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Low-carbohydrate diets comprised mostly of plant-based proteins and fats with healthy carbohydrates such as whole grains were associated with slower long-term weight gain than low-carbohydrate diets comprised mostly of animal proteins and fats with unhealthy carbohydrates like refined starches, according to a new study led by Harvard T.H. Chan School of Public Health.
The study will be published on December 27, 2023, in JAMA Network Open.
“Our study goes beyond the simple question of, ‘To carb or not to carb?'” said lead author Binkai Liu, research assistant in the Department of Nutrition. “It dissects the low-carbohydrate diet and provides a nuanced look at how the composition of these diets can affect health over years, not just weeks or months.”
While many studies have shown the benefits of cutting carbohydrates for short-term weight loss, little research has been conducted on low-carbohydrate diets’ effect on long-term weight maintenance and the role of food group quality.
Using data from the Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study, the researchers analyzed the diets and weights of 123,332 healthy adults from as early as 1986 to as recently as 2018. Each participant provided self-reports of their diets and weights every four years. The researchers scored participants’ diets based on how well they adhered to five categories of low-carbohydrate diet: total low-carbohydrate diet (TLCD), emphasizing overall lower carbohydrate intake; animal-based low-carbohydrate diet (ALCD), emphasizing animal-based proteins and fats; vegetable-based low-carbohydrate diet (VLCD), emphasizing plant-based proteins and fats; healthy low-carbohydrate diet (HLCD), emphasizing plant-based proteins, healthy fats, and fewer refined carbohydrates; and unhealthy low-carbohydrate diet (ULCD), emphasizing animal-based proteins, unhealthy fats, and carbohydrates coming from unhealthy sources such as processed breads and cereals.
The study found that diets comprised of plant-based proteins and fats and healthy carbohydrates were significantly associated with slower long-term weight gain. Participants who increased their adherence to TLCD, ALCD, and ULCD on average gained more weight compared to those who increased their adherence to HLCD over time. These associations were most pronounced among participants who were younger (

Scientists at the Johns Hopkins University School of Medicine and the National Institutes of Health have identified a protein in the visual system of mice that appears to be key for stabilizing the body’s circadian rhythms by buffering the brain’s response to light. The finding, published Dec. 5 in PLoS Biology, advances efforts to better treat sleep disorders and jet lag, the study authors say.
“If circadian rhythms adjusted to every rapid change in illumination, say an eclipse or a very dark and rainy day, they would not be very effective in regulating such periodic behaviors as sleep and hunger. The protein we identified helps wire the brain during neural development to allow for stable responses to circadian rhythm challenges from day to day,” says Alex Kolodkin, Ph.D., professor in the Johns Hopkins Department of Neuroscience and deputy director for the Institute for Basic Biomedical Sciences.
Kolodkin co-led the study with Samer Hattar, Ph.D., chief of the Section on Light and Circadian Rhythms at the National Institute of Mental Health.
Scientists have long known that most living things have a circadian “clock,” a set of biological rhythms that operate on about a 24-hour cycle and that affect alertness, sleepiness, appetite and body temperature, among other cyclic behaviors. Upsetting this system — through shift work or long-distance travel over multiple time and light zones in humans, for example — can have severe consequences. Previous studies link persistent upsets in circadian rhythm to increased risk of cancer, depression and a host of other medical problems.
Circadian systems are essentially “trained” by exposure to light. Although researchers have made significant headway over the last few decades in outlining the mechanisms responsible for circadian rhythms, it has remained unclear how the brain becomes wired for them.
To learn more, Kolodkin and Hattar, along with study first authors John Hunyara and Kat Daly and their colleagues, searched a database for biological molecules present during development in the mouse brain’s control center for circadian rhythms — the suprachiasmatic nucleus (SCN).
Located deep within both the mouse and human brain in the hypothalamus, the SCN sits near areas that control vision and makes connections with brain cells that lead to the retina, the light-sensing part of the eye.

The research team quickly zeroed in on a cell surface protein called teneurin-3 (Tenm3), part of a larger family of proteins that play key roles in the visual system circuit assembly and more generally in other central nervous system circuits.
When the researchers genetically altered mice to prevent Tenm3 production, the animals developed fewer connections between the retina and the SCN, compared with animals with intact Tenm3. However, the mice lacking Tenm3 developed far more connectivity between cells in the core and shell of the SCN, where Tenm3 tends to localize.
To see how Tenm3 might stabilize circadian rhythms or subject them to disruption by even a tiny bit of light, the scientists designed a set of experiments.
First, they trained mice lacking Tenm3 on a 12-hour light/dark cycle, then shifted the dark period ahead by six hours. Mice with intact Tenm3 took about four days to readjust their circadian rhythms to the shift, as measured by activity patterns diagnostic of normal sleep cycles. The animals without Tenm3, however, adjusted far more rapidly, in about half the time.
When the researchers performed a similar experiment with light twice as dim as in the earlier test, it took the Tenm3-intact mice about eight days to adjust their circadian cycles, but only about four days for the mice without Tenm3. Even just a 15-minute pulse of dim light triggered the Tenm3-lacking mice — but not the mice with normal Tenm3 protein — to produce a brain chemical that serves as a proxy for light exposure, suggesting a heightened sensitivity to light cues necessary for setting or resetting the circadian clock.
These findings suggest to the authors that Tenm3 helps wire the brain to maintain stable circadian rhythms even when light exposure is variable. By learning more about this system and Tenm3’s role, says Hattar, researchers may eventually be able to diagnose and treat glitches that lead to insomnia and other sleep disorders in people, or possibly develop treatments for jet lag.
“There are very clear implications for human health,” he says.
Other Johns Hopkins researchers who contributed to this study include Katherine Torres.
This study was funded by grants from the NIH (R01EY032095) and the Intramural Research Program at the NIMH (ZIAMH002964).

We’ve learned plenty about eating well. Here’s the advice we’ll carry with us into 2024.As a health reporter who’s been following nutrition news for decades, I’ve seen a lot of trends that made a splash — and then sank. Remember olestra, the Paleo diet and celery juice?Watch enough food fads come and go, and you realize that the most valuable nutrition guidance is built on decades of research, in which scientists have looked at a question from multiple perspectives and arrived at something like a consensus.Here are 10 science-backed pearls to carry you into the new year.1. The Mediterranean diet really is that good for you.Decades of research support the Mediterranean diet — which is centered on fruits and vegetables, whole grains, legumes, olive oil, nuts, herbs and spices — as one of the healthiest ways you can eat. Its heart-health benefits are numerous, and it has been linked to a lower risk of Type 2 diabetes, cognitive decline and certain types of cancer.If you’re interested in adopting the Mediterranean diet but aren’t sure where to start, stay tuned. Starting Jan. 15, we’ll be sharing a week of practical guidance and recipes for Mediterranean-style eating in the Well newsletter, which you can sign up for here.2. It’s OK to drink coffee on an empty stomach.Some people may experience heartburn, but there’s no evidence that drinking coffee on an empty stomach can damage your gastric lining or otherwise harm your digestive system, experts say. And there are reasons to feel good about your morning brew: Drinking coffee has been linked to a longer life and a lower risk of heart disease and Type 2 diabetes.3. Start your day with a healthy breakfast.Mornings can be hectic, and it may be tempting to grab a quick muffin or skip breakfast altogether. But nutrition experts say it’s worth prioritizing that morning meal — especially if it contains a balanced mix of protein, fiber and healthy fats. It will fuel your day, and studies have found that those who eat breakfast tend to enjoy a range of health benefits, including a lower risk of cardiovascular disease, Type 2 diabetes and obesity.4. Take good care of your gut.Keeping your digestive system healthy and running smoothly can protect you from life’s discomforts — like heartburn, bloating and constipation — as well as lead to better overall health. Unsurprisingly, the best way to care for your gut is to feed yourself (and by extension, your gut microbes) well, by prioritizing fiber and consuming a variety of plant-based and fermented foods.5. You probably don’t need protein bars.They’re often marketed as a health food or as essential fuel for athletic performance, but most protein bars are loaded with sugar. You’re better off meeting your protein needs with whole foods like yogurt, nuts, beans or eggs, experts say.6. Go easy on the dark chocolate.File this as one of the saddest nutrition news stories of 2023. Dark chocolate has some of the highest levels of lead and cadmium (heavy metals that can harm the body) when compared with other foods. Fortunately, you don’t have to give up your dark chocolate habit entirely. Enjoying it in moderation — no more than about an ounce per day, experts say — will keep your risk low.7. Blending fruits and veggies won’t destroy their nutrients.Puréeing fruits and vegetables in a blender won’t strip them of their vitamins, minerals or fiber. And, somewhat surprisingly, several small studies suggest that sipping your fruit in blended form won’t spike your blood sugar any more than when you eat it whole. So go ahead — enjoy your smoothie. And check out our tips for making yours more nutritious.8. Cottage cheese is back.You might associate cottage cheese with fad diets from the 1970s, but it’s a food that has stood the test of time. Cottage cheese was a breakout hit on TikTok this summer, and for good reason. You can eat it plain or use it as a versatile ingredient in both sweet and savory snacks, and it offers an impressive array of nutrients including protein, calcium, selenium and more.9. Tofu really is good for you, too.In past decades, people have worried that tofu and other soy foods might be linked with cancer or fertility problems because they contain estrogen-like compounds. But studies have put those fears to bed, scientists say. In fact, research suggests that eating soy-based foods may reduce your risk of heart disease and even some types of cancer.10. It’s challenging to separate nutrition myths from facts.Myths about nutrition tend to linger in American culture and in our minds, leaving us confused and sometimes even anxious about our eating decisions. We asked 10 nutrition experts which myths they wished would disappear like plate of fresh cookies at a holiday party.

These simple and proven strategies will help you manage stress and find meaning in the new year.Since the height of the pandemic, there has been a cultural shift in the way we talk about mental health. It’s as though the years of isolation and uncertainty helped us understand how vital our emotional needs were to our overall well-being.Now that we’re paying more attention to our inner lives, it’s also essential that we take action. Fortunately, there are a number of things that everyone can do to nourish their mental health and find moments of joy.Here are some of our favorite tips from the past year as we prepare to enter 2024.1. Try a proven way to sleep better.Experts say that getting enough sleep is one of the most important things we can do for our mental health. If you’re having trouble falling or staying asleep, studies have found that cognitive behavioral therapy for insomnia, or C.B.T.-I., is as effective as using sleep medications in the short term — and more effective in the long term. C.B.T.-I. helps people address anxieties about sleep and find ways to relax. To find a provider, try the Society of Behavioral Sleep Medicine directory.2. Learn how to tell whether your anxiety is protective or problematic.It’s normal to feel anxious from time to time. In fact, having some anxiety can actually be useful. Experts say an internal alarm system can improve our performance, help us recognize danger and even encourage us to be more conscientious. So we asked Dr. Petros Levounis, the president of the American Psychiatric Association: How much anxiety is too much?“If you start to notice that worry and fear are there constantly, that is a signal that you need some help,” he said.Other signs to look out for include restlessness, a sense of fear or doom, increased heart rate, sweating, trembling and trouble concentrating.3. Stop the worry cycle.If you have a tendency to ruminate, there are a few simple ways to curb the habit. The first is to distract yourself: Research shows that diversions can help get your mind off whatever is stressing you out. Try playing a word game or listening to music, paying close attention to the lyrics.Other times, it’s better not to fight the urge — but that doesn’t mean you should let your thoughts spiral out of control. Set a timer for 10 to 30 minutes of dedicated rumination time, and give yourself permission to mentally mull things over. When the timer goes off, it’s time to move on.4. Practice ‘5 things tidying.’When you’re struggling with your mental health, basic tasks like washing dishes or doing laundry can feel impossible. But living amid mess can make you feel even worse. KC Davis, a licensed professional counselor and author of the book “How to Keep House While Drowning,” advises focusing on function over aesthetics — your home doesn’t have to be perfect, but it should be livable.An efficient way to keep things from getting out of hand is to practice what she calls “five things tidying.” Tackle the five main categories of clutter — trash, dishes, laundry, things with a place and things without a place — one at a time to help cleaning feel more manageable.5. Embrace gratitude.Gratitude is a positive emotion that can arise when you acknowledge that you have goodness in your life and that other people — or higher powers, if you believe in them — have helped you achieve that goodness.To really reap the benefits of gratitude, experts say, it’s important to express it whenever possible. That might include writing letters of thanks or listing the positive things in your life in a journal. Giving thanks to friends, romantic partners and even co-workers can also offer a relationship boost.6. Be optimistic about aging.Research shows that mindset really matters when it comes to health, and it can even extend your life. A classic study found that people who were optimistic about aging lived seven and a half years longer than those who had negative perceptions of it.To adopt a more positive outlook about getting older, shift your focus to the benefits of aging, like better emotional well-being and higher emotional intelligence. Look for aging role models, too: older people who stay physically active and engaged in their communities, or those with traits that you admire.7. Participate in the arts.The notion that art can improve mental well-being is something many people intuitively understand but don’t necessarily put into practice.You don’t need talent to give it a try, experts say. Writing a poem, singing or drawing can all help elevate your mood, no matter how creative you consider yourself to be. One of the easiest ways to get started is to color something intricate: Spending 20 minutes coloring a mandala (a complex geometric design) is more helpful for reducing anxiety than free-form coloring for the same length of time, research has found.8. Look for a little bit of awe every day.Sometimes we have to remind ourselves to connect with the physical world around us. Enter the awe walk.Pick a walking spot (either new or familiar) and imagine that you’re seeing it for the first time. Then pay attention to your senses. Feel the wind on your face, touch the petals of a flower. Simply notice the sky. It can be more restorative than you might expect.9. Take a tech break.If you’re having trouble focusing, it’s not just you. Research has found that over the past two decades, the amount of time we spend on a given task has shrunk to an average of just 47 seconds, down from two and a half minutes. Technology is often to blame.To regain control of your concentration, Larry Rosen, a professor emeritus of psychology at California State University, Dominguez Hills, suggested a strategy he calls “tech breaks.” Set a timer for 15 minutes, then silence and set aside your phone. When time is up, take one or two minutes to check your favorite apps — that’s your tech break — and get back to work for another 15-minute cycle. The goal is to gradually increase the time between your tech breaks, building up to 45 minutes (or more) away from your phone.10. Take a deep breath.One of the fastest, easiest ways you can calm your mind and body is by taking slow, deep breaths. Doing so helps to turn up your parasympathetic nervous system — the counterbalance to the “fight or flight” stress response — and lower your blood pressure and regulate your heart rate.One breathing exercise that can be particularly helpful for mitigating fear and anxiety is 4-4-8 breathing, where you inhale for four counts, hold your breath for four counts and exhale for eight counts.

Published25 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Fergus WalshMedical editor Hospital admissions from a winter virus could be reduced by more than 80% if babies are given a single dose of a new antibody treatment, a study says.Respiratory syncytial virus (RSV) usually causes mild, cold-like symptoms, but can lead to bronchiolitis and pneumonia. More than 30,000 under fives are hospitalised with RSV in the UK annually, resulting in 20 to 30 deaths.One parent said her son getting RSV was “very scary” as a first-time mother.Lorna and Russell Smith’s eldest son, Caolan, got the virus when he was eight months old and was admitted to hospital twice – each time requiring oxygen. Now aged two, he has made a full recovery. “I hadn’t heard of RSV and wasn’t sure what to do. He had laboured breathing due to high temperature and was quite lethargic. It brought a lot of anxiety and stress,” Lorna said.The family, from Southampton, hope their one-month-old Rian will be able to have the RSV antibody injection if it is approved for use in the NHS.Image source, Lorna and Russell SmithThe Harmonie study involved 8,000 children up to the age of 12 months in the UK, France and Germany, with half receiving a single dose of the monoclonal antibody treatment nirsevimab.The results, published in the New England Journal of Medicine, showed that RSV-related hospitalisation was reduced by 83% in those receiving the jab and admissions for all chest infections were cut by 58%. Side effects were similar in both groups and mostly mild. Kate and Matt Parker’s twin daughters, Jessica and Ellie, took part in the trial in Southampton when they were three months old. Kate told the BBC: “I hoped that if one of them got the jab they would have a good chance of remaining healthy over the winter season. Jess was immunised, but both were well.” She said the trial results were “fantastic” and “if it could prevent thousands of children going into hospital and putting more strain on the NHS during the winter, that would be great.”Nirsevimab, produced by Sanofi, was licensed for use in the UK last year. The Joint Committee on Vaccination and Immunisation (JCVI), which advises the government, is considering whether to recommend the jab to protect infants. It is also analysing data on a RSV vaccine given to pregnant women which was licensed last month.The JCVI says a cost-effective RSV immunisation programme should be developed for both infants and older adults.Unlike a vaccine, which prompts the body to create antibodies and takes a few weeks to be effective, nirsevimab gives immediate protection. Prof Saul Faust, co-study leader at the University of Southampton and a consultant paediatrician, said: “These latest results show that this long-acting antibody is safe and could protect thousands of babies from hospitalisation when used in conditions similar to routine clinical practice. It is really important information for the UK to help decide on options for the future national RSV immunisation programme.”In July, the US Food and Drug Administration (FDA) approved nirsevimab for babies and it has also been rolled out in parts of Spain. How to spot RSV•RSV starts with a blocked or runny nose and can progress to a dry cough, fever and sometimes breathing problems•For most children, it will be mild and can be treated at home with infant paracetamol or ibuprofen•Call your GP or seek medical advice if your child is not feeding normally, is breathing fast or has a high temperature that will not go down•Call 999 if your child is exhausted from trying to breathe – you may see the muscles under their ribs sucking in with each breath or they may be pale and sweaty More on this storyHospital hails winter virus jab trial for babiesPublished19 MayMother’s RSV warning as vaccine trial progressesPublished19 FebruaryBe alert to RSV risk to children, parents urgedPublished30 September 2022

Here’s what to know about the coronavirus variant, which was first detected in the United States in September. As the holiday season winds down and Covid-19 cases start to pick up, a variant called JN.1 has now become the most common strain of the virus spreading across the United States.JN.1, which emerged from the variant BA.2.86 and was first detected in the United States in September, accounted for 44 percent of Covid cases nationwide by mid-December, up from about 7 percent in late November, according to data from the Centers for Disease Control and Prevention. To some extent, this jump is to be expected. “Variants take some time to get going,” said Dr. William Schaffner, an infectious disease specialist at Vanderbilt University Medical Center. “Then they speed up, they spread widely, and just when they’re doing that, after several months, a new variant crops up.”JN.1’s momentum this month suggests that it may be more transmissible or better at evading our immune systems than other variants currently circulating, according to a C.D.C. report published Dec. 22. The agency said that Covid remains “a serious public health threat,” especially for those who have always been at high risk of severe disease, such as older adults, infants, people with compromised immune systems or chronic medical conditions and those who are pregnant. As far as experts can tell, JN.1 does not seem to be causing severe illness in most other people, though even a mild case can still make you feel “quite miserable for three or four days,” Dr. Schaffner said. The symptoms of a JN.1 infection are similar to those caused by previous Covid variants, including a cough, fever, body aches and fatigue. To protect yourself against infection and severe disease, experts continue to recommend wearing masks, improving ventilation indoors when possible, staying home when sick and getting the latest Covid vaccine.Preliminary research shows that the updated Covid vaccines released in September produce antibodies effective against JN.1, which is distantly related to the XBB.1.5 variant that the vaccines were designed to target. People may not build up as many antibodies to JN.1 as they would to XBB.1.5, but the levels should still decrease the risk. “For those who were recently infected or boosted, the cross-protection against JN.1 should be decent, based on our laboratory studies,” said Dr. David Ho, a virologist at Columbia University who led the research on JN.1 and Covid vaccines, which was released as a preprint paper in early December. Rapid tests also continue to be a valuable tool, and the C.D.C. has said tests already on the market work well at detecting JN.1. There are signs that Covid cases are once again creeping up. There were just under 26,000 hospitalizations due to Covid the week of Dec. 10, a 10 percent increase from about 23,000 hospitalizations the week prior. But Covid hospitalizations are still far lower than they were during the peak of the first Omicron wave in January 2022, and so far only about half as high as they were during the peak of the tripledemic last winter, when Covid-19, flu and R.S.V. cases all surged at the same time. It is too early to know whether JN.1 is responsible for the rise in hospitalizations or whether cases are picking up partly because of an increase in travel and large get-togethers for Thanksgiving and the winter holidays.“When people are gathered inside close to each other, having parties and traveling and the like, those are the kind of circumstances where all respiratory viruses, including JN.1, have opportunities to spread,” Dr. Schaffner said. Covid generally also has some seasonality, he added; countries in the Northern Hemisphere tend to see a lull in cases in the fall before infections and hospitalizations rise again in the winter. JN.1 will most likely remain the dominant version of the coronavirus through spring, Dr. Schaffner said. He and other experts noted that while vaccines offer protection against it and other variants, uptake remains low, with only 18 percent of adults having received the latest shots. Experts said everyone should consider getting vaccinated, especially those who are over age 65, are immunocompromised, have health conditions that put them at higher risk of severe illness or are traveling to visit loved ones who may be vulnerable.“Give yourself a New Year’s present by getting this vaccine if you haven’t done it yet,” Dr. Schaffner said.

Researchers have identified a wide range of risk factors for young-onset dementia. The findings challenge the notion that genetics are the sole cause of the condition, laying the groundwork for new prevention strategies.
The largescale study identified 15 risk factors, which are similar to those for late-onset dementia. For the first time, they indicate that it may be possible to reduce the risk of young-onset dementia by targeting health and lifestyle factors.
Relatively little research has been done on young-onset dementia, though globally there are around 370,000 new cases of young-onset dementia each year.
Published in JAMA Neurology, the new research by the University of Exeter and Maastricht University followed more than 350,000 participants younger than 65 across the United Kingdom from the UK Biobank study. The team evaluated a broad array of risk factors ranging from genetic predispositions to lifestyle and environmental influences. The study revealed that lower formal education, lower socioeconomic status, genetic variation, lifestyle factors such as alcohol use disorder and social isolation, and health issues including vitamin D deficiency, depression, stroke, hearing impairment and heart disease significantly elevate risk of young-onset dementia
Professor David Llewellyn of the University of Exeter emphasized the importance of the findings: “This breakthrough study illustrates the crucial role of international collaboration and big data in advancing our understanding of dementia. There’s still much to learn in our ongoing mission to prevent, identify, and treat dementia in all its forms in a more targeted way. This is the largest and most robust study of its kind ever conducted. Excitingly, for the first time it reveals that we may be able to take action to reduce risk of this debilitating condition, through targeting a range of different factors.
Dr Stevie Hendriks, Researcher at Maastricht University, said: “Young-onset dementia has a very serious impact, because the people affected usually still have a job, children, and a busy life. The cause is often assumed to be genetic, but for many people we don’t actually know exactly what the cause is. This is why we also wanted to investigate other risk factors in this study.”
Sebastian Köhler, Professor of Neuroepidemiology at Maastricht University, said: “We already knew from research on people who develop dementia at older age that there are a series of modifiable risk factors. In addition to physical factors, mental health also plays an important role, including avoiding chronic stress, loneliness and depression. The fact that this is also evident in young-onset dementia came as a surprise to me, and it may offer opportunities to reduce risk in this group too.”
The study’s support was supported by Alzheimer’s Research UK, The Alan Turing Institute/Engineering and Physical Sciences Research Council, Alzheimer Nederland, Gieskes Strijbis Fonds, the Medical Research Council, the National Institute for Health and Care Research (NIHR) Applied Research Collaboration South West Peninsula (PenARC), the National Health and Medical Research Council, the National Institute on Aging, and Alzheimer Netherlands.

Dr Janice Ranson, Senior Research Fellow at the University of Exeter, said: “Our research breaks new ground in identifying that the risk of young-onset dementia can be reduced. We think this could herald a new era in interventions to reduce new cases of this condition.”
Dr Leah Mursaleen, Head of Clinical Research at Alzheimer’s Research UK, which co-funded the study, said: “We’re witnessing a transformation in understanding of dementia risk and, potentially, how to reduce it on both an individual and societal level. In recent years, there’s been a growing consensus that dementia is linked to 12 specific modifiable risk factors such as smoking, blood pressure and hearing loss . It’s now accepted that up to four in 10 dementia cases worldwide are linked to these factors.
“This pioneering study shines important and much-needed light on factors that can influence the risk of young-onset dementia. This starts to fill in an important gap in our knowledge. It will be important to build on these findings in broader studies.’

A drug screening system that models cancers using lab-grown tissues called organoids has helped uncover a promising target for future pancreatic cancer treatments, according to a new study from researchers at Weill Cornell Medicine.
In the study, published Dec. 26 in Cell Stem Cell, the scientists tested more than 6,000 compounds on their pancreatic tumor organoids, which contain a common pancreatic cancer-driving mutation. They identified one compound — an existing heart drug called perhexiline maleate — that powerfully suppresses the organoids’ growth.
The researchers discovered that the cancer-driving mutation in the organoids forces the abnormally high production of cholesterol, which the drug largely reverses.
“Our findings identify hyperactive cholesterol synthesis as a vulnerability that may be targetable in most pancreatic cancers,” said study co-senior author Dr. Todd Evans, vice chair for research in surgery, the Peter I. Pressman MD Professor in Surgery, and a member of the Hartman Institute for Therapeutic Organ Regeneration at Weill Cornell Medicine.
“This study also highlights the value of using genetically well-defined organoids to model cancer and discover new treatment strategies,” said co-senior author Dr. Shuibing Chen, director of the Center for Genomic Health, the Kilts Family Professor Surgery and a member of the Hartman Institute for Therapeutic Organ Regeneration at Weill Cornell Medicine.
The other co-senior author was Dr. Fong Cheng Pan, a research assistant professor in the department of surgery at Weill Cornell Medicine during the study.
The study’s co-first authors were postdoctoral researcher Dr. Xiaohua Duan, instructor Dr. Tuo Zhang, and a visiting fellow, Dr. Lingling Feng, all at Weill Cornell Medicine during the study.

A Tumor Organoid-Based Screening System
Organoids have become popular tools for studying tissues in health and disease. They can be made from human or animal tissue, they can recreate much of an organ’s complex architecture, and they can be genetically engineered for precision modeling. Organoids can also model specific tumor types with their cancer-driving gene mutations. Indeed, when these tumor organoids are derived from human tissue, they have the potential to model human cancers better than any animal model.
In the study, the researchers set up an organoid-based automated drug-screening system for the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) — one of the most untreatable and lethal of cancers. The organoids, made from normal mouse pancreatic tissue, were engineered to contain various sets of mutations known to drive human pancreatic tumors. All the organoids contained KrasG12D, the mouse version of a cancer-driving mutant gene found in most cases of PDAC.
The researchers tested a library of more than 6,000 compounds, including FDA-approved drugs, on the organoids, identifying several that could substantially disrupt their growth. The best of these was perhexiline maleate, an older drug used to treat the heart condition called angina. A modest dose of the drug blocked growth in all the KrasG12D-containing organoids, destroying some of them outright within days, while having no adverse impact on healthy organoids lacking the mutation. The drug had similar effects against mouse and human PDAC-derived tumor organoids transplanted into mice, and in human tumor organoids carrying other types of Kras mutation.
By comparing gene activity patterns in treated and untreated organoids, the researchers found that cancer-associated mutant Kras greatly boosts the production of cholesterol in organoid cells, and that perhexiline maleate opposes this effect by inhibiting a key cholesterol metabolic pathway regulatory factor called SREBP2.
Cholesterol as an Emerging Cancer Target
The discovery of cholesterol’s role was not entirely surprising, since cholesterol is an essential building-block used in making new cells, and a promoter of cell survival; it is already known to be an important sustainer of malignant growth for some other tumors, including lung tumors. Now, the results suggest that targeting it may be an effective new treatment strategy against PDAC.

Perhexiline maleate’s effectiveness in human organoids harboring several different Kras mutations also suggests that turbo-charged cholesterol synthesis can be a general treatment target in KRAS-mutant cancers.
“We hope that our cholesterol-targeting strategy will be independent of particular KRAS mutations and will make it hard for treated tumors to evolve resistance,” said Dr. Evans, who is also a member of the Sandra and Edward Meyer Cancer Center .
Perhexiline maleate is unlikely to be used as-is for treating PDAC. Although it is still prescribed as an angina drug in Australia and some other countries, it can have serious side effects, including liver damage and peripheral nerve damage — which is why it was withdrawn from several European markets in the 1980s, and was never approved in the United States.
“We want a better compound for cancer treatment,” said Dr. Chen. The simplicity of the drug’s chemical structure suggests that it probably can be modified to improve its potency, safety, bloodstream half-life and other properties, she said.
The team now plans to use perhexiline maleate as a starting point for the development of a more refined candidate PDAC drug, and as a laboratory tool for studying cholesterol synthesis in PDAC and other cancers.

Published12 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, PA MediaBy Nick TriggleHealth correspondentNearly 89,000 NHS appointments had to be cancelled because of last week’s junior doctor strike in England.Most – just over 86,300 – were hospital check-ups and operations, but 1,500 community and mental health appointments were also affected. Overall more than 1.2 million appointments have been affected since strikes began in the NHS a year ago.Next week junior doctors will take part in a six-day walkout – the longest in the history of the NHS.It begins on 3 January and comes after talks between the British Medical Association (BMA) and government broke down, earlier this month.NHS England medical director Prof Sir Stephen Powis said that walkout comes at what is “one of the busiest times for the health service”.”Strike action is once again going to bring significant challenges to the NHS as it struggles to provide for patients amid severe disruption”As well as having an impact on planned care, industrial action is putting pressure on wider services and prioritising emergency care takes staff away from other areas.”How double pay rise for senior doctors is backfiringWhy talk of a UK doctor exodus is prematureHow much do junior doctors really get paid? Nearly half of NHS doctors are junior doctors – a group that spans those just out of university through to some who have 10 years or more experience.Two-thirds are members of the BMA – and they were also joined by members of the much-smaller Hospital Consultants and Specialists Association union.It meant senior doctors had to be drafted across from other services to staff emergency care – although in some places A&E units still had to close.Matthew Taylor, of the NHS Confederation, which represents managers, said his members were in “despair” over the impact of strikes on services.He said the figures released on Wednesday were likely to be an underestimate as many NHS trusts would have reduced the amount of activity they had been planning anyway because of the strike action.’Extremely disappointed’Ahead of that walkout, the BMA said it was “extremely disappointed” to be taking action again, after a previous stoppage in early October.It has urged the government to make a new offer. The BMA had ended talks after setting a deadline of early December for a resolution.An offer of a pay rise averaging 3%, from January, was being discussed, which would have been on top of the average of nearly 9% junior doctors received in April.But the BMA said that was too little – junior doctors had asked for an extra 35%, to make up for below-inflation pay rises since 2008. Industrial action in the NHS in England, which began last December with walkouts by ambulance staff and nurses, is estimated to have cost more than £2bn in planning, preparations and paying for cover.A pay offer to NHS staff other than doctors was accepted in May, while strike action by consultants has been put on hold as they vote on a fresh offer from the government. Junior doctors in Wales will also go on strike in January, while in Northern Ireland they are being balloted. But in Scotland a pay deal has been agreed.More on this storyFresh pay offer could end NHS consultant strikesPublished27 NovemberNurses react with fury over doctor pay offerPublished28 NovemberWhat is the NHS pay offer?Published2 MayWhy talk of a UK doctor exodus is prematurePublished9 AugustNHS pay deal signed off for one million staffPublished2 MaySome NHS temporary staff miss out on full pay dealPublished21 JulyHow much do junior doctors really get paid?Published11 AugustRelated Internet LinksStatistics ? Consultant-led Referral to Treatment Waiting Times Data 2023-24.websiteThe BBC is not responsible for the content of external sites.

The NewsA federal judge in Idaho temporarily blocked the enforcement of a state law on Tuesday that bans gender transition care for minors and threatens medical professionals with a felony conviction if they provide such care, just six days before it was set to take effect. Protesters at the Indiana Statehouse in Indianapolis in February after Republican governors in Indiana and Idaho signed bills banning gender care for minors.Darron Cummings/Associated PressBackgroundThe law, House Bill 71, specifically bans gender transition surgeries, puberty blockers and hormone therapy for those under 18 with gender dysphoria. It also makes it a felony for medical professionals to provide the care, with a penalty of up to 10 years in prison.Idaho’s Republican-controlled Legislature passed the bill, also known as the Vulnerable Child Protective Act, in February, and Gov. Brad Little, also a Republican, signed it into law in April. The ban was set to take effect on Jan. 1, 2024.Mr. Little said the ban sought to “protect children.” But major medical organizations, including the American Academy of Pediatrics, have come out in support of gender transition care, saying bans pose serious mental health risks to young people.In May, two Idaho families, along with the American Civil Liberties Union and other organizations, filed a lawsuit to block the ban from taking effect, claiming that it was unconstitutional and harmful to the well-being of transgender minors.“Where the adolescent patient, their parents and their doctor all agree that gender-affirming medical care is medically necessary, the law strips families of the ability to access such care,” the complaint said.“Being able to live my life as my true self has been a long journey, and my medical care has been an important part of that journey,” one plaintiff, a 16-year-old transgender girl listed as Jane Doe in the case, said in a statement. On Dec. 27, Judge B. Lynn Winmill, who was appointed by President Bill Clinton in 1995, issued a preliminary injunction, saying in the ruling that the plaintiffs had “shown a strong likelihood of success on the merits of their claims.”Why It MattersIdaho’s legislation is part of a national wave of laws that aim to restrict the rights of transgender minors. So far this year, at least 20 states, all of which have Republican-controlled legislatures, have passed bans or restrictions on gender transition care for young people.In more than half of the states that have passed such bans, court challenges have been filed. Many judges over recent months have ruled in favor of plaintiffs seeking to block these bans temporarily while challenges to them proceed. But appeals court rulings in Georgia, Alabama, Kentucky and Tennessee have reversed those decisions, creating even more uncertainty for transgender minors and their families. In November, plaintiffs in the case against Tennessee’s ban became the first to ask the Supreme Court to weigh in on the issue.In Idaho, the Vulnerable Child Protective Act is not the only law restricting the rights of transgender youth that is currently the subject of legal battles.Days before signing the Vulnerable Child Protective Act, the governor signed a separate bill affecting transgender minors, known as Senate Bill 1100. This law prohibited transgender students from using public bathrooms not aligned with their gender assigned at birth and allowed students to take legal action against schools if they encountered a transgender student not abiding by the rule.The bathroom ban took effect on July 1, and inAugust, a judge issued a temporary restraining order, pausing the enforcement of the law until the court rules on whether to grant a preliminary injunction.What’s NextFor now, transgender minors in Idaho will still be able to receive gender transition care while the challenge to the constitutionality of the state ban continues to move through the legal system.Adeel Hassan