a growing body of evidence has indicated that interoception plays an important role in shaping both emotions and psychological health. A large chunk of this work has focused on the heart. With every heartbeat, blood rushes into the arteries and triggers sensors known as baroreceptors, which shoot off messages to the brain conveying information about how strongly and rapidly the heart is beating.

In one pivotal 2014 study, Hugo Critchley, a neuropsychiatrist at Brighton and Sussex Medical School in England, and his team reported that this process can affect a person’s sensitivity to fear. By monitoring volunteers’ heartbeats while they viewed fearful or neutral faces, they found that people detected fearful faces more easily and judged them as more intense when their heart was pumping out blood than when it was relaxing and refilling. But participants with higher levels of anxiety often perceived fear even when their hearts relaxed.

Researchers have also demonstrated that bodily signals such as breathing patterns and gut rhythms can influence emotional reactions. People are quicker to react to fearful faces while breathing in than while breathing out, and breathing rate can affect how someone perceives the intensity and unpleasantness of pain.In more recent work, some neuroscientists have turned their attention to the gastrointestinal system. In 2021, Nord and her colleagues discovered that people given a dose of an antinausea drug that affects gut rhythms—processes within the stomach that help digestion—were less likely to look away from pictures of feces than they normally would have been. These disgust-related visceral signals, Nord speculates, may be relevant to eating disorders. “It’s possible that some of these signals contribute to feeling aversion to signals of satiety, making satiety very uncomfortable, a feeling you don’t want to feel,” she says.

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‘The supreme court is at the brink of illegitimacy. Far from pulling it back from the edge, our goal has to be to push it off. Photograph: Stefani Reynolds/AFP via Getty Images

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